CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

More documents

Recommendations

Info

IIIIII. .22 METAL DEPPENDENT MODULATIION OFF DIIASSTEREOSSELECTIIVIITY IIN THE BARBIIER TYPPE ALLYLATIION/ /CROTYLATIION For the past decade, our group has established the aldehyde 1 as a versatile chiral template for carrying out different asymmetric transformations. The homoallyl alcohol diastereomers 68 and 69 contain several stereogenic centres and are highly functionalized for subsequent chemo- and enantio-selective reactions. In particular, the alkene functions in these are amenable to (i) oxidative degradation to aldehyde/acids, 111,130 (ii) stereoselective epoxidation, (iii) different types of metathesis reactions etc. Many of these methodologies have been used in this investigation for the synthesis of a large number of bioactive compounds and some of them have been published. The detailed synthetic procedures will be discussed in chapter IV. The previous deliberation on allylation of 1 revealed moderate to good diastereoselectivity, which is of significance when the different diastereomers are required for the syntheses of the target compounds. Nevertheless, improvement of the diastereoselectivity of such a reaction is highly desirable. The influence of the substrate and its substituents as well as the influence of the solvent on the course of the metal mediated Barbier reaction was previously reported. 55a However, the dependence of the stereochemical outcome of such a Barbier reaction on the metal as well as on the halide used has been rarely studied. 131 This prompted us to look into the metal dependent modulation of stereoselectivity in Barbier type reactions. IIIIII. .22. .11 PPrreesseennt t Woorrkk The initial motivation for the present work stems from our own results with the bimetallic system and the previous observation by Rübsam et. al. 131 that the 110
stereochemistry of allylation of β-hydroxy-α-aminoaldehydes could be tuned by changing the metals. Hence for the present work, we surveyed a range of pure metals viz. In, Ga and Bi for the allylation of 1 (Scheme III.2.1) was performed with different in different media e.g. THF, H 2 O and a room temperature ionic liquid (RTIL), and the results are presented in Table III.2.1. i allyl bromide O O OH + O O OH O O CHO 68a 68b 1 i O O R + O O R + O O R OH OH OH 69a 69b 69c R = CH 3 , C 6 H 13 (i) Metal, Solvent, 25 o C. Scheme III.2.1 The choice of group 13 elements, In and Ga, was mainly based on their stability towards air/moisture and also their non-toxicity 66a,132 (discussed previously in Chapter II). Bismuth is also attractive as a reagent for the reductive allylation of carbonyl compounds, since it is also non-toxic and low-priced. 133 Earlier, Bi mediated allylation has been performed in DMF, 134 and also in H 2 O. 135 In this study, we have used Bi metal for allylation of aldehyde 1 in different solvents viz. THF, H 2 O and a room temperature ionic liquid (RTIL). Amongst different RTILs, [bmim][Br] was of our choice, since, due to its excellent hydrophilicity, it was expected to mimic aqueous medium and appeared best 111
Page 1:
ASYMMETRIC STRATEGIES FOR THE SYNTH
Page 6 and 7:
ACKNOWLEDGEMENTS First of all, I wa
Page 8 and 9:
CONTENTS SYNOPSIS LIST OF FIGURES L
Page 10:
SYNOPSIS
Page 13 and 14:
models (e. g. Cram’s model, Felki
Page 15 and 16:
4 1d 4-(CH 3 ) 2 CH-C 6 H 4 1 : 1.5
Page 17 and 18:
14. 1n C 6 H 5 CO C 6 H 5 2n 8 77 1
Page 19 and 20:
imetallic systems. In all the cases
Page 21 and 22:
For the benzylation reaction, the c
Page 23 and 24:
O O 3 CHO i O O + OH 13a O O OH O O
Page 25 and 26:
10 3.5 Ga (2.5) THF KI+LiCl 10 55 5
Page 27 and 28:
multidrug-resistant (MDR) cancer ce
Page 29 and 30:
directly afforded the furanose, whi
Page 31 and 32:
References 1. Stephenson, G. R. Adv
Page 33 and 34:
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 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 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 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: Fig. III.1.22. 13 C NMR spectrum of
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 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 201 and 202: Fig. IV.2.2. 1 H NMR spectrum of 13
Page 203 and 204:
Fig. IV.2.6. 1 H NMR spectrum of 14
Page 205 and 206:
IIV. .33: : SSYNTHESSIISS OFF 33' '
Page 207 and 208:
For the actual synthesis, (Scheme I
Page 209 and 210:
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 217 and 218:
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
Page 225 and 226:
Page 227 and 228:
IV.6 EXPERIMENTAL SECTION (2R,3S,4R
Page 229 and 230:
As described earlier, compound 108
Page 231 and 232:
19.5, 23.8, 23.9, 25.1, 26.9, 34.6,
Page 233 and 234:
74.2, 74.4, 110.1, 116.7, 127.6, 12
Page 235 and 236:
mmol) in MeOH (10 mL), work up, fol
Page 237 and 238:
7.51 (m, 3H), 7.92-8.08 (m, 2H); 13
Page 239 and 240:
subsequent isolation afforded rotam
Page 241 and 242:
4.18 (t, J = 3.4 Hz, 1H), 4.75-4.84
Page 243 and 244:
-4.21 (c 1.2, CHCl 3 ); IR: 3466, 1
Page 245 and 246:
(3R)- 3,4-O-Cyclohexylidene-2-oxo-1
Page 247 and 248:
Water and EtOAc was added to the mi
Page 249 and 250:
24 179. Yield: 1.49 g (77.5%); colo
Page 251 and 252:
24 furnished pure 183. Yield: 0.37
Page 253 and 254:
1. Wender, P. A. Chem. Rev. 1996, 9
Page 255 and 256:
17. Hanessian, S.; Maji, D. K.; Gov
Page 257 and 258:
32. For some selective references s
Page 259 and 260:
43. (a) Cleare, M. J.; Hydes, P. C.
Page 261 and 262:
54. Barbero, A.; Pulido, F. J.; Rin
Page 263 and 264:
2008, 1681. (d) Fargeas, V.; Zammat
Page 265 and 266:
72. Karodia, N.; Guise, S.; Newland
Page 267 and 268:
Kaminski, J.; Millhauser, G.; Ortiz
Page 269 and 270:
Böhm, V. P. W.; Reisinger, C. J. O
Page 271 and 272:
119. Wender, P. A.; Holt, D. A.; Si
Page 273 and 274:
140. (a) Chemler, S. R.; Roush, W.
Page 275 and 276:
Lett. 1996, 107, 53. (c) Smith, C.
Page 277 and 278:
158. Mitsuya, H.; Weinhold, K. J.;
Page 279 and 280:
L.; Zugay, J. A. J. Med. Chem. 1993
Page 281 and 282:
1. Goswami, D.; Chattopadhyay, A.;
show all

CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

Create successful ePaper yourself

Delete template?

Save as template?