Quaternary and Tertiary Carbon Centers Synthesized via Gallium-Catalyzed Direct Substitution of Unfunctionalized Propargylic Alcohols with Boronic Acids

Clayton P Donald; Amy Boylan; Truong N Nguyen; Po-An Chen; Jeremy A May

doi:10.1021/acs.orglett.2c02612

Quaternary and Tertiary Carbon Centers Synthesized via Gallium-Catalyzed Direct Substitution of Unfunctionalized Propargylic Alcohols with Boronic Acids

Org Lett. 2022 Sep 23;24(37):6767-6771. doi: 10.1021/acs.orglett.2c02612. Epub 2022 Sep 13.

Authors

Clayton P Donald¹, Amy Boylan¹, Truong N Nguyen^{1

2}, Po-An Chen^{1

3}, Jeremy A May¹

Affiliations

¹ Department of Chemistry, University of Houston, 3585 Cullen Blvd, Fleming Bldg 112, Houston, Texas 77204-5003, United States.
² Pfizer, 280 Shennecossett Rd, Groton, Connecticut 06340, United States.
³ AnHorn Medicines Co. Ltd., C522, No. 99, Ln. 130, Sec. 1, Academia Rd., Nangang Dist., Taipei 11517, Taiwan, R.O.C.

PMID: 36099564
DOI: 10.1021/acs.orglett.2c02612

Abstract

(IPr)GaCl₃/AgSbF₆, AgSbF₆, and GaCl₃ catalyzed substitution of the hydroxyl of secondary and tertiary propargylic alcohols with organoboronic acids via C-C bond formation, and GaCl₃ effectively synthesized all-carbon quaternary propargylic centers. These catalysts performed the substitution at carbons bearing alkyl substituents, which has been problematic for other systems. Highly hindered carbon stereocenters were thus produced, including quaternary centers bearing doubly ortho-substituted aryl rings, that are difficult to access with traditional methods.