DOI: 10.1021/acs.joc.6c01771 ISSN: 0022-3263
Intramolecular [2 + 2] Cycloaddition of Cu-Catalyzed Azide–Alkyne Cycloaddition Generated Ketenimines and Alkoxyalkynes for the Synthesis of 7-Azabicyclo[4.2.0]octa-1(8),5-dienes
Josie Ascione, Gordon Farley, Rodrigo De Leon, Sheila Namirembe, Brian Carvalho, Michael Chaoui, Henry Noe, Michael Beauchamp, André K. IsaacsAbstract
A general approach to the synthesis of 7-azabicyclo[4.2.0]octadienes was achieved via the Cu-catalyzed azide-alkyne cycloaddition (CuAAC) of readily accessible carbon- and oxygen-based 1,6-diynes synthesized in two steps starting from aldehydes/ketones or alkylidene malonates. The reaction proceeds through a probable [2 + 2] cycloaddition reaction of an activated alkyne with the C═N bond of a CuAAC-generated ketenimine intermediate. This underexplored mode of ketenimine reactivity provides rapid access to fused 2-azetines and expands the scope of carbon-based π-nucleophiles capable of intercepting CuAAC-generated ketenimines.