The asymmetric addition of an N–H bond to various alkenes via a direct catalytic method is a powerful way of synthesizing value-added chiral amines. Therefore, the enantio- and regioselective hydroamination of unactivated alkenes remains an appealing goal. Here, we report the highly enantio- and regioselective Ni-catalyzed hydroamination of readily available unactivated alkenes bearing weakly coordinating native amides or esters. This method succeeds for both terminal and internal unactivated alkenes and has a broad amine coupling partner scope. The mild reaction process is well suited for the late-stage functionalization of complex molecules and has the potential to gain modular access to enantioenriched β- or γ-amino acid derivatives and 1,2- or 1,3-diamines. Mechanistic studies reveal that a chiral bisoxazoline-bound Ni specie effectively leverages carbonyl coordination to achieve enantio- and regioselective NiH insertion into alkenes.

Pyrroloazocine indole alkaloids consisting of eight-membered azacycle fused to pyrrole and indole units exhibit intriguing pharmacological functions but still pose a synthetic challenge. Here, we report an alternative synthetic strategy for the pyrroloazocine indole core from two key steps: (i) regioselective Fischer indolization and (ii) transition-metal-mediated C–N cross-coupling reaction of N-Boc aryl hydrazine with azacyclic vinyl triflate. In our investigation, Pd(0)- and Cu­(I)-catalysts are found to display distinct and complementary selectivities for the ring size of cyclic vinyl triflates. For rings that are five- and six-membered, a Pd(0)-catalyst afforded the corresponding ene-hydrazines while completely ineffective for seven-membered or larger rings. A Cu­(I)-catalyst exhibited the opposite selectivities. Computational studies reveal that their ring size dependency is due to the two bottlenecks of reductive elimination for Pd and oxidative addition for Cu along with bond strengths in products and reactants and degree of stage at transition states. These findings led us to establish a straightforward protocol for accessing a variety of ring-fused indoles highlighted with the formal synthesis of (−)-lundurine A.

Kinetic resolution is a powerful strategy for the isolation of enantioenriched compounds from racemic mixtures, and the development of selective catalytic processes is an active area of research. Here, we present a nickel-catalyzed kinetic resolution of racemic αsubstituted unconjugated carbonyl alkenes via the enantio-, diastereo-, and regioselective hydroamination. This protocol affords both chiral α-substituted butenamides and syn-β 2,3 -amino acid derivatives with high enantiomeric purity (up to 99 % ee) and selectivity factor up to > 684. The key to the excellent kinetic resolution efficiency is the distinctive architecture of the chiral nickel complex, which enables successful resolution and enantioselective CÀ N bond construction. Mechanistic investigations reveal that the unique structure of the chiral ligand facilitates a rapid migratory insertion step with one enantiomer. This strategy provides a practical and versatile approach to prepare a wide range of chiral compounds.