Novel and stereoselective methods for the preparation of aromatic lactams via reductive coupling reactions mediated by SmI2

Samarium(II) diiodide-mediated reductive cross-coupling of N-alkylated phthalimides with carbonyl compounds is shown to afford hydroxylated α-hydroxylactams. Ketoamides obtained by dehydration of these compounds through keto-enol tautomer isomerization were reduced with NaBH4 in a completely stereoselective manner in the presence of CeCl3 to give threo-aromatic lactams as the sole product. Direct reductive deoxygenation of these α-hydroxylactam intermediates with Et3SiH in the presence of Lewis acid also displayed high stereoselectivity to afford the same threo-lactams exclusively. The mechanistic origins of this stereoselectivity are briefly documented.