CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

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Mechanistic studies: For the mechanistic insight of the activating role of [bmim][Br] and the recycling of the metal, the nature of the organometallic species responsible for the reaction was probed. For this, the reactions between In (1 mmol) and allyl bromide (1 mmol) in D 2 O / THF / [bmim][Br] (3 mL) were followed by recording the 1 H NMR spectra of the aliquots of the reaction mixture over a time period of 8 h. The intensity of the NMR peak due to the allyl-indium species was quantified by comparing with that of the CH 2 Br signal. The 1 H NMR spectra of the reaction carried out in D 2 O showed the appearance of a new doublet at δ 1.63 (J = 8.4 Hz) after 10 min, at the expense of the –CH 2 Br signal at δ 3.9. However, no new olefinic resonances were observed. The intensity of the peak (δ 1.63) reached maximum (33.6%) in 25 min, and thereafter declined gradually to vanish in 2 h. Fig II.3.4 shows the 1 H NMR spectrum of the reaction between In and allyl bromide in D 2 O, recorded after 25 min of stirring. The 1 H NMR spectrum was attributed to CH 2 =CHCH 2 ─In (I). 65b The NMR investigations clearly revealed that the active In-species I produced in H 2 O is unstable and gets hydrolyzed. This was evident from the fact that the depletion of its 1 H NMR resonances (δ 1.63) was associated with an increase in the intensity of the resonances at ~ δ 3.8. This suggested the formation of allyl alcohol, which was detected earlier. 77a Thus, during allylation of an aldehyde in H 2 O, the species I reacts via two competitive routes viz. with H 2 O (leading to its decomposition) and the aldehyde. The former process prevails due to its higher rate (revealed from the 1 H NMR experiments) and the high concentration of H 2 O. This accounts for the need of the large excess the reagents (In and allyl bromide) in the allylation of aldehydes in H 2 O. 45
The reaction in THF was also followed as above. However, due to the overlapping resonances of the solvent in the region of interest (δ 1-2.5), the allylic methylene signals of the allyl-In species could not be seen. Nevertheless, the appearance of the new olefinic multiplets at δ 4.67 and at δ 4.80 after 4 h confirmed formation of CH 2 =CHCH 2 ─InBr 2 (II). 77a,65a In this case, although the allyl-In species remained stable up to 6.5 h (revealed by the NMR spectra), its formation required a long induction time. This might possibly account for the need to use the reagents in large excesses. Figure II.3.4. 1 H NMR spectrum of the reaction mixture of In and allyl bromide in D 2 O. The 1 H NMR spectra of the reaction mixtures obtained in [bmim][Br] showed a new doublet at δ 2.01 as well as new olefinic multiplets at δ 4.59 and at δ 4.78, with 46
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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
Page 35 and 36: II.3.13 III.1.1 III.1.2 III.1.3 III
Page 37 and 38: 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: in [bmim][BF 4 ] using sub-stoichio
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 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,
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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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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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