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142. (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.; Foreman, M. I. J. Chem. Soc., Perkin Trans. 1 1973, 977. (b) Khand, I. U.; Pauson, P. L. J. Chem. Soc, Chem. Commun. 1974, 379. (c) Khand, I. U.; Pauson, P. L. J. Chem. Soc., Perkin Trans. 1 1976, 30. (d) Pauson, P. L. Tetrahedron 1985, 41, 5855. 143. For reviews, see reference 41. For some recent examples, see: (a) Kaasalainen, E.; Tois, J.; Russo, L.; Rissanen, K.; Helaja, J. Tetrahedron Lett. 2006, 47, 5669. (b) Thornton, P. D.; Burnell, D. J. Org. Lett. 2006, 8, 3195. (c) Mukai, C.; Yoshida, T.; Sorimachi, M.; Odani, A. Org. Lett. 2006, 8, 83. (d) Caldwell, J. J.; Cameron, I. D.; Christie, S. D. R.; Hay, A. M.; Johnstone, C.; Kerr, W. J.; Murray, A. Synthesis, 2005, 3293. (e) Gibson, S. E.; Mainolfi, N. Angew. Chem. Int. Ed. 2005, 44, 3022. (e) Jiang, B.; Xu, M. Angew. Chem., Int. Ed. 2004, 43, 2543. (f) Velcicky, J.; Lanver, A.; Lex, J.; Prokop, A.; Wieder, T.; Schmalz, H.- G. Chem. Eur. J. 2004, 10, 5087. (g) Winkler, J. D.; Lee, E. C. Y.; Nevels, L. I. Org. Lett. 2005, 7, 1489. 144. Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985, 26, 4851. 145. (a) Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van Pelt, C. E. J. Am. Chem. Soc. 1993, 115, 7199. (b) Krafft, M. E.; Juliano, C. A.; Scott, I. L.; Wright, C.; McEachin, M. D. J. Am. Chem. Soc. 1991, 113, 1693. 146. Schore, N. E.; Croudace, M. C. J. Org. Chem. 1981, 46, 5436. 147. For a summary <strong>of</strong> additive effects on the Co-mediated reaction, see references 41a and 41b. 148. (a) Rautenstrauch, V.; Mégard, P.; Conesa, J.; Kuéster, W. Angew. Chem., Int. Ed. Engl. 1990, 29, 1413. (b) Jeong, N.; Hwang, S. H.; Lee, Y.; Chung, Y. K. J. Am. Chem. Soc. 1994, 116, 3159. (c) Lee, B. Y.; Chung, Y. K.; Jeong, N.; Lee, Y.; Hwang, S. H. J. Am. Chem. Soc. 1994, 116, 8793. (d) Krafft, M. E.; Hirosawa, C.; Bonaga, L. V. R. Tetrahedron Lett. 1999, 40, 9171. (e) Krafft, M. E.; Bonaga, L. V. R.; Hirosawa, C. Tetrahedron Lett. 1999, 40, 9177. (f) Lee, N. Y.; Chung, Y. K. Tetrahedron Lett. 1996, 37, 3145. (g) Kim, J. W.; Chung, Y. K. Synthesis 1998, 142. 324
149. (a) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688. (b) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026. 150. Jeong, N.; Lee, S. J.; Lee, B. Y.; Chung, Y. K. Tetrahedron Lett. 1993, 34, 4027. 151. Recently, a Mo-catalyzed allenic Pauson-Khand reaction was reported, but the conditions are limited to substrates with two atoms in the tether: Gupta, A. K.; Park, D. I.; Oh, Tetrahedron Lett. 2005, 46, 4171. 152. Adrio, J.; Rivero, M. R.; Carretero, J. C. Org. Lett. 2005, 7, 431. 153. Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J. Org. Chem. 1997, 67, 3762. 154. Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am. Chem. Soc. 1997, 119, 6187. 155, (a) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998, 249. (b) Kobayashi, T.; Koga, Y.; Narasaka, K. J. Organomet. Chem. 2001, 624, 73. 156. Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17, 3642. 157. (a) Jeong, N.; Sung, B. K.; Choi, Y. K. J. Am. Chem. Soc. 2000, 122, 6771. (b) Suh, W. H.; Choi, M.; Lee, S. I.; Chung, Y. K. Synthesis 2003, 2169. (c) Jeong, N.; Kim, D. H.; Choi, J. H. Chem. Commun. 2004, 1134; (d) Suh, W. H.; Choi, M.; Lee, S. I.; Chung, Y. K. Synthesis 2003, 2169; (e) Schmid, T. M.; Consiglio, G. Chem. Commun. 2004, 2318; (f) Fuji, K.; Morimoto, T.; Tsutsumi, K.; Kakiuchi, K. Tetrahedron Lett. 2004, 45, 9163; (g) Park, K. H.; Chung, Y. K. Adv. Synth. Catal. 2005, 347, 854. 158. For some previous examples <strong>of</strong> asymmetric Pauson-Khand reactions, see: (a) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1996, 118, 11688. (b) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026. (c) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tetrahedron Lett. 2000, 41, 891. (d) Derdau, V.; Laschat, S.; Dix, I.; Jones, P. G. Organometallics 1999, 18, 3859. (e) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 1999, 64, 5547. (f) Sturla, S. J.; Buchwald, S. L. J. Org. Chem. 2002, 67, 3398. 325
Page 1 and 2:
TRANSITION METAL-CATALYZED REACTION
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Transition Metal-Catalyzed Reaction
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List of Abbreviations Ac acetyl AcO
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Table of Contents 1.0 Introduction.
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Appendix A : X-ray crystal structur
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Table 4.8 Rh(I)-catalyzed cyclocarb
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List of Schemes Scheme 1.1 Three fo
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Scheme 3.24 Preparation of amide-te
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Scheme 4.16 Formation of bicyclo[5.
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1.0 Introduction 1.1 The Role of Di
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According to these guidelines, the
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Scheme 1.1 Three forms of diversity
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Another example from the Schreiber
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1.1.1 Transition Metal-Catalyzed Re
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37, , such reactions include transi
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the proximal olefin of allenyne 38
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2.0 Design and Synthesis of the Piv
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The allenic amino acid derivatives
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This protocol proved particularly u
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ZnCl2, which results in a Zn-chelat
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Scheme 2.7 Synthesis of trisubstitu
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THF), the yield was increased from
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the terminus of the alkyne led to d
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N-Alkylation of the glycine-derived
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circumvent this issue, variants suc
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BINAP as a chiral ligand to obtain
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stereochemistry of the exocyclic ol
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3.2 Rhodium(I)-Catalyzed Allenic Cy
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exocyclic olefin geometry is not re
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3.2.1 Preparation of Enol-ether Tri
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Scheme 3.15 Synthesis of cycloisome
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Scheme 3.17 Cycloisomerization of a
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Scheme 3.19 Tandem cycloadditions o
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Scheme 3.21 Intermolecular Diels-Al
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attractive, since additional functi
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increased yield of the triene (47%)
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as an isobutyl-amide 155b was prepa
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group) demonstrated that this cyclo
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in 1M HCl/dioxane (1 : 1) for 1h, t
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ppm (dd, J = 7.1, 4.6 Hz, 1H) assig
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http://ccc.chem.pitt.edu/). Using f
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Notably, exclusive cycloisomerizati
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intermediate in the reaction we sou
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epulsive dipole interactions (Schem
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Table 3.4 Diels-Alder reactions of
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allenic Alder-ene reaction, ene-all
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Figure 3.4 Examples of natural prod
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species onto the proximal double bo
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Scheme 3.49 Rh(I)-catalyzed ene rea
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y Magnus 144 and it involves the in
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usually is DMSO. Heating to 100 ºC
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that require high pressures of CO.
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In contrast to the Mo(CO)6-mediated
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Scheme 4.15 Rh(I)-catalyzed allenic
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4.2 Rhodium(I)-Catalyzed Cyclocarbo
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lack of double bond selectivity, si
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Table 4.2 Cyclocarbonylation reacti
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Notably, the allenic cyclocarbonyla
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Scheme 4.22 Cyclocarbonylation reac
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neat or in solution. This decomposi
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the newly synthesized fulvenes (e.g
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stereocenters and mixture of E/Z is
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proximal double bond to give α-alk
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the methyl ester and Ha are syn. Sc
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that the major diastereomer in the
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We were motivated to first examine
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Scheme 4.42 Synthesis of pyrrole 29
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periodic acid (H5IO6). 209 These hi
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eaction failed to go to completion,
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4.5.2 Synthesis of a Library of Tri
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diketones 312{1-3,1-2} in yields ra
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Figure 4.2 Distribution for physico
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tricyclic pyrrole 314{3,2,26} (Figu
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4.6 Synthesis of α-Alkylidene Cycl
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anched and linear carboxylic acid i
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eactivity of the species prepared i
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considerably lower than the ratio o
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diastereomer. Next, allenyne 328 wa
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Conclusions In summary, we have dem
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Experimental Section General Method
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General procedure A for esterificat
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F Bz N H 56f 2-Benzoylamino-3-(4-fl
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MeO2C Bz N H 58c 2-Benzoylamino-2-m
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MeO MeO2C Bz N H 58e 2-Benzoylamino
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mL) and MeOH (10 mL) instead of sat
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hexanes-EtOAc, 19 : 1 to 4 : 1, v/v
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which was immediately used in the C
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Boc TMS N H Bn 64f tert-Butyl-1-((4
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MeI (38 µL, 0.62 mmol). Yield 65a
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with brine and concentrated under v
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H MeO 2C • H Bn NHBoc tert-Butyl-
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TMS MeO 2C • 70 H H NHBoc 2-tert-
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185 (10), 141 (21), 57 (100); EI-HR
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dispersion in mineral oil, 1.0 mmol
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EI-HRMS calcd for C30H26NO3 m/z [M-
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CbzN MeO 2C Me 73h 2-[Benzyloxycarb
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CbzN MeO 2C Me 2-(Benzyloxycarbonyl
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dispersion in mineral oil, 3.85 mmo
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completion of the addition, the rea
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BzN MeO 2C S 74h 2-(Benzoylprop-2-y
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BzN MeO 2C Bn 75b 2-(Allylbenzoylam
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BzN MeO 2C TBSO 75e 2-(Benzoylbut-2
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Hz, 1H), 5.85 (s, 1H), 5.52 (dd, J
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1H), 3.69 (s, 3H), 1.58 (d, J = 7.1
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µmol), [Rh(CO)2Cl]2 (1 mg, 3 µmol
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1.25 (m, 6H), 0.88 (t, J = 6.9 Hz,
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6.72 (d, J = 7.6 Hz, 0.5H), 6.68 (d
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BzN MeO2C Bn 122a Methyl-2-(N-(but-
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Bz N MeO2C Bn 1-Benzoyl-2-benzyl-4-
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13.9, 5.3 Hz, 1H), 2.51-2.47 (m, 1H
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15 min the solvent was removed unde
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Benzoyl chloride (0.169 mL, 1.46 mm
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mg, 0.11 mmol), [Rh(CO)2Cl]2 (4 mg,
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mL). kk The aqueous layer was extra
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ºC. After quenching the reaction b
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129.8, 129.0, 128.7, 128.4, 126.2,
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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.
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1H), 5.49 (dd, J = 17.3, 1.8 Hz, 1H
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was stirred at rt for 1 h when it w
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BzN HOOC 2-(N-(but-2-ynyl)benzamido
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°C and DIBAL-H (0.440 mL of a 1.0M
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129 (62), 91 (100); EI-HRMS calcula
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(d, J = 18.0 Hz, 1H), 4.14 (d, J =
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4.98 (dt, J = 7.7, 5.1 Hz, 1H), 4.1
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N Bz MeO2C OTBS 214 1-Benzoyl-2-(te
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270a (major diastereomer-eluting fi
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CDCl3): δ 7.42-7.17 (m, 13H), 7.04
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18.6 Hz, 1H), 4.34 (d, J = 18.0 Hz,
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Bz N MeO2C 2-Benzoyl-3,7-dimethyl-6
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v/v) afforded a mixture of compound
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(435 mg, 1.21 mmol), DMSO (429 µL,
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4.02 (s, 1H), 3.88 (s, 3H), 1.82 (s
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(207 mg, 96%) consisting of 287e (7
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procedure O, using: 74f (110 mg, 0.
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Bz N O H CO2Me BocN 287i 3-(2-Benzo
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4.17 (d, J = 15.0 Hz, 1H), 4.10 (d,
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137.1, 136.9, 130.4, 129.8, 128.5,
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H BzN MeO2C Bn H N C3H7 298b CO 2Me
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NMR (75 MHz, CDCl3): δ 172.3, 169.
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following the general procedure Q,
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H BzN MeO2C Bn H 5-Benzoyl-1,4-dibe
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119.9, 114.1, 109.9, 108.6, 73.0, 5
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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: 130. Oppolzer, W.; Snieckus, V. Ang
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
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