Two‐Step Synthesis of 2‐Aminoindolizines from 2‐Alkylpyridines

Abstract

An efficient method for the synthesis of 2‐aminoindolizines by the 5‐exo‐dig cyclization of 2‐alkyl‐1‐(1‐cyanoalkyl)pyridinium salts has been developed. These substrates were prepared by N‐alkylation of 2‐alkylpyridines with readily available cyanohydrin triflates. The method allows the introduction of various substituents at the 1‐, 3‐, 6‐, 7‐, and 8‐positions and leaves no undesired acceptor groups in the products.

Microwave-Assisted Synthesis of Fluorescent Pyrido[2,3-b]indolizines from Alkylpyridinium Salts and Enaminones

“…The reaction presumably starts with the intramolecular cyclization of a deprotonated α-methyl group on a nitrile moiety, eventually giving an aminoindolizine intermediate A [ 27 ] ( Scheme 3 ). The interaction of the latter with enaminone produces an intermediate B .…”

“…Another approach towards the indolizine scaffold is based on intramolecular cyclization of 2-alkylpyridinium ylides. For instance, Opatz et al used 2-alkyl-1-(cyanomethyl)pyridinium salts to prepare aminoindolizines [ 27 ]. Following our interest in the chemistry of cyanomethylpyridinium salts [ 28 , 29 , 30 ], we recently showed that the interaction of N -(cyanomethyl)pyridinium chlorides with enaminones under basic conditions proceeds as a pseudo-three-component reaction, resulting in the formation of pyridoindolizine-10-carbonitriles [ 31 ].…”