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Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes

Nature Chemistry volume 8, pages 610–617 (2016)Cite this article

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Abstract

The mechanistic foundation behind the identity of a phosphine ligand that best promotes a desired reaction outcome is often non-intuitive, and thus has been addressed in numerous experimental and theoretical studies. In this work, multivariate correlations of reaction outcomes using 38 different phosphine ligands were combined with classic potentiometric analyses to study a Suzuki reaction, for which the site selectivity of oxidative addition is highly dependent on the nature of the phosphine. These studies shed light on the generality of hypotheses regarding the structural influence of different classes of phosphine ligands on the reaction mechanism(s), and deliver a methodology that should prove useful in future studies of phosphine ligands.

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Figure 1: Strategy for parameterizing monodentate phosphine ligands.
Figure 2: General steps used for deriving a suitable model.
Figure 3: Models identified with optimal predictive ability.
Figure 4: Mechanistic hypothesis and studies of ligand concentration effects.
Figure 5: Models of predicted versus measured ΔΔG‡ values for subsets of the phosphines using parameters from the maximum and minimum cone-angle conformers.

References

  1. Miyaura, N., Yamada, K. & Suzuki, A. A new stereospecific cross-coupling by the palladium-catalyzed reaction of 1-alkenylboranes with 1-alkenyl or 1-alkynyl halides. Tetrahedron Lett. 20, 3437–3440 (1979).

    Google Scholar 

  2. Wolfe, J. P., Wagaw, S. & Buchwald, S. L. An improved catalyst system for aromatic carbon−nitrogen bond formation: the possible involvement of bis(phosphine) palladium complexes as key intermediates. J. Am. Chem. Soc. 118, 7215–7216 (1996).

    CAS  Google Scholar 

  3. Driver, M. S. & Hartwig, J. F. A second-generation catalyst for aryl halide amination: mixed secondary amines from aryl halides and primary amines catalyzed by (DPPF)PdCl2. J. Am. Chem. Soc. 118, 7217–7218 (1996).

    CAS  Google Scholar 

  4. Knowles, W. S. & Sabacky, M. J. Catalytic asymmetric hydrogenation employing a soluble, optically active, rhodium complex. Chem. Commun. 1445–1446 (1968).

  5. Strohmeier, W. & Müller, F.-J. Klassifizierung phosphorhaltiger Liganden in Metallcarbonyl-Derivaten nach der π-Acceptorstärke. Chem. Ber. 100, 2812–2821 (1967).

    CAS  Google Scholar 

  6. Tolman, C. A. Electron donor–acceptor properties of phosphorus ligands. Substituent additivity. J. Am. Chem. Soc. 92, 2953–2956 (1970).

    CAS  Google Scholar 

  7. Tolman, C. A. Phosphorus ligand exchange equilibriums on zerovalent nickel. Dominant role for steric effects. J. Am. Chem. Soc. 92, 2956–2965 (1970).

    CAS  Google Scholar 

  8. Tolman, C. A. Steric effects of phosphorus ligands in organometallic chemistry and homogeneous catalysis. Chem. Rev. 77, 313–348 (1977).

    CAS  Google Scholar 

  9. Lohan, M. et al. Synthesis, electrochemistry, spectroelectrochemistry, and solid-state structures of palladium biferrocenylphosphines and their use in C,C cross-coupling reactions. Organometallics 31, 2310–2326 (2012).

    CAS  Google Scholar 

  10. Lin, H.-J. et al. Steric and electronic control of the spin state in three-fold symmetric, four-coordinate iron(II) complexes. J. Am. Chem. Soc. 136, 13326–13332 (2014).

    CAS  PubMed  Google Scholar 

  11. Kirchhoff, J. H., Dai, C. & Fu, G. C. A method for palladium-catalyzed cross-couplings of simple alkyl chlorides: Suzuki reactions catalyzed by [Pd2(dba)3]/PCy3 . Angew. Chem. Int. Ed. 41, 1945–1947 (2002).

    CAS  Google Scholar 

  12. Smith, J. M., Coville, N. J., Cook, L. M. & Boeyens, J. C. A. Steric parameters of conformationally flexible ligands from X-ray structural data. 1. P(OR)3 ligands in equivalent ligand environments. Organometallics 19, 5273–5280 (2000).

    CAS  Google Scholar 

  13. Chin, M., Durst, G. L., Head, S. R., Bock, P. L. & Mosbo, J. A. Molecular mechanics (MM2) calculations and cone angles of phosphine ligands. J. Organomet. Chem. 470, 73–85 (1994).

    CAS  Google Scholar 

  14. Hughes, R. P. et al. Syntheses and crystallographic studies of [Ir(η5-C5Me5)(L)(RF)I] (L = CO, PMe3; RF = CF2CF3, CF2CF2CF3, CF2C6F5, CF(CF3)2) complexes. Cone and solid angle steric parameters for perfluoroalkyl ligands. J. Chem. Soc. Dalton Trans. 873–880 (2000).

  15. Bartik, T., Himmler, T., Schulte, H. G. & Seevogel, K. Substituenteneinflüsse auf die Basizität von Phosphorliganden in R3P-Ni(CO)3-komplexen. J. Organomet. Chem. 272, 29–41 (1984).

    CAS  Google Scholar 

  16. Mansson, R. A., Welsh, A. H., Fey, N. & Orpen, A. G. Statistical modeling of a ligand knowledge base. J. Chem. Inf. Model. 46, 2591–2600 (2006).

    CAS  PubMed  Google Scholar 

  17. Golovin, M. N., Rahman, M. M., Belmonte, J. E. & Giering, W. P. Quantitative separation of σ- and π-components of transition metal–phosphorus bonding and the application of ligand effects in organometallic chemistry. Organometallics 4, 1981–1991 (1985).

    CAS  Google Scholar 

  18. Dunne, B. J., Morris, R. B. & Orpen, A. G. Structural systematics. Part 3. Geometry deformations in triphenylphosphine fragments: a test of bonding theories in phosphine complexes. J. Chem. Soc. Dalton Trans. 653–661 (1991).

  19. Rahman, M. M., Liu, H. Y., Prock, A. & Giering, W. P. Quantitative analysis of ligand effects. 2. Steric and electronic factors influencing transition-metal–phosphorus(III) bonding. Organometallics 6, 650–658 (1987).

    CAS  Google Scholar 

  20. Brown, T. L. A molecular mechanics model of ligand effects. 3. A new measure of ligand steric effects. Inorg. Chem. 31, 1286–1294 (1992).

    CAS  Google Scholar 

  21. Fey, N. et al. Development of a ligand knowledge base, part 1: computational descriptors for phosphorus donor ligands. Chem. Eur. J. 12, 291–302 (2006).

    CAS  Google Scholar 

  22. Jover, J. et al. Expansion of the ligand knowledge base for monodentate P-donor ligands (LKB-P). Organometallics 29, 6245–6258 (2010).

    CAS  Google Scholar 

  23. Milo, A., Neel, A. J., Toste, F. D. & Sigman, M. S. A data-intensive approach to mechanistic elucidation applied to chiral anion catalysis. Science 347, 737–743 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Littke, A. F., Dai, C. & Fu, G. C. Versatile catalysts for the Suzuki cross-coupling of arylboronic acids with aryl and vinyl halides and triflates under mild conditions. J. Am. Chem. Soc. 122, 4020–4028 (2000).

    CAS  Google Scholar 

  25. Harper, K. C., Vilardi, S. C. & Sigman, M. S. Prediction of catalyst and substrate performance in the enantioselective propargylation of aliphatic ketones by a multidimensional model of steric effects. J. Am. Chem. Soc. 135, 2482–2485 (2013).

    CAS  PubMed  Google Scholar 

  26. Milo, A., Bess, E. N. & Sigman, M. S. Interrogating selectivity in catalysis using molecular vibrations. Nature 507, 210–214 (2014).

    CAS  PubMed  Google Scholar 

  27. Bess, E. N. et al. Analyzing site selectivity in Rh2(esp)2-catalyzed intermolecular C–H amination reactions. J. Am. Chem. Soc. 136, 5783–5789 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Bess, E. N., Bischoff, A. J. & Sigman, M. S. Designer substrate library for quantitative, predictive modeling of reaction performance. Proc. Natl Acad. Sci. 111, 14698–14703 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Mougel, V. et al. Quantitatively analyzing metathesis catalyst activity and structural features in silica-supported tungsten imido–alkylidene complexes. J. Am. Chem. Soc. 137, 6699–6704 (2015).

    CAS  PubMed  Google Scholar 

  30. Zhang, C., Santiago, C. B., Kou, L. & Sigman, M. S. Alkenyl carbonyl derivatives in enantioselective redox relay Heck reactions: accessing α,β-unsaturated systems. J. Am. Chem. Soc. 137, 7290–7293 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Guzei, I. A. & Wendt, M. An improved method for the computation of ligand steric effects based on solid angles. Dalton Trans. 3991–3999 (2006).

  32. Harper, K. C., Bess, E. N. & Sigman, M. S. Multidimensional steric parameters in the analysis of asymmetric catalytic reactions. Nature Chem. 4, 366–374 (2012).

    CAS  Google Scholar 

  33. Molecular Modeling Pro v. 6.36 (Norgwyn Montgomery Software Inc., 2012).

  34. Verloop, A. Drug Design Vol. III (Academic Press, 1976).

    Google Scholar 

  35. Tebby, J. C. CRC Handbook of Phosphorus-31 Nuclear Magnetic Resonance Data (CRC Press, 1991).

    Google Scholar 

  36. Surry, D. S. & Buchwald, S. L. Dialkylbiaryl phosphines in Pd-catalyzed amination: a user's guide. Chem. Sci. 2, 27–50 (2011).

    CAS  PubMed  Google Scholar 

  37. Schoenebeck, F. & Houk, K. N. Ligand-controlled regioselectivity in palladium-catalyzed cross coupling reactions. J. Am. Chem. Soc. 132, 2496–2497 (2010).

    CAS  PubMed  Google Scholar 

  38. McMullin, C. L., Jover, J., Harvey, J. N. & Fey, N. Accurate modelling of Pd(0) + PhX oxidative addition kinetics. Dalton Trans. 39, 10833–10836 (2010).

    CAS  PubMed  Google Scholar 

  39. Lyngvi, E., Sanhueza, I. A. & Schoenebeck, F. Dispersion makes the difference: bisligated transition states found for the oxidative addition of Pd(PtBu3)2 to Ar-OSO2R and dispersion-controlled chemoselectivity in reactions with Pd[P(iPr)(tBu2)]2 . Organometallics 34, 805–812 (2015).

    CAS  Google Scholar 

  40. Kozuch, S. & Martin, J. M. L. What makes for a bad catalytic cycle? A theoretical study on the Suzuki−Miyaura reaction within the energetic span model. ACS Catal. 1, 246–253 (2011).

    CAS  Google Scholar 

  41. McMullin, C. L., Fey, N. & Harvey, J. N. Computed ligand effects on the oxidative addition of phenyl halides to phosphine supported palladium(0) catalysts. Dalton Trans. 43, 13545–13556 (2014).

    CAS  PubMed  Google Scholar 

  42. Kuhn, M. & Johnson, K. Applied Predictive Modeling (Springer, 2013).

    Google Scholar 

  43. Amatore, C., Jutand, A., Khalil, F., M'Barki, M. A. & Mottier, L. Rates and mechanisms of oxidative addition to zerovalent palladium complexes generated in situ from mixtures of Pd0(dba)2 and triphenylphosphine. Organometallics 12, 3168–3178 (1993).

    CAS  Google Scholar 

  44. Hartwig, J. F. & Paul, F. Oxidative addition of aryl bromide after dissociation of phosphine from a two-coordinate palladium(0) complex, bis(tri-o-tolylphosphine)palladium(0). J. Am. Chem. Soc. 117, 5373–5374 (1995).

    CAS  Google Scholar 

  45. Barder, T. E., Walker, S. D., Martinelli, J. R. & Buchwald, S. L. Catalysts for Suzuki−Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 127, 4685–4696 (2005).

    CAS  PubMed  Google Scholar 

  46. Amatore, C. & Jutand, A. Role of dba in the reactivity of palladium(0) complexes generated in situ from mixtures of Pd(dba)2 and phosphines. Coord. Chem. Rev. 178–180(Part 1), 511–528 (1998).

    Google Scholar 

  47. Ito, N., Saji, T. & Aoyagui, S. Voltammetric studies of the metal–ligand interaction in low-valent metal-olefin π-complexes: Part I. [Pd(O)2(dibenzylideneacetone)3] and [Pt(O)2(dibenzylideneacetone)3]. J. Electroanal. Chem. Interfacial Electrochem. 144, 153–162 (1983).

    CAS  Google Scholar 

  48. Kurbangalieva, A., Carmichael, D., Hii, K. K., Jutand, A. & Brown, J. M. Oxidative addition to palladium(0) diphosphine complexes: observations of mechanistic complexity with iodobenzene as reactant. Chem. Eur. J. 20, 1116–1125 (2014).

    CAS  PubMed  Google Scholar 

  49. Suzuki, K., Hori, Y., Nishikawa, T. & Kobayashi, T. A novel (2,2-diarylvinyl)phosphine/palladium catalyst for effective aromatic amination. Adv. Synth. Catal. 349, 2089–2091 (2007).

    CAS  Google Scholar 

  50. Allen, D. W. & Taylor, B. F. The chemistry of heteroarylphosphorus compounds. Part 15. Phosphorus-31 nuclear magnetic resonance studies of the donor properties of heteroarylphosphines towards selenium and platinum(II). J. Chem. Soc. Dalton Trans. 51–54 (1982).

  51. Schrödinger Release 2014-3: MacroModel v. 10.5 (Schrödinger, 2014).

  52. Gaussian 09, Revision D.01 (Gaussian, Inc., 2009).

  53. MATLAB and Statistics Toolbox Release 2014a (The MathWorks, Inc., 2014).

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Acknowledgements

This work was supported by the National Science Foundation (CHE-1361296). The support and resources from the Center for High Performance Computing at the University of Utah are gratefully acknowledged.

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Authors and Affiliations

  1. Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, 84112, Utah, USA

    Zachary L. Niemeyer, Anat Milo, David P. Hickey & Matthew S. Sigman

  2. Department of Chemistry, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel

    Anat Milo

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  1. Zachary L. Niemeyer
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  2. Anat Milo
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  4. Matthew S. Sigman
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Contributions

Z.L.N., A.M. and M.S.S. conceived and designed the experiments; Z.L.N. performed the experiments; D.P.H. helped perform and analyse the electrochemical experiments; Z.L.N., A.M., D.P.H. and M.S.S. analysed the data; Z.L.N., A.M., D.P.H. and M.S.S. co-wrote the paper.

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Correspondence to Matthew S. Sigman.

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Niemeyer, Z., Milo, A., Hickey, D. et al. Parameterization of phosphine ligands reveals mechanistic pathways and predicts reaction outcomes. Nature Chem 8, 610–617 (2016). https://doi.org/10.1038/nchem.2501

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