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A visible light-mediated, decarboxylative, desulfonylative Smiles rearrangement for general arylethylamine syntheses

David M. Whalley, Hung A. Duong, Michael F. Greaney

2020Chemical Communications40 citationsDOIOpen Access PDF

Abstract

A decarboxylative, desulfonylative Smiles rearrangement is presented that employs activated-ester/energy transfer catalysis to decarboxylate β-amino acid derived starting materials at room-temperature under visible light irradiation. The radical Smiles rearrangement gives a range of biologically active arylethylamine products highly relevant to the pharmaceutical industry, chemical biology and materials science. The reaction is then applied to the synthesis of a chiral unnatural amino acid, 2-thienylalanine, used in the treatment of phenylketonuria. We also show how the reaction can proceed under metal-free and catalyst-free conditions.

Topics & Concepts

Smiles rearrangementChemistryVisible spectrumSigmatropic reactionDecarboxylationPhotochemistryStereochemistryMaterials scienceOptoelectronicsOrganic chemistryCatalysisRadical Photochemical ReactionsSulfur-Based Synthesis TechniquesCatalytic C–H Functionalization Methods