Synfacts 2011(4): 0372-0372  
DOI: 10.1055/s-0030-1259749
Synthesis of Heterocycles
© Georg Thieme Verlag Stuttgart ˙ New York

1,3-Dipolar Cycloaddition Route to 1,3-Benzodiazepinones

Contributor(s): Victor Snieckus, Cédric Schneider
A. M. D’Souza, N. Spiccia, J. Basutto, P. Jokisz, L. S.-M. Wong, A. G. Meyer, A. B. Holmes, J. M. White, J. H. Ryan*
CSIRO, Clayton South and University of Melbourne, Parkville, Australia
Further Information

Publication History

Publication Date:
18 March 2011 (online)


Reported is the synthesis of 1,3-benzodiazepin-5-one derivatives 4 by the reaction of N-(methoxymethyl)-N-(trimethylsilylmethyl)-benzylamine 2 with substituted isatoic anhydrides 1. The transformation involved 1,3-dipolar cycloaddition of azomethine ylide 5 formed from compound 2 with LiF or TFA (A. Padwa, W. Dent Org. Synth. 1993, 231) with isatoic anhydride to give the oxazolidine intermediate 3. The latter, observed by NMR and IR spectroscopy, undergoes a ring opening/decarboxylation/ring closing cascade to afford the 1,3-benzodiazepinone products 4. The scope of this reaction has been explored with various N-substituted derivatives 1 to afford 1,3-benzodiazepin-5-ones 4 in high yield, except when R¹ = H. Moreover, the reaction proceeded in high yield with isatoic anhydrides 1 substituted by EWGs, whereas in the presence of EDGs ortho or para to the C4 carbonyl group, no reaction occurs presumably due to carbonyl deactivation. A plausible mechanism is proposed based on NMR and IR evidence.