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. Ru-catalyzed asymmetric ring-closing metathesis (ARCM) reactions are less reported and restricted to the synthesis of tertiary stereocenters. Herein, the authors report ARCM to produce chiral heterocyclic compounds with quaternary stereocenters, by synthesizing stereogenic-at-Ru catalysts via controllable C–H activation.
Li et al. (Tue,) studied this question.