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intro

Eliminations (to form double bond) Addition (to double bond). Also in this chapter: the electron-sink coenzymes thiamine and pyridoxal. intro. We’re used to seeing a nucleophile attack a carbonyl carbon:. . . .but the b -carbon of a - b unsaturated carbonyl is also an electrophile. 14.1A.

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intro

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  1. Eliminations (to form double bond) Addition (to double bond) Also in this chapter: the electron-sink coenzymes thiamine and pyridoxal intro

  2. We’re used to seeing a nucleophile attack a carbonyl carbon: . . .but the b-carbon of a-b unsaturated carbonyl is also an electrophile 14.1A

  3. Michael (conjugated) addition: The reverse: E1cb elimination 14.1A

  4. E1 and E2 mechanisms:

  5. . . But most biological eliminations are E1cb, not E1 or E2! 14.1A

  6. Note: next chapter, we’ll study electrophilic additions: 14.1A

  7. Stereochemistry of alkene addition: (review: hydroboration-oxidation catalytic hydrogenation addition of Br2) A syn addition: 14.1B

  8. 14.1B

  9. Eliminations are also syn or anti: Differences between synthetic and degradative directions - common theme! Important for regulation 14.1B

  10. skip 14.1C

  11. E1cb can occur with enamine intermediate: 14.1D

  12. Pro-chiral ‘arms’ on citrate How does this happen? 14.1D

  13. Answer: molecule flips in the active site! 14.1D

  14. Laboratory aldol reactions often are followed by dehydration (E1cb) Robinson annulation: Michael addition, ring-forming aldol, dehydration) 14.1D

  15. Double bond isomerization via Michael addition 14.2A

  16. Reaction requires glutathione 14.2A

  17. skip next fig (organometalic Michael additions) go to 14.2B

  18. Nucleophilic aromatic substitution 14.2B

  19. Can also occur para to EWG 14.2B

  20. Example: ‘tagging’ the N-terminus of proteins/peptides Biosynthesis of purines DNA/RNA bases 14.2B

  21. E2 and E1 eliminations 14.3

  22. Competition between SN and E 14.3A

  23. Primary electrophile - SN 14.3A

  24. 2o electrophile – SN vs E competition Weak base, more likely to act as nucleophile Strong, hindered base favors elimination 14.3A (recall – Williamson ether synthesis)

  25. Solvolysis of tertiary electrophile leads to mix of SN and E products 14.3A

  26. Regiochemistry, stereochemistry of eliminations trans> cis more substituted > less substituted 14.3A

  27. skip Hoffman, Cope reactions go to 14.3B (p. 541 middle)

  28. In reality, E reactions can be hybrid between E1 and E2 14.3B

  29. Biochemical E1/E2 reactions - notice, not adjacent to EWG 14.3B

  30. Conjugated E1-like elimination 14.3B

  31. Combination decarboxylation / elimination 14.3B

  32. ‘Electron sink’ coenzymes 14.4

  33. PLP-dependent reactions common in amino acid metabolism - Schiff base linkages 14.4A

  34. PLP-dependent a.a. racemization 14.4B

  35. Notice: PLP plays role of ‘electron sink’ 14.4B

  36. 14.4B

  37. PLP-dependent decarboxylation amino acids can racemize without PLP – can they decarboxylate without PLP? 14.4C

  38. PLP-dependent retro-aldol 14.4D

  39. Transaminase reactions: as part ammonia elimination, N atoms from amino acids are transferred to Glu 14.4E

  40. part 1: ammonia transferred to coenzyme 14.4E

  41. next, ammonia is transferred to a-ketoglutarate (exact reverse of the previous step) (you draw the mechanism in E14.5) 14.4E

  42. Beta elimination: (degradation of serine) 14.4F

  43. 14.4F

  44. B-substitution: elim followed by addition 14.4F

  45. synthesis of cysteine from serine is a good example – first, make the OH a better LG: 14.4F

  46. elimination: addition: 14.4F

  47. gamma-eliminations/substitutions: 14.4G

  48. 14.4G

  49. gamma substitution an example: 14.4G

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