A General Amino Acid Synthesis Enabled by Innate Radical Cross‐Coupling. Issue 44 (15th October 2018)

• Record Type: Journal Article
• Authors: Ni, Shengyang; Garrido‐Castro, Alberto F.; Merchant, Rohan R.; de Gruyter, Justine N.; Schmitt, Daniel C.; Mousseau, James J.; Gallego, Gary M.; Yang, Shouliang; Collins, Michael R.; Qiao, Jennifer X.; Yeung, Kap‐Sun; Langley, David R.; Poss, Michael A.; Scola, Paul M.; Qin, Tian; Baran, Phil S.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 44(2018)
• Page Start: 14560
• Page End: 14565
• Publication Date: 2018-10-15
• Subjects: amino acid synthesis -- decarboxylative radical addition -- library synthesis -- redox-active esters -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201809310
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: The direct union of primary, secondary, and tertiary carboxylic acids with a chiral glyoxylate‐derived sulfinimine provides rapid access into a variety of enantiomerically pure α‐amino acids (>85 examples). Characterized by operational simplicity, this radical‐based reaction enables the modular assembly of exotic α‐amino acids, including both unprecedented structures and those of established industrial value. The described method performs well in high‐throughput library synthesis, and has already been implemented in three distinct medicinal chemistry campaigns. Abstract : Acids to acids : A practical method for the preparation of highly valuable enantiomerically pure α‐amino acids has been developed. The described transformation rapidly converts feedstock alkyl carboxylic acids to α‐amino acids, and is enabled by innate radical cross‐coupling with a chiral imine radical acceptor. The scope of this transformation is broad and has been field‐tested in three different industrial medicinal chemistry laboratories.