R. Kashif M. Khan

Readily accessible and easily modifiable Ru-based catalysts for efficient and Z-selective ring-opening metathesis polymerization and ring-opening/cross-metathesis.

Rationally designed Ru-based catalysts for efficient Z-selective olefin metathesis are featured. The new complexes contain a dithiolate ligand and can be accessed in a single step from commercially available precursors in 68-82% yield. High efficiency and exceptional Z selectivity (93:7 to >98:2 Z:E) were achieved in ring-opening metathesis polymerization (ROMP) and ring-opening/cross-metathesis (ROCM) processes; the transformations typically proceed at 22 °C and are operationally simple to perform. Complete conversion was observed with catalyst loadings as low as 0.002 mol %, and turnover numbers of up to 43,000 were achieved without rigorous substrate purification or deoxygenation protocols. X-ray data and density functional theory computations provide support for key design features and shed light on mechanistic attributes.

Broadly Applicable Z‐ and Diastereoselective Ring‐Opening/Cross‐Metathesis Catalyzed by a Dithiolate Ru Complex

A broadly applicable Ru-catalyzed protocol for Z-selective ring-opening/cross-metathesis (ROCM) is disclosed. In addition to reactions relating to terminal alkenes of different sizes, the first examples of Z-selective ROCM processes involving heteroaryl olefins, 1,3-dienes, and O- and S-substituted alkenes as well as allylic and homoallylic alcohols are reported. Z-Selective transformations with an α-substituted allylic alcohol are shown to afford congested Z alkenes with high diastereoselectivity. Transformations are performed in the presence of 2.0-5.0 mol % of a recently disclosed Ru-based dithiolate complex that can be easily prepared in a single step from commercially available starting materials. Typically, transformations proceed at ambient temperature and are complete within eight hours; products are obtained in up to 97 % yield, >98:2 Z/E, and >98:2 diastereomeric ratio. The present investigations reveal a mechanistically significant attribute of the Ru-based dithiolates that arises from electrostatic interactions with anionic S-based ligands.

Z- and Enantioselective Ring-Opening/Cross-Metathesis with Enol Ethers Catalyzed by Stereogenic-at-Ru Carbenes: Reactivity, Selectivity, and Curtin–Hammett Kinetics

The first instances of Z- and enantioselective Ru-catalyzed olefin metathesis are presented. Ring-opening/cross-metathesis (ROCM) reactions of oxabicyclic alkenes and enol ethers and a phenyl vinyl sulfide are promoted by 0.5-5.0 mol % of enantiomerically pure stereogenic-at-Ru complexes with an aryloxy chelate tethered to the N-heterocyclic carbene. Products are formed efficiently and with exceptional enantioselectivity (>98:2 enantiomer ratio). Surprisingly, the enantioselective ROCM reactions proceed with high Z selectivity (up to 98% Z). Moreover, reactions proceed with the opposite sense of enantioselectivity versus aryl olefins, which afford E isomers exclusively. Preliminary DFT calculations in support of Curtin-Hammett kinetics as well as initial models that account for the stereoselectivity levels and trends are provided.

Reactivity and selectivity differences between catecholate and catechothiolate Ru complexes. Implications regarding design of stereoselective olefin metathesis catalysts.

The origins of the unexpected finding that Ru catechothiolate complexes, in contrast to catecholate derivatives, promote exceptional Z-selective olefin metathesis reactions are elucidated. We show that species containing a catechothiolate ligand, unlike catecholates, preserve their structural integrity under commonly used reaction conditions. DFT calculations indicate that, whereas alkene coordination is the stereochemistry-determining step with catecholate complexes, it is through the metallacyclobutane formation that the identity of the major isomer is determined with catechothiolate systems. The present findings suggest that previous models for Z selectivity, largely based on steric differences, should be altered to incorporate electronic factors as well.

Synthesis, isolation, characterization, and reactivity of high-energy stereogenic-at-Ru carbenes: stereochemical inversion through olefin metathesis and other pathways.

The synthesis, isolation, purification (routine silica gel chromatography), and spectroscopic characterization of high-energy endo stereogenic-at-Ru complex isomers, generated by ring-opening/cross-metathesis (ROCM) reaction of the corresponding exo carbenes, are disclosed. We provide experimental evidence showing that an endo isomer can undergo thermal or Brønsted acid-catalyzed polytopal rearrangement, causing conversion to the energetically favored exo carbene.

The Influence of Anionic Ligands on Stereoisomerism of Ru Carbenes and Their Importance to Efficiency and Selectivity of Catalytic Olefin Metathesis Reactions

Investigations detailed herein provide insight regarding the mechanism of stereochemical inversion of stereogenic-at-Ru carbene complexes through a nonolefin metathesis-based polytopal rearrangement pathway. Computational analyses (DFT) reveal that there are two key factors that generate sufficient energy barriers that are responsible for the possibility of isolation and characterization of high-energy, but kinetically stable, intermediates: (1) donor-donor interactions that involve the anionic ligands and the strongly electron donating carbene groups and (2) dipolar effects arising from the syn relationship between the anionic groups (iodide and phenoxide). We demonstrate that a Brønsted acid lowers barriers to facilitate isomerization, and that the positive influence of a proton source is the result of its ability to diminish the repulsive electronic interactions originating from the anionic ligands. The implications of the present studies regarding a more sophisticated knowledge of the role of anionic units on the efficiency of Ru-catalyzed olefin metathesis reactions are discussed. The electronic basis for the increased facility with which allylic alcohols participate in olefin metathesis processes will be presented as well. Finally, we illustrate how a better understanding of the role of anionic ligands has served as the basis for successful design of Ru-based Z-selective catalysts for alkene metathesis.