1. Mechanistic Aspects of Olefin Hydroarylation:
Are Efficient 1-2 Insertion and C-H Activation Mutually Exclusive?
Jonas Oxgaard

2. Outline Introduction Methodology Results Ir.acac Ru.Tp.CO
Insertion vs. Activation
Improvements
Conclusions

3. Matsumoto et al.; J. Am. Chem. Soc. 2000, 122, 7414
Introduction 4 1 2 3
Matsumoto et al.; J. Am. Chem. Soc. 2000, 122, 7414

4. Matsumoto et al.; J. Mol. Cat. A 2002, 1
Introduction
Regioselectivity 4 R
TOF (x10-4 s-1)
Ratio
421
N/A
110 61 : 39 3 82 18
180 98 2 68 32
Matsumoto et al.; J. Mol. Cat. A 2002, 1

5. Introduction Other catalytic compounds5
TOF = 100 6
TOF = 24 4
TOF = 110 7
TOF = 130 8
TOF = 32
Periana et al., Chem. Comm. 2002, 3000

6. Introduction Experimental observations:
Dimer splits to a catalytically active mono-nuclear species
At low ethene:benzene ratios, reaction pseudo-first order in ethene.
At ethene:benzene ratios > 0.2, reaction inhibited by ethene
No styrene byproducts observed
Reaction not inhibited by radical scavengers such as O2
Addition of acac-H or H2O does not affect either product distribution or activity
Ligand acac’s are not exchanged with labeled free acac even at elevated temperature
No ionic intermediates are present
Matsumoto et al J. Am. Chem. Soc. 2000, 122, 7414
Matsumoto et al J. Mol. Cat. A 2002, 1
Periana et al., Chem. Comm. 2002, 3000

7. Methodology Computational methods:
Geometries optimized using B3LYP/LACVP**
Energies corrected for solvation using single point B3LYP/LACVP** with benzene as solvent (ε=2.284, rprobe= )
Energies corrected for ZPEs at 0K
Energies NOT corrected for temperature or ΔGs, unless noted

8. Rel. Energyb (kcal/mol)
Ir.acac - Mechanism 4 5 6 7 8
Relative Energy
(kcal/mol) 7 4 5
Catalyst
TOFa
( 10-4 s-1)
Isomer ratioa
Rel. Energyb (kcal/mol) 8 6
ln (TOF) 4
110
61:39
1.8 5
100
61:39
-1.0 6 24
61:39
-9.9 7
130
61:39
0.0
Linear relationship between TOF and calculated isomer stability confirms common rate determining step – More stable catalysts have lower activity due to ground state effect 8 32
61:39
-7.0
a: Experimental b: Theoretical
Constant isomer ratio indicates a common rate determining step

9. Ir.acac - Mechanism
Rate determining step TS1 (insertion). Activation energy corresponds well to experiment.
ΔH(0K)
(kcal/mol)
TS1
27.0 8
15.7
TS2
16.6 7
5.6 9
4.6 10
4.5
7.4 6
2.5
-19.2
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

10. Ir.acac – Migratory Insertion
Arylation of substituted olefins lead preferably to linear products in an anti-Markovnikov fashion
Empty space
– No steric crowding
2.08
2.07
1.88
1.94
Steric crowding
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

11. Ir.acac – Migratory Insertion
Predicted isomer ratios are in excellent agreement with experimental values. Regioselectivity traced to electron density on olefin (major effect) and sterics (minor effect).
Experimental data*
Calculated Energies (kcal/mol)
Bond Lengths (Å)
Olefin
Isomer
Ratio
ΔΔG
ΔH(0K)
ΔΔH ΔG
Ir-C1
C1-C2
C2-C3
Ir-C3
ethene
N/A
100
27.0
29.3
2.07
1.47
1.90
2.20
propene
2,2 39
0.4
29.8
34.3
0.6
1.94
1,2 61
0.0
30.2
33.7
2.08
1.88
iso-butene 18
1.4
34.8
0.7
39.1
1.2
2.06
1.48
1.98
2.21 82
34.1
37.9
2.09
1.49
1.85
styrene 2
3.5
2.4
39.2
2.5
1.97 98
31.8
36.7
2.11 --
30.9
6.1
37.0
7.9
1.46
2.18
24.8
29.1
1.93
2.19
26.0
-4.0
32.5
-2.5
30.0
34.5
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

12. Ir.acac - Mechanism
ΔH(0K)
(kcal/mol)
TS1
27.0 8
15.7
TS2
16.6 7
5.6 9
4.6 10
4.5
7.4 6
2.5
-19.2
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

13. Ir.acac – Inhibition by Ethene
Inhibition by Excess Olefin
Experimentally observed inhibition by olefins at olefin:benzene ratios above 1:4*
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

14. Ir.acac – Inhibition by Ethene
Experimentally observed inhibition by olefins at olefin:benzene ratios above 1:4* explained by significantly increased activation energy for CH activation
TS2
TS3
TS4
*Matsumoto, T.; Periana, R. A.; Taube, D. J.; Yoshida, H. J. Mol. Cat. A 2002, 1-18

15. Ir.acac – β-hydride Elimination14
5.6 18
-3.9 21
-8.3
24.6
TS5
27.2 23
3.7 24
-0.2 22
-4.4
8.1 ΔE
(kcal/mol)
9 + C2H6
-27.0
Styrene forms rapidly but reversibly
Further reactions kinetically inaccessible
No styrene products are observed experimentally. Use of hydride scavenger (such as Cu(OAc)2 ) exclusively yield styrene*
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

16. Ir.acac - Mechanism
ΔH(0K)
(kcal/mol)
TS1
27.0 8
15.7
TS2
16.6 7
5.6 9
4.6 10
4.5
7.4 6
2.5
-19.2
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

17. Ir.acac – C-H activation
Transition structure characterized as concerted mechanism with character of oxidative addition: Oxidative Hydrogen Migration (OHM)
Analysis of bonding suggests that there is a full bond between Ir-H, two half-order bonds between Ir-CH2R and H-CH2R, a more than half-order bond between Ir-Ph and less than half-order between H-Ph.
The imaginary frequency corresponds to movement of the hydride on a path between the two carbons.
The Ir-H has a stretching mode at 2353 cm-1, further confirming the presence of a full bond between Ir and H. No mode of this magnitude is present in sigma-bond metathesis transition states.
νC-H-C = cm-1
νIr-H = cm-1
2.21
1.69
1.58
1.99
2.09
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

18. Ir.acac – C-H activation
Bergman chemistry:
IrV is a viable intermediate
1.69 Å
1.99 Å
C-H =
2.20 Å
The lack of a stable seven-coordinate IrV species traced to steric crowding and low electron density at the metal center.
Hypothesis: the OHM mechanism occurs when true Oxidative Addition is energetically inaccessible
Intermediate Transition State
Charge on Ir:
Int TS ΔE
Decreased electron density at metal center ->
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

19. Ir.acac - Mechanism
ΔH(0K)
(kcal/mol)
TS1
27.0 8
15.7
TS2
16.6 7
5.6 9
4.6 10
4.5
7.4 6
2.5
-19.2
Oxgaard, Muller, Periana and Goddard J. Am. Chem. Soc. 2003, in press

20. Gunnoe and coworkers J. Am. Chem. Soc. 2003, 125, 7506
Ru.Tp.CO
Gunnoe and coworkers J. Am. Chem. Soc. 2003, 125, 7506

21. Ru.Tp.CO - Catalytic Cycle
Ir.acac in dotted lines
Oxgaard and Goddard J. Am. Chem. Soc. 2003, in press

22. Ru.Tp.CO - Catalytic Cycle
Ru.Tp.CO exhibits similar regioselectivity as Ir.acac
Empty space
– No steric crowding
Oxgaard and Goddard J. Am. Chem. Soc. 2003, in press

23. Ru.Tp.CO - Catalytic Cycle
2.27
1.65
1.61
1.56
2.17
νC-H-C = cm-1
νRu-H = cm-1
OHM transition state similar to Ir.acac, but further away from an intermediate. This is reflected in shorter C-H bond lengths, and consistent with the higher energy of TS2Ru.Tp.CO vs. TS2Ir.acac.
Oxgaard and Goddard J. Am. Chem. Soc. 2003, in press

24. Ru.Tp.CO - Excess Olefin Ru.Tp.CO Ir.acac Excess olefin inhibits rate
Excess olefin polymerizes readily
(experimentally confirmed by Dr. Gunnoe)
Excess olefin inhibits rate
but will not polymerize
Ru.Tp.CO is faster, but must operate at significantly reduced ethylene pressures
Oxgaard and Goddard J. Am. Chem. Soc. 2003, in press

25. RuII is MORE electron rich than IrIII, yet MORE reactive!
Ir.acac vs. Ru.Tp.CO
Why is Ru.Tp.CO faster? vs
Ir.acac
TS1 = 24.5
Ru.Tp.COTS1 = 21.1
Insertions known to be improved by reduced electron density on the metal
BUT!
RuII is MORE electron rich than IrIII, yet MORE reactive!

26. Ir.acac vs. Ru.Tp.CO Ru.acac(-) TS1 = 28.3 Ir.acac TS1 = 24.5
Ru.Tp.COTS1 = 21.1
Ir.Tp.CO(+)
TS1 = 17.0
TS2 = 6.9
TS2 = 11.8
TS2 = 18.0
TS2 = 25.3

27. Ir.acac vs. Ru.Tp.CO

28. Other metals?

29. Other metals?
TARGET

30. Correlation What is the origin of this correlation? Hypothesis:
Species with higher insertion and lower C-H activation energies appear to contain metal centers with more easily accessible oxidation states

31. Correlation Is this hypothesis chemically reasonable? C-H Activation
C-H activation operates through an oxidative mechanism
 More easily accessible oxidized state should lower barrier.

32. Correlation Insertion Back-bonding lost Back-bonding:
Metal d  C2H4 π*
Forward-bonding compensated by Ph σ
Forward-bonding:
C2H4 π  Metal d
Sigma-bonding:
Ph σ  Metal d
Sigma-bonding maintained

33. Correlation Insertion Proof:
If the forward-bonding energy is maintained in the insertion transition state, but the back bonding energy is lost, the barrier for insertion should correlate to back bonding character of the olefin
Amount of back-bonding determined by hybridization of C2H4 carbons:
sp2 character  mainly forward-bonding
sp3 character  mainly back-bonding
C1 = sp2
Ha-Hb-C1-C2
= 180º
C1 = sp3
Ha-Hb-C1-C2
= 120º

34. Correlation
Clear correlation: insertion favored by decreased back-bonding in the resting state of the catalyst

35. Correlation
Additional points from other late metal polymerization catalysts – the correlation appears to be general, not just valid for hydroarylation catalysts

36. But why does that make Ru.Tp.CO faster?
Correlation
But why does that make Ru.Tp.CO faster? vs
Ir.acac
TS1 = 24.5
Ru.Tp.COTS1 = 21.1
CO is a strong π-acceptor  Less electron density in Ru d-orbitals  Less back-bonding to the resting state olefin (and a less stable C-H activation transition state)

37. Correlation
Hypothesis: CO is a strong π-acceptor  More efficient catalyst
Test: replace CO with a non-π-acceptor, e.g. NH3.
Ru.Tp.NH3 should have higher barrier for insertion, and lower for C-H activation
Ru.Tp.COTS1 = 21.1
TS2 = 18.0
Ru.Tp.NH3
TS1 = 25.7
TS2 = 15.4
Hypothesis appears to be true

38. Correlation
Is simultaneous improvement of insertion and C-H activation impossible?
Modifications based on π-ligands will not improve overall efficiency
– what about modifying the sigma framework?
Insertions favored by lower electron density on the metal:
Add electron withdrawing groups to the ligand
Replace nitrogens with less donating oxygens

39. Improvements
Ru.Tp.COTS1 = 21.1
TS2 = 18.0
Ir.acac
TS1 = 24.5
Ir.acac.4CF3
TS1 = 21.6
TS2 = 11.8
TS2 = 14.0
Contrary effect still present, although at somewhat lower level -
Lower electron density should disfavor a higher oxidation state, but should also reduce forward-bonding and thus barrier for insertion

40. Improvements TARGET Ir.acac.4CF3
Ir.acac.4CF3 almost at the target – further modifications to follow

41. Conclusions
The mechanism features two key steps: 1,2 insertion and C-H activation.
1,2- insertion step is reminiscent of the Heck insertion step. Regioselectivity depends on steric and electronic character of the olefin, where bulky and electron withdrawing groups favor linear product.
C-H occurs through a concerted reaction with characteristics of oxidative addition
Experimentally observed absence of beta-hydride elimination products caused by kinetic factors.
In systems with low energy insertion and high energy C-H activation will polymerize olefin at high olefin loading
The C-H activation is favored and the activation disfavored by an easily accessible Mn  Mn+2 oxidation state
π-accepting ligands makes the Mn  Mn+2 oxidation state less accessible
Novel catalysts with greatly improved activities are suggested, based on sigma-withdrawing substituents without modifications to the π-framework

42. Acknowledgements Dr. William Goddard, III WAG group
the catalysis subgroup
Mr. Robert (Smith) Nielsen
Dr. Roy Periana (USC)
Dr. Xiang Yang Liu
Mr. Guarav Bhalla
$$$$$$$$$$$$ Funding $$$$$$$$$$$$
ChevronTexaco Energy Research and Technology Co.
The computer facilities of the MSC were provided by support from DURIP and MURI