Nickel- and Photocatalytic Enantioselective Alkylation of α-Amino C(sp³)–H Bonds

Key words

nickel catalysis - photoredox catalysis - C–H alkylation - bromide activation

Significance

The authors report the nickel and photoredox co-catalyzed enantioselective coupling of α-amino C–H bonds and redox active esters (RAEs). The reaction proceeds via the generation and coupling of two different alkyl radicals. The enantioselectivity of the reaction remained very high even when the groups were of similar steric bulk. The authors also showed the RAEs could be generated in situ resulting in similar yields and ee values.

Comment

The reaction was shown to require bromide as an hydrogen atom transfer (HAT) source. NiBr₂ has the benefit of adding the nickel catalyst and the HAT catalyst from the same source. Trapping with radical acceptors suggest that the α-amino radical is formed, and trapping with TEMPO indicates that the alkyl radical from the RAE is also formed. The parallel KIE experiment gave a result of 3.4, indicating the HAT step likely plays a role in the rate-determining step.

Publication History

Article published online:
16 August 2024