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

Chapter 4 – Synthesis of carbasugars
OsO 4
L
R 2 O
R 1
H
R c
R t
Kishi model:
ground state-like transition state
governed by A(1,3) strain
Scheme 4.22 – Kishi model for dihydroxylation of allylic alcohols
It was later found by Evans 193 that for 1,1-disubstituted olefins (R t = R c = H), that
decreasing the size of R 2 or increasing L enhanced facial selectivity, despite reducing
the conformational preference for the ground state. These observations lent support to
reacting conformer models of Houk and Vedejs. 192 Interestingly, these models all
assume a single [3+2] cycloaddition to form the osmate ester, even though this was not
shown until computational and kinetic studies were performed almost 10 years later. 170
Subsequent computational modelling by Houk 164 showed that whilst for 1,2-cissubstituted
alkenes the dominant factor in the transition state conformation was in fact
A(1,3) strain, in all other cases, the transition state was determined primarily by the
inside alkoxy effect, with a further contribution to minimise σ* C-O -π interactions which
withdraw electron density from the nucleophilic olefin.
E +
OsO 4
(Outside) (Inside)
H OR 2
R 1
L (Anti)
H
L
R 1 R t
H
OR 2
Houk model:
transition state determined by
inside alkoxy effect
Scheme 4.23 – Houk model for dihydroxylation of allylic alcohols
Although many studies have investigated the origin of the asymmetry of
dihydroxylation in acyclic systems, little attention has been given to cyclic systems. 194
The stereochemical outcome of the reaction is attributed to a minimisation of the
dipole in the transition state, consistent with the increased diastereoselectivity observed
for oxidation of pseudo-axial allylic alcohol 295 by Donohoe (Scheme 4.24).
151