Copper-Catalyzed Chan–Lam Cyclopropylation of Phenols and Azaheterocycles

Derosa, Joseph; O�Duill, Miriam L.; Holcomb, Matthew; Boulous, Mark N.; Patman, Ryan L.; Wang, Fen; Tran-Dub�, Michelle; McAlpine, Indrawan; Engle, Keary M.

Abstract

Small molecules containing cyclopropane-heteroatom linkages are commonly needed in medicinal chemistry campaigns yet are problematic to prepare using existing methods. To address this issue, a scalable Chan-Lam cyclopropylation reaction using potassium cyclopropyl trifluoroborate has been developed. With phenol nucleophiles, the reaction effects O-cyclopropylation, whereas with 2-pyridones, 2-hydroxybenzimidazoles, and 2-aminopyridines the reaction brings about N-cyclopropylation. The transformation is catalyzed by Cu(OAc)2 and 1,10-phenanthroline and employs 1 atm of O2 as the terminal oxidant. This method is operationally convenient to perform and provides a simple, strategic disconnection toward the synthesis of cyclopropyl aryl ethers and cyclopropyl amine derivatives bearing an array of functional groups.

Citation

Derosa, J., O’Duill, M. L., Holcomb, M., Boulous, M. N., Patman, R. L., Wang, F., Tran-Dubé, M., McAlpine, I., & Engle, K. M. (2018). Copper-Catalyzed Chan–Lam Cyclopropylation of Phenols and Azaheterocycles. Journal of Organic Chemistry, 83(7), 3417-3425. https://doi.org/10.1021/acs.joc.7b03100

• Journal Article Type: Article
• Acceptance Date: Mar 2, 2018
• Online Publication Date: Mar 2, 2018
• Publication Date: Apr 6, 2018
• Deposit Date: Jun 26, 2020
• Publicly Available Date: Jan 19, 2021
• Journal: The Journal of Organic Chemistry
• Print ISSN: 0022-3263
• Electronic ISSN: 1520-6904
• Publisher: American Chemical Society
• Peer Reviewed: Peer Reviewed
• Volume: 83
• Issue: 7
• Pages: 3417-3425
• DOI: https://doi.org/10.1021/acs.joc.7b03100
• Keywords: Organic Chemistry
• Public URL: https://nottingham-repository.worktribe.com/output/4711247
• Publisher URL: https://pubs.acs.org/doi/10.1021/acs.joc.7b03100
• Additional Information: This document is the Accepted Manuscript version of a Published Work that appeared in final form in The Journal of Organic Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acs.joc.7b03100.