CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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Fig. III.1.4. 13 C NMR spectrum of 68b Due to large values of ΔE 0 Zn-Cu (1.098 V), reduction of Cu(II) by Zn was highly exothermic, requiring the reaction mixture to be cooled (0 o C) during the addition of Zn dust. In comparison, the reduction of Co(II) was slow. In general, the Co-mediated reactions required longer time to obtain good yield. Interestingly, the Fe-mediated reaction was complete within few minutes. In view of the heterogeneity of the reaction mixtures, the metal salts and Zn dust were used in excess. To compensate for the evaporative loss of the volatile allyl bromide, it was also used in excess. (i( ii) ) Reaction of aldehyde 1 with γγ- -SSuubbsst ti iit tuut teedd allylic bromide Different allylic bromides with varied γ-substitutions (viz. CH 3 , C 6 H 13 and CH 2 OTBDPS) have been reacted with 1, and these are discussed in the following section. 82
Reaction with crotyl bromide: In case of crotylation of 1 (Scheme III.1.3), all these four low valent metals (Cu, Co, Fe and Sn) were found to be successful mediators. 111 Of them, Fe- and Sn-mediated reactions took place faster compared to Luche’s procedure 3b (entries 1, 3 and 5, Table III.1.2); whereas the reactions with Cu and Co metals were sluggish (entries 2 and 4, Table III.1.2). All the reactions yielded two diastereomers (69b and 69c) as the major products that were chromatographically isolable in homochiral forms. The other diastereisomer 69a was produced in minor amounts, whereas the syn, syn-isomer was not formed at all. As usual, the ratio of 69a, 69b and 69c in each reaction was determined by their actual isolation by column chromatography. O O O O i O + + O CHO crotyl OH bromide OH 1 69a 69b O O OH 69c (i) Zn, aqueous satd. NH 4 Cl, THF, 25 o C; or CuCl 2 , 2H 2 O, Zn, THF, 0 o C-25 o C; or FeCl 3 , Zn, THF, 10 o C-25 o C; or CoCl 2 , 8H 2 O, Zn, THF, 10 o C-25 o C; or Zn, SnCl 2 .2H 2 O, THF, 10 o C-25 o C. Scheme III.1.3 Table III.1.2: Course of crotylation of 1 using the bi-metallic strategy a Entry Reagents 1 : bromide : Time Yield b Products ratio c metal : metal salt (%) (69a : 69b: 69c) 1 Zn/ Aq. Satd. NH 4 Cl 1 : 3.0 : 3.5 : --- 5 h 74 2.4 : 32.5 : 65.1 2 Zn/ CoCl 2 , 6H 2 O 1 : 3.5 : 2.5 : 2.0 24 h 77.8 3.8 : 47.5 : 48.7 3 Zn/ FeCl 3 1 : 3.0 : 2.0 : 2.0 10 min 86.9 1.5 : 48.4 : 50.1 83
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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
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
Page 97 and 98: 5 3.0 5.0 THF LiCl+KI c 14 d 71 6 1
Page 99 and 100: 3 59d 4-(CH 3 ) 2 CH-C 6 H 4 H 60d
Page 101 and 102: 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
Page 113 and 114: 1H), 7.90-7.93 (m, 1H); 13 C NMR:
Page 115 and 116: 662, 980, 1079, 1332, 1374 cm -1 .
Page 117 and 118: IIIIII. .11 DIIASSTEREOSSELECTIIVE
Page 119 and 120: cyclohexylideneglyceraldehyde (1) 3
Page 121 and 122: mixture of Zn dust, allyl or γ-sub
Page 123: Fig. III.1.2. 13 C NMR spectrum of
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
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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
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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.;
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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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