Strained enamines as versatile intermediates for stereocontrolled construction of nitrogen heterocycles

Gang Chen; Mikio Sasaki; Xinghan Li; Andrei K Yudin

doi:10.1021/jo0607921

Strained enamines as versatile intermediates for stereocontrolled construction of nitrogen heterocycles

J Org Chem. 2006 Aug 4;71(16):6067-73. doi: 10.1021/jo0607921.

Authors

Gang Chen¹, Mikio Sasaki, Xinghan Li, Andrei K Yudin

Affiliation

¹ Davenport Research Laboratories, Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.

PMID: 16872190
DOI: 10.1021/jo0607921

Abstract

This contribution assesses the synthetic utility of molecules that impose conformational constrains onto aziridine-derived enamines. Synthetically versatile [3.1.0] and [4.1.0] bicyclic enamines have been prepared by intramolecular oxidative cycloamination of aziridine-containing olefins. This process is initiated by N-bromosuccinimide followed by base-mediated elimination of HBr to afford highly strained exo-bicyclic enamines. In addition, intramolecular aziridine addition to aldehyde functionality was found to afford the [3.1.0] and [4.1.0] bicyclic hemiaminals. These routes highlight possibilities for chemoselective oxidative transformations of aziridine-containing precursors without nitrogen protection/deprotection steps. The resulting products provide straightforward synthetic entries into a wide range of pyrrolidine- and piperidine-containing heterocycles that are positioned toward subsequent transformations via aziridine ring opening.