How does the nickel catalyst control the doubly enantioconvergent coupling of racemic alkyl nucleophiles and electrophiles? The rebound mechanism

Abstract

A DFT mechanistic study was performed to account for the nickel-catalyzed doubly enantioconvergent C(sp³)–C(sp³) coupling of racemic alkyl nucleophiles and electrophiles. After generating an active Ni⁰ species, the coupling proceeds via the Ni⁰/Ni^II catalytic cycle, but the Ni^II species can undergo a rebound process using Ni^I as the transient species for erasing and resetting the chiralities of the substrates. Reductive elimination is the stereoselectivity-determining step, thus enabling the ligand to control the stereoselectivity by favoring the one leading to the major (S)(S)-product through the steric effect among the four stereoisomers of the reductive elimination transition state. Expectedly, the disclosure of the rebound mechanism offers an inspiration for developing doubly enantioconvergent C(sp³)–C(sp³) couplings, as well as general enantioconvergent couplings.