CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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organic layer was separated and the aqueous layer extracted with EtOAc (20 mL). The combined organic extracts were washed successively with H 2 O and brine, and dried. Removal of solvent under reduced pressure and column chromatography (silica gel, 0-5% EtOAc/hexane) of the residue afforded pure 181. Yield: 0.760 g (71.8%); colourless oil; [ 24 α] D +17.2 (c 1.64, CHCl3 ); IR: 1720 cm -1 ; 1 H NMR: δ 0.74 (t, J = 7.6 Hz, 3H), 1.01 (d, J = 6.8 Hz, 3H), 1.09 (s, 9H), 1.44-1.62 (m, 2H), 1.62-1.88 (m, 3H), 4.23-4.30 (m, 2H), 4.35-4.42 (m, 1H), 5.29-5.45 (m, 2H), 7.33-7.48 (m, 9H), 7.66-7.71 (m, 4H), 8.00-8.05 (m, 2H); 13 C NMR: δ 13.7, 14.2, 19.2, 20.9, 26.8, 31.1, 37.0, 63.2, 72.4, 127.1, 127.3, 128.1, 128.3, 128.9, 129.2, 129.3, 130.3, 132.6, 132.8, 134.1, 135.7, 135.8, 166.4. Anal. Calcd. for C 32 H 40 O 3 Si: C, 76.75; H, 8.05%. Found: C, 76.98; H, 7.86%. (3S,4S)- 3-Methyl-4-O-tert-butyldiphenylsilyl-octan-1,4-diol 183. A mixture of 181 (0.70 g, 1.40 mmol) and 10% Pd-C (0.03 g) in EtOH (10mL) was magnetically stirred under a positive pressure of H 2 gas. After stirring for ~8 h, the mixture was diluted with Et 2 O (15 ml), and the supernatant was passed through a 5 cm pad of silica gel. Removal of 24 solvent under reduced pressure afforded crude 182 in almost quantitative yield. [α] D + 12.6 (c 1.2, CHCl3); colourless oil; IR: 1722 cm -1 ; 1 H NMR: δ 0.71 (t, J = 6.6 Hz, 3H), 1.05 (s merged with d, 12H), 1.10-1.14 (m, 2H), 1.25-1.35 (m, 2H), 1.37-1.40 (m, 1H), 1.79-1.92 (m, 4H), 3.56-3.63 (m, 1H), 4.17-4.31 (m, 2H), 7.32-7.44 (m, 9H), 7.63-7.94 (m, 4H), 7.95-7.98 (m, 2H); 13 C NMR: δ 13.7, 15.2, 19.4, 22.4, 26.9, 27.8, 30.6, 32.3, 34.6, 63.4, 76.8, 127.1, 127.2, 128.1, 129.2, 129.3, 130.2, 132.6, 134.5, 135.8, 166.4. Hydrolysis of 182 (0.60 g, 1.19 mmol) with K 2 CO 3 (0.42 g, 2.98 mmol) in MeOH (5 mL), usual work up and column chromatography (silica gel, 0-10% EtOAc/hexane) 207
24 furnished pure 183. Yield: 0.37 g (78.1%); colourless oil; [α] D + 4.6 (c 1.4, CHCl3 ); IR: 3471 cm -1 ; 1 H NMR: δ 0.76 (t, J = 3.2 Hz, 3H), 0.94 (d, J = 6.8 Hz, 3H), 1.08 (m merged with s, 13H), 1.41-1.46 (m, 4H), 1.50-1.54 (m, 1H), 1.97 (broad s, 1H), 3.50-3.58 (m, 3H), 7.37-7.44 (m, 6H), 7.68-7.73 (m, 4H); 13 C NMR: δ 13.9, 15.5, 19.5, 22.5, 27.1, 28.0, 32.6, 34.3, 34.5, 60.6, 77.4, 127.3, 127.4, 129.4, 129.5, 124.1,134.5, 136.0. Anal. Calcd. for C 25 H 38 O 2 Si: C, 75.32; H, 9.61%. Found: C, 75.11; H, 9.77%. trans-Oak lactone VII: Oxidation of 183 (0.350 g, 0.88 mmol) with PCC (0.218 g, 1.49 mmol) and NaOAc (0.041 mg, 0.50 mmol) in CH 2 Cl 2 (30 mL), and work-up followed by removal of solvent in vacuo yielded crude aldehyde (0.310 g). This was desilylated with Bu 4 NF (1.3 mL, 1.3 mmol, 1 M in THF) in THF (10 mL) at 0 °C. Usual work-up and removal of solvent in vacuo yielded relatively unstable lactol 184 (0.080 g), which on oxidation with PCC (0.185 g, 0.860 mmol) in CH 2 Cl 2 (10 mL), followed by usual work-up and colum chromatography (silica gel, 0-15 % EtOAc/hexane) afforded pure VII. Yield: 24 0.065 g (47.7% overall yield in three steps); colourless oil; [α] D + 93.5 (c 0.25, CHCl 3) [lit. 36e 24 [α] D + 93 (c 0.2, CHCl 3)]; 1 H NMR: δ 0.91 (t, J = 7.2 Hz, 3H), 1.02 (d, J = 6.8 Hz, 3H), 1.19-1.65 (m, 6H), 2.16-2.21 (m, 2H), 2.62-2.71 (m. 1H), 3.96-4.02 (m, 1H); 13 C NMR: δ 14.3, 17.2, 22.7, 27.5, 33.8, 36.0, 37.9, 87.6, 176.7. 208
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 +
Page 199 and 200: (OH). Oxidative cleavage of its α-
Page 201 and 202: Fig. IV.2.2. 1 H NMR spectrum of 13
Page 205 and 206: IIV. .33: : SSYNTHESSIISS OFF 33' '
Page 207 and 208: For the actual synthesis, (Scheme I
Page 211 and 212: IV.4: SSYNTHESSIISS OFF 22( (SS) )-
Page 213 and 214: (i) PhCHO, triethyl orthoformate, M
Page 215 and 216: O N 3 II Ph HO OH b1 N 3 Ph O O Ben
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 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: 24 179. Yield: 1.49 g (77.5%); colo
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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