NMR Detection of the Enamine Intermediate in Proline-Catalyzed Aldol Reactions

Significance

An enamine intermediate in proline-catalyzed aldol reactions was indentified in situ by NMR studies on self-aldolization of aldehydes in DMSO. Only E-configured s-trans-enamines were detected in accordance with the generally accepted mechanism of enamine catalysis. The enamines were found to form directly from oxazoli­din­ones (e.g., 3), and not via central iminium or iminium-like intermediates (e.g., 2) as evidenced by NMR exchange spectroscopy (EXSY). These results indicate a possible role of oxazolidinones in the catalytic cycle, beyond their involvement in ‘parasitic equilibria’.