CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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The acceleration of the reaction in [bmim][Br] suggested activation of In metal by the RTIL so that its subsequent conversion to the species II is triggered. For investigating this aspect, the 1 H NMR spectrum of the RTIL (5 mL) was recorded after incubating with In (1.0 mmol) for 0.5 h. This led to upfield shifts of its imidazole protons. The shift followed the expected trend, and was maximum (4.2 Hz) for H-2, and less (3.8 Hz) for H-4 and H-5. The same trend could also been seen for the imidazole carbons, where an upfield shift of 10 Hz for C-2 and 6 Hz for both C-4 and C-5 were noticed. Addition of allyl bromide to the above mixture restored the 1 H and 13 C NMR resonances of the imidazole moiety of the RTIL. The upfield shifts of the 1 H and 13 C NMR resonances suggested electron transfer from In to [bmim][Br], activating the In-metal surface. Earlier surface reaction with In metal has been reported. 79 The metal-mediated Barbier reaction is proposed to be mediated through radicals on metal surface 80a,b as well as metal surface activation especially in aqueous acidic media. 80c The occurrence of charge transfer (CT) in RTILs is not also unprecedented. 79b,c Although, The possibility of having free cations in ILs is quite remote, 81a the imidazolium-based ILs have remarkable ability to promote electron transfer reactions. 79b,81b-c However, the direct involvement of a metal in this process is unprecedented. Possibly the combination of In and [bmim][Br] forms ion pairs or more complex ion-aggregates such as 61 with a partially charged activated In as shown in Scheme II.3.3. H H H H Br - N + N + In N +δ In +δ N Br - C4 H 9 C4 H 9 H H 61 Scheme II.3.3 49
The standard reduction potential of [bmim][Br], measured using cyclic voltammetry (std. Calomel electrode as reference) was found to be 0.641 V. This also supported the possibility of CT between In and the RTIL. Regeneration of the RTIL on addition of allyl bromide also confirmed that the CT generated an activated In transient species. This facilitates its subsequent reaction with allyl bromide to furnish the active allylating species II. Although the allyl-In species I has been reported to be more reactive than the species II, our results revealed otherwise. This might be due to the polar nature of [bmim][Br]. The reduction potential of [bmim][Br] also suggested that In metal may got oxidized by [bmim][Br] to generate InBr 3 , which would for 62 by reaction with [bmim][Br] (Scheme II.3.4). This was isolated and characterized by comparing the 1 H and 13 C NMR spectra with those reported 82 for the analogous chloride compound, as well as from the elemental analysis data. Addition of demineralized water to the above mixture produced In(OH) 3 , which also indicated the presence of In(III) in the mixture. H H H H Br N + + InBr 3 N N + N InBr 4 C4 H 9 C4 H 9 H H 62 Scheme II.3.4 The formation of the species II and the catalytic role of In could be partially rationalized considering the reactions shown in Scheme II.3.5. In the 1st path, the reaction of allyl bromide with the ([bmim][Br]—In) species directly produced the active species II along with propene or its precursor (eq. 1). Formation of the alkene was confirmed by trapping it with Br 2 /CCl 4 to produce 1,2-dibromopropane that was characterized by 1 H NMR spectrum. The RTIL subsequently reacts with the evolved propene or most likely its 50
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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
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: The integration of the signal at δ
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 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
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fast and gave a significantly bette
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espectively) due to the cyclohexyli
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Fig. III.1.19. 13 C NMR spectrum of
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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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Fig. III.1.22. 13 C 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 +
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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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