Lecture2: 123.702

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More substrate control, including allylic strain and directed reactions.

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Lecture2: 123.702

  1. 1. LECTURE TWO substrate control gareth j rowlands ©fensterbme@flickr
  2. 2. acyclic substrate control O O Me m-CPBA Me Me Me SiMe2Ph Me SiMe2Ph Me SiMe2Ph >95% <5% Me Me O O m-CPBA Me Me Me Me SiMe2Ph SiMe2Ph SiMe2Ph 61% 39% epoxidation
  3. 3. no in change ©e-magic@flickr stereocentre
  4. 4. 1,3) allylic (A Me H strain Me Me H H Me H H Me Me H Me Me Me H disfavoured
  5. 5. 1,3) allylic (A Me H strain Me Me H H Me H H Me Me H Me Me Me H disfavoured
  6. 6. 1,3) allylic (A Me H strain Me H H Me H H Me H H H Me Me H little difference
  7. 7. 1,3) allylic (A Me H strain Me H H Me H H Me H H H Me Me H little difference
  8. 8. acyclic Me m-CPBA O Me substrate control Me SiMe2Ph Me SiMe2Ph >95% "O " Me Ph Me Ph O X H H Si Me H H Si Me Me H Me H Me Me
  9. 9. acyclic Me m-CPBA O Me substrate control Me SiMe2Ph Me SiMe2Ph >95% "O " Me Ph Me Ph O X H H Si Me H H Si Me Me H Me H Me Me
  10. 10. acyclic Me m-CPBA O Me substrate control Me SiMe2Ph Me SiMe2Ph >95% Me Ph Me Ph H H Si Me H H Si Me Me H Me OH Me Me "O "
  11. 11. acyclic Me Me m-CPBA Me O Me Me O Me substrate SiMe2Ph SiMe2Ph SiMe2Ph 61% 39% control Ph Me Ph Me Me H Si Me Me H Si Me H H H OH Me Me Me Me m-CPBA attacks least hindered face H SiMe2Ph O Me H H Me H H H Me H Me Si Me Si Me Ph Me Ph Me
  12. 12. acyclic substrate control S H R preferred L R1 approach S H L S H L R 1 R 1 R L H 3 S 3 R1 R1 R1 destabilised by repulsion favoured between C-1 & C-3 substituents known as A(1,3) strain
  13. 13. other examples of substrate control Me Bu OEt i. LDA Me O Bu OEt ii. MeI 83% Me O Me Bu OEt Me O 27%
  14. 14. 1,3) allylic (A i. LDA Me Bu OEt ii. MeI Bu OEt Me O strain Me O I Me Me H Me OEt Me OEt H O O H Li H Bu Bu favoured conformation
  15. 15. 1,3) allylic (A strain S H O LDA S H OEt S H OLi L OEt L OLi L OEt ≡ ≡ preferred preferred approach approach O S H S H S H E OEt OLi L OEt L L E H OLi OEt
  16. 16. other examples of substrate control H Me Me H Me H Me H2O2 H Me H Me BH3 NaOH O OBn O H2B OBn O OH OBn 74% de O O H CH2OBn H CH2OBn H Me H Me H2B H Me Me 1,3) allylic (A H2B H strain
  17. 17. 1,3) allylic (A strain H2B H Me H H BH2 O Me H OBn Me H BnO H O Me favoured
  18. 18. H OH O H OH O Et H O H O OH O H O O HO monensi,n60&262 , 101 2979 J. Am. Chem. Soc, 1 ©AJC1@flickr
  19. 19. acyclic O Et substrate O H HO H O H O H H control O O O HO OH OH i. BH3 H Me Me ii. H2O2 H Me H Me NaOH 74% de O OBn O OH OBn OH i. BH3 OH H Me H Me ii. H2O2 H Me H Me NaOH Me 85% de Me H O OMe OH O OMe
  20. 20. directed reactions
  21. 21. normal OAc epoxidation O OAc mCPBA 63% OAc O 37%
  22. 22. reason... OAc H "O "
  23. 23. directed OH epoxidation O OH mCPBA 8% OH O 92%
  24. 24. reason... Ar O O O H H O H
  25. 25. acyclic directed epoxidation O Me Me Me H OH Me Me m-CPBA 95 O Me H OH Me Me Me H OH 5
  26. 26. acyclic Me Me m-CPBA Me O Me directed Me H OH Me H OH epoxidation Ar O O O Me H OH O H H Me H Me H O Me H Me Me 1,3) allylic (A strain
  27. 27. acyclic Me Me m-CPBA Me O Me directed Me H OH Me H OH epoxidation 120° OH Me H Me H Me 1,3) favoured allylic (A strain
  28. 28. acyclic Me Me m-CPBA Me O Me directed Me H OH Me H OH epoxidation Me H H Me Me H O O O H O Ar disfavoured allylic (A 1,3) strain
  29. 29. acyclic directed Me epoxidation Me O Me t-BuO2H OH VO(acac)2 19 Me Me H OH Me O OH 1
  30. 30. how why no C3 substituent
  31. 31. R 50° HO R R R R R HO H R H R 50° 1,2) (A strain
  32. 32. Me t-Bu O L H V O H O L H Me H Me O L O Me V H O L t-Bu H favoured 1,2) (A strain
  33. 33. myc,i1n323 oleaen.do1996, 118 1 h m Soc, J. Am. C O O OH O O O NMe2 H OH O O H O O OH ©Microbiology 148, 405 (2002)
  34. 34. O O Ph O OH NMe 2 O O O O OH OH OTIPS O O H OH O O H O O N Me O Me Me Me Me Me OH Bn VO(acac)2 t-BuOOH 91% 100% de Ph O O O O OH OH OTIPS O N Me Me Me Me O Me Me Bn
  35. 35. H t-Bu O L H V O R2 O L H R1 versus H R1 O L O H V H O L t-Bu R2 favoured 1,2) (A strain
  36. 36. OH O H HO O H Et CO2H Et O OH Et alocid8,A0, 2933 las c, 197 10 J. Am. Chem. So
  37. 37. long range directed OH O H epoxidation HO CO2H Et H O Et O OH Et Et Et OH MeO t-BuO2H VO(acac)2 dr = 8:1 Et H O AcOH Et Ar O OH Et 75% OH Et MeO
  38. 38. cyclic transition state Et R H Ar H L O V t-Bu O O L
  39. 39. other directed reactions O O Ir PF6 Py PCy3 N N H2 dr = 99:1 H H

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