Bis(pinacolato)Diboron‐Enabled Nickel‐Catalyzed Regio‐ and Enantioselective Reductive [3 + 2] Annulation of β‐Bromoenones with Alkynes

Chiral five-membered cyclic tertiary alcohols are important structural motifs in functional materials, pharmaceuticals, and bioactive molecules. Hence, developing efficient methodologies for synthesizing compounds featuring these privileged scaffolds represents a crucial pursuit within synthetic chemistry. Herein, we present a regio- and enantioselective Ni-catalyzed strategy for the reductive [3 + 2] annulation of β-bromoenones with alkynes, providing convenient access to chiral five-membered cyclic tertiary alcohols with high levels of regio-, and enantioselectivity via axial chirality transfer to central chirality. The utilization of an environmentally sustainable bis(pinacolato)diboron (B₂pin₂) is crucial for the success of this asymmetric reductive cyclization reaction. Simultaneously, the mild reaction environment greatly enhances functional group compatibility. This has been demonstrated by the broad substrate scope, late-stage functionalizations of bioactive compounds or drug molecules, and subsequent transformations. Amongst, it is worth emphasizing that these functionally enriched chiral five-membered cyclic tertiary alcohols can efficiently participate in Diels-Alder reactions to synthesize enantioenriched polycyclic and heterocyclic molecules, thereby further validating the significance of introducing a cyclopentadiene skeleton. The preliminary mechanistic studies revealed the mode of action of B₂pin₂ in mononuclear Ni-catalyzed asymmetric reductive [3 + 2] annulation reactions and density functional theory (DFT) calculations clarified the origin of the experimentally observed regio- and enantioselectivity.