Author:
Berger Kathleen J.,Dherange Balu D.,Morales Megan,Driscoll Julia L.,Tarhan A. Kaan,Levin* Mark D.
Abstract
Abstract
This chapter presents the procedure for the N‐(Benzyloxy)‐N‐(pivaloyloxy)‐4‐(trifluoromethyl)‐benzamide which belongs to the N‐(alkoxy)‐N‐(acyloxy)benzamide class of anomeric amides. In this class of compounds, in order to satisfy the electron demand of the two oxygen substituents, the resonance of the nitrogen lone pair with the amide carbonyl is largely diminished. This results in an sp
3
configuration and pyramidalization at nitrogen. The authors have used N‐(Benzyloxy)‐N‐(pivaloyloxy)‐4‐(trifluoromethyl)‐benzamide to selectively edit secondary amines containing a range of functional groups and heterocycles. Nitrogen deletion of cyclic secondary amines results in a ring contraction, which has been applied to give substituted cyclobutene products from pyrrolidine precursors. This methodology also enabled a new synthetic route to the chemotherapeutic Pemetrexed and enabled the late‐stage editing of the kinase inhibitor Lapatinib.
Reference18 articles.
1. Department of Chemistry University of Chicago Chicago Illinois 60637 United States. Email:marklevin@uchicago.eduORCID: 0000‐0002‐4461‐363X. The University of Chicago is thanked for start‐up funding. K.J.B. thanks the George Van Dyke Tiers Foundation for fellowship support. J.L.D. thanks the NSF GRFP (DGE: 1746045) for fellowship support. M.M. and A.K.T. thank the Odyssey Scholars program for funding.
2. Direct Deamination of Primary Amines via Isodiazene Intermediates
3. The role of steric effects in the direct mutagenicity of N-acyloxy-N-alkoxyamides
4. Steric effects on the direct mutagenicity of N-acyloxy-N-alkoxyamides—Probes for drug–DNA interactions
5. Mutagenicity of N‐acyloxy‐N‐alkoxyamides as an indicator of DNA intercalation: The role of fluorene and fluorenone substituents as DNA intercalators;Glover S. A.;Mut. Res. Genet. Toxicol. Environ. Mutagen.,2021