Downsizing Lactams via Rh-Catalyzed C-C Activation
Rui Zhang1,2, Kangmin Wen1,2, Guangbin Dong1,3
1Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Abstract:
Ring-contraction reactions are valuable transformations to access harder-to-synthesize smaller-sized rings from more available larger-sized precursors. Herein, we report an unprecedented lactam downsizing strategy by taking advantage of removable directing groups (DGs) and Rh-catalyzed C-C activation. An efficient method for DG installation to common lactam substrates is developed by employing silylated amines and Ti catalysts, and the resulting amidine moiety can be converted back to lactams via acid-mediated hydrolysis. The ring-contraction reaction exhibits a broad substrate scope, excellent functional group tolerance, and high selectivity for yielding γ-lactams, facilitating "6-to-5", "7-to-5", and "8-to-5" ring contractions. Additionally, by carefully selecting DGs and ligands, preliminary results on selective "7-to-6" ring contraction have been obtained. Finally, density functional theory (DFT) calculations reveal the origin of the product selectivity.
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