Ketone-Catalyzed Asymmetric Epoxidation Reactions

1. Ketone-Catalyzed Asymmetric Epoxidation Reactions

2. Application of Asymmetric Epoxidation in Natural Product Syntheses MacDonald, F. et al Org. Lett2000, 2, 2917. Yang, D. et al J.Org. Chem.2000, 65, 2208-2217. Danishefsky, S. et al J. Org.Chem.2001, 66, 4369-4378.

3. Conditions for Converting Ketones into Dioxiranes • H2O2 may also employed as a primary oxidant

4. Inductive Effects on Dioxirane Reactivity Yang, D. et al J.Org. Chem.2000, 65, 2208-2217.

5. First Generation Chiral Ketone Catalyst Design Curci’s Chiral Ketones: ee’s were less that 20% olefins investigated Curci, R. et al Chem. Commun1984, 156-156. 4

6. First Generation C2 Chiral Ketone Catalyst Design trans-stilbene was the alkene substrate 5 Yang, D. et al J.Org. Chem.2000, 65, 2208-2217.

7. Stereoelectronic Effect on C2 Symmetric Catalyst Activity Yang, D. et al J.Org. Chem.2000, 65, 2208-2217.

8. Stereoelectronic Effect on C2 Symmetric Catalyst Activity Behar, V. et al Tetrahedron Lett. 2002, 43, 1943-1946.

9. Stereoelectronic Effect on C2 Symmetric Catalyst Activity Tomioka, K. et al Tetrahedron Lett.2002, 43, 631-633.

10. Stereoelectronic Effect on C2 Symmetric Catalyst Activity 9 *ND = not determined Denmark, K. et al J. Org. Chem.2002, 67, 3479-3486.

11. Chiral Ketones Derived from Sugars Mechanistic Hypothesis 10

12. Epoxidation of Trisubstituted and trans-Substituted Alkenes ee’s determined and compared to % conversion Shi, Y et al J. Am. Chem. Soc. 2002, 43, 631-633.

13. Use of H2O2 as a Primary Oxidant Use of H2O2 as a Primary Oxidant Mechanistic Hypothesis Mechanistic Hypothesis Shi, Y et al Tetrahedron 2001, 57, 5213-5218. Shi, Y et al Tetrahedron 2001, 57, 5213-5218. 12 12

14. Evaluation of Asymmetric Epoxidation with H2O2 as a Primary Oxidant ee’s determined and compared to % conversion Shi, Y et al Tetrahedron 2001, 57, 5213-5218. 13

15. Mechanistic Hypotheses for Epoxidation Stereoselectivity Shi, Y et al Tetrahedron 2001, 57, 5213-5218. 14 Singleton D. et al J. Am. Chem.Soc 2001,127, ASAP.

16. Inductive Effect on the Reactivity of the Chiral Ketone Catalyst Shi, Y et al Tetrahedron 2001, 57, 5213-5218. 15

17. Inductive Effect on the Reactivity of the Chiral Ketone Catalyst * results obtained withcatalyst 3 Shi, Y et al J. Am. Chem. Soc. 2002, 124, 8792-8793.

18. Design of a Catalyst which is More Suitable for cis Olefins rationale for incompatibility with cis alkenes and terminal alkenes Shi, Y et al J. Org. Chem.2002, 67,2435-2446.

19. Synthesis of Modified Catalyst Synthesis of Modified Catalyst Shi, Y et al J. Org. Chem. 2003, 68, 4963-4965.

20. Typical Enantiomeric Excess Values Obtained from the Modified Catalyst Shi, Y et al J. Am. Chem. Soc. 2002, 67, 2435-2446. 19

21. Kinetic Resoluion of With Asymmetric Epoxidation Shi, Y et al J. Am. Chem. Soc. 2005, ASAP. 20

22. Rationale for Kinetic Resolution of epoxides Shi, Y et al J. Am. Chem. Soc. 2005, ASAP

23. Chiral Ketones Derived from D-Glucose Shing et al Tetrahedron2002, 58, 7545-7552. 22

24. Evaluation of a Chiral Ketone Derived from Glucose Shing et al Tetrahedron 2002, 58, 7545-7552. 23

25. Evaluation of a Chiral Ketone Derived from Glucose Shing et al Tetrahedron 2002, 58, 7545-7552. 24

26. Chiral Ketones Derived From L-Arabinose Shing et al Tetrahedron 2003, 59, 2159-2168

27. Evaluation of a Chiral Ketone Derived From L-Arabinose The Effect of pH on Catalyst Activity Shing et al Tetrahedron 2003, 59, 2159-2168.

28. Chiral Ketones Derived from D-(-)-Quinic Acid Shi, Y. et al 1997, 62, 8622-8623. 27

29. Chiral Ketones Derived from D-(-)-Quinic Acid Shi, Y. et al 1997, 62, 8622-8623.

30. Chiral Ketones Derived from D-(-)-Quinic Acid Shing et al Tetrahedron 2003, 59, 2159-2168. 29

31. Evaluation of Chiral Ketones Derived from D-(-)-Quinic Acid Shing et al Tetrahedron 2003, 59, 2159-2168. 30

32. Asymmetric Epoxidation with Chiral Cyclohexanones Roberts, S. M. J. Synth. Org. Chem. Jpn.2002,60, 342-349. 31