Investigación

 

Rhodium (II) Catalyzed Wolff Rearrangement of a Carbenoid Derived from an Indolyl Diazopropanedione

 

Erick Cuevas Yañez* and Raymundo Cruz Almanza^†

 

Instituto de Química de la Universidad Nacional Autónoma de México. Circuito Exterior, Ciudad Universitaria, Coyoacán, 04510, México, D.F. Tel. (52) 56 22 44 08; fax (52) 56 16 22 17. E-mail: erick.cuevas@correo.unam.mx

 

Recibido 27 de febrero del 2004.
Aceptado el 31 de marzo del 2004.

 

Abstract

The Rhodium (II) acetate catalyzed reaction of 3-diazo-1-(indol-3-yl)- propane-1,2-dione did not give the expected intramolecular cyclization product, affording only 3-acetylindole in 70% yield. A reaction mechanism which involves a Wolff rearrangement is proposed.

Key Words: Carbenoid, rearrangement, indole.

 

Resumen

La reacción catalizada por acetato de rodio (II) de la 3-diazo-1-(3-indoil)-1,2-propanodiona no dio el producto de ciclación intramolecular esperado, generando solamente 3-acetilindol en un rendimiento del 70% . Se propone un mecanismo de reacción que involucra una transposición de Wolff.

Palabras clave: Carbenoide, transposición, indol.

 

Introduction

The diazo group chemistry has taken a new interest as a consequence of the development of catalytic methods with transition metals which particularly convert diazoketones in to valuable tools in organic synthesis with several applications in homologations, X-H bond insertions, ylide formations, and reactions with alkenes and aromatic compounds [1].

The carbenoid reactions over rich-electron heterocyclic compounds have been useful in the synthesis of polyenes from furans [2] and in the indolizidine alkaloids synthesis from pyrroles [3].

Even though, the first reactions of carbenoids derived from α-diazoketo compounds and copper bronzes over indoles were described almost 70 years ago [4], however these reactions were of limited scope and only ethyl diazoacetate or diazoacetone were used as carbenoid precursors, while the yields were moderate or low [5,6]. This perspective changed when rhodium (II) carboxylates were introduced and catalytic processes were performed. Thus, intermolecular carbenoid insertions on indoles were used by the Muthusamy [7] and Kerr's [8] groups to prepare several 3- and 2- substituted indoles. Additionally, there are many reports on the intramolecular carbenoid insertion and subsequent cyclization of diazoalkanoylindoles wherein the side chain is appended at the nitrogen position [9], and at the C-2 [10], C-3 [11] and C-4 [12] positions of indole.

In connection with other synthetic studies, we believed that carbenoid intramolecular insertions on indole could be used in the syntheses of biologically active substances, particularly in the synthesis of Nostodione A, a potent mitotic spindle poison from a blue-green alga Nostoc commune [13]. Nevertheless, we found in this way a collateral reaction which does not have precedent in the indole moiety that occurs instead of the carbenoid insertion. Therefore, this is the first report on a Wolff type rearrangement in carbenoids derived from 3-diazoalkanoylindoles.

 

Results and discussion

Initially we prepared the indoleglyoxylic acid chloride 1 by addition of an ethereal solution of indole into an ethereal solution of oxalyl chloride in a modification of the procedures reported by the Armstrong [14] and Lingens [15] research groups, in quantitative yield.

The next step in the synthetic route consisted on the treatment of compound 1 with an excess of ethereal diazomethane (3:1) at o °C to afford the 3-diazo-1-(indol-3-yl)- propane-1,2-dione (2) in 97 % yield [15, 16].

Finally, exposure of diazoketone 2 to a catalytic amount of rhodium (II) acetate in dichloromethane solution at room temperature afforded after alumina column chromatography purification, the unexpected 3-acetylindole 3 as the only isolable product in 70% yield.

Mechanistically, one can rationalize the 3-acetylindole formation as a consecutive Wolff rearrangement-carbon dioxide extrusion process, such as scheme 4 summarizes. In the first step the catalyst electrophilic addition causes the loss of molecular nitrogen and the production of a metal stabilized carbene (4). The subsequent Wolff rearrangement from carbenoid 4 to ketene 5 has preceding reports in other aliphatic and aromatic diazoketones [17-20]. However, at the moment indolyl diazocompounds have not been reported. Once ketene 5 has been formed, reaction with water from alumina (grade III activity) used in the purification gives the β-ketoacid 6 which rapidly generates carbon dioxide and 3-acetylindole. Similar decarboxylation reactions were reported by Meier, et al. [21] in some 2-diazo-1,3-dicarbonyl compounds. In addition, β-ketoacids can be decarboxylated in slight acid conditions [22-25].

In conclusion, we proposed a mechanism that involves a Wolff rearrangement to explain the formation of 3-acetylindole from 3-diazo-1-(indol-3-yl)- propane-1,2-dione (2). We are currently performing further experiments in order to elucidate the mechanistic details that would help us to predict the course of these carbenoid reactions.

 

Experimental

The starting materials were purchased from Aldrich Chemical Co. and were used without further purification. Solvents were distilled before use, ether and tetrahydrofuran (THF) were dried over sodium using benzophenone as indicator. Diazomethane was prepared from N-methyl-N-nitroso-p-toluenesulfonamide (Diazald ^®) using a minimum amount of water and ethanol as cosolvent, and dried over KOH pellets before use. Silica gel (230-400 mesh) and neutral alumina were purchased from Merck. Silica plates of 0.20 mm thickness were used for thin layer chromatography. Melting points were determined with a Fisher-Johns melting point apparatus and they are uncorrected. ¹H and ¹³C NMR spectra were recorded using a Varian Gemini 200, the chemical shifts (δ) are given in ppm relative to TMS as internal standard (0.00). For analytical purposes the mass spectra were recorded on a JEOL JMS-5X 10217 in the EI mode, 70 eV, 200 °C via direct inlet probe. Only the molecular and parent ions (m/z) are reported. IR spectra were recorded on a Nicolet Magna 55-X FT instrument.

Indol-3-yl-oxoacetyl chloride (1). To a stirred solution of indole (0.5 g, 4.2 mmol) in anhydrous ether (35 mL), at 0 °C, oxalyl chloride ( 0.41 mL, 0.59 g, 4.7 mmol) was added drop-wise during 30 min; stirring and cooling were continued for 1 hr. more. The resulting yellow crystals of 1 (0.97 g, 100% yield), were collected on a filter, washed with anhydrous ether, and dried in vacuo over potassium hydroxide; mp 134 °C ( lit. 134-136 °C) [14, 15].

3-diazo-1-(indol-3-yl)- propane-1,2-dione (2). An ice-cold solution of the acid chloride 1 (0.207g, 1 mmol) in freshly distilled ether (5 mL) was treated with then an ether solution of diazomethane (3 mmol) from N-methyl-N-nitroso-4-toluene-sulfonamide at 0 °C under a nitrogen atmosphere. A vigorous evolution of nitrogen occurred, and the mixture was allowed to warm to room temperature overnight. The solvent was removed in vacuo and the product was purified by column chromatography (Al₂O₃, hexane/ethyl acetate 9:1), to afford a yellow solid (0.21 g, 97%); mp 145 °C, IR (film) ν_max 3456, 3126, 2113, 1628 cm^-1; ¹H NMR (CDCl₃, 200 MHz) δ 6.33 (s, 1H), 7.25-7.45 (m, 2H), 8.42 (m, 2H), 8.73(d, 1H), 9.15 (s, 1H) ; ¹³C NMR (CDCl₃, 50 MHz) δ 54.5, 111.7, 122.4, 123.4, 124.3, 126.4, 134.3, 135.8, 137.2, 172.5, 185.7; MS [EI+] m/z : 213 [M]⁺ (15), 144 [M - COCHN₂]⁺ (100).

Reaction of 3-diazo-1-(indol-3-yl)- propane-1,2-dione (2) with rhodium (II) acetate. A solution of the diazopropanedione 2 (0.214 g, 1 mmol) in dry CH₂Cl₂ (10 mL) was stirred with Rh₂(OAc)₄ (2 mg) under nitrogen atmosphere at room temperature. After 2 h, the mixture was evaporated in vacuo and purified by column chromatography (Al₂O₃, activity III, hexane/ethyl acetate 8:2) to yield 3-acetylindole 3 (0.111 g, 70%); mp 189-190 °C. IR (CHCl₃). ν_max 3463, 1649 cm^-1; ¹H NMR (CDCl₃, 200 MHz) δ 2.48 (s, 3H), 7.19 (m, 4H), 7.99 (m, 1H), 9.01 (s, 1H); ¹³C NMR (CDCl₃, 50 MHz) δ 26.8, 111.5, 116.7, 121.2, 121.3, 122.3, 125.0, 132.7, 136.4, 192.3; MS [EI+] m/z (%): 159 [M]⁺ (50), 144 [M -CH₃]⁺ (100).

 

Acknowledgments

Financial support from CONACyT (No. 37312-E) is gratefully acknowledged. The authors would like to thank Rocío Patiño, Angeles Peña, Nieves Zavala, Francisco Javier Pérez Flores and Luis Velasco for their technical support.

 

References

1. Doyle, M. P.; McKervey, M.A.; Ye, T.; Modern synthetic methods using diazocompounds: from cyclopropanes to ylides. John Wiley & Sons: New York, 1998.         [ Links ]

2. (a) Wenkert, E.; Guo, M.; Lavilla, R.; Porter, B.; Ramachandran, K.; Sheu, J. H. J. Org. Chem. 1990, 55, 6203-6214.         [ Links ] (b) Wenkert, E.; Decorzant R.; Naf, F. Helv. Chim. Acta 1989, 72, 756-766.         [ Links ] (c) Wenkert, E.; Guo, M.; Pizzo, F.; Ramachandran, K. Helv. Chim. Acta 1987, 70, 1429-1438.         [ Links ]

3. (a) Jefford, C. W.; Wang, J. B. Tetrahedron Lett. 1993, 34, 3119-3122.         [ Links ] (b) Jefford, C. W.; Tang, Q.; Zaslona , A. J. Am. Chem. Soc. 1991, 113, 3513-3518.         [ Links ] (c) Jefford, C. W.; Tang, Q.; Zaslona, A. Helv. Chim. Acta 1989, 72, 1749-1752.         [ Links ] (d) Jefford, C. W.; Kubota, T.; Zaslona, A. Helv. Chim. Acta 1986, 69, 2048-2061.         [ Links ]

4. Jackson, R. W.; Manske, R. H. Can. J. Res. B 1935, 13, 170-174.         [ Links ]

5. Novak, J.; Ratusky, J.; Sneberk, V.; Sorm, F. Collect. Czech. Chem. Commun. 1957, 22, 1836-1851.         [ Links ]

6. Nametkin, S. S.; Melnikov, N. N.; Bokarev, K. S. Zhur. Priklad. Khim. 1956, 29, 459-463;         [ Links ] Chem. Abs. 1956, 50, 13867f.         [ Links ]

7. Muthusamy, S.; Gunanathan, C.; Babu, S. A.; Suresh, E.; Dastidar, P. J. Chem. Soc. Chem. Commun. 2002, 824-825.         [ Links ]

8. Gibe, R.; Kerr, M. A. J. Org. Chem. 2002, 67, 6247-6249.         [ Links ]

9. Jefford, C. W.; Johncock, W. Helv. Chim. Acta 1983, 66, 2666-2671.         [ Links ]

10. Salim, M.; Capretta, A. Tetrahedron 2000, 56, 8063-8069.         [ Links ]

11. Cuevas-Yañez, E.; Muchowski, J. M.; Cruz-Almanza, R. Tetrahedron 2004, 60, 1505-1511.         [ Links ]

12. Matsumoto, M.; Watanabe, N.; Kobayashi, H. Heterocycles 1987, 26, 1479-1482.         [ Links ]

13. Kobayashi, A.; Kajiyama, S. I.; Inakawa, K.; Kanzaki, H.; Kawazu, K. Z. Naturforsch. C: Biosci. 1994, 49, 464-470.         [ Links ]

14. Shaw, K. N. F; McMillan, A; Gudmudson, A. G; Armstrong, M. D. J. Org. Chem. 1958, 23, 1171-1178.         [ Links ]

15. Lingens, F.; Lange, J. Liebigs Ann. Chem. 1970, 738, 46-53.         [ Links ]

16. Nogrady, T.; Doyle, T. W; Morris L. J. Med. Chem. 1965, 8, 656-659.         [ Links ]

17. Taber, D. F.; Ruckle, R.E. J. Am. Chem. Soc. 1986, 108, 7686-7693.         [ Links ]

18. Lee, Y. R; Suk J. Y; Kim B.S. Tetrahedron Lett. 1999, 40, 8219-8221.         [ Links ]

19. Maguire, A. R; Kelleher, P. G; Lawrence S.E. Tetrahedron Lett. 1998, 39, 3819-3852.         [ Links ]

20. Nakano, H; Ibata, T. Bull. Chem. Soc. Jpn. 1993, 66, 238-244.         [ Links ]

21. Meier, H.; Wengenroth, H.; Lauer, W.; Krause, V. Tetrahedron Lett. 1989, 30, 5253-5256.         [ Links ]

22. Noyce, D. S.; Matesich, M. A. J. Org. Chem. 1967, 32, 3243-3244.         [ Links ]

23. Swain, C. G.; Bader, R. F. W.; Esteve, R. M.; Griffin, R. N. J. Am. Chem. Soc. 1961, 83, 1951-1955.         [ Links ]

24. Ferris, J. P.; Miller, N. C. J. Am. Chem. Soc. 1966, 88, 3522-3527.         [ Links ]

25. Pedersen, K. J. Acta Chem. Scand. 1961, 15, 1718-1722.         [ Links ]

 

Nota

^†Deceased, October 2003.