Design and Synthesis of Tunable Chiral 2,2′‐Bipyridine Ligands: Application to the Enantioselective Nickel‐Catalyzed Reductive Arylation of Aldehydes

Abstract

A new class of chiral 2,2'-bipyridine ligands, SBpy, featuring minimized short-range steric hindrance and structural tunability was rationally designed and developed, and the effectiveness was demonstrated in the first highly enantioselective Ni-catalyzed addition of aryl halides to aldehydes. In comparison with known approaches using preformed aryl metallic reagents, this reaction is more step-economical and functional group tolerant. The reaction mechanism and a model of stereocontrol were proposed based on experimental and computational results.

Nickel-Catalyzed Enantioselective Coupling of Acid Chlorides with α-Bromobenzoates: An Asymmetric Acyloin Synthesis

“…Since then, extensive efforts have been devoted to developing Grignard-type carbonyl addition reactions using a great diversity of premetalated C -nucleophiles, including aryl, alkyl, alkenyl, alkynyl, and allyl metal reagents . In this context, the nucleophilic addition of this range of organometallic reagents to aldehydes has been strikingly popularized as the most convenient and widely used method for the general construction of diverse (chiral) secondary alcohol compounds and, more importantly, with significant success in the context of (asymmetric) catalytic versions (Figure a, left) . In stark contrast, although the homologous acyl-metal species have long been marked as an important class of coupling handles in chemical synthesis, the utilization of this common species in the reaction with aldehydes has received a much lesser extent of the investigations .…”

“…Like the well-established asymmetric Grignard-type carbonyl addition reactions, , inventing a catalytic enantioselective method that enables the efficient reaction of acyl-metal species and aldehydes would be ideal and highly appealing for accessing enantioenriched acyloins. Three methods have been established for the direct utilization of aldehydes in the coupling reaction with preformed acyl-metal species to furnish acyloins (Figure d). − However, these methods suffered from (1) additional steps for synthesizing stoichiometric acyl-metal reagents with a cautious operation at a low temperature under air/moisture and (2) the need for specialized reagents, hard-to-access acyl-metal precursors, and a limited substrate scope.…”