Asymmetric Radical-Type Clayden Rearrangement for the Synthesis of Enantiopure 1,2-Aminothiols and 1,2-Aminoalcohols

Abstract

We report herein an expedient method for the construction of enantiopure 1,2-aminothiols and 1,2-aminoalcohols starting from polar amino acids cysteine and serine via a photoredox-catalyzed, decarboxylation-enabled asymmetric radical-type Clayden rearrangement. The strategy of “self-regeneration of stereocenters (SRS)” is employed to enable the stereoselective 1,4-N-to-C radical aryl migration of heterocyclic ureas, which serve as rigid-scaffold substrates and can be readily derived from serine and cysteine. A wide range of migrating groups, including multisubstituted and heterocyclic aryls, are well tolerated and afford the aryl migration products with excellent diastereoselectivity. This strategy not only offers a practical route to enantiopure 1,2-aminothiols and 1,2-aminoalcohols but also paves a new way for asymmetric radical Truce–Smiles rearrangement, holding great potential for the construction of aryl-containing chiral building blocks.