Pd‐Catalyzed Regioselective Activation of gem‐Difluorinated Cyclopropanes: A Highly Efficient Approach to 2‐Fluorinated Allylic Scaffolds

Abstract

An unprecedented Pd‐catalyzed regioselective activation of gem‐difluorinated cyclopropanes induced by CC bond cleavage is reported. It provides a general and efficient access to a variety of 2‐fluoroallylic amines, ethers, esters, and alkylation products in high Z‐selectivity, which are important skeletons in many biologically active molecules. In addition, the transformation represents the first general application of gem‐difluorinated cyclopropanes as reaction partners in transition‐metal‐catalyzed cross‐coupling reaction.

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

“…to provide the key fluoroallyl-metal intermediate, which exhibit versatile reactivity with various nucleophilic reagents. [12][13][14][15][16] However, the low nucleophilicity of fluoride ions has overshadowed the potential for fluorine atom recycling in the previous transformations of gem-DFCPs. Thus, one fluorine atom, originating from β-F elimination process, was always disposed of as waste.…”

“…Furthermore, we also investigated the effect of different solvents, and found that PhCl was superior to other similar solvents such as PhCF3 and PhF, while more polar solvents like 1,4-dioxane and THF resulted in significantly lower yields (entries 8-10). Decreasing the reaction temperature and shortening the reaction time led to worse results with incomplete conversion of the substrates (entries [11][12].…”