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Acrobat Distiller, Job 6 β-Acryloyloxysulfonyl Tethers for Intramolecular Diels-Alder Cycloaddition Reactions A dissertation submitted to Kent State University in partial fulfillment of the requirements for the degree of Doctor of Philosophy by Natasha Chumachenko November 2005 Dissertation written by Natasha Chumachenko M.S., Lviv Polytechnic Institute, Ukraine, 1984 Ph.D., Kent State University, 2005 Approved by Dr. Paul Sampson, Chair, Doctoral Dissertation Committee Dr. Roger Gregory, Members, Doctoral Dissertation Committee Dr. Alexander Seed Dr. Brett Ellman Dr. Laura Leff Accepted by Dr. Roger Gregory, Chair, Department of Chemistry Dr. John Stalvey, Dean, College of Arts and Sciences ii TABLE OF CONTENTS LIST OF SCHEMES.......................................................................................................VI LIST OF FIGURES ........................................................................................................XI LIST OF TABLES ........................................................................................................ XII ACKNOWLEDGMENTS .......................................................................................... XIII LIST OF ABBREVIATIONS AND DEFINITIONS ................................................. XV 1. INTRODUCTION......................................................................................................... 1 1.1. GENERAL ............................................................................................................... 1 1.2. CYCLOADDITION REACTIONS OF SULFONYL DIENES..............................9 1.2.1. CYCLOADDITION OF 1-SULFONYL-1,3-DIENES..................................... 9 1.2.2. CYCLOADDITION OF 2-SULFONYL-1,3-DIENES................................... 15 1.2.2.1. Synthesis and Diels-Alder dimerization of 2-sulfonyl-1,3-dienes........... 15 1.2.2.2. Diels-Alder cycloaddition reactions of 2-sulfonyl-1,3-dienes. ................ 21 1.2.2.3. Diels-Alder cycloaddition reactions of heteroatom-substituted 2-sulfonyl- 1,3-dienes .............................................................................................................. 36 1.2.3. CYCLOADDITION OF DISULFONYLATED 1,3-DIENES ....................... 41 1.3. DIELS-ALDER REACTIONS EMPLOYING DISPOSABLE TETHERS..........54 2. SYNTHESIS OF Β-HYDROXY SULFONE-BASED TETHERS FOR INTRAMOLECULAR DIELS-ALDER CYCLOADDITION REACTIONS ..........60 2.1. SYNTHESIS OF β-HYDROXY SULFONES via EPOXIDE OPENING WITH ZINC SULFINATES IN AQUEOUS MEDIA............................................................. 60 iii 2.1.1. GENERAL ...................................................................................................... 60 2.1.2. SYNTHESIS OF SIMPLE ZINC SULFINATES AND THEIR REACTIONS WITH EPOXIDES .................................................................................................... 67 2.1.3. EPOXIDE OPENING WITH ZINC (Z)-1,3-BUTADIENYL SULFINATE (195) ..........................................................................................................................72 2.2. SYNTHESIS OF β-HYDROXY SULFONES via COUPLING OF ..................... 88 SULFINATE ANIONS WITH -BROMO KETONES FOLLOWED BY REDUCTION................................................................................................................ 88 2.3. ESTERIFICATION OF β-HYDROXY SULFONES............................................ 91 3. DIELS-ALDER CYCLOADDITION REACTIONS OF Β- ACRYLOYLOXYALKYL BUTADIENYL SULFONES.........................................100 4. SOME SYNTHETIC TRANSFORMATIONS OF THE OBTAINED DIELS- ALDER CYCLOADDUCT 223D. ............................................................................... 115 5. CONCLUSIONS ....................................................................................................... 122 6. EXPERIMENTAL SECTION .................................................................................125 6.1. GENERAL ........................................................................................................... 125 6.2. SYNTHESIS OF β-HYDROXY SULFONES via EPOXIDE OPENING WITH ZINC SULFINATES IN AQUEOUS MEDIA........................................................... 128 6.2.1. SYNTHESIS OF SIMPLE ZINC SULFINATES AND THEIR REACTIONS WITH EPOXIDES .................................................................................................. 128 6.2.2. EPOXIDE OPENING WITH ZINC (Z)-1,3-BUTADIENYL SULFINATE (195) ........................................................................................................................ 139 iv 6.2.3. SYNTHESIS OF β-HYDROXY SULFONES via CONDENSATION OF SULFINATE ANION WITH -BROMO KETONES FOLLOWED BY REDUCTION.......................................................................................................... 153 6.2.4. ESTERIFICATION OF β-HYDROXY SULFONES ................................... 159 6.3. INTRAMOLECULAR DIELS-ADER CYCLOADDITION OF -ACYLOXY SULFONES 215a-d, 216a-d AND 217b,c.................................................................. 168 6.4. SOME SYNTHETIC TRANSFORMATIONS OF THE OBTAINED DIELS- ALDER CYCLOADDUCT 223d. .............................................................................. 184 7. REFERENCES.......................................................................................................... 194 v LIST OF SCHEMES Scheme 1. Synthesis and DA dimerization of 1-sulfonyl cyclopentadienes from sulfenyl chlorides. ................................................................................................................... 10 Scheme 2. Synthesis and DA dimerization of 1-sulfonyl cyclopentadienes from sulfonyl bromides .................................................................................................................... 11 Scheme 3. Synthesis of 1-sulfonyl-5,5-dimethyl-cyclopentadienes 25a-c ....................... 12 Scheme 4. Diels-Alder reactions of 1-sulfonyl-5,5-dimethyl-cyclopentadiene 25c ......... 13 Scheme 5. Diels-Alder reactions of 3-p-tolylsulfonyl-2-pyrone 31.................................. 13 Scheme 6. Diels-Alder reaction of 3-p-tolylsulfonyl-2-pyrone 31 in the presence of Yamamoto's "MAD" Lewis acid............................................................................... 14 Scheme 7. Diels-Alder reactions of 3-p-tolylsulfonyl-2-pyridones 35............................. 14 Scheme 8. Dimerization pathways of 2-sulfonyl-1,3-dienes ............................................ 16 Scheme 9. Synthesis and dimerization of 2-p-tolylsulfonyl-1,3-diene 38. ....................... 17 Scheme 10. Synthesis and dimerization of 2-phenylsulfonyl-1,3-diene 43...................... 17 Scheme 11. Synthesis and dimerization of 3-methyl-2-phenylsulfonyl-1,3-diene 48 ...... 18 Scheme 12. Synthesis of 2-sulfonyl-1,3-dienes by Julia coupling.................................... 19 Scheme 13. Backvall synthesis of 2-sulfonyl-1,3-dienes by sulfonylmercuration- elimination sequence ................................................................................................. 19 Scheme 14. Backvall synthesis of 2-sulfonyl-1,3-dienes by selenosulfonation-oxidation sequence .................................................................................................................... 19 vi Scheme 15. Synthesis and dimerization of 4-alkyl-2-sulfonyl-1,3-diene 52 by Hoffmann method....................................................................................................................... 20 Scheme 16. Dimerization of 2-acyl-4-alkyl-1,3-dienes 56 ............................................... 21 Scheme 17. Diels-Alder reactions of 2-p-tolylsulfonyl-1,3-diene 38 with electron deficient dienophiles ................................................................................................. 23 Scheme 18. Diels-Alder reactions of 2-phenylsulfonyl-1,3-diene 43............................... 24 Scheme 19. Diels-Alder reactions of 2-phenylsulfonyl-1,3-diene 52a ............................. 25 Scheme 20. Diels-Alder cycloaddition of 2-phenylsulfonyl 1,3-dienes with 1-indolyl magnesium iodide ..................................................................................................... 28 Scheme 21. Two possible mechanisms of DA cycloaddition of 2-phenylsulfonyl 1,3- dienes with 1-indolyl magnesium iodide .................................................................. 28 Scheme 22. Diels-Alder cycloaddition of 2-phenylsulfonyl 1,3-dienes with 1-indolyl magnesium iodide, substituted at C-2 or/and C3 ......................................................29 Scheme 23. Diels-Alder cycloaddition of 2-phenylsulfonyl 1,3-diene with chiral enol ethers ......................................................................................................................... 30 Scheme 24. Diels-Alder cycloaddition of 2-phenylsulfonyl 1,3-dienes with chiral enamine ..................................................................................................................... 30 Scheme 25. Diels-Alder cycloaddition of chiral 2-phenylsulfonyl-1,3-dienes with N- phenylmaleimide and phenyltriazolinedione ............................................................ 31 Scheme 26. Cross Diels-Alder reactions of 2-phenylsulfonyl-1,3-dienes and Danishefsky diene ..........................................................................................................................32 vii Scheme 27. Cross Diels-Alder reactions of 2-phenylsulfonyl-1,3-dienes and cyclopentadiene........................................................................................................
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