Synthesis of Pheromones: Highlights from 2002-2004
Synthesis of Pheromones: Highlights from 2002-2004
Synthesis of Pheromones: Highlights from 2002-2004
Create successful ePaper yourself
Turn your PDF publications into a flip-book with our unique Google optimized e-Paper software.
Current Organic Chemistry, 2009, 13, 299-338 299<br />
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong>: <strong>Highlights</strong> <strong>from</strong> <strong>2002</strong>-<strong>2004</strong><br />
P. H. G. Zarbin 1,* , J. A. F. P. Villar 1 , I. Marchi 1 , J. Bergmann 2 and A. R. M. Oliveira 1<br />
1 Departamento de Química, Universidade Federal do Paraná, CP 19081, 81531-990, Curitiba-PR, Brazil<br />
2 Instituto de Química, Pontificia Universidad Católica de Valparaíso, Avenida Brasil 2950, Valparaíso, Chile<br />
Abstract: This review summarizes the synthesis <strong>of</strong> pheromones published in the triennium <strong>2002</strong>-<strong>2004</strong>. The syntheses <strong>of</strong> a<br />
total <strong>of</strong> 66 pheromone compounds (65 <strong>from</strong> insects, 1 <strong>from</strong> a crustacean species), belonging to 9 different structural categories,<br />
are presented in schemes. New methodologies, but also well-known reactions have been employed to achieve the<br />
(in many cases stereoselective) synthesis <strong>of</strong> the compounds.<br />
1. INTRODUCTION<br />
Since its very beginnings in the mid 19th century, organic<br />
chemistry has made advances unimaginable to the<br />
early pioneers <strong>of</strong> the field. Among the experimental key<br />
techniques contributing to these advances are chromatography,<br />
which made possible the separation <strong>of</strong> complex mixtures,<br />
and spectroscopic (UV, IR, NMR) and mass spectrometric<br />
methods, giving organic chemists powerful tools for<br />
the structure determination <strong>of</strong> organic compounds. This, in<br />
turn, stimulated research in organic synthesis, as products<br />
and by-products <strong>of</strong> reactions could be easily isolated and<br />
characterized. As once stated by Meinwald, “Organic chemistry<br />
blossomed into a self-contained, inward-looking science,<br />
bringing order and understanding to the synthesis and<br />
reactions <strong>of</strong> millions <strong>of</strong> compounds” [1]. This order and understanding<br />
allowed the development <strong>of</strong> countless reactions<br />
<strong>of</strong> carbon-carbon bond formation or modification <strong>of</strong> functional<br />
groups, applicable to all classes <strong>of</strong> organic molecules,<br />
which would later eventually be modified or improved, e.g.<br />
in terms <strong>of</strong> scope, yields, reaction conditions, or stereochemical<br />
selectivities. Research in chemical communication<br />
has been pr<strong>of</strong>iting <strong>from</strong> these decade-lasting and ongoing<br />
efforts, as the synthesis <strong>of</strong> pheromones is <strong>of</strong> great importance<br />
in the process <strong>of</strong> identifying these chemical messengers.<br />
Moreover, a sort <strong>of</strong> mutualism has been evolving, as many<br />
new synthetic methods have been developped with the explicit<br />
aim to improve the synthetic route towards a pheromone.<br />
<strong>Pheromones</strong> are compounds which are produced and liberated<br />
by an individual, provocing a behavioural or physiological<br />
response in another individual <strong>of</strong> the same species.<br />
As pheromones are usually produced in minute amounts,<br />
thus preventing crystallographic or extensive NMR experiments,<br />
their independent synthesis is required to confirm the<br />
identification and to establish the absolute configuration in<br />
case <strong>of</strong> chiral compounds. Furthermore, chemical synthesis<br />
<strong>of</strong> pheromones provides the amounts necessary for the<br />
evaluation <strong>of</strong> their biological activity in the laboratory or in<br />
the field.<br />
*Address correspondence to this author at the Departamento de Química,<br />
Universidade Federal do Paraná, CP 19081, 81531-990, Curitiba-PR, Brazil;<br />
Tel: +55 41 33613174; Fax: +55 41 33613186;<br />
E-mail: pzarbin@quimica.ufpr.br<br />
The chemical structures <strong>of</strong> pheromones identified so far<br />
are diverse and their complexity ranges <strong>from</strong> simple n-<br />
alkanes to highly complex molecules bearing (multiple) cyclic<br />
substructures, double or triple bonds, heteroatoms,<br />
and/or (multiple) stereogenic centers. In many cases, only<br />
one stereoisomer or a defined mixture <strong>of</strong> stereoisomers is<br />
biologically active, while the unnatural isomers or a different<br />
ratio <strong>of</strong> isomers may be inactive or even inhibit the response<br />
to the natural compounds. Against this background, methods<br />
are required which lead in high yields and with high stereoselectivity<br />
to the desired compounds. Pheromone syntheses<br />
published over the last few decades have been reviewed repeatedly.<br />
The most comprehensive reviews are probably<br />
those written by Mori in 1981 and 1992 [2, 3]. Other accounts,<br />
relating pheromone synthesis to specific topics [4-6]<br />
and a partial, nevertheless impressive update [7] were published<br />
by the same author. Most recently, and reflecting a<br />
growing branch in organic synthesis, the application <strong>of</strong> biocatalysis<br />
to the synthesis <strong>of</strong> pheromones has been reviewed<br />
[8].<br />
In this article, we review the syntheses <strong>of</strong> pheromones<br />
published in the triennium <strong>2002</strong>-<strong>2004</strong>. The aim is to provide<br />
a comprehensive overview <strong>of</strong> the syntheses, and we sincerely<br />
apologize to the authors <strong>of</strong> those articles which may<br />
have escaped our attention. The presentation <strong>of</strong> the syntheses<br />
is done according to the compound class <strong>of</strong> the respective<br />
target compound, adopting the style established by Mori [3].<br />
2. SYNTHESIS OF ALKANES AS PHEROMONES<br />
2.1. 5,9-Dimethylpentadecane (1)<br />
The c<strong>of</strong>fee leaf miner, Leucoptera c<strong>of</strong>feella, is an economically<br />
important pest <strong>of</strong> c<strong>of</strong>fee trees in Brazil. It has been<br />
demonstrated by Francke and co-workers [9] that the main<br />
component <strong>of</strong> the female-produced sex pheromone <strong>of</strong> this<br />
species is 5,9-dimethylpentadecane (1), however, the stereochemistry<br />
<strong>of</strong> the natural pheromone remains unknown.<br />
Moreira and Corrêa [10] described an enantioselective<br />
synthesis <strong>of</strong> three stereoisomers <strong>of</strong> 1, <strong>from</strong> commercial<br />
isopulegol and synthetic neo-isopulegol [11, 12] (Scheme 1).<br />
Zarbin et al. [13] described a straightforward synthesis <strong>of</strong><br />
racemic 1 employing an unsymmetrical double Wittig olefination<br />
as the key reaction to build the carbon skeleton <strong>of</strong> the<br />
1385-2728/09 $55.00+.00 © 2009 Bentham Science Publishers Ltd.
300 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
OH<br />
1) B 2 H 6<br />
2) H 2 O 2 , NaOH,<br />
THF, 0 °C, 84%<br />
H<br />
OH<br />
OH<br />
1) NaH, BnBr, THF, 83%<br />
2) PCC, CH 2 Cl 2 , 93%<br />
3) m-CPBA/NaHCO 3 , 75%<br />
H<br />
O<br />
O<br />
(-)- isopulegol<br />
OBn<br />
1) MeOH, H + (cat), 93%<br />
2) TsCl, Py, 72%<br />
OTs<br />
n-BuMgBr, Li 2 CuCl 4<br />
3) LiAIH 4 , THF<br />
4) TsCl, Py, 93%<br />
OBn<br />
THF, -78 o C, 90%<br />
OBn<br />
1) H 2 , Pd/C, MeOH, 73%<br />
n-PrMgBr, Li 2 CuCl 4<br />
2) MsCl, Py, CH 2 Cl 2 , 91%<br />
THF, -78 o C, 90%<br />
OMs<br />
(5S,9S) - 1<br />
From<br />
(+)-neoisopulegol<br />
similarly<br />
OTs<br />
n-BuMgBr,<br />
Li 2 CuCl 4<br />
OBn<br />
OBn<br />
(5R,9S) - 1<br />
EtMgBr,<br />
Li 2 CuCl 4<br />
OBn<br />
Scheme 1.<br />
(5S,9R) - 1<br />
Br<br />
Br<br />
1) 1.1 equiv n-BuLi, - 90 o C<br />
2) 1 equiv 2-octanone, - 90 o C to rt.<br />
2.1 equiv PPh 3 , DMF, 92%<br />
3) 1.1 equiv n-BuLi, -90 o C<br />
4) 1 equiv 2-hexanone, -90 o C to rt., 64%<br />
H 2 , Pd/C,<br />
BrPh 3 P<br />
PPh 3 Br<br />
Scheme 2.<br />
hexane, 93%<br />
1 54% overall yield<br />
molecule. The bis-phosphonium salt obtained <strong>from</strong> 1,3-<br />
dibromopropane and triphenylphosphine, was reacted consecutively<br />
with the ketones 2-octanone and 2-hexanone, affording<br />
the asymmetric diene, which was readily hydrogenated<br />
over Pd/C, furnishing 1 in 54% overall yield (Scheme<br />
2). Synthetic 1 showed high biological activity when tested<br />
in field experiments.<br />
2.2. (S)-9-Methylnonadecane (2) and meso-13,23-<br />
dimethylpentatriacontane (3)<br />
(S)-9-Methylnonadecane (2) is a sex pheromone component<br />
<strong>of</strong> the cotton leafworm Alabama argillacea [14], and<br />
meso-13,23-dimethylpentatriacontane (3), is the sex pheromone<br />
<strong>of</strong> the tse tse fly Glossina pallidipes [14].
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 301<br />
H<br />
O<br />
H<br />
O<br />
H<br />
H<br />
H<br />
H<br />
Ref. [16]<br />
H<br />
HO<br />
CBr 4 , PPh 3 , CH 2 Cl 2 , 78%<br />
H<br />
Br<br />
O<br />
1) m-CPBA, MgSO 4 , CH 2 Cl 2<br />
OH<br />
O<br />
1) NaOEt, NaBH 4 , EtOH, 77%<br />
2) PTSA, EtOH, 59% overall<br />
H<br />
Br<br />
2) H 2 , Pd/C, EtOAc, 83%<br />
HO<br />
A<br />
O<br />
O<br />
1) PCC, CH 2 Cl 2 , 78%<br />
2) [C 7 H 15 PPh 3 ] + I - , n-BuLi,<br />
THF, -78 o C, 98%<br />
O<br />
O<br />
1) DIBAL-H, toluene, -78 o C, 86%<br />
2) [C 2 H 5 PPh 3 ] + I - , n-BuLi, THF,<br />
-78 o C, 92%<br />
3) H 2 , Pd/C, EtOAc, 95%<br />
( ) 8 ( ) 6<br />
2<br />
A<br />
1) PCC, CH 2 Cl 2 , 78%<br />
2) [C 9 H 19 PPh 3 ] + I - , n-BuLi,<br />
THF, -78 o C, 89%<br />
3) DIBAL-H, toluene, -78 o C, 80%<br />
B<br />
O<br />
A<br />
1) TBDPSCl, imidazole,<br />
DMAP, DMF, 81%<br />
2) DIBAL-H, toluene, -78 o C, 80%<br />
3) [C 6 H 13 PPh 3 ] + I - , n-BuLi,<br />
THF, -78 o C, 89%<br />
( ) 7 ( ) 4<br />
TBDPSO<br />
( ) 3<br />
1) TBAF, THF, 94%<br />
2) I 2 , PPh 3 , imidazole, CH 3 CN,<br />
Et 2 O, 0 o C to rt. 87%<br />
3) PPh 3 , toluene, reflux, 80%<br />
IPh 3 P<br />
1) n-BuLi, THF, B, -78 o C<br />
( ) 4<br />
2) H 2 , Pd/C, 99%<br />
( ) 10<br />
( ) 10<br />
3<br />
Scheme 3.<br />
Lamers et al. [15] reported the synthesis <strong>of</strong> these two<br />
pheromones starting <strong>from</strong> the readily available (+)-<br />
aromadendrene via the chiral intermediate A [16] (Scheme<br />
3).<br />
2.3. 7,11-Dimethylheptadecane (4)<br />
The hydrocarbons 7-methylheptadecane and 7,11-<br />
dimethylheptadecane (4) have been identified as constituents<br />
<strong>of</strong> the female-produced sex pheromone <strong>of</strong> the spring hemlock<br />
looper (Lambdina athasaria) and the pitch pine looper<br />
(L. pellucidaria) [17, 18]. Subsequently, bioassays confirmed<br />
that (S)-7-methylheptadecane and meso-4, that is<br />
(7S,11R), are the bioactive stereoisomers [19]. Chow et al.<br />
[20] described the synthesis <strong>of</strong> a mixture <strong>of</strong> all isomers <strong>of</strong> 4<br />
in 6 steps, starting <strong>from</strong> hepta-1,6-diene. Pure (R,R)-4 was<br />
synthesized by hydrolytic kinetic resolution <strong>of</strong> the bisepoxide<br />
obtained <strong>from</strong> hepta-1,6-diene using 1.4 % equiv. <strong>of</strong><br />
[(R,R)-(salen)Co(III)(OAc)]-Z complex (Fig. 1), followed by<br />
a Grignard reaction and methylation (Scheme 4).<br />
3. SYNTHESIS OF ALKENES AS PHEROMONES<br />
3.1. (6Z,9Z)-Heneicosa-6,9-diene (5), (3Z,6Z,9Z)-<br />
heneicosa-3,6,9-triene (6), and heneicosane (7)<br />
(6Z,9Z)-Heneicosa-6,9-diene (5), (3Z,6Z,9Z)-heneicosa-<br />
3,6,9-triene (6), and heneicosane (7), have been identified as
302 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
m-CPBA, CH 2 Cl 2<br />
1) n-C 5 H 11 MgBr, CuI,<br />
O O O<br />
O<br />
Et 2 O<br />
1) MeMgI, Et 2 O<br />
2) DMSO<br />
( ) 5 ( ) 5<br />
2) Jones Reagent.<br />
( ) 4 H 2 , Pd/C<br />
( ) 5<br />
( ) 5<br />
( ) 5<br />
racemic and meso-4<br />
O<br />
O<br />
1) (R,R)-Z, H 2 O<br />
O<br />
+<br />
HO<br />
O<br />
OH<br />
+<br />
O<br />
OH<br />
OH<br />
OH<br />
OH<br />
O<br />
O<br />
1) n-C 5 H 11 MgBr, CuI<br />
OMs<br />
OMs<br />
Me 2 CuLi,<br />
Scheme 4.<br />
2) MsCl, Et 3 N<br />
( ) 5 ( ) 5<br />
( ) 5 ( ) 5<br />
Et 2 O<br />
(R,R)-4<br />
t Bu<br />
H<br />
N<br />
H<br />
H 2 O<br />
N<br />
Co<br />
OAc O<br />
t Bu<br />
t Bu<br />
H<br />
N<br />
H<br />
H 2 O<br />
N<br />
Co<br />
OAc O<br />
t Bu<br />
Fig. (1).<br />
t Bu O t Bu<br />
(R,R)-Z<br />
t Bu O t Bu<br />
(S,S)-Z<br />
R<br />
O<br />
OH<br />
SOCl 2 , 50 o C<br />
benzene, 24h<br />
R<br />
O<br />
Cl<br />
O<br />
NH<br />
CHCl 3 , Py, 16h<br />
R<br />
O<br />
N<br />
O<br />
1) n-C 3 H 7 MgCl, CeCl 3 ,<br />
THF, -78 o C, 1.5 h<br />
2) 10% AcOH<br />
R<br />
O<br />
TsNH-NH 2<br />
EtOH, rt., 24h<br />
TsHN<br />
R<br />
N<br />
( ) 4 ( ) 7<br />
( ) 4<br />
( ) 16<br />
1) DIBAL-H, CH 2 Cl 2<br />
0 o C, 30 min<br />
2) 3N NaOH<br />
5<br />
6<br />
7<br />
Scheme 5.<br />
pheromone components <strong>of</strong> Achaea janata, a destructive oligophagus<br />
insect for castor crops, especially when young<br />
crops are attacked.<br />
Badioli et al. [21] described the synthesis <strong>of</strong> these three<br />
hydrocarbons <strong>from</strong> linoleic, linolenic, and stearic acid, respectively,<br />
by addition <strong>of</strong> organocerium reagents to the corresponding<br />
morpholine amides. The resulting propyl ketones<br />
were reduced via their tosylhydrazones (Scheme 5).<br />
3.2. (9E,11Z)-Hexadeca-9,11-dienal (8)<br />
(9E,11Z)-Hexadeca-9,11-dienal (8) has been identified as<br />
a female-produced sex pheromone <strong>of</strong> the pecan nut casebearer<br />
(Acrobasis nuxvorella) [22].
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 303<br />
O<br />
OH<br />
H<br />
MeC(OEt) 3 , H +<br />
O<br />
OEt<br />
basic Alumina,<br />
benzene<br />
O<br />
OEt<br />
1) LiAlH 4 , Et 2 O, 0 o C<br />
2) Ac 2 O, Py<br />
OAc<br />
1) BrMg(CH 2 ) 7 OTHP, CuI<br />
2) PTSA, MeOH<br />
(E,Z:E,E 2:1)<br />
OH<br />
1) tetracyanoetylene, THF<br />
2) P 2 O 5 , DMSO, then Et 3 N<br />
8<br />
O<br />
H<br />
H<br />
1) n-BuLi, Et 2O<br />
2) acrolein<br />
OH<br />
MeC(OEt) 3 , H +<br />
O<br />
OEt<br />
1) LiAlH 4 , Et 2 O, 0 o C<br />
2) TsCl, Et 3 N<br />
OTs<br />
1) BrMg(CH 2 ) 5 OTHP, CuI, -78 o C<br />
2) PTSA, MeOH<br />
3) recrystallization<br />
OH<br />
1) Zn, C 2 H 4 Br 2 , LiCuBr 2<br />
2) P 2 O 5 , DMSO, then Et 3 N<br />
O<br />
H<br />
>99% E<br />
8<br />
Scheme 6.<br />
HO<br />
Br<br />
1) Ref. [25]<br />
2) 2-propyne-1-ol/LiNH 2 , fl. NH 3<br />
THPO<br />
OH<br />
1) LiAlH 4 , Et 2 O, rt.<br />
2) (COCl) 2 , DMSO<br />
3) Et 3 N, CH 2 Cl 2 , -78 o C<br />
THPO<br />
O<br />
H<br />
Separation <strong>of</strong> (E,E)-isomer by<br />
[n-BuPPh3] + Br -<br />
NaHMDS, THF, -20 o C<br />
1) PTSA, MeOH, rt.<br />
THPO<br />
H<br />
Diels-Alder reaction with<br />
tetracyanoethylene<br />
2) (COCl) 2 , DMSO<br />
3) Et 3 N, CH 2 Cl 2 , -78 o C<br />
O<br />
Scheme 7.<br />
9<br />
Two alternative syntheses were described by Passaro and<br />
Webster [23]. The key steps in both sequences is an orthoester<br />
Claisen rearrangement (Scheme 6).<br />
3.3. (8E,10Z)-8,10-Tetradecadienal (9)<br />
Francke et al. described the synthesis <strong>of</strong> (8E,10Z)-8,10-<br />
tetradecadienal (9), the female produced sex pheromone <strong>of</strong><br />
the horse-chestnut leafminer (Cameraria ohridella) [24].<br />
The synthesis <strong>of</strong> 9 was carried out in 30% overall yield,<br />
starting <strong>from</strong> 7-bromoheptanol. The (8E) configuration was<br />
achieved by stereoselective reduction <strong>of</strong> an acetylene, while<br />
the (10Z) configuration results <strong>from</strong> a stereoselective Wittig<br />
reaction (Scheme 7).<br />
4. SYNTHESIS OF EPOXY PHEROMONES<br />
4.1. (6Z,9Z,11S,12S)-trans-11,12-Epoxyheneicosa-6,9-<br />
diene (10) (Posticlure)<br />
Wakamura et al. [26] identified posticlure [(6Z,9Z,<br />
11S,12S)-trans-11,12-epoxyheneicosa-6,9-diene, 10] as the<br />
female-produced pheromone <strong>of</strong> the tussock moth Orgyia<br />
postica. Fernandes and Kumar [27] described a highly enantioselective<br />
synthesis <strong>of</strong> (+)- and (-)-posticlure employing<br />
the Sharpless asymmetric dihydroxylation <strong>of</strong> olefin A or the<br />
regio- and stereoselective mono-dihydroxylation <strong>of</strong> the trans<br />
olefin bond <strong>of</strong> the (Z,Z,E)-triene B to obtain the enantiomerically<br />
pure diols C and D, which were transformed into (+)-
304 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
OH<br />
O<br />
O<br />
H<br />
(DHQ) 2 -PHAL or (DHQD) 2 -PHAL, ( ) 8 OEt<br />
OsO<br />
O<br />
4 , MeSO 2 NH 2 , K 3 Fe(CN) 6 ,<br />
OH<br />
Ph 3 P=CHCO 2 Et,<br />
K 2 CO 3 , t-BuOH/H 2 O [1:1],<br />
or<br />
THF, rt., 12 h, 86% ( ) 8 OEt<br />
OH O<br />
A<br />
24 h, 0 o C, 94%<br />
( ) 4<br />
( ) 8 OEt<br />
OH<br />
1) 2,2-DMP, (CH 3 ) 2 CO,<br />
O<br />
1) (COCl) 2 , DMSO, CH 2 Cl 2 ,<br />
O<br />
PTSA, rt., 8 h, 99%<br />
( ) 8 OH Et 3 N, -78 o to -60 o C<br />
( )8<br />
( ) 8 OEt<br />
( ) 8<br />
( ) 4<br />
O<br />
O<br />
2) LiAlH 4 , Et 2 O,<br />
2) [(Z)-C 5 H 11 CH=CHCH 2 CH 2 P + Ph 3 ]I - ,<br />
0 o C to rt., overnight, 97%<br />
n-BuLi, THF, -80 o C, 8 h, 76%<br />
3N HCl, MeOH, rt., 12 h, 90%<br />
OH<br />
OH<br />
( ) 8 or ( ) 8<br />
( ) 4<br />
OH<br />
OH<br />
C<br />
D<br />
O<br />
1) DIBAL-H, Et 2 O, 0 o C, 0.5 h, 90%<br />
A<br />
2) PCC, CH 2 Cl 2 , rt., 8 h<br />
B<br />
3) [(Z)-C 5 H 11 CH=CHCH 2 CH 2 P + Ph 3 ]I - ,<br />
LiHMDS, THF, -80 o C, 8 h, 74%<br />
(DHQ) 2 -PHAL, OsO 4 , MeSO 2 NH 2 ,<br />
K 3 Fe(CN) 6 , K 2 CO 3 , t-BuOH/H 2 O [1:1],<br />
( ) 4<br />
( ) 4<br />
OH<br />
B<br />
10 h, 0 o C, 78%<br />
( ) 8<br />
OH<br />
C<br />
(DHQD) 2 -PHAL, OsO 4 , MeSO 2 NH 2 ,<br />
K 3 Fe(CN) 6 , K 2 CO 3 , t-BuOH/H 2 O [1:1],<br />
OH<br />
B<br />
10 h, 0 o C, 79%<br />
OH<br />
D<br />
C or D<br />
( ) 8<br />
(+) - 10<br />
1) CH 3 C(OMe) 3 , PTSA (cat),<br />
CH 2 Cl 2 , rt, 30 min<br />
( )8<br />
OAc<br />
( ) 8<br />
( ) 8<br />
( )4<br />
+<br />
( ) 4<br />
( ) 4<br />
Br<br />
2) CH 3 COBr, CH 2 Cl 2 , rt., 4 h<br />
Br<br />
OAc<br />
Scheme 8.<br />
K 2 CO 3 , MeOH, rt., 4 h,<br />
86 - 88% overall<br />
H<br />
H<br />
( )<br />
( )<br />
4 or<br />
4<br />
( ) H<br />
( ) 8 H<br />
8<br />
O<br />
O<br />
(-) - 10<br />
and (-)-10 via the respective acetoxybromides in a one-pot<br />
reaction (Scheme 8).<br />
4.2. (3Z)-cis-6,7-cis-9,10-Diepoxyheneicos-3-ene (11) (leucomalure)<br />
Gries et al. identified leucomalure [(3Z)-cis-6,7-cis-9,10-<br />
diepoxyheneicos-3-ene, 11] as the major component <strong>of</strong> the<br />
female-produced sex pheromone <strong>of</strong> the Satin moth, Leucoma<br />
salicis [28]. Muto and Mori [29] employed the lipase PS-<br />
C(Amano)-catalyzed asymmetric acetylation <strong>of</strong> (±)-4-(tertbutyldiphenylsilyloxy)-cis-2,3-epoxybutan-1-ol,<br />
which afforded<br />
the (2R,3S)-epoxy alcohol A and the (2S,3R)-<br />
epoxyacetate B as optically active building blocks to prepare<br />
all isomers <strong>of</strong> 11 (Scheme 9).
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 305<br />
HO<br />
OH<br />
1) NaH, TBDPSCl, THF, 92%<br />
TBDPSO<br />
O<br />
OH<br />
Lipase PS-C,<br />
CH 2 =CHOAc, Et 2 O<br />
2) m-CPBA, CH 2 Cl 2 , 94%<br />
TBDPSO<br />
O<br />
OH<br />
+<br />
TBDPSO<br />
O<br />
OAc<br />
(2R,3S)-A<br />
49%, 99.5% e.e.<br />
(2S,3R)-B<br />
48%, 98.1% e.e.<br />
K 2 CO 3 , MeOH, 99%<br />
TBDPSO<br />
O<br />
OH<br />
(2S,3R)-A<br />
98.1% e.e.<br />
TBDPSO<br />
O<br />
OH<br />
n-BuLi, Tf 2 O; then<br />
THF, HMPA, 77%<br />
Me(H 2 C) 10 C CLi<br />
TBDPSO<br />
O<br />
( ) 10<br />
(2R,3S)-A<br />
1) H 2 , Pd/CaCO - 3 Pb + 2 , cyclohexane<br />
2) m-CPBA, CH 2 Cl 2 ; then MPLC<br />
separation.<br />
1) TBAF, THF, 81%<br />
2) n-BuLi, Tf 2 O; then<br />
THF, HMPA, 77%<br />
Et<br />
O O<br />
TBDPSO<br />
(2S,3R,5R,6S)-C<br />
( ) 10<br />
( ) 10<br />
( ) 10<br />
O O<br />
O O<br />
TBDPSO<br />
+ TBDPSO<br />
( ) 10<br />
(2S,3R,5S,6R)-C 23%<br />
(2S,3R,5R,6S)-C 58%<br />
Me(H 2 C) 10 C CLi<br />
O O<br />
H 2 , Pd/CaCO - 3 Pb + 2 ,<br />
O O<br />
cyclohexane<br />
Et<br />
( ) 10<br />
Et<br />
( ) 10<br />
(3Z,6S,7R,9S,10R)-11<br />
Similarly<br />
O O<br />
(3Z,6S,7R,9R,10S)-11<br />
O O<br />
TBDPSO<br />
O<br />
OH<br />
Similarly<br />
Et<br />
(3Z,6R,7S,9R,10S)-11<br />
( ) 10<br />
(2S,3R)-A<br />
O<br />
O<br />
Et<br />
( ) 10<br />
Scheme 9.<br />
All four isomers <strong>of</strong> 11 have also been synthesized by<br />
Wimalaratne and Slessor, using D-xylose as the optically<br />
pure starting material [30]. The epoxy alcohol A was transformed<br />
to chain-elongated epoxy alcohols B and C, respectively,<br />
which were subsequently epoxidized by the method<br />
<strong>of</strong> Sharpless and finally alkenylated to give the pure isomers<br />
<strong>of</strong> 11 (Scheme 10).<br />
(3Z,6R,7S,9S,10R)-11<br />
4.3. (6Z)-cis-9,10-Epoxyheneicos-6-ene (12) and (6Z)-cis-<br />
9,10-epoxyeicos-6-ene (13)<br />
The pure enantiomers <strong>of</strong> epoxide A used in Mori’s synthesis<br />
<strong>of</strong> 11 [29] (Scheme 9) were also the key intermediates<br />
for the synthesis <strong>of</strong> the enantiomers <strong>of</strong> (6Z)-cis-9,10-<br />
epoxyheneicos-6-ene (12) and (6Z)-cis-9,10-epoxyeicos-6-<br />
ene (13) [31] (Scheme 11).
306 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
HO<br />
HO<br />
O<br />
OH<br />
OH<br />
1) EtSH/H +<br />
2) acetone/I 2<br />
3) t-BuOK<br />
O<br />
O<br />
OH<br />
SEt<br />
SEt<br />
1) LiAlH 4<br />
2) TBDMSCl .<br />
3) HgO/BF 3 Et 2 O<br />
O<br />
O<br />
OH<br />
CHO<br />
O<br />
O<br />
OTBDMS<br />
CHO<br />
1) [Me(CH 2 ) 8 PPh 3 ] + Br -<br />
2) H 2 , Pd/C,<br />
3) TFA, aq. THF<br />
HO<br />
OH<br />
OH<br />
1) TsCl<br />
( ) 10<br />
OH<br />
2) K 2 CO 3<br />
O<br />
( )10<br />
A<br />
A<br />
1) TBDMSCl<br />
2) TBDMSOCH 2 CC - Li + ,<br />
BF 3 .Et 2 O<br />
3) TsCl<br />
OTBDMS<br />
TBDMSO<br />
1) TsCl<br />
2)TBDMSOCH 2 CC - Li + ,<br />
BF 3 . Et 2 O<br />
3)K 2 CO 3<br />
O<br />
TBDMSO<br />
OTs<br />
( ) 10<br />
( ) 10<br />
O<br />
O<br />
OH<br />
HO<br />
( ) 10 ( ) 10<br />
B<br />
1) TBAF<br />
1) TBAF<br />
2) P<br />
2) P 2 -Ni, H 2 -Ni, H 2<br />
2<br />
B<br />
C<br />
1) (+)-(L)-DET<br />
1) (-)-(D)-DET<br />
2) TsCl<br />
2) TsCl<br />
3) (C 4 H 7 ) 2 CuLi<br />
3) (C 4 H 7 ) 2 CuLi<br />
O<br />
O<br />
O<br />
O<br />
( ) 10 Et<br />
( )10<br />
(Z)-3-(6S,7R,9S,10R)-11<br />
(Z)-3-(6R,7S,9S,10R)-11<br />
C<br />
Et<br />
1) (+)-(L)-DET<br />
2) TsCl<br />
3) (C 4 H 7 ) 2 CuLi<br />
1) (-)-(D)-DET<br />
2) TsCl<br />
3) (C 4 H 7 ) 2 CuLi<br />
O<br />
O<br />
O<br />
O<br />
Et<br />
( ) 10 Et<br />
( ) 10<br />
(Z)-3-(6R,7S,9R,10S)-11<br />
(Z)-3-(6S,7R,9R,10S)-11<br />
Scheme 10.<br />
5. SYNTHESIS OF NON-ISOPRENOIDAL PHERO-<br />
MONE ALCOHOLS AND THEIR ESTERS<br />
5.1. 2-Methyl-4-octanol (14)<br />
2-Methyl-4-octanol (14) has been described as a component<br />
<strong>of</strong> the aggregation pheromones <strong>of</strong> several weevil species<br />
[32, 33]. Baraldi et al. [34] reported the enantioselective<br />
synthesis <strong>of</strong> (R)- and (S)-14 starting <strong>from</strong> isovaleryl chloride.<br />
The key step <strong>of</strong> this synthetic route is the asymmetric reduction<br />
<strong>of</strong> ethyl 5-methyl-3-oxohexanoate with Saccharomyces<br />
cerevisiae to the corresponding hydroxyester (S)-A in<br />
high enantiomeric excess (Scheme 12). The (S) isomer was
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 307<br />
TBDPSO<br />
O<br />
OH<br />
n-BuLi, Tf 2 O<br />
TBDPSO<br />
O<br />
OTf<br />
LiC<br />
C(CH 2 ) 4 Me, THF<br />
A<br />
HMPA, 74% overall<br />
TBDPSO<br />
TsO<br />
O<br />
O<br />
( ) 4 Similarly<br />
O<br />
H 1) TBAF, THF, 99%<br />
2 , Pd/CaCO 3 -Pb<br />
+ 2<br />
TBDPSO<br />
( ) 4<br />
cyclohexane, quant.<br />
2) TsCl, Py, 77%<br />
O<br />
(n-C 10 H 21 ) 2 CuLi, Et 2 O, 80%<br />
( ) 10 ( ) 4<br />
(9S,10R)-12<br />
( ) 4<br />
(n-C<br />
O<br />
9 H 19 ) 2 CuLi, Et 2 O, 80%<br />
TBDPSO<br />
O<br />
OH<br />
( ) 9 ( ) 4<br />
O<br />
(9S,10R)-13<br />
( ) 10 ( ) 4<br />
(9R,10S)-12<br />
A<br />
O<br />
( ) 9 ( ) 4<br />
Scheme 11.<br />
(9R,10S)-13<br />
O<br />
LiCH 2 CO 2 Et, 85%<br />
Cl<br />
1) p-NO 2 C 6 H 6 CO 2 H<br />
Ph 3 P, DEAD<br />
OH<br />
O<br />
CO 2 Et<br />
CO 2 Et<br />
S. cerevisiae<br />
allyl alcohol<br />
50%, 99% e.e.<br />
OH<br />
(S) - A<br />
CO 2 Et<br />
2) NaOH, EtOH<br />
70%, 99% e.e.<br />
(R) - A<br />
(R) - A or (S) - A<br />
1) LiAlH 4 , THF, 85%<br />
OH<br />
or<br />
OH<br />
2) TsCl, Et 3 N, 80%<br />
3) EtMgBr,<br />
(R) - 14<br />
(S) - 14<br />
Scheme 12.<br />
Li 2 CuCl 4 , 70%<br />
prepared in five steps and 20% overall yield, while the (R)<br />
enantiomer was obtained in six steps and 14% overall yield.<br />
The key step <strong>of</strong> the synthesis <strong>of</strong> (R)-14 described by<br />
Dhotare et al. [35] is the K-selectride reduction <strong>of</strong> the intermediate<br />
ketone A obtained <strong>from</strong> D-mannitol. The reduction<br />
proceeded with absolute syn selectivity (Scheme 13).<br />
D-mannitol was also used by Zarbin et al. [36] to obtain<br />
(S)-14 by a new and higly enantioselective approach, involving<br />
the known (R)-glyceraldehyde acetonide A as key intermediate<br />
(8.8% overall yield) (Scheme 14).<br />
5.2. 4-Methylheptan-3-ol (15)<br />
(3S,4S)-4-Methylheptan-3-ol [(3S,4S)-15] is the major<br />
component <strong>of</strong> the aggregation pheromone <strong>of</strong> the bark beetles<br />
Scolytus scolytus and S. multistriatus [37-40]. Recently,<br />
(3S,4S)-15 was tentatively identified as the main component<br />
<strong>of</strong> the aggregation pheromone <strong>of</strong> the almond bark beetle,<br />
Scolytus amygdali, along with (3S,4S)-4-methyl-3-hexanol,<br />
which functions as a synergist. Substitution <strong>of</strong> the pure<br />
(3S,4S) isomer with racemic 4-methyl-3-heptanol in field<br />
tests resulted in a lower trap catch <strong>of</strong> beetles in the field,<br />
indicating the possibility that one or more <strong>of</strong> the unnatural<br />
stereoisomers has an inhibitory effect [41].<br />
Zada et al. [42] described the synthesis <strong>of</strong> all four<br />
stereoisomers <strong>of</strong> 15. Key steps included preparation <strong>of</strong> enantiomerically<br />
pure (R)- and (S)-4-methyl-3-heptanone (A) by<br />
the SAMP/RAMP method, reduction to the corresponding<br />
alcohols, and stereospecific transesterification with vinyl<br />
acetate by lipase AK catalysis (Scheme 15). In field tests,
308 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
D-Mannitol<br />
O O<br />
OH<br />
Steps<br />
A<br />
1) n-BuMgBr, THF<br />
K-selectride,<br />
2) TFA, H 2 O, CH 2 Cl 2 OBn<br />
2) NaH, DMSO,<br />
O O<br />
O O<br />
THF, -78 o C<br />
CHO<br />
O<br />
2) PCC, CH 2 Cl 2<br />
1) NaH, BnBr, THF<br />
OH<br />
HO<br />
1) NaIO 4 , aq. MeCN<br />
[Me 2 CHPPh + 3 ]Br - , THF<br />
H 2 , Pd/C, EtOH<br />
OH<br />
Scheme 13.<br />
OBn<br />
(R) - 14<br />
HO<br />
OH OH<br />
OH OH<br />
OH<br />
MeO OMe<br />
1) SnCl 2 , , 55%<br />
2) NaIO 4 , NaHCO 3 , CH 2 Cl 2 , 61%<br />
O<br />
O<br />
A<br />
O<br />
H<br />
1) [n-C 3 H 7 PPh 3 + Br] - ,<br />
n-BuLi, THF, 88%<br />
2) H 2 , Pd/CaCO 3 , hexane, 81%<br />
O<br />
O<br />
1) acidic DowexÆ W 50 ,<br />
H 2 O, 79%<br />
TsO<br />
OH<br />
i-C 3 H 7 MgBr,<br />
OH<br />
2) TsCl, Py, 60%<br />
CuI, THF, 78%<br />
(S)-14<br />
Scheme 14.<br />
8.8% overall yield; 99.5% e.e.<br />
O<br />
Ref. 43<br />
LiAlH 4 , Et 2 O, 25 o C<br />
Lipase AK, vinyl acetate<br />
O<br />
(S) - A<br />
OH<br />
+<br />
KOH, MeOH<br />
OH<br />
(3S,4S)-15<br />
OAc<br />
OH<br />
(3R,4S)-15<br />
Similarly<br />
OH<br />
(3R,4R)-15<br />
Scheme 15.<br />
O<br />
(R) - A<br />
OH<br />
(3S,4R)-15<br />
only (3S,4S)-15 attracted beetles in combination with the<br />
synergist (3S,4S)-4-methyl-3-hexanol, whereas the (3R,4S)<br />
and (3R,4R) isomers were inhibitory.<br />
5.3. (2S,3R)-3-Methylpentadecan-2-ol (16)<br />
Larsson et al. [44] described the synthesis <strong>of</strong> (2S,3R)-3-<br />
methylpentadecan-2-ol [(2S,3R)-16], a putative pheromone<br />
precursor isolated <strong>from</strong> some pine sawflies <strong>of</strong> the genus Gilpinia.<br />
The enantiomers <strong>of</strong> 2-methyl-3-(phenylsulfanyl)propanal<br />
[(S)-A or (R)-A] were prepared <strong>from</strong> readily available<br />
(S)- and (R)-3-hydroxy-2-methylpropanoic acid methyl ester<br />
and were reacted with dimethylzinc to give the isomers<br />
(2S,3S)-B or (2R,3R)-B, respectively, both <strong>of</strong> high d.e. and<br />
e.e. These products were further purified by lipase catalysed
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 309<br />
HO<br />
O<br />
OMe<br />
1) (PhS) 2 , (n-Bu) 3 P, DMF,<br />
0 o C, rt., 95%<br />
PhS<br />
OH<br />
1) DMSO, oxalyl chloride, -78 o C<br />
2) DIPEA, CH 2 Cl 2 , -78 o C<br />
PhS<br />
O<br />
H<br />
2) LiAlH 4 , THF, 96%<br />
3) extractive workup with KH 2 PO 4<br />
(R)-A or (S)-A<br />
CH 2 Cl 2 , -78 o C,<br />
TiCl 4 (1.0 equiv),<br />
PhS<br />
OH<br />
+<br />
PhS<br />
OH<br />
+<br />
PhS<br />
OH<br />
+<br />
PhS<br />
OH<br />
10 min, Me 2 Zn (1.0 equiv)<br />
75% 2 steps<br />
(2S,3S)-B (2R,3S)-B (2R,3R)-B (2S,3R)-B<br />
From (S) - A 91,5% 7% 1.4% 0.1%<br />
From (R) - A 2.9% 0.2% 92% 4.9%<br />
Mixture <strong>of</strong> the<br />
stereoisomers<br />
<strong>of</strong> B obtained<br />
<strong>from</strong> (S)-A<br />
CAL-B 9%<br />
OH<br />
PhS<br />
>1000/1 d.r.<br />
1) TBDMSCl, DMF, imidazole, 99%<br />
2) m-CPBA, CH 2 Cl 2 , 88%<br />
O 2 SPh<br />
OTBDMS<br />
>99.9% e.e.<br />
1) THF, DMPU, -40 o C, n-BuLi (2.1 equiv),<br />
up to 0 o C, cool to -40 o C<br />
90% yield<br />
PhSO 2<br />
OTBDMS<br />
2) 1-Iodoundecane (1.2 equiv),<br />
THF, up to 20 o C (96%)<br />
1) 10% Na/Hg, MeOH, Na 2 HPO 4 , rt., 94%<br />
OH<br />
2) i) TBAF, THF, reflux<br />
ii) acetylchloride, Py, CH 2 Cl 2 , 84%<br />
3) i) Raney Ni, EtOH, H 2. ii) KOH/MeOH, rt., 82%<br />
16<br />
Scheme 16.<br />
acylation to give the enantiomerically and diastereomerically<br />
highly pure enantiomers (>99% d.e., >99.9% e.e.). Pure<br />
(2S,3S)-B was transformed to (2S,3R)-16 in 54% yield over<br />
eight steps (Scheme 16).<br />
5.4. 3-Methylpentadecan-2-ol (16), 3,7-dimethyltridecan-<br />
2-ol (17), 3,7,11-trimethyltridecan-2-ol (18), 3,7,9-<br />
trimethyltridecan-2-ol (19), and 3,7-dimethyltetradecan-<br />
2-ol (20)<br />
Hedenström et al. [45] reported the synthesis <strong>of</strong> precursors<br />
<strong>of</strong> the sex pheromones <strong>of</strong> females <strong>of</strong> pine sawfly species<br />
[46-49]. The key reaction sequence in the syntheses was the<br />
ring opening <strong>of</strong> either cis- or racemic trans-2,3-epoxybutane<br />
using a higher order cyanocuprate as nucleophile, obtained<br />
<strong>from</strong> iodides or chlorides E – I, followed by a highly efficient<br />
lipase catalysed stereoselective acylation <strong>of</strong> the resulting<br />
3-methylalkan-2-ols (Scheme 17).<br />
5.5. (2S,3R,7RS)-3,7-Dimethyltridec-2-yl acetate (21) and<br />
propanoate (22)<br />
3,7-Dimethyltridec-2-yl acetate (21) and propanoate (22)<br />
are sex attractants <strong>of</strong> the sawfly Diprion pini [48].<br />
Bekish et al. [50] described a synthesis <strong>of</strong> a mixture <strong>of</strong><br />
the diastereomers (2S,3R,7S)- and (2S,3R,7R)-21, as well as<br />
(2S,3R,7S)- and (2S,3R,7R)-22 by cyclopropanation <strong>of</strong> the<br />
ethoxycarbonyl group in O-THP protected ethyl (S)-lactate<br />
with ethylmagnesium bromide in the presence <strong>of</strong> titanium(IV)<br />
isopropoxide, and subsequent C2–C3 ring opening<br />
<strong>of</strong> the resulting cyclopropanol (Scheme 18). The resulting<br />
(S) configured bromoalkenol A (stereoisomeric purity 98%)<br />
was chain-elongated and hydrogenated. The (3R) configuration<br />
was established by esterification with phthalic anhydride<br />
followed by salt formation with pure (S)-1-phenylethylamine<br />
and several recrystallisations <strong>of</strong> this salt to give the alcohol<br />
with 92 % e.e. at C-3.
310 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
O<br />
1) t-BuLi, THF<br />
2) 1-iodohexane<br />
O<br />
1) (Ph 3 P) 2 NiCl 2 , benzene<br />
2) MeMgBr<br />
3) add 2-hexyl-4,5-dihydr<strong>of</strong>uran,<br />
80 o C 5 h<br />
OH<br />
Pd/C, H 2 MeOH<br />
OH<br />
A<br />
R<br />
OH<br />
R = 1-hexyl S or R<br />
R = 2-hexyl<br />
PPh 3 , Br 2 , CH 2 Cl 2<br />
R<br />
Br<br />
1) Na(s), EtOH<br />
2) CH 2 (CO 2 Et) 2<br />
3) KOH, EtOH<br />
4) 180 - 200 o C<br />
R<br />
O<br />
OH<br />
R = 1-(3-methylpentyl)<br />
LiAlH 4 , Et 2 O<br />
R<br />
OH<br />
B R = 1-hexyl S or R<br />
C R = 2-hexyl<br />
D R = 1-(3-methylpentyl)<br />
A, B, C, or D<br />
PPh 3 , CCl 4 or<br />
PPh 3 , I 2 , imidazole,<br />
THF/MeCN<br />
1) Li, hexane<br />
R<br />
X<br />
R'<br />
2) add to MeCu(CN)Li,<br />
Et 2 O, -78 o C<br />
3) add cis- or racemic<br />
trans-epoxybutane<br />
E R = 1-pentyl, R' = CH 3 , X = I<br />
F R = 1-hexyl, R' = CH 3 , X = I, S or R<br />
G R = 2-hexyl, R' = CH 3 , X = Cl or I<br />
H R = 1-(3-methylpentyl), R' = CH 3 , X = I<br />
and I - 1-Chlorododecane<br />
OCOR''<br />
R<br />
OH<br />
lipase, vinyl ester,<br />
heptane, 3 Å.<br />
*<br />
R<br />
*<br />
R'<br />
threo-(2R,3R) or erythro-(2R,3S) esters<br />
R'' = Me, Pr, or Bu<br />
R'<br />
threo or erythro 16-20<br />
+<br />
OH<br />
17 R = 1-pentyl, R' = CH 3 ,<br />
18 R = 1-hexyl, R' = CH 3 , S or R<br />
19 R = 2-hexyl, R' = CH 3 ,<br />
20 R = 1-(3-methylpentyl), R' = CH 3 ,<br />
*<br />
R<br />
*<br />
R'<br />
threo-(2S,3S) or erythro-(2S,3R)<br />
16 R = 1-heptyl, R' = H<br />
Scheme 17.<br />
5.6. 3,7-Dimethyltridec-2-yl propanoate (23)<br />
Dandapani et al. described a synthesis <strong>of</strong> all 16 stereoisomers<br />
<strong>of</strong> 3,7-dimethyltridec-2-yl propanoate (23), the sex<br />
pheromone <strong>of</strong> the pine sawfly Microdiprion pallipes, by a<br />
fluorous mixture-synthesis approach [51]. Each <strong>of</strong> the four<br />
stereoisomers <strong>of</strong> 2-methyl-1,3-butanediol was marked separately<br />
with a different fluorine-containing group, then the<br />
quasi isomers were mixed and subjected to reactions, and<br />
finally demixed by fluorous silica chromatography, making<br />
use <strong>of</strong> the different fluorine tag <strong>of</strong> each isomer. In the first<br />
step <strong>of</strong> the reaction sequence, each <strong>of</strong> the cuasi isomer in the<br />
mixture M-1 was reduced, partially oxidized, then the mixture<br />
was split and each part chain-elongated using the chiral<br />
building block (S)-E or (R)-E. Each mixture obtained [M-2<br />
(R) and M-2 (S)] was split again and chain-elongated sepa-
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 311<br />
OH<br />
CO 2 Et<br />
1) DHP, PPTS (5 mol %),<br />
CH 2 Cl 2 , 89%<br />
2) EtMgBr, Ti(Oi-Pr) 4 ,<br />
Et 2 O/THF<br />
OTHP<br />
OH<br />
1) MsCl, Et 3 N, Et 2 O.<br />
2) MgBr 2 , CHCl 3 /Et 2 O<br />
59% (3 steps)<br />
OH<br />
A<br />
Br<br />
1) DHP, PPTS (5 mol %), CH 2 Cl 2 , 96%<br />
OTHP<br />
1) MeOH, PPTS (5 mol %.), 95%<br />
2) 3-methylnonylmagnesium bromide,<br />
CuI (5 mol %), 91%<br />
.<br />
2) NaBH 4 , NiCl 2 .6H 2 O, MeOH, 86%<br />
OH<br />
1) phthalic anhydride, Et 3 N, benzene<br />
OH<br />
CH 3 COCl or C 2 H 5 COCl,<br />
Et 3 N, Et 2 O, 85 - 90%<br />
OR<br />
2) (S)-(-)-1-phenylethylamine, acetone<br />
3) four recrystallizations <strong>from</strong> acetone<br />
4) KOH, MeOH, 33% overall yield<br />
Scheme 18.<br />
(2S, 3R, 7RS)-21 R=COMe<br />
(2S, 3R, 7RS)-22 R=COEt<br />
rately with the same reagent (S)-E or (R)-E, giving rise to<br />
four mixtures M-3. After hydrogenation, each mixture was<br />
separated by HPLC and the fluorine-containing group was<br />
removed to give the target compounds (Scheme 19).<br />
5.7. (R)-2-Methyl-4-octanol (14), (R)- and (S)-3-octanol<br />
(24), (R)-2-dodecanol (25), and (R)-2-methyl-4-heptanol<br />
(26)<br />
(R)-3-Octanol [(R)-24] is the sex attractant pheromone <strong>of</strong><br />
the ant Myrmica scabrinodis [52] while (S)-24 is an alarm<br />
pheromone found in the ants Crematogaster castanea and C.<br />
liengmei [53, 54]. (R)-2-Dodecanol (25) is a component <strong>of</strong><br />
the hind leg tibial gland secretion <strong>of</strong> worker ants <strong>of</strong> C. auberti<br />
[55]. (R)-2-Methyl-4-heptanol (26) and (R)-2-methyl-4-<br />
octanol (14) were identified as the male-produced aggregation<br />
pheromones <strong>of</strong> the West Indian sugarcane weevils<br />
Metamasius hemipterus [32, 56]. Scheme 20 shows the synthesis<br />
<strong>of</strong> the optically active insect pheromones 14 and 24-26<br />
described by Cho and Kim, starting <strong>from</strong> enantiomerically<br />
pure -hydroxy sulfides [57]. The -hydroxy sulfides were<br />
OH<br />
OH<br />
1) TMSCl, ET 3 N<br />
C 6 H 4 -p-O(CH 2 ) 3 Rf<br />
2) TMSOTf,<br />
O<br />
O<br />
Rf(CH 2 ) 3 OC 6 H 6 CHO (A-D),<br />
4 isomers<br />
3) Mix in equimolar amts<br />
A: Rf = C 4 F 9 (S,S)<br />
B: Rf = C 6 F 13 (R,S)<br />
C: Rf = C 7 F 15 (S,R)<br />
M-1 (4 quasi isomers)<br />
M-1<br />
1) DIBAL-H<br />
2) Dess -<br />
Martin<br />
periodinane<br />
(S) - E<br />
NaHMDS<br />
(R) - E<br />
NaHMDS<br />
O F PAB<br />
D: Rf = C 8 F 17 (R,R)<br />
OTBS<br />
M-2 (R), 90%<br />
O F PAB<br />
OTBS<br />
M-2 (S), 89%<br />
Ph<br />
N<br />
N<br />
N N<br />
Ph<br />
N<br />
N<br />
N N<br />
O<br />
S<br />
O<br />
O<br />
S<br />
O<br />
(S) - E<br />
(R) - E<br />
OTBS<br />
OTBS
312 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
Scheme 19. Contd….<br />
M-2 (R)<br />
1) TBAF<br />
2) Dess -<br />
Martin<br />
periodinane<br />
(S) - E<br />
NaHMDS<br />
(R) - E<br />
NaHMDS<br />
O F PAB<br />
M-3 (R,R), 75%<br />
O F PAB<br />
M-3 (R,S), 75%<br />
OTBS<br />
OTBS<br />
1) TBAF<br />
2) Dess-Martin<br />
periodinane<br />
3) CH 2 =PPh 3<br />
4) NH=NH<br />
O F PAB<br />
M-4 (R,R), 77%<br />
O F PAB<br />
M-4 (R,S), 77%<br />
(S) - E<br />
O F PAB<br />
O F PAB<br />
M-2 (S)<br />
1) TBAF<br />
NaHMDS<br />
M-3 (S,R), 80%<br />
OTBS<br />
M-4 (S,R), 77%<br />
2) Dess -<br />
Martin<br />
periodinane<br />
(R) - E<br />
NaHMDS<br />
O F PAB<br />
OTBS<br />
O F PAB<br />
M-3 (S,S), 80%<br />
O<br />
M-4 (S,S), 77%<br />
M-4 (R,R)<br />
1) HPLC separation<br />
O<br />
2) Pd/C, H 2 , 97%<br />
3) EtCOCl (8 equiv.)<br />
Then PS-trisamine (97%)<br />
23 - 4 individual isomers<br />
M-4 (R,S)<br />
M-4 (S,R)<br />
M-4 (S,S)<br />
Scheme 19.<br />
Similarly<br />
23 - 12 individual isomers<br />
prepared by enantioselective reduction <strong>of</strong> the corresponding<br />
-keto sulfides, catalyzed by oxazaborolidine (R)- or (S)-X<br />
with 74 – 81% e.e. Recrystallization <strong>of</strong> the acylated -<br />
hydroxy sulfides in appropriate solvents increased the enantiomeric<br />
purity to 96 – 99% e.e. The sulfides were deacylated,<br />
oxidized to the sulfoxides, alkylated if necessary, and<br />
reduced with Raney-Ni to furnish the target compounds.<br />
5.8. (-)-(2R,6Z)-Undec-6-en-2-ol (27) (nostrenol)<br />
Nostrenol [(2R,6Z)-undec-6-en-2-ol, 27] was identified<br />
<strong>from</strong> thoracic glands <strong>of</strong> the ant-lion species Euroleon nostras<br />
and Grocus bore [58]. Chow and Kitching [59] described the<br />
synthesis <strong>of</strong> this and other insect pheromones (sections 5.9.,<br />
5.11., 5.12., and 6.4.) by hydrolytic kinetic resolution (HKR)<br />
<strong>of</strong> functionalised epoxides, using (salen)Co(OAc) complexes<br />
(R,R)-Z and (S,S)-Z (Fig. 1), providing enantiomerically<br />
enriched epoxides and diols. The synthesis <strong>of</strong> 27 started <strong>from</strong><br />
undec-1-en-6-yne (A), which was epoxidised with m-<br />
chloroperbenzoic acid in dichloromethane [59]. HKR <strong>of</strong> the<br />
resulting epoxide furnished the (S)-epoxide B and diol C.<br />
(S)-B was further transformed to 27 (Scheme 21)<br />
5.9. (-)-(R)- and (+)-(S)-10-Methyldodecyl acetate (28)<br />
(R)- and (S)-10-Methyldodecyl acetate (28) are components<br />
<strong>of</strong> the pheromone <strong>of</strong> the lesser tea tortrix moth, Adoxophes<br />
spp. [60, 61]. Chow and Kitching [59] described the<br />
synthesis <strong>of</strong> both enantiomers. Benzyl ether A was epoxidized<br />
with m-CPBA and the enantiomers <strong>of</strong> the resulting<br />
epoxide B were kinetically resolved by stirring with 0.5<br />
mol% <strong>of</strong> (R,R)-Z and 0.55 mol equiv. <strong>of</strong> H 2 O at room temperature<br />
(22°C) for ca. 24 h, giving (R)-epoxide B and (S)-<br />
diol C, which were straightforwardly converted to (R)-28<br />
and (S)-28, respectively (Scheme 22).<br />
5.10. 6-Acetoxy-19-methylnonacosane (29) and 7-acetoxy-<br />
15-methylnonacosane (30)<br />
In 1993, Pomonis et al. reported the identification <strong>of</strong> sixteen<br />
compounds in a pheromonally active HPLC fraction<br />
extracted <strong>from</strong> the females <strong>of</strong> the screw-worm fly Cochliomyia<br />
hominivorax [62]. In <strong>2002</strong>, Furukawa et al. synthesized<br />
five possible pheromone candidates [63], and a bioassay <strong>of</strong><br />
these five compounds showed activity for 6-acetoxy-19-
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 313<br />
R<br />
Ar<br />
O<br />
R = n-C 5 H 11<br />
R = i-Bu<br />
R = n-C 10 H 21<br />
O<br />
R<br />
A R = n-C 5 H 11 , 96% e.e.<br />
B R = i-Bu, 98% e.e.<br />
R<br />
O<br />
OH<br />
S-p-tolyl<br />
N<br />
(S) - X<br />
S-p-tolyl<br />
B<br />
O<br />
S-p-tolyl<br />
H<br />
Me<br />
O<br />
D R = n-C 5 H 11 , 96% e.e.<br />
E R = i-Bu, 98% e.e.<br />
(R) or (S)-MeCBS (X, 0.1 equiv.)<br />
N-ethyl-N-isopropylanilineborane<br />
complex (Y, 1.0 equiv.),<br />
THF, 25 o C 98 - 99%<br />
Ph<br />
Et<br />
Ph<br />
N<br />
Ph<br />
Pr-i<br />
BH 3<br />
(Y)<br />
1) 2N, NaOH,<br />
MeOH, rt., 98 - 99%<br />
2) m-CPBA, CH 2 Cl 2 ,<br />
rt. 95%<br />
n-BuLi(2.8 eq.), R' I,<br />
THF, -78 o - 20 o C, 72 - 93%<br />
OH<br />
Ar<br />
R = n-C 5 H 11 , 74% e.e.<br />
R = i -Bu, 81% e.e.<br />
R = n-C 10 H 21 , 79% e.e.<br />
O<br />
R<br />
R<br />
O<br />
OH<br />
OH O<br />
S-p-tolyl<br />
R<br />
D R = n-C 5 H 11 , 96% e.e.<br />
E R = i-Bu, 98% e.e.<br />
F R = n-C 10 H 21 , 79% e.e.<br />
S-p-tolyl<br />
OH O<br />
S-p-tolyl<br />
R<br />
R'<br />
G R = n-C 5 H 11 , R' = Me<br />
H R = i-Bu, R' = Et<br />
I R = i-Bu, R' = n-Pr<br />
OH<br />
S-p-tolyl<br />
2N, NaOH,<br />
MeOH, rt.<br />
Ar<br />
3,5-(NO 2 ) 2 C 6 H 3 COCl,<br />
TMEDA, CH 2 Cl 2 , 97 - 99%<br />
A R = n-C 5 H 11 , 74% e.e.<br />
B R = i -Bu, 81% e.e.<br />
C R = n-C 10 H 21 , 79% e.e.<br />
Ar<br />
O<br />
R<br />
O<br />
R<br />
O<br />
C<br />
recrystallization<br />
C'<br />
O<br />
m-CPBA, CH 2 Cl 2 ,<br />
rt. 95%.<br />
O<br />
S-p-tolyl<br />
O<br />
S-p-tolyl<br />
C' R = n-C 10 H 21<br />
A, 96% e.e.<br />
B, 98% e.e.<br />
C', 99% e.e.<br />
G<br />
ent-G<br />
H<br />
I<br />
Raney Ni, MeOH,<br />
rt., 89 - 92%<br />
(R)-24<br />
OH<br />
(R)-26<br />
OH<br />
(S)-24<br />
OH<br />
(R)-14<br />
F<br />
Scheme 20.<br />
methylnonacosane (29) and 7-acetoxy-15-methylnonacosane<br />
(30).<br />
Mori et al. described a synthesis <strong>of</strong> all possible stereoisomers<br />
<strong>of</strong> 29 [64] and 30 [65]. Starting <strong>from</strong> the enantiomers<br />
<strong>of</strong> citronellal and oct-1-yn-3-ol, all four stereoisomers <strong>of</strong> 29<br />
(R)-25<br />
(Scheme 23) were synthesized with high stereochemical purities<br />
(more than 90% e.e. at C-6; about 97% e.e. at C-19).<br />
The stereoisomers <strong>of</strong> 30 (Scheme 24) were obtained<br />
starting with the pure enantiomers <strong>of</strong> citronellal. The (R) and<br />
(S) configuration, respectively, was carried through to C-15,
314 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
( ) 3 m-CPBA, CH 2 Cl 2<br />
( ) 3<br />
A<br />
O<br />
0.5% equiv. (S,S)-Z,<br />
0.55 equiv. H 2 O<br />
( ) 3 ( )<br />
O<br />
3<br />
+<br />
OH<br />
OH<br />
B<br />
C<br />
B<br />
NaBH4, EtOH<br />
( ) 3<br />
OH<br />
1) DHP, H +<br />
2) Ti(Oi-Pr) 4 , i-PrMgBr,<br />
Et 2 O then H 2 O<br />
3) MeOH, H +<br />
( ) 3<br />
27<br />
OH<br />
Scheme 21.<br />
B<br />
C<br />
) 7<br />
OH<br />
1) m-CPBA, CH 2 Cl 2<br />
O<br />
OBn<br />
( ) 7 OBn HO<br />
( ) 7 OBn<br />
1) Me 2 CuLi, Et 2 O, 0 o C<br />
( 1) O 3 , Me 2 S<br />
)7 OBn<br />
( OAc<br />
+<br />
A<br />
2) 0.5% equiv (R,R)-Z,<br />
B<br />
C<br />
0.55 equiv. H 2 O, rt. 24 h<br />
( ) 7 OBn<br />
( ) 7 OBn<br />
2) MsCl, Et 3 N,<br />
2) K 2 CO 3 , MeOH<br />
(R)-28<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
3) Ac 2 O, Py<br />
1) MsCl, Et 3 N<br />
OH<br />
1) MsCl, Et 3 N<br />
2) K 2 CO 3 , MeOH<br />
2) Me 2 CuLi, Et 2 O, 0 o C<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
( ) 7 ( ) 7<br />
1) H 2 , Pd/C<br />
OAc<br />
2) Ac 2 O, Py<br />
(S)-28<br />
Scheme 22.<br />
while a lipase-catalyzed asymmetric acetylation defined the<br />
absolute configuration at C-7.<br />
5.11. (2S,11S)-2,11-Diacetoxytridecane (31) and (2S,12S)-<br />
2,12-diacetoxytridecane (32)<br />
(2S,11S)-2,11-Diacetoxytridecane (31) and (2S,12S)-<br />
2,12-diacetoxytridecane (32) are two <strong>of</strong> the three active<br />
components identified by coupled gas chromatography–<br />
electroantennography <strong>of</strong> extracts <strong>from</strong> the pheromone glands<br />
<strong>of</strong> female pea midges (Contarinia pisi) which are serious<br />
pests <strong>of</strong> commercial peas [67]. The key step in the synthesis<br />
<strong>of</strong> diester 31 was the HKR <strong>of</strong> a stereoisomeric mixture <strong>of</strong> the<br />
diepoxide A affording the epoxi-diol (2R,11S)-B, which was<br />
transformed to (2S,11S)-31 [59] (Scheme 25).<br />
Similarly, HKR <strong>of</strong> a stereoisomeric mixture <strong>of</strong> diepoxide<br />
C afforded pure (2R,12R)-C, which was transformed to<br />
(2S,12S)-32 [59] (Scheme 26).<br />
5.12. (1R,7R)-1,7-Dimethylnonyl propanoate (33)<br />
Various isomers <strong>of</strong> 1,7-dimethylnonyl propanoate (33)<br />
exhibit attractancy for males <strong>of</strong> corn rootworms, with the<br />
western corn rootworm (Diabrotica virgifera virgifera) and<br />
the northern corn rootworm (D. barberi) responding strongly<br />
to the (1R,7R)-isomer [68]. The synthesis <strong>of</strong> this isomer is<br />
shown in Scheme 27. The racemic bisepoxide A obtained by<br />
m-CPBA epoxidation <strong>of</strong> 1,8-nonadiene was treated with<br />
1.0% equiv. <strong>of</strong> (R,R)-Z and 0.8 equiv. <strong>of</strong> H 2 O, providing a<br />
mixture <strong>of</strong> the (S,S)-bisepoxide, the (S,S)-epoxydiol B and<br />
the (S,S)-tetraol. After column chromatography, epoxydiol B
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 315<br />
OHC<br />
Ref. [66]<br />
OTs<br />
1) THPO(CH 2 ) 7 MgBr,<br />
Li 2 CuCl 4 , THF<br />
OH<br />
1) TsCl, Py<br />
( ) 9 ( ) 10<br />
(6R,19S)-29<br />
2) NaI, DMF (77%, 2 steps)<br />
( ) 9<br />
( ) 4<br />
I<br />
( ) 9 ( ) 10<br />
(S)-A<br />
2) PTSA, MeOH (69%, 2 steps)<br />
( ) 9 ( )<br />
Similarly<br />
OHC<br />
I<br />
10<br />
( ) 4<br />
then (S)-A 68%<br />
(R)-A<br />
OH<br />
2.2 eq. n-BuLi, THF/HMPA,<br />
(S)-B<br />
1) H 2 , PtO 2 , EtOAc<br />
(15 min at rt. 85%)<br />
2) Ac 2 O, DMAP, Py,<br />
CH 2 Cl 2 (98%)<br />
(R)-A<br />
(R)-A<br />
(S)-A<br />
+<br />
+<br />
+<br />
(S)-B<br />
(R)-B<br />
(R)-B<br />
( ) 9 ( ) 10<br />
OAc<br />
( ) 9 ( ) 12 ( ) 4<br />
(6S,19S)-29<br />
OAc<br />
( ) 9 ( ) 12 ( ) 4<br />
( ) 9 ( ) 12<br />
(6S,19R)-29<br />
OAc<br />
( ) 4<br />
(6R,19R)-29<br />
OAc<br />
( ) 9 ( ) 12 ( ) 4<br />
OH<br />
Scheme 23.<br />
was transformed to (1R,7R)-33 in nine steps [59] (Scheme<br />
27).<br />
6. SYNTHESIS OF NON-ISOPRENOIDAL ALDE-<br />
HYDES, KETONES, ACIDS, AND ESTERS AS<br />
PHEROMONES<br />
6.1. (R)-4-Methylnonan-1-ol (34) and (4R,8RS)-4,8-<br />
dimethyldecanal (35)<br />
(R)-4-Methylnonan-1-ol (34) was identified as a sex attractant<br />
<strong>of</strong> the yellow mealworm Tenebrio molitor by Tanaka<br />
[69, 70] et al. In 1980, Suzuki identified 4,8-dimethyldecanal<br />
(35) as the aggregation pheromone <strong>of</strong> the red flour beetle<br />
(Tribolium castaneum) and <strong>of</strong> the confused beetle (Tribolium<br />
confusum), notorious pests <strong>of</strong> various stored products [71,<br />
72] Mori and co-workers [73, 74] established the absolute<br />
configuration <strong>of</strong> natural 35 as (4R,8R). Suzuki et al. [75]<br />
later found that a 8:2 mixture <strong>of</strong> the isomers (4R,8R)- and<br />
(4R,8S) was about 10 times more active than (4R,8R)-35<br />
alone.<br />
Ismuratov and co-workers [76] described a synthesis <strong>of</strong><br />
34 and 35 starting <strong>from</strong> (S)-3,7-dimethyl-1,6-octadiene. The<br />
hydroxyketone B, obtained by ozonolysis <strong>of</strong> the unsaturated<br />
ketone A followed by reductive workup, was either transformed<br />
to (R)-34 or (4R,8RS)-35 (Scheme 28).<br />
6.2. (E)-2-(4-Methyl-3-pentenylidene)butanedial (36) (acaridial)<br />
-Acaridial [(E)-2-(4-methyl-3-pentenylidene)butanedial,<br />
36] is known as the sex pheromone [78] and aggregation<br />
pheromone [79] <strong>of</strong> Caloglyphus polyphyllae and as the alarm<br />
pheromone [80] <strong>of</strong> Tyrophagus longior.<br />
Shimizu et al. [81] described the synthesis <strong>of</strong> 36 in five<br />
steps <strong>from</strong> 1,2,4-butanetriol with 19 % overall yield (Scheme<br />
29). Z-selective Wittig reaction allowed the preparation <strong>of</strong>
316 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
( ) 13 ( ) 13<br />
( ) 7<br />
( ) 3<br />
( ) 5<br />
)<br />
1) LiAlH 4 , Et 2 O, 96%<br />
1) Me(CH 2 ) 11 MgBr, Li 2 CuCl 4 , THF<br />
OHC<br />
TsO<br />
2) TsCl, Py<br />
2) OsO 4 , NMO, tert-BuOH, Me 2 CO,<br />
H 2 O, 3 d., rt. then Na 2 SO 4 , 94% (3 Steps)<br />
OH 1) HIO 4.2 H 2 O, THF, (quant.)<br />
( ) 5<br />
OTHP<br />
1) MsCl, CH 2 Cl 2 , Py<br />
EtOH, 39 % (3 Steps)<br />
O<br />
LiC CTMS, THF, 86%<br />
OTHP<br />
( ) 13 ( ) 8<br />
( ) 13 ( ) 7 H<br />
2) PCC, NaOAc, MS 4Å,<br />
OH<br />
2) THPO(CH 2 ) 5 MgBr, THF, 64%<br />
OH<br />
2) LiAlH 4 , THF<br />
1) PTSA, THF,<br />
( ) 13 ( ) 7<br />
CH 2 =CHOAc,<br />
(3R,11R)<br />
TMS<br />
(3R,11R)-D<br />
CH 2 Cl 2 , 72%<br />
OAc<br />
OH<br />
K 2 CO 3 , MeOH<br />
( ) 13 ( ) 7<br />
TMS<br />
OH<br />
OH<br />
(i-Pr) 2 O, 14 d., rt.<br />
(3RS,11R)-C<br />
( ) 13 ( ) K 7<br />
2 CO 3 , MeOH<br />
( ) 13 ( ) 7<br />
OH<br />
Lipase PS-D,<br />
( ) 13 ( ) 7<br />
99.5% e.e. 92.5% e.e.<br />
Similarly<br />
( ) 13 ( ) Similarly<br />
7<br />
OHC<br />
97.5% e.e. 79% e.e.<br />
(3S,11R) TMS<br />
98% e.e. 98.5% e.e.<br />
(3S,11R)-D<br />
OH<br />
OH<br />
( ) 13<br />
( ) 13 ( ) 7<br />
TMS<br />
(3R,11S)-D<br />
(3RS,11S)-C<br />
OH<br />
(3R,11R)-D<br />
( ) 13 ( ) 7<br />
98% e.e. 94% e.e.<br />
(3S,11S)-D<br />
1) TBSCl, imidazole, DMF, 76%<br />
OH<br />
1) H 2 , PtO 2 , EtOAc, 15 min, rt.<br />
2) n-BuLi, n-BuI, THF, HMPA, 75%<br />
2) TBAF, THF, 92% (2 steps)<br />
( ) 13 ( ) 7 ( )5<br />
( ) 13 ( ) 7<br />
OH<br />
Ac 2 O, DMAP,<br />
CH 2 Cl 2 , Py, 83%<br />
OAc<br />
(3S,11R)-D<br />
( ) 13 ( ) 7 ( 5<br />
98.5% e.e. 91% e.e.<br />
(7S,15R)-30<br />
OAc<br />
Similarly<br />
(3R,11S)-D<br />
( ) 13 ( ) 7 ( ) 5<br />
98% e.e. 97% e.e.<br />
(7R,15R)-30<br />
OAc<br />
Similarly<br />
(3S,11S)-D<br />
( ) 13 ( ) 7 ( ) 5<br />
98% e.e. 83% e.e.<br />
(7S,15S)-30<br />
OAc<br />
Similarly<br />
98% e.e. 96% e.e.<br />
Scheme 24.<br />
(7R,15S)-30
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 317<br />
Scheme 25.<br />
Br<br />
1) Allyl MgBr, THF<br />
Br<br />
O<br />
( )6 ( ) 6 ( ) 6<br />
1.0% equiv. (S,S)-Z<br />
O 0.6 equiv. H 2 O<br />
2) m-CPBA, CH 2 Cl 2<br />
O<br />
O<br />
OH<br />
OH OH<br />
O<br />
+<br />
OH + HO<br />
( ) 6 OH<br />
OR<br />
1) LiAlH 4 , Et 2 O<br />
OAc OAc<br />
O<br />
( ) 6 ( ) 6<br />
(2R,11S)-B<br />
( ) 6 O<br />
A<br />
(2R,11S)-B<br />
1) 2,2-DMP, H +<br />
OR<br />
O<br />
1) MeOH, H +<br />
2) MeMgBr, CuI, Et 2 O, 0 o C<br />
2) MsCl, Et 3 N<br />
3) Ph 3 P, p-chlorobenzoic<br />
(R = p-ClPhCO)<br />
3) K 2 CO 3 , MeOH<br />
acid, DEAD, THF<br />
2) Ac 2 O, Py<br />
(2S,11S)-31<br />
O<br />
( ) 7<br />
C<br />
(2R,12R)-C<br />
1.0% equiv. (R,R)-Z<br />
O<br />
0.6 equiv. H 2 O<br />
1) NaBH 4 , EtOH<br />
2) Ac 2 O, Py<br />
OH<br />
OAc<br />
OH<br />
+<br />
O<br />
(<br />
(2R,12R)-C<br />
HO<br />
OH +<br />
O<br />
) 7 O<br />
OAc<br />
OH<br />
OH<br />
(2S,12S)-32<br />
Scheme 26.<br />
O<br />
( ) 3 ( ) 3<br />
1.0% equiv.<br />
m-CPBA, CH 2 Cl 2 O<br />
O (R,R)-Z, 0.8 equiv. H 2 O<br />
OH<br />
OH OH<br />
O O<br />
( ) 3 ( ) 3 OH HO<br />
( ) 3 OH<br />
+<br />
+<br />
B<br />
B<br />
2,2-DMP, H +<br />
O<br />
O<br />
1) Me 2 CuLi, Et 2 O, 0 o C<br />
( ) 3 O<br />
( ) 3<br />
2) MsCl, Et 3 N<br />
( ) 3<br />
O<br />
O<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
1) MeOH, H +<br />
2) MsCl, Et 3 N<br />
3) K 2 CO 3 , MeOH<br />
O<br />
1) NaBH 4 , EtOH<br />
2) (EtCO) 2 O, Py<br />
( ) 3<br />
33<br />
OCOEt<br />
Scheme 27.<br />
the geometric isomer, (Z)-36 (-(Z)-acaridial), which was<br />
detected as a trace component in the secretion <strong>of</strong> C. polyphyllae,<br />
together with the (E)-configured hydroxy aldehyde<br />
B.<br />
6.3. (R)-10-Methyl-2-tridecanone (37)<br />
10-Methyl-2-tridecanone (37) is the sex pheromone <strong>of</strong><br />
the southern corn rootworm (Diabrotica undecimpunctata<br />
howardi), and biological evaluation <strong>of</strong> the enantiomers indi-
318 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
O<br />
A<br />
O<br />
LiI<br />
Ref. [77]<br />
AcCH 2 CO 2 Et<br />
Br<br />
NaH<br />
DMF<br />
CO 2 Et<br />
N 2 H 4 , H 2 O<br />
1) O<br />
O<br />
3<br />
KOH<br />
OH<br />
34<br />
2) NaBH(OAc) 3 B<br />
OH<br />
B<br />
MeCH=PPh 3<br />
OH<br />
H 2 , Pd/C<br />
OH<br />
PCC<br />
O<br />
Scheme 28.<br />
35<br />
H<br />
HO<br />
A<br />
OH<br />
TBSCl, DMAP,<br />
OH Et 3 N, CH 2 Cl 2<br />
P + Ph 3 Br -<br />
OTBS<br />
OTBS<br />
n-BuLi, Et 2 O<br />
P + Ph 3 Br -<br />
NaHMDS, THF<br />
TBSO<br />
TBAF, THF<br />
OTBS<br />
OTBS<br />
OH<br />
PDC, CH 2 Cl 2<br />
OTBS<br />
TBSO<br />
OH<br />
Dess-Martin periodinane,<br />
CH 2 Cl 2<br />
OH<br />
H O<br />
PDC, CH 2 Cl 2<br />
OH<br />
H<br />
B<br />
1) TBAF, THF<br />
2) Dess-Martin periodinane,<br />
O<br />
CH 2 Cl 2<br />
O<br />
A<br />
H O<br />
(E)-36<br />
O<br />
H<br />
OTBS<br />
O<br />
H<br />
Scheme 29.<br />
(Z)-36<br />
O<br />
1) EtMgBr, CuI<br />
1) n-BuLi, THF, -78 o C<br />
( ) 7 OBn ( )7 OBn<br />
( ) 7<br />
(R)-37<br />
O<br />
B<br />
2) MsCl, Et 3 N<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
2) PdCl 2 , CuCl, DMF/H 2 O, O 2<br />
Scheme 30.<br />
cated that the (R) enantiomer was preferred by males [82].<br />
The epoxide (R)-B <strong>from</strong> scheme 22 was converted to (R)-37<br />
in five steps (Scheme 30).<br />
Another synthesis took a similar approach as shown in<br />
scheme 3, starting <strong>from</strong> (+)-aromadendrene [16] (Scheme<br />
31).<br />
6.4. (6R,12R)-6,12-Dimethylpentadecan-2-one (38)<br />
(6R,12R)-6,12-Dimethylpentadecan-2-one (38) is the female<br />
produced sex pheromone <strong>of</strong> the banded cucumber beetle<br />
(Diabrotica balteata), the larvae <strong>of</strong> which are serious<br />
pests <strong>of</strong> crops such as cucurbits and sweet potatoes [83].
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 319<br />
H<br />
Ref. 16<br />
H O<br />
CBr 4 , PPh 3 , CH 2 Cl 2 , 78%<br />
H O<br />
H<br />
H<br />
H<br />
H<br />
OH<br />
O<br />
H<br />
Br<br />
1) m-CPBA, MgSO 4 , CH 2 Cl 2<br />
OH<br />
OEt<br />
1) NaOEt, NaBH 4 , EtOH, 77%<br />
2) PTSA, EtOH, 59% overall<br />
H<br />
Br<br />
2) H 2 , Pd/C, EtOAc, 83%<br />
HO<br />
OEt<br />
1) TsCl, Py, 79%<br />
I<br />
A<br />
O<br />
2) LiAlH 4 , THF, 95%<br />
3) I 2 , PPh 3 , imidazole, CH 2 Cl 2 , 91%<br />
1) allylMgCl, THF, 83%<br />
2) PdCl 2 , CuCl, O 2 , DMF<br />
(wet) (100%).<br />
37<br />
O<br />
Scheme 31.<br />
1.0% equiv.<br />
( ) 3 m-CPBA, CH 2 Cl 2<br />
O<br />
O<br />
( ) 3<br />
(R,R)-Z, 0.8 equiv.<br />
H 2 O<br />
OH<br />
OH OH<br />
O<br />
( O O<br />
)3 ( ) 3 OH HO<br />
( ) 3 OH<br />
+<br />
+<br />
B<br />
O<br />
1) EtMgBr, CuI, Et 2 O, 0 o C<br />
DMP, H + O<br />
B<br />
( ) 3 O<br />
( ) 3<br />
( ) 2<br />
2) MsCl, Et 3 N<br />
C<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
1) MeOH, H +<br />
O<br />
( ) 3 1) H 2 C=CH(CH 2 ) 2 MgBr, CuI, Et 2 O, 0 o C<br />
( ) 2<br />
2) MsCl, Et 3 N<br />
2) MsCl, Et 3 N<br />
3) K 2 CO 3 , MeOH<br />
3) Me 2 CuLi, Et 2 O, 0 o C<br />
( ) 3 1) PdCl 2 , CuCl,<br />
( ) ( ) 3<br />
2<br />
( ) 2<br />
O<br />
O<br />
O<br />
Scheme 32.<br />
DMF/H 2 O, O 2<br />
38<br />
Chow and Kitching [59] described the synthesis <strong>of</strong> (6R,12R)-<br />
38 <strong>from</strong> epoxy-acetonide C (Scheme 32).<br />
6.5. (6Z,8E)-Heneicosa-6,8-dien-11-one (39) and (Z)-6-<br />
heneicosen-11-one (40)<br />
(6Z,8E)-Heneicosa-6,8-dien-11-one (39) and (6Z)-<br />
heneicos-6-en-11-one (40) are sex pheromone components<br />
<strong>of</strong> the Douglas-fir tussock moth (Orgyia pseudotsugata)<br />
[84]. Addionally, 39 has been identified as a major sex<br />
pheromone component <strong>of</strong> O. vetusta [85] and was also found<br />
in the painted apple moth (Teia anartoides) [86].<br />
Jury et al. [87] reported the synthesis <strong>of</strong> 39 in seven steps<br />
<strong>from</strong> 1,2-epoxydodecane in an overall yield <strong>of</strong> 25% (Scheme<br />
33). (E)-Vinyl iodide B was obtained as a single stereoisomer<br />
in good yield by the hydrozirconation–iodination <strong>of</strong><br />
acetylene A with Schwartz’s reagent and freshly sublimed
320 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
1) LiC CH:H 2 NCH 2 CH 2 NH 2<br />
OTBS 1) Cp 2 ZrHCl, benzene, rt.,<br />
OTBS<br />
O DMSO, rt., 86%<br />
( ) 9<br />
( )<br />
dark, 48 h<br />
9<br />
( ) 9<br />
2) TBDMSCl, imidazole,<br />
A<br />
2) I 2 , 65%<br />
B<br />
DMF, 0 o C, 97%<br />
OTBS<br />
( )<br />
1-heptyne, PdCl 4<br />
1) Ni(OA ) 2 .4H 2 O, NaBH 4 , EtOH, 0 o 2 (CH 3 CN) 2 ,<br />
C<br />
( ) 9<br />
CuI, piperidine, rt., quant.<br />
C<br />
2) H 2 NCH 2 CH 2 NH 2 , H 2 , rt., 69%<br />
O<br />
OTBS<br />
1) TBAF, CH 2 Cl 2 , rt., 78%<br />
( ) 9<br />
( ) 4<br />
( ) 9 ( ) 4<br />
2) PCC, K 2 CO 3 , rt., CH 2 Cl 2 , 87%<br />
39<br />
I<br />
Scheme 33.<br />
MeO 2 C<br />
O<br />
( ) 9<br />
1) NaBH 4 , THF, 74%<br />
2) TBDMSC , imidazo e,<br />
DMF, 98%<br />
MeO 2 C<br />
OTBDMS<br />
( ) 9<br />
1) DIBAL-H, to uene, 94%<br />
2) PPh 3 = CHCO 2 Me,<br />
to uene, 96%<br />
MeO 2 C<br />
OTBDMS<br />
( ) 9<br />
1) DIBAL-H, to uene, 94%<br />
2) MnO 2 , CH 2 C 2 , 96%<br />
OHC<br />
OTBDMS<br />
( ) 9<br />
1) CBr 4 , Ph 3 P, CH 2 C 2 , 88%<br />
2) Pd(PPh 3 ) 3 , (n-Bu) 2 SnH,<br />
benzene, quant.<br />
OTBDMS<br />
1) n-C 5 H 11 MgBr,<br />
NiC 2 , Et 2 O, 86%<br />
OH<br />
Br<br />
( ) 9<br />
2) TBAF, THF, quant.<br />
( ) 9<br />
Dess-Martin periodinane,<br />
CH 2 C 2 , 79%<br />
O<br />
( ) 9<br />
39<br />
Scheme 34.<br />
iodine. The (E,Z)-diene system was obtained in good yield<br />
by the partial reduction <strong>of</strong> C in the presence <strong>of</strong> catalytic P2-<br />
Ni under a hydrogen atmosphere.<br />
Muto and Mori [31] described the synthesis <strong>of</strong> 39, employing<br />
a Wittig reaction for the formation <strong>of</strong> the (8E) double<br />
bond, while the conjugated (6Z) double bond was established<br />
by Uenishi’s procedure (CBr 4 , PPh 3 ) [88] (Scheme<br />
34).<br />
Comeskey et al. [89] described the stereospecific synthesis<br />
<strong>of</strong> all four isomers <strong>of</strong> 39, using the Suzuki coupling <strong>of</strong><br />
vinylic boronic acids A and C and vinylic iodide intermediates<br />
B and D (Scheme 35).<br />
Muto and Mori [31] described the synthesis <strong>of</strong> (Z)-6-<br />
heneicosen-11-one (40), starting <strong>from</strong> 2-dodecanone in three<br />
steps and 65% overall yield (Scheme 36).<br />
6.6. (4S,6S,7S)-7-Hydroxy-4,6-dimethyl-3-nonanone (41)<br />
(Serricornin)<br />
Serricornin [(4S,6S,7S)-7-hydroxy-4,6-dimethyl-3-<br />
nonanone), (4S,6S,7S)-41] is the sex pheromone produced by<br />
female cigarette beetle, Lasioderma serricorne.[90-95]. Zlokazov<br />
and Veselovsky [96] developed a synthesis <strong>of</strong> 41 starting<br />
<strong>from</strong> (4S,5E)-4-methylhept-5-enenitrile [97] (Scheme<br />
37).<br />
6.7. (4R,6S,7R)-7-Hydroxy-4,6-dimethyl-3-nonanone (41)<br />
and (3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-octanone (42)<br />
In 1999, Francke et al. found a stereoisomer <strong>of</strong> serricornin<br />
as a pheromone component <strong>of</strong> the beetle Dinoderus<br />
bifoveolatus [98]. The synthesis <strong>of</strong> (4R,6S,7R)-41 and<br />
(3R,5S,6R)-6-hydroxy-3,5-dimethyl-2-nonanone (42) and
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 321<br />
catecholborane 70 o C, 55%<br />
t 2 O, NaOH, I 2 , 53%<br />
( ) 4<br />
(E)-B<br />
B(OH) 2<br />
( ) 4<br />
I<br />
( ) 4<br />
( ) 4<br />
4<br />
(E)-A<br />
I<br />
AgNO 3 , acetone, NBS, 46%<br />
Br<br />
B(OH) 2<br />
HBBr 2 then KIPBH, 78%<br />
( ) 4<br />
t 2 O, THF, I 2 , 37%<br />
( ) 4<br />
(Z)-B<br />
(E)-C + (E)-B<br />
( ) 4<br />
( )<br />
2) Dess - Martin periodinane, 72%<br />
9<br />
OH<br />
O lithium acetylide/ DA<br />
OH<br />
catecholborane 70 o C, 29%<br />
( ) complex, DMSO, 82%<br />
9<br />
( ) 9<br />
B(OH) 2<br />
( ) 9<br />
(Z)-A<br />
( ) 9 I<br />
t 2 O, THF, I 2 , 46%<br />
OH<br />
(E)-C<br />
(Z)-D<br />
1) Pd(PPh 3 ) 4 , NaO t, 36%<br />
O<br />
(E)-C + (Z)-B<br />
( ) 9 ( )<br />
2) Dess - Martin periodinane, 66%<br />
(E,Z)-39<br />
(E,E)-39<br />
O<br />
1) Pd(PPh 3 ) 4 , NaO t, 66%<br />
(Z)-D + (Z)-A<br />
1) Pd(PPh 3 ) 4 , NaO t, 8%<br />
( ) 4<br />
( ) 9<br />
2) Dess - Martin periodinane, 78%<br />
(Z,Z)-39<br />
O<br />
1) Pd(PPh 3 ) 4 , NaO t, 40%<br />
(Z)-D + (E)-A<br />
( ) 9<br />
2) Dess - Martin periodinane, 64%<br />
(Z,E)-39<br />
( ) 4<br />
O<br />
( ) 4<br />
Scheme 35.<br />
O<br />
O<br />
NaH, CO(OMe) 2 ,<br />
( ) 9<br />
MeO 2 C<br />
( ) 9<br />
toluene, heat, 93%<br />
(Z)-3-nonenyl iodide<br />
K 2 CO 3 , MeCOEt, 83%<br />
O<br />
O<br />
Scheme 36.<br />
CO 2 Me<br />
( ) 9<br />
KOH, MeOH/H 2 O, 84%<br />
40<br />
( ) 9<br />
their stereoisomers was performed by Masuda et al. [99].<br />
The starting chiral building block A was obtained by lipase<br />
AK-catalyzed asymmetric acetylation <strong>of</strong> meso-2,4-dimethyl-<br />
1,5-pentanediol. Asymmetric acetylation with vinyl acetate<br />
and lipase PS-D (Amano) furnished the acetate (2R,4S,5R)-B<br />
and the alcohol (2R,4S,5S)-C, which were further transformed<br />
to the target compounds (Scheme 38).<br />
6.8. (E)-2,4-Dimethyl-2-hexenoic acid (43)<br />
(E)-2,4-Dimethyl-2-hexenoic acid (43) is a caste-specific<br />
substance present in the mandibular glands <strong>of</strong> male ants in<br />
the genus Camponotus [100]. Fernandes et al. [101] described<br />
a synthesis <strong>of</strong> 43 with high stereoselectivity and 39%<br />
overall yield, by zinc-promoted reduction <strong>of</strong> the 2-(bromo-
322 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
I<br />
I<br />
CN<br />
NaOH E,OH,<br />
sealed ,ube, 200 + C<br />
HO<br />
O<br />
1) NIS, DMF, 20 + C<br />
2) )hr+ma,+graphy<br />
O<br />
O<br />
+<br />
O<br />
O<br />
A<br />
3:2<br />
4<br />
4<br />
Scheme 37.<br />
1) n-Bu 3 SnH AIBN, benzene, 80 + C<br />
2) (TMS) 2 NLi, THF HMPA,<br />
-78 + C ,+ 10 + C, ,hen MeI, -78 + C<br />
O<br />
O<br />
E,MgBr, THF, - 40 + C<br />
OH<br />
(4S,6S,7S)-41<br />
O<br />
O<br />
O<br />
O<br />
HO<br />
OH<br />
CH 2 =CHOAc, lipase AK, 86%<br />
HO<br />
OAc<br />
1)TB MSCl, imidazole, MF, 95%<br />
A<br />
2) K 2 CO 3 , MeOH, 96%<br />
3) TPAP, NMO, CH 2 Cl 2<br />
4) EtMgBr, THF, (2 steps, 73%)<br />
TB MSO<br />
TB MSO<br />
CH 2 =CHOAc,<br />
lipase PS-<br />
(2R,4S,5R)-B, 27%<br />
OAc<br />
OH<br />
TB MSO<br />
(2R,4S,5S)-C, 64%<br />
OH<br />
EtMgBr, THF<br />
O<br />
OH<br />
(2R,4S,5R)-B<br />
1) TBAF, THF, %uant.<br />
2) KOH, MeOH, 87%<br />
3) TPAP, NMO, CH 2 Cl 2 , 79%<br />
O<br />
O<br />
MeMgBr, THF<br />
(4R,6S,7R)-41<br />
O<br />
OH<br />
(3R,5S,6R)-42<br />
EtMgBr, THF<br />
1) TBAF, THF, 92%<br />
O<br />
OH<br />
(2R,4S,5S)-C<br />
2) TPAP, NMO, CH 2 Cl 2 , 78%<br />
O<br />
O<br />
(4R,6S,7S)-41<br />
MeMgBr, THF<br />
Scheme 38.<br />
O<br />
(3R,5S,6S)-42<br />
OH
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 323<br />
O O<br />
OH O<br />
DABCO, 72%<br />
H + OCH 3<br />
OCH 3<br />
A<br />
O<br />
O<br />
OCH<br />
1) Zn/A%OH, 88%<br />
3<br />
OH<br />
HBr, H 2 SO 4 , 75%<br />
Scheme 39.<br />
O<br />
B<br />
O<br />
Br<br />
O<br />
O<br />
P<br />
O<br />
2) N OH, MeOH/H 2 O, 83%<br />
1) (CH 3 ) 2 CH 2 I,<br />
t-BuOK, DMSO<br />
2) LiHMDS, CH 3 CHO,<br />
O<br />
O<br />
43 39% ) / er ll yield<br />
1) AD-mix-, H 2 O/t-BuOH, 0 o C<br />
2) KOH, H 2 O/ tOH<br />
HO<br />
O<br />
OH<br />
OH<br />
THF, -78 o C<br />
MsCl, Py, 0 o C<br />
O<br />
O<br />
OH<br />
(S,S)-44<br />
O<br />
O<br />
AD-mix-, H 2 O/t-BuOH, 0 o C<br />
Similarly<br />
O<br />
O<br />
OH<br />
(R,R)-44<br />
1) (CH 3 ) 2 CH 2 I,<br />
O<br />
O<br />
O<br />
P<br />
O<br />
O<br />
t-BuOK, DMSO<br />
2) PCl 5 , 75 o C<br />
O<br />
O<br />
O<br />
P<br />
O<br />
O<br />
CF 3<br />
CF 3<br />
NaHMDS, 18-crown-6,<br />
CH 3 CHO, THF, -78 o C<br />
3) CF 3 CH 2 OH,<br />
toluene, t 3 N<br />
O<br />
O<br />
1) AD-mix-, H 2 O/t-BuOH, 0 o C<br />
HO<br />
O<br />
OH<br />
MsCl, Py, 0 o C<br />
O<br />
O<br />
2) LiOH, H 2 O/i-PrOH<br />
OH<br />
OH<br />
Scheme 40.<br />
O<br />
O<br />
AD-mix-, H 2 O/t-BuOH, 0 o C<br />
Similarly<br />
O<br />
O<br />
OH<br />
(R,R)-45<br />
(S,S)-45<br />
methyl) alkenoate B derived <strong>from</strong> the corresponding Baylis–<br />
Hillman adduct A (Scheme 39).<br />
7. SYNTHESIS OF LACTONES AS PHEROMONES<br />
7.1. 2-Hydroxy-2-(1-methylethyl)-3-butanolide (44), 2-<br />
ethyl-2-hydroxy-3-butanolide (45), 7-hydroxy-5-<br />
dodecanolide (46)<br />
Schulz and Nishida [102, 103] reported that males <strong>of</strong> the<br />
giant white butterfly Idea leuconoe release a complex mixture<br />
<strong>of</strong> compounds containing alkaloids, aromatics, terpenoids,<br />
hydrocarbons, and lactones, during courtship.<br />
The pure (S,S) and (R,R) enantiomers <strong>of</strong> the -lactones 2-<br />
hydroxy-2-(1-methylethyl)-3-butanolide (44) and 2-ethyl-2-<br />
hydroxy-3-butanolide (45) were synthesized based on a controlled<br />
C-C coupling by a Horner-Wadsworth-Emmons approach,<br />
followed by asymmetric dihydroxylation (Scheme<br />
40). The absolute configuration <strong>of</strong> the natural lactones was<br />
determined to be (S,S) by enantioselective gas chromatography<br />
[104].
324 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
O<br />
1) SnC 2 , N 2 CH 2 COOEt, CH 2 C 2<br />
O O O<br />
H<br />
2) Mg(OEt) 2 , C CO(CH 2 ) 3 COOMe, Et 2 O<br />
O<br />
3) NaC , D, DMSO/H 2 O<br />
1) H 2 , (R)-Ru-BINAP, MeOH<br />
o( NaBH 4 , MeOH, <br />
OH OH O<br />
O<br />
o(<br />
OH OH O<br />
O<br />
O<br />
O<br />
PTSA, CHC 3<br />
O<br />
OH<br />
(R,R) - 46<br />
o(<br />
O OH<br />
O<br />
rac - 46<br />
1) PPh 3 , DEAD,<br />
benzoic acid, CH 2 C 2<br />
O<br />
O<br />
OH<br />
2) NaOMe, MeOH<br />
Scheme 41.<br />
(R,S) - 46<br />
SiMe 3 O<br />
O<br />
LDA, -78 o C, then<br />
CH 3 CH 2 CHO, 3 h, 93%<br />
SiMe 3 O<br />
O<br />
OH<br />
1%HF aq., rt., 1.5 h, 96%<br />
2%TBDPSCl, imidazole,<br />
DMF, rt., 12 h, 94%<br />
HO<br />
O<br />
OTBDPS<br />
1%CAN, acetonitrile,<br />
0 o C, 20 min, 92%<br />
2%BH 3 THF, 0.<br />
o C,<br />
then rt., 4 h, 95%<br />
HO<br />
OTBDPS<br />
1%MsCl, Et 3 N, 0 o C, 3h<br />
2%NaI, acetone, reflux. 12 h<br />
3%NaCN, DMSO, rt.,<br />
12 h, 80% overall<br />
NC<br />
OTBDPS<br />
1%NaOH, 2-methoxyethanol,<br />
reflux, 21 h, then HCl, 90%<br />
2%TBAF, THF, rt., 4 h, 86%<br />
Scheme 42.<br />
O<br />
R%-47<br />
O<br />
The -lactone 7-hydroxy-5-dodecanolide (46) was synthesized<br />
as a mixture <strong>of</strong> stereoisomers and as the pure (R,R)<br />
isomer, the latter by enantioselective reduction <strong>of</strong> the methyl<br />
dioxoalkanoate precursor employing Ru-BINAP catalyst.<br />
The (R,S) isomer was obtained by Mitsunobu inversion <strong>of</strong><br />
the (R,R) isomer (Scheme 41). The natural product was<br />
shown to be a mixture <strong>of</strong> all stereoisomers [104].<br />
7.2. (R)-4-Hexanolide (47)<br />
(R)-4-Hexanolide (47) was identified as a component <strong>of</strong><br />
the sex pheromone <strong>of</strong> females <strong>of</strong> the dermestid beetle Trogoderma<br />
glabrum [105, 106].<br />
Arceo et al. [107] described the synthesis <strong>of</strong> 47 with 45%<br />
overall yield in high enantiomeric purity using a chiral auxiliary<br />
derived <strong>from</strong> (S)-camphor (Scheme 42).<br />
7.3. (4R,9Z)-Octadec-9-en-4-olide (48)<br />
Cossé et al. [108] reported the occurrence <strong>of</strong> a femalespecific<br />
compound <strong>from</strong> the currant stem girdler (Janus integer),<br />
which they identified as the chiral lactone (Z)-octadec-<br />
9-en-4-olide (48). The structure was proven by synthesis <strong>of</strong><br />
the racemic compound. Upon chiral GC analysis, only one<br />
enantiomer was detected to be produced by the insects, but<br />
the absolute configuration was not determined.
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 325<br />
OH<br />
HO<br />
A, THF, 0 o C, then<br />
NH 4 C , MeOH, ref ux<br />
NH 2<br />
HOOC<br />
COOH<br />
NaOMe,<br />
anhydrous MeOH, rt.<br />
A BrMg<br />
C BrMg<br />
DHP, CH 2 C 2<br />
0,1N HC , rt.<br />
HO<br />
HONO<br />
O<br />
O<br />
D<br />
PDC, CH 2 C 2<br />
H<br />
OH<br />
THPO<br />
THPO<br />
MgSO 4 , rt.<br />
O<br />
B<br />
TPAP, NMO<br />
( ) 7<br />
O<br />
( ) 7<br />
O<br />
OH<br />
CH 2 C 2 , rt.<br />
(±)-48<br />
1) BH 3. Me 2 S<br />
O O COOH<br />
OTs<br />
O O<br />
2) TsC , TMPDA, 0 - 5 o C<br />
C, THF, 0 o C<br />
( ) 7<br />
O<br />
O O<br />
(R)-48<br />
( ) 7<br />
( ) 7<br />
( ) 6<br />
( ) 7 ( ) 4<br />
Scheme 43.<br />
HO OH<br />
Ref. 111<br />
TBDPSO<br />
O CH CLi . H 2 N(CH 2 ) 2 NH 2 ,<br />
THF, 62%<br />
( ) 5 H<br />
OH<br />
OAc<br />
OH Lipase AH-S (Amano),<br />
TBDPSO<br />
TBDPSO<br />
TBDPSO<br />
CH 2 CHOAc,<br />
( ) 5<br />
+<br />
( ) 5<br />
( ) 5<br />
(+)-A<br />
OTBS<br />
1) TBSCl, imidazole, DMF, 94%<br />
OH<br />
1) H 2 , PtO 2 , hexane, 89%<br />
TBDPSO<br />
( ) 5<br />
HO<br />
( ) 5<br />
rac. - A<br />
SiO 2 chromatography<br />
(+)-A 29% yield, 96% e.e.<br />
B<br />
OH<br />
TBDPSO<br />
( ) 5<br />
K 2 CO 3 , MeOH<br />
(-)-A 24% yield (2 steps), 93% e.e.<br />
HO<br />
( ) 5 O<br />
O<br />
O<br />
O<br />
2) n-BuLi, ClCO 2 Me, THF, 94%<br />
CO 2 Me 2) TBAF, THF<br />
1) PCC, MS 4Å<br />
1) KOH, MeOH, H 2 O<br />
sieves, CH 2 Cl 2 , 68%<br />
( ) 7 ( ) 4 O<br />
O<br />
2) dil. HCl (79%; 3 steps)<br />
2) [Me(CH 2 ) 8 PPh + 3 ]Br - , NaHMDS,<br />
(R)-48<br />
hexane, THF, -100 o C, 68%<br />
Similarly<br />
(95.9% e.e., E/Z 1.6:98.4)<br />
(-)-A<br />
(S)-48<br />
CO 2 Me<br />
(94.9% e.e., E/Z 1.6:98.4)<br />
Scheme 44.<br />
James et al. [109] described the synthesis <strong>of</strong> racemic and<br />
the pure enantiomers <strong>of</strong> 48 and determined the absolute configuration<br />
<strong>of</strong> the natural compound to be (R). In the racemic<br />
route, Grignard reagent A was added to aldehyde B, followed<br />
by deprotection and selective oxidation <strong>of</strong> the primary<br />
hydroxyl group with tetrapropylammonium perruthenate<br />
(TPAP). (R)-48 was synthesized by addition <strong>of</strong> Grignard<br />
reagent C to the chiral epoxide D prepared <strong>from</strong> (S)-(+)-<br />
glutamic acid (Scheme 43).<br />
Shibata and Mori [110] synthesized both enantiomers <strong>of</strong><br />
48. The key step was the lipase-catalyzed asymmetric acetylation<br />
<strong>of</strong> a racemic mixture <strong>of</strong> the acetylenic alcohol A with<br />
vinyl acetate and lipase AH-S, which furnished (+)-A (96%<br />
e.e.) and the acetylated product B, which was hydrolyzed to<br />
give (-)-A (93% e.e.). (+)-A and (-)-A were transformed to<br />
(R)-48 and (S)-48, respectively (Scheme 44).
326 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
O<br />
N<br />
1) n-BuLi, THF, -78 o C<br />
N<br />
OH<br />
H 3 O +<br />
2)<br />
HO H 92% O<br />
85%<br />
O<br />
O<br />
H<br />
+<br />
O<br />
O<br />
H<br />
I<br />
(S)-A (<strong>from</strong> ref. 115)<br />
HO H<br />
I<br />
(R)-A (<strong>from</strong> ref. 115)<br />
similarly<br />
cis - (2R,5S)-49 trans - (2S,5S)-49<br />
(cis/trans = 7:3)<br />
78% overall <strong>from</strong> iodide (S)-A<br />
O<br />
O<br />
O<br />
O<br />
H +<br />
H<br />
cis - (2S,5R)-49 trans -(2R,5R)-49<br />
(cis/trans = 7:3)<br />
80% overall <strong>from</strong> iodide (R)-A<br />
O<br />
N<br />
n-BuLi, THF, -78 o C<br />
85%<br />
O<br />
O<br />
I<br />
O<br />
O<br />
N<br />
O<br />
H + , MeOH<br />
60%<br />
H<br />
HO<br />
O<br />
O<br />
51% overall yield <strong>from</strong> iodide B<br />
B (<strong>from</strong> ref. [116])<br />
Ref. [117]<br />
Scheme 45.<br />
O<br />
Ac 2 O, Py, DMAP, rt., 100%<br />
A<br />
m-CPBA, CH 2 Cl 2 ,<br />
NaHCO 3 , r.t., 82 - 85%<br />
A<br />
H<br />
( ) 9<br />
OAc<br />
O<br />
O<br />
50<br />
O L-proline (20 mol%),<br />
OH O<br />
OH<br />
+<br />
CHCl 3 , 24 h, 80%<br />
( ) 9<br />
+<br />
( ) 9<br />
A<br />
85 : 15<br />
OAc O m-CPBA, CH 2 Cl 2 ,<br />
96% e.e.<br />
NaHCO 3 , rt., 82 - 85%<br />
( ) 9<br />
OH<br />
O O Ac 2 O, Py, DMAP, rt., 100%<br />
O<br />
O<br />
O<br />
Scheme 46.<br />
51<br />
7.4. cis- and trans-2-Methyl-5-hexanolide (49) and (4R,<br />
5Z)-tetradec-5-en-4-olide (50)<br />
cis-2-Methyl-5-hexanolide (49) is a component <strong>of</strong> the<br />
pheromone blend <strong>of</strong> the carpenter bee Xylocopa hirutissima<br />
[112], while (4R,5Z)-tetradec-5-en-4-olide (50) is the sex<br />
pheromone <strong>of</strong> the Japanese beetle, Popillia japonica [113].<br />
Zarbin et al. [114] proposed a general approach to the synthesis<br />
<strong>of</strong> chiral pheromone lactones using readily available<br />
starting materials derived <strong>from</strong> 2-oxazolines. To show the<br />
usefulness <strong>of</strong> this approach, the diastereoselective synthesis<br />
<strong>of</strong> cis- and trans-49 and a formal synthesis <strong>of</strong> (4R,5Z)-50<br />
were performed (Scheme 45).<br />
7.5. (5R,6S)-6-Acetoxyhexadecane-5-olide (51)<br />
Laurence and Pickett described for the first time a natural<br />
mosquito oviposition attractant pheromone in 1982 [118]. A<br />
synthesis <strong>of</strong> the compound, (5R,6S)-6-acetoxyhexadecane-5-
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 327<br />
OH<br />
O<br />
OH<br />
1) CrCO 3 , DMF/MeOH,<br />
pH 7.0, BnBr, rt., 17 h, 84%<br />
O<br />
O<br />
OBn<br />
O<br />
O<br />
2) NaBH 4 , Et 2 O/MeOH,<br />
-20 o C, 2h, 95%<br />
O<br />
(S)-A; 92% e.e.<br />
3) PPL, Et 2 O, 30 o C, 24 h, 74%<br />
1) Pd/C 10%, H 2 , 1 atm, 3 h, 95%<br />
2) BH 3 .DMS, THF, rt., 2 h, 90%<br />
3) PCC, CH 2 Cl 2 , rt., 2 h 90%<br />
O<br />
O<br />
(S)- B<br />
O<br />
H<br />
(S)-A<br />
DIBAL-H, THF,<br />
-78 o C, 2h, 71%<br />
HO<br />
O<br />
(R)- C<br />
O<br />
OBn<br />
( ) 6<br />
PPh 3<br />
(S)-B, THF, -100 o C, 1.5 h, 60%<br />
O<br />
O<br />
(S) - 52<br />
Z/E = 96:4; 27% overall yield; 92% e.e.<br />
(R)-C, THF, -100 o C, 1.5 h, 55%<br />
Scheme 47.<br />
O<br />
O<br />
(R) - 52<br />
Z/E = 96:4; 18% overall yield; 92% e.e.<br />
isoprene<br />
Br 2<br />
Br<br />
Br<br />
DMPU<br />
Br<br />
+ vinylic isomers<br />
Scheme 48.<br />
1) In, NaI, DMF,<br />
3-methylbutanal, 91%<br />
2) NH 4 Cl/H 2 O<br />
OH<br />
53<br />
olide (51) was carried out by Sun et al. [119], employing a<br />
L-proline-catalyzed asymmetric aldol condensation between<br />
cyclopentanone and undecanal, followed by oxidation and<br />
acetylation (Scheme 46).<br />
7.6. (Z)-Hexadeca-7,15-dien-4-olide (52)<br />
(Z)-Hexadeca-7,15-dien-4-olide (52) was described by<br />
Leal et al. [120] as the female sex pheromone <strong>of</strong> the yellowish<br />
elongate chafer (Heptophylla picea). Clososki et al.<br />
[121] described an enzymatic synthesis <strong>of</strong> (R)- and (S)-52. A<br />
known lipase-catalysed enantiolactonization in the key step<br />
afforded the common precursor (S)-A for both enantiomers<br />
<strong>of</strong> the pheromone, in 92% e.e. (overall yield: 27% for (S) and<br />
18% for (R)-isomer) (Scheme 47).<br />
8. SYNTHESIS OF ISOPRENOIDS AS PHEROMONES<br />
8.1. <strong>Synthesis</strong> <strong>of</strong> Isoprenoidal Alcohols As <strong>Pheromones</strong><br />
8.1.1. 2-Methyl-6-methyleneoct-7-en-4-ol (53) (ipsenol)<br />
Ipsenol (2-methyl-6-methyleneoct-7-en-4-ol, 53) was<br />
identified as the aggregation pheromone <strong>of</strong> the California<br />
bark beetle (Ips paraconfusus) [122]. Ceschi et al. [123] described<br />
a short synthesis <strong>of</strong> racemic 53 employing a selective<br />
indium insertion on a mixture <strong>of</strong> 2-bromomethylbuta-1,3-<br />
diene and its vinylic isomers, in good yields (Scheme 48).<br />
8.1.2. (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)<br />
methyl 3-methyl-3-butenoate (54)<br />
(1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)methyl<br />
3-methyl-3-butenoate (54) has been identified as the sex<br />
pheromone produced by virgin females <strong>of</strong> the mealybug<br />
Pseudococcus cryptus [124].<br />
Nakahata et al. [125] acetylated (+)--pinene with lead<br />
acetate and cleaved the resulting acetate by ozonolysis. The<br />
triol obtained by reductive workup was reacted with<br />
trimethyl orth<strong>of</strong>ormate, and subsequent treatment with acetic<br />
acid yielded the alcohol A, which was esterified to give 54 in<br />
43% overall yield (Scheme 49).<br />
8.1.3. (1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)<br />
methyl acetate (55)<br />
(1R,3R)-(3-Isopropenyl-2,2-dimethylcyclobutyl)methyl<br />
acetate (55) has been identified as the female-produced sex<br />
pheromone <strong>of</strong> the citrus mealybug (Planococcus citri) which
328 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
Pd(OAc) 4 ,<br />
benzene, 75%<br />
OAc<br />
+<br />
(95:5)<br />
OAc<br />
O 3 , MeOH, then<br />
NaBH 4 , K 2 CO 3 , 72%<br />
HO<br />
OH<br />
OH<br />
DCC, DMAP,<br />
1) HC(OMe) 3 , PPTS, THF<br />
2) Ac 2 O, then NaOH (88% overall)<br />
HO<br />
CH 2 Cl 2 , 91%<br />
OH<br />
O<br />
O<br />
A<br />
O<br />
54<br />
Scheme 49.<br />
1) Pb(OAc) 4 , benzene<br />
RuCl 3 - NaIO 4 ,<br />
CH 3 CN/CCl 4 /H 2 O<br />
COOH<br />
2) MeOH, KOH, 55% (2 steps)<br />
(+)--pinene<br />
COOH<br />
1) (CH 3 ) 3 SiCH 2 MgCl<br />
OH<br />
(+)-trans-verbenol - A<br />
1) LiAlH 4 , Et 2 O<br />
OAc<br />
O<br />
2) Ac 2 O<br />
2) Ac 2 O, Py<br />
55<br />
Zn, CH 2 Br 2 , TiCl 4<br />
1) LiAlH 4 , Et 2 O<br />
RuCl 3 - NaIO 4 ,<br />
acetone, N-hydroxyphthalimide,<br />
t-BuOH/H 2 O<br />
(+)--pinene<br />
CrO 3 , 36%<br />
O<br />
(+)-R-verbenone - B<br />
COOH<br />
OAc<br />
O<br />
COOH<br />
2) Ac 2 O, Py<br />
55<br />
Scheme 50.<br />
is a major pest <strong>of</strong> c<strong>of</strong>fee, citrus, and cocoa in both the southern<br />
U. S. and the Mediterranean [126].<br />
Pássaro and Webster described two alternative syntheses<br />
<strong>of</strong> 55 [127]. Compound 55 was synthesized starting <strong>from</strong><br />
(+)-trans-verbenol A or (+)-(R)-verbenone B, obtained <strong>from</strong><br />
-pinene. The key step for both syntheses is the oxidative<br />
decarboxylation using RuCl 3 -NaIO 4 (Scheme 50).<br />
8.1.4. cis-2-(2-Isopropenyl-1-methylcyclobutyl)ethanol (56)<br />
(grandisol)<br />
Grandisol [cis-2-(2-isopropenyl-1-methylcyclobutyl)<br />
ethanol, 56] is the major component <strong>of</strong> the male-produced<br />
pheromone <strong>of</strong> the cotton boll weevil (Anthonomus grandis)<br />
[128] and was also identified <strong>from</strong> other pests, like bark<br />
weevils [129, 130] and bark beetles [131].<br />
The synthesis <strong>of</strong> a mixture <strong>of</strong> grandisol and its diastereomer<br />
fragranol was described by Bernard et al. [132]<br />
and is shown in Scheme 51. Key step is the palladium(0)-<br />
catalysed reduction <strong>of</strong> the 2-cyclobutylidenepropyl sulfonic<br />
ester A (E:Z 30:70) by ammonium formate to furnish (±)-56<br />
and (±)-fragranol in 70:30 ratio.<br />
8.2. <strong>Synthesis</strong> <strong>of</strong> Isoprenoidal Aldehydes and Ketones as<br />
<strong>Pheromones</strong><br />
8.2.1. (Z)-exo--Bergamotenal (57)<br />
Alizadeh et al. [133] described the synthesis <strong>of</strong> a racemic<br />
mixture <strong>of</strong> (Z)-exo--bergamotenal (57), a sex pheromone<br />
component <strong>of</strong> the white-spotted spined bug Eysarcoris parvus,<br />
<strong>from</strong> racemic exo--bergamotene by a five-step se-
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 329<br />
SPh<br />
H<br />
+<br />
O<br />
OBn<br />
n-BuLi<br />
THF, 0 o C<br />
SPh<br />
OH<br />
OBn<br />
PTSA<br />
benzene, , 98%<br />
O<br />
OBn<br />
COOEt<br />
P(O)OEt 2<br />
CH 2 OTs<br />
Pd(dba)2, PPh3,<br />
1) NaH, TDA-1, THF, <br />
OBn<br />
CH3CN, HCOONH4<br />
OBn<br />
+<br />
OBn<br />
2) LiAlH 4<br />
(70:30)<br />
3) TsCl, DMAP, NEt<br />
A<br />
3<br />
Li/NH 3<br />
+<br />
OH<br />
OH<br />
56 (70:30)<br />
Scheme 51.<br />
O<br />
COCl<br />
Ref. 134<br />
1) N 2 H 4 , AcOH, EtOH<br />
2) t-BuOK, DMSO<br />
m-CPBA, aq.<br />
O<br />
H 5 IO 6 , H 2 O/THF<br />
OHC<br />
NaHCO 3 , CH 2 Cl 2<br />
57<br />
1) NaH, (o-Tolyl-O) 2 P(O)CH(CH 3 )CO 2 Et, THF<br />
2) DIBAL - H, THF<br />
3) MnO 2 , hexane<br />
CHO<br />
Scheme 52.<br />
quence involving regioselective epoxidation and (Z)-<br />
selective Wittig olefination reactions (Scheme 52).<br />
8.2.2. Iridodial (58)<br />
In <strong>2004</strong>, Zhang et al. [135] identified iridodial [(1R,2S,<br />
5R,8R)-(2-(1-formylethyl)-3-methylcyclopentanecarboxaldehyde,<br />
58] as a male-produced male-aggregation pheromone<br />
<strong>of</strong> Chrysopa oculata, the first pheromone identified <strong>from</strong><br />
lacewings.<br />
Chauhan et al. [136] described the synthesis <strong>of</strong><br />
(1R,2S,5R,8R)-58 and <strong>of</strong> the diastereomers (1R,2S,5R,8S)-<br />
58, (1S,2S,5R,8R)-58, and (1S,2S,5R,8S)-58 in five steps<br />
<strong>from</strong> (4aS,7S,7aR) and (4aS,7S,7aS)-nepetalactones, which<br />
have been isolated by chemical separation <strong>from</strong> catnip (Nepeta<br />
cataria) oil [137] (Scheme 53).<br />
8.2.3. 3,7-Dimethyl-2-oxooct-6-ene-1,3-diol (59)<br />
Dickens et al. [138] identified 3,7-dimethyl-2-oxooct-6-<br />
ene-1,3-diol (59) as the male-produced aggregation pheromone<br />
<strong>from</strong> the Colorado potato beetle (Leptinotarsa decemlineata).<br />
The absolute configuration <strong>of</strong> natural 59 was determined<br />
to be (S) by syntheses <strong>of</strong> the racemate and both<br />
enantiomers <strong>from</strong> geraniol and (R)- and (S)-linalool, respectively,<br />
by Oliver et al. [139] (Scheme 54).<br />
9. SYNTHESIS OF ACETALS AS PHEROMONES<br />
9.1. 4-Hydroxy-1,7-dioxaspiro[5.5]undecane (60)<br />
Baker and co-workers described the isolation and identification<br />
<strong>of</strong> 4-hydroxy-1,7-dioxaspiro[5.5]undecane (60), a<br />
minor component <strong>of</strong> the female-produced sex pheromone <strong>of</strong><br />
the olive fruit fly, Bactrocera oleae, establishing the most<br />
favorable configuration as (4S,6S) [140, 141]. Hao and Forsyth<br />
[142] described a short total synthesis <strong>of</strong> 60 employing<br />
a double intramolecular hetero-Michael addition strategy,<br />
applicable to spiroketal synthesis (Scheme 55).
330 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
O<br />
O<br />
NaHCO 3 (5%),<br />
MeOH/H 2 O (95:5), rt.<br />
COOCH 3<br />
CHO<br />
1) HOCH 2 CH 2 OH, toluene, cat.<br />
TsOH, azeotropic dehydration<br />
2) flash chromatography<br />
COOCH 3<br />
O<br />
O<br />
+<br />
COOCH 3<br />
O<br />
O<br />
A<br />
B<br />
A<br />
1) DIBAL - H, toluene, -78 to 0 o C<br />
2) PDC, dry CH 2 Cl 2 , rt.<br />
CHO<br />
O<br />
O<br />
THF, 2N HCl, rt.<br />
CHO<br />
CHO<br />
Similarly<br />
CHO<br />
(1R,2S,5R,8R)-58<br />
B<br />
CHO<br />
(1R,2S,5R,8S)-58<br />
O<br />
CHO<br />
CHO<br />
O<br />
Similarly<br />
CHO<br />
CHO<br />
Scheme 53.<br />
(1S,2S,5R,8R)-58<br />
(1S,2S,5R,8S)-58<br />
OH<br />
1) t-BuOOH, VO(acac) 2<br />
O<br />
OAc<br />
2) Ac 2 O, Py<br />
OH<br />
geraniol<br />
*<br />
OH<br />
t-BuOOH, VO(acac) 2<br />
*<br />
OH<br />
O<br />
1) HClO 4 , DMF<br />
2) K 2 CO 3 , MeOH<br />
*<br />
OH<br />
A: racemic<br />
B: 3-(S)<br />
C: 3-(R)<br />
OH<br />
(R)- and (S)-linalool<br />
OH<br />
OH<br />
A: racemic<br />
B: 3-(S)<br />
C: 3-(R)<br />
1)TBDPSCl, imidazole<br />
2) Swern oxidation<br />
*<br />
O<br />
OTBDPS<br />
TBAF<br />
*<br />
O<br />
OH<br />
racemic 59<br />
(S)-59<br />
(R)-59<br />
Scheme 54.
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 331<br />
O<br />
OTBS<br />
1) n-BuLi, TBSOCH 2 CH 2 CHO<br />
2) MnO 2 , 75% (2 steps)<br />
TBSO<br />
OTBS<br />
CSA, MeOH<br />
O<br />
1) NaBH 4 , MeOH<br />
O<br />
Scheme 55.<br />
then benzene, 70%<br />
O<br />
O<br />
2) PTSA, MeOH<br />
82% (2 steps)<br />
HO<br />
60<br />
O<br />
(Z) or (E)<br />
OH<br />
1) MsCl, Py<br />
2) LiBr, Acetone<br />
Br<br />
1) Mg, Et 2 O<br />
2)<br />
Br<br />
(Z) or (E)<br />
O<br />
O<br />
m-CPBA, CH 2 Cl 2<br />
or<br />
rac-cis- A<br />
rac-trans- B<br />
Mycobacterium<br />
rac-cis- A<br />
paraffinicum<br />
NCIMB 10420<br />
buffer pH 7.5, 83%<br />
OH<br />
OH<br />
PdCl 2 , cat. CuCl 2<br />
MeO(CH 2 ) 2 OMe<br />
O<br />
O<br />
Mycobacterium<br />
92% e.e.<br />
(+)-exo - 61<br />
rac-trans- B<br />
paraffinicum<br />
NCIMB 10420<br />
buffer pH 7.5, 83%<br />
OH<br />
OH<br />
PdCl 2 , cat. CuCl 2<br />
MeO(CH 2 ) 2 OMe<br />
O<br />
O<br />
92% e.e.<br />
(-)-endo - 62<br />
Scheme 56.<br />
9.2. 7-Ethyl-5-methyl-6,8-dioxabicyclo[3.2.1]octane (61)<br />
[exo-(61) and endo-brevicomin (62)]<br />
exo-Brevicomin (61) and endo-brevicomin (62) are typical<br />
components <strong>of</strong> the aggregation pheromone system <strong>of</strong><br />
several bark beetle species <strong>of</strong> the genera Dendroctonus and<br />
Dryocoetes [143-146]. Mayer et al. [147] synthesized<br />
(1R,5S,7R)-61 and (1S,5R,7R)-62, employing an enantioconvergent<br />
biocatalytic hydrolysis <strong>of</strong> cis-configured 2,3-<br />
disubstituted oxiranes by bacterial epoxide hydrolases<br />
(Scheme 56).<br />
9.3. (1R,5S,7R)-exo-Brevicomin (61), (1R,1’R,5’R,7’R)-<br />
and (1S,1’R,5’R,7’R)-1-hydroxy-exo-brevicomin (63)<br />
Francke et al. [148] have identified 1-hydroxy-exobrevicomin<br />
(63) <strong>from</strong> the pine beetle Dendroctonus ponderosae.<br />
Kumar and Rao [149] described a synthesis <strong>of</strong><br />
(1R,1’R,5’R,7’R)-63 and (1S,1’R,5’R,7’R)-63 and <strong>of</strong><br />
(1R,5S,7R)-61, starting <strong>from</strong> -picoline ((Scheme 57) (Table<br />
1)).<br />
9.4. 1,5-Dimethyl-6,8-dioxabicyclo[3.2.1octane (64) (frontalin)<br />
Frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane,<br />
64) was first isolated by Kinzer [151], and is a component <strong>of</strong><br />
the aggregation pheromone <strong>of</strong> the southern pine beetle (Dendroctonus<br />
frontalis), and <strong>of</strong> the western pine beetle, Dendroctonus<br />
brevicomis. By means <strong>of</strong> bioassays with pure synthetic<br />
enantiomers, Mori [145, 152] has shown that the absolute<br />
configuration <strong>of</strong> natural 64 is (1S,5R). Chênevert and<br />
Caron [153] described an enantioselective synthesis <strong>of</strong><br />
(1S,5R)-(–)-64 in 90% e.e. via enzymatic desymmetrization<br />
<strong>of</strong> an achiral triol (Scheme 58).<br />
A synthesis <strong>of</strong> racemic 64 was performed by Yang [154]<br />
et al. Diene A was subjected to a double dihydroxylation<br />
with catalytic osmium tetroxide and 4-methylmorpholine-Noxide<br />
in MeCN–MeCOMe–H 2 O (1:1:1), generating tetraol<br />
B. Subsequently, mono cleavage and acid-catalyzed intramolecular<br />
acetalation led to 64. Use <strong>of</strong> AD-mix- in the
332 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
Ph 3 PCHCOCH 3 , CH 2 Cl 2 , 3 h<br />
N<br />
Na in liq. NH3.EtOH<br />
N<br />
H<br />
4N HCl<br />
O<br />
A<br />
O<br />
H<br />
(overall yield<br />
for three steps 35%)<br />
O<br />
O<br />
AD-mix-, t-BuOH/H 2 O,<br />
1:1, 3 h, 0 o C<br />
O<br />
OH<br />
O<br />
PTSA (cat.),<br />
CH 2 Cl 2 , 54% (2 steps)<br />
OH<br />
O<br />
O<br />
Table 1<br />
O<br />
O<br />
+<br />
O<br />
O<br />
O<br />
OH<br />
(1R,1'R,5'R,7'R)-63<br />
OH<br />
(1S,1'R,5'R,7'R)-63<br />
A<br />
Ph 3 PCHCOOEt, CH 2 Cl 2 30 min<br />
(overall yield for three steps 25%)<br />
O<br />
O<br />
OEt<br />
AD-mix-, t-BuOH/H 2 O,<br />
1:1, 3 h, 0 o C<br />
O<br />
OH<br />
O<br />
OEt<br />
OH<br />
PTSA (cat.),<br />
CH 2 Cl 2 , 54% (2 steps)<br />
O<br />
O<br />
OEt<br />
LiCl, NaBH 4 ,<br />
EtOH, THF, 77%<br />
O<br />
O<br />
Ref. 150<br />
O<br />
O<br />
Scheme 57.<br />
O<br />
OH<br />
61<br />
Table 1.<br />
Solv.s and Temperature Yield (%) (1R,1’R,5’R,7’R)-(63) (1S,1’R,5’R,7’R)-(63)<br />
Li AlH 4 THF, 0 o C 86 32 68<br />
NaBH 4 MeOH, 0 o C 92 36 64<br />
Zn(BH 4) 2 THF, 0 o C 84 25 75<br />
K-Selectride Toluene, -78 o C 79 22 78<br />
DIBAL-H THF, 0 o C 92 20 80<br />
dihydroxylation step resulted in only poor enantioselectivity<br />
(16% e.e.) (Scheme 59).<br />
9.5. 1,3,8-Trimethyl-2,9-dioxabicyclo[3.3.1]non-7-ene (65)<br />
In 2001, Nakashima [155] reported the identification <strong>of</strong><br />
1,3,8-trimethyl-2,9-dioxabicyclo[3.3.1]non-7-ene (65) <strong>from</strong><br />
the hexane extract <strong>of</strong> the brush organ located at the hind legs<br />
<strong>of</strong> male swift moths Endoclita excrescens.<br />
The absolute configuration was determined by synthesis<br />
in a preliminary communication by Marukawa and Mori<br />
[156]. The same authors reported the synthesis <strong>of</strong> the<br />
(1R,3S,5S)- and (1S,3R,5R)-isomers, starting <strong>from</strong> the pure<br />
enantiomers <strong>of</strong> ethyl 3-hydroxybutanoate [157] (Scheme 60).<br />
9.6. (+)-Lineatin (66)<br />
Lineatin [3,3,7-trimethyl-2,9-dioxatricyclo[3.3.1.0 4,7 ]nonane,<br />
66] is the most important constituent <strong>of</strong> the aggregation<br />
pheromone isolated <strong>from</strong> the frass <strong>of</strong> the female ambrosia<br />
beetle Trypodendron lineatum, which is a deleterious pest<br />
to coniferous forests in Europe and North America [158].<br />
Alibés [159] et al. described a highly stereoselective<br />
formal synthesis <strong>of</strong> (+)-lineatin in 14 steps and 14% overall<br />
yield <strong>from</strong> the homochiral furanone A (Scheme 61). Key<br />
steps <strong>of</strong> this synthetic approach feature the diastereoselective<br />
construction <strong>of</strong> the cyclobutene derivative B by a photochemical<br />
cycloaddition, and a regiocontrolled oxymercuration<br />
reaction to form the dihydroxy compound C.<br />
10. SYNTHESIS OF AN AMIDE AS PHEROMONE<br />
10.1. (1’S,2R,2’S,3’R)-N-(1’-(Hydroxymethyl)-2’,3’-dihydroxytetradecyl)-2-hydroxy-21-methyldocosanamide<br />
(67)<br />
Asai et al. [162] reported in 2000 the ceramide (1’S,2R,<br />
2’S,3’R)-N-(1’-(hydroxymethyl)-2’,3’-dihydroxytetradecyl)-<br />
2-hydroxy-21-methyldocosanamide (67) to be the sex phero-
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 333<br />
O<br />
O O<br />
MgBr<br />
+ TBDPSO<br />
OTBDPS<br />
1) THF -78 o C<br />
2) TBAF, THF<br />
Pseudomonas sp. lipase,<br />
O O<br />
OH<br />
vinyl acetate, benzene<br />
OAc +<br />
O O<br />
(R)-A OH<br />
1) TsCl, DMAP, Py,<br />
O<br />
2) PTSA, CH 2 Cl 2 , H 2 O.<br />
(R)-A<br />
OTs<br />
LiEt 3 BH, THF,<br />
O<br />
reflux<br />
TsCl, Et 3 N, DMAP, CH 2 Cl 2<br />
PTSA,<br />
OAc<br />
OH<br />
Et 2 O, H 2 O<br />
O O<br />
O<br />
LiAlH 4 , THF<br />
O O OH<br />
OH<br />
O O<br />
OH<br />
OH<br />
OH<br />
OAc<br />
OAc<br />
O<br />
O<br />
64<br />
Scheme 58.<br />
OsO 4 , NMO<br />
MeCN/acetone/H 2 O<br />
OH<br />
OH<br />
(1:1:1), 0°C, rt.<br />
OH<br />
OH<br />
A<br />
HCl, H 5 IO 6 , H 2 O,<br />
O<br />
B<br />
Et 2 O, , 64%<br />
64<br />
O<br />
O<br />
1) AD-mix-, t-BuOH, H 2 O<br />
(1:1), 0°C, rt.<br />
O<br />
Scheme 59.<br />
A<br />
2) HCl, H 5 IO 6 , H 2 O,<br />
Et 2 O, , 55%<br />
(-)-64 16% e.e.<br />
OH<br />
A<br />
O<br />
O<br />
m-CPBA,CH 2 Cl 2 , 89%<br />
1) NaBH 4 , CeCl 3.7 H 2 O,<br />
MeOH, 94%<br />
2) n-BuLi, CS 2 ,<br />
MeI, THF, 98%<br />
1) TBDMSCl, imidazole, DMF, 91%<br />
2) DIBAL-H, CH 2 Cl 2 , 88%<br />
3) 2,3-dimethylfuran, t-BuLi,<br />
Et 2 O/HMPA<br />
4) chromatography<br />
O<br />
O<br />
OH<br />
O<br />
O<br />
H<br />
OCS 2 Me<br />
O<br />
OTBDMS<br />
OH<br />
(n-Bu) 3 SnH, AIBN,<br />
toluene, 76%<br />
OTBDMS<br />
A 35% B 27%<br />
48% HF aq.,<br />
MeCN, 79%<br />
+<br />
O<br />
O<br />
O<br />
O<br />
(1R,3S,5S) - 65<br />
O<br />
OH<br />
O<br />
OTBDMS<br />
Scheme 60.<br />
OH<br />
O<br />
O<br />
Similarly<br />
O<br />
O<br />
(1S,3R,5R) - 65
334 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
PivO<br />
O<br />
A<br />
O<br />
(Z)-1,2-dichloroethylene, hn,<br />
CH 3 CN, -15 o C, 89%<br />
PivO<br />
Cl<br />
O<br />
H<br />
Cl<br />
O<br />
Zn, EtOH (80%),<br />
MW, 105 o C<br />
PivO<br />
O<br />
B<br />
anti<br />
O<br />
H<br />
PivO<br />
76% d.e.<br />
O<br />
O<br />
+<br />
H<br />
syn<br />
B<br />
1) MeLi, THF, -78 o C, 86%<br />
2) PTSA, acetone, rt. 91%<br />
O<br />
O<br />
OH<br />
H<br />
1) Hg(OAc) 2 , THF/H 2 O, rt.<br />
2) NaBH 4 , NaOH, rt., 92%<br />
O<br />
O<br />
OH<br />
H<br />
OH<br />
C<br />
1) NaH, BnBr, THF, rt., 79%<br />
2) TFA, MeOH/H 2 O, rt., 94%<br />
HO<br />
OH<br />
OH<br />
H<br />
OBn<br />
1) TsCl, DMAP (cat.), Py, reflux, 84%<br />
2) TCDI, THF, 70 o C, 90%<br />
ImCSO<br />
O<br />
H<br />
OBn<br />
1) Bu 3 SnH, AIBN, toluene, 100 o C, 93%<br />
2) H 2 , Pd/C, HOAc, rt. 98%.<br />
O<br />
H<br />
OH<br />
1) Dess-Martin periodinane, CH 2 Cl 2 , rt.<br />
2) RuCl 3 , NaIO 4 , CCl 4 ,/H 2 O, rt. (81%, 2 steps)<br />
O<br />
O<br />
H<br />
O<br />
Ref. [160, 161]<br />
O<br />
O<br />
H<br />
Scheme 61.<br />
>99.5% e.e.<br />
(+)-66<br />
HO<br />
1) (CH 3 ) 2 CH(CH 2 ) 2 MgBr,<br />
Br Li 1) PTSA, EtOH, 97%<br />
2 CuCl 4 , THF, 99%<br />
( ) 11 THPO ( )19 HO 2 C ( ) 19<br />
2) TsCl, Py, 89%<br />
2) Jones' CrO 3 , acetone, 74%<br />
3) THPO(CH 2 ) 6 MgBr,<br />
Li 2 CuCl 4 , THF, 79%<br />
1) Br 2 , P, , 84%<br />
2) NaOH, H 2 O, 90%<br />
CO 2 H<br />
OH<br />
1) CH 2 =CHOCOCH 3 ,<br />
TBDMSO<br />
Lipase PS, BHT, THF, 23%<br />
( ) 18<br />
CO 2 H ( ) 18<br />
2) TBDMSCl, imidazole, DMF, 80%<br />
A<br />
(S) - Serine<br />
Ref. [164,165]<br />
O<br />
NBoc<br />
CHO<br />
HC<br />
C(CH 2 ) 9 CH 3 ,<br />
n-BuLi, THF, 85%<br />
O<br />
NBoc<br />
OH<br />
( ) 9<br />
1) Li, C 2 H 5 NH 2<br />
OTBDMS<br />
1) TsCl, Py, 90%<br />
OTBDMS<br />
2) TBDMSOTf, 2,6-lutidine,<br />
CH 2 Cl 2 , 72% (2 steps)<br />
TBDMSO<br />
NH 2<br />
( ) 9<br />
TBDMSO<br />
( ) 9<br />
2) DMD, acetone, 68%<br />
NHTs<br />
3) DIBAL-H, toluene, 84%
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 335<br />
Scheme 61 contd....<br />
1) Na, naphthalene, DME<br />
2) TBSOTf, 2,6-lutidine,<br />
CH 2 Cl 2 , 81% (2 steps)<br />
TBDMSO<br />
OTBDMS<br />
( ) 9<br />
NH 2 OTBDMS<br />
B<br />
OH<br />
A + B<br />
1) EDC, HOBt, CH 2 Cl 2 , 55%<br />
2) TBAF, THF, 71%<br />
HO<br />
HN<br />
OH<br />
OH<br />
Scheme 62.<br />
O<br />
67<br />
mone <strong>of</strong> the female hair crab, Erimacrus isenbeckii. Masuda<br />
et al. [163] described a enantiodivergent synthesis, employing<br />
12-bromododecan-1-ol for the synthesis <strong>of</strong> the acid moiety<br />
A with a lipase-catalyzed resolution <strong>of</strong> hydroxy-acid in<br />
the key step, and (S)-serine for the construction <strong>of</strong> the amine<br />
moiety B, which were reacted to give the amide 67 (Scheme<br />
62).<br />
ACKNOWLEDGEMENTS<br />
The Brazilian authors want to thank Capes, Fundação<br />
Araucária and CNPq for financial support. JB thanks the<br />
Dirección de Investigación <strong>of</strong> PUCV and Fondecyt for financial<br />
support.<br />
ABBREVIATIONS<br />
Ac = acetyl<br />
AIBN = azobisisobutyronitrile<br />
BnBr = benzyl bromide<br />
CAN = ceric ammonium nitrate<br />
CSA = camphorsulfonic acid<br />
DABCO = 1,4-diazabicyclo[2.2.2]octane<br />
DEAD = diethyl azodicarboxylate<br />
DET = diethyl tartrate<br />
DHP = 3,4-dihydro-2H-pyran<br />
(DHQ) 2 -PHAL = hydroquinine 1,4-phthalazinediyl<br />
diether<br />
DIBAL-H = diisobutylaluminium hydride<br />
DIPEA = ethyldiisopropylamine<br />
DMAP = 4-dimethylaminopyridine<br />
DME = dimethoxyethane<br />
2,2-DMP = 2,2-dimethoxypropane<br />
DMF = N,N-dimethylformamide<br />
DMPU = 1,3-dimethyltetrahydropyrimidin-<br />
2(1H)-one<br />
DMSO = dimethylsulfoxide<br />
HMPA = hexamethylphosphoramide<br />
HOBt = 1-hydroxybenzotriazole<br />
HONO = gaseous nitrous acid<br />
KIPBH = potassium tri-isopropoxyborohydride<br />
LDA = lithium diisopropylamide<br />
LiHMDS = lithium hexamethyldisilazide<br />
m-CPBA = m-chloroperbenzoic acid<br />
MeCBS = methyl oxazaborolidine<br />
MsCl = methanesulfonyl chloride (mesyl<br />
chloride)<br />
NaHMDS = sodium hexamethyldisilazide<br />
NIS = N-iodosuccinimide<br />
NMO = N-methylmorpholine-N-oxide<br />
PCC = pyridinium chlorochromate<br />
PDC = pyridinium dichromate<br />
PPh 3 = triphenyl phosphine<br />
PPL = porcine pancreatic lipase<br />
PPTS = pyridinium p-toluenesulfonate<br />
PTSA = p-toluenesulfonic acid<br />
Py = pyridine<br />
SOCl 2 = thionyl chloride<br />
TBAF = tetra-n-butylammonium fluoride<br />
TBDMSCl = tert-butyldimethylsilyl chloride<br />
TBDPSCl = tert-butyldiphenylchlorosilane<br />
TCDI = 1,1'-thiocarbonyldiimidazole<br />
TDA-1 = tris-(3,6-dioxaheptyl)amine<br />
TFA = trifluoroacetic acid<br />
THF = tetrahydr<strong>of</strong>urane<br />
THP = tetrahydropyranyl<br />
TMEDA = tetramethylethylenediamine<br />
TMPDA = tetramethylpropylenediamine<br />
TMSCl = trimethylsilyl chloride<br />
TMSOTf = trimethylsilyl trifluoromethanesulfonate<br />
TPAP = tetrapropylammonium perruthenate
336 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
TsCl = p-toluenesulfonyl chloride (tosyl<br />
chloride)<br />
TsNHNH 2 = p-toluenesulfonyl hydrazine<br />
REFERENCES<br />
[1] Meinwald, J. Proc. Natl. Acad. Sci. USA, 2003, 100, 14514<br />
[2] Mori, K. in The total synthesis <strong>of</strong> natural products, (ApSimon, J.<br />
Ed.:), Wiley, New York, 1981, Vol. 4.<br />
[3] Mori, K. in The total synthesis <strong>of</strong> natural products, (ApSimon, J.<br />
Ed.:), Wiley, New York, 1992, Vol. 9.<br />
[4] Mori, K. Chem. Commun., 1997, 1153.<br />
[5] Mori, K. Eur. J. Org. Chem., 1998, 1479.<br />
[6] Mori, K. Acc. Chem. Res., 2000, 33, 102.<br />
[7] Mori, K. in Chemistry <strong>of</strong> <strong>Pheromones</strong> and Other Semiochemicals I,<br />
<strong>2004</strong>, Vol. 239, pp. 1-50.<br />
[8] Aleu, J.; Bustillo, A. J.; Hernandez-Galan, R., Collado, I. G., Curr.<br />
Org. Chem., 2007, 11, 693.<br />
[9] Francke, W.; Toth, M.; Szocs, G.; Krieg, W.; Ernst, H., Buschmann,<br />
E., Z. Naturforsch. C., 1988, 43, 787<br />
[10] Moreira, J. A., Correa, A. G. Tetrahedron Asymmetry, 2003, 14,<br />
3787.<br />
[11] Ferreira, J. T. B., Zarbin, P. H. G. Bioorg. Med. Chem., 1996, 4,<br />
381.<br />
[12] Moreira, J. A., Correa, A. G. J. Braz. Chem. Soc., 2000, 11, 614.<br />
[13] Zarbin, P. H. G.; Princival, J. L.; de Lima, E. R.; dos Santos, A. A.;<br />
Ambrogio, B. G., de Oliveira, A. R. M., Tetrahedron Lett., <strong>2004</strong>,<br />
45, 239.<br />
[14] Hall, D. R.; Beevor, P. S.; Campion, D. G.; Chamberlain, D. J.;<br />
Cork, A.; White, R.; Almestre, A.; Henneberry, T. J.; Nandagopal,<br />
V.; Wightman, J. A.; Ranga Rao, G. V. Bull. OILB-SROP., 1993,<br />
16, 1.<br />
[15] Lamers, Y.; Rusu, G.; Wijnberg, J.; de Groot, A. Tetrahedron,<br />
2003, 59, 9361.<br />
[16] Gijsen, H. J. M.; Kanai, K.; Stork, G. A.; Wijnberg, J.; Orru, R. V.<br />
A.; Seelen, C.; Vanderkerk, S. M., Degroot, A. Tetrahedron, 1990,<br />
46, 7237.<br />
[17] Gries, R.; Gries, G.; Li, J. X.; Maier, C. T.; Lemmon, C. R.; Slessor,<br />
K. N. J. Chem. Ecol., 1994, 20, 2501.<br />
[18] Maier, C. T.; Gries, R., Gries, G. J. Chem. Ecol., 1998, 24, 491.<br />
[19] Duff, C. M.; Gries, G.; Mori, K.; Shirai, Y.; Seki, M.; Takikawa,<br />
H.; Sheng, T.; Slessor, K. N.; Gries, R.; Maier, C. T.; Ferguson, D.<br />
C. J. Chem. Ecol., 2001, 27, 431.<br />
[20] Chow, S.; Koenig, W. A.; Kitching, W. Eur. J. Org. Chem., <strong>2004</strong>,<br />
1198.<br />
[21] Badioli, M.; Ballini, R.; Bartolacci, M.; Bosica, G.; Torregiani, E.;<br />
Marcantoni, E. J. Org. Chem., <strong>2002</strong>, 67, 8938.<br />
[22] Millar, J. G.; Knudson, A. E.; McElfresh, J. S.; Gries, R.; Gries, G.;<br />
Davis, J. H. Bioorg. Med. Chem., 1996, 4, 331.<br />
[23] Passaro, L. C.; Webster, F. X. <strong>Synthesis</strong>-Stuttgart., 2003, 1187.<br />
[24] Francke, W.; Franke, S.; Bergmann, J.; Tolasch, T.; Subchev, M.;<br />
Mircheva, A.; Toshova, T.; Svatos, A.; Kalinova, B.; Karpati, Z.;<br />
Szocs, G.; Toth, M. Z. Naturforsch. C., <strong>2002</strong>, 57, 739.<br />
[25] Miyashita, M.; Yoshikoshi, A.; Grieco, P.A. J. Org. Chem., 1977,<br />
42, 3772.<br />
[26] Wakamura, S.; Arakaki, N.; Yamamoto, M.; Hiradate, S.; Yasui,<br />
H.; Yasuda, T.; Ando, T. Tetrahedron Lett., 2001, 42, 687.<br />
[27] Fernandes, R. A.; Kumar, P. Tetrahedron, <strong>2002</strong>, 58, 6685.<br />
[28] Gries, R.; Holden, D.; Gries, G.; Wimalaratne, P. D. C.; Slessor, K.<br />
N.; Saunders, C. Naturwissenschaften., 1997, 84, 219.<br />
[29] Muto, S.; Mori, K. Eur. J. Org. Chem., 2003, 1300.<br />
[30] Wimalaratne, P. D. C.; Slessor, K. N. J. Chem. Ecol., <strong>2004</strong>, 30,<br />
1225.<br />
[31] Muto, S.; Mori, K. Biosci. Biotechnol., Biochem., 2003, 67, 1559.<br />
[32] Perez, A. L.; Campos, Y.; Chinchilla, C. M.; Oehlschlager, A. C.;<br />
Gries, G.; Gries, R.; GiblinDavis, R. M.; Castrillo, G.; Pena, J. E.;<br />
Duncan, R. E.; Gonzalez, L. M.; Pierce, H. D.; McDonald, R.: Andrade,<br />
R. J. Chem. Ecol., 1997, 23, 869.<br />
[33] Giblin-Davis, R. M.; Gries, R.; Crespi, B.; Robertson, L. N.; Hara,<br />
A. H.; Gries, G.; O'Brien, C. W.; Pierce, H. D. J. Chem. Ecol.,<br />
2000, 26, 2763.<br />
[34] Baraldi, P. T.; Zarbin, P. H. G.; Vieira, P. C.; Correa, A. G., Tetrahedron<br />
Asymmetry, <strong>2002</strong>, 13, 621.<br />
[35] Dhotare, B.; Salaskar, A.; Chattopadhyay, A. <strong>Synthesis</strong>-Stuttgart.,<br />
2003, 2571.<br />
[36] Zarbin, P. H. G.; Princival, J. L.; dos Santos, A. A.; de Oliveira, A.<br />
R. M. J. Braz. Chem. Soc., <strong>2004</strong>, 15, 331.<br />
[37] Gore, W. E.; Pearce, G. T.; Lanier, G. N.; Simeone, J. B.; Silverst.Rm;<br />
Peacock, J. W.; Cuthbert, R. A. Abstr. Am. Chem. Soc.,<br />
1974, 65.<br />
[38] Blight, M. M.; Wadhams, L. J.; Wenham, M. J. Insect Biochemistry,<br />
1979, 9, 525.<br />
[39] Blight, M. M.; Wadhams, L. J.; Wenham, M. J.; King, C. J. Forestry,<br />
1979, 52, 83.<br />
[40] Pignatello, J. J.; Grant, A. J. J. Chem. Ecol., 1983, 9, 615.<br />
[41] Ben-Yehuda, S.; Tolasch, T.; Francke, W.; Gries, R.; Gries, G.;<br />
Dunkelblum, E.; Mendel, Z. IOBC-WPRS Bull., <strong>2002</strong>, 25, 259.<br />
[42] Zada, A.; Ben-Yehuda, S.; Dunkelblum, E.; Harel, M.; Assael, F.,<br />
Mendel, Z. J. Chem. Ecol., <strong>2004</strong>, 30, 631.<br />
[43] Enders, D.; Kipphardt, H.; Fey, P. in Organic <strong>Synthesis</strong> Coll., Vol.<br />
VIII, Wiley, Canada, 1993, pp. 403-414.<br />
[44] Larsson, M.; Andersson, J.; Liu, R.; Högberg, H. E. Tetrahedron<br />
Asymmetry, <strong>2004</strong>, 15, 2907.<br />
[45] Hedenström, E.; Edlund, H.; Lund, S.; Abersten, M.; Persson, D. J.<br />
Chem. Soc., Perkin Trans. 1., <strong>2002</strong>, 1810,<br />
[46] Wassgren, A. B.; Bergström, G.; Sierpinski, A.; Anderbrant, O.;<br />
Högberg, H. E.; Hedenström, E. Naturwissenschaften., 2000, 87,<br />
24.<br />
[47] Bergström, G.; Wassgren, A. B.; Anderbrant, O.; Ochieng, S. A.;<br />
Ostrand, F.; Hansson, B. S.; Hedenström, E.; Högberg, H. E. Naturwissenschaften.,<br />
1998, 85, 244.<br />
[48] Bergström, G.; Wassgren, A. B.; Anderbrant, O.; Fagerhag, J.;<br />
Edlund, H.; Hedenström, E.; Högberg, H. E.; Geri, C.; Auger, M.<br />
A.; Varama, M.; Hansson, B. S.; Löfqvist, J. Experientia., 1995,<br />
51, 370.<br />
[49] Tai, A.; Higashiura, Y.; Kakizaki, M.; Naito, T.; Tanaka, K.; Fujita,<br />
M.; Sugimura, T.; Hara, H.; Hayashi, N. Biosci. Biotechnol. Biochem.,<br />
1998, 62, 607.<br />
[50] Bekish, A. V.; Prokhorevich, K. N.; Kulinkovich, O. G. Tetrahedron<br />
Lett., <strong>2004</strong>, 45, 5253.<br />
[51] Dandapani, S.; Jeske, M.; Curran, D. P. Proc. Natl. Acad. Sci.,<br />
USA, <strong>2004</strong>, 101, 12008.<br />
[52] Cammaerts, M. C.; Attygalle, A. B.; Evershed, R. P.; Morgan, E.<br />
D. Physiol. Entomol., 1985, 10, 33.<br />
[53] Brand, J. M. J. Chem. Ecol., 1985, 11, 177.<br />
[54] Cammaerts, M. C.; Mori, K. Physiol. Entomol., 1987, 12, 381.<br />
[55] Pinyarat, W.; Mori, K. Biosci. Biotechnol. Biochem., 1992, 56,<br />
1673.<br />
[56] RamirezLucas, P.; Malosse, C.; Ducrot, P. H.; Lettere, M.; Zagatti,<br />
P. Bioorg. Med. Chem., 1996, 4, 323.<br />
[57] Cho, B. T.; Kim, D. J. Tetrahedron, 2003, 59, 2457.<br />
[58] Baeckström, P.; Bergström, G.; Bjorkling, F.; He, H. Z.; Högberg,<br />
H. E.; Jacobsson, U.; Lin, G. Q.; Löfqvist, J.; Norin, T.; Wassgren,<br />
A. B. J. Chem. Ecol., 1989, 15, 61.<br />
[59] Chow, S.; Kitching, W. Tetrahedron Asymmetry, <strong>2002</strong>, 13, 779.<br />
[60] Suguro, T.; Mori, K. Agric. Biol. Chem., 1979, 43, 869.<br />
[61] Tamaki, Y.; Noguchi, H.; Sugie, H.; Sato, R.; Kariya, A. Appl. Ent.<br />
Zool., 1979, 14, 101.<br />
[62] Pomonis, J. G.; Hammack, L.; Hakk, H. J. Chem. Ecol., 1993, 19,<br />
985.<br />
[63] Furukawa, A.; Shibata, C.; Mori, K. Biosci. Biotechnol. Biochem.,<br />
<strong>2002</strong>, 66, 1164.<br />
[64] Mori, K.; Ohtaki, T.; Ohrui, H.; Berkebile, D. R.; Carlson, D. A.<br />
Eur. J. Org. Chem., <strong>2004</strong>, 1089.<br />
[65] Mori, K.; Ohtaki, T.; Ohrui, H.; Berkebile, D. R.; Carlson, D. A.<br />
Biosci. Biotechnol. Biochem., <strong>2004</strong>, 68, 1768.<br />
[66] Shirai, Y.; Seki, M.; Mori, K. Eur. J. Org. Chem., 1999, 3139.<br />
[67] Hillbur, Y.; Anderson, P.; Arn, H.; Bengtsson, M.; Löfqvist, J.;<br />
Biddle, A. J.; Smitt, O.; Högberg, H. E.; Plass, E.; Franke, S.; Francke,<br />
W. Naturwissenschaften., 1999, 86, 292.<br />
[68] Guss, P.L.; Tumlinson, J.H.; Sonnet, P.E.; Proveaux, A.T. J. Chem.<br />
Ecol., 1982, 8, 545.<br />
[69] Tanaka, Y.; Honda, H.; Ohsawa, K.; Yamamoto, I. J. Pest. Sci.,<br />
1986, 11, 49.<br />
[70] Tanaka, Y.; Honda, H.; Ohsawa, K., Yamamoto, I., J. Pest. Sci.,<br />
1989, 14, 197.<br />
[71] Suzuki, T. Agric. Biol. Chem., 1981, 45, 1357.<br />
[72] Suzuki, T. Agric. Biol. Chem., 1981, 45, 2641.<br />
[73] Mori, K.; Kuwahara, S., Ueda, H., Tetrahedron, 1983, 39, 2439.<br />
[74] Levinson, H. Z.; Mori, K. Naturwissenschaften., 1983, 70, 190.
<strong>Synthesis</strong> <strong>of</strong> <strong>Pheromones</strong> Current Organic Chemistry, 2009, Vol. 13, No. 4 337<br />
[75] Suzuki, T.; Kozaki, J.; Sugawara, R.; Mori, K. Appl. Ent. Zool.,<br />
1984, 19, 15.<br />
[76] Ismuratov, G. Y.; Yakovleva, M. P.; Galyautdinova, A.V.; Tolstikov,<br />
G.A. Chem. Nat. Compd., 2003, 39, 31.<br />
[77] Odinokov, V.N.; Akhmetova, V.R.; Khasanov, K.D.; Abduvakhabov,<br />
A.A.; Tolstikov, G.A. Khimiya Prirodnykh Soedinenii., 1991,<br />
568.<br />
[78] Leal, W. S.; Kuwahara, Y.; Suzuki, T.; Kurosa, K. Naturwissenschaften.,<br />
1989, 76, 332.<br />
[79] Shimizu, N.; Mori, N.; Kuwahara, Y. Biosci. Biotechnol. Biochem.,<br />
2001, 65, 1724.<br />
[80] Noguchi, S.; Mori, N.; Kurosa, K.; Kuwahara, Y. Appl. Ent. Zool.,<br />
1998, 33, 53.<br />
[81] Shimizu, N.; Mori, N.; Kuwahara, Y. Biosci. Biotechnol. Biochem.,<br />
2003, 67, 1732.<br />
[82] Guss, P.L.; Tumlinson, J.H.; Sonnet, P.E.; McLaughlin, J.R. J.<br />
Chem. Ecol., 1983, 9, 1363.<br />
[83] Chuman, T.; Guss, P.L.; Doolittle, R.E.; McLaughlin, J.R.; Krysan,<br />
J.L.; Schalk, J. M.; Tumlinson, J. H. J. Chem. Ecol., 1987, 13,<br />
1601.<br />
[84] Gries, G.; Slessor, K.N.; Gries, R.; Khaskin, G.; Wimalaratne,<br />
P.D.C.; Gray, T. G.; Grant, G. G.; Tracey, A. S.; Hulme, M. J.<br />
Chem. Ecol., 1997, 23, 19.<br />
[85] Gries, R.; Schaefer, P. W.; Yoo, H.J.S.; Greaves, M.; Gries, G.<br />
Can. Entomol., 2005, 137, 471.<br />
[86] El-Sayed, A.M.; Gibb, A.R.; Suckling, D.M.; Bunn, B.; Fielder, S.;<br />
Comeskey, D.; Manning, L.A.; Foster, S.P.; Morris, B.D.; Ando,<br />
T.; Mori, K. J. Chem. Ecol., 2005, 31, 621.<br />
[87] Jury, J.C.; Fielder, S.; Vigneswaran, M. Tetrahedron Lett., 2003,<br />
44, 27.<br />
[88] Uenishi, J.; Kawahama, R.; Izaki, Y.; Yonemitsu, O. Tetrahedron,<br />
2000, 56, 3493.<br />
[89] Comeskey, D.J.; Bunn, B.J.; Fielder, S. Tetrahedron Lett., <strong>2004</strong>,<br />
45, 7651.<br />
[90] Burkholder, W. E. In Pheromone Research with Stored-Product<br />
Coleoptera., Academic Press, New York., 1970.<br />
[91] Chuman, T.; Kato, K., Noguchi, M., Agric. Biol. Chem., 1979, 43,<br />
2005.<br />
[92] Chuman, T.; Kohno, M.; Kato, K., Noguchi, M. Tetrahedron Lett.,<br />
1979, 2361.<br />
[93] Ono, M.; Onishi, I.; Chuman, T.; Kohno, M., Kato, K. Agric. Biol.<br />
Chem., 1980, 44, 2259.<br />
[94] Mori, K.; Nomi, H.; Chuman, T.; Kohno, M.; Kato, K.; Noguchi,<br />
M. Tetrahedron., 1982, 38, 3705.<br />
[95] Mori, M.; Chuman, T.; Kohno, M.; Kato, K.; Noguchi, M.; Nomi,<br />
H.; Mori, K. Tetrahedron Lett., 1982, 23, 667.<br />
[96] Zlokazov, M.V.; Veselovsky, V.V. Russ. Chem. Bull., <strong>2002</strong>, 51,<br />
1600.<br />
[97] Zlokazov, M.V.; Veselovsky, V.V. Russ. Chem. Bull., 2000, 49,<br />
154.<br />
[98] Tolasch, T.; Borgemeister, C.; Masuda, Y.; Fujita, K.; Mori, K.;<br />
Francke, W. Abstracts <strong>of</strong> papers, 19th Annual Meeting <strong>of</strong> International<br />
Chemical Ecology, Hamburg Germany, <strong>2002</strong>, 147.<br />
[99] Masuda, Y.; Fujita, K.; Mori, K. Biosci. Biotechnol. Biochem.,<br />
2003, 67, 1744.<br />
[100] Brand, J.M.; Duffield, R.M.; MacConnell, J.G.; Blum, M.S.; Fales,<br />
H.M. Science, 1973, 179, 388<br />
[101] Fernandes, L.; Bortoluzzi, A.J.; Sá, M.M. Tetrahedron., <strong>2004</strong>, 60,<br />
9983.<br />
[102] Schulz, S.; Nishida, R. Bioorg. Med. Chem., 1996, 4, 341.<br />
[103] Nishida, R.; Schulz, S.; Kim, C.S.; Fukami, H.; Kuwahara, Y.;<br />
Honda, K.; Hayashi, N. J. Chem. Ecol., 1996, 22, 949.<br />
[104] Stritzke, K.; Schulz, S.; Nishida, R. Eur. J. Org. Chem., <strong>2002</strong>,<br />
3884.<br />
[105] Yarger, R.G.; Silverstein, R.M.; Burkholder, W.E. J. Chem. Ecol.,<br />
1975, 1, 323.<br />
[106] Ravid, U.; Smith, L.R.; Silverstein, R.M. Tetrahedron, 1978, 34,<br />
1449.<br />
[107] Arceo, E.; Odriozola, J.M.; Garcia, J.M.; Gonzalez, A.; Gil, P.<br />
Tetrahedron Asymmetry, 2003, 14, 1617.<br />
[108] Cossé, A.A.; Bartelt, R.J.; James, D.G.; Petroski, R.J. J. Chem.<br />
Ecol., 2001, 27, 1841.<br />
[109] James, D.G.; Petroski, R.J.; Cossé, A.A.; Zilkowski, B.W.; Bartelt,<br />
R.J. J. Chem. Ecol., 2003, 29, 2189.<br />
[110] Shibata, C.; Mori, K. Eur. J. Org. Chem., <strong>2004</strong>, 1083.<br />
[111] Posner, G. H.; Johnson, N. J. Org. Chem., 1994, 59, 7855.<br />
[112] Wheeler, J.W.; Evans, S.L.; Blum, M.S.; Velthius, H.H.V.;<br />
Camargo, J. Tetrahedron Lett., 1976, 4029.<br />
[113] Tumlinson, J.H.; Klein, M.G.; Doolittle, R.E.; Ladd, T.L.;<br />
Proveaux, A.T. Science, 1977, 197, 789.<br />
[114] Zarbin, P.H.G.; Oliveira, A.R.M.; Simonelli, F.; Villar, J.; Delay,<br />
O. Tetrahedron Lett., <strong>2004</strong>, 45, 7399.<br />
[115] Zarbin, P.H.G.; de Oliveira, A.R.M.; Delay, C.E. Tetrahedron<br />
Lett., 2003, 44, 6849.<br />
[116] Zarbin, P.H.G.; Arrigoni, E.D.; Reckziegel, A.; Moreira, J.A.;<br />
Baraldi, P.T.; Vieira, P.C. J. Chem. Ecol., 2003, 29, 377.<br />
[117] Kang, S.K.; Shin, D.S.; Lee, J.O.; Goh, H.G. Bull. Korean Chem.<br />
Soc., 1986, 7, 444.<br />
[118] Laurence, B.R.; Pickett, J.A. J. Chem. Soc. Chem. Commun., 1982,<br />
59.<br />
[119] Sun, B.; Peng, L.Z.; Chen, X.S.; Li, Y.L.; Li, Y. Chin. Chem. Lett.,<br />
<strong>2004</strong>, 15, 1177.<br />
[120] Leal, W.S.; Kuwahara, S.; Ono, M.; Kubota, S. Bioorg. Med.<br />
Chem., 1996, 4, 315.<br />
[121] Clososki, G.C.; Ricci, L.C.; Costa, C.E.; Comasseto, J. V. J. Braz.<br />
Chem. Soc., <strong>2004</strong>, 15, 809.<br />
[122] Light, D.M.; Birch, M.C. Naturwissenschaften., 1979, 66, 159.<br />
[123] Ceschi, M.A.; Petzhold, C.; Schenato, R.A. J. Braz. Chem. Soc.,<br />
2003, 14, 759.<br />
[124] Arai, T.; Sugie, H.; Hiradate, S.; Kuwahara, S.; Itagaki, N.; Nakahata,<br />
T. J. Chem. Ecol. 2003, 29, 2213.<br />
[125] Nakahata, T.; Itagaki, N.; Arai, T.; Sugie, H.; Kuwahara, S. Biosci.<br />
Biotechnol. Biochem., 2003, 67, 2627.<br />
[126] Bierlleonhardt, B.A.; Moreno, D.S.; Schwarz, M.; Fargerlund, J.;<br />
Plimmer, J.R. Tetrahedron Lett., 1981, 22, 389.<br />
[127] Passaro, L.C.; Webster, F.X. J. Agric. Food Chem., <strong>2004</strong>, 52, 2896<br />
[128] Tumlinson, J.H.; Hardee, D.D.; Gueldner, R.C.; Thompson, A.C.;<br />
Hedin, P.A. Science, 1969, 166, 1010.<br />
[129] Booth, D.C.; Phillips, T.W.; Claesson, A.; Silverstein, R.M.;<br />
Lanier, G.N.; West, J. R. J. Chem. Ecol., 1983, 9, 1.<br />
[130] Phillips, T.W.; West, J.R.; Foltz, J.L.; Silverstein, R.M.; Lanier, G.<br />
N. J. Chem. Ecol., 1984, 10, 1417.<br />
[131] Francke, W.; Pan, M. L.; Konig, W. A.; Mori, K.; Puapoomchareon,<br />
P.; Heuer, H.; Vite, J. P. Naturwissenschaften., 1987, 74, 343.<br />
[132] Bernard, A.M.; Frongia, A.; Secci, F.; Delogu, G.; Ollivier, J.;<br />
Piras, P.P.; Salaun, J. Tetrahedron., 2003, 59, 9433.<br />
[133] Alizadeh, B.H.; Kuwahara, S.; Leal, W.S.; Men, H.C. Biosci. Biotechnol.<br />
Biochem., <strong>2002</strong>, 66, 1415.<br />
[134] Kulkarni, Y.S.; Niwa, M.; Ron, E.; Snider, B. B. J. Org. Chem.,<br />
1987, 52, 1568.<br />
[135] Zhang, Q.H.; Chauhan, K.R.; Erbe, E.F.; Vellore, A.R.; Aldrich,<br />
J.R. J. Chem. Ecol., <strong>2004</strong>, 30, 1849.<br />
[136] Chauhan, K.R.; Zhang, Q.H.; Aldrich, J.R. Tetrahedron Lett., <strong>2004</strong>,<br />
45, 3339.<br />
[137] Birkett, M.A.; Pickett, J.A. Phytochemistry., 2003, 62, 651.<br />
[138] Dickens, J.C.; Oliver, J.E.; Hollister, B.; Davis, J.C.; Klun, J.A. J.<br />
Exp. Biol., <strong>2002</strong>, 205, 1925.<br />
[139] Oliver, J.E.; Dickens, J.C.; Glass, T.E. Tetrahedron Lett., <strong>2002</strong>, 43,<br />
2641.<br />
[140] Baker, R.; Herbert, R.H.; Parton, A.H. J. Chem. Soc. Chem. Commun.,<br />
1982, 601.<br />
[141] Baker, R.; Herbert, R.H. J. Chem. Soc. Perkin Trans. 1., 1987,<br />
1123.<br />
[142] Hao, J.L.; Forsyth, C.J. Tetrahedron Lett., <strong>2002</strong>, 43, 1.<br />
[143] Silverstein, R.M.; Brownlee, R.G.; Bellas, T.E.; Wood, D.L.;<br />
Browne, L.E. Science, 1968, 159, 889.<br />
[144] Bedard, W.D.; Tilden, P.E.; Wood, D.L.; Silverstein, R.M.; Brownlee,<br />
R.G.; Rodin, J.O. Science, 1969, 164, 1284.<br />
[145] Wood, D.L.; Browne, L.E.; Ewing, B.; Lindahl, K.; Bedard, W.D.;<br />
Tilden, P. E.; Mori, K.; Pitman, G.B.; Hughes, P.R. Science, 1976,<br />
192, 896.<br />
[146] Vite, J.P.; Billings, R.F.; Ware, C.W.; Mori, K. Naturwissenschaften.,<br />
1985, 72, 99.<br />
[147] Mayer, S.F.; Mang, H.; Steinreiber, A.; Saf, R.; Faber, K. Can. J.<br />
Chem., <strong>2002</strong>, 80, 362.<br />
[148] Francke, W.; Schroder, F.; Philipp, P.; Meyer, H.; Sinnwell, V.;<br />
Gries, G. Bioorg. Med. Chem., 1996, 4, 363.<br />
[149] Kumar, D.N.; Rao, B.V. Tetrahedron Lett., <strong>2004</strong>, 45, 2227.<br />
[150] Johnston, B.D.; Oehlschlager, A.C. J. Org. Chem., 1982, 47, 5384.<br />
[151] Kinzer, G.W.; Fentiman, A.F.; Page, T.F.; Foltz, R.L.; Vite, J.P.;<br />
Pitman, G.B. Nature, 1969, 221, 477.<br />
[152] Mori, K. Tetrahedron, 1975, 31, 1381.
338 Current Organic Chemistry, 2009, Vol. 13, No. 4 Zarbin et al.<br />
[153] Chenêvert, R.; Caron, D. Tetrahedron Asymmetry, <strong>2002</strong>, 13, 339<br />
[154] Yang, X.B.; Luo, S.J.; Hua, C.W.; Zhai, H.B. Tetrahedron, 2003,<br />
59, 8551.<br />
[155] Nakashima, T. 2nd Asia-Pacific Conference on Chemical Ecology<br />
2001, Penang, Malaysia, Abstract No. 27.<br />
[156] Marukawa, K.; Mori, K. Chem. Lett., <strong>2002</strong>, 40.<br />
[157] Marukawa, K.; Mori, K. Eur. J. Org. Chem., <strong>2002</strong>, 3974.<br />
[158] MacConnell, J.G.; Borden, J.H.; Silverstein, R.M.; Stokkink, E. J.<br />
Chem. Ecol., 1977, 3, 549.<br />
[159] Alibés, R.; de March, P.; Figueredo, M.; Font, J.; Racamonde, M.;<br />
Parella, T. Org. Lett., <strong>2004</strong>, 6, 1449.<br />
[160] Johnston, B.D.; Slessor, K.N.; Oehlschlager, A.C. J. Org. Chem.,<br />
1985, 50, 114.<br />
[161] Skattebol, L.; Stenstrom, Y. Acta Chem. Scand. B., 1985, 39, 291<br />
[162] Asai, N.; Fusetani, N.; Matsunaga, S.; Sasaki, J. Tetrahedron,<br />
2000, 56, 9895.<br />
[163] Masuda, Y.; Yoshida, M.; Mori, K. Biosci. Biotechnol. Biochem.,<br />
<strong>2002</strong>, 66, 1531.<br />
[164] Garner, P.; Park, J. M. J. Org. Chem., 1987, 52, 2361.<br />
[165] Garner, P.; Park, J. M. Malecki, E. J. Org. Chem., 1988, 53, 4395.