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Transition‐Metal‐Free Deconstructive Lactamization of Piperidines
Author(s) -
RomeroIbañez Julio,
CruzGregorio Silvano,
SandovalLira Jacinto,
HernándezPérez Julio M.,
Quintero Leticia,
SartilloPiscil Fernando
Publication year - 2019
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201903880
Subject(s) - chemistry , intramolecular force , regioselectivity , transition metal , catalysis , tandem , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , materials science , composite material
One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp 3 )–C(sp 3 ) 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 3 )–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.