Selective sp 3 C-H Hydroxylation. Xin Zhang Department of Chemistry Michigan State University 11/10/2010

Transcription

1 Selective sp 3 C-H Hydroxylation Xin Zhang Department of Chemistry Michigan State University 11/10/2010

2 Content Introduction Tertiary sp 3 C-H Hydroxylation Secondary sp 3 C-H Hydroxylation Primary sp 3 C-H Hydroxylation Example of sp 3 C-H Hydroxylation in Total Synthesis

3 The Versatility and Application of Alcohol in Chemistry

4 The Versatility and Demand of Alcohol in Industry and Daily Life Isopropanol is good solvent and anticeptic Reed, T. B.; Lerner, R. M.; Science 1973, 182, Worldwatch Institute and Center for American Progress (2006). American energy: The renewable path to energy security

5 The Advantage of Hydroxylation from sp 3 C-H Petroleum reserves on the earth <Petroleum Resources Management System>, Society of Petroleum Engineers Retrieved

6 The Advantage of Hydroxylation from sp 3 C-H 6-Deoxyerythronolide B Corey, E. J.; Trybulski, E. J.; Melvin, L. S.; Nicolaou, K. C. et al. J. Am. Chem. Soc. 1987, 100, Stang, E. M.; White, M. C. Nature Chemistry 2009, 1, 547.

7 Challenges in C-H Oxidation The inertness of C-H bond primary sp3 C-H secondary sp3 C-H tertiary sp3 C-H C-H Bond dissociation energy/ kcal/mol Berkowitz, J.; Ellison, G. B.; Gutman, D. J. Phys. Chem. 1994, 98, 2744.

8 Challenges in C-H Oxidation The over oxidation of alcohol product Mello, R.; Fiorentino, M.; Fusco, C.; Curc, R.; J. Am. Chem. Soc. 1989, 111, 6749.

9 Challenges in C-H Oxidation The selective oxidation of specific one type Nomura, K.; Uemura, S. J. Chem. Soc., Chem. Commun. 1994, 129.

10 Content Introduction Tertiary sp 3 C-H Hydroxylation Secondary sp 3 C-H Hydroxylation Primary sp 3 C-H Hydroxylation Example of sp 3 C-H Hydroxylation in Total Synthesis

11 Tertiary sp 3 C-H Hydroxylation with Ru Catalyst Mechanism of this Reaction 2RuCl3+5KBrO3+3H2O = 2RuO4+5KBrO2+6HCl McNeill, E.; Bois, J. D. J. Am. Chem. Soc. 2010, 132,

12 Substrate Scope of the Ru Catalyzed Reaction McNeill, E.; Bois, J. D. J. Am. Chem. Soc. 2010, 132,

13 More Complex Case with Multiple Tertiary C-H Centers 4-epiajanol dihydroxyeudesmane pygmol 13 C NMR of 3 carbon C-H1 C-H2 C-H3 C-H4 C-H5 δ(ppm) common intermediate 3 C-H1 and C-H5 is most likely to be oxidized with electrophilic oxidant Chen, K.; Baran, P. S. Nature 2009, 459, 824.

14 Total Synthesis of Dihydroxyeudesmane Chen, K.; Baran, P. S. Nature 2009, 459, 824.

15 Selective Hydroxylation of H5 Crystal structure of 3 Chen, K.; Baran, P. S. Nature 2009, 459, 824. Chen, K.; Richter, J. M.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7247.

16 Selective Hydroxylation of H5 Chen, K.; Baran, P. S. Nature 2009, 459, 824. Chen, K.; Richter, J. M.; Baran, P. S. J. Am. Chem. Soc. 2008, 130, 7247.

17 Total Synthesis of 4-epiajanol Chen, K.; Baran, P. S. Nature 2009, 459, 824.

18 Selective Hydroxylation of H1 Strain release is proposed to be the key in this selective hydroxylation on H1 Chen, K.; Baran, P. S. Nature 2009, 459, 824.

19 Strain Release of 1,3-Diaxial Interaction δ + δ - δ. δ. 6-3lG* Calculation Charged or radical transition state sp 3 sp 2 Tetrahedral Planar Bath, R. D.; Andri, J. L.; Su, M.-D.; McDouall, J. J. W. J. Am. Chem. Soc. 1993, 115, Chen, K.; Baran, P. S. Nature 2009, 459, 824.

20 Total Synthesis of pygmol Chen, K.; Baran, P. S. Nature 2009, 459, 824.

21 Total Synthesis of pygmol Chen, K.; Baran, P. S. Nature 2009, 459, 824.

22 Content Introduction Tertiary sp 3 C-H Hydroxylation Secondary sp 3 C-H Hydroxylation Primary sp 3 C-H Hydroxylation Example of sp 3 C-H Hydroxylation in Total Synthesis

23 Over Oxidation of Secondary C-H Hydroxylation Over oxidation on secondary C-H Is there any method to avoid the over oxidation? Mello, R.; Fiorentino, M.; Fusco, C.; Curc, R.; J. Am. Chem. Soc. 1989, 111, 6749.

24 Secondary sp 3 C-H Hydroxylation with Rh Catalyst Nomura, K.; Uemura, S. J. Chem. Soc., Chem. Commun. 1994, 129.

25 Secondary sp 3 C-H Hydroxylation without Rh Catalyst GC signal of product Reaction time/h With Rh Without Rh cyclohexane oxidation product comparison Moody, C. J. ; O Connell, J. L. Chem. Commun. 2000, 1311.

26 Mechanism of Hydroxylation with Peroxy Acid Moody, C. J. ; O Connell, J. L. Chem. Commun. 2000, 1311.

27 Directing Group in Secondary Hydroxylation Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

28 Mechanism of Carbonyl Directed Intramolecular Hydroxylation Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

29 Rationale of Trans Stereoselectivity of 2-Methyl Substrate Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

30 Rationale of Cis Stereoselectivity of 3-Methyl Substrate Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

31 Rationale of Ttans Stereoselectivity of 4-Methyl Substrate Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

32 Bulky Group Strongly Favor One Stereochemistry Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

33 Oxygen Substituent at C-3 Inverse the Stereoselectivity Why the stereoselectivity is inversed? Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

34 Rationale of Inverse Stereoselectivity Wong, M.-K.; Chung, N.-W.; He, L.; Yang, D. J. Am. Chem. Soc. 2003, 125, 158.

35 Secondary C-H Hydroxylation Activated by alkene group Chen, M. S.;Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970

36 Mechanism of Pd Catalyzed C-H Oxidation Chen, M. S.;Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970

37 Substrate Scope of Pd Catalyzed Reaction Chen, M. S.;Prabagaran, N.; Labenz, N. A.; White, M. C. J. Am. Chem. Soc. 2005, 127, 6970

38 Secondary Hydroxylation by Bulky Polyoxometalate Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

39 Crystal Structure of the Metal Catalyst O V W P [HPV2W10O40] 4- Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

40 Catalytic Cycle of C-H Hydroxylation m/z=3583 {[nbu4n]4[h2pv2w10o40]} + m/z=3599 {[nbu4n]4[hpv2w10o39(ooh)]} + Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

41 Kinetic Study for the Catalytic Cycle [1B]/[1A] [H2O2]/[H2O] Step 1 1A+H2O2 1B+H2O Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

42 Kinetic Study for the Catalytic Cycle [1C]/[1A] [H2O2]/[H2O] 2 + 1A+H2O2 1B 1A+H2O2 1B+H2O 1C+H2O 1C+2H2O Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

43 Kinetic Isotope Effect of the Hydroxylation Reaction Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

44 Substrate Scope of the Hydroxylation Reaction Kamata, K.; Yonehara, K.; Nakagawa, Y.; Uehara, K. and Mizuno, N.; Nature chemistry, 2010, 2, 478.

45 Content Introduction Tertiary sp 3 C-H hydroxylation Secondary sp 3 C-H hydroxylation Primary sp 3 C-H hydroxylation Example of sp 3 C-H hydroxylation in total synthesis

46 Primary sp 3 C-H Hydroxylation : Barton Reaction Barton, D. H. R.; Beato, J. M. J. Am. Chem. Soc. 1960, 82, Reese, P. B. Steroids 2001, 66, 481.

47 Stepwise Hydroxylation of Primary C-H 0.5 mol% Cp*Rh(η 4 -C6Me6) Primary alcohol is obtained Chen,H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science, 2000, 287, Wei, C. S.; Jimenez-Hoyos, C. A.; Videa, M. F.; Hartwig,J. F.; Hall, M. B. J. Am. Chem. Soc. 2010, 132, 3078.

48 Calculated Energy Diagram for Boration Reaction Chen,H.; Schlecht, S.; Semple, T. C.; Hartwig, J. F. Science, 2000, 287, Wei, C. S.; Jimenez-Hoyos, C. A.; Videa, M. F.; Hartwig,J. F.; Hall, M. B. J. Am. Chem. Soc. 2010, 132, 3078.

49 Content Introduction Tertiary sp 3 C-H Hydroxylation Secondary sp 3 C-H Hydroxylation Primary sp 3 C-H Hydroxylation Example of sp 3 C-H Hydroxylation in Total Synthesis

50 Previous Strategy of Total Synthesis of 6- Deoxyerythronolide B 6-Deoxyerythronolide B Corey, E. J.; Trybulski, E. J.; Melvin, L. S.; Nicolaou, K. C. et al. J. Am. Chem. Soc. 1987, 100, 4620.

51 Total Synthesis of 6-Deoxyerythronolide B with Late-Stage sp 3 C-H Oxidation Strategy 6-Deoxyerythronolide B intermediate 2 Task 1: C-H oxidation Task 2: Stereochemistry Task 3: Lactonization Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

52 Total Synthesis of 6-Deoxyerythronolide B Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

53 Energy Difference between 3 and epi-3 3 is calculated (MMFF94s force-field) to be 3 kcal/mol more stable than epi-3 Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

54 The Macrolactonization is Proposed to be a Closed Transition State Chelated, product-like structure More stable Non-chelated Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

55 Total Synthesis of 6-Deoxyerythronolide B Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

56 Non-Chelated Leads to Poor Stereoselectivity Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

57 Proof of Stereochemistry : Crystal Structure of Derivative of the 6-Deoxyerythronolide B Stang, E. M.; White, M. C. Nature Chemistry, 2009, 1, 547.

58 Summary: 1. Tertiary hydroxylation could be selectively achieved with one or more tertiary centers present by the electronic, steric factors. 2. Secondary hydroxylation could be selectively achieved with directing group, protecting group, alkene activation or steric factors. 3. Primary hydroxylation could be selectively achieved with directing group or stepwise method.

59 Acknowledgement Dr. Wulff Dr. Jackson Dr. Maleczka Anil, Dima, Li, Munmun, Nilanjana, Yong, Hong, Wynter, Wenjun Jason, Zhe, Greg, Li, Yimeng

60 Thank you for your attention