Gem-Difluoroalkene, Bis(silanes)
ABSTRACT: Development of efficient methods to access multifunctional gem-difluoroalkenes is of great importance for medicinal and materials chemistry. While monofunctionalized derivatives of such molecules are well-established, scaffolds bearing two transformable handles remain scarce, particularly those featuring silicon groups. Herein, we report a copper-catalyzed disilylative defluorination of readily available 1-chloro-1-trifluoromethylalkenes. This reaction employs commercial organosilylboranes to directly furnish gem-difluoroalkene-based bis(silanes) with broad substrate scope, excellent functional-group tolerance, under mild conditions. The protocol establishes the first general access to this valuable class of compounds, installing two silicon groups often with distinct steric and electronic profiles in a single operation. This method demonstrates scalability and versatility, as evidenced by gram-scale synthesis and diverse downstream derivatizations of the products. An asymmetric variant has also been developed, delivering enantioenriched bis(silanes) with high efficiency and selectivity. This work fills a critical gap in fluorinated building block synthesis and provides a robust platform for accessing complex, silicon-bearing fluoroorganic architectures.
INTRODUCTION
Organofluorine compounds hold paramount importance in modern synthetic chemistry, pharmaceutical science, and materials research.1−6 Among fluorinated motifs, gem-difluoroalkenes constitute a versatile class of scaffolds with high value in medicinal chemistry.1efg−h They serve as pivotal precursors to monofluoroalkenes via selective C−F bond cleavage. These products are valuable isosteres in drug discovery, mimicking amides and other carbonyl groups with enhanced stability.7 Indeed, such structural units are prominent in bioactive molecules, including insecticidal agents and artemisinin analogues, highlighting their broad utility in medicinal and agrochemical sciences8 (Figure 1A). Consequently, developing efficient methods to synthesize and further functionalize gemdifluoroalkenes is crucial.1efg−h Such advances not only enrich fundamental organofluorine chemistry but also supply vital building blocks for pharmaceuticals, agrochemicals, and functional materials. To fully exploit their synthetic potential, equipping gem-difluoroalkenes with transformable functional handles is highly desirable. In particular, boron-9−11 or silicon-12−15 substituted derivatives offer unique opportunities for downstream diversification through cross-coupling,14 oxidation,16 or fluorine-specific transformations.17,18 While monofunctionalized gem-difluoroalkenes (e.g., silyl- or borylsubstituted) have been extensively documented19−23 (Figure 1B, top left), scaffolds bearing multiple, distinct, and tunable functional groups remain scarce. Pioneering work in this area emains limited, with only two reported examples accessing boron-containing bis-functionalized gem-difluoroalkene scaffolds to date. Among these, Song and co-workers developed a facile, enantioselective copper-catalyzed diborylation of readily accessible 1-chloro-1-trifluoromethylalkenes.24 This method employs a commercial diboron reagent and an inexpensive
copper catalyst to deliver diverse enantioenriched gemdifluoroallyl diboronates (Figure 1B, top right). Similarly, Xu et al. reported a copper-catalyzed, switchable defluoroborylation/hydrodefluorination of trifluoromethylated alkynes to access diborylated CF2-containing compounds.25 These advances underscore the growing interest in polyfunctional fluorinated building blocks, capable of undergoing chemoselective transformations.