Visible Light Induced Cu-Catalyzed Asymmetric C(sp³)–H Alkylation

Abstract

The asymmetric functionalization of C–H is one of the most attractive strategies in asymmetric synthesis. In the past decades, catalytic enantioselective C­(sp3)–H functionalization has been intensively studied and successfully applied in various asymmetric bond formations, whereas asymmetric C­(sp3)–H alkylation was not well developed. Photoredox catalysis has recently emerged as an efficient way to synthesize organic compounds under mild conditions. Despite many photoinduced stereoselective reactions that have been achieved, the related enantioselective C­(sp3)–C­(sp3) coupling is challenging, especially of the photocatalytic asymmetric C­(sp3)–H radical alkylation. Here, we report a visible light induced Cu catalyzed asymmetric sp 3 C–H alkylation, which is effective for coupling with unbiased primary, secondary, and tertiary alkyl fragments in high enantioselectivities. This reaction would provide a new approach for the synthesis of important molecules such as unnatural α-amino acids and late-stage functionalization of bioactive compounds, and will be useful for modern peptide synthesis and drug discovery.

Site‐Selective Itaconation of Complex Peptides by Photoredox Catalysis

“…[6] Major advances in visible‐light‐induced functionalization of amino acid residues [7] has been achieved, including cysteine, [8] glycine, [9] dehydroalanine, [10] tryptophan, [11] tyrosine, [12] methionine, [13] histidine [14] and peptide C ‐termini [15] . Despite the significant advancement, the development of photoredox methods for site‐selective modification of complex peptides is still in its infancy in comparison with highly established small molecules synthesis [16] . Thus, it is of great importance to introduce new photoredox tactics and expand the toolbox for peptide functionalization [17] .…”

“…[15] Despite the significant advancement, the development of photoredox methods for site-selective modification of complex peptides is still in its infancyi nc omparison with highly established small molecules synthesis. [16] Thus,itis of great importance to introduce new photoredox tactics and expand the toolbox for peptide functionalization. [17] Given the various functional groups presence,c hemoselective peptide modification with minimal interference with the peptidyl skeleton is still af ormidable challenge.I ti sk nown that the most of N-termini of peptides are exposed at the surface.…”

α-Branched amines through radical coupling with 2-azaallyl anions, redox active esters and alkenes

“…Before initiating our investigation, reaction conditions used in 2-azaallyl coupling reactions, 19,42 alkene functionalization reactions 75,76 and reductive activation of RAEs 60,77–82 were studied. Based on these works, Ni(COD) 2 was selected as the metal source, 33 DIPEA as base, 31,59,69,83 THF/DMF as solvent (4 : 1, based on literature precedence 50,51,84 ).…”

Visible‐Light‐Promoted Stereoselective C(sp3)−H Glycosylation for the Synthesis of C‐Glycoamino Acids and C‐Glycopeptides

“…Based on above mechanistic studies and the previous research, [14,18] a plausible pathway was given in Scheme 4B. Initially, photosensitive species A in situ forms via the coordination of [L*Cu I ] with glycinate ester 1.…”