Concise Synthesis of 3-(Aminomethyl)pyrrolizidines via an In(OTf)₃-Mediated Ring Rearrangement of 2-[2-(1-Pyrrolin-2-yl)-alkyl]aziridines

Abstract

In this study, an efficient ring rearrangement of 2-[2-(1-pyrrolin-2-yl)alkyl]aziridines, prepared from 2-(bromomethyl)aziridines, toward novel trans- and cis-3-aminomethyl-substituted pyrrolizidines was developed. To that end, addition of In(OTf)₃ as an appropriate Lewis acid catalyst resulted in the formation of intermediate pyrrolizidinium salts via regioselective aziridine ring opening, which were then trapped by a hydride or cyanide nucleophile. Column chromatographic purification allowed the isolation of the major trans-isomers, exclusively.

Key words

pyrrolizidines - aziridines - ring rearrangement - α-amino­nitriles - In(OTf)₃

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