Regio- and Stereoselective Rhodium(II)-Catalyzed C–H Functionalization of Cyclobutanes

• Type of Material: Article
• Authors: Zachary J. Garlets, Emory University; Benjamin D. Wertz, Emory University; Wenbin Liu, Emory University; Eric A. Voight, AbbVie; Huw Davies, Emory University
• Language: English
• Date: 2020-01-09
• Publisher: Cell Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: 2020
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chempr.2019.12.014
• Title of Journal or Parent Work: Chem
• Volume: 6
• Issue: 1
• Start Page: 304
• End Page: 313
• Grant/Funding Information: This work was supported by the NSF Center for Selective C-H Functionalization (CHE 1700982) and NIGMS of the NIH under award number F32GM130020 (Z.J.G.). Additional financial support was provided by AbbVie. Instrumentation used in this work was supported by the National Science Foundation (CHE1531620 and CHE1626172). We wish to thank the members of the NSF Center for C-H Functionalization (CHE 1700982) for helpful discussions regarding this work. We thank Dr. John Bacsa and Mr. Thomas Pickel at the Emory X-ray Crystallography Facility for the X-ray structural analysis.
• Research Categories: Chemistry, General

Abstract

Recent developments in controlled C–H functionalization transformations continue to inspire new retrosynthetic disconnections. One tactic in C–H functionalization is the intermolecular C–H insertion reaction of rhodium-bound carbenes. These intermediates can undergo highly selective transformations through the modulation of the ligand framework of the rhodium catalyst. This work describes our continued efforts toward differentiating C–H bonds in the same molecule by judicious catalyst choice. Substituted cyclobutanes that exist as a mixture of interconverting conformers and possess neighboring C–H bonds within a highly strained framework are the targets herein for challenging the current suite of catalysts. Although most C–H functionalization tactics focus on generating 1,2-disubstituted cyclobutanes via substrate-controlled directing-group methods, the regiodivergent methods discussed in this paper provide access to chiral 1,1-disubstituted and cis-1,3-disubstituted cyclobutanes simply by changing the catalyst identity, thus permitting entry to novel chemical space.