Visible Light-Driven Benzylic C(sp <sup>3</sup> )–H Carboxylation Enables Synthesis of <sup>13</sup> C-Labeled (±)-α-Amino Acids with <sup>13</sup> C-Formate
Hao Zhang, Xiaoyang Wu, Panpan Gao, Li Zhu, Shangde Ai, Yang-Tong Ma, Zhuofan Jian, Gang Li
Abstract
13 C-labeled α-amino acids are important molecules in biological studies and drug development. Cost-effective synthesis of α-amino acids with a high level of 13 C incorporation under mild conditions remains limited. Herein, we report the development of a benzylic C(sp 3 )–H carboxylation method to prepare highly 13 C-labeled α-amino acids, i.e., arylglycines, using near-stoichiometric and user-friendly sodium 13 C-formate. The sequential reaction pathway of in situ 13 C-carbon dioxide (CO 2 ) generation followed by C–H carboxylation via 1,2-HAT was suggested by mechanistic studies.
Topics & Concepts
CarboxylationChemistryCombinatorial chemistryOrganic chemistryMoleculeCarbonylationIn situSodiumReaction conditionsCarbon dioxideChemical synthesisStereochemistryCatalysisSelectivityCarbon dioxide utilization in catalysisChemical Reactions and IsotopesFluorine in Organic Chemistry