Thiourea-catalyzed enantioselective oxa-Pictet-Spengler reactions

ORGN 76

Abigail G. Doyle and Eric N. Jacobsen, jacobsen@chemistry.harvard.edu. Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138
Oxocarbenium ions are reactive intermediates in many important synthetic transformations, including glycosylation, Prins–Pinacol cyclizations, and oxa-Pictet–Spengler reactions. We have recently reported a highly enantioselective variant of the acyl-Pictet–Spengler reaction, in which N-acyliminium ions undergo cyclization in the presence of a chiral thiourea catalyst. The extension of this strategy to reactions involving oxocarbenium ions has led to the discovery of an enantioselective oxa-Pictet–Spengler reaction. Catalyst and reaction development, as well as substrate scope, will be described. Experiments probing the role of the catalyst in promoting reactions of highly electrophilic intermediates will also be presented.