Title Page
Abstract
Contents
List of Abbreviations 14
Chapter 1. New synthetic methods for a molecular skeleton of Cephalotaxus troponoids 16
Introduction 16
1. Introduction of Cephalotaxus troponoids 16
2. Cephalotaxus troponoid framework 17
3. Previous synthetic studies toward harringtonolide 19
4. Radical anionic coupling reaction 22
Result and Discussion 24
1. Retrosynthetic analysis of harringtonolide 24
2. Preparation of α,β-unsaturated tricycloketone (6) and its stereoselective hydrogenation. 26
3. Synthesis of phenolic nitronate (3) and its Kende coupling rection 33
4. Model structure of phenolic nitronates 38
5. Synthesis of cis-3-Me and stereochemistry analysis. 39
6. Finalization of harringtonolide derivative 45
Conclusion 46
Experimental Details 48
1. General information 48
2. General synthetic method 49
Chapter 2. Regioselective synthesis of 2,3-disubstituted indoles 73
Introduction 73
1. Biological activity of indoles 73
2. Regioselectivity issue in the classical indole synthesis. 75
3. Indole syntheses from the o-haloanilines 76
4. Plausible mechanism of PIFA mediated aminocyclization 82
Result and Discussion 83
1. Preparation of indole substrate, o-alkenyl anilines 83
2. Intramolecular aminocyclization with hypervalent iodines (PIFA) 94
Conclusion 101
Experimental Details 102
1. General information 102
2. General synthetic method 103
References 131
Appendices 135
List of ¹H-NMR Spectra of Selected Compounds 135
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 6 138
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 10 139
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 11 140
400 MHz ¹H-NMR spectrum (CDCl₃) of compound cis-12 141
400 MHz ¹H-NMR spectrum (CDCl₃) of compound trans-12 142
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 5 143
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 13 144
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 4 145
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 14 146
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 3 147
400 MHz ¹H-NMR spectrum (Acetone-d6) of compound 15[이미지참조] 148
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 16 149
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 17 150
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 18 151
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 20 152
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 21 153
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 22 154
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 23 155
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 24 156
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 25 157
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 26 158
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 28 159
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32a 160
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32b 161
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32c 162
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32d 163
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32e 164
400 MHz ¹H-NMR spectrum (CDCl₃) of compound Z-32e 165
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32f 166
400 MHz ¹H-NMR spectrum (CDCl₃) of compound Z-32f 167
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32g 168
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32h 169
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32i 170
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32j 171
400 MHz ¹H-NMR spectrum (CDCl₃) of compound Z-32k 172
400 MHz ¹H-NMR spectrum (CDCl₃) of compound E-32l 173
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32m 174
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32n 175
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32o 176
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32p 177
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 32q 178
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33a 179
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33b 180
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33c 181
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33d 182
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33e 183
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33f 184
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33g 185
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33h 186
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33i 187
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33j 188
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33k 189
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33l 190
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33m 191
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33n[내용없음] 137
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33o 192
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33p 193
400 MHz ¹H-NMR spectrum (CDCl₃) of compound 33q 194
List of ¹³C-NMR Spectra of Selected Compounds 195
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 6 198
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 10 199
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 11 200
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound cis-12 201
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound trans-12 202
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 5 203
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 13 204
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 4 205
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 14 206
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 3 207
100 MHz ¹³C-NMR spectrum (Acetone-d6) of compound 15[이미지참조] 208
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 17 209
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 18 210
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 20 211
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 22 212
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 23 213
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 24 214
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 25 215
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 28 216
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32a 217
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32b 218
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32c 219
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32d 220
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32e 221
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound Z-32e 222
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32f 223
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound Z-32f 224
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32g 225
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32h 226
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32i 227
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32j 228
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound Z-32k 229
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound E-32l 230
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32m 231
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32n 232
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32o 233
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32p 234
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 32q 235
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33a 236
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33b 237
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33c 238
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33d 239
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33e 240
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33f 241
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33g 242
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33h 243
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33i 244
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33j 245
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33k 246
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33l 247
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33m 248
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33o 249
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33p 250
100 MHz ¹³C-NMR spectrum (CDCl₃) of compound 33q 251
국문초록 252
Table 1. Preparation of alkenyl boronates with method A and B 84
Table 2. Preparation of alkenyl stannanes with method C 86
Table 3. Synthesis of o-alkenyl anilines via Suzuki coupling reaction 89
Table 4. Synthesis of o-alkenyl anilines via Stille coupling reaction 91
Table 5. Optimization studies with hypervalent iodines. 95
Table 6. Intramolecular aminocyclization of o-alkenyl anilines 97
Table 7. Further oxidation of intramolecular aminocyclization 99
Figure 1. The several Cephalotaxus troponoid species 17
Figure 2. The Cephalotaxus troponoid framework 18
Figure 3. Stereoselective hydrogenation with Crabtree reagent. 30
Figure 4. Configurational analysis of trans-12 and cis-12 in ¹H NMR 31
Figure 5. The Cephalotaxus benzenoid framework 36
Figure 6. Model structure of phenolic nitronate (3, trans-3, and cis-3) 38
Figure 7. Selective homonuclear decoupling in ¹H NMR of 24 43
Figure 8. Stereochemistry and configurational analysis of 24 44
Figure 9. Representative biologically active 2,3-disubstituted indoles 74
Figure 10. Regioselectivity for alkyne hydrostannation 85
Figure 11. Suzuki coupling reaction mechanism 87
Figure 12. Pd(II)-catalyzed E- to Z- isomerization 88
Figure 13. Stereochemistry analysis of (a) E- and Z-32e (b) E- and Z-32f 93
Figure 14. 3D structure of E- and Z-32e 96
Scheme 1. Syntheses of harringtonolide and its precursor 21
Scheme 2. Intramolecular oxidative coupling reaction of phenolic nitronates 22
Scheme 3. Mechanism of intramolecular oxidative coupling reaction 23
Scheme 4. Retrosynthetic analysis of harringtonolide 25
Scheme 5. Synthesis of configurational isomers trans-12 and cis-12 28
Scheme 6. Chemoselective hydrogenation of Luche reduction 29
Scheme 7. Chemoselectivity issue of nitroethylation on trans-12 and cis-12 32
Scheme 8. Nitration of olefin mechanism 33
Scheme 9. Synthesis of α,β-unsaturated phenolic nitronate (3) and its Kende coupling reaction 34
Scheme 10. Deprotection condition of lactonized 17 37
Scheme 11. Stereoselective Robinson annulation 40
Scheme 12. Synthesis of stereocontrolled cis-3-Me 42
Scheme 13. Finalization of harringtonolide 45
Scheme 14. Regioselectivity issue in the classical Fischer indole synthesis 75
Scheme 15. Aminocyclization of o-alkynyl anilines 78
Scheme 16. Aminocyclization of o-alkenyl anilines 80
Scheme 17. PIFA mediated free N-H indole synthesis of o-alkenyl anilines 81
Scheme 18. Intramolecular aminocyclization via nitrene intermediate 82
Scheme 19. Plausible mechanism of PIFA-mediated aminocyclization 100