Carbofluorination of Alkenes with gem-Difluorinated Cyclopropanes as Bifunctional Reagents Enabled by Well-Define Rhodium Catalysts

Abstract

Herein, we report a Rh-catalyzed carbofluorination of alkenes using gem-difluorinated cyclopropanes as bifunctional reagents. The developed method tolerates a wide range of alkenes, providing access to secondary, tertiary fluorides and gem-difluorides with 100% atom-economy under mild conditions. The resulting fluorides can be further transformed to yield C−C, C−N, and C−O bifunctionalization products. Cationic dicarbonyl rhodium tetrafluoroborate has been identified to be the only highly efficient catalyst in this reaction. Preliminary mechanistic studies reveal that the addition of fluorine atom to alkenes is mediated by tetrafluoroborate ion, which acts as a fluorine anion shuttle.

Selectivity in Rh-catalysis with gem-difluorinated cyclopropanes

“…Third, extending the reaction scope by employing gem-DFCPs as difunctionalized reagents deserves investigation. 22,23 Finally, although the cycloaddition of gem-DFCPs under Rh-catalysis has been proposed to occur via the formation of a gem-difluorinated metallacyclobutane intermediate, the exact mechanism of this transformation needs further study. Given the huge developments in recent years, we believe further progress in the chemistry of gem-DFCPs in new reaction models with different transition-metal catalysts will contribute to organic synthesis and medicinal chemistry in the near future.…”

“…This was the first application using gem-DFCPs as bifunctional reagents (Scheme 5); 22 we have posted our results a week later online, realizing carbofluorination of alkenes with gem-DFCPs. 23 Since 2019, our group has been devoted to the exploration of the reactivity of gem-DFCPs in rhodium catalysis. In the beginning, we hypothesized that Rh-catalyzed ring-opening of gem-DFCPs will also form a Rh(III)-allyl species.…”

Observation of unusual outer-sphere mechanism using simple alkenes as nucleophiles in allylation chemistry

“…1C). This mechanistic mutation offers an opportunity for the fluorine recycling of gem-DFCPs via C-F bond cleavage/reformation 42,43 , delivering allylic carbonfluorination products [44][45][46][47][48] beyond our previously reported Heck-type allylation 21 or cycloaddition 39 . Just as the advantages of the outer-sphere pathway, this ASR protocol can indeed tolerate a wide range of simple alkenes, even trisubstituted ones, enabling the synthesis of secondary, tertiary fluorides, and gem-difluorides with 100% atom-economy under mild conditions.…”

Palladium-Catalyzed Fluorinative Bifunctionalization of Aziridines and Azetidines with gem-Difluorocyclopropanes

“…该反应的原料简单易得, 底物范围广, 具有良好的 官能团耐受性和优秀的立体选择性. 最重要的是, 该策 略不仅为 β,β'-双氟胺和 β,γ-双氟胺化合物的合成提供了 一种直接有效的方法, 还是偕二氟环丙烷作为氟双官能 团化试剂的首次应用 [9] .…”