Alkene isomerization can be an atom-economical approach to generating a wide range of alkene intermediates for synthesis, but fully equilibrated mixtures of disubstituted internal alkenes typically contain significant amounts of the positional as well as geometric (E and Z) isomers. Most classical catalyst systems for alkene isomerization struggle to kinetically control either positional or E/Z isomerism. We report coordinatively unsaturated, formally 16-electron Cp*Ru catalyst 5, which facilitates simultaneous regio- and stereoselective isomerization of linear 1-alkenes to their internal analogues, providing consistent yields of (E)-2-alkenes greater than 95%. Because nitrile-free catalyst 5 is more than 400 times faster than previously published nitrile-containing analogues 2 + 2a, very reasonable 0.1–0.5 mol % loadings of 5 complete ambient-temperature reactions within 15 min to 4 h. UV–vis, NMR, and computational studies depict the imidazolyl fragment on the phosphine as a hemilabile, four-electron donor in κ2-P,N coordination. For the first time, we show direct experimental evidence that the PN ligand has accepted a proton from the substrate by characterizing the intermediate Cp*Ru­[η3-allyl]­[κ1-P)­P–N+H], which highlights the essential role of the bifunctional ligand in promoting rapid and selective alkene isomerizations. Moreover, kinetic studies and computations reveal the role of alkene binding in selectivity of unsaturated catalyst 5.

Optimised isomerisation catalysts are found using an iterative approach combining experimental studies and descriptor modelling.

Here we examine in detail two catalysts for their ability to selectively convert 1-alkenes to (E)-2-alkenes while limiting overisomerization to 3-or 4-alkenes. Catalysts 1 and 3 are composed of the cations CpRu(κ 2 -PN)(CH 3 CN) + and Cp*Ru(κ 2 -PN) + , respectively (where PN is a bifunctional phosphine ligand), and the anion PF 6 − . Kinetic modeling of the reactions of six substrates with 1 and 3 generated firstand second-order rate constants k 1 and k 2 (and k 3 when applicable) that represent the rates of reaction for conversion of 1-alkene to (E)-2-alkene (k 1 ), (E)-2-alkene to (E)-3-alkene (k 2 ), and so on. The k 1 :k 2 ratios were calculated to produce a measure of selectivity for each catalyst toward monoisomerization with each substrate. The k 1 :k 2 values for 1 with the six substrates range from 32 to 132. The k 1 :k 2 values for 3 are significantly more substratedependent, ranging from 192 to 62 000 for all of the substrates except 5-hexen-2-one, for which the k 1 :k 2 value was only 4.7. Comparison of the ratios for 1 and 3 for each substrate shows a 6−12-fold greater selectivity using 3 on the three linear substrates as well as a >230-fold increase for 5-methylhex-1-ene and a 44-fold increase for a silyl-protected 4-penten-1-ol substrate, which are branched three and five atoms away from the alkene, respectively. The substrate 5-hexen-2-one is unique in that 1 was more selective than 3; NMR analysis suggested that chelation of the carbonyl oxygen can facilitate overisomerization. This work highlights the need for catalyst developers to report results for catalyzed reactions at different time points and shows that one needs to consider not only the catalyst rate but also the duration over which a desired product (here the (E)-2-alkene) remains intact, where 3 is generally superior to 1 for the title reaction.

ǂ authors contributed equally Table of Contents General experimental S1-S2 Catalytic reactions reported in manuscript Table 1 S2-S24 Catalytic reactions reported in manuscript Scheme 2 S25-S26 Catalytic reactions reported in manuscript Scheme 3 S26-S27 Catalytic reactions reported in manuscript Scheme 4 S28-S32 References S32 General Experimental Reactions were perfomed under dry nitrogen, using a combination of Schlenk line and glovebox techniques. Acetone-d 6 received from Cambridge Isotope Labs was further deoxygenated by bubbling nitrogen gas through the liquid. Methylene chlorided 2 and chloroform-d received from Cambridge Isotope Labs were distilled over calcium hydride and deoxygenated via freeze pump thaw technique. NMR tube reactions were performed in resealable NMR tubes (J. Young).