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

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.