CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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chromatography (silica gel, 5-10% EtOAc/hexane) afforded pure 78a (Yield 9.14g, 90%) or 78b (Yield 9.34g, 92%). 78a: light yellow oil; IR: 2956, 2856, 1665, 1249, 964 cm -1 ; 1 H NMR: δ 0.87 (t, J = 6.8 Hz, 3H), 1.22-1.41 (m, 8H), 1.97-2.07 (m, 2H), 3.92-4.04 (dd, J = 6.2 and 6.6 Hz, 2H), 5.52-5.84 (m, 2H). 13 C NMR (CDCl 3 ): δ 13.9, 22.6, 28.7, 31.6, 32.0, 45.2, 125.9, 135.9. Anal. Calcd. for C 9 H 17 Br: C, 52.70; H, 8.35. Found, C, 52.79; H, 8.12. 78b : light yellow oil; IR: 2958, 2929, 2252, 1465, 1251, 903, 733 cm -1 ; 1 H NMR: δ 0.88 (t, J = 6.4 Hz, 3H), 1.21-1.47 (m, 8H), 1.99-2.06 (m, 2H), 3.92-4.15 (m, 2H), 5.59-5.73 (m, 2H). 13 C NMR (CDCl 3 ): δ 14.0, 22.6, 27.0, 29.1, 31.6, 39.5, 125.1, 135.5. Anal. Calcd. for C 9 H 17 Br: C, 52.70; H, 8.35%. Found, C, 52.82; H, 8.47%. 1,2-Cyclohexylidenedioxy-4-vinyl-decan-3-ol 79 : As described before, the reactions between 1 and 78a or 78b were carried out using bi-metal system or Zn dust. For the Znmediated reaction, aqueous saturated NH 4 Cl was used for the activation of Zn. After the work up, the crude product, in each case was subjected to column chromatography (silica gel, 0-20 % EtOAc/Hexane) to isolate pure 79a, 79b and 79c sequentially. (2R,3R,4R)-1,2-Cyclohexylidenedioxy-4-vinyldecan-3-ol 79a : Colourless oil; [α] D 23 - 0.29 (c 1.4, CHCl 3 ); IR: 3464, 2931, 2856, 1637, 1103 cm -1 ; 1 H NMR: δ 0.84 (broad t, 3H), 1.23 (m, 10H), 1.37 (m, 2H), 1.46-1.60 (m, 8H), 1.91 (broad s, 1H), 2.13 (m, 1H), 3.44 (dd, J = 6.6, 3.2 Hz, 1H), 3.62 (t, J = 6.6 Hz, 1H), 3.9-4.1 (m, 2H), 5.0-5.2 (m, 2H), 5.4-5.8 (m, 1H); 13 C NMR: δ 14.06, 22.61, 23.78, 23.99, 25.09, 27.13, 29,21, 31.30, 31.75, 35.01, 36.39, 47.20, 65.63, 74.88, 76.37, 109.84, 116.70, 138.08. Anal. calcd. for C 18 H 32 O 3 : C, 72.93; H, 10.88%. Found, C, 72.65; H, 10.78%. 128
23 (2R,3S,4R)-1,2-Cyclohexylidenedioxy-4-vinyldecan-3-ol 79b : Colourless oil; [α] D 12.04 (c 4.6, CHCl 3 ); IR: 3476, 2931, 2857, 1639, 1103 cm -1 ; 1 H NMR: δ 0.82 (broad t, 3H), 1.24 (m, 10H), 1.38 (m, 2H), 1.5-1.7 (m, 8H), 1.95 (broad s, 1H), 2.32 (m, 1H), 3.72 (dd, J = 8.8, 3.4 Hz, 1H), 3.80-3.95 (m, 2H), 4.07-4.16 (m, 1H), 5.0-5.2 (m, 2H), 5.5-5.7 (m, 1H). 13 C NMR: δ 13.95, 22.53, 23.67, 23.84, 24.89, 26.66, 29,20, 30.33, 31.71, 34.82, 36.02, 47.52, 63.37, 72.50, 76.47, 109.01, 116.67, 138.50. Anal. calcd. for C 18 H 32 O 3 : C, 72.93; H, 10.88%. Found, C, 72.95; H, 10.67%. 23 (2R,3R,4S)-1,2-Cyclohexylidenedioxy-4-vinyldecan-3-ol 79c : Colourless oil; [α] D +17.71 (c 2.6, CHCl 3 ); IR: 3465, 2931, 2856, 1101, 913 cm -1 ; 1 H NMR: δ 0.84 (broad t, 3H), 1.25 (m, 10H), 1.38 (m, 2H), 1.56-1.66 (m, 8H), 2.19-2.38 (m, 1H), 3.68 (t, J = 4.5 Hz, 1H), 3.8-4.0 (m, 3H), 4.71 (broad s, 1H), 5.0-5.2 (m, 2H), 5.6-5.8 (m, 1H); 13 C NMR: δ 14.0, 22.6, 23.8, 24.0, 25.1, 27.1, 29,2, 31.0, 31.7, 34.8, 36.3, 46.40, 65.4, 73.9, 76.4, 109.0, 117.5, 137.9. Anal. calcd. for C 18 H 32 O 3 : C, 72.93; H, 10.88%. Found, C, 73.05; H, 10.80%. 4-(tert)-Butyldiphenylsilyloxy-2Z-buten-1-ol 81. To a cooled (0 o C) and stirred solution of 80 (5.0 g, 56.81 mmol) and imidazole (4.25 g, 62.5 mmol) in CH 2 Cl 2 (75 mL) was added TBDPSCl (17.12 g, 62.5 mmol) in CH 2 Cl 2 (25 mL). After stirring for 2.5 h (cf. TLC), the mixture was poured into water, the organic layer separated and the aqueous layer extracted with CHCl 3 . The combined organic extracts were washed with water and brine, and dried. Solvent removal in vacuo and column chromatography (silica gel, 2-10% EtOAc/hexane) of the residue afforded pure 81. Yield 14.22 g (77%); colourless oil; IR: 3450, 3397, 3063, 3028 cm -1 ; 1 H NMR: δ 1.1 (s, 9H), 1.93 (broad s, D 2 O exchangeable, 129
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
Page 119 and 120: cyclohexylideneglyceraldehyde (1) 3
Page 121 and 122: mixture of Zn dust, allyl or γ-sub
Page 123 and 124: 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 147 and 148: was treated with excess amount of b
Page 149 and 150: Fig. III.1.20. 1 H 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: 31.6, 32.2, 63.4, 128.8, 133.0. Ana
Page 173 and 174: (2R,3S,4S)-1,2-Cyclohexylidenedioxy
Page 175 and 176: (m, 1H), 3.50-4.02 (m, 5H), 4.10-4.
Page 177 and 178: 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 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
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167 and subsequent reduction gave 1
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from the appearance of 13 C NMR pea
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Fig. IV.5.2. 1 H NMR spectrum of 17
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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.;
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L.; Zugay, J. A. J. Med. Chem. 1993
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1. Goswami, D.; Chattopadhyay, A.;
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