CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

More documents

Recommendations

Info

CONTENTS SYNOPSIS LIST OF FIGURES LIST OF TABLES i-xxii xxiii-xxvi xxvii CHAPTER I INTRODUCTION I.1 Preamble 1 I.2 Introduction to Chirality and Asymmetric Synthesis 3 I.3 Strategies of Enantiomeric Synthesis 6 CHAPTER II [BMIM][Br]: A GREEN AND EFFICIENT MEDIA FOR ALLYLATION OF CARBONYLS II.1 Introduction to Chiral Carbinols 20 II.2 Introduction to Homoallylic Alcohols: Allylation of 31 Carbonyls II.3 Present Work II.3.1 Introduction to Ionic Liquids 36 II.3.2 Indium Mediated Allylation in [bmim][Br] 39 II.3.3 Gallium Mediated Allylation in [bmim][Br] 54 II.4 Experimental Section 69 CHAPTER III DIASTEREOSELECTIVE SYNTHESIS OF CHIRAL CARBINOLS III.1 Diastereoselective Synthesis of Chiral Carbinols via Bi-metallic Redox Strategies III.1.1 Introduction 75 III.1.2 Present Work 76 III.2 Metal Dependent Modulation of Diastereoselectivity in the Barbier Type Allylation/ Crotylation III.2.1 Present Work 110 III.3 Experimental Section 119 CHAPTER IV ASYMMETRIC SYNTHESIS OF SOME BIO- ACTIVE ORGANIC COMPOUNDS IV.1 Synthesis of Enantiopure (R)-Arundic Acid IV.1.1 Introduction 138 IV.1.2 Previous Syntheses 139 IV.1.3 Present Work 142 IV.2 Synthesis of Octadienoic Acid Unit of Cryptophycins
IV.2.1 Introduction 147 IV.2.2 Previous Syntheses of Unit-A 149 IV.2.3 Present Work 151 IV.3 Synthesis of 3'-C Branched 2',3'-Dideoxynucleosides IV.3.1 Introduction 162 IV.3.2 Present Work 163 IV.4 Synthesis of 2(S)-[1(S)-Azido-2phenylethyl]oxirane IV.4.1 Introduction 168 IV.4.2 Previous Syntheses 169 IV.4.3 Present Work 171 IV.5 Synthesis of trans-Oak Lactone IV.5.1 Introduction 177 IV.5.2 Previous Syntheses 177 IV.5.3 Present Work 179 IV.6 Experimental Section 184 REFERENCES 209 LIST OF 236 PUBLICATIONS
Page 1: ASYMMETRIC STRATEGIES FOR THE SYNTH
Page 6 and 7: ACKNOWLEDGEMENTS First of all, I wa
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:
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:
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
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:
Page 203 and 204:
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 ...

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?