Lecture9:123.702

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Here because I love the use of radicals in synthesis (and yes, this lecture includes a quick re-cap of radical chemistry).

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Lecture9:123.702

  1. 1. hirsutene LECTURE NINE N gareth j rowlands ©Axpd@en.wikipedia
  2. 2. H H H hirsutene J. Am. Chem. Soc., 1985, 107, 1448 & Tetrahedron, 1985, 41, 3943 ©AJC1@flickr
  3. 3. O Bu3SnH, AIBN O 40% I O O H Org. Biomol. Chem., 2007, 5, 1776 multiple-bond for ming steps ©tallkev@flickr
  4. 4. O Bu3SnH, O AIBN O 40% I O O O O O O O H O O multiple-bond for ming steps ©tallkev@flickr
  5. 5. ✓ radicals neutral conditions functional group tolerance rarely solvated (small) highly reactive
  6. 6. ✗ radicals unselective(?) unpredictable highly reactive misunderstood
  7. 7. 3 radical reactions O Bu3SnH AIBN R 1 R 2 heat O Br 1 2 R R
  8. 8. 1. initiation N CN 2x NC N NC N N H SnBu3 SnBu3 NC NC H
  9. 9. 1. initiation N CN 2x NC N NC N N H SnBu3 SnBu3 NC NC H
  10. 10. 2. propagation Bu3Sn Br Bu3Sn Br O O R1 R2 R1 R2 O O H SnBu3 SnBu3 R1 R2 R1 R2 H
  11. 11. 2. propagation Bu3Sn Br Bu3Sn Br O O R1 R2 R1 R2 O O H SnBu3 SnBu3 R1 R2 R1 R2 H
  12. 12. 2. propagation Bu3Sn Br Bu3Sn Br O O R1 R2 R1 R2 O O H SnBu3 SnBu3 R1 R2 R1 R2 H chain carrier
  13. 13. 3. termination O O R1 R2 R1 R2 SnBu3 SnBu3
  14. 14. ©gonzales2010@flickr problem tin is another lecture toxic course
  15. 15. of retrosynthesis hirsutene 5-exo-dig radical H cyclisation H H H H H 5-exo-trig radical cyclisation I H H H H H H H radical cascade
  16. 16. simplificatio n
  17. 17. of retrosynthesis hirsutene C–C bond I formation I I H H H H FGI PGO I O FGI O OH OH H H H H
  18. 18. of retrosynthesis hirsutene C–C bond I formation I I H H H H FGI PGO I O FGI O OH OH H H H H
  19. 19. of retrosynthesis hirsutene C–C bond I formation I I H H H H FGI PGO I O FGI O OH OH H H H H
  20. 20. of retrosynthesis hirsutene C–C bond PGO formation PGO O O OH OH H H H
  21. 21. of retrosynthesis hirsutene O SN2 O OH OH ≡ X H H
  22. 22. of retrosynthesis hirsutene O SN' O O OH ≡ H H
  23. 23. the synthes is ©deqalb@flickr
  24. 24. O O 1. NaBH4, CeCl3 2. Ac2O, Et3N O LDA tBuMe2SiCl OTBS of synthesis O hirsutene
  25. 25. Luche reduction H H H H H B H B CeLn O H CeLn H δ+ O tethered hardness
  26. 26. how would you achieve enantioselectivity? ©youngrobv (Rob & Ale)@flickr
  27. 27. Ireland -Claisen rearrangement OTBS CHCl3 reflux O O OTBS H
  28. 28. O O H H Δ H H TBSO TBSO ≡ H H O Ireland -Claisen OTBS rearrangement
  29. 29. of synthesis bicyclic lactone 1. PhSeCl O 2. H2O2 O O OTBS 62% from H acetate H
  30. 30. Ph H Se H O O OTBS OTBS PhSe lactonisation O O H
  31. 31. Ph PhSe O Se O O O H O H H H O elimination O H
  32. 32. of synthesis hirsutene O O Br Li naphthalenide then OTHP CuBr•SMe2 CO2H O 50-75% H O H H
  33. 33. of synthesis hirsutene HO OTHP 1. PPTS 2. LiAlH4 OH CO2H H 64% H H H 1. (CF3SO2)2O, pyr 2. n-Bu4NI 64% I I 1. nuc 2. CsF I 78% H H H H Me3Si Li
  34. 34. radical cascade I n-Bu3SnH, AIBN 5-exo-trig H PhH, reflux cyclisation 80% H H H H H H 5-exo-dig cyclisation H Bu3Sn H H H H H H H
  35. 35. of power radical cascades ©ǝoɾoqɹnʇ@flickr

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