Rhodium-Catalyzed Regio- and Diastereoselective [3+2] Cycloaddition of gem-Difluorinated Cyclopropanes with Internal Olefins

Direct synthesis of gem-difluorinated carbocyclic molecules represents a longstanding challenge in organic chemistry. Herein, a Rh-catalyzed [3+2] cycloaddition reaction between readily available gem-difluorinated cyclopropanes (gem-DFCPs) and internal olefins has been developed, enabling the efficient synthesis of gem-difluorinated cyclopentanes with good functional group compatibility, excellent regioselectivity and good diastereoselectivity. The resulting gem-difluorinated products can undergo downstream transformations to access various mono-fluorinated cyclopentenes and cyclopentanes. This reaction demonstrates the use of gem-DFCPs as a type of CF2 C3 synthon for cycloaddition under transition metal catalysis, which provides potential strategy for synthesizing other gem-difluorinated carbocyclic molecules.

Automated summary

The direct synthesis of gem-difluorinated carbocyclic molecules has long been a challenge in organic chemistry. Here, a Rh-catalyzed [3+2] cycloaddition reaction between gem-difluorinated cyclopropanes and internal olefins has been developed, providing an efficient method to synthesize gem-difluorinated cyclopentanes with good functional group compatibility, excellent regioselectivity, and good diastereoselectivity. The resulting products can also be further transformed into various mono-fluorinated cyclopentenes and cyclopentanes, demonstrating the potential of this reaction as a strategy for synthesizing other gem-difluorinated carbocyclic molecules.