CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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were washed with water and brine, and dried. Removal of solvent in vacuo followed by chromatography of the residue (silica gel, 5% CHCl 3 /MeOH) afforded 86. Colourless thick oil; Yield: 1.12 g (86%); IR: 3411, 3074, 1724 cm -1 ; 1 H NMR: δ 1.00 (s, 9H), 1.50 (broad s, D 2 O exchangeable, 2H), 2.66 (m, 1H), 3.0-3.35 (m, 2H), 3.8-4.1 (m, 3H), 5.21-5.29 (m, 2H), 5.43-5.47 (m, 1H), 5.77-5.88 (m, 1H), 7.09-7.16 (m, 2H), 7.25-7.38(m, 8H), 7.46- 7.61 (m, 3H), 7.98-8.02 (m, 2H); 13 C NMR: δ 19.0, 26.6, 46.7, 62.4, 63.4, 70.4, 72.0, 120.0, 127.4, 127.6, 128.4, 129.4, 129.6, 129.8, 132.9, 133.1, 133.4, 135.4, 137.5, 167.5. Anal. Calcd. for C 30 H 36 O 5 Si: C, 71.39 H, 7.19%. Found, C, 71.23; H, 7.12%. (2R,3S,4S)-1-(tert)-Butyldiphenylsilyloxy-3-Benzoyloxy-4-C-(tert)-butyldiphenylsilyl oxy-5-hexene 87. Silylation of 86 (1.0 g, 1.98 mmol) with TBDPSCl (0.60 g, 2.18 mmol) and imidazole (0.15 g, 2.18 mmol) in CH 2 Cl 2 (40 mL) followed by work up and column chromatography (silica gel, 5-15% EtOAc/hexane) afforded 87. Colourless oil; Yield: 1.12 g (80%); IR: 3450, 3074, 1726 cm -1 ; 1 H NMR: δ 1.10 (s, 18H), 1.12 (broad s, D 2 O exchangeable, 1H), 2.66-2.70 (m, 1H), 3.00-3.35 (m, 2H), 3.81-4.12 (m, 3H), 5.21-5.29 (m, 2H), 5.43-5.47 (m, 1H), 5.77-5.88 (m, 1H), 7.09-7.16 (m, 4H), 7.25-7.38 (m, 16H), 7.46-7.61 (m, 3H), 7.98-8.02 (m, 2H). Anal. Calcd. for C 46 H 54 O 5 Si 2 : C, 74.35 H, 7.32%. Found, C, 74.49; H, 7.36%. 5-(tert)-butyldiphenylsilyloxy-3-benzoyloxy-2-C-(tert)-butyldiphenylsilyloxy-2-deoxy- 1-ribofuranose 88. Ozone was bubbled for 20 min through a solution of 87 (0.50 g, 0.67 mmol) and methanolic NaOH (1.5 mL, 2.5 M) in CH 2 Cl 2 (20 mL) at -78 o C. After stirring the mixture for 3 h at the same temperature, it was diluted with CHCl 3 and water, and brought to room temperature. The organic layer was separated and the aqueous layer extracted with CHCl 3 . The combined organic extracts were washed with water and brine, 134
and dried. Removal of solvent in vacuo followed by chromatography (silica gel, 5-25% 25 CHCl 3 /MeOH) afforded 88. Colourless oil; Yield: 0.35 g (72%); [α] D +2.3 (c 1.4, CHCl 3 ); IR: 1742 cm -1 ; 1 H NMR: δ 0.97 (s, 9H), 1.1 (s, 9H), 3.40-.3.50 (m, 1H, H-2), 3.90-4.20 (m, 4H), 4.63-4.70 (m, 1H, H-4), 5.96 (dd, J = 13.7 and 2.4 Hz, 1H, H-3), 7.10- 7.90 (m, 25H); Anal. Calcd. for C 45 H 50 O 6 Si 2 : C, 72.74; H, 6.78%. Found: C, 72.96; H, 7.01%. Benzylation of aldehydes : Benzylation of aldehydes were accomplished according to the procedure described above. The products 90a-g were isolated in pure form. In case of benzylation of 1, the products 91a and 91b were isolated as a non-separable mixture. 1-Phenyl-octan-2-ol 90a. 1 H NMR: δ 1.00 (t, J = 6.2 Hz, 3H), 1.38-1.69 (m, 10H), 1.70 (broad s, 1H), 2.70-2.81 (m, 1H), 2.91-3.00 (m, 1H), 3.79-3.93 (m, 1H), 7.32-7.49 (m, 5H); 13 C NMR: δ 14.1, 22.6, 25.7, 29.3, 31.8, 36.8, 44.0, 72.7, 126.4, 128.5, 129.4, 138.6. Anal. Calcd. for C 14 H 22 O: C, 81.50; H, 10.75%. Found: C, 81.34; H, 10.49%. 1-Phenyl-undecan-2-ol 90b. 1 H NMR: δ 1.04 (t, J = 6.6 Hz, 3H), 1.42-1.62 (m, 16H), 1.91 (broad s, 1H), 2.71-2.82 (m, 1H), 2.91-3.00 (m, 1H), 3.89-3.94 (m, 1H), 7.33-7.49 (m, 5H); 13 C NMR: δ 14.1, 22.7, 25.8, 29.4, 29.7, 31.9, 36.8, 44.0, 72.7, 126.4, 128.5, 129.4, 138.7. Anal. Calcd. for C 17 H 28 O: C, 82.20; H, 11.36%. Found: C, 82.31; H, 11.24%. 1-Phenyl-pentadecan-2-ol 90c. 1 H NMR: δ 0.97 (broad t, 3H), 1.2-1.6 (m, 24H), 1.7 (bs, 1H), 2.73 (dd, j = 13.4 & 8.4 Hz, 1H), 2.93 (dd, j = 13.6 & 4.4 Hz, 1H), 3.8-3.9 (m, 1H), 7.2-7.5 (m, 5H); 13 C NMR: δ 14.1, 22.6, 25.7, 29.3, 29.6, 31.9, 36.8, 44.0, 72.6, 126.4, 128.5, 129.4, 138.6. Anal. Calcd. for C 21 H 36 O: C, 82.83; H, 11.91%. Found: C, 82.64; H, 12.14%. 135
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
Page 125 and 126: Reaction with crotyl bromide: In ca
Page 127 and 128: Fig. III.1.5. 1 H NMR spectrum of 6
Page 129 and 130: The formation of the 2,3-anti addit
Page 131 and 132: To establish the C-4 configuration
Page 133 and 134: Allylation with (E) and (Z)-1-bromo
Page 135 and 136: (i) Zn, aqueous satd. NH 4 Cl, THF,
Page 137 and 138: Fig. III.1.12. 1 H NMR spectrum of
Page 139 and 140: Allylation with 1-Bromo-4-(tert)-bu
Page 141 and 142: fast and gave a significantly bette
Page 143 and 144: espectively) due to the cyclohexyli
Page 145 and 146: Fig. III.1.19. 13 C NMR spectrum of
Page 147 and 148: was treated with excess amount of b
Page 149 and 150: Fig. III.1.20. 1 H NMR spectrum of
Page 151 and 152: Fig. III.1.22. 13 C NMR spectrum of
Page 153 and 154: stereochemistry of allylation of β
Page 155 and 156: of the products were modest (48-62%
Page 157 and 158: 6 1.2 In (2.0) H 2 O LiCl+ KI 14 72
Page 159 and 160: 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-
Page 165 and 166: for an additional 2 h, gradually br
Page 167 and 168: (m, 2H), 5.82-5.98 (m, 1H), 7.25-7.
Page 169 and 170: 31.6, 32.2, 63.4, 128.8, 133.0. Ana
Page 171 and 172: 23 (2R,3S,4R)-1,2-Cyclohexylidenedi
Page 173 and 174: (2R,3S,4S)-1,2-Cyclohexylidenedioxy
Page 175: (m, 1H), 3.50-4.02 (m, 5H), 4.10-4.
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 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
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IV.6 EXPERIMENTAL SECTION (2R,3S,4R
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As described earlier, compound 108
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19.5, 23.8, 23.9, 25.1, 26.9, 34.6,
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74.2, 74.4, 110.1, 116.7, 127.6, 12
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mmol) in MeOH (10 mL), work up, fol
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7.51 (m, 3H), 7.92-8.08 (m, 2H); 13
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subsequent isolation afforded rotam
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4.18 (t, J = 3.4 Hz, 1H), 4.75-4.84
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-4.21 (c 1.2, CHCl 3 ); IR: 3466, 1
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(3R)- 3,4-O-Cyclohexylidene-2-oxo-1
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Water and EtOAc was added to the mi
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24 179. Yield: 1.49 g (77.5%); colo
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24 furnished pure 183. Yield: 0.37
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1. Wender, P. A. Chem. Rev. 1996, 9
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17. Hanessian, S.; Maji, D. K.; Gov
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32. For some selective references s
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43. (a) Cleare, M. J.; Hydes, P. C.
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54. Barbero, A.; Pulido, F. J.; Rin
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2008, 1681. (d) Fargeas, V.; Zammat
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72. Karodia, N.; Guise, S.; Newland
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Kaminski, J.; Millhauser, G.; Ortiz
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Böhm, V. P. W.; Reisinger, C. J. O
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119. Wender, P. A.; Holt, D. A.; Si
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140. (a) Chemler, S. R.; Roush, W.
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Lett. 1996, 107, 53. (c) Smith, C.
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158. Mitsuya, H.; Weinhold, K. J.;
Page 279 and 280:
L.; Zugay, J. A. J. Med. Chem. 1993
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1. Goswami, D.; Chattopadhyay, A.;
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