Enantioselective Ni‐Catalyzed Three‐Component Dicarbofunctionalization of Alkenes

Abstract

Asymmetric multicomponent reactions are considered as efficient protocols for constructing complex chiral molecules because of their step‐ and atom‐economy. Nickel‐catalyzed asymmetric three‐component dicarbofunctionalization of alkenes has been well developed in recent years, which is used in the area of total synthesis of natural products and late‐stage modification of drugs because of the rapid incorporation of chiral sp3‐enriched carbon centers. In this concept, the significant breakthroughs of this field are summarized, together with the related mechanisms. Moreover, the remaining challenges and potential opportunities of multicomponent dicarbofunctionalization are also highlighted.

Enantioselective Directed Nickel-Catalyzed Three-Component Reductive Arylalkylation of Alkenes via the Carbometalation/Radical Cross-Coupling Sequence

“…As a continuation of our interest in this area, we herein disclose the first enantioselective nickel-catalyzed reductive three-component arylalkylation between terminal or internal alkenes, aryl halides, and alkyl halides through carbonickelation/Csp 3 –Csp 3 cross-coupling sequence (Figure d). This reductive asymmetric arylalkylation of alkenes makes it reasonable to proceed with the chiral aryl–[Ni] complex in situ catalytically generated from aryl halides performing stereoselective carbonickelation of alkene ,,,− to afford the chiral α-branched Csp 3 –Ni intermediate with opposite regioselectivity to those radical relay strategies. − A coordinating-group-based chelation strategy is employed to stabilize the enantiomerically enriched Csp 3 –Ni intermediate as a transient nickelacycle followed by radical cross-coupling with alkyl halides to deliver aryl/alkyl difunctionalized products with exquisite control of regio-, chemo-, and enantioselectivity. Additionally, this reaction, devoid of the need for preprepared and sensitive organometallic reagents, is compatible with a broad range of electrophilic aryl and alkyl sources possessing various reactive functional groups.…”

(Primary Amido)-ene(amido) Ni(II) Catalysts Containing a P-Chirogenic Substituted Ferrocene Moiety for Highly Enantioselective Asymmetric Transfer Hydrogenation of Ketones

“…Recently, some nickel catalysts 16,17 exhibited high activities and enantioselectivities in synthesizing compounds with chiral C−N bonds via reductive aminations of ketones. 18−22 However, more challenging ATH and AH reactions of ketones have been developed slowly.…”

“…Recently, some nickel catalysts , exhibited high activities and enantioselectivities in synthesizing compounds with chiral C–N bonds via reductive aminations of ketones. − However, more challenging ATH and AH reactions of ketones have been developed slowly. Despite reports of a number of hydrogenation or transfer hydrogenation reactions of ketones catalyzed by nickel complexes, most of them are not asymmetric. ,− To the best of our knowledge, , there are only three examples of nickel-catalyzed ATH reactions of ketones to date.…”