Nickel-Catalyzed Enantioselective Reductive Arylation and Heteroarylation of Aldimines via an Elementary 1,4-Addition

Abstract

Nickel catalysts of chiral pyrox ligands promoted enantioselective reductive arylation and heteroarylation of aldimines, using directly (hetero)aryl halides and sulfonates. The catalytic arylation can also be conducted with crude aldimines generated from condensation of aldehydes and azaaryl amines. Mechanistically, density functional theory (DFT) calculations and experiments pointed to an elementary step of 1,4-addition of aryl nickel(I) complexes to Nazaaryl aldimines.

Enantioselective Reductive Conjugate Alkenylation of α,β-Unsaturated Ketones and Amides via Nickel Catalysis

“…By analogy to asymmetric reductive arylation of enones and N- 2-pyridyl aldimines that we reported recently, we propose a catalytic cycle for the reductive alkenylation of enones (Figure ). In a productive catalytic cycle, an alkenyl nickel I species (rather than a nickel II complex) is mainly responsible for the asymmetric addition to enones.…”

“…The new mechanism of elementary 1,4-addition is also supported by some experimental observations, which bear resemblance to reductive arylation of enones that we reported: (a) very poor reactivity of cyclic enones (e.g., 2-cyclopentenone and 2-cyclohexenone), which cannot assume s -cisoid conformation in this kind of cyclic transition states; (b) exclusive β-addition to a 2,4-dienone that form product 4t ; (c) formation of a pair of diastereomers of product 4x (1.4:1) from 2-benzylidene-1-tetralone. Each diastereomer of 4x was formed in identical 92% ee, supporting nonstereoselective α-protonation of nickel enolates after alkenyl insertion.…”

Recent Advances in Nonprecious Metal Catalysis

“…Zhou and co-workers reported an enantioselective reductive arylation (>90% ee ) of N -3-picolyl aldimines using NiBr 2 ·DME (5 mol %) and chiral t Bu-pyrox ligand L2 (6 mol %) (Scheme ). DMF was identified as the optimal solvent, and Mn was identified as the best reductant for this transformation. A range of functional groups on the aryl bromide (e.g., aldehydes, ketones, esters, and nitriles) and examples of heteroaryl bromides (e.g., indoles, quinolines, 2-methylpyridines, and pyridones) were tolerated in this reaction.…”

Nickel-Catalyzed Enantioselective Reductive Arylation of Common Ketones

“…We herein report the first intermolecular examples of enantioselective reductive arylation of common ketones using aryl halides (see Figure ). Certainly, catalytic reductive couplings and addition using organohalides have several practical advantages in synthesis: direct use of commercially available or readily prepared aryl halides, almost neutral conditions, avoidance of using basic organometallic reagents or bases which are needed for transmetalation of aryl boronic acids, and excellent compatibility of reacted polar groups or weakly acidic groups.…”