Models for the Asymmetric Enol borinate reduction of a ketone
Henry S. Rzepa
Department of Chemistry, Imperial College.
A key stage in the reaction sequence shown below 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.
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:
- The chair form is the most stable
- The chiral centre (
- The alternative relative stereochemistry (
- Another way of avoiding steric congestion is for the boat comformation to form. The most stable boat isomer is also 3 kcal/mol higher, eliminating this possibility as well.
The Absolute Stereochemistry
The methyl group X (