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α-C–H/N–H Annulation of Alicyclic Amines via Transient Imines: Preparation of Polycyclic Lactams

Weijie Chen, Daniel Seidel

2021Organic Letters24 citationsDOIOpen Access PDF

Abstract

Polycyclic lactams are prepared in a single operation from o-toluamides and cyclic amines in a process that involves transient cyclic imines, species that are conveniently obtained in situ from the corresponding lithium amides and simple ketone oxidants. Imines thus generated, such as 1-pyrroline and 1-piperideine, engage lithiated o-toluamides in a facile annulation process. Undesired side reactions such as imine deprotonation and o-toluamide dimerization are suppressed through the judicious choice of reaction conditions.

Topics & Concepts

AnnulationChemistryDeprotonationAlicyclic compoundImineKetoneLithium (medication)Combinatorial chemistryMedicinal chemistryOrganic chemistryCatalysisIonEndocrinologyMedicineAdvanced Synthetic Organic ChemistryCatalytic C–H Functionalization MethodsCoordination Chemistry and Organometallics
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