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

Polycyclic lactams are prepared in a single operation from otoluamides 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.

Automated summary

Polycyclic lactams are prepared in a single operation from otoluamides and cyclic amines, utilizing transient cyclic imines generated in situ from lithium amides and simple ketone oxidants. The annulation process involves imines like 1-pyrroline and 1-piperideine engaging lithiated o-toluamides, with undesired side reactions suppressed through careful selection of reaction conditions.