Angew. Chem., Int. Ed. Engl. 1986, 25, 1. (d) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett 1992, 539. (e) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96, 49. 37. (a) Trost, B. M. Angew. Chem. Int. Ed. 1995, 34, 259. (b) Trost, B. M. Science, 1991, 254, 1471. 38. Trost, B. M.; Krische, M. J. Synlett, 1998, 1. 39. Aubert, C.; Buisine, O.; Malacria, M. Chem. Rev. 2002, 102, 813. 40. (a) Wender, P. A.; Jenkins, T. E. J. Am. Chem. Soc. 1989, 111, 6432. (b) Wang, B.; Cao. P.; Zhang, X. Tetrahedron Lett. 2000, 41, 8041. (c) Murakami, M.; Ubukata, M.; Itami, K.; Ito, Y. Angew. Chem. Int. Ed. 1998, 37, 2248. 41. (a) Brummond, K. M.; Kent, J. L. Tetrahedron, 2000, 56, 3263. (b) Gibson, S. E.; Stevanazzi, A. Angew. Chem. Int. Ed. 2003, 42, 1800. (c) Rivero, M. R.; Adrio, J.; Carretero, J. C. Eur. J. Org. Chem. 2002, 2881. 42. Jolly, R. S.; Luedtke, G.; Sheehan, D.; Livinghouse, T. J. Am. Chem. Soc. 1990, 112, 4965 43. Bolton, G. L.; Hodges, J. C.; Rubin, J. R. Tetrahedron 1997, 53, 6611. 44. Hotha, S.; Tripathi, A. J. Comb. Chem. 2005, 7, 968-976. 45. Burton, B. S.; Pechman, H. V. Chem. Ber. 1887, 20, 145. 46. Hendrickson, J. B.; Cram. D. J.; Hammond, G. S. Organic Chemistry, 3rd ed.; McGraw- Hill Book Co.: New York, 1970; pp 104-105. 47. For the most recent review, see: Ma, S. Chem. Rev. 2005, 105, 2829. 48. (a) Modern Allene Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004. (b) The Chemistry <strong>of</strong> Ketenes, Allenes, and Related Compounds Part 1; Patai, S., Ed.; John Wiley & Sons: New York, 1980. (c) Allenes in Organic Synthesis; Schuster, H. F., Coppola, G. M., Eds.; John Wiley & Sons: New York, 1984. 314
49. For reviews on reactions <strong>of</strong> allenes, see: (a) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590. (b) Marshall, J. Chem. Rev. 2000, 100, 3163. (c) Zimmer, R.; Dinesh, C.; Nandanan, E.; Khan, F. Chem. Rev. 2000, 100, 3067 (d) Bates, R.; Satcharoen, V. Chem. Soc. Rev. 2002, 31, 12. (e) Ma, S. Topics in Organometallic Chemistry; Tsuji, J., Ed.; Springer-Verlag: Heidelberg, 2005; pp 183-210. (f) Sydnes, L. Chem. Rev. 2003, 103, 1133. (g) Brandsma, L.; Nedolya, N. A. Synthesis 2004, 735. (i) Tius, M. Acc. Chem. Res. 2003, 36, 284. (h) Wei, L.-L.; Xiong, H.; Hsung, R. P. Acc. Chem. Res. 2003, 36, 773. (i) Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535. (j) Wang, K. K. Chem. Rev. 1996, 96, 207. 50. Padwa, A.; Filipkowski, M. A.; Meske, M.; Murphree, S. S.; Watterson, S. H.; Ni, Z. J. Org. Chem. 1994, 59, 591. 51. For examples <strong>of</strong> [4+2] reaction, see: (a) Wender, P. A.; Jenkins, T. E.; Suzuki, S. J. Am. Chem. Soc. 1995, 117, 1843. For examples <strong>of</strong> [5+2] reaction, see: (b) Wender, P. A.; Bi, F. C.; Gamber, G. G.; Gosselin, F.; Hubbard, R. D.; Scanio, M. J. C.; Sun, R.; Williams, T. J.; Zhang, L. Pure Appl. Chem. 2002, 74, 25. (c) Wender, P. A.; Glorious, F.; Husfield, C. O.; Langkopf, E.; Love, J. A. J. Am. Chem. Soc. 1999, 121, 5348. For an example <strong>of</strong> a [2+2+2] reaction, see: (d) Aubert, C.; Llerena, D.; Malacria, M. Tetrahedron Lett. 1994, 35, 2341. 52. (a) Wender, P. A.; Fuji, M.; Husfield, C. O.; Love, J. A. Org. Lett. 1999, 1, 137. (b) Wender, P. A.; Zhang, L. Org. Lett. 2000, 2, 2323. 53. Please see reference 51a for an additional example <strong>of</strong> catalyst-based double bond selectivity in a [4+2] reaction. 54. (a) Spry, D. O.; Bhala, A. R. Heterocycles, 1986, 24, 4641. (b) Ley, S. V.; Gutteridge, C. E.; Pape, A. R.; Spilling, C. D.; Zumbrunn, C. Synlett, 1999, 1295. (d) Aoki, Y.; Kuwajima, I. Tetrahedron Lett. 1990, 51, 7457. (e) Henderson, M. A.; Heathcock, C. H. J. Org. Chem. 1988, 53, 4736. 55. Fujusawa, T.; Maehata, E.; Kohama, H.; Sato, T. Chem. Lett. 1985, 1475. 315
- 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 and 276:
4.17 (d, J = 15.0 Hz, 1H), 4.10 (d,
- Page 277 and 278:
137.1, 136.9, 130.4, 129.8, 128.5,
- 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 315 and 316: 1 H and 13 C NMRs of 155a 297
- Page 317 and 318: 1 H and 13 C NMRs of 156a 299
- Page 319 and 320: 1 H and 13 C NMRs of 186b 301
- Page 321 and 322: 1 H and 13 C NMRs of 270h 303
- Page 323 and 324: 1 H and 13 C NMRs of 287b 305
- 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: Hu, Y. J. Comb. Chem. 2006, 8, 286.
- 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