Asymmetric N-1,5-Addition and Cascade: Facile Route to Various N-Heterocycles

Catalytic asymmetric 1,4- and 1,6-conjugate addition between electron-deficient conjugated dienes and amine nucleophiles are one of the valuable basic transformations. In contrast, the corresponding N-1,5-conjugate addition reaction is electronically forbidden and considered unfeasible. We demonstrate that the N-1,5-addition can work efficiently via a palladium catalyst with a group of modified chiral PHOX ligands. The amine nucleophiles are introduced to the umpolung γ-position of electron-deficient ester groups in moderate to good yield and with high stereoselectivity. Four types of cascade processes have been established to provide convenient routes for the synthesis of enantioenriched N-heterocycles, including 2-imidazolidones, tetrahydroquinoxalines, benzomorpholines, and 2-oxazolidones. Mechanistic studies suggest C–N bond formation as the rate-determining step.