CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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147. For reviews: (a) Moore, R. E.; Corbett, T. H.; Patterson, G. M. L.; Valeriote, F. A. Curr. Pharm. Des. 1996, 2, 317. (b) Corbett, T. H.; Valeriote, F. A.; Demchik, L.; Lowichik, N.; Polin, L.; Panchapor, C.; Pugh, S.; White, K.; Kushner, J.; Rake, J.; Wentland, M.; Golakoti, T.; Hetzel, C.; Ogino, J.; Patterson, G.; Moore, R. Invest. New Drugs 1997, 15, 207. (c) Polin, L.; Valeriote, F.; White, K.; Panchapor, C.; Pugh, S.; Knight, J.; LoRusso, P.; Hussain, M.; Liversidge, E.; Peltier, N.; Golakoti, T.; Patterson, G.; Moore, R.; Corbett, T. H. Invest. New Drugs 1997, 15, 99. (d) Shih, C.; Al-Awar, R. S.; Fray, A. H.; Martinelli, M. J.; Moher, E. D.; Norman, B. H.; Patel, V. F.; Shultz, R. M.; Toth, J. E.; Varie, D. L.; Corbett, T. H.; Moore, R. E. Anticancer Agents: Frontiers in Cancer Chemotherapy, ed. Ojima, I.; Vite, G. D.; Altmann, K. American Chemical Society, Washington, DC, 2001; Vol. 796, pp. 171. (e) Eggen, M.; Georg, G. I. Med. Res. Rev. 2002, 22, 85. (f) Tius, M. A. Tetrahedron 2002, 58, 4343. (g) Eissler, S.; Stoncius, A.; Nahrwold, M.; Sewald, N. Synthesis 2006, 3747. 148. (a) Schwartz, R. E.; Hirsch, C. F.; Sesin, D. F.; Flor, J. E.; Chartrain, M.; Fromtling, R. E.; Harris, G. H.; Salvatore, M. J.; Liesch, J. M.; Yudin, K. J. Ind. Microbiol. 1990, 5, 113. (b) Trimurtulu, G.; Ohtani, I.; Patterson, G. M. L.; Moore, R. E.; Corbett, T. H.; Valeriote, F. A.; Demchik, L. J. Am. Chem. Soc. 1994, 116, 4729. (c) Subbaraju, G. V.; Golakoti, T.; Patterson, G. M. L.; Moore, R. E. J. Nat. Prod. 1997, 60, 302. 149. (a) Kerksiek, K.; Mejillano, M.; Schwartz, R. E.; Georg, G. I.; Himes, R. FEBS Lett. 1995, 377, 59. (b) Mooberry, S. L.; Taoka, C. R.; Busquets, L. Cancer 230
Lett. 1996, 107, 53. (c) Smith, C. D.; Zhang, X. J. Biol. Chem. 1996, 271, 6192. (d) Bai, R.; Schwartz, R. E.; Kepler, J. A.; Pettit, G. R.; Hamel, E. Cancer Res. 1996, 56, 4398. (e) Panda, D.; Himes, R. H.; Moore, R. E.; Wilson, L.; Jordan, M. A. Biochemistry 1997, 36, 12948. 150. (a) Kobayashi, M.; Aoki, S.; Ohyabu, N.; Kuroso, M.; Wang, W.; Kitagawa, I. Tetrahedron Lett. 1994, 35, 7969. (b) Kobayashi, M.; Kuroso, M.; Ohyabu, N.; Wang, W.; Fujii, S.; Kitagawa, I. Chem. Pharm. Bull. 1994, 42, 2196. (c) Golakoti, T.; Ogino, J.; Heltzel, C. E.; Husebo, T. L.; Jensen, C. M.; Larsen, L. K.; Patterson, G. M. L.; Moore, R. E.; Mooberry, S. L.; Corbett, T. H.; Valeriote, F. A. J. Am. Chem. Soc. 1995, 117, 12030. (d) Koiso, Y.; Morita, K.; Kobayashi, M.; Wang, W.; Ohyabu, N.; Iwasaki, S. Chem.-Biol. Interact. 1996, 102, 183. 151. Golakoti, T.; Ogino, J.; Heltzel, C. E.; Husrebo, T. L.; Jensen, C. M.; Larsen, L. K.; Patterson, G. M. L.; Moore, R. E.; Moobery, S. L.; Corbett, T. H.; Valeriote, F. A. J. Am. Chem. Soc. 1995, 117, 12030. 152. (a) Ali, S. M.; Georg, G. I. Tetrahedron Lett. 1997, 38, 1703. (b) Eggen, M.; Georg, G. I. Bioorg. Med. Chem. Lett. 1998, 8, 3177. (c) Varie, D. L.; Brennan, J.; Briggs, B.; Cronin, J. S.; Hay, D. A.; Rieck, J. A. I.; Zmijewski, M. J. Tetrahedron Lett. 1998, 39, 8405. (d) Fray, A. H. Tetrahedron: Asymmetry 1998, 9, 2777. (e) Liang, J.; Hoard, D. W.; Khau, V. V.; Martinelli, M. J.; Moher, E. D.; Moore, R. E.; Tius, M. A. J. Org. Chem. 1999, 64, 1459. (f) Liang, J.; Moher, E. D.; Moore, R. E.; Hoard, D. W. J. Org. Chem. 2000, 65, 3143, and references cited therein. 231
Page 1:
ASYMMETRIC STRATEGIES FOR THE SYNTH
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ACKNOWLEDGEMENTS First of all, I wa
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CONTENTS SYNOPSIS LIST OF FIGURES L
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SYNOPSIS
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models (e. g. Cram’s model, Felki
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4 1d 4-(CH 3 ) 2 CH-C 6 H 4 1 : 1.5
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14. 1n C 6 H 5 CO C 6 H 5 2n 8 77 1
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imetallic systems. In all the cases
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For the benzylation reaction, the c
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O O 3 CHO i O O + OH 13a O O OH O O
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10 3.5 Ga (2.5) THF KI+LiCl 10 55 5
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multidrug-resistant (MDR) cancer ce
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directly afforded the furanose, whi
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References 1. Stephenson, G. R. Adv
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LIST OF FIGURES
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II.3.13 III.1.1 III.1.2 III.1.3 III
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IV.5.2 IV.5.3 IV.5.4 IV.5.5 1 H NMR
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Table Title Page No. II.3.1 II.3.2
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II. .11 PPREAMBLE Demand for specia
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II. .22 IINTRODUCTIION TO CHIIRALII
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The most dramatic example in this a
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H H 2 N OH COOH i PhH 2 CO O H N H
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Methods of Asymmetric Synthesis: 15
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O O O O i, ii iii iv HO HO N N OH O
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Models for Asymmetric Synthesis. 21
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If a strongly electronegative group
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enantiomeric products are formed at
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vi) The balance between chiral auxi
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IIII. .11 IINTRODUCTIION TO CHIIRAL
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Scheme II.1.2 However, availability
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Prof. R. Noyori received the Nobel
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Apart from the cinchona alkaloids,
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ligand, it assumes a tetrahedral co
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Marshall. 53 More recently, Barbero
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Various protocols have been develop
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In the absence of a sterically-bulk
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IIII. .33. . PPRESSENT WORK It is w
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[pyridinium][Sn 2 Cl 5 ] etc. can b
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RCHO 59a-j i R OH 60a-j (i) Allyl b
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Fig. II.3.2. 1 H NMR spectrum of 60
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in [bmim][BF 4 ] using sub-stoichio
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The reaction in THF was also follow
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The integration of the signal at δ
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The standard reduction potential of
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It has also been reported, 83a,b th
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IIII. .33. .33 Gaal lliuum meeddi i
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5 3.0 5.0 THF LiCl+KI c 14 d 71 6 1
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3 59d 4-(CH 3 ) 2 CH-C 6 H 4 H 60d
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Fig. II.3.8. 13 C NMR spectrum of 6
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Fig. II.3.10. 13 C NMR spectrum of
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fragmentation peak at m/z 138 (19%)
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Fig. II.3.13. 13 C NMR spectrum of
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active catalyst, as suggested for t
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1-(4-Bromophenyl)-but-3-en-1-ol 59b
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1H), 7.90-7.93 (m, 1H); 13 C NMR:
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662, 980, 1079, 1332, 1374 cm -1 .
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IIIIII. .11 DIIASSTEREOSSELECTIIVE
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cyclohexylideneglyceraldehyde (1) 3
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mixture of Zn dust, allyl or γ-sub
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Fig. III.1.2. 13 C NMR spectrum of
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Reaction with crotyl bromide: In ca
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Fig. III.1.5. 1 H NMR spectrum of 6
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The formation of the 2,3-anti addit
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To establish the C-4 configuration
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Allylation with (E) and (Z)-1-bromo
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(i) Zn, aqueous satd. NH 4 Cl, THF,
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Fig. III.1.12. 1 H NMR spectrum of
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Allylation with 1-Bromo-4-(tert)-bu
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fast and gave a significantly bette
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espectively) due to the cyclohexyli
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was treated with excess amount of b
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Fig. III.1.20. 1 H NMR spectrum of
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stereochemistry of allylation of β
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of the products were modest (48-62%
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6 1.2 In (2.0) H 2 O LiCl+ KI 14 72
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are consistent with our previous re
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III.3 EXPERIMENTAL SECTION: General
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(2R,3R)-1,2-Cyclohexylidenedioxy-5-
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for an additional 2 h, gradually br
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(m, 2H), 5.82-5.98 (m, 1H), 7.25-7.
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31.6, 32.2, 63.4, 128.8, 133.0. Ana
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23 (2R,3S,4R)-1,2-Cyclohexylidenedi
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(2R,3S,4S)-1,2-Cyclohexylidenedioxy
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(m, 1H), 3.50-4.02 (m, 5H), 4.10-4.
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and dried. Removal of solvent in va
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ine, and dried. Solvent removal und
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IIV. .11 SSYNTHESSIISS OFF ENANTIIO
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Scheme IV.1.1 The same group also d
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IV.1.3: Present work Although sever
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O O C 6 H 13 i O C 6 H 13 ii OH C 6
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Fig. IV.1.4. 1 H NMR spectrum of 10
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the unit-C contribute positively to
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tartrate, Ti(O-i-Pr) 4 , CH 2 Cl 2
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Based on this hypothesis, the alcoh
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OR 3 O R 1 R 2 NaBH 4 H H R 1 R 1 +
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(OH). Oxidative cleavage of its α-
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IIV. .33: : SSYNTHESSIISS OFF 33' '
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For the actual synthesis, (Scheme I
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IV.4: SSYNTHESSIISS OFF 22( (SS) )-
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(i) PhCHO, triethyl orthoformate, M
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O N 3 II Ph HO OH b1 N 3 Ph O O Ben
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Thus, easily accessible 1 has been
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167 and subsequent reduction gave 1
Page 223 and 224: from the appearance of 13 C NMR pea
Page 225 and 226: Fig. IV.5.2. 1 H NMR spectrum of 17
Page 227 and 228: IV.6 EXPERIMENTAL SECTION (2R,3S,4R
Page 229 and 230: As described earlier, compound 108
Page 231 and 232: 19.5, 23.8, 23.9, 25.1, 26.9, 34.6,
Page 233 and 234: 74.2, 74.4, 110.1, 116.7, 127.6, 12
Page 235 and 236: mmol) in MeOH (10 mL), work up, fol
Page 237 and 238: 7.51 (m, 3H), 7.92-8.08 (m, 2H); 13
Page 239 and 240: subsequent isolation afforded rotam
Page 241 and 242: 4.18 (t, J = 3.4 Hz, 1H), 4.75-4.84
Page 243 and 244: -4.21 (c 1.2, CHCl 3 ); IR: 3466, 1
Page 245 and 246: (3R)- 3,4-O-Cyclohexylidene-2-oxo-1
Page 247 and 248: Water and EtOAc was added to the mi
Page 249 and 250: 24 179. Yield: 1.49 g (77.5%); colo
Page 251 and 252: 24 furnished pure 183. Yield: 0.37
Page 253 and 254: 1. Wender, P. A. Chem. Rev. 1996, 9
Page 255 and 256: 17. Hanessian, S.; Maji, D. K.; Gov
Page 257 and 258: 32. For some selective references s
Page 259 and 260: 43. (a) Cleare, M. J.; Hydes, P. C.
Page 261 and 262: 54. Barbero, A.; Pulido, F. J.; Rin
Page 263 and 264: 2008, 1681. (d) Fargeas, V.; Zammat
Page 265 and 266: 72. Karodia, N.; Guise, S.; Newland
Page 267 and 268: Kaminski, J.; Millhauser, G.; Ortiz
Page 269 and 270: Böhm, V. P. W.; Reisinger, C. J. O
Page 271 and 272: 119. Wender, P. A.; Holt, D. A.; Si
Page 273: 140. (a) Chemler, S. R.; Roush, W.
Page 277 and 278: 158. Mitsuya, H.; Weinhold, K. J.;
Page 279 and 280: L.; Zugay, J. A. J. Med. Chem. 1993
Page 281 and 282: 1. Goswami, D.; Chattopadhyay, A.;
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