A nice looking Russian chick gave this to me today:
Synlett 12 (1998) 1335-1336A Mild and Efficient Nef Reaction for the Conversion of Nitro to Carbonyl Group by
Dimethyldioxirane (DMD) Oxidation of Nitronate Anions
Waldemar Adam, Mieczyslaw Makosza, Chantu R. Saha-Möllera, Cong-Gui Zhao*
Institut für Organische Chemie, Universität Würzburg, am Hubland, D-97074 Würzburg, Germany
Tel: +49-931-8885340; Fax: +49-931-8884756; E-mail: adam@chemie.uni-wuerzburg.de
Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland
Received 1 September 1998
Abstract: DMD oxidation of nitronate anions, generated in situ from the corresponding nitroalkanes, affords the corresponding carbonyl products. Highest yields were obtained when one equivalent of water was added before the oxidation with DMD.
Nitroalkanes are useful building blocks in organic synthesis since the nitro group may be transformed into numerous functionalities,[1] most importantly, into the carbonyl group which is known as the Nef reaction.[2] The Nef reaction was originally carried out under acidic conditions, e.g. with strong acid such as aqueous HCl.[1,2] To avoid such drastic conditions, some oxidative methods with KMnO4,[3] K2S2O8,[4] O3,[5] O2,[6] and most recently, Caroate [7] (known also as OxoneTM) have been developed. However, all these stoichiometric methods usually give only moderate yields of the carbonyl products, especially when an aldehyde is formed. Bartlett et al. [8] reported the first metal-catalyzed oxidation in which tBuOOH/VO(acac)2 was employed, but concentrated tBuOOH (90%) is required. Clearly, a milder and more efficient method for such conversions is still in demand, and we presently demonstrate that dimethyldioxirane serves this purpose well.
Dioxiranes, especially dimethyldioxirane (DMD) and methyl-(trifluoromethyl)dioxirane (TFD), either in the isolated form [9,10] or generated in situ, have been established as very powerful yet highly selective oxidants.[11] The regeneration of the carbonyl functionality from acetals,[12] orthoesters [12] and hydrazones [13] by DMD or TFD is well-known in the literature. Recently, we reported [14] that the DMD oxidation of sigma-H adducts generated from the addition of the carbanion of 2-phenylpropionitrile to nitroarenes which can be considered as cyclohexadiene nitronates produces high yields of phenols, a transformation which is mechanistically akin to the Nef reaction. We envisaged that the DMD oxidation of the nitronate anions derived from nitroalkanes should lead to the corresponding carbonyl products as a convenient and efficient alternative to the traditional Nef reaction, as confirmed by the high yields in Table 1.
When a slight excess of DMD was added as acetone solution to the nitronate anion 2a, generated in situ from the nitroalkane 1a, a good yield of the keto ester 3a was obtained (entry 1). Without DMD, no conversion of the nitronate to the carbonyl product 3a took place (data not shown). Since we have observed a pronounced water effect in the DMD oxidation of sigma-H adducts derived from nitroarenes,[14] one equivalent of water was intentionally added to the nitronate prior to DMD and an excellent yield of the keto ester 3a was obtained (entry 2); however, the reverse addition of water and DMD was ineffective (entry 3). A similar water effect was found for substrate 1b (entries 4-6). In this way, very good yields of the carbonyl products 3c-e were also obtained from the corresponding nitro compounds 1c-1e (entries 7-9). Noteworthy is that the aldehyde 3e was prepared in good yield with the present method (entry 9). The beneficial water effect in enhancing the oxidation yield is presumably due to the increased reactivity of DMD through hydrogen-bonding with water, as suggested by experimental [22] and theoretical [23] studies.
In summary, the DMD oxidation of nitronate anions provides a mild and efficient alternative to the traditional Nef reaction. Since the required nitro compounds are conveniently prepared by the Michael addition of simple nitroalkanes to a,b-unsaturated carbonyl derivatives,[15,16] this transformation is recommended for its high yields and convenient workup.[24] Of interest for preparative applications, the keto diester 3d has been used in natural product synthesis [5] and is now readily available in high yield by the DMD oxidation of the nitronate 2d.
(-)O R1 R1
R1-CH-R2 tBuOK | | H2O DMD aq NH4Cl |
| -----------------> (+)N=CH -------> -------> --------> C=O
NO2 THF/ca 20°C/5 min | | 2 min 5 min |
(-)O R2 R2
(1) (2) (3)
TABLE 1
ENTRY SUBSTRATE H2O(eqv) DMD(eqv) PRODUCT YIELD(%) (*)
1 Et-C(-NO2)-C2H4-COOMe 0 1.2 Et-C(=O)-C2H4-COOMe 67
2 1.0 1.2 90
3 (**) 1.0 1.2 64
4 Et-C(-NO2)-C2H4-C(=O)-Me 0 1.2 Et-C(=O)-C2H4-C(=O)-Me 56
5 (**) 1.0 1.2 80
6 1.0 1.2 99
7 Et-C(-NO2)-C2H4-CN 1.0 1.2 Et-C(=O)-C2H4-CN 86
8 O2N-CH-(C2H4-COOMe)2 1.0 1.2 O=CH-(C2H4-COOMe)2 83
9 O2N-C3H6-COOMe 1.0 1.2 OHC-C2H4-COOMe 73
(*) Yield of isolated product after silica gel chromatography; products 3a [17],
3b [18], 3c [19], 3d [20] and 3e [21] have identical spectral data and physical
constants as those reported.
(**) Water was added after DMD
1a = Et-C(-NO2)-C2H4-COOMe
1b = Et-C(-NO2)-C2H4-C(=O)-Me
1c = Et-C(-NO2)-C2H4-CN
1d = O2N-CH-(C2H4-COOMe)2
1e = O2N-C3H6-COOMe
3a = Et-C(=O)-C2H4-COOMe
3b = Et-C(=O)-C2H4-C(=O)-Me
3c = Et-C(=O)-C2H4-CN
3d = O=CH-(C2H4-COOMe)2
3e = OHC-C2H4-COOMe
Acknowledgement: Generous financial support of the Deutsche Forschungsgemeinschaft (Schwerpunktprogramm: Peroxidchemie) and the Fonds der Chemischen Industrie is gratefully appreciated. M. Makosza thanks the Alexander von Humboldt Foundation for the research award which made this collaboration possible. C.-G. Z. thanks the DAAD (Deutscher Akademischer Austauschdienst) for a doctoral fellowship.
References and Notes:
(1) Seebach, D.; Colvin, E. W.; Lehr, F.; Weller, T. Chimia 1979, 33,1.
(2) Noland, W. E. Chem. Rev. 1955, 55, 137; Pinnick, H. W. Org. React. 1990, 38, 655.
(3) Schechter, H.; Williams, F. T. J. Org. Chem. 1962, 27, 369.
(4) Pagano, A.H.; Schechter, H. J. Org. Chem. 1970, 35, 295.
(5) McMurry, J. E.; Melton, J.; Padgett, H. J. Org. Chem. 1974, 39,259.
(6) Williams, J. R.; Unger, L. R.; Moore, R. H. J. Org. Chem. 1978,43, 1271.
(7) Ceccherelli, P.; Curini, M.; Epifano, F.; Marcotullio, M. C.;Rosati, O. Synth. Commun. 1998, 28, 3057.
(
Bartlett, P. A.; Green III, F. R.; Webb, T. R. Tetrahedron Lett. 1977, 331.
(9) Murray, R. W.; Jeyaraman, R. J. Org. Chem. 1985, 50, 2847.
(10) Adam, W.; Bialas, J.; Hadjiarapoglou, L. P. Chem. Ber. 1991, 124, 2377.
(11) For reviews see: Adam, W.; Curci, R.; Edwards, J. O. Acc. Chem. Res. 1989, 22, 205; Murray, R. W. Chem. Rev. 1989, 89, 1187; Curci, R. In Advances in Oxygenated Process; Baumstark, A. L. Ed.; JAI: Greenwich CT, 1990, Vol 2, Chapter I, pp 1; Adam, W.; Hadjiarapoglou, L. P.; Curci, R.; Mello, R. In Organic Peroxides; Ando, W. Ed.; Wiley: New York, 1992, Chapter 4, pp 195; Curci, R.; Dinoi, A.; Rubino, M. F. Pure Appl. Chem. 1995, 67, 811; Adam, W.; Smerz, A. K. Bull. Soc. Chim. Belg. 1996, 105, 581; Adam, W.; Smerz, A. K.; Zhao, C.-G. J. Prakt. Chem. 1997, 339, 298.
(12) Curci, R.; D’Accolti, L.; Fiorentino, M.; Fusco, C.; Adam, W. González-Nuñez, M. E.; Mello, R. Tetrahedron Lett. 1992, 33, 4225.
(13) Altamura, A.; Curci, R.; Edwards, J. O. J. Org. Chem. 1993, 58, 7289.
(14) Adam, W.; Ma, kosza, M.; Stalin`ski, K.; Zhao, C.-G. J. Org. Chem 1998, 63, 4390.
(15) Ballini, R.; Bosica, G. Eur. J. Org. Chem. 1998, 355; Ballini, R.; Bosica, G. Tetrahedron Lett. 1996, 44, 8027.
(16) Chasar, D. W. Synthesis 1982, 841-842.
(17) Baldwin, J. E.; Adlington, R. M.; Jain, A. U.; Kolhe, J. N.; Perry, M. W. D. Tetrahedron 1986, 42, 4247.
(18) Macias, F. A.; Molinillo, J. M. G.; Massanet, G. M.; Rodriguez-Luis, F. Tetrahedron 1992, 48, 3345.
(19) Coveney, D. J.; Patel, V. F.; Pattenden, G.; Thompson, D. M. J. Chem. Soc., Perkin Trans. 1 1990, 2721.
(20) Huisgen, R.; Fliege, W.; Kolbeck, W. Chem. Ber. 1983, 116, 3027.
(21) Ono, N.; Katayama, H.; Nisyiyama, S.; Ogawa, T. J. Heterocycl. Chem. 1994, 31, 707.
(22) Baumstark, A. L.; Vasquez, P. C. J. Org. Chem. 1988, 53, 3437; Murray, R. W.; Gu, D. J. Chem. Soc., Perkin Trans. 2, 1993, 2203; Murray, R. W.; Gu, D. Ibid. 1994, 451; Buxton, P. C.; Ennis, J. N.; Marples, B.A.; Waddington, V. L.; Boehlow, T. R. Ibid. 1998, 265.
(23) Miaskiewicz, K.; Teich, N. A.; Smith, D. A. J. Org. Chem. 1997, 62, 6493.
(24) General Procedure: To a solution of the nitroalkane (1.0 mmol) in THF (10 mL, freshly distilled over potassium) was added t-BuOK (123 mg, 1.1 mmol) and the mixture was stirred at room temperature (ca. 20 °C) for 5 min. Then H2O (18.0 mL, 1.0 mmol) was added, stirred for 2 min, and a solution of DMD (1.2 mmol, 0.07-0.10 M) in acetone (dried over molecular sieves 4Å) was added in one portion. After 5 min, the reaction mixture was neutralized with aqueous NH4Cl (0.5 mL) and dried over MgSO4. The MgSO4 was removed by filtration and washed with acetone (3´10 mL). The crude product, obtained after evaporation (20 °C, 30 mbar) of the solvent, was purified by silica gel chromatography with 30-50% ether in petroleum ether (b.p. 30-50 °C) as eluent (1:1 EtOAc/n-hexane was used for 3d).
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