Subject: Chiral Selectivity -Reply

From: <[email-masked]>
Date: Fri, 12 Jan 1996 11:26:05 -0500

With regards to Paddy Kanes enquiry concerning chiral selectivity. I
performed a little work in this area using HyperChem to look at
Enantioselective hydrogenation of methyl pyruvate cataysed by
cinchona alkaloid modified Pt catalysts. The problem being that
calculations are not really possible in this system, hence I ended up
performing integrations by eye. The results were however satisfactory.

Simons et al Rec. Trav. Chim Pay-Bas 1994 113 465
cf Schwalm et al Catal Lett 23 1994 271

One of the problems to be aware of is that in real life there will not be
100 % enantioselectivity. Hence there are probably two pathways to
product, one going through a higher energy pathway than the other,
which corresponds to the chiral selectivity observed. This real energy
difference only has to be small to give large enantiomeric excesses.
Unfortunately,  I feel the accuracy of the calculations involved can be
less than the accuracy required. The good minimisers available today
would prefer to seek out this global minimum - corresponding to the
product in excess, and hide the pathway that gives the other
enantiomer - hence hiding valuable information.

My advice is therefore to try and explain things in terms of steric
hindrance to explain the observed chiral selectivity, and apply a little
chemical  intuition before trusting the numbers generated. Try to think of
how the enantiodifferentiation could occur, and place the reactant in a
relavant orientation wrt to the chiral adduct and then perform a
minimisation. Do this for both enantiomers. Not an ideal situation I know
but it may help.

Cheers,

Keith

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 Dr. Keith Simons			TEL:	+44-(0)1763-253126
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