Catalytic Asymmetric Aza-Diels-Alder Reaction of Ketimines and Unactivated Dienes.

The enantioselective aza-Diels-Alder reaction represents one of the most efficient method for constructing chiral tetrahydropyridines. Nevertheless, the catalytic asymmetric aza-Diels-Alder reaction of ketimines with unactivated dienes is still a challenging topic. Herein, guided by computational screening, a highly enantioselective aza-Diels-Alder reaction of 2-aryl-3 H -indol-3-ones with unactivated dienes was realized by using a B(C 6 F 5 ) 3 /chiral phosphoric acid catalyst system under mild conditions. The reaction has a broad scope with respect to both aza-Diels-Alder reaction partners and hence offers rapid access to an array of tetrahydropyridine derivatives with pretty outcomes (up to 99% yield, >20:1 dr and 98:2 er). Notely, the reaction is very efficient, in which the catalyst loadings for the model reaction can be reduced to 0.1 mol% and the enantioselectivity is still maintained. Besides, the synthetic utility of the protocol was proved by transformations of the products. Moreover, DFT calculations provide convincing evidence for the interpretation of stereoselection.