Radical-Polar Crossover Enabled Triple Cleavage of CF2Br2: A Multicomponent Tandem Cyclization to 3-Fluoropyrazoles

Org Lett. 2023 Aug 18;25(32):6062-6066. doi: 10.1021/acs.orglett.3c02305. Epub 2023 Aug 8.

Abstract

The elaboration of step-economy and catalytic approaches for accessing diverse fluorinated heterocyclics is highly desirable. Described herein is a radical-polar crossover enabled three-component cyclization to polysubstituted fluoropyrazoles by using CF2Br2 as a novel C1F1 synthon. Mechanistic experiments revealed that the in situ generation of the reactive intermediate gem-difluorovinylimine ion is the key to this transformation. This protocol unlocks the novel reactivity of CF2Br2 and adds significant synthetic values to fluorine chemistry.