Enantioselective Construction of Aza-bicyclo[3.2.1]octane Skeletons via Substituted π-Allyl Palladium Dipoles Originated from Neutral η³-Propargyl Palladium Species

A catalytic strategy for insitu generation of substituted π-allyl palladium dipoles from neutral η³ -propargyl palladium complexes has been disclosed, enabling the construction of enantiomerically enriched aza-bicyclo[3.2.1]octane frameworks through cascade cyclization reactions based on neutral zwitterionic π-propargyl palladium species derived from vinylidenecyclopropane-diesters (VDCP-diesters) and their analogues. This protocol demonstrates remarkable synthetic efficiency under mild reaction conditions, achieving moderate to good yields (42 examples) with excellent stereochemical control (>90% ee in most cases). This asymmetric catalytic reaction can be applied in a series of semigram-scale manipulations, and the obtained cycloadducts can be transformed into diverse functionalized products while retaining excellent enantioselectivities. On the basis of mechanistic investigations and DFT calculations, the critical "<i>palladacyclobutenization-protonolysis</i>" sequence has been elucidated as the pivotal chirality-determining step in the whole plausible reaction pathway.