Persulfate‐Mediated Oxidative C−H Functionalization of Glycinates to Access Diverse Unnatural Amino Acids. Issue 46 (8th December 2022)

• Record Type: Journal Article
• Authors: Hari Babu, Madala; Jang, Hyesu; Han, Miseon; Kyum Kim, Sang; Sim, Jaehoon
• Is Part Of: European journal of organic chemistry. Volume 2022:Issue 46(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-12-08
• Subjects: Alkylation -- C−H functionalization -- Unnatural amino acids -- Phosphonation -- Radical addition; Chemistry, Organic -- Periodicals; Organic compounds -- Synthesis -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1002/ejoc.202201259
• Languages: English
• ISSNs: 1434-193X

Abstract

Abstract: We have developed an operationally simple and green approach to prepare robust α ‐alkyl unnatural amino acids through the dual oxidative activation of glycine derivatives and alkylcarboxylic acids with persulfate as the sole oxidizing agent. This method allows for the utilization of naturally abundant alkylcarboxylic acids as radical sources without the assistance of catalysts. Notably, this method allows for the late‐stage decoration of biologically relevant carboxylic acids and peptides to construct diverse unnatural amino acids. In addition, the generality of the oxidative activation method enables a facile synthetic approach to α‐phosphonyl glycine derivatives by using phosphites and phosphine oxides. Abstract : Metal‐free and an operationally simple radical‐mediated reaction was developed to access diversified unnatural amino acids with alkyl carboxylic acids, H‐phosphonates and H‐phosphinates by using persulfate as the sole oxidizing agent. The overall reaction proceeds via oxidative generation of iminium ion from glycine derivatives followed by radical addition of alkyl and phosphonyl groups to yield α‐alkyl and α‐phosphonyl glycine derivatives.