intro

1. Electrophilic reactions The electrophilic step: leads to carbocation intermediate thus, carbocation stability is key! intro

2. electrophilic C-C bond-forming steps 15.1

3. next, we can get nucleophilic addition: 15.1

4. or, carbocation intermediate can be deprotonated: an important variant - the electrophilic aromatic substitution 15.1

5. Thinking about the electrophilic attack: 15.2A

6. the thermodynamic picture: 15.2A

7. review from fall semester! Regiochemistry of electrophilic addition – two possible outcomes: it depends on C+ stability! 15.2B

8. two possible addition products 15.2B

9. reaction A has more stable intermediate – goes faster 15.2B

10. Markovnikov’s rule: when acid is added to double bond, the more substituted carbon gets the heteroatom there can be exceptions! 15.2B

11. enzymatic electrophilic additions (SAM) 15.2C

12. another example: can you rationalize the regiochemistry? 15.2C

13. regiochemistry: 15.2C

14. 15.2C

15. 15.2C

16. (we’ve already seen the hydroboration-oxidation rxn)

17. Good review – draw out mechanism for these! 15.2D

18. a way to ‘protect’ alcohols (we saw one way to protect ketones in 11.4B) more stable C+ acetal – stable to bases, nucleophiles 15.2D

19. protection example: 15.2D

20. (skip TBDMS ethers – go to section 15.3)

21. Electrophilic addition followed by elimination: 15.3

22. isomerization example: 15.3A

23. substitution example: 15.3B

24. 15.3B

25. next reaction in the pathways extends the chain: 15.3B

26. Is this SN1 or SN2? Compare to protein prenylation reaction from Chapter 9: 15.3B

27. again, F-labeling experiment was done: F substitution slows down reaction dramatically! 15.3B

28. A slightly different kind of electrophilic addition-elimination: (step 1) steps 1&2 are the targets of Roundup we saw steps 2 & 3 in Chapter 14 15.4

29. Question: is this a Michael or electrophilic addition?

30. It cannot be a Michael! 15.4

31. 15.4

32. experiment: reaction run in D2O with deoxy analog 15.4

33. 15.4

34. skip to section 2.1C supplement (aromaticity)

35. Electrophilic aromatic substitution: the MCAT-writer’s best friend (abbreviated SEAr) 15.5A

36. pi-bonds are very stable: high energy barrier for electrophilic attack! 1: electrophile needs to be extra reactive 2: carbocation intermediate needs to be stabilized 15.5A

37. C+ stabilized by EDG 15.5A

38. enzymatic example intermediate is stabilized by N! 15.5B

39. 15.5B

40. (read next two examples on your own)

41. SEAr / decarboxylation (see p. 602, top) 15.5B

42. SEAr in the lab: the Friedel-Crafts reactions alkylation – plain vanilla alkyl halide won’t cut it! We need a carbocation 15.6A

43. or, you can generate the C+ electrophile using alkene + strong acid . . .or, alcohol plus strong acid! 15.6A

44. Friedel-Crafts acylation 15.6A

45. 15.6A

46. Ring-activating/directing effects ortho-para director meta-director 15.6B

47. ring-activating, ortho-para directing substitutuents: 15.6B

48. 15.6B

49. 15.6B

50. ring-deactivating, m-directing substituents: the exception: halogens are o/p directors! 15.6B