HETEROCYCLES

Communication | Special issue | Vol. 80, No. 1, 2010, pp. 207-211
Received, 21st July, 2009, Accepted, 18th August, 2009, Published online, 20th August, 2009.
DOI: 10.3987/COM-09-S(S)62

■ A Hetero Pauson-Khand Reaction of Ketenimines: A New Synthetic Method for γ-Exomethylene-α,β-unsaturated γ-Lactams

Takao Saito,* Katsuya Sugizaki, Hiroyuki Osada, Noriki Kutsumura, and Takashi Otani

Department of Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka 1-3, Shinjuku-ku, Tokyo 162-8601, Japan

Abstract

A novel ketenimine Pauson–Khand reaction has been described for the first time. C,C,N-Triarylketenimines reacted with alkyne–dicobalthexacarbonyl complexes upon heating in toluene in the presence of dimethyl sulfoxide as a promoter to afford γ-lactams, 5-(diphenylmethylene)-1H-pyrrol-2(5H)-ones, in good yields.

The Pauson–Khand reaction, formally a cobalt-mediated three-component [2 + 2 + 1] cocyclization of an alkyne, an alkene and carbon monoxide, constitutes one of the most useful, convergent and atom-economical methods for the synthesis of a cyclopentenone.1-4 Since the first publications in the early 70s,1 many advances in this method and its related processes have been made, involving discovery or improvement of promoters to effect the reaction, the Pauson–Khand type reaction mediated by other metals, the allenic or electron-deficient alkenic Pauson–Khand type reaction, and the catalytic variant as well as the asymmetric version.2-4 A hetero Pauson–Khand type reaction has also been developed in which a hetero-alkene π-component such as a carbonyl (ketone and aldehyde) or an imine is used instead of an alkene or alkyne partner to give a γ-butyrolactone5 or a γ-butyrolactam.6 Recently, a heterocumulenic Pauson–Khand type reaction was reported from our laboratory in which alkyne-carbodiimides were used as an alkyne-hetero-alkene partner to give [2 + 2 + 1] cyclocarbonylation products, pyrrolo- or indolo-fused γ-lactams.7-9 Mukai et al. applied a catalytic version of this carbodiimide Pauson–Khand reaction for synthesis of hexahydropyrrolo[2,3-b]indole alkaloids.10 The synthetic utility of such heterocumulenic Pauson–Khand type cyclocarbonylation has also been enhanced by the synthesis of poly-substituted maleimides, in which the reaction involved the ruthenium-catalyzed intermolecular [2 + 2 + 1] cocyclization of isocyanates, alkynes, and carbon monoxide.11 Alkyne-isothiocyanates have also been used successfully in the heterocumulenic Pauson–Khand type method leading to indolo-γ-thiolactones (thieno[2,3-b]indol-2-ones).12 A ketenimine is now our target molecule for evaluating the heterocumulene-mediated [2 + 2 + 1] cocyclization reaction. We herein report the first example of the ketenimine Pauson–Khand reaction.
We took a fundamental protocol using Co2(CO)8 for the intermolecular Pauson–Khand reaction among a ketenimine (1),13 an alkyne (2), and CO. In a model reaction between ketenimine 1a and the preformed methyl propiolate-Co2(CO)6 complex 3a (Scheme 1), the desired ketenimine Pauson–Khand reaction did not proceed in the absence of a promoter even after refluxing in toluene for 8 h (Table 1, entry 1). Therefore, in order to find an efficient promoter for accelerating the ketenimine Pauson–Khand reaction, the reactions in the presence of promoters such as P(OPh)3, N-methylmorpholine oxide (NMO), (CH2)5S, CH3CN, dimethylformamide (DMF), and dimethyl sulfoxide (DMSO) were examined (entries 2-7). Among the promoters tested, DMSO3,14 was found to most effectively accelerate the Pauson–Khand reaction for producing 5-(diphenylmethylene)-2-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate methyl ester (4a)15,16 in a fair yield (50%, entry 7).

With the optimal promoter (DMSO) and conditions identified, the scope of the reaction with respect to both substrates, ketenimine (1) and alkyne-complex (3), bearing a variety of substituents (R1, R2, and R3) was then examined (Scheme 2). The results are shown in Table 2. Thermally stable C,C,N-triarylketenimines 1a-d were found to be good components in the Pauson–Khand reaction with the cobalt-alkyne complex 3a-d having a variety of substituents to give the desired γ-methylene-γ-lactams 4a-m in moderate to good yields (entries 1-13). In contrast, the reaction of ketenimine 1e (R2 = H) with 3a failed, and the product 4n was not detected (entry 14). This is probably due to the thermal instability of ketenimine 1e and its cobalt complex, which readily isomerize and/or polymerize under the employed conditions.13

In summary, the ketenimine Pauson–Khand reaction was realized yielding γ-methylene-γ-lactams, though usable ketenimines were limited to thermally tolerant triarylketenimines.

References

1. (a) I. U. Khand, G. R. Knox, P. L. Pauson, and W. E. Watts, J. Chem. Soc., Chem. Commun., 1971, 36; CrossRef (b) I. U. Khand, G. R. Knox, P. L. Pauson, W. E. Watts, and M. I. Foreman, J. Chem. Soc., Perkin Trans. 1, 1973, 977; CrossRef (c) P. L. Pauson, Tetrahedron, 1985, 41, 5855. CrossRef
2. For discussions on the [2 + 2 + 1] reaction: N. Jeong, ‘Transition Metals for Organic Synthesis,’ ed. by M. Beller, C. Bolm, Wiley-VCH, Weinheim, 1998, Vol. I, pp. 560-577; CrossRef D. Strübing and M. Beller, ‘Transition Metals for Organic Synthesis,’ ed. by M. Beller and C. Bolm, Wiley-VCH, Weinheim, 2004, Vol. I, pp. 619-632; CrossRef N. E. Schore, ‘Org. Reactions’ 1991, 40, 1, ed. by L. A. Paquette, John Wiley & Sons, Inc.; N. E. Schore, ‘Comprehensive Organometallic Chemistry II,’ ed. by E. W. Abel, F. A. Stone, and G. Wilkinson, Elsevier, New York, 1995, Vol. 12, p. 703.
3. For reviews on the Pauson-Khand reaction (using mainly cobaltcarbonyl complexes): (a) T. Sugihara, M. Yamaguchi, and M. Nishizawa, Chem. Eur. J., 2001, 7, 1589; CrossRef (b) A. J. Fletcher and S. D. R. Christie, J. Chem. Soc., Perkin Trans. 1, 2000, 1657. CrossRef
4. For reviews on the Pauson-Khand type reaction (a) K. M. Brummond and J. L. Kent, Tetrahedron, 2000, 56, 3263; CrossRef (b) L. V. R. Boñaga and M. E. Krafft, Tetrahedron, 2004, 60, 9795; CrossRef (c) J. Blanco-Urgoiti, L. Añorbe, L. Pérez-Serrano, G. Domînguez, and J. Pérez-Castells, Chem. Soc. Rev., 2004, 33, 32; CrossRef (d) S. E. Gibson and A. Stevenazzi, Angew. Chem. Int. Ed., 2003, 42, 1800 (catalytic); CrossRef (e) B. Alcaide and P. Almendros, Eur. J. Org. Chem., 2004, 3377 (allenic); CrossRef (f) M. Rodrîguez Rivero, J. Adrio, and J. C. Carretero, Synlett, 2005, 26 (electron-deficient alkenic); CrossRef (g) M. Rodrîguez Rivero, J. Adrio, and J. C. Carretero, Eur. J. Org. Chem., 2002, 2881(electron-deficient alkenic); CrossRef (h) O. Geis and H.-G. Schmalz, Angew. Chem. Int. Ed., 1998, 37, 911; CrossRef (i) H.-W. Frühauf, Chem. Rev., 1997, 97, 523; CrossRef (j) S. Laschat, A. Becheanu, T. Bell, and A. Baro, Synlett, 2005, 2547. CrossRef
5. For oxa-PK, Ti: (a) N. M. Kablaoui, F. A. Hicks, and S. L. Buchwald, J. Am. Chem. Soc., 1996, 118, 5818 (catalytic); CrossRef (b) W. E. Crowe and A. T. Vu, J. Am. Chem. Soc., 1996, 118, 1557; CrossRef (c) S. K. Mandal, R. Amin, and W. E. Crowe, J. Am. Chem. Soc., 2001, 123, 6457 (catalytic, asymmetric); CrossRef Ru (d) N. Chatani, T. Morimoto, Y. Fukumoto, and S. Murai, J. Am. Chem. Soc., 1998, 120, 5335 (catalytic); CrossRef (e) N. Chatani, M. Tobisu, T. Asaumi, Y. Fukumoto, and S. Murai, J. Am. Chem. Soc., 1999, 121, 7160 (catalytic, intermolecular); CrossRef (f) S.-K. Kang, K.-J. Kim, and Y.-T. Hong, Angew. Chem. Int. Ed., 2002, 41, 1584 (catalytic); CrossRef Mo: (g) C.-M. Yu, Y.-T. Hong, and J.-H. Lee, J. Org. Chem., 2004, 69, 8506 (allenic); CrossRef (h) J. Adrio and J. C. Carretero, J. Am. Chem. Soc., 2007, 129, 778 (Mo(CO)3DMF3); CrossRef Ni: (i) S. Ogoshi, M. Oka, and H. Kurosawa, J. Am. Chem. Soc., 2004, 126, 11802. CrossRef
6. For aza-PK, Ru: (a) A. Göbel and W. Imhof, Chem. Commun., 2001, 593; CrossRef (b) N. Chatani, T. Morimoto, A. Kamitani, Y. Fukumoto, and S. Murai, J. Organomet. Chem., 1999, 579, 177; CrossRef Fe: (c) H. Kisch, Z. Naturforsch., 1997, 52b, 994.
7. T. Saito, M. Shiotani, T. Otani, and S. Hasaba, Heterocycles, 2003, 60, 1045 (Mo, stoichiometric). CrossRef
8. T. Saito, K. Sugizaki, T. Otani, and T. Suyama, Org. Lett., 2007, 9, 1239 (Rh, catalytic). CrossRef
9. Before our first report on the heterocumulenic Pauson–Khand type reaction appeared, only two examples of such heterocumulenic [2 + 2 + 1] cocyclization had been reported. These involved the intermolecular reaction of diphenylcarbodiimide or phenyl isocyanate with diphenylacetylene and Fe(CO)5 or Ni(cod)2, which indeed afforded a hetero Pauson–Khand type product: (a) Y. Ohshiro, K. Kinugasa, T. Minami, and T. Agawa, J. Org. Chem., 1970, 35, 2136; CrossRef (b) H. Hoberg and B.W. Oster, J. Organomet. Chem., 1982, 234, C35. CrossRef
10. (a) C. Mukai, T. Yoshida, M. Sorimachi, and A. Odani, Org. Lett., 2006, 8, 83; CrossRef (b) D. Aburano, T. Yoshida, N. Miyakoshi, and C. Mukai, J. Org. Chem., 2007, 72, 6878. CrossRef
11. T. Kondo, M. Nomura, Y. Ura, K. Wada, and T. Mitsudo, J. Am. Chem. Soc., 2006, 128, 14816. See also ref. 9b. CrossRef
12. T. Saito, H. Nihei, T. Otani, T. Suyama, N. Furukawa, and M. Saito, Chem. Commun., 2008, 172. CrossRef
13. (a) M. Shimizu, Y. Gama, T. Takagi, M. Shibakami, and I. Shibuya, Synthesis, 2000, 517; CrossRef (b) G. R. Krow, Angew. Chem., Int. Ed. Engl., 1971, 10, 435; CrossRef (c) R. Aumann, Angew. Chem. Int. Ed., 1988, 27, 1456; CrossRef (d) D. G. McCarthy and A. F. Hegarty, J. Chem. Soc., Perkin Trans. 2, 1980, 579. CrossRef
14. Y. K. Chung, B. Y. Lee, N. Jeong, M. Hudecek, and P. L. Pauson, Organometallics, 1993, 12, 220. CrossRef
15. A mixture of the dicobaltoctacarbonyl (622 mg, 1.82 mmol) and methyl propiolate (2a, 153 mg, 1.82 mmol) in CH2Cl2 (10 mL) was stirred at room temperature for 2 hours. Removal of the solvent and column chromatography of the residue on silica gel (hexane/EtOAc (3:1)) afforded quantitatively the dicobalthexacarbonyl-methyl propiolate complex (3a) as an oil. A mixture of 3a　(112 mg, 0.303 mmol), C,C,N-triphenylketenimine (1a,13 97.8 mg, 0.363 mmol) and DMSO (0.11 mL, 1.52 mmol) in toluene (5 mL) was heated at 115 ˚C for 2 hours. The reaction mixture was evaporated and the residue was chromatographed on silica gel, eluting with hexane/ EtOAc (3:1), to give the P—K product 4a (57.8 mg, 50%).
Methyl 5-(diphenylmethylene)-2-oxo-1-phenyl-2,5-dihydro-1H-pyrrole-3-carboxylate (4a): Yellow solid, mp 149.0-151.0 °C; 1H-NMR (300 MHz, CDCl3) δ: 7.82 (s, 1H), 7.24-7.47 (m, 5H), 6.83-7.01 (m, 10H), 3.89 (s, 3H); 13C-NMR (76 MHz, CDCl3) δ: 166.8 (CO), 162.7 (CO), 146.4 (CH), 140.0 (C), 137.5 (C), 137.0 (C), 135.8 (C), 135.3 (C), 132.0 (2CH), 131.1 (2CH), 129.5 (CH), 128.7 (CH), 128.4 (2CH), 128.0 (2CH), 127.3 (2CH), 127.0 (2CH), 126.3 (CH), 122.6 (C), 52.2 (CH3).; IR (KBr): 1754, 1686, 1560, 1346, 1190, 1064, 740, 688 cm-1. HRMS-ESI (m/z): Calcd for C25H19NO3: [M]+ 381.1365. Found: 381.1358.
16. The structure 4 was determined spectroscopically (IR, 1H- and 13C-NMR). Particularly, the observed prominent 13C-NMR chemical shift values are in good agreement with those calculated for the structure 4 rather than those for the other possible chemo- and regio-isomers. The structure 4 was further supported by the fact that in the HMBC measurement, the correlation between the olefinic proton and the carbons (3JH-C , enamino β-carbon, two carbonyl carbons) was observed.