δ C–H (hetero)arylationviaCu-catalyzed radical relay

Abstract

A radical relay strategy has been developed to enable selective δ C–H arylation. The approach employs a chiral copper catalyst, which serves the dual roles of generating an N-centered radical to promote intramolecular H-atom transfer, and then intercepting a distal C-centered radical for C–C bond formation with (hetero)aryl boronic acids.

The Persistent Radical Effect in Organic Synthesis

“…In the alkylcyanation, the alkyl radical adding to the styrene derivative can also be generated by decarboxylation from the corresponding active ester by SET reduction, [316] by intermolecular Habstraction with NFSI in alkylarenes, [317] or by 1,5-HATofappropriately designed activated alcohols [318] or amides. [319] Along with the arylation and cyanation of benzylic radicals,p rotocols for Cu-mediated azidation [318,320] and thiocyanation [318, 320d, 321] of stabilized Cradicals have also been developed.…”

Dual Photoredox/Copper Catalysis for the Remote C(sp3)−H Functionalization of Alcohols and Alkyl Halides by N‐Alkoxypyridinium Salts

“…[12a, 16] To expand the repertoire of the aforementioned remote C(sp 3 )ÀHf unctionalization processes,w er ecently became interested in merging the radical 1,5-HAT [17] with the metalcatalyzed cross-coupling reactions. [18,19] While generation of alkoxy radical directly from alcohols are well developed, the oxidative conditions [Pb(OAc) 4 ,P IDA/I 2 ,C e 4+ /photoredox catalysis] associated with such processes may impose certain limitation to the subsequent functionalization of the translocated carbon radical B.T oc omplement this oxidative approach, we have been searching for alkoxy radical precursors that can be homolytically cleaved under reductive conditions to streamline the subsequent metal-catalyzed cross coupling/ligand transfer reactions.T ot his end, the easily available N-alkoxypyridinium salts 1 attracted our attention. Lakhdar and co-workers were the first to demonstrate that the ethoxy radicals can be generated from 1a (R = Et, R 1 = 2-Me) under mild photocatalytic conditions.…”

An Update on Distal C(sp3)−H Functionalization Involving 1,5‐HAT Emerging from Nitrogen Radicals

“…[46] Recently, in contrast to Zhu's work, Nagib group developed Cu(I) catalyst to be used as both radical initiating and radical trapping tool in a same catalytic cycle for remote hetero arylation of aliphatic amines (Scheme 17). [47] Guo group developed an iron-catalyzed intermolecular distal C(sp 3 )À H heteroarylation of alkyl ketones via iminyl radical-triggered 1,5-HAT cascade in aqueous media (Scheme 18a). [48] Shifting towards a more economical strategy, Zhu group have developed two novel iron catalysed protocols enabled by 1,5-HAT for the synthesis of γ-azido ketones and β-azido alcohols via O-acyl oximes and N-acyloxy imidates, respectively (Scheme 18b).…”