Enantioselective (4+2) Annulation of Donor-Acceptor Cyclobutanes by N-Heterocyclic Carbene Catalysis

Alison Levens; Adam Ametovski; David W Lupton

doi:10.1002/anie.201609330

Enantioselective (4+2) Annulation of Donor-Acceptor Cyclobutanes by N-Heterocyclic Carbene Catalysis

Angew Chem Int Ed Engl. 2016 Dec 23;55(52):16136-16140. doi: 10.1002/anie.201609330. Epub 2016 Nov 28.

Authors

Alison Levens¹, Adam Ametovski¹, David W Lupton¹

Affiliation

¹ School of Chemistry, Monash University, Clayton, 3800, Victoria, Australia.

PMID: 27891746
DOI: 10.1002/anie.201609330

Abstract

Herein we report the enantioselective (4+2) annulation of donor-acceptor cyclobutanes and unsaturated acyl fluorides using N-heterocyclic carbene catalysis. The reaction allows a 3-step synthesis of cyclohexyl β-lactones (25 examples) in excellent chemical yield (most ≥90 %) and stereochemical integrity (all >20:1 d.r., most ≥97:3 e.r.). Mechanistic studies support ester enolate Claisen rearrangement, while derivatizations provide functionalized cyclohexenes and dihydroquinolinones.

Keywords: N-heterocyclic carbenes; cyclohexanes; donor-acceptor cyclobutanes; enantioselective catalysis; organocatalysis.

Publication types

Research Support, Non-U.S. Gov't