C(sp³)−H Cyanation Promoted by Visible‐Light Photoredox/Phosphate Hybrid Catalysis

Abstract

Inspired by the reaction mechanism of photo-induced DNA cleavage in nature, a C(sp )-H cyanation reaction promoted by visible-light photoredox/phosphate hybrid catalysis was developed. Phosphate radicals, generated by one-electron photooxidation of phosphate salt, functioned as a hydrogen-atom-transfer catalyst to produce nucleophilic carbon radicals from C(sp )-H bonds with a high bond-dissociation energy. The resulting carbon radicals were trapped by a cyano radical source (TsCN) to produce the C-H cyanation products. Due to the high functional-group tolerance and versatility of the cyano group, the reaction will be useful for realizing streamlined building block syntheses and late-stage functionalization of drug-like molecules.

Arene dearomatization through a catalytic N-centered radical cascade reaction

“…This result suggests that single-electron oxidation of a sulfonamidyl anion is not the dominant route to the nitrogen-centered radical. Qualitatively, these results together are consistent with a phosphate radical being generated under the reaction conditions and serving as a hydrogen-atom abstracting species and is at least partly responsible for the generation of the nitrogen radical 61,62 . HAT between heteroatoms is known to occur rapidly, even in the presence of weaker C-H bonds 63 .…”

Recent Advances in Rapid Synthesis of Non-proteinogenic Amino Acids from Proteinogenic Amino Acids Derivatives via Direct Photo-Mediated C–H Functionalization

“…Additionally, TMSCN was used as an alternative cyanation reagent to provide the cyanated glycine derivative under the visible-light catalysis in 2018 (Scheme 38b) [84]. Particularly in 2018, Kanai and Oisaki's group reported a C(sp 3 )-H cyanation of methionine and its dipeptide through the cooperative visible-light photoredox/phosphate acid catalysis (Scheme 39) [85]. However, because of two possible reaction sites adjacent to the sulfur atom, this cyanation reaction proceeded in poor regioselectivity, albeit in good to excellent yields.…”

Tyrosine and Drug-like Late-stage Benzylic Functionalization via Photoredox Catalysis

“…The con guration of the major diastereoisomer of product 3b was determined as (2S,3S) by NOESY experiments (see S.I.). Similarly, other activated alkenes like benzylidene malonitrile (2c) or electron acceptors with aryl sulfonyl leaving groups 2d-f [42][43][44] could be e ciently enrolled in the reaction. As a result, valuable cyano, allyl and alkynyl groups could be selectively introduced in excellent yields (up to 96%) and good diastereoselectivities (up to 6:1 d.r).…”