Ketone-Imide versus Ketone-Oxime Reductive Cross-Coupling Promoted by Samarium Diiodide:  New Mechanistic Insight Gained from a Failed Aminocyclopentitol Synthesis

The intramolecular 1,6-ketone/imide reductive coupling promoted by samarium diiodide competes favorably with an alternative 1,5-ketone/oxime ether coupling in a keto-oxime substrate derived from d-glucosamine N-protected with a phthalimido group. This pinacol coupling reaction affords new homochiral α-hydroxylactam scaffolds that could be useful in diversity-oriented synthesis. A mechanistic proposal for this reaction that explains the experimental results is supported by DFT quantum-mechanical calculations on model compounds.