Free Energy ab Initio Metadynamics: A New Tool for the Theoretical Study of Organometallic Reactivity? Example of the C-C and C-H Reductive Eliminations from Platinum(IV) Complexes Carine Michel, † Alessandro Laio, ‡ Fawzi Mohamed, ‡ Matthias Krack, ‡ Michele Parrinello, ‡ and Anne Milet* ,† LEDSS, UMR 5616 FR2607, UniVersity Joseph Fourier-CNRS, 301 rue de la Chimie DU BP, 53 F-38041 Grenoble Cedex 9, France, and Computational Science and Department of Chemistry and Applied Biosciences, ETH Zurich, USI Campus, Via Giuseppe Buffi 13, CH-6900 Lugano, Switzerland ReceiVed October 24, 2006 Metadynamics and static DFT calculations have been performed on the C-H and C-C reductive elimination from Pt(IV) octahedral complexes L 2 Pt(CH 3 ) 3 X (X ) H or CH 3 ,L 2 ) diphosphine ligand, viz., a model of a dppe and dppbz ligand). The use of metadynamics simulations is shown to be a powe tool to describe the reactivity of organometallic compounds and provide us with the activation free ene of the different processes involved in these reactions: ligand dissociation; C-C and C-H formation. The computational results bring to the fore three mechanisms: direct and dissociative pathways, but also a concomitant mechanism with a simultaneous C-H formation and Pt-P dissociation. The dissociative pathway, which proceeds through a five-coordinate intermediate, is favored for the C-C reductive elimination, whereas the two other mechanims are observed for the C-H reductive elimination. The basicity of the phosphine used as much as its intrinsic rigidity strongly influences the mechanism of th C-H reductive elimination: direct or with concomitant dissociation of one arm of the diphosphine ligand. On the contrary, it has no influence on the C-C reductive elimination. The computed free activation energies from metadynamics calculations are in good agreement with experimental values measured f the different complexes. We also report computed activation free energy with inclusion of the entropy effect for the dissociation of the diphosphine ligand, a necessary step for the C-C reductive elimination Introduction Reductive elimination leading to a carbon-carbon or carbon- hydrogen bond is the usual product-forming step in organo- metallic catalytic cycles to generate various organic compounds. Like its microscopic reverse, the oxidative addition of a carbon- carbon or carbon-hydrogen bond, reductive elimination is a key activation step of metal-mediated organic transformations, both stoichiometric and catalytic. 1 Thus,the questforthe understanding of the mechanism of thesebond cleavage/ formation processes from Pt complexes has produced a large amount of experimental and theoretical studies. 2-4 Despite all these efforts, the detailed mechanism for this reaction especi for the Pt(IV) octahedral complex is still a matter of intense debate. 2,3a The key question concerns the initial ligand dissocia- tion and the formation, or not, of an intermediate prior to the reductive elimination. The lack of unambiguous evidence for a direct elimination for reductive C-H and C-C elimination from d 6 octahedral Pt(IV) complexes has strongly supported the belief that such reductive eliminations occur only in conjunction with ligand dissociation and formation of a five-coordinate intermediate. For C-C reductive elimination from octahedral Pt(IV) com- plexes with phosphine ligands, the inhibition role of added phosphine has been early 5 interpreted as a clue in favor of formation ofa five-coordinated intermediate priorto the reductive elimination. In the presence of a chelating diphosph ligand,reductiveeliminationstilloccursthroughafive- coordinate intermediate but with dissociation of the X - group (with X - ) I - or carboxylate, for example) for fac-(diphos- phine)-PtMe 3 X complexes 6 or dissociation of an arm of the diphosphine ligand for (diphosphine)-PtMe 4 systems. 2,4a C-H reductive elimination was not supposed to proceed through a different mechanism, and most of the proposed mechanisms * Corresponding author. Phone: (+33) 4 76 51 48 04. Fax: (+33) 4 76 51 44 96. E-mail:Anne.Milet@ujf-grenoble.fr. † LEDSS,UMR 5616 FR2607. ‡ ETH Zurich. (1) (a) Crabtree, R. H. The Organometallic Chemistry of the Transition Metals, 3rd ed.; John Wiley & Sons: New York, 2001. (b) Atwood, J. D. Inorganic and Organometallic Reaction Mechanisms, 2nd ed.;Wyley- VCH: New York, 1997. (c) Collman, J. P.; Hegedus, L. S.; Norton, J. R.; Finke,R. G. 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