Nickel‐Catalyzed Asymmetric Reductive Heck Cyclization of Aryl Halides to Afford Indolines

Abstract

A nickel-catalyzed asymmetric reductive Heck reaction of aryl chlorides has been developed that affords substituted indolines with high enantioselectivity. Manganese powder is used as the terminal reductant with water as a proton source. Mechanistically, it is distinct from the palladium-catalyzed process in that the nickel-carbon bond is converted into a C-H bond to release the product through protonation instead of hydride donation followed by C-H reductive elimination on Pd.

Mechanisms of Nickel-Catalyzed Cross-Coupling Reactions

“…Hydroarylation reactions proceeding through two-electron pathways via Ni(I)/Ni(III) intermediates disregard the position of the olefin in the substrate but form C-C bonds from the most stable benzylic organonickel intermediate via reversible chain walking [83]. Asymmetric variants have been achieved by intramolecular hydroarylation of indoles to form indoline products 63 [84], the coupling of vinylarenes with aryl boron reagents [85], and the coupling of 1,3-dienes with enolates [86]. Most hydroalkylation reactions are conducted with electrophiles under reductive conditions and proceed through radical pathways.…”

Palladium‐Catalyzed Asymmetric Intramolecular Reductive Heck Desymmetrization of Cyclopentenes: Access to Chiral Bicyclo[3.2.1]octanes

“…However, because of the high propensity of the β‐hydride elimination pathway (Heck reaction), the asymmetric version of the reductive Heck reaction is still in its infancy. Prior works on the asymmetric intramolecular reductive Heck reactions of either 1,1‐disubstituted olefins or 2‐substituted indoles have been realized by the groups of Diaz, Jia,, Zhu,, Lautens, Tong, and Zhang (Scheme a). In these elegant works, the in situ generated alkylpalladium intermediates were efficiently trapped by the hydride donors to deliver the asymmetric reductive Heck products because they lacked the β‐hydrogen.…”

Catalytic Asymmetric Synthesis of Isoindolinones

“…Additionally, a nickel catalyst could also be used in reductive Heck‐type transformations. In 2017, Zhou's group developed a nickel‐catalyzed intramolecular dearomatization of N‐substituted indoles 172 to afford isoindolones 173 with high enantioselectivity (Scheme ) . It is worth noting that water was necessary with manganese powder as the terminal reductant.…”

“…2019, 14,1306-1322 www.chemasianj.org velopedanickel-catalyzed intramolecular dearomatization of N-substituted indoles 172 to afford isoindolones 173 with high enantioselectivity (Scheme 49). [71] It is worth noting that water was necessary with manganese powder as the terminal reductant. Mechanistically,t he NiÀCb ond was converted to aC ÀH bond by protonation, which was distinct from hydride donation, followed by CÀHr eductiveelimination from Pd.…”