CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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the aldehyde 31. Finally, desilylation of 31 afforded the lactol which on oxidation produced our desired trans-oak lactone (32). 7d i-iii O O OR 1 iv OR 2 HO OH OTBDPS OBz v-vii C 4 H 9 OTBDPS OBz 28.R 1 = TBDPS, R 2 = Bz 29 30 viii,ix C 4 H 9 OTBDPS CHO x, ix C 4 H 9 O 31 32 i) TBDPSCl, Imidazole, CH 2 Cl 2 , 25 o C; ii)Me 2 S. BH 3 , hexane, NaOH-H 2 O 2 ; iii) BzCN, pyridine, CH 2 Cl 2 , 0 o C; iv) aqueous CF 3 CO 2 H, CH 2 Cl 2 ,0 o C; v) NaIO 4 ,25 o C; vi) n-C 3 H 7 PPh + 3 Br - , n-BuLi, THF, -60 o C; vii) 10% Pd-C, H 2 ,EtOH, 0 o C; viii) K 2 CO 3 , MeOH, 25 o C; ix) PCC, CH 2 Cl 2 , 25 o C; x) n BuN + F - , THF. O Scheme 11 xx
References 1. Stephenson, G. R. Advanced Asymmetric Synthesis. Chapman and Hall, 1996. 2. (a) Miller, S.J.; Blackwell, H.E.; Grubbs, R.H. J. Am. Chem. Soc. 1996, 118, 9606- 9614. (b) Loh. T.P.; Hu. Q.Y.; Ma. L.T. J. Am. Chem. Soc. 2001, 123, 2450-2451. (c) Adam. W.; Saha-Moller, C.R.; Schmidt, K.S. J. Org. Chem. 2001, 66, 7365-7371. 3. Lin, G.Q.; Li, Y-M.; Chan, A.S.C. Principles and Applications of Asymmetric Synthesis, 1st ed.; Wiley, John & Sons, 2001. 4. (a) Sui, M.; Panek, J.S. Org. Lett. 2001, 3, 2439-2442. (b) Hirashita, T.; Kamei, T.; Satake, M.; Horie, T.; Shimizu, H.; Araki, S. Org. Biomol. Chem. 2003, 1, 3799- 3803. (c) Chemler, S.R..; Roush, W.R. J. Org. Chem. 2003, 68, 1319-1333. 5. (a) Yamamoto, Y.; Asao, N. Chem Rev. 1993, 93, 2207-2293. (b) McCluskey, A. Green Chem. 1999, 167-168. (c) Fukama, T.; Lock, S.; Miyoshi, N.; Wada, M. Chem. Lett. 2002, 376-377. 6. (a) Welton. T. Chem. Rev. 1999, 99, 2071-2083. (b) Wasserscheid, P.; Kiem, W. Angew. Chem. Int. Ed. 2000, 39, 3772-3789. 7. (a) Chattopadhyay, A.; Mamdapur, V. R. J Org. Chem. 1995, 60, 585-587. (b) Chattopadhyay, A. J Org. Chem. 1996, 61, 6104-6107. 8. (a) Klemeyer, H. J.; Paquette, L. A. J Org. Chem. 1994, 59, 7924-7927. (b) Lindsay, H. A.; Salisbury, C. L.; Cordes, W.; McIntosh, M. C. Org. Lett. 2001, 3, 4007-4010. 9. (a) Sorbera, l. A.; Castaner, J.; Castaner, R. M. Drugs Future 2004, 29, 441-448. (b) Pelotier, B.; holmes, T.; Piva, O. Tetrahedron Asymmetry 2005, 16, 1513-1520. 10. (a) Barrow, R.; Hemscheidt, T.; Paik, S.;Liang, J.; Moore, R.E.; Tius, M.A. J. Am. Chem. Soc. 1995, 117, 2479-2490. (b) Shih, C.; Teicher, B.A. Curr. Pharm. Des. xxi
Page 1: ASYMMETRIC STRATEGIES FOR THE SYNTH
Page 6 and 7: ACKNOWLEDGEMENTS First of all, I wa
Page 8 and 9: CONTENTS SYNOPSIS LIST OF FIGURES L
Page 10: SYNOPSIS
Page 13 and 14: models (e. g. Cram’s model, Felki
Page 15 and 16: 4 1d 4-(CH 3 ) 2 CH-C 6 H 4 1 : 1.5
Page 17 and 18: 14. 1n C 6 H 5 CO C 6 H 5 2n 8 77 1
Page 19 and 20: imetallic systems. In all the cases
Page 21 and 22: For the benzylation reaction, the c
Page 23 and 24: O O 3 CHO i O O + OH 13a O O OH O O
Page 25 and 26: 10 3.5 Ga (2.5) THF KI+LiCl 10 55 5
Page 27 and 28: multidrug-resistant (MDR) cancer ce
Page 29: directly afforded the furanose, whi
Page 33 and 34: LIST OF FIGURES
Page 35 and 36: II.3.13 III.1.1 III.1.2 III.1.3 III
Page 37 and 38: IV.5.2 IV.5.3 IV.5.4 IV.5.5 1 H NMR
Page 39 and 40: Table Title Page No. II.3.1 II.3.2
Page 41 and 42: II. .11 PPREAMBLE Demand for specia
Page 43 and 44: II. .22 IINTRODUCTIION TO CHIIRALII
Page 45 and 46: The most dramatic example in this a
Page 47 and 48: H H 2 N OH COOH i PhH 2 CO O H N H
Page 49 and 50: Methods of Asymmetric Synthesis: 15
Page 51 and 52: O O O O i, ii iii iv HO HO N N OH O
Page 53 and 54: Models for Asymmetric Synthesis. 21
Page 55 and 56: If a strongly electronegative group
Page 57 and 58: enantiomeric products are formed at
Page 59 and 60: vi) The balance between chiral auxi
Page 61 and 62: IIII. .11 IINTRODUCTIION TO CHIIRAL
Page 63 and 64: Scheme II.1.2 However, availability
Page 65 and 66: Prof. R. Noyori received the Nobel
Page 67 and 68: Apart from the cinchona alkaloids,
Page 69 and 70: ligand, it assumes a tetrahedral co
Page 71 and 72: Marshall. 53 More recently, Barbero
Page 73 and 74: Various protocols have been develop
Page 75 and 76: In the absence of a sterically-bulk
Page 77 and 78: IIII. .33. . PPRESSENT WORK It is w
Page 79 and 80: [pyridinium][Sn 2 Cl 5 ] etc. can b
Page 81 and 82:
RCHO 59a-j i R OH 60a-j (i) Allyl b
Page 83 and 84:
Fig. II.3.2. 1 H NMR spectrum of 60
Page 85 and 86:
in [bmim][BF 4 ] using sub-stoichio
Page 87 and 88:
The reaction in THF was also follow
Page 89 and 90:
The integration of the signal at δ
Page 91 and 92:
The standard reduction potential of
Page 93 and 94:
It has also been reported, 83a,b th
Page 95 and 96:
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
Page 103 and 104:
Fig. II.3.10. 13 C NMR spectrum of
Page 105 and 106:
fragmentation peak at m/z 138 (19%)
Page 107 and 108:
Fig. II.3.13. 13 C NMR spectrum of
Page 109 and 110:
active catalyst, as suggested for t
Page 111 and 112:
1-(4-Bromophenyl)-but-3-en-1-ol 59b
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1H), 7.90-7.93 (m, 1H); 13 C NMR:
Page 115 and 116:
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
Page 125 and 126:
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
Page 139 and 140:
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
Page 145 and 146:
Page 147 and 148:
was treated with excess amount of b
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Fig. III.1.20. 1 H NMR spectrum of
Page 151 and 152:
Page 153 and 154:
stereochemistry of allylation of β
Page 155 and 156:
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
Page 161 and 162:
III.3 EXPERIMENTAL SECTION: General
Page 163 and 164:
(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
Page 179 and 180:
ine, and dried. Solvent removal und
Page 181 and 182:
IIV. .11 SSYNTHESSIISS OFF ENANTIIO
Page 183 and 184:
Scheme IV.1.1 The same group also d
Page 185 and 186:
IV.1.3: Present work Although sever
Page 187 and 188:
O O C 6 H 13 i O C 6 H 13 ii OH C 6
Page 189 and 190:
Fig. IV.1.4. 1 H NMR spectrum of 10
Page 191 and 192:
the unit-C contribute positively to
Page 193 and 194:
tartrate, Ti(O-i-Pr) 4 , CH 2 Cl 2
Page 195 and 196:
Based on this hypothesis, the alcoh
Page 197 and 198:
OR 3 O R 1 R 2 NaBH 4 H H R 1 R 1 +
Page 199 and 200:
(OH). Oxidative cleavage of its α-
Page 201 and 202:
Page 203 and 204:
Page 205 and 206:
IIV. .33: : SSYNTHESSIISS OFF 33' '
Page 207 and 208:
For the actual synthesis, (Scheme I
Page 209 and 210:
Page 211 and 212:
IV.4: SSYNTHESSIISS OFF 22( (SS) )-
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(i) PhCHO, triethyl orthoformate, M
Page 215 and 216:
O N 3 II Ph HO OH b1 N 3 Ph O O Ben
Page 217 and 218:
Page 219 and 220:
Thus, easily accessible 1 has been
Page 221 and 222:
167 and subsequent reduction gave 1
Page 223 and 224:
from the appearance of 13 C NMR pea
Page 225 and 226:
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
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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 and 274:
140. (a) Chemler, S. R.; Roush, W.
Page 275 and 276:
Lett. 1996, 107, 53. (c) Smith, C.
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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