Double Strain-Release Enables Formal C–O/C–F and C–N/C–F Ring-Opening Metathesis

Abstract

Metathesis reactions have been established as a powerful tool in organic synthesis. While great advances were achieved in double-bond metathesis, like olefin metathesis and carbonyl metathesis, the single-bond metathesis has received less attention in the past decade. Herein, we describe the first C(sp3)−O/C(sp3)−F bond formal cross metathesis reaction between gem-difluorinated cyclopropanes (gem-DFCPs) and epoxides under rhodium catalysis. The reaction involves the formation of a highly electrophilic fluoroallyl rhodium intermediate, which is capable of reacting with the oxygen atom in epoxides as weak nucleophiles followed by C–F bond reconstruction. The use of two strained ring substrates is the key to the success of the formal cross metathesis, in which the double strain release accounts for the driving force of the transformation. Additionally, azetidine also proves to be a suitable substrate for this transformation. The reaction offers a novel approach for the metathesis of C(sp3)−O and C(sp3)-N bond, presenting new opportunities for single-bond metathesis.