Download (3249Kb) - D-Scholarship@Pitt - University of Pittsburgh

More documents

Recommendations

Info

7.50-7.45 (m, 5H), 7.31-7.27 (m, 3H), 7.16-7.14 (m, 2H), 5.91 (s, 1H), 4.24 (d, J = 15.5 Hz, 1H), 4.08 (d, J = 14.1 Hz, 1H), 4.06 (d, J = 15.5 Hz, 1H), 3.76 (s, 3H), 3.55 (s, 1H), 3.28 (d, J = 14.2 Hz, 1H), 3.04 (dd, J = 18.5, 5.0 Hz, 1H), 2.84 (dd, J = 18.5, 3.6 Hz, 1H), 2.49 (t, J = 7.2 Hz, 2H), 2.15 (q, J = 4.2 Hz, 1H), 1.66 (sex, J = 7.3 Hz, 2H), 0.98 (t, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl3): δ 208.4, 207.6, 173.7, 171.5, 171.3, 135.9, 135.7, 131.0, 130.5, 128.6, 128.4, 127.2, 124.1, 123.7, 123.3, 71.6, 53.2, 52.5, 51.7, 45.9, 44.4, 40.6, 37.6, 17.0, 13.7; IR (thin film): ν 2960, 1713, 1645, 1383 cm -1 ; MS m/z (%) 459 (7), 388 (58), 358 (54), 298 (78), 105 (100); EI- HRMS calcd for C28H29NO5 m/z [M] + 459.2046, found 459.2061. General procedure Q for reduction of enones. BzN Bn MeO 2C H 2-Benzoyl-1-benzyl-4-methyl-5-oxo-6-(2-oxopentyl)octahydrocyclopenta[c]pyrrole-1- H 296 carboxylic acid methyl ester (296). To a solution of the enone 293a (121 mg, 0.256 mmol) in MeOH (15 mL) was added Pd/C (100 mg of 10 % by wt.) at rt. The reaction vessel was connected to a hydrogenation apparatus and purged with H2 three times. The reaction mixture was stirred at rt under H2 pressure (2.5 atm) for 4 h. The mixture was then filtered using a fritted funnel through a plug of celite and washed with CH2Cl2. The filtrate was concentrated under vacuum to afford 296 (115 mg, 95%). 1 H NMR (300 MHz, CDCl3): δ 7.47-7.42 (m, 5H), 7.34-7.24 (m, 5H), 4.22 (d, J = 13.8 Hz, 1H), 3.84 (s, 3H), 3.27 (d, J = 13.8 Hz, 1H), 3.20-3.00 (m, 3H), 2.85 (dd, J = 10.2, 6.9 Hz, 1H), 2.63- 2.46 (m, 3H), 2.39 (t, J = 7.3 Hz, 2H), 1.79-1.68 (m, 1H), 1.61 (sex, J = 7.4 Hz, 2H), 0.94 (t, J = 7.3 Hz, 3H), 0.75 (d, J = 7.3 Hz, 3H); 13 C NMR (75 MHz, CDCl3): δ 218.2, 208.6, 171.9, 169.9, 258 O O C 3H 7
137.1, 136.9, 130.4, 129.8, 128.5, 127.1, 126.1, 72.8, 52.6, 51.5, 50.3, 44.4, 44.2, 44.0, 41.6, 41.4, 39.8, 17.2, 13.6, 10.2; IR (thin film): ν 2962, 1737, 1712, 1639, 1404, 1250 cm -1 ; MS m/z (%) 416 (16), 384 (43), 352 (21), 324 (23), 105 (100); EI-HRMS calcd for C27H30NO3 m/z [M- 59] + 416.2226, found 416.2239. H BzN Bn MeO 2C H 297 2-Benzoyl-1-benzyl-5-oxo-6-(2-oxopentyl)octahydrocyclopenta[c]pyrrole-1-carboxylic acid methyl ester (297). Prepared by following the general procedure Q, using: 294a (140 mg, 0.305 mmol), MeOH (10 mL), Pd/C (50 mg of 10% by wt.), H2 (1 atm). The reaction mixture was stirred for 4 h at rt. Yield of 297 (140 mg, >95%). Note: The reaction was performed under 1 atm of H2 using a balloon. 1 H NMR (300 MHz, CDCl3): δ 7.49-7.24 (m, 10H), 4.18 (d, J = 13.7 Hz, 1H), 3.83 (s, 3H), 3.37- 3.12 (m, 3H), 2.96-2.88 (m, 2H), 2.66-2.57 (m, 2H), 2.43 (t, J = 7.3 Hz, 2H), 2.33 (dd, J = 19.0, 8.3 Hz, 1H), 1.99 (d, J = 19.0 Hz, 1H), 1.89-1.77 (m, 1H), 1.64 (sex, J = 7.3 Hz, 2H), 0.96 (t, J = 7.3 Hz, 3H); 13 C NMR : δ 216.6, 208.4, 171.8, 169.6, 137.0, 136.7, 130.5, 129.9, 128.5, 127.1, 126.2, 72.9, 56.5, 52.6, 52.2, 45.1, 44.5, 41.6, 39.6, 36.1, 17.2, 13.6; IR (thin film): ν 2959, 1740, 1712, 1636, 1405, 1250 cm -1 ; EI-HRMS calcd for C26H28NO3 m/z [M-59] + 402.2069, found 402.2069. 259 O O C 3H 7
Page 1 and 2:
TRANSITION METAL-CATALYZED REACTION
Page 3 and 4:
Transition Metal-Catalyzed Reaction
Page 5 and 6:
List of Abbreviations Ac acetyl AcO
Page 7 and 8:
Table of Contents 1.0 Introduction.
Page 9 and 10:
Appendix A : X-ray crystal structur
Page 11 and 12:
Table 4.8 Rh(I)-catalyzed cyclocarb
Page 13 and 14:
List of Schemes Scheme 1.1 Three fo
Page 15 and 16:
Scheme 3.24 Preparation of amide-te
Page 17 and 18:
Scheme 4.16 Formation of bicyclo[5.
Page 19 and 20:
1.0 Introduction 1.1 The Role of Di
Page 21 and 22:
According to these guidelines, the
Page 23 and 24:
Scheme 1.1 Three forms of diversity
Page 25 and 26:
Another example from the Schreiber
Page 27 and 28:
1.1.1 Transition Metal-Catalyzed Re
Page 29 and 30:
37, , such reactions include transi
Page 31 and 32:
the proximal olefin of allenyne 38
Page 33 and 34:
2.0 Design and Synthesis of the Piv
Page 35 and 36:
The allenic amino acid derivatives
Page 37 and 38:
This protocol proved particularly u
Page 39 and 40:
ZnCl2, which results in a Zn-chelat
Page 41 and 42:
Scheme 2.7 Synthesis of trisubstitu
Page 43 and 44:
THF), the yield was increased from
Page 45 and 46:
the terminus of the alkyne led to d
Page 47 and 48:
N-Alkylation of the glycine-derived
Page 49 and 50:
circumvent this issue, variants suc
Page 51 and 52:
BINAP as a chiral ligand to obtain
Page 53 and 54:
stereochemistry of the exocyclic ol
Page 55 and 56:
3.2 Rhodium(I)-Catalyzed Allenic Cy
Page 57 and 58:
exocyclic olefin geometry is not re
Page 59 and 60:
3.2.1 Preparation of Enol-ether Tri
Page 61 and 62:
Scheme 3.15 Synthesis of cycloisome
Page 63 and 64:
Scheme 3.17 Cycloisomerization of a
Page 65 and 66:
Scheme 3.19 Tandem cycloadditions o
Page 67 and 68:
Scheme 3.21 Intermolecular Diels-Al
Page 69 and 70:
attractive, since additional functi
Page 71 and 72:
increased yield of the triene (47%)
Page 73 and 74:
as an isobutyl-amide 155b was prepa
Page 75 and 76:
group) demonstrated that this cyclo
Page 77 and 78:
in 1M HCl/dioxane (1 : 1) for 1h, t
Page 79 and 80:
ppm (dd, J = 7.1, 4.6 Hz, 1H) assig
Page 81 and 82:
http://ccc.chem.pitt.edu/). Using f
Page 83 and 84:
Notably, exclusive cycloisomerizati
Page 85 and 86:
intermediate in the reaction we sou
Page 87 and 88:
epulsive dipole interactions (Schem
Page 89 and 90:
Table 3.4 Diels-Alder reactions of
Page 91 and 92:
allenic Alder-ene reaction, ene-all
Page 93 and 94:
Figure 3.4 Examples of natural prod
Page 95 and 96:
species onto the proximal double bo
Page 97 and 98:
Scheme 3.49 Rh(I)-catalyzed ene rea
Page 99 and 100:
y Magnus 144 and it involves the in
Page 101 and 102:
usually is DMSO. Heating to 100 ºC
Page 103 and 104:
that require high pressures of CO.
Page 105 and 106:
In contrast to the Mo(CO)6-mediated
Page 107 and 108:
Scheme 4.15 Rh(I)-catalyzed allenic
Page 109 and 110:
4.2 Rhodium(I)-Catalyzed Cyclocarbo
Page 111 and 112:
lack of double bond selectivity, si
Page 113 and 114:
Table 4.2 Cyclocarbonylation reacti
Page 115 and 116:
Notably, the allenic cyclocarbonyla
Page 117 and 118:
Scheme 4.22 Cyclocarbonylation reac
Page 119 and 120:
neat or in solution. This decomposi
Page 121 and 122:
the newly synthesized fulvenes (e.g
Page 123 and 124:
stereocenters and mixture of E/Z is
Page 125 and 126:
proximal double bond to give α-alk
Page 127 and 128:
the methyl ester and Ha are syn. Sc
Page 129 and 130:
that the major diastereomer in the
Page 131 and 132:
We were motivated to first examine
Page 133 and 134:
Scheme 4.42 Synthesis of pyrrole 29
Page 135 and 136:
periodic acid (H5IO6). 209 These hi
Page 137 and 138:
eaction failed to go to completion,
Page 139 and 140:
4.5.2 Synthesis of a Library of Tri
Page 141 and 142:
diketones 312{1-3,1-2} in yields ra
Page 143 and 144:
Figure 4.2 Distribution for physico
Page 145 and 146:
tricyclic pyrrole 314{3,2,26} (Figu
Page 147 and 148:
4.6 Synthesis of α-Alkylidene Cycl
Page 149 and 150:
anched and linear carboxylic acid i
Page 151 and 152:
eactivity of the species prepared i
Page 153 and 154:
considerably lower than the ratio o
Page 155 and 156:
diastereomer. Next, allenyne 328 wa
Page 157 and 158:
Conclusions In summary, we have dem
Page 159 and 160:
Experimental Section General Method
Page 161 and 162:
General procedure A for esterificat
Page 163 and 164:
F Bz N H 56f 2-Benzoylamino-3-(4-fl
Page 165 and 166:
MeO2C Bz N H 58c 2-Benzoylamino-2-m
Page 167 and 168:
MeO MeO2C Bz N H 58e 2-Benzoylamino
Page 169 and 170:
mL) and MeOH (10 mL) instead of sat
Page 171 and 172:
hexanes-EtOAc, 19 : 1 to 4 : 1, v/v
Page 173 and 174:
which was immediately used in the C
Page 175 and 176:
Boc TMS N H Bn 64f tert-Butyl-1-((4
Page 177 and 178:
MeI (38 µL, 0.62 mmol). Yield 65a
Page 179 and 180:
with brine and concentrated under v
Page 181 and 182:
H MeO 2C • H Bn NHBoc tert-Butyl-
Page 183 and 184:
TMS MeO 2C • 70 H H NHBoc 2-tert-
Page 185 and 186:
185 (10), 141 (21), 57 (100); EI-HR
Page 187 and 188:
dispersion in mineral oil, 1.0 mmol
Page 189 and 190:
EI-HRMS calcd for C30H26NO3 m/z [M-
Page 191 and 192:
CbzN MeO 2C Me 73h 2-[Benzyloxycarb
Page 193 and 194:
CbzN MeO 2C Me 2-(Benzyloxycarbonyl
Page 195 and 196:
dispersion in mineral oil, 3.85 mmo
Page 197 and 198:
completion of the addition, the rea
Page 199 and 200:
BzN MeO 2C S 74h 2-(Benzoylprop-2-y
Page 201 and 202:
BzN MeO 2C Bn 75b 2-(Allylbenzoylam
Page 203 and 204:
BzN MeO 2C TBSO 75e 2-(Benzoylbut-2
Page 205 and 206:
Hz, 1H), 5.85 (s, 1H), 5.52 (dd, J
Page 207 and 208:
1H), 3.69 (s, 3H), 1.58 (d, J = 7.1
Page 209 and 210:
µmol), [Rh(CO)2Cl]2 (1 mg, 3 µmol
Page 211 and 212:
1.25 (m, 6H), 0.88 (t, J = 6.9 Hz,
Page 213 and 214:
6.72 (d, J = 7.6 Hz, 0.5H), 6.68 (d
Page 215 and 216:
BzN MeO2C Bn 122a Methyl-2-(N-(but-
Page 217 and 218:
Bz N MeO2C Bn 1-Benzoyl-2-benzyl-4-
Page 219 and 220:
13.9, 5.3 Hz, 1H), 2.51-2.47 (m, 1H
Page 221 and 222:
15 min the solvent was removed unde
Page 223 and 224:
Benzoyl chloride (0.169 mL, 1.46 mm
Page 225 and 226: mg, 0.11 mmol), [Rh(CO)2Cl]2 (4 mg,
Page 227 and 228: mL). kk The aqueous layer was extra
Page 229 and 230: ºC. After quenching the reaction b
Page 231 and 232: 129.8, 129.0, 128.7, 128.4, 126.2,
Page 233 and 234: MeO 2C O O O N H N R 1 O N Ph [10c-
Page 235 and 236: The crude residue was purified by f
Page 237 and 238: 14.4 Hz, 1H), 3.49-3.39 (m, 2H), 3.
Page 239 and 240: 1H), 5.49 (dd, J = 17.3, 1.8 Hz, 1H
Page 241 and 242: was stirred at rt for 1 h when it w
Page 243 and 244: BzN HOOC 2-(N-(but-2-ynyl)benzamido
Page 245 and 246: °C and DIBAL-H (0.440 mL of a 1.0M
Page 247 and 248: 129 (62), 91 (100); EI-HRMS calcula
Page 249 and 250: (d, J = 18.0 Hz, 1H), 4.14 (d, J =
Page 251 and 252: 4.98 (dt, J = 7.7, 5.1 Hz, 1H), 4.1
Page 253 and 254: N Bz MeO2C OTBS 214 1-Benzoyl-2-(te
Page 255 and 256: 270a (major diastereomer-eluting fi
Page 257 and 258: CDCl3): δ 7.42-7.17 (m, 13H), 7.04
Page 259 and 260: 18.6 Hz, 1H), 4.34 (d, J = 18.0 Hz,
Page 261 and 262: Bz N MeO2C 2-Benzoyl-3,7-dimethyl-6
Page 263 and 264: v/v) afforded a mixture of compound
Page 265 and 266: (435 mg, 1.21 mmol), DMSO (429 µL,
Page 267 and 268: 4.02 (s, 1H), 3.88 (s, 3H), 1.82 (s
Page 269 and 270: (207 mg, 96%) consisting of 287e (7
Page 271 and 272: procedure O, using: 74f (110 mg, 0.
Page 273 and 274: Bz N O H CO2Me BocN 287i 3-(2-Benzo
Page 275: 4.17 (d, J = 15.0 Hz, 1H), 4.10 (d,
Page 279 and 280: H BzN MeO2C Bn H N C3H7 298b CO 2Me
Page 281 and 282: NMR (75 MHz, CDCl3): δ 172.3, 169.
Page 283 and 284: following the general procedure Q,
Page 285 and 286: H BzN MeO2C Bn H 5-Benzoyl-1,4-dibe
Page 287 and 288: 119.9, 114.1, 109.9, 108.6, 73.0, 5
Page 289 and 290: 4.11 (m, 1H), 4.07-3.98 (m, 1H), 3.
Page 291 and 292: 126.8, 126.2, 109.0, 72.9, 58.7, 56
Page 293 and 294: NMR (75 MHz, CDCl3): δ 172.2, 169.
Page 295 and 296: 3.0 Hz, 1H), 5.82-5.80 (m, 1H), 5.2
Page 297 and 298: 87%). The diastereomeric ratio (288
Page 299 and 300: APPENDIX A: X-ray crystal structure
Page 301 and 302: APPENDIX B: X-ray crystal structure
Page 303 and 304: APPENDIX C: X-ray crystal structure
Page 305 and 306: APPENDIX D: X-ray crystal structure
Page 307 and 308: APPENDIX E: X-ray crystal structure
Page 309 and 310: APPENDIX F: QikProp property predic
Page 311 and 312: 1 H and 13 C NMRs of 74b 293
Page 313 and 314: 1 H and 13 C NMRs of 111a 295
Page 321 and 322: 1 H and 13 C NMRs of 270h 303
Page 325 and 326: 1 H and 13 C NMRs of 307 307
Page 327 and 328:
1 H and 13 C NMRs of 308n 309
Page 329 and 330:
10. (a) Burke, M. D.; Schreiber, S.
Page 331 and 332:
Hu, Y. J. Comb. Chem. 2006, 8, 286.
Page 333 and 334:
49. For reviews on reactions of all
Page 335 and 336:
69. (a) Trost, B. M.; Lautens, M.;
Page 337 and 338:
containing cross-conjugated trienes
Page 339 and 340:
Vaillancourt, J.; Rasper, D. M.; Ta
Page 341 and 342:
130. Oppolzer, W.; Snieckus, V. Ang
Page 343 and 344:
149. (a) Hicks, F. A.; Buchwald, S.
Page 345 and 346:
Maiese, W. M. J. Antibiot. 2000, 53
Page 347 and 348:
192. The mechanism of decomposition
Page 349 and 350:
Boger, D. L.; Boyce, C. W.; Labroli
Page 351:
Generated Inhibitors of Human Mitog
show all

Download (3249Kb) - D-Scholarship@Pitt - University of Pittsburgh

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

Delete template?

Save as template?