Florida State University Libraries Electronic Theses, Treatises and Dissertations The Graduate School 2005 Synthetic Studies Towards the Total Syntheses of the Tetracyclic Diquinane Lycopodium Alkaloids Magellanine and Magellaninone Aimin Wang Follow this and additional works at the FSU Digital Library. For more information, please contact [email protected] THE FLORIDA STATE UNIVERSITY COLLEGE OF ARTS AND SCIENCES SYNTHETIC STUDIES TOWARDS THE TOTAL SYNTHESES OF THE TETRACYCLIC DIQUINANE LYCOPODIUM ALKALOIDS MAGELLANINE AND MAGELLANINONE By AIMIN WANG A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy Degree Awarded: Spring Semester, 2005 The members of the Committee approve the dissertation of Aimin Wang defended on March 29, 2005. _________________________ Marie E. Krafft Professor Directing Dissertation _________________________ Laura R. Keller Outside Committee Member _________________________ Robert A. Holton Committee Member _________________________ Martin A. Schwartz Committee Member _________________________ Kenneth A. Goldsby Committee Member The Office of Graduate Studies has verified and approved the above named committee members. ii ACKNOWLEDGMENT Finishing this dissertation turned out to be quite an adventure and I would like to thank the following people who helped along the way: Professor Marie E. Krafft, my research adviser, for her guidance and help in these years. Past and current Krafft group members, thank you all for the help and laughter in the lab. To name a few, Dr. Chitaru Hirosawa, Dr. Masaharu Sugiura, Dr. Peter Schmidt, James Wright, Moonki Seok. Florida State University and the Chemistry department for this opportunity and the International Student Center staff for their genuine help! iii TABLE OF CONTENTS LIST OF SCHEMES............................................................................................... vi LIST OF FIGURES ................................................................................................ ix LIST OF ABBREVIATIONS................................................................................ xii ABSTRACT............................................................................................................xv INTRODUCTION ....................................................................................................1 Retrosynthetic analysis....................................................................................9 PAUSON-KHAND APPROACH...........................................................................12 Pauson-Khand reaction..................................................................................12 Mechanism...........................................................................................12 Scope of the reaction............................................................................16 Regioselectivity....................................................................................19 Triquinane-type tricyclic systems........................................................21 Results and Discussion..................................................................................32 Summary and Conclusions............................................................................43 Experimental Section.....................................................................................46 PALLADIUM ASSISTED DOMINO PROCESS APPROACH ...........................57 Heck Reaction ...............................................................................................57 Mechanism...........................................................................................58 Dehydropalladation..............................................................................60 Palladium Assisted Domino Reactions .........................................................63 Intermolecular carbopalladations.........................................................64 Intramolecular carbopalladations.........................................................66 Results and Discussion..................................................................................74 Summary and Conclusions............................................................................87 Experimental Section.....................................................................................90 iv REFERENCES......................................................................................................157 BIOGRAPHICAL SKETCH ................................................................................162 v LIST OF SCHEMES Scheme Page Scheme 1. Acid-promoted Prins-pinacol reaction ....................................... 2 Scheme 2. Overman’s approach .................................................................. 3 Scheme 3. Sequential Michael reactions ..................................................... 4 Scheme 4. Paquette’s approach ................................................................... 5 Scheme 5. Oxa-di-π-methane (ODPM) rearrangement............................... 6 Scheme 6. Liao’s approach.......................................................................... 7 Scheme 7. Hoshino’s approach.................................................................... 8 Scheme 8. Pauson-Khand Approach ........................................................... 9 Scheme 9. Palladium assisted domino process approach ........................... 10 Scheme 10. Biscyclization............................................................................ 11 Scheme 11. Pauson-Khand Reaction............................................................ 12 Scheme 12. Working Pauson-Khand reaction mechanism........................... 13 Scheme 13. Interrupted Pauson-Khand Reaction......................................... 15 Scheme 14. Cis labilization .......................................................................... 15 Scheme 15. Labilization trans to an electron-donating group ...................... 16 Scheme 16. Electron deficient alkenes......................................................... 17 Scheme 17. Conjugated 1,3-diene ................................................................ 18 Scheme 18. Multicomponent cycloadditions................................................ 19 Scheme 19. Interrupted Pauson-Khand of 11 and 12 ................................... 20 Scheme 20. Regioselectivity......................................................................... 21 Scheme 21. Endo-cyclic enynes ................................................................... 21 Scheme 22. Exo-cyclic enynes ..................................................................... 22 vi Scheme 23. Tricyclic angularly fused [5.5.5] enone 17 ............................... 23 Scheme 24. Intramolecular cycloaddition of enyne 19................................. 24 Scheme 25. (+)-15-nor-pentalenene ............................................................. 25 Scheme 26. Tricyclic angularly fused [5.5.5] and [5.5.6] enones ................ 26 Scheme 27. Tricyclic angularly fused [5.6.5] and [5.6.6] enones ................ 26 Scheme 28. Tricyclic angularly fused [5.5.6] and [5.6.6] enones ................ 27 Scheme 29. Pauson-Khand reaction of enyne 22 and 23............................. 28 Scheme 30. Pauson-Khand reaction of enyne 24 ........................................ 28 Scheme 31. Pauson-Khand reaction of enyne 25, 26, 27, 28 ....................... 29 Scheme 32. Dendrobine................................................................................ 29 Scheme 33. Asymmetric synthesis of (-)-dendrobine................................... 30 Scheme 34. Tetracyclic pyrrolidine (+)-30................................................... 30 Scheme 35. Tricyclic core of nakadomarin and manzamine........................ 31 Scheme 36. α- and β-cedrene ....................................................................... 32 Scheme 37. Synthesis of 38 ......................................................................... 33 Scheme 38. Enyne 39 and 40........................................................................ 35 Scheme 39. Synthesis of 48 .......................................................................... 36 Scheme 40. Synthesis of 53 .......................................................................... 38 Scheme 41. Substrates 54-64........................................................................ 38 Scheme 42. Syntheses of 54 and 55............................................................. 39 Scheme 43. Synthesis of 56 ......................................................................... 39 Scheme 44. Synthesis of 59 ......................................................................... 40 Scheme 45. Synthesis of 60 ......................................................................... 40 Scheme 46. Synthesis of 57 ......................................................................... 41 Scheme 47. Synthesis of 58 ......................................................................... 41 Scheme 48. Syntheses of 61-64................................................................... 42 Scheme 49. Heck reaction ............................................................................ 57 Scheme 50. Mechanism................................................................................ 58 Scheme 51. Reduction .................................................................................