Construction of quaternary stereocenters via Ru-catalyzed asymmetric ring-closing metathesis

Asymmetric olefin metathesis, which forms C = C double bonds while simultaneously inducing chirality in molecules, is highly valuable in chemical synthesis. The investigation of strategies for the creation of quaternary stereocenters has mostly focused on Mo-based catalytic systems, whilst the utilization of user-friendly Ru-catalysts has been rarely reported. Here, by precisely synthesizing stereogenic-at-Ru catalysts via controllable C-H activation, we accomplish highly efficient asymmetric ring-closing metathesis (ARCM) for the production of chiral heterocyclic compounds with quaternary stereocenters. These Ru-catalysts facilitate the ARCM of trienes with distinct olefins for the synthesis of six-membered ethers and amines, as well as ARCM of trienes with all-terminal olefins to yield five- and six-membered ethers. Mechanistic investigations involving the initiation of the ARCM reaction by ring-opening metathesis of a "single-addition" cyclopropene derivative provide strong evidence for the interconversion between the essential exo and endo Ru-alkylidenes, and DFT calculations help to further substantiate the favored pathway and the stereo-controlling mechanism. This study provides an attractive approach for the design and production of chiral Grubbs catalysts, thereby promoting a variety of asymmetric olefin metathesis processes.