Models for the Asymmetric Enol borinate reduction of a ketone
Source: 2nd Year Organic Problems, 1999, Set 1.
A key stage in the reaction sequence shown as part of the problem is
the following step involving C-C bond formation to an aldehyde, mediated by the chiral auxilliary
X=di-isopinocampheyl (see I. Paterson et al, Tetrahedron, 1990, vol 46, p 4663; 1991, Vol.47, pp.3471-3484 )
Other than the chiral auxiliary, all the reagent components are achiral. However, two entirely new chiral
centres are formed in the product. We need to understand two features of these new chiral centres and why they form so specifically.
their relative stereochemistry
their absolute stereochemistry.
The Relative Stereochemistry
A 3D model for the basic framework (i.e. replacing all substituents with H) of the transition state must be constructed. Since this involves
bond formation and cleavage, a QM (Quantum Mechanics) based model must be used, in this case the
AM1 semi-empirical method (Table 1). Ab initio programs can also be used, but they take much longer, and yield very similar results. These calculations
reveal that both chair and boat forms of the transition state are possible.
Prototypic Chair transition state
Prototypic Boat transition state
One next needs to understand how the various substitution sites interact sterically. To do this, methyl
groups are inserted into the various positions (including one for the chiral auxilliary X) and the energies of some of the various
possible isomers are calculated. Note the following: