Defluoroalkylation of Trifluoromethylarenes with Hydrazones: Rapid Access to Benzylic Difluoroarylethylamines

• Type of Material: Article
• Authors: Cecilia M Hendy, Emory University; Cameron Pratt, Emory University; Nathan Jui, Emory University; Simon Blakey, Emory University
• Language: English
• Date: 2023-03-10
• Publisher: American Chemical Society
• Publication Version: Preprint (Prior to Peer Review)
• Copyright Statement: © 2023 The Authors. Published by American Chemical Society
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1021/acs.orglett.3c00126
• Title of Journal or Parent Work: ORGANIC LETTERS
• Volume: 25
• Issue: 9
• Start Page: 1397
• End Page: 1402
• Keywords: Arylethylamines; Benzylic Difluoroarylethylamines
• Research Categories: Health Sciences, Oncology; Chemistry, General

Abstract

Here, we report an efficient and modular approach toward the formation of difluorinated arylethylamines from simple aldehyde-derived N,N-dialkylhydrazones and trifluoromethylarenes (CF3-arenes). This method relies on selective C–F bond cleavage via reduction of the CF3-arene. We show that a diverse set of CF3-arenes and CF3-heteroarenes react smoothly with a range of aryl and alkyl hydrazones. The β-difluorobenzylic hydrazine product can be selectively cleaved to form the corresponding benzylic difluoroarylethylamines.