Radical‐Mediated C−H Alkylation of Glycine Derivatives: A Straightforward Strategy for Diverse α‐Unnatural Amino Acids

• Published in: European journal of organic chemistry 2022-12, Vol.2022 (45), p.n/a
• Main Authors: Hari Babu, Madala, Sim, Jaehoon
• Format: Article
• Language: English
• Subjects: Alkylation; Amino acids; C−H alkylation; Glycine; Natural products; Radical addition; Radical coupling; Radicals; Unnatural amino acids
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.202200859

Unnatural amino acids are important scaffolds for novel drug candidates, and especially α‐alkyl amino acids have emerged as a valuable variant. This is due to the ubiquity of alkyl groups, which are pervasive as key motifs in natural products, biological and pharmaceutical molecules. The development of radical‐based approaches in organic synthesis has expanded dramatically in recent years. It has enabled site‐ and region‐specific installation of a variety of functionalities in small molecules, which has been spontaneously applied in the preparation of versatile amino acid building blocks. The glycine motif in the backbone of amino acids has gained significant attention for allowing access to a variety of complex α‐unnatural amino acids via radical‐mediated α‐C−H alkylation. This review summarizes the last decade's development of radical‐based α‐C−H alkylation of glycine derivatives to provide unnatural α‐amino acids. The advantages, current limitations, and perspectives of glycine‐based unnatural amino acid synthesis are also discussed. Modification of glycine is the one of the most straightforward strategy to access diverse unnatural amino acids. This review outlines an overview of recently developed transformations employing radical‐mediated C−H alkylation of N‐aryl glycine derivatives.