Proline-catalysed asymmetric ketol cyclizations: the template mechanism revisited

Abstract

A modified template mechanism based on modelling studies of energy minimised complexes is presented for the asymmetric proline-catalysed cyclization of triketones1,2 and3 to the 2S,3S-ketols1a,2a and3a respectively. The template model involves a three-point contact as favoured in enzyme-substrate interactions. Our minimisation studies are in agreement with the divergent behaviour of the 6,5-, 6,6-and 6,7-bicyclic systems. They support the high 93.4%ee observed with the 6,5-bicyclic ketol and the lower 73%ee found with the 6,6-bicyclic ketol. The calculations also explain the lack of asymmetric induction with the 6,7-bicyclic system.