Photoredox-Induced Radical Relay toward Functionalized β-Amino Alcohol Derivatives

Abstract

A radical relay strategy is described to synthesize functionalized β-amino alcohols. This strategy is enabled by photoredox-catalyzed and nitrogen-centered radical-triggered cascade reactions of styrenes (or phenylacetylenes), enol derivatives, and O-acyl hydroxylamines in DMSO. The broad synthetic application of this method is demonstrated by the reaction of structurally diverse reaction components, including complex molecular scaffolds. Multiple functional groups of the resultant highly functionalized β-amino alcohol derivatives facilitate their further transformations.

Intermolecular radical carboamination of alkenes

“…Radical carboamination of vinyl ethers by photoredox catalysis [55][56][57] was achieved by Yu and co-workers in 2018 (Scheme 9). 58 Diverse b-amino alcohol derivatives 33 were obtained in high yields from the O-acyl hydroxylamine derivative 32, benzyl vinyl ether and phenylacetylenes under mild conditions. Upon visible light irradiation, the easily prepared O-acyl hydroxylamine 32 is reduced by a photoexcited Ir(III)complex to provide the electrophilic amidyl radical 34, which undergoes chemoselective radical addition to the electronrich benzyl vinyl ether to give the a-oxy-alkyl radical 35.…”

Anti‐Markovnikov Radical Hydro‐ and Deuteroamidation of Unactivated Alkenes

“…Compared to previous methods for radical hydroamidation, our process uses only two equivalents of the alkene component and a small amount of both photocatalyst and thiophenol polarity reversal catalyst . Notably, the carbobenzyloxy (Cbz) group used herein is a common N‐protecting group in organic synthesis . Considering the alkene deuteroamidation, satisfactory D incorporation of diverse alkenes can be achieved, demonstrating the high efficiency of thiophenol acting as a radical deuteration reagent in combination with D 2 O.…”

“…[12] Notably,t he carbobenzyloxy (Cbz) group used herein is ac ommon N-protecting group in organic synthesis. [13] Considering the alkene deuteroamidation, satisfactory D incorporation of diverse alkenes can be achieved, demonstrating the high efficiency of thiophenol acting as ar adical deuteration reagenti nc ombination with D 2 O.…”

“…Ru ( lysts, such as Ru(bpy) 3 (PF 6 ) 2 (PC-II), Ru(bpz) 3 (PF 6 ) 2 (PC-III)a nd the organic systems4 -CzIPN (PC-IV)a nd Mes-Acr-Me (PC-V), providedw orse results (entries [12][13][14][15].…”

Transition‐Metal‐Free Three‐Component Radical 1,2‐Amidoalkynylation of Unactivated Alkenes

“…Such transformations have gained great interests in modern organic synthesis. [1] In this regard, alkene carboamination is av aluable approachf or the preparation of diverse amines.T ransition-metal-catalyzed or radical carboaminations of activateda lkenesi ncluding styrenes, [2] vinyl amides, [3] vinyl ethers [4] and acrylates [5] have been reported. Considering unactivated terminal alkenes as substrates, 1,2-carboamination generatingaC ÀC s-bonda tt he terminal position of the starting alkeneh as been successfully investigated in recenty ears by several groups.…”