Nickel-Catalyzed Asymmetric Reductive Cross-Coupling between Heteroaryl Iodides and α-Chloronitriles

Abstract

A Ni-catalyzed asymmetric reductive cross-coupling of heteroaryl iodides and α-chloronitriles has been developed. This method furnishes enantioenriched α,α-disubstituted nitriles from simple organohalide building blocks. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, quinolines, thiophenes, and piperidines. The reaction proceeds under mild conditions at room temperature, and precludes the need to pre-generate organometallic nucleophiles.

Nickel-Catalyzed Asymmetric Reductive Cross-Coupling To Access 1,1-Diarylalkanes

“…Suzuki, 5 Negishi, 6 Kumada 7 reactions), 8 less progress has been made in the development of asymmetric reductive cross-coupling reactions. 9 Given that many of these reactions work well for secondary alkyl substrates and provide chiral products, it would be of value to develop enantioselective variants. In this communication, we report an enantioselective Ni-catalyzed reductive cross-coupling between aryl iodides and secondary benzylic chlorides (Figure 1).…”

“…Based on our previously disclosed research, 9c we hypothesized that Ni-catalyzed reductive cross-coupling could provide improved access to heterocycle containing products. However, a challenge in the development of such enantioselective reactions is that as one changes electrophile class (e.g.…”

Nickel-Catalyzed Reductive Couplings

“…A highest 65 % ee was disclosed, requiring further endeavors for this type of reaction [52]. The observation that activated alkyl halides are critical for high enantioselectivities is further evidenced in Reisman's recent success in the Ni-catalyzed asymmetric arylation of a-chloronitriles (Scheme 28) [81]. A myriad of heteroaromatic iodides are incorporated into the formation of a-aryl nitriles in good yields and good-to-excellent ees.…”

Nickel-Catalyzed Enantioselective Cross-Coupling of N-Hydroxyphthalimide Esters with Vinyl Bromides

“…5 Recognizing that the ability to render these transformations enantioselective would enhance their utility, 7 our laboratory has recently developed enantioselective Ni-catalyzed reductive cross-coupling reactions of both benzylic chlorides 8 and a-chloronitriles. 9 An important objective for further improving the synthetic usefulness of asymmetric reductive cross-coupling reactions is to develop reactions of new electrophile classes. Just as in conventional cross-coupling reactions, where different organometallic reagents (e.g.…”