Investigations into transition-state geometry in the Mukaiyama directed aldol reaction.

A model compound was designed to study the relative orientation of enol silane and carbonyl moieties in the Mukaiyama aldol reaction. The cyclization must proceed with either a synclinal or an antiperiplanar orientation of the aldehyde with respect to the enol silane. These two orientations lead to diastereomeric products, thus allowing for unambiguous correlation between product configuration and transition-state geometry. As steric bias is minimal, the product distribution should reflect the intrinsic preferences for reactant geometry in the transition state. Cyclizations of the model compound showed a modest preference for reaction via an antiperiplanar (open transition state) orientation of reactants in the presence of a wide range of Lewis acids (TiCl4, SnCl4, SnCl2, BF3OEt2, TMSBr, trityl perchlorate, EtAlCl2) and triflic acid. The cyclizations promoted by tin(II) salts were syn-selective and dependent on the nature of the counterion. Fluoride ion promoted reactions were anti-selective and were independent of the nature of the cation.