A Route to Carbasugar Analogues - Jonathan Clayden - The ...

Chapter 4 – Synthesis of carbasugars
Norbornenes have featured as key intermediates in the synthesis of many carbasugars
in the laboratories of Ogawa; an early example of which is shown in the divergent
synthesis of carbasugars 250b, 257, and 260. 160 Norbornene 255 was made by
cycloaddition, oxidation of which gave lactone 256 and subsequent reduction,
acylation and hydrolysis gave an equimolar mixture of diastereomers 257 and 250b.
O
a
O
b
HO
O
O
256
O
c
HO
HO
HO
257
OH
OH
+
HO
HO
OH
HO OH
250b
HO 2 C
CO 2 H
255
d
Br
O
O
O
e
AcO
AcO
AcO
Br
OAc
f
HO
HO
HO
OH
OH
258
259
d.r. 12:5 260 d.r. 3:1
Major diastereomers drawn. a) hydroquinone, Δ, 45%; b) H 2 O 2 , formic acid, 45%; c) i)
LiAlH 4 , ii) Ac 2 O, pyr., DMAP, iii) Ac 2 O, AcOH H 2 SO 4 , iv) NaOMe, MeOH: 257 (18%), 250b
(19%). d) HOBr, 91%; e) i) LiAlH 4 , ii) AcOH, Ac 2 O, H 2 SO 4 , 46%; f) i) NaOAc, ii) NaOMe,
MeOH, 41%.
160
Scheme 4.6 – Ogawa’s divergent syntheses of carbasugars
Alternatively, treatment of 255 with hydrobromous acid gave bromolactone 258,
which upon reduction and hydrolysis yielded a similar mixture of diastereomers of
bromosugar 259. Acetolysis of the major diastereomer gave a 3:1 mixture of 260 and
250b, whilst acetolysis of the minor diastereomer of 259 yielded further carbasugars.
Using similar methods, Ogawa and colleagues have synthesised many carbasugars and
aminocarbasugar analogues, often simultaneously.
A number of methods offering higher degrees of stereocontrol have come from
unsaturated carbocyclic starting material; the traditional way to access such materials
is by the dissolving metal reduction of benzene derivatives (section 1.2). Landais and
co-workers developed a selective reduction of benzylsilanes to give the meso diene
261 (Scheme 4.7) which was desymmetrised using the Sharpless AD conditions with
good diastereo- and enantioselectivity. Benzylation and a highly selective
cyclopropanation gave bicycle 262, ready for fragmentation. Electrophile-driven
fragmentation of the cyclopropane gave the homoallylic iodide, which was lithiated to
give the Fleming silane 263. Highly anti-selective dihydroxylation of the allylic ether
135