The Tetrafluoroethylene-Mediated Ring-Closing Metathesis: Enabling Unfavored Reactions

While ring-closing metathesis (RCM) is a powerful method for constructing medium and large cyclic alkenes, its application to the synthesis of heterocycles faces considerable limitations. For instance, RCM of divinyloxyalkanes does not proceed under the conventional conditions of RCM. The challenge lies in the formation of stable Fischer-type carbene intermediates with heteroatom(s) bound to the carbene carbon, impeding subsequent metathesis. In the present research, we develop a novel reaction system termed "tetrafluoroethylene (TFE)-mediated RCM", which enables the RCM of divinyloxyalkanes. In this system, a divinyloxyalkane and a TFE molecule are converted to the corresponding ring-closing product (cyclic 1,2-dioxyethene) and two molecules of 1,1-difluoroethylene. This method facilitates the construction of six- to eight-membered rings with various functional groups. The addition of TFE has two key effects: thermodynamically, it renders the entire reaction exergonic, while kinetically, it ensures that all ruthenium-carbene intermediates in the catalytic cycle are Fischer-type.