Regulation of Orthogonal Functions in a Dual Catalyst System. Subservient Role of a Non-chiral Lewis Acid in an Asymmetric Catalytic Heteroatom Diels-Alder Reaction

摘要

A catalytic asymmetric heteroatom Diels-Alder reaction of unactivated imines with Danishefsky’s diene is described which gives high asymmetric induction for N-benzhydryl imines derived from a variety of aldehydes. The catalyst is derived from B(OPh)3 and the VAPOL ligand and gives good induction but the reaction stalls and does not give high conversion (~50%). It was found that in the presence of the both the chiral catalyst and excess amounts of B(OPh)3 the reaction proceeds to completion and gives high yields of the dihydropiperidinone product. Despite the presence of large quantities of the non-chiral Lewis acid B(OPh)3 the asymmetric induction of the product remains constant (90% ee) as the amount of B(OPh)3 is steadily increased and does not drop off until the ratio of B(OPh)3 to VAPOL is 100:1 (82% ee). These observations are interpreted as involving highly separated and different activities for the chiral and non-chiral Lewis acids present in the reaction. Specifically, the excess B(OPh)3 serves to bind to the product and release the chiral catalyst to turnover more starting material. The B(OPh)3 does not compete in turning over of the starting material and a series of binding studies reveals that this likely due to a combination of two factors. The binding studies reveals that the chiral catalyst binds to the starting imine seven times more strongly than does B(OPh)3. However, in order to explain the constant asymmetric induction observed despite the addition of increasing amounts of B(OPh)3 the rate of the reaction of the imine complexed with the chiral catalyst must be at least 10 times faster than the reaction of the imine complexed with B(OPh)3. Finally, a catalyst generated from BINOL and B(OPh)3 does not show this phenomenon.