Relevance of cis- and trans-dichloride Ru intermediates in Grubbs-II olefin metathesis catalysis (H(2)IMesCl(2)Ru=CHR)

Using density functional theory with the B3LYP and M06 functionals, we show conclusively that the (H2IMes)(Cl)2Ru olefin metathesis mechanism is bottom-bound with the chlorides remaining trans throughout the reaction, thus attempts to effect diastereo- and enantioselectivity should focus on manipulations that maintain the trans-dichloro Ru geometry

Conformational analysis of olefin-carbene ruthenium metathesis catalysts

We settle a long-standing disagreement of DFT with experiment (both solution and gas phase) for the phosphine dissociation process in Grubbs metathesis catalysis. Our findings with the M06 functional provide further support to gas-phase experimental work, concluding that for the ring-closing metathesis of norbornene, the resting state is the alkylidene−olefin complex and the rate-determining step is the loss of norbornene as a ligand and generation of the 14-electron activated species. Comparing to recent solution NMR data on olefin−carbene Ru complexes relevant to olefin metathesis, we find that the M06 density functional leads to accurate predictions for the stability of conformers, ~0.5 kcal/mol better than is found by B3LYP. Using this methodology, we suggest that Piers and co-workers observed the cis-dichloro “down” isomer exclusively following the ring opening of acenaphthalene

The Isomerization Equilibrium between Cis and Trans Chloride Ruthenium Olefin Metathesis Catalysts from Quantum Mechanics Calculations

The cis−trans chloride isomerization of a ruthenium olefin metathesis catalyst is studied using quantum mechanics (B3LYP DFT), including the Poisson−Boltzmann (PBF) continuum approximation. The predicted geometries agree with experiment. The energies in methylene chloride, lead to ΔG = −0.70 kcal/mol and a cis:trans ratio of 76:24, quite close to the experimental value of ΔG = −0.78 kcal/mol or c:t 78:22. In contrast, we predict that in benzene c:t = 4:96 in agreement with the experimental observation of only the trans isomer. Our calculated relative activation energies explain the observed difference in initiation rates and suggest that each isomer should be isolable in high ratio by simply changing solvent

Two Metals Are Better Than One in the Gold Catalyzed Oxidative Heteroarylation of Alkenes

We present a detailed study of the mechanism for oxidative heteroarylation, based on DFT calculations and experimental observations. We propose binuclear Au(II)–Au(II) complexes to be key intermediates in the mechanism for gold catalyzed oxidative heteroarylation. The reaction is thought to proceed via a gold redox cycle involving initial oxidation of Au(I) to binuclear Au(II)–Au(II) complexes by Selectfluor, followed by heteroauration and reductive elimination. While it is tempting to invoke a transmetalation/reductive elimination mechanism similar to that proposed for other transition metal complexes, experimental and DFT studies suggest that the key C–C bond forming reaction occurs via a bimolecular reductive elimination process (devoid of transmetalation). In addition, the stereochemistry of the elimination step was determined experimentally to proceed with complete retention. Ligand and halide effects played an important role in the development and optimization of the catalyst; our data provides an explanation for the ligand effects observed experimentally, useful for future catalyst development. Cyclic voltammetry data is presented that supports redox synergy of the Au···Au aurophilic interaction. The monometallic reductive elimination from mononuclear Au(III) complexes is also studied from which we can predict a ~ 15 kcal/mol advantage for bimetallic reductive elimination

Phosphoramidite Gold(I)-Catalyzed Diastereo- and Enantioselective Synthesis of 3,4-Substituted Pyrrolidines

In this article the utility of phosphoramidite ligands in enantioselective AuI catalysis was explored in the development of highly diastereo- and enantioselective AuI-catalyzed cycloadditions of allenenes. A Au^I-catalyzed synthesis of 3,4-disubstituted pyrrolidines and γ-lactams is described. This reaction proceeds through the enantioselective AuI-catalyzed cyclization of allenenes to form a carbocationic intermediate that is trapped by an exogenous nucleophile, resulting in the highly diastereoselective construction of three contiguous stereogenic centers. A computational study (DFT) was also performed to gain some insight into the underlying mechanisms of these cycloadditions. The utility of this new methodology was demonstrated through the formal synthesis of (−)-isocynometrine

Mechanistic Study of Gold(I)-Catalyzed Intermolecular Hydroamination of Allenes

The intermolecular hydroamination of allenes occurs readily with hydrazide nucleophiles, in the presence of 3-12% Ph_3PAuNTf_2. Mechanistic studies have been conducted to establish the resting state of the gold catalyst, the kinetic order of the reaction, the effect of ligand electronics on the overall rate, and the reversibility of the last steps in the catalytic cycle. We have found the overall reaction to be first order in gold and allene and zero order in nucleophile. Our studies suggest that the rate-limiting transition state for the reaction does not involve the nucleophile and that the active catalyst is monomeric in gold(I). Computational studies support an “outersphere” mechanism and predict that a two-step, no intermediate mechanism may be operative. In accord with this mechanistic proposal, the reaction can be accelerated with the use of more electron-deficient phosphine ligands on the gold(I) catalyst