1. Outline Slide 1 Lecture 1 - Redox-Active Ligands: What Are They? How Do They Work? and How Might They Be Improved? Lecture 2 - The Development of a Highly Active Manganese Hydrosilylation Catalyst Lecture 3 - Hydrosilylation and Beyond: Expanding the Scope of Redox- Active Ligand Assisted Catalysts

2. Homogeneous Transition Metal Catalysis Slide 2 Hydrogenation (2001)Dihydroxylation (2001) Olefin Metathesis (2005)Cross Coupling (2010)

3. Homogeneous Transition Metal Catalysis Slide 3 Hydrogenation (2001)Dihydroxylation (2001) Olefin Metathesis (2005)Cross Coupling (2010) Can First Row Transition Metals be Used Instead?

4. Advantages Slide 4 Cost Per Mole: Based on Cheapest Available Starting Material Offered by Strem Chemicals (08/13) First Row Metals Are: - Three Orders of Magnitude Cheaper

5. Advantages Slide 5 Cost Per Mole: Based on Cheapest Available Starting Material Offered by Strem Chemicals (08/13) First Row Metals Are: - Three Orders of Magnitude Cheaper - Earth Abundant

6. Advantages Slide 6 Cost Per Mole: Based on Cheapest Available Starting Material Offered by Strem Chemicals (08/13) First Row Metals Are: - Three Orders of Magnitude Cheaper - Earth Abundant - Significantly Less Toxic RDAs: Mn (2.3 mg), Fe (8 mg) 5 ppm Limit for Precious Metals

7. Mn Catalysis: The Road Less Traveled Slide 7 Oxidation: Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801.

8. Mn Catalysis: The Road Less Traveled Slide 8 Oxidation: Reduction: Zhang, W.; Loebach, J. L.; Wilson, S. R.; Jacobsen, E. N. J. Am. Chem. Soc. 1990, 112, 2801. Cavanaugh, M. D.; Gregg, B. T.; Cutler, A. R. Organometallics 1996, 15, 2764. Pt Hydrosilylation Catalysts Currently Used for Coatings, Adhesives, and Cured Rubbers

9. Catalyst Design Inspiration Slide 9 Improved Mn Hydrosilylation Catalysts?

10. Metallation of N PDI Ligands Slide 10 Tufan Mukhopadhyay - κ 3 -PDI Coord. Verified by XRD - μ eff = 6.0 μ B - High-Spin Mn(II) - μ eff = 6.3 μ B - High-Spin Mn(II)

11. Chemical Chelate Activity Slide 11 Tufan Mukhopadhyay - Mn Center Remains Divalent - Redox-Activity Leads to Deprotonation - Observed with xs. K and COT (cat.) - ( Me 2 NPr PDI)MnCl 2 Reduction Resulted in Decomposition - μ eff = 3.8 μ B - Intermediate-Spin Mn(II)

12. Crystallographic Confirmation Slide 12 Tufan Mukhopadhyay

13. ( Ph 2 PPr PDI)MnCl 2 Slide 13 Tufan Mukhopadhyay - μ eff = 6.1 μ B - High-Spin Mn(II)

14. ( Ph 2 PPr PDI)MnCl 2 Slide 14 Tufan Mukhopadhyay - μ eff = 6.1 μ B - High-Spin Mn(II) κ 3 -N,N,N-PDI Rather Than κ 2 -P,P-PDI Coordination

15. Analyzing Chelate Reduction by XRD Slide 15 NeutralRadical MonoanionDianion 1.28 Å Knijnenburg, Q.; Gambarotta, S.; Budzelaar, P. H. M. Dalton Trans. 2006, 5442. 1.32 Å 1.36 Å 1.50 Å1.44 Å1.40 Å 1.278(4) Å 1.493(4) Å1.502(4) Å 1.282(3) Å Tufan Mukhopadhyay

16. Analyzing Chelate Reduction by XRD Slide 16 NeutralRadical MonoanionDianion 1.28 Å Knijnenburg, Q.; Gambarotta, S.; Budzelaar, P. H. M. Dalton Trans. 2006, 5442. 1.32 Å 1.36 Å 1.50 Å1.44 Å1.40 Å ( Ph 2 PPr PDI)MnCl 2 : HS Mn(II), PDI 0 1.278(4) Å 1.493(4) Å1.502(4) Å 1.282(3) Å Tufan Mukhopadhyay

17. ( Ph 2 PPr PDI)Mn Preparation Slide 17 Tufan Mukhopadhyay - Without COT, Reduction Takes 3.5 Days - Formally Zerovalent, Deprotonation Not Observed - For Pyridine vs. PR 3 Substituents, It’s All About Covalency - μ eff = 2.2 μ B (S = 1/2)

18. ( Ph 2 PPr PDI)Mn Characterization Slide 18 Tufan Mukhopadhyay 1 H NMR

19. ( Ph 2 PPr PDI)Mn Electronic Structure Slide 19 Tufan Mukhopadhyay

20. ( Ph 2 PPr PDI)Mn Electronic Structure Slide 20 Tufan Mukhopadhyay Dianion 1.36 Å 1.40 Å

21. ( Ph 2 PPr PDI)Mn Electronic Structure Slide 21 Tufan Mukhopadhyay Electronic Structure: Low-Spin Mn(II), PDI 2- Dianion 1.36 Å 1.40 Å Confirmed by observation of an anisotropic 6-line EPR signal at 77K (S Mn = 1/2)

22. Hydrosilylation Activity Slide 22 Tufan Mukhopadhyay >99% Conversion TOF = 1,485 h -1

23. Other Silanes? Slide 23 Tufan Mukhopadhyay SilaneProduct% ConversionTOF (h -1 ) >991,485 26390 ---

24. Other Silanes? Slide 24 Tufan Mukhopadhyay SilaneProduct% ConversionTOF (h -1 ) 28420 575 345 ---

25. Scope of Ketone Hydrosilylation Slide 25 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.TimeTOF (h -1 ) PhSiH(OCH(Me)(Ph)) 2 PhSi(OCH(Me)(Ph)) 3 (3:1) >994 min1,485 PhSiH(OCH(Me)(Ar)) 2 PhSi(OCH(Me)(Ar)) 3 (5:1) >9925 min238 PhSiH(OCH(Me)(Ar)) 2 >996 h17

26. Scope of Ketone Hydrosilylation Slide 26 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.TimeTOF (h -1 ) PhSiH(OCH(Me)(Ar)) 2 PhSi(OCH(Me)(Ar)) 3 (7:1) >994 h25 PhSiH(OCH(Me)(Ar)) 2 PhSi(OCH(Me)(Ar)) 3 (3:1) >993.5 h28 PhSiH(OCH(CF 3 )(Ph)) 2 PhSi(OCH(CF 3 )(Ph)) 3 (2:1) >9912 h8

27. Scope of Ketone Hydrosilylation Slide 27 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.TimeTOF (h -1 ) PhSiH(OCH( i Pr) 2 ) 2 PhSiH 2 (OCH( i Pr) 2 ) (1:1) >9936 min165 PhSiH(OCH(Cy) 2 ) 2 PhSiH 2 (OCH(Cy) 2 ) (3:1) >9924 h4 PhSiH(OCH(Me)(Ar)) 2 805 d<1

28. Scope of Ketone Hydrosilylation (0.1 mol %) Slide 28 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.TimeTOF (h -1 ) PhSiH(OCH(Me)(Ph)) 2 PhSi(OCH(Me)(Ph)) 3 (5:1) >994 min14,850 PhSiH(OCy) 2 >994 min14,850 PhSiH(OCH(Me)( n Bu)) 2 >994 min14,850 Exothermic!

29. Improving Atom-Efficiency Slide 29 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.TimeTOF (h -1 ) PhSi(OCy) 3 >994 h74 PhSi(OCH(Me)(Ph)) 3 >996.5 h46 PhSiH(OCH(Me)( n Bu)) 2 PhSi(OCH(Me)( n Bu)) 3 (3:1) 7424 h9

30. Only the Beginning... Slide 30 Tufan Mukhopadhyay >99% Conversion

31. Only the Beginning... Slide 31 Tufan Mukhopadhyay Ester Dihydrosilylation by way of Reductive C-O Bond Cleavage >99% Conversion

32. Only the Beginning... Slide 32 Tufan Mukhopadhyay - >99% Conversion - TOF = 18 h -1 (vs. EtOAc) - Selective for PhSi(OEt) 3 >99% Conversion

33. Other Esters Slide 33 Tufan Mukhopadhyay SubstrateProduct (Ratio)% Conv.Time PhSi(OEt) 3 PhSiH(O i Pr) 2 PhSi(O i Pr) 3 PhSiH(OEt) 2 (2:1.5:1:1) >99 3 d (80 °C) PhSi(OPh) 3 PhSi(OEt) 3 PhSi(OEt) 2 (OPh) (1.25:1.25:1) 95 10 d (25 °C) PhSiH(O t Bu) 2 PhSiH(OEt)(O t Bu) PhSi(OEt) 3 (1.25:1.25:1) 85 10 d (80 °C) Consistent with Previously Reported Acyl C-O Bond Cleavage Preferences

34. A Curious Observation Slide 34 Tufan Mukhopadhyay 1 H NMR: -2.98 (t, J PH = 112.5 Hz, 1H, Mn-H)

35. A Curious Observation Slide 35 Tufan Mukhopadhyay 1 H NMR: -2.98 (t, J PH = 112.5 Hz, 1H, Mn-H) Active Catalyst? Are Activities (TOFs) Really 10x-1,000x Higher?

36. Alternate Preparation Slide 36 Tufan Mukhopadhyay - Diamagnetic - 31 P NMR: 69.20 (s) - Converts to ( Ph 2 PPr PDI)Mn After Days 1 H NMR

37. Alternate Preparation Slide 37 Tufan Mukhopadhyay - Diamagnetic - 31 P NMR: 69.20 (s) - Converts to ( Ph 2 PPr PDI)Mn After Days 1 H NMR Low-Spin Mn(I)?

38. ( Ph 2 PPr PDI)MnH Electronic Structure Slide 38 Tufan Mukhopadhyay

39. ( Ph 2 PPr PDI)MnH Electronic Structure Slide 39 Tufan Mukhopadhyay ( Ph 2 PPr PDI)MnH( Ph 2 PPr PDI)Mn

40. ( Ph 2 PPr PDI)MnH Electronic Structure Slide 40 Tufan Mukhopadhyay ( Ph 2 PPr PDI)MnH Electronic Structure: Low-Spin Mn(III), PDI 2-

41. Activity Comparison Slide 41 Tufan Mukhopadhyay CatalystSubstrate% Conv.TimeTOF (h -1 ) ( Ph 2 PPr PDI)Mn>994 min14,850 ( Ph 2 PPr PDI)MnH874 min13,050 ( Ph 2 PPr PDI)Mn>994 min14,850 ( Ph 2 PPr PDI)MnH804 min12,000

42. Activity Comparison Slide 42 Tufan Mukhopadhyay Catalyst% Conv.TimeTOF (h -1 ) ( Ph 2 PPr PDI)Mn>995.5 h18 ( Ph 2 PPr PDI)MnH>997 h14

43. Mn-H Ketone Reduction Mechanism Slide 43 Tufan Mukhopadhyay Mn(III), PDI 2- Maintained Throughout Transformation

44. Radical Ketone Reduction Mechanism Slide 44 Tufan Mukhopadhyay Are Both Pathways Operative?

45. Mn-H Ester Reduction Mechanism Slide 45 Tufan Mukhopadhyay Mn(III), PDI 2- Maintained Throughout Transformation

46. Mn-H Ester Reduction Mechanism Slide 46 Tufan Mukhopadhyay Mn(III), PDI 2- Maintained Throughout Transformation

47. Radical Ester Reduction Mechanism Slide 47 Tufan Mukhopadhyay Are Both Pathways Operative?

48. Radical Ester Reduction Mechanism Slide 48 Tufan Mukhopadhyay Are Both Pathways Operative?

49. A Revealing Experiment Slide 49 Tufan Mukhopadhyay ‘Insertion’ of ketone into Mn-H is very slow! Not part of the catalytic cycle. Bright Blue

50. Summary Slide 50 Lecture 2 - The Development of a Highly Active Manganese Hydrosilylation Catalyst A formally zerovalent (PDI)Mn precatalyst was prepared

51. Summary Slide 51 Lecture 2 - The Development of a Highly Active Manganese Hydrosilylation Catalyst A formally zerovalent (PDI)Mn precatalyst was prepared This complex is highly active for the hydrosilylation of ketones

52. Summary Slide 52 Lecture 2 - The Development of a Highly Active Manganese Hydrosilylation Catalyst A formally zerovalent (PDI)Mn precatalyst was prepared This complex is highly active for the hydrosilylation of ketones The reductive acyl C-O cleavage of esters has been observed

53. Slide 53