Enantioselective Palladium(II)-Catalyzed Desymmetrizative Coupling of 7-Azabenzonorbornadienes with Alkynylanilines

A PdII-catalyzed, domino enantioselective desymmetrizative coupling of 7-azabenzonorbornadienes with alkynylanilines is disclosed herein. This operationally simple transformation generates three covalent bonds and two contiguous stereocenters with excellent enantio- and diastereo-selectivity. The resulting functionalized indole-dihydronaphthalene-amine conjugates served as an appealing platform to streamline the diversity-oriented synthesis (DOS) of other valuable enantioenriched compounds. DFT calculations revealed that the two stabilizing non-covalent interactions contributed to the observed enantioselectivity. A palladium-catalyzed enantioselective desymmetrizative coupling of prochiral 7-azabenzonorbornadienes with readily available alkynylanilines afforded dihydronaphthalenes via concomitant generation of three covalent bonds. The methods also allows to build two stereocenters and an indole motif in a highly diastereo- and enantioselective as well as atom-economic manner.+#image