ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
0/0

Highly Enantioselective Synthesis of Indazoles with a C3-Quaternary Chiral Center Using CuH Catalysis

preprint
submitted on 18.11.2019 and posted on 27.11.2019 by Yuxuan Ye, Ilia Kevlishvili, Sheng Feng, Peng Liu, Stephen L. Buchwald

C3-substituted 1H-indazoles are useful and important substructures in many pharmaceuticals. Methods for direct C3- functionalization of indazoles are relatively rare, compared to reactions developed for the more nucleophilic N1 and N2 positions. Herein, we report a highly C3-selective allylation reaction of 1H-N-(benzoyloxy)indazoles using CuH catalysis. A variety of C3-allyl 1H-indazoles with quaternary stereocenters were efficiently prepared with high levels of enantioselectivity. Density functional theory (DFT) calculations suggest that the indazole addition to copper allyl complex proceeds through an enantioselectivity-determining six- membered Zimmerman-Traxler-type transition state. The enantioselectivity is governed both by the ligand-substrate steric interac- tions and the steric repulsions with the pseudoaxial substituent in the six-membered allylation transition state.

History

Email Address of Submitting Author

yuxuanye@princeton.edu

Institution

MIT, University of Pittsburgh

Country

USA

ORCID For Submitting Author

0000-0003-3516-5270

Declaration of Conflict of Interest

no conflict of interest

Exports

Logo branding

Exports