Work

Synthesis of Substituted Cyclic Amines From Protected Amino Acids Using Oxidative Decarboxylation and Alkylation

Year: 2026

Type: article

Abstract: ABSTRACT Cyclic amines are vital scaffolds in bioactive molecules and drug discovery, often functionalized via electrochemical Shono‐type oxidation to access N ‐acyliminium intermediates. However, electrochemical methods can pose scalability and operational challenges. Here, we report a radical oxidative decarboxylation of four‐, five‐, and six‐membered cyclic protected amino acids bearing Cbz, Boc, or tosyl groups, employing iodine with (diacetoxyiodo)benzene or iodosylbenzene to generate N ‐acyliminium ions. These intermediates were trapped with alcohols and subsequently alkylated using various organometallic reagents in the presence of BF 3 •Et 2 O, yielding substituted cyclic amines efficiently. This protocol circumvents the need for electrochemical apparatus and harsh conditions, offering a versatile and practical route to alkylated cyclic amines. The methodology expands the toolbox for constructing 3D heterocyclic scaffolds relevant to medicinal chemistry and natural product synthesis.

Source: Asian Journal of Organic Chemistry

DOI: 10.1002/ajoc.70319