Palladium‐Catalyzed Inverse and Normal Dehydrogenative Aza‐Morita–Baylis–Hillman Reactions with γ,δ‐Unsaturated Compounds

Abstract

Abstractσ‐Lewis base‐catalyzed regio‐ and enantioselective aza‐Morita–Baylis–Hillman (MBH) reaction of α,β,γ,δ‐unsaturated systems remains a challenge due to the intrinsic covalent activation mode. Here we demonstrate that a Pd0 complex can mediate the dehydrogenative reaction of γ,δ‐unsaturated compounds to give corresponding electron‐poor dienes, which further undergo δ‐regioselective umpolung Friedel–Crafts‐type addition to imines via auto‐tandem Pd0‐π‐Lewis base catalysis. After β‐H elimination of in situ formed PdII‐complexes, unprecedented and chemically inverse aza‐MBH‐type adducts are finally furnished with fair to outstanding enantioselectivity, and a diversity of functional groups and both ketimine and aldimine acceptors can be well tolerated. Moreover, switchable α‐regioselective normal aza‐MBH‐type reaction also can be realized by tuning catalytic conditions, whereas moderate to good enantioselectivity with low to excellent Z/E‐selectivity is attained.