Enantioselective C(sp3)–C(sp3) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis

Abstract

Cross-Coupling of Non-activated Alkyl Electrophiles via Nickel Hydride Catalysis. ChemRxiv. Preprint.

Enantioselective access to chiral aliphatic amines and alcohols via Ni-catalyzed hydroalkylations

“…Based on the mechanistic results and literature precedence [28][29][30][31][32][33][34][42][43][44][45]48,49 , two tentative mechanistic pathways are proposed and depicted in Fig. 7.…”

“…Recently, our group developed the Ni-H-catalyzed hydroalkylation of acrylates via anti-Markovnikov hydrometalation, giving the enantioenriched α-tertiary amides by forging a stereogenic center originating from acrylates 48 . In 2021, Hu group reported a hydroalkylation of vinyl boronates to give chiral secondary alkyl boronates enabled by the anchoring effect of boron 49 . These examples showcased the feasibility of building a stereogenic carbon center originating from alkenes via Ni-catalyzed hydroarylation [36][37][38] and hydroalkylation [48][49][50][51] of alkenes.…”

“…In 2021, Hu group reported a hydroalkylation of vinyl boronates to give chiral secondary alkyl boronates enabled by the anchoring effect of boron 49 . These examples showcased the feasibility of building a stereogenic carbon center originating from alkenes via Ni-catalyzed hydroarylation [36][37][38] and hydroalkylation [48][49][50][51] of alkenes.…”

NiH-catalyzed asymmetric hydroarylation of N-acyl enamines to chiral benzylamines

“…Benefiting from the economical and facile chain-walking and cross-coupling [12][13][14] , and use of simple ligands, NiH catalysis has emerged in recent years as an efficient means of achieving enantioselective C-C bond formation . In these general synthetic processes: (1) both of the starting alkenes and aryl halides/ alkyl halides are commercially or synthetically available; (2) no prior generation of organometallic reagents is necessary; and (3) the newly formed sp 3 -hybridized stereocenters could potentially be enantioselectively controlled at the carbons originating in the achiral olefins [39][40][41][42][43] or at the carbons from racemic alkyl electrophiles [35][36][37][38] . Recently, we reported the enantioselective hydroarylation of styrenes using a novel chiral nickel-bis(imidazoline) catalyst (Fig.…”

Nickel-Catalyzed Benzylic Alkynylation: Migratory Hydroalkynylation and Enantioselective Hydroalkynylation of Olefins with Bromoalkynes

“…[1] Reductive migratory hydrofunctionalization catalyzed by nickel hydride [2,3] has recently been recognized as an alternative protocol for selective functionalization of remote C(sp 3 )-H bonds (Figure 1a). [4][5][6][7][8][9][10][11][12][13] Compared to conventional cross-coupling, this process (i) employs readily available, benchstable alkenes or alkene precursors instead of specially generated organometallic reagents as starting materials and (ii) could selectively functionalize a remote C(sp 3 )-H site instead of the conventional ipso-position. Since its conception, significant progress has been made toward this synthetically useful process, [8][9][10][11] which requires that the cross-coupling partner (e.g., aryl halide or alkyl halide) could selectively capture an alkylnickel species generated through iterative migratory insertion/β-hydride elimination.…”