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

4.1 – Introduction
followed by Fleming-Tamao oxidation gave the β-L-altrose analogue 264 in 16% from
261.
SiMe 2 t-Bu
i) AD mix α
ii) NaH, BnBr
SiMe 2 t-Bu
OBn
OBn
ZnEt 2 , CH 2 I 2
rt
SiMe 2 t-Bu
OBn
OBn
261 76%
262 88%
71% ee
>99:1 dr
OAc
i) NIS, MeCN
rt, 12 hr
OBn
i) OsO 4 , NMO, rt AcO OBn
ii) t-BuLi, PhMe 2 SiCl
−100 °C
OBn ii) Hg(OAc) 2 , CH 3 CO 3 H
OBn
iii) Ac 2 O, pyr, rt
SiMe 2 Ph
OAc
263 66% 264 79%
>99:1 dr
Scheme 4.7 – Landais’ synthesis of altrose analogue 161
Using another desymmetrised diene, Landais reported a complementary synthesis
starting from the Tamao silane 265, which was oxidised and alkylated to give ether
266, ready for [2,3]-Wittig rearrangement. Rearrangement occurred in modest yield
and with high facial selectivity to give allylic ether 267, which again underwent highly
selective anti-dihydroxylation, giving α-D-galactopyranose analogue 268 in 20%
overall yield.
SiMe 2 OMe
O
H 2 O 2 , KF
OH
O
Bu 3 Sn
KH, Bu 3 SnCH 2 I
O
O
265
O
KHCO 3
60 °C, 12 hr
O
O
75%
>99:1 dr 266 82%
n-BuLi
−60 °C 12 hr
OH
267
O
O
51%
i) Ac 2 O, pyr rt
ii) OsO 4 , NMO, rt
HO
OH
OAc
268
O
O
92%
>99:1 dr
Scheme 4.8 – Landais’ synthesis of galactose analogue 161
An alternative method for accessing unsaturated carbocycles is the enzymatic
oxidation of benzene by Pseudomonas putida mutants, first used by Ley and coworkers
in the syntheses of racemic cyclitols. 162 The formation of a meso diol
restricted its utility, but Pseudomonas putida mutants were developed that could
oxidise substituted benzenes, yielding desymmetrised, enantiomerically pure diols
136