Synthesis of --Cl,CF-Substituted Alkenes by Stereoselective Cross-Metathesis and the Role of Disubstituted Mo Alkylidenes.

Stereochemically defined organofluorine compounds are central to drug discovery and development. Here, we present a catalytic cross-metathesis method for the synthesis of -trisubstituted olefins that contain a Cl- and a CF-bound carbon terminus. Notably, the process is stereo, which is in contrast to the existing stereoretentive strategies that also involve a trisubstituted olefin as starting material. Reactions are catalyzed by a Mo monoaryloxide pyrrolide alkylidene, involve a trisubstituted alkene and -Cl,CF-substituted alkene, and are fully -selective. Catalytic cross-coupling can be used to convert the C-Cl bond of the trisubstituted olefin to C-B, C-D, and different C-C bonds. We elucidate the role of Cl,CF-disubstituted Mo alkylidenes. Experimental and computational (DFT) data show that in some instances a disubstituted alkylidene is formed and then transformed to a more active complex. In other cases, the Cl,CF-disubstituted alkylidene is a direct participant in a catalytic cycle. The studies described shed new light on the chemistry of high oxidation-state disubstituted alkylidenes-scarcely investigated entities likely to be pivotal to approaches for stereocontrolled synthesis of tetrasubstituted alkenes through olefin metathesis.