Organic Chemistry II

1. Organic Chemistry II Dr. Christopher Cioffi Monday 3/20/2017 9:00AM – 9:50AM

2. Dienes and Conjugation

3. Dienes and Conjugation

4. Dienes and Conjugation

5. Dienes and Conjugation Which systems are conjugated? Which ones are not conjugated?

6. Which systems are conjugated? Which ones are not conjugated?

7. The Diels-Alder Reaction

8. The Diels-Alder Reaction

9. The Diels-Alder Reaction: Highlights Pericyclic reaction A concerted (one-step) reaction that proceeds via a cyclic transition state [4+2] Cycloaddition reaction between a conjugated diene and a dienophile Forms six-membered ring systems (cyclohexene products) Generates molecular complexity efficiently Accommodates several functional groups, generates a new double-bond, and controls stereochemistry and regiochemistry: can establish up to four stereogenic centers Important reaction in the synthetic chemist’s toolbox

10. The Diels-Alder Reaction: Use in Total Synthesis cortisone prostaglandin reserpine taxol 1. J. Am. Chem. Soc. 1952, 74, 4223-4251. 2. J. Am. Chem. Soc. 1969, 91, 5675-5677. 3. J. Am. Chem. Soc. 1987, 109, 6124-6134. 4. Nature 1994,367,630-634.

11. Active Pharmaceutical Ingredients (APIs) Agrochemicals Flavors and fragrances The Diels-Alder Reaction: Highlights Funel, J. A.; Abele, S.; Industrial applications of the Diels-Alder reaction. Angew. Chem. Int. Ed. Engl. 2013, 52, 3822-3863.

12. The Diels-Alder Reaction: A [4+2] Cycloaddition

13. The Diels-Alder Reaction: A [4+2] Cycloaddition

14. The Diels-Alder Reaction: [4+2] Cycloaddition • The reaction involves 4-p electrons of the diene and 2-p electrons of the dieneophile • Converts two p-bonds into two s-bonds • Concerted reaction: all bond breaking and bond making happens simultaneously in a single step

15. The Diels-Alder Reaction: Requirements

16. The Diels-Alder Reaction: Electronics Requirements Which diene is least reactive? Which diene is most reactive? Why?

17. The Diels-Alder Reaction: Electronics Requirements Which diene is least reactive? Which diene is most reactive? Why?

18. Which dieneophile is least reactive? Which dieneophile is most reactive? Why?

19. Which dieneophile is least reactive? Which dieneophile is most reactive? Why?

20. Which of the following are expected to be good Diels-Alder dienophiles? Why?

21. Which of the following are expected to be good Diels-Alder dienophiles? Why?

22. Diene Requirement: Conjugation and s-Cis Conformation

23. Diene Requirement: Conjugation and s-Cis Conformation

24. How would you rank the reactivity of the following dienes?

25. How would you rank the reactivity of the following dienes?

26. The Diels-Alder Reaction: Mechanism

27. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

28. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

29. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

30. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

31. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

32. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

33. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

34. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry

35. The Diels-Alder Reaction: Mechanism and Syn Stereochemistry Racemic mixtures of enantiomers

36. Regioselectivity: 1,4- and 1,2-Products

37. The Diels-Alder Reaction: Pushing and Pulling Electrons via Resonance

39. The Diels-Alder Reaction: Pushing and Pulling Electrons

40. The Diels-Alder Reaction: Pushing and Pulling Electrons Can you predict the Diels-Alder Products?

41. The Diels-Alder Reaction: Pushing and Pulling Electrons Can you predict the Diels-Alder Products?

42. The Diels-Alder Reaction: The Endo Rule

43. The Diels-Alder Reaction: The Endo Rule

44. The Diels-Alder Reaction: The Endo Rule

45. The Diels-Alder Reaction: The Endo Rule

46. The Diels-Alder Reaction: Use in Total Synthesis cortisone prostaglandin reserpine taxol 1. J. Am. Chem. Soc. 1952, 74, 4223-4251. 2. J. Am. Chem. Soc. 1969, 91, 5675-5677. 3. J. Am. Chem. Soc. 1987, 109, 6124-6134. 4. Nature 1994,367,630-634.