Diastereoselective Radical Aminoacylation of Olefins through N‑Heterocyclic Carbene Catalysis
journal contributionposted on 24.11.2022, 20:03 authored by Wen-Deng Liu, Woojin Lee, Hanyu Shu, Chuyu Xiao, Huiwei Xu, Xiangyang Chen, Kendall N. Houk, Jiannan Zhao
There have been significant advancements in radical-mediated reactions through covalent-based organocatalysis. Here, we present the generation of iminyl and amidyl radicals via N-heterocyclic carbene (NHC) catalysis, enabling diastereoselective aminoacylation of trisubstituted alkenes. Different from photoredox catalysis, single electron transfer from the deprotonated Breslow intermediate to O-aryl hydroxylamine generates an NHC-bound ketyl radical, which undergoes diastereocontrolled cross-coupling with the prochiral C-centered radical. This operationally simple method provides a straightforward access to a variety of pyrroline and oxazolidinone heterocycles with vicinal stereocenters (77 examples, up to >19:1 d.r.). Electrochemical studies of the acyl thiazolium salts support our reaction design and highlight the reducing ability of Breslow-type derivatives. A detailed computational analysis of this organocatalytic system suggests that radical–radical coupling is the rate-determining step, in which π–π stacking interaction between the radical intermediates subtly controls the diastereoselectivity.
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undergoes diastereocontrolled crosssingle electron transferorganocatalytic system suggestsenabling diastereoselective aminoacylationdetailed computational analysisdiastereoselective radical aminoacylationbound ketyl radicaldeprotonated breslow intermediatecentered radicalvicinal stereocenterstype derivativestrisubstituted alkenesstraightforward accesssignificant advancementsreducing abilityreaction designr .).prochiral coxazolidinone heterocyclesmediated reactionsheterocyclic carbeneelectrochemical studiesdetermining stepbased organocatalysis77 examples