Transition-Metal-Free Deconstructive Lactamization of Piperidines.

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp )-C(sp ) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3-alkoxyamino-2-piperidones, which were prepared from piperidines through a dual C(sp )-H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3-alkoxyamino-2-piperidones to 3-keto-2-piperidones, followed by a regioselective Baeyer-Villiger oxidation to give N-carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.