A Novel Rearrangement of Cyclic Glutamine Derivatives: Ring Contraction in 3,6‐Diamino‐2,3,4,5‐tetrahydropyridin‐2‐ones to Yield 5‐Iminoproline Amides

A new rearrangement of the cyclic L‐glutamine derivative(S)‐6‐carbamoylamino‐3‐(methylamino)‐2,3,4,5‐tetrahydropyridin‐2‐one (2) and its descarbamoyl analogue 10‐H was found to yield enantiomerically pure 5‐carbamoylimino‐1‐methyl‐L‐proline amide (12‐CONH2) and its descarbamoyl analogue 12‐H, respectively. Cyclic amidines 2and 10‐H were generated from the amide N2‐ZGlnOEt 3in seven and six steps, respectively. Deprotection of (S)‐6‐amino‐3‐[(N‐benzyloxycarbonyl‐N‐methyl)amino]‐2,3,4,5‐tetrahydropyridin‐2‐one (8) led directly to 5‐iminoproline amide 12‐H (via 10‐H and the bicyclic orthoamidine 11‐H) in 66 % overall yield from 3. Carbamoylation of 8with ZNCO (Z = PhCH2OCO) followed by hydrolytic removal of both Z groups gave 5‐(carbamoylimino)proline amide 12‐CONH2(via 2and orthoamidine 11‐CONH2) in 70 % overall yield from 3.