N. Moitessier et al., Molecular dynamics-based models explain the unexpected diastereoselectivity of the sharpless asymmetric dihydroxylation of allyl D-xylosides, EUR J ORG C, (6), 2000, pp. 995-1005
The catalytic asymmetric dihydroxylation of several allyl 2-O-benzyl-alpha-
D-xylosides with AD-mix beta and PYR(DHQD)(2) shows almost no diastereofaci
al selectivity if the 3- and 4-OH groups are unprotected or acetylated. Ace
tal, benzyl ethers and benzoyl esters enhance the diastereoselectivity, in
the opposite sense to that predicted by the "AD mnemonic", which is complet
ely lost using AD-mix alpha. In an attempt to understand this behaviour, co
mputational studies of the asymmetric dihydroxylation (AD) of olefins using
Sharpless' and Corey's catalysts have been carried out using molecular dyn
amics. A three-step algorithm was developed taking advantage of the enzyme-
like behaviour of catalyst-olefin systems and applied using an ESFF force f
ield. To validate our approach, the first sampling step procedure was then
refined and performed using a modified CVFF force field. This led to a U-sh
aped model in good agreement with that proposed by Corey for the AD of ally
l 4-methoxybenzoates, which brings to the fore a role for the methoxy group
. This model also accounts for the observed enantioselectivity of styrene d
ihydroxylation. When applied to the AD of allyl xylosides using AD-mix beta
, our model accounts well for the observed diastereoselectivity. Both synth
etic and modelling results confirmed that aromatic groups on the olefin cou
ld be involved in pi-pi stacking interactions with the aromatic rings of th
e catalyst and should be important, if not a prerequisite, to achieve high
enantio- and diastereoselectivity.