Acid/Base-Tuned Asymmetric Reductive Heck and Denitrogenative Heck Reactions of In Situ-Formed α,β-Unsaturated Hydrazone

Despite significant progress in the catalytic asymmetric
1,4-additions
between various Michael donors and acceptors, the exploration of organohalide
donors remains elusive. Herein, we report the Pd(0)-catalyzed asymmetric
intramolecular 1,4-additions of vinyl/aryl iodides to α,β-unsaturated
hydrazones, featuring in situ-formed hydrazone and acid/base-tuned
reaction pathways. Due to its strong coordination ability, the hydrazone
is capable of steering the C–C bond formation to follow the
1,4-addition mechanism instead of the conventional alkene insertion,
thus enabling the generation of vinylhydrazinyl–Pd2+ species via the Zimmerman–Traxler chairlike transition state.
Notably, this species preferentially undergoes protonation under acidic
conditions, furnishing a reductive Heck reaction with the aid of a
native hydrazine reductant, while it is susceptible to β-HN elimination under basic conditions to achieve a denitrogenative
Heck reaction. The catalytic protocol affords highly enantioselective
access to diverse heterocycles, with alkene and hydrazone groups poised
for further chemical manipulations.