Enantioselective Synthesis of Fluoro-Dihydroquinazolones and -Benzooxazinones by Fluorination-Initiated Asymmetric Cyclization Reactions

Kenichi Hiramatsu; Takashi Honjo; Vivek Rauniyar; F Dean Toste

doi:10.1021/acscatal.5b02182

Enantioselective Synthesis of Fluoro-Dihydroquinazolones and -Benzooxazinones by Fluorination-Initiated Asymmetric Cyclization Reactions

ACS Catal. 2015 Jan 4;6(1):151-154. doi: 10.1021/acscatal.5b02182. Epub 2015 Dec 4.

Authors

Kenichi Hiramatsu¹, Takashi Honjo², Vivek Rauniyar², F Dean Toste²

Affiliations

¹ Department of Chemistry, University of California Berkeley, California 94720, United States; Department of Medicinal Chemistry, Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062, Japan.
² Department of Chemistry, University of California Berkeley, California 94720, United States.

Abstract

Stereoselective synthesis of two fluorine-bearing drug-like scaffolds, dihydroquinazolone and benzooxazinone, has been accomplished through asymmetric fluorocyclization reactions initiated by the fluorination process. The reaction employs double axially chiral anionic phase-transfer catalysts to achieve high diastereo- and enantioselectivities, and a wide range of fluorine-containing dihydroquinazolones were obtained (>20:1 dr, up to 98% ee).

Keywords: asymmetric synthesis; chiral anion; cyclization; fluorination; phase-transfer catalyst.

Grants and funding

R01 GM104534/GM/NIGMS NIH HHS/United States