Conformational Analysis of Olefin-Carbene Ruthenium Metathesis Catalysts Diego Benitez, Ekaterina Tkatchouk, and William A. Goddard III* Materials and Process Simulation Center, Beckman Institute (139-74), DiVision of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125 ReceiVed January 18, 2009 Summary: 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 me- tathesis 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. Ruthenium-catalyzed olefin metathesis 1 has become a power- ful tool for forming organic carbon-carbon double bonds, making it useful for synthetic challenges ranging from natural products 2 to novel polymeric architectures. 3 The nature of the general mechanism has been explored 4,5 experimentally in solution by variable-temperature NMR spectroscopy and in the gas phase by tandem ESI-MS, 6 leading to conclusive observa- tions of intermediates presumed to be part of the catalytic pathway. The mechanism has also been studied 7 quantum mechanically (QM), with many reports of degenerate and nondegenerate metathesis reactions involving full and simplified models using density functional theory (DFT) and high-level ab initio QCISD(T) methods. However, the geometrical details and the relative stability of the intermediates and transition states remain under debate. 8 We recently reported 7e DFT studies using B3LYP and M06 functionals and concluded that the general mechanism involves only intermediates that retain the trans-dichloro Ru geometry. The M06 functional is a hybrid meta-GGA exchange-correlation functional 9 developed to include attractive medium-range (van der Waals or London dispersion) interactions. Truhlar and Zhao reported 10 that, using the M06-L (no Hartree-Fock exchange) functional, the relative ruthenium tricyclohexylphosphine (PCy 3 ) bond dissociation energies for both the first- and second- generation Grubbs catalysts were predicted with much higher accuracy than for B3LYP when compared to solution activation parameters measured by Grubbs and co-workers. 4 Chen et al. reported 11 also that M06-L predicted phosphine dissociation energies for Ru and Au complexes were in better agreement with gas-phase threshold collision-induced dissociation (T-CID) data than were B3LYP values. To resolve these issues, here we report validation for the new M06 functional. There has been a longstanding question about the accuracy of DFT methods for predicting the bond dissociation energy of Ru phosphine in Grubbs catalysts. 10 We have extended the M06-L studies of Truhlar to the M06 level. Using M06 and the LACV3P++**(2f) small-core pseudopotential and basis set (see the Supporting Information for detailed computational methods), we find that the PCy 3 dissociation (Scheme 1) energy for the second-generation Grubbs catalyst is ΔH 298 ) 39.0 kcal mol -1 (ΔG ) 32.1 kcal mol -1 ) in the gas phase. Using the “0 K model”, 12 we calculate ΔH ) 37.1 kcal mol -1 , in excellent agreement with the experimental collision-induced dissociation * To whom correspondence should be addressed. E-mail: wag@ wag.caltech.edu. (1) (a) Hoveyda, A. H.; Zhugralin, A. R. Nature (London) 2007, 450, 243–251. (b) Grubbs, R. H. Angew. Chem., Int. Ed. 2006, 45, 3760–3765. (c) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18–29. (d) Calderon, N. Acc. Chem. Res. 1972, 5, 127–132. (e) Michrowska, A.; Grela, K. Pure Appl. Chem. 2008, 80, 31–43. (f) Bieniek, M.; Michrowska, A.; Usanov, D. L.; Grela, K. Chem. Eur. J. 2008, 14, 806–818. (2) (a) Nicolau, K. C.; Bulger, P. G.; Sarlah, D. Angew. 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