Enantioselective Reductive Cross-Couplings of Olefins by Merging Electrochemistry with Nickel Catalysis

Abstract

The merger of electrochemistry and transition metal catalysis has emerged as a powerful tool to join two electrophiles in an enantioselective manner. However, the development of enantioselective electroreductive cross-couplings of olefins remains a challenge. Inspired by the advantages of the synergistic use of electrochemistry with nickel catalysis, we present here a Ni-catalyzed enantioselective electroreductive cross-coupling of acrylates with aryl halides and alkyl bromides, which affords chiral α-aryl carbonyls in good to excellent enantioselectivity. Additionally, this catalytic reaction can be applied to (hetero)­aryl chlorides, which is difficult to achieve by other methods. The combination of cyclic voltammetry analysis with electrode potential studies suggests that the NiI species activates aryl halides by oxidative addition and alkyl bromides by single-electron transfer.

When transition-metal catalysis meets electrosynthesis: a recent update

“…86 Recently, Mei and co-workers developed a nickel-catalyzed asymmetric eXEC of acrylates with two different organohalides to synthesize enantioenriched α-aryl carbonyls. 87…”

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

“…However, in addition to the facile β–H elimination from the Csp 3 –[M] intermediate, the inherent challenge with asymmetric alkene arylalkylation involving the simultaneous incorporation of two distinct natures of Csp 2 and Csp 3 -hydridized carbogenic groups across the double bond lies in the simultaneous control of all aspects of selectivity, including chemo-, regio-, and stereoselectivity. − While the intramolecular two-component alkene arylalkylation has been widely explored by cyclizative coupling of aryl-tethered alkenes − (Figure a), the development of an enantioselective intermolecular, three-component variant in a regioselective manner remains an unmet challenge. Until recent years, building on the landmark achievements in base-metal catalysis for the utilization of a wide range of Csp 3 -based coupling partners through a 1e-logic process, ,− tremendous advances on three-component asymmetric arylalkylation of alkenes by transition metal, dual electrochemical/nickel, or photoredox/nickel catalysis have been therefore achieved with high regioselectivity via the radical relay strategy. ,− However, in this event, the radical-trapping π-systems were severely restricted to terminal alkenes, thus being limited to the incorporation of alkyl units at the terminal olefinic position (Figure b). In stark contrast to the well-established radical relay strategy, the catalytic enantioselective, three-component arylalkylation of alkenes via stereoselective migratory insertion strategy in an enantio- and regioselective manner has been largely underdeveloped so far (Figure d).…”

“…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.…”

“…However, Z -alkenes exhibited higher enantioselectivity than the analogous E -alkene ( 27 vs 28 ). It is worth stressing that the radical relay approach generally fails to tolerate internal alkene substrates. ,− The absolute stereochemistries of the enantioenriched products ( S )- 7 and 28 were established by X-ray crystallographic analysis, and all others were assigned by analogy.…”

Nickel-Catalyzed Reductive Alkene Cross-Dialkylation with Unactivated Alkyl Electrophiles

“…In particular, Ni-catalyzed alkene dicarbonfunctionalization has attracted considerable attention, and the past decade has witnessed a booming development . A plethora of elegant work has been reported, focusing mainly on diarylation and aryl-alkylation , (Scheme A). Reports in dialkylation of unactivated alkenes are still limited, especially in an intermolecular mode …”