Lecture 21 February 23 2011 CH 4 CH

Lecture 21 February 23, 2011 CH 4 CH 3 OH catalysis Nature of the Chemical Bond with applications to catalysis, materials science, nanotechnology, surface science, bioinorganic chemistry, and energy William A. Goddard, III, wag@wag. caltech. edu 316 Beckman Institute, x 3093 Charles and Mary Ferkel Professor of Chemistry, Materials Science, and Applied Physics, California Institute of Technology Teaching Assistants: Wei-Guang Liu <wgliu@wag. caltech. edu> Caitlin Scott <cescott@caltech. edu> Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 1

Last time Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all

OLEFIN METATHESIS Catalytically make and break double bonds! Mechanism: actual catalyst is a metal-alkylidene

Ru Olefin Metathesis Basics Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard

Well-defined metathesis catalysts Schrock 1991 alkoxy imido molybdenum complexa Bazan, G. C. ; Oskam, J. H. ; Cho, H. N. ; Park, L. Y. ; Schrock, R. R. J. Am. Chem. Soc. 1991, 113, 6899 -6907 Ch 120 a-Goddard-L 21 Grubbs 1991 ruthenium benzylidene complexb Wagener, K. B. ; Boncella, J. M. ; Nel, J. G. Macromolecules 1991, 24, 2649 -2657 Grubbs 1999 1, 3 -dimesityl-imidazole-2 -ylidenes P(Cy)3 mixed ligand system”c Scholl, M. ; Trnka, T. M. ; Morgan, J. P. ; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247 -2250. © copyright 2011 William A. Goddard III, all rights reserved 5

Examples 2 nd Generation Grubbs Metathesis Catalysts General mechanism of Metathesis Ch 120 a-Goddard-L

Ru-Methylidene Double Bond z x Cz=Cp Ruxz Ru dxz-C pz. Ru-C Pi bond C 3 B 1 CH 2 Ru 2 xx-yy-zz Ru dx 2 - C sp 2 Ru-C Sigma bond CH 2 is triplet state with singly occupied and orbitals get spin pairing bond to copyrightand bond. A. Goddard III, all rights reserved Ru dx 2 2011 William to Ruxz Ch 120 a-Goddard-L 21 © 7

Ru-Methylidene Double Bond CH 2 is triplet state with singly occupied and orbitals get spin pairing bond to Ru dx 2 and bond to Ruxz z x Ru-C Sigma bond (covalent) Ru dx 2 - C sp 2 Ru-C Pi bond (covalent) Ru dxz - C pz Bond dist. Theory Experiment Ru-CH 2 1. 813 1. 841 Ru-Carbene 2. 109 2. 069 Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 8

Carbene sp 2 -Ru dz 2 Don-Accep Bond Planar N with 3 bonds and 2 e in pp orbital Singlet methylene or carbene with 2 bonds to C and 2 electrons in C lone pair but empty p orbital Ru-Carbene Sigma donor bond (Lewis base-Lewis acid) C sp 2 Ru dz 2 Singlet Carbene (Casey Carbene or Fisher carbene Bond dist. Theory Experiment stablized by donation of N Ru-CH 2 1. 813 1. 841 lone pairs, leads to LUMO 2011 William A. Ru-Carbene 2. 109 2. 069 9 Ch 120 a-Goddard-L 21 © copyright Goddard III, all rights reserved

Carbene sp 2 -Ru dz 2 Don-Accep Bond Ru-Carbene Sigma donor bond (Lewis base-Lewis acid) C sp 2 Ru dz 2 Carbene p- LUMO) Antibonding to N lone pairs Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 10

Ru-dyz - Carbene py Don-Accep Bond Ru dyz Lone Pair (Lewis base-Lewis acid) Ru dyz Carbene py LUMO Ru dyz Lewis Base to Carbene py pi acid stabilizes the Ru. CH 2 in the xy plane This aligns Ru. CH 2 to overlap incoming olefin Carbene p- LUMO) Antibonding to N lone pairs Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 11

Ru LP and Ru-CH 2 Acceptor Orbitals Ru dxy Lone Pair Want perpendicular to C-Ru-C plane Avoid overlap with NCN bonds Orients Methylidene Perpendicular to Plane Ru-CH 2 * (antibonding) LUMO Acceptor for olefin bond Orients Olefin Perpendicular to plane Ch 120 a-Goddard-L 21 Because Ru. CH 2 is perpendicular to plane, the empty antibonding orbital overlaps the bonding pi orbital of the incoming olefin © copyright 2011 William A. Goddard III, all rights reserved 12

Ru Electronic Configuration Ru(CH 2)Cl 2(phosphine)(carbene) Ru-Cl bonds partially ionic (50% charge transfer), consider as Ru. II (Cl-)2 Ru. II: (dxz)1(dx 2)1 (dxy)2(dyz)2(dz 2)0 Ru (dx 2)1 covalent sigma bond to singly-occupied sp 2 orbital of CH 2 Ru (dxz)1 covalent pi bond to singly-occupied p z orbital of CH 2 ( the CH 2 is in the triplet or methylidene form) Ru (dxy)2 nonbonding Ru (dyz)2 overlaps empty carbene y orbital stabilizing Ru. CH 2 in xy plane Ru (dz 2)0 stabilizes the carbene and phosphine donor orbitals Ru. CH 2 * (antibonding) LUMO overlaps the bonding orbital of incoming olefin stabilizing it in the confirmation required for metallacycle formation. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 13

Generally Accepted Mechanism E or Z olefin products Ch 120 a-Goddard-L 21 © copyright

Metal [2+2] cycloaddition is thermally allowed All-carbon [2+2] cycloaddition is forbidden HOMO LUMO d orbital has different phase overlaps; other orbitals available (more details to follow in upcoming lectures!) Woodward-Hoffman rules still apply, but d-orbitals now participate Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 15

Product-Substrate exchange is rate determining step 10 [Ru]+P 6 ΔG‡ (Kcal/mol) 2 -2 5. 2 3. 5 [Ru]+S 0. 0 -2. 4 TSAB -6 -10 -5. 7 -8. 2 B A -12. 7 -12. 5 -14. 6 -18. 8 -18 -22 TSBC -13. 3 -16. 2 -21. 9 -21. 6 -23. 1 -10. 9 -10. 2 -13. 7 -15. 0 -19. 2 -20. 2 -24. 9 C -21. 4 -21. 8 E B 3 LYP Z B 3 LYP E MO 6 Z MO 6 -26 Ch 120 a-Goddard-L 21 -30 -28. 1 © copyright 2011 William A. Goddard III, all rights reserved 16

New material Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all

Catalyst Challenges for the Selective Chemistry needed for Sustainable Development Challenge: improved catalysts for industrial applications including • Low temperature conversion of methane to fuels and organic feedstocks • High selectivity and activity for converting alkanes to organic feedstocks • Fuel cell cathode catalysts for the oxygen reduction reaction (ORR) with decreased overpotential, much less Pt, and insensitive to deactivation • Fuel cell anode catalysts capable of operating with a variety of fuels but insensitive to CO and to deactivation • A methane fuel cell (CH 4 + H 2 O CO 2 + power [8 (H+ and e-)] • Efficient catalysts for photovoltaic production of energy and H 2 • Efficient catalysts for storing and recovering hydrogen • Catalysts for high performance Li ion and F ion batteries Enormous experimental efforts have been invested in solving these problems but better solutions are needed more quickly I claim that Theory and Modeling are poised to provide guidance to achieve these goals much more quickly Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 18

Projects in Catalysis: First establish mechanism then use mechanism to design improved catalyst • Propane ammoxidation - structure of new phases in Mixed Metal Oxide (Mitsubishi, BP) catalysts: Mo. VNb. Ta. Te. Ox TUESDAY • butane MA over VOPO and ODH over V 2 O 5 • Fuel Cell cathode electrocatalysis: non. Pt and Co. Pt, Ni. Pt alloys • Direct methanol fuel cell: Pt. Ru-Ru. OHy at anode • Cu. Six catalysis of Me. Cl to Si(Me)2 Cl 2 and role additives • Organometallic Catalysts CH 4 to liquids: Pt, Ir, Os, Re, Rh, Ru TODAY • Pd-mediated activation of molecular oxygen • Mechanism of the Wacker reaction in aqueous solution • Single Site Polymerization catalysts for polar monomers Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 19

Role of Theory in Developing Catalysts 1. Establish Mechanism of current catalysts: Use QM to predict all plausible reaction paths, Determine transition states (TS) and stable reaction intermediates (RI) Calculate vibrational frequencies (vf) to prove TS (one negative curvature) and RI Use frequencies to calculate entropy, Cp. Use QM and Poisson-Boltzmann to get free solvation energy. Get free energy at reaction temperatures G = Eelec + ZPE + Hvib(T) + Hlib(T) –TSvib – TSlib + Gsolv Use to estimate rates This provides the conceptual framework to interpret experiments 2. Validation: Predict new experiments to test mechanism 3. Lead discovery: Combinatorial Computational Rapid Prototyping In silico search for new lead candidates for Ligands, Metals, Solvents 4. Experiments: optimize best predicted ligands and reaction conditions. Continue theory and simulation in collaboration with experiments Critical to new role of theory: accuracy and reliability for novel systems Must trust theory well enough to do only 1 to 10% of the systems Focus experiments on these copyright 10%William A. Goddard III, best reserved Ch 120 a-Goddard-L 21 © 1% to 2011 predicted to be all rights 20

Has theory ever contributed to catalysis development? Over last 30 years quantum mechanics (QM) theory has played an increased role in analyzing and interpreting experimental results on catalytic systems But has QM led to new catalysts before experiment and can we count on the results from theory to focus experiments on only a few systems? Case study: New catalysts for low temperature activation of CH 4 and functionalization to form liquids (CH 3 OH) Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 21

Experimental discovery: Periana et al. , Science, 1998 (NH 3)2 Pt. Cl 2 TOF: 1 x 10 -2 s-1 t½ = 15 min Rate ok, but decompose far too fast. Why? (bpim)Pt. Cl 2 TOF: 1 x 10 -3 s-1 t½ = >200 hours Not decompose but rate 10 times too slow Also poisoned by H 2 O product How improve rate and eliminate poisoning Two Platinum compounds (out of laaarge number examined) catalyze conversion of methane to methylbisulfate in fuming sulphuric acid (102%) CH 4 + H 2 SO 4 + SO 3 CH 3 OSO 3 H + H 2 O + SO 2 CH 3 OSO 3 H + H 2 O CH 3 OH + H 2 SO 4 SO 2 + ½O 2 SO 3 Catalytica: Many $$$ trying to solve these problems experimentally, failed, cancelled project. 22 Periana came to USC, teamed copyright 2011 William A. Goddard III, all rights reserved Ch 120 a-Goddard-L 21 © up with Goddard, Chevron funded. Found success

Extremely important for these systems (p. H from -10 to +30) in very highly polar solvents: accuracy of predicting Solvation effects in QM The Poisson-Boltzmann Continuum Model in Jaguar/Schrödinger is extremely accurate Calculate Solvent Accessible Surface of the solute by rolling a sphere of radius Rsolv over the surface formed by the vd. W radii of the atoms. Calculate electrostatic field of the solute based on electron density from the orbitals Calculate the polarization in the solvent due to the electrostatic field of the solute (need dielectric constant ) This leads to Reaction Field that acts back on solute atoms, which in turn changes the orbitals. Iterated until selfconsistent. Solvent: = 99 Calculate solvent forces on solute atoms Rsolv= 2. 205 A Use these forces to determine optimum geometry of solute in Implementation in Jaguar solution. (Schrodinger Inc): Can treat solvent stabilized zwitterions p. K organics to ~0. 2 units, Difficult to describe weakly bound solvent molecules solvation to ~1 kcal/mol interacting with solute (low frequency, many local minima) (p. H from -20 to +20) Short cut: Optimize structure in the gas phase and do single 23 point solvation calculation. Some calculations done this wayall rights reserved Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III,

Comparison of Jaguar p. K with experiment p. Ka: Jaguar (experiment) E_sol: zero (H+) 6. 9 (6. 7) -3. 89 (-52. 35) 5. 8 (5. 8) 4. 96 (-49. 64) 6. 1 (6. 0) 3. 98 (-55. 11) 5. 3 (5. 3) 3. 90 (-57. 94) Ch 120 a-Goddard-L 21 5. 0 (4. 9) 4. 80 (-51. 84) © copyright 2011 William A. Goddard III, all rights reserved 24

Jaguar predictions of Metal-aquo p. Ka’s Protonated Complex Experimental p. Ka Calculated (B 3 LYP) p. Ka(MAD: 1. 1) (diethylenetriamine)Pt(OH 2)2+ 6. 3 5. 5 Pt. Cl 3(OH 2)17. 1 4. 1 Pt(NH 3)2(OH 2)22+ 5. 5 5. 2 Pt(NH 3)2(OH)(OH 2)1+ 7. 4 6. 5 cis-(bpy)2 Os(OH)(H 2 O)1+ 11. 0 11. 3 Calculated (M 06//B 3 LYP) p. Ka Experimental p. Ka (MAD: 1. 6) 2+ cis-(bpy)2 Os(H 2 O)2 7. 9 9. 1 1+ cis-(bpy)2 Os(OH)(H 2 O) 11. 0 8. 8 2+ trans-(bpy)2 Os(H 2 O)2 8. 2 6. 2 1+ trans-(bpy)2 Os(OH)(H 2 O) 10. 2 10. 9 2+ cis-(bpy)2 Ru(H 2 O)2 8. 9 13. 0 1+ cis-(bpy)2 Ru(OH)(H 2 O) >11. 0 15. 2 2+ trans-(bpy)2 Ru(H 2 O)2 9. 2 11. 0 1+ trans-(bpy)2 Ru(OH)(H 2 O) >11. 5 13. 9 2+ (tpy)Os(H 2 O)3 6. 0 5. 6 1+ (tpy)Os(OH)(H 2 O)2 8. 0 6. 3 (tpy)Os(OH)2(H 2 O) 11. 0 10. 9 25 Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved

Use theory to predict optimal p. H for each catalyst Predict the relative free energies of possible catalyst resting states as a function of p. H. Ln. Os. II(OH 2)3+2 Ln. Os. II(OH 2)2(OH)+ Ln. Os. II(OH 2)(OH)2 Ln. Os. II(OH)3 Ln. Os. II(OH 2)3+2 Ln. Os. II(OH 2)(OH)2 is stable Ch 120 a-Goddard-L 21 Ln. Os. II(OH)3 is stable Ln. Os. II(OH 2)2(OH)+ never most stable © copyright 2011 William A. Goddard III, all rights reserved 26

Use theory to predict optimal p. H for each catalyst p. H-dependent free energies of formation for transition states are added to determine the effective activation barrier as a function of p. H. Insertion transition states Resting states Optimum p. H region Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 27

Use theory to predict optimal p. H for each catalyst we determine the p. H at which an elementary step’s rate is maximized. Insertion transition states 32. 6 37. 9 34. 6 40. 0 Resting states Best, 2 kcal/mol better than p. H 14 Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 28

Predicted Pourbaix Diagram for Trans(bpy)2 Ru(OH)2 • Black experimental data from Meyer, • Red is from QM calculation (no fitting) using M 06 functional, no explicit solvent • Maximum errors: – 200 me. V, 2 p. H units Experiment: Dobson and Meyer, Inorg. Chem. Vol. 27, No. 19, 1988. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 29

Evaluating multi-oxidation state cycles for nucleophilic metals V Os Os. III 0. 5 V Os. IV 1 Volt Os. II (trpy)(bpy)Os(OHn) Oxidation states VI→II are present within ~0. 5 V window. Aqua ligands stabilize many oxidation states. Odd-electron oxidations are common. (trpy)Os(OHn)3 Ligands, anions influence the redox Pipes and Meyer, Inorg. Chem. 1986, 25, 4042. Meyer, et al. Inorg. Chem. 1984, © copyright 2011 William A. Goddard III, all a very wide range. 30 23, 1845. properties over rights reserved Ch 120 a-Goddard-L 21

First Step: Nature of (Bpym)Pt. Cl 2 catalyst Is H+ on the Catalytica Pt catalyst in fuming H 2 SO 4 (p. H~-10)? H kcal/mol ( G kcal/mol) Ch 120 a-Goddard-L 21 In acidic media (bpym)Pt. Cl has one proton 31 2 © copyright 2011 William A. Goddard III, all rights reserved

Mechanisms for CH activation To discuss kinetics of C-H activation for (NH 3)2 Pt Cl 2 and (bpym)Pt. Cl 2 Need to consider the mechanism Oxidative addition Form 2 new bonds in TS Sigma metathesis (2 s + 2 s) Concerted, keep 2 bonds in TS Ch 120 a-Goddard-L 21 32 Electrophilic addition Stabilize Occupied Orb. in TS © copyright 2011 William A. Goddard III, all rights reserved

Use QM to determine mechanism: C-H activation step. Requires high accuracy (big basis, good DFT) Oxidative addition -bond metathesis Theory led to new mechanism, formation of ion pair intermediate, proved with D/H exchange Electrophilic addition 1. Form Ion-Pair intermediate 2. Rate determining step is CH 4 ligand association NOT CH activation! (bpym)Pt. Cl 2 Start Ch 120 a-Goddard-L 21 CH 4 complex H(sol, 0 K) kcal/mol 3. Electrophilic CH complex 33 Addition. III, all rights reserved 3 wins © copyright 2011 William A. Goddard

C-H Activation Step for (bpym. H+)Pt(Cl)(OSO 3 H) Solution Phase QM (Jaguar) RDS is CH 4 ligand association NOT CH activation! Oxidative addition Electrophilic substitution CH 4 complex Form Ion-Pair intermediate Start Ch 120 a-Goddard-L 21 Differential of 33. 1 -32. 4=0. 7 kcal/mol confirmed with detailed H/D exchange experiments CH 3 all rights reserved © copyright 2011 William A. Goddard III, complex 34

Theory based mechanism: Catalytic Cycle Adding CH 4 leads to ion pair with displaced anion Start here 1 st turnover Catalytic step Ch 120 a-Goddard-L 21 After first turnover, the catalyst is (bpym) Pt. Cl(OSO 3 H) not (bpym)Pt. Cl 2 © copyright 2011 William A. Goddard III, all rights reserved 35

L 2 Pt. Cl 2 – Water Inhibition Experimental Observation: Reaction strongly inhibited by water, shuts off as solvent goes from 102% to 96% Is this because of interaction of water with reactant, catalysis, transition state or product? Barrier 33. 1 kcal/mol Barrier 39. 9 kcal/mol Theory: Complexation of water to activated catalyst is 7 kcal/mol exothermic, making barrier 7 kcal/mol higher. Product formation 0 Thus inhibition is a ground state effect Challenge: since H 2 O is a product of the reaction, must make the catalyst less attractive to H 2 O but still attractive to CH 4 36

Summary less positive Pt leads to easier CH 4 oxidation addition activation more positive Pt makes electrophilic substitution easier. Lower oxidation state, easier oxidation step less water inhibition A strong Pt-L bond prevents precipitation Ch 120 a-Goddard-L 21 A weak Pt-Cl bond facilitates electrophilic substitution © copyright 2011 William A. Goddard III, all rights reserved 37

A catalyst that can activate CH 4 should even more easily activate CH 3 OH. CH bond CH 4 is 105 kcal/mol CH bond of CH 3 OH is 94 kcal/mol How can the Periana Catalyst work? Product Protection, the Key to Developing High Performance Methane Selective Oxidation Catalysts, M. Ahlquist, RJ Neilsen, RA Periana, and wag Marten Ahlquist Ch 120 a-Goddard-L 21 JACS, just published © copyright 2011 William A. Goddard III, all rights reserved 38

Recall mechanism (1 m. M of CH 4 in solution) Assuming a 1 m. M of CH 4 in solution, reaction barrier for methane coordination 27. 5 kcal/mol, Followed by insertion of Pt into CH bond and Reductive deprotonation to give the platinum(II) methyl intermediate Add CH 4 Pt-CH deprotonation Mechanism for the C‑H activation of methane by the Periana-Catalytica catalyst. 39 Free energies (kcal/mol) at 500 K including solvation by H 2 SO 4. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved

Next step: Oxidation of the Pt. II‑Me intermediate by sulfuric acid Get CH 3 OSO 3 H + SO 2 products CH 3 -O-SO 3 H Free energies (kcal/mol) at 500 K including solvation by H 2 SO 4. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved SO 2 40

reaction path for C‑H activation of methyl bisulfate by the Periana-Catalytica catalyst. 41. 5 kcal/mol Barrier react with CH 3 -O-SO 3 H 27. 5 kcal/mol Barrier react with CH 4 27. 2 kcal/mol Barrier react with CH 3 OH Get product Free energies (kcal/mol) at 500 K including solvation by H protection SO. 2 4 41

Proposed pathway for oxidation of activated CH 3 -O-SO 3 H The rate limiting step in the oxidation of methyl bisulfate is C‑H cleavage (41. 5) rather than oxidation (35. 3) For methane the activation barrier is (27. 5) while the oxidation barrier is 32. 4 Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 42

Activation of CH 3 OH by the Periana Catalyst include the energy formation of free methanol from methyl bisulfate, Assuming free methanol, Ch 120 a-Goddard-L 21 Free energies (kcal/mol) at 500 K including solvation by H 2 SO 4. 43 © copyright 2011 William A. Goddard III, all rights reserved

A simple kinetic model can be used to illustrate the dependence of selectivity and product concentration over the course of a batch reaction: Begin with 100% selectivity, no product. A (bpym)Pt. Cl 2 reaction in 102% sulfuric acid has a best selectivity of 80%, which is why we need dry sulfuric acid (large KP) and a large ratio of k 1: k 3. Meeting these requirements will be a challenge for less 44 electrophilic metals.

Quantum Mechanics Rapid Prototyping (QM-RP) With an understanding of basic mechanistic steps, use QM to quickly test other ligands and metals computationally Other metals (Ir, Rh, Pd? ) Other activating Ligands X Other stabilizing ligands L Identify leads for further theory Other solvents Ch 120 a-Goddard-L 21 For best cases do experiment synthesis, characterization © copyright 2010 William A. Goddard III, all rights reserved 45

Quantum Mechanical Rapid Prototyping • • QMRP: computational analogue of combinatorial chemistry Three criteria for CH 4 activation: 1. Thermodynamic Criterion: Energy cost formation of R-CH 3 must be less than 10 kcal mol-1. Fast to calculate because need only minimize stable M-CH 3 Reaction Intermediate 2. Poisoning Criterion: Species must be resistant to poisoning from water (i. e. water complexation is endothermic) Fast to calculate because minimize only M-H 2 O intermediate. 3. Kinetic Criterion: Barrier to product formation must be less than 35 kcal mol-1. Test for minimized M-(CH 4). Barrier only a few kcal/mol higher. Slower to calculate because of weakly bound anion and CH 4, but minimize only intermediate. 4. Do real barriers only when DH 3 is less than 35 kcal/mol Many cases of Metal, ligand, solvent Muller, Ch 120 a-Goddard-L 21 1 2 3 4 exper pilot Small set systems for lab experiment Philipp, copyright 2010 Williamin Catalysis 2003, 23, 81 © Goddard Topics A. Goddard III, all rights reserved 46

Tri-site ligands We considered first a class of tri-site ligands analogous to those studied by Brookhart in Fe and Cr based catalysts for olefin polymerization. However we considered alternate ligands in which the 3 coordination sites [(N, N, N) in this case] are be replaced by various other ligands such as C, O, P, S We simplify the ligands to include the parts that affect the chemistry but not the modifications (ligands on the outer N such as mesityl, the embedding the middle N into an aromatic ring) used to protect and stabilize the catalyst under experimental conditions (but which are expected to have only a modest effect on controlling rates). We validated the accuracy of the simplified ligands by doing the Brookhart catalysts both ways. We also consider various metals and oxidation states. Ch 120 a-Goddard-L 21 © copyright 2010 William A. Goddard III, all rights reserved 47

Switch from Ir. III NCN to Ir. III NNC Eliminate trans-effect by switching ligand central C to N Get some water inhibition, but low ligand lability Continue 20. 6 -OH- -H 2 O 8. 0 0. 0 Solvated (H 2 O) Ch 120 a-Goddard-L 21 © copyright 2010 William A. Goddard III, all rights reserved 48

Further examine Ir. III NNC CH 4 activation by Sigma bond metathesis - Neutral species Kinetically accessible with total barrier of 28. 9 kcal/mol 28. 9 -H 2 O 8. 0 0. 0 -9. 0 Passes Test Ch 120 a-Goddard-L 21 Solvated (H 2 O) © copyright 2010 William A. Goddard III, all rights reserved 49

Oxidize with N 2 O prior to Functionalization Ir. III - NNC Passes Test 24. 5 +N 2 O -N 2 -9. 0 -OH- -7. 4 Solvated (H 2 O) -19. 8 Ch 120 a-Goddard-L 21 Oxidation by N 2 O Kinetically accessible © copyright 2010 William A. Goddard III, all rights reserved 50

Re-examine Functionalization for Ir. III NNC Passes Test 8. 3 -2. 1 -11. 2 -19. 8 Solvated (H 2 O) Ch 120 a-Goddard-L 21 Thus reductive elimination from Ir. V Is kinetically -65. 9 accessible © copyright 2010 William A. Goddard III, all rights reserved 51

CH activation 28. 9 8. 0 -H 2 O CH 4 CH 3 OH To avoid H 2 O poisoning, work in strong base instead of strong acid. Use lower oxidation states, e. g. Ir. III and Ir. I QM optimum ligands (Goddard) 2003 Tested experimentally (Periana) 2009 It works +CH 4 0. 0 -9. 0 Oxidation 24. 5 +N 2 O -N 2 -9. 0 -OH- -7. 4 -19. 8 Functionalization Experimental ligand A solution Ir. III – NNC 8. 3 -2. 1 -11. 2 -19. 8 Ch 120 a-Goddard-L 21 Predicted: Muller, Philipp, Goddard © copyright 2010 William A. Goddard III, all rights reserved Topics in Catalysis 2003, 23, 81 -65. 9 52

Xray of Ir. III NNC Experimental realization of catalytic CH 4 hydroxylation predicted for an iridium NNC pincer complex, demonstrating thermal, protic, and oxidant stability; Young, KJH; Oxgaard, J; Ess, DH; Meier SK, Stewart T, Goddard WA, Periana RA; Chem. Comm. , (22): 3270 -3272 (2009) bond lengths (Å): Ir(1)-N(2) 2. 017(6), Ir(1)-C(16) 2. 078(8), Ir(1)-C(27) 2. 174(9), Ir(1)N(1) 2. 164(6), Ir(1)-C(29) 2. 081(11), Ir(1)-O(1) 2. 207(6). bond angles (deg): N(2)-Ir(1)-C(16) 78. 7(3), N(2)-Ir(1)-C(27) 161. 0(3), N(2)-Ir(1)-N(1) 76. 8(2), C(16)-Ir(1)-N(1) 155. 4(3), C(27)-Ir(1)-N(1) 84. 2(3), C(29)-Ir(1)-O(1) 171. 1(5). Thermal ellipsoid plot of 1 -TFA with 50% probability. Hydrogens, and benzene co-solvent removed. William A. Goddard III, all rights reserved angles (deg): 53 for clarity. bond lengths (Å): bond Ch 120 a-Goddard-L 21 © copyright 2010

Final step: QM for Experimental Ligand Ch 120 a-Goddard-L 21 Message: it took 2 years of experiments to synthesize the desired ligand incorporate the Ir in the correct ox. state. Periana persisted only because he was confident it would work. Not practical to do this for the 1000’s of cases examined in QMRP enthalpy solvent corrections in kcal mol-1 (453 K) for HTFA ( = 8. 42 Chem. Comm. , (22): 3270 -3272 (2009) © copyright 2010 William A. Goddard III, all rightsradius = 2. 479 Å). 54 reserved

From here on I would like to summarize each of the systems we understand, with orbitals and discussion electronic structure • Hg based • MTO oxidation Ch 120 a-Goddard-L 21 © copyright 2010 William A. Goddard III, all rights reserved 55

Electronic effects in CH activation by Os. II-IV: Os. II: Already shows low barriers to C-H activation (Oxidative Addition) Liable to be oxidized by even weak oxidants or protonated Os. III: (acac)2 Os. III-Ph complex shows a low C-H activation barrier More stable to oxidation (than Os. II) and disproportionation (than Os. IV) Os. IV: Has not shown low barriers in C-H activation Prone to disproportionation Within 2 electrons of Os. VI, an oxidant useful for functionalization. Let’s consider this CH activation step as a function of oxidation state. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 56

(acac)2 Os. II(Ph) in benzene: • Anionic Os. II: Highly nucleophilic, wants to get rid of electron density • The d-orbital used to form the Os-H bond drops in energy (27 kcal/mol lower in 7 -coordinate intermediate). • The mechanism is Oxidative Addition (a stable Os-H intermediate appears) with almost no barrier. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 57

(acac)2 Os. III(Ph) in benzene: Spin density in transition state • The mechanism is a concerted oxidative hydrogen migration with a 14. 1 kcal/mol barrier. • The d-orbital used to form the Os-H bond stays at the same energy during the reaction. • Singly occupied orbital is ‘delta’ with respect to Os-H bond, since a doubly occupied d-orbital is used to bond to the hydrogen. • 2. 42 A Os-C bonds suggest moderate backbonding from Os d-orbitals to Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved benzene. 58

(acac)2 Os. IV(Ph) in benzene: • Cationic Os. IV: not strongly nucleophilic (Os. II) nor electrophilic (Pt. II) relative to CH 4. • The d-orbital used to form the Os-H bond rises in energy in the TS (16 kcal/mol), as it is pulled from the metal. • Os d-orbitals do little back-bonding to benzene. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 59

(acac)2 Os. III(OH)2 in water: CH activation by Os. III hydroxides: We’d like to work in an inert medium, like water. The higher oxidation state (e. g. Os. III vs Os. II) instantly extends the catalyst’s stability another ~0. 5 V, but the CH activation barriers are much higher than for Os. II-OH and Os. III-Ph: Weaker base than Os. II-OH Bound more strongly than in Os. II-OH Through several ligand/anion combinations, no Os. III-OH has yielded a calculated H-CH 3 activation barrier <35 kcal/mol. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 60

(acac)2 Os. III(OH)2 in water (1 M OH-): • Why does Os. III(OH) give a higher C-H activation barrier than Os. III(C 6 H 5) and Os. II(OH)? Spin densities • OH- is bound more strongly to Os. III (than to Os. II) due to the decrease in d -p repulsion, so the coordination step is endothermic. • The singly-occupied orbital “follows” the remaining hydroxide lone-pair, making the hydroxide less basic. Since the hydroxide lone-pair accepts the hydrogen from methane, the cleavage barrier is also high. (This contrasts the Os-Ph case, where a doubly occupied dorbital was oriented to stabilize the hydrogen in the TS. ) • C-H activation mechanism becomes Electrophilic Substitution (-OH, not Os, accepts H). Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 61

stopped Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights

Catalytic cycle: Au in H 2 SO 4/H 2 Se. O 4 Product. Au. I to III Act. CH 4 I Au. I to III Cycle: oxidation → CH activation → SN 2 attack Problem: Inhibited by water Accessibility of both Au. I and Au. III oxidation states Jones, Periana, Goddard, et al. , prevents deactivation due to oxidization of catalyst Angew. Chem. Int Ed. 2004, 43, 1. CH activation by electrophilic substitution. 4626. -. 63 2. Functionalization by nucleophilic attack by HSO 4 III, 180°C, 27 bar CH 4, TOF 10 -3 s-1 Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard all rights reserved

Consider Au. III in H 2 SO 4/H 2 Se. O 4: CH activation by Au. III Add CH 4 to Au. III complex Start with Au. III Protonated Au. III complex H extracted by bound HSO 4 Assisted by solvent H 2 SO 4 Form Au-CH 3 bond to Au. III complex Equilibrium Complex with Au-CH 3 CH activation relies on solvent, Jones, Periana, Goddard, et al. , Angew. H 2 SO 4, or conjugate base. 2011 William A. Goddard III, all rights reserved 4626. 64 Chem. Int Ed. 2004, 43, Ch 120 a-Goddard-L 21 © copyright

Au. III in H 2 SO 4/H 2 Se. O 4: Functionalization CH 3 OSO 3 H product HSO 4 - solvent SN 2 attack on Au-CH 3 bond Separate by adding H 2 O Functionalization relies on solvent, H 2 SO 4, or conjugate base. Jones, Periana, Goddard, et al. , Angew. Chem. Int Ed. 2004, 43, all rights reserved Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, 4626. 65

General strategy to developing new catalysts Ln. M-X Y ½ O 2 reoxidation YO functionalization CH 3 OH CH 4 Identify and elucidate elementary mechanistic steps for activation, functionalization/oxidation and reoxidation that connect to provide a complete, electronically consistent cycle. CH Activation Ln. M-CH 3 + HX Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 66

Mo Tc Ru Rh Pd Ag Cd W Re Os Ir Pt Au Hg Early successes in methane functionalization used the electrophilic paradigm: Electronegative Metals Pt, Au, Hg, Pd: ∙ good selectivity, rates, and stability ∙ product protection by esterification -but∙ inhibited by water and methanol ∙ require strong oxidants Consequently we shifted to the nucleophilic paradigm, which can coordinate CH 4 under milder acid or concentrated base conditions. Ch 120 a-Goddard-L 21 (NH 3)2 Pt. Cl 2 TOF: 1 x 10 -2 s-1 t½ = 15 min (bpim)Pt. Cl 2 TOF: 1 x 10 -3 s-1 t½ = >200 hours Pt: Periana et al. , Science, 1998 Au: Periana, wag; Angew. Chem. 2004 Hg: Periana et al. , Science, 1993 © copyright 2011 William A. Goddard III, all rights reserved 67

Progress towards CH 4 + ½O 2→ CH 3 OH • Pt. Cl 4= (Shilov) (not commercial, requires strong oxidant) • Au, Hg/H 2 SO 4 (not commercial, inhibited by water, Au requires strong oxidant) • (bpym)Pt. Cl 2/H 2 SO 4 (impressive, but not commercial, inhibited by water) – 70% one pass yield – 95% selectivity for CH 3 OSO 3 H – TOF ~ 10 -3 s-1, TON > 1000 • Pd. II/H 2 SO 4 (modest selectivity for CH 3 COOH) • (NNC)Ir. III(OH)2 (requires strong oxidant) Progress, but major problems Need new strategy Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 68

Mo Tc Ru Rh Pd Ag Cd W Re Os Ir Pt Au Hg Nucleophilic p. H = 14 K+/Na+ OH- Electrophilic Solvent p. H 1 M OHH 2 O 1 M H+ p. H < 0 H 2 SO 4 H 2 Se. O 4 Oxidant (H 2 O) DMSO H 2 Se. O 3 Product protection CH 3 O- CH 3 OH 2+ Ru, Re, Os, Ir are good nucleophilic metals for base or weak acid Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 69

We have identified 3 Mechanistic pathways CH 3 X Ln. M-X CH 4 Insertion New mechanisms for nucleophilic metals Electrophilic Nucleophilic Base-assisted Substitution CH Activation Functionalization Ln. M-CH 3 We are discovering new and manipulating old mechanistic steps that will be 70 active for less electrophilic 2011 William A. Goddard in aqueous solution. Ch 120 a-Goddard-L 21 © copyright metals operating III, all rights reserved

Functionalization by nucleophilic attack (SN 2) (bpy)Ir. III(pyr)(OH)2(CH 3) (trpy)Os. IV(OH)2(CH 3) SN 2 barriers (reductive functionalization) very high for earlier (electron-rich) metals. A. Goddard III, all rights reserved Ch 120 a-Goddard-L 21 © copyright 2011 William 71

Switch to less electronegative metals, e. g. Os Functionalize (acac)2 Os. IV(CH 3)(OH) using (acac)2 Os. VI(=O) 3+2 VI IV Migratory Insertion [Oxidant] 3+2 Backside attack Ch 120 a-Goddard-L 21 G 298 K, p. H = 14 Barriers are p. H dependent. VI 72 This oxidant, Goddard III, all rights reserved © copyright 2011 William A. [cis-(acac)2 Os (O)2], is privileged.

Functionalization of (acac)2 Os. IV(CH 3)(OH) Reactant M-CH 3 bond [Oxidant] Oxidant LUMO accepting 2 electrons and CH 3 in TS Electrophilic attack on methyl by the more stable [trans-(acac)2 Os. VI(O)2] is exciting. Oxidation is consistently 2 -electron in the backside attack mechanism, regardless of Mn 73 CH 3 Ch 120 a-Goddard-L 21 = II, IV). oxidation state (n © copyright 2011 William A. Goddard III, all rights reserved

Functionalization using transfer of CH 3 to Se SN 2 process Ch 120 a-Goddard-L

Full cycle Re(CO)5 -OH Re(CO)5 -CH 3 Catalytic Oxy-Functionalization of a Low Valent Metal Carbon Bond with Se(IV) William J. Tenn, III, Brian L. Conley, Mårten Ahlquist, Robert J. Nielsen, ‡ Jonas Oxgaard, William A. Goddard, 2011 William A. Goddard III, all rights reserved III and Roy A. Periana Ch 120 a-Goddard-L 21 © copyright 75

Homogeneous CH 4 functionalization: how to best choose new metals Our QM mechanistic studies for a variety of complexes from Au. III to Re. I show the continuum of charge transfer to methane Charge transfer Electron-rich methyl groups HX + Electron-poor methyl groups 76

CH activation and functionalization by nucleophilic d 6 metals M-CH 3 polarization based on C 1 s chemical shift The carbon 1 s orbital energy is an excellent measure of the electron density on the methyl carbon. This illustrates the extremes of the polarity scale, which require very different functionalization mechanisms. 77

Ongoing Work in Homogeneous CH 4 Functionalization Insertion Substitution We modeled bipyridine complexes of Ru. II, Os. II and Re. I to determine the dependence of ground states (protonation), H 3 C-H activation barriers (substitution and insertion) and functionalization barriers on metal and -donating ligand substituents. Going forward, we are considering the kinetics of these steps using d 5 and d 4 metals and new coordinated bases (i. e. –NH 2). 78

Ongoing Work in Homogeneous CH 4 Functionalization substitution insertion metal substituent Ru. II X=H =NH 2 Os. II X=H =NH 2 Re. I X=H =NH 2 -1. 1 0. 0 5. 2 31. 1 12. 7 n. a. -7. 5 0. 0 -1. 7 23. 6 9. 4 n. a. 7. 8 0. 0 11. 1 41. 8 21. 7 30. 7 1. 5 0. 0 3. 1 34. 5 17. 1 20. 5 17. 0 4. 8 0. 0 41. 9 26. 5 26. 9 18. 5 0. 1 0. 0 -0. 6 36. 6 23. 6 19. 4 7. 1 (bpy)2 Ru(OH)2 complexes do not participate in insertion mechanisms (i. e. , the products are not a minimum on the potential energy surface), only in the substitution path. (bpy)2 Os(OH)2 complexes allow both pathways (each are identifiable saddle points). However, the insertion pathway is preferred. Electron-donating substituents labilize hydroxide, creating vacancies. Insertion barriers decrease with the electron-donating ability of the substituent. The catalyst’s susceptibility to oxidation also increases with the C-H activation rate. After the resting state switches to Ru(OH)(OH 2), the substituents weakly effect substitution barriers. Insertion barriers can be tuned over an extreme range by varying the ligand metal. Substitution barriers cannot be similarly tuned. 79

CH 4 functionalization with homogeneous catalysts Reductive functionalization mechanisms (red. elim. , SN 2) well known for late metals (M-CH 3 d+). With Periana we have sought complimentary mechanisms appropriate for electron rich metals: Barrier Baeyer-Villiger Nucleophilic attack Electrophilic attack HX + Periodic table Reductive elimination Transalkylation • Going forward: Determine what combinations of Group 9 and 10 metals, ligands and nucleophiles will allow SN 2 functionalization with thermally accessible barriers. 80

Going forward in homogeneous CH 4 functionalization We explore functionalization mechanisms in which the oxidant is a higher oxidation state of the hypothetical CH activation catalyst: Os. VI + Os. IV L = (acac)2 Os. VI + Os. III L = terpyridine 81

Catalytic cycle: Au in H 2 SO 4/H 2 Se. O 4 Product. Au. I to III Act. CH 4 I Au. I to III Accessibility of both Au. I and Au. III oxidation states prevents deactivation due to oxidization of catalyst 1. CH activation by electrophilic substitution. 2. Functionalization by nucleophilic attack by HSO 4 -. Cycle: oxidation → CH activation → SN 2 attack Problem: Inhibited by water Jones, Periana, Goddard, et al. , Angew. Chem. Int Ed. 2004, 43, 4626. 180°C, 27 bar CH 4, TOF 10 -382 -1 s

Plan for bringing to pilot new CH 4 to liquids catalysts Mo Tc Ru Rh Pd Ag Cd W Re Os Ir Pt Au Hg Middle Transition Metals Late Transition Metals Now couple our new functionalization Mechanistic steps sufficient to get mechanisms with our proven CH through a complete cycle, with activation mechanisms using either mechanisms for protection, are proven nucleophilic substitution or insertion and understood. mechanisms with product protection by Plan: Use theory to address the likely acid or base. performance-limiting aspect of each Plan Use theory to identify and study metal, then design the ligand, p. H, and scope of new functionalization oxidant around the rate-limiting step. mechanisms, and to study the effect of high p. H on CH activation of CH 4 and OCH 3 -. Ch 120 a-Goddard-L 21 © copyright 2011 William A. Goddard III, all rights reserved 83