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

Abstract 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 (B 2 pin 2 ) 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 B 2 pin 2 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.