Regioselectivity of the Reactions of Heteroatom-Stabilized Allyl ...

Scheme 16
Scheme 17
106) (Scheme 16) (trans opening of epoxides). The
fate of the primary open-chain product 107 depends
on the leaving group X. Hence, epichlorhydrin 106
(R 1 ) R 2 ) H, X ) Cl) allows isolation of the alcohol
109 while with tosylate in situ ring closure to a new
oxirane 108 is observed. 78,79
Exclusive R-attack is observed on converting 101
into triethylaluminum or trialkylboron “ate” complexes
for both carbonyl compounds 80 and reactive
halides, 42 although “ate” complexes produce with
aldehydes a mixture of the syn- 104 and anti-isomers
105. 81 In general, “ate” complexes should facilitate
the coupling reaction, because of the more ionic
nature of the C-Al bond and the longer bond imposes
less steric hindrance (Scheme 16).
“Titanation” of the lithioallyl sulfides causes high
regioselectivity, and also excellent chemical selectivity
of the resulting nucleophilic reagents. Such
titanium reagents give R-products with carbonyl
compounds in a stereocontrolled manner with high
diastereoselectivity, 82 save for γ-substituted allyl
sulfides where γ-selectivity is observed. 83
Lithio-γ-(methylthio)crotonate esters 84 and γ-(phenylthio)crotonate
115 esters when deprotonated with
potassium tert-butoxide undergo γ-alkylation to 116
and to 117 when excess of alkylating agent is applied.
By contrast, 112 having both groups CO2R and RS
at the same end of the allyl moiety, undergoes
exclusive R-alkylation to 113 as both groups increase
Scheme 18
Scheme 19
673
the coefficient of the HOMO at their point of attachment
on the allyl anion (Scheme 18). 85
1-(Vinylthio)allyllithium from 118 reacts with halides
RX to give R-products 119 from which subsequent
thio-Claisen rearrangements produce γ,δunsaturated
aldehydes 120 highly stereoselectively
(Scheme 19). 86
In the absence of HMPA, 3-[[(trimethylsilyl)methyl]thio]allyllithium
from 121 reacts with allyl halides
to give a mixture of R- 124 and γ-products 125
(Scheme 20). The presence of HMPA enhances the
nucleophilicity of the allylic anion and facilitates the
rearrangement of the initially formed R-orγ-adducts.
An intramolecular attack at the R- and γ-positions,
respectively, on Si takes place. After deprotonation
to 122 the mechanism is thought to involve a pentacoordinated
silicate intermediate 123, giving the
lithium alkenyl sulfide 126 which is then trapped by
alkyl halides to form 129. On the other hand, the
rearrangement from 127 to 131 is assumed to proceed
upon deprotonation to 128 via a four-membered
five-coordinated silicate intermediate 130 to give 132
which is then alkylated to 131 (Scheme 20). 87
The coupling of an allyl sulfide anion from 134 with
a ketone represents the key step in a synthesis of
erythronolide B. 88 The use of THF/TMEDA gives the
γ-adduct 133, while the system THF/TMEDA/
5HMPA produces the R-adduct 137 (“unnatural stereoisomer”)
(Scheme 21). This reaction is thought to
proceed via a η 1 -complex 135 due to the presence of
HMPA while under the former conditions ( n BuLi/
THF/TMEDA) a η 3 -complex is assumed. In contrast,