Ruthenium and Iron-Catalysed Decarboxylative N-alkylation of Cyclic α-Amino Acids with Alcohols: Sustainable Routes to Pyrrolidine and Piperidine Derivatives

Abstract

A modular and waste-free strategy for constructing N-substituted cyclic amines via decarboxylative N-alkylation of α-amino acids employing ruthenium- and iron-based catalysts is presented. The reported method allows the synthesis of a wide range of five- and six-membered N-alkylated heterocycles in moderate-to-excellent yields starting from predominantly proline and a broad range of benzyl alcohols, and primary and secondary aliphatic alcohols. Examples using pipecolic acid for the construction of piperidine derivatives, as well as the one-pot synthesis of α-amino nitriles, are also shown.

Keywords: N-alkylation; N-heterocycles; decarboxylation; iron; proline.