J. Org. Chem. 1999, 64, 2433-2439
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Efficient, Ecologically Benign, Aerobic Oxidation of Alcohols† Istva´n. E. Marko´,*,‡ Paul R. Giles,‡ Masao Tsukazaki,‡ Isabelle Chelle´-Regnaut,‡ Arnaud Gautier,‡ Stephen M. Brown,§ and Christopher J. Urch⊥ Universite´ Catholique de Louvain, De´ partement de Chimie, Laboratoire de Chimie Organique, Baˆ timent Lavoisier, Place Louis Pasteur 1, B-1348 Louvain-la-Neuve, Belgium Received November 10, 1998
The oxidation of alcohols into aldehydes and ketones can be efficiently performed using catalytic amounts of CuCl‚Phen and molecular oxygen or air. This novel, ecologically friendly procedure releases water as the only byproduct. The transformation of alcohols into aldehydes and ketones is of paramount importance in organic chemistry, both for laboratory-scale experiments and in the manufacturing processes.1 Unfortunately, the vast majority of the common oxidants have to be used at least in stoichiometric amount. Moreover, they are usually hazardous or toxic and generate large quantities of noxious byproducts.2 While many ecologically benign processes have been developed for the reduction of carbonyl derivatives,3 similar procedures have been far less investigated for the oxidation of alcohols.4 Despite their obvious economical and ecological importance, few catalytic systems are available for the transformation of alcohols into aldehydes and ketones, using molecular oxygen or air as the ultimate, stoichiometric oxidant.5 Moreover, most of the currently available catalytic oxidation processes suffer from severe limitations, being usually only effective with reactive alcohols, such as benzylic and allylic ones, or requiring high pressures, temperatures, and catalyst loading. We have already described in preliminary form the * To whom correspondence should be addressed. Fax: 32-10-47 27 88. E-mail:
[email protected]. † Dedicated with deep respect to Professor Theodore Cohen. ‡ Universite ´ Catholique de Louvain. § Zeneca Process Technology Department, Huddersfield Works, P.O. Box A38, Leeds Road, Huddersfield HD2 1FF, U.K. ⊥ Zeneca Agrochemicals, Jealott’s Hill Research Station, Bracknell, Berkshire RG42 6ET, U.K. (1) For general reviews on oxidation reactions, see: (a) Larock, R. C. In Comprehensive Organic Transformations; VCH Publishers Inc.: New York, 1989; p 604. (b) Procter, G. In Comprehensive Organic Synthesis; Ley, S. V., Ed.; Pergamon: Oxford, 1991; Vol. 7, p 305. (c) Ley, S. V.; Madin, A. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 251. (d) Lee, T. V. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 7, p 291. (2) Trahanovsky, W. S. In Oxidation in Organic Chemistry; Blomquist, A. T., Wasserman, H., Eds.; Academic Press: New York, 1978; Part A-D. (3) Noyori, R.; Hashigushi, S. Acc. Chem. Res. 1997, 30, 97 and references therein. (4) (a) Sheldon, R. A.; Kochi, J. K. In Metal-Catalyzed Oxidations of Organic Compounds; Academic Press: New York, 1981. (b) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639. (c) Murahashi, S.-I.; Naota, T.; Oda, Y.; Hirai, N. Synlett 1995, 733. (d) Krohn, K.; Vinke, I.; Adam, H. J. Org. Chem. 1996, 61, 1467 and references therein. (5) (a) Sheldon, R. A. In Dioxygen Activation and Homogeneous Catalytic Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 573. (b) James, B. R. In Dioxygen Activation and Homogeneous Catalytic Oxidation; Simandi, L. L., Ed.; Elsevier: Amsterdam, 1991; p 195. (c) Ba¨ckvall, J.-E.; Chowdhury, R. L.; Karlsson, U. J. Chem. Soc., Chem. Commun. 1991, 473. (d) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett. 1995, 36, 6923. (e) Mandal, A. K.; Iqbal, J. Tetrahedron 1997, 53, 7641 and references therein.
Figure 1.
discovery of a novel and ecologically friendly, catalytic aerobic protocol for the efficient oxidation of alcohols 1 into carbonyl derivatives 2 (Figure 1).6 In this paper, we wish to report full details on the establishment of this useful catalytic process and develop further its synthetic utility. In light of some of our preliminary mechanistic studies, a plausible catalytic cycle will also be discussed. Our own work in the area of aerobic oxidations was inspired by the exquisite research performed on the structure and reactivity of the binuclear copper proteins,7 hemocyanin and tyrosinase, and by the seminal contribution of Rivie`re and Jallabert.8 These two authors have shown that the simple copper complex CuCl‚Phen (Phen ) 1,10-phenanthroline) pro(6) (a) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Brown, S. M.; Urch C. J. Science 1996, 274, 2044. (b) Marko´, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle´-Regnaut, I.; Urch C. J.; Brown, S. M. J. Am. Chem. Soc. 1997, 119, 12661. (c) Marko´, I. E.; Tsukazaki, M.; Giles, P. R.; Brown, S. M.; Urch C. J. Angew. Chem., Int. Ed., Engl. 1997, 36, 2208. For an independent report of the aerobic TPAP-catalyzed oxidation of alcohols, see: Lenz, R.; Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1997, 3291. (7) For excellent reviews on the formation, isolation, and reactions of dinuclear copper(II) peroxides, see: (a) Karlin, K. D.; Gultneh, Y. Progr. Inorg. Chem. 1987, 35, 219-327. (b) Zuberbu¨hler, A. D. In Copper Coordination Chemistry: Biochemical and Inorganic Perspectives; Karlin, K. D., Zubieta, J., Ed.; Adenine: Guilderland, New York, 1983. (c) Sakharov, A. M.; Skibida, I. P. Kinet. Catal. 1988, 29, 96102. (d) Tyleklar, Z.; Jacobson, R. R.; Wei, N.; Murthy, N. N.; Zubieta, J.; Karlin, K. D. J. Am. Chem. Soc. 1993, 115, 2677-2689. (e) Kitajima, N.; Fujisawa, K.; Fujimoto, C.; Moro-oka, Y.; Hashimoto, S.; Kitagawa, T.; Toriumi, K.; Tatsumi, K.; Nakamura, A. Ibid. 1992, 114, 12771291. (f) Fox, S.; Nanthakumar, A.; Wikstrom, M.; Karlin, K. D.; Blackburn, N. J. Ibid. 1996, 118, 24-34. (g) Solomon, E. I.; Sundaram, U. M.; Machonkin, T. E. Chem. Rev. 1996, 96, 2563-2605. (8) (a) Jallabert, C.; Rivie`re, H. Tetrahedron Lett. 1977, 1215. (b) Jallabert, C.; Lapinte, C.; Rivie`re, H. J. Mol. Catal. 1980, 7, 127. (c) Jallabert, C.; Rivie`re, H. Tetrahedron 1980, 36, 1191. (d) Jallabert, C.; Lapinte, C.; Rivie`re, H. J. Mol. Catal. 1982, 14, 75. For other pertinent studies on aerobic oxidation of alcohols using copper complexes, see, for example: (a) Capdevielle, P.; Sparfel, D.; BaranneLafont, J.; Cuong, N. K.; Maumy, M. J. Chem. Res., Synop. 1993, 10 and references therein. (b) Munakata, M.; Nishibayashi, S.; Sakamoto, H. J. Chem. Soc., Chem. Commun. 1980, 219. (c) Bhaduri, S.; Sapre, N. Y. J. Chem. Soc., Dalton Trans. 1981, 2585. (d) Semmelhack, M. F.; Schmid, C. R.; Cortes, D. A.; Chon, C. S. J. Am. Chem. Soc. 1984, 106, 3374.
10.1021/jo982239s CCC: $18.00 © 1999 American Chemical Society Published on Web 03/18/1999
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Marko´ et al.
Figure 2.
moted the aerobic oxidation of benzylic alcohols to the corresponding aromatic aldehydes and ketones (Figure 2). Unfortunately, 2 equiv of the copper complex have to be used to achieve good conversions and the system is severely limited to benzylic substrates. Aliphatic alcohols proved to be either unreactive or underwent competing C-C bond cleavage.9 Our fascination for the Rivie`re and Jallabert procedure prompted us to reinvestigate this system and to modify various parameters with the hope of achieving catalyst turnover and establishing a useful and efficient aerobic protocol for the oxidation of all classes of alcohols into carbonyl derivatives. Our initial experiments were performed on p-chlorobenzyl alcohol and employed 2 equiv of CuCl‚Phen. It was rather disappointing to find that, besides NaOAc, all the other bases tested were far less efficient than K2CO3.10 However, during the course of these optimization studies, a dramatic influence of the solvent on the reaction rate was uncovered. For example, a 3-4-fold acceleration was obtained when toluene was substituted for benzene. In contrast, replacing benzene by m- or p-xylene resulted in a decrease in the rate of the reaction. Although it is difficult to offer a rational explanation for the profound effect displayed by minute changes in the structure of the solvent, it is quite reasonable to assume that the coordinating properties of these aromatic solvents may alter significantly the stability and reactivity of the copper complexes.11 Finally, it was also discovered that molecular oxygen could be replaced by air, a more readily available and inexpensive stoichiometric oxidant.12 But the real breakthrough was achieved when it was decided to lower the amount of the catalyst (Figure 3). Under the original Rivie`re and Jallabert conditions (2 equiv of CuCl‚Phen; benzene) any attempt at decreasing the concentration of the catalyst resulted in a disastrous curtailment in the reaction conversion. However, in (9) See, for example, ref 8a. (10) Other bases tested include, e.g., Na2CO3, Li2CO3, Na2HPO4, NaH2PO4, Al2O3, NaOAc, KOAc, KOH, and CuCO3. Only KOBut appears to act as an efficient base in the catalytic oxidation process. Its use is, however, limited at present to the oxidation of secondary alcohols (Marko´, I. E.; Gautier, A.; Chelle´-Re´gnaut, I.; Mutokole K. Unpublished results). (11) Solomon, R. G.; Kochi, J. K. J. Am. Chem. Soc. 1973, 95, 3300. (12) The use of air instead of oxygen results in a slower reaction rate. The oxidation can be increased by passing the air through a porous glass frit, which creates microbubbles. Under these conditions, the speed of the catalytic oxidation of alcohols using air matches the one employing oxygen.
Figure 3.
Figure 4.
toluene, reducing the quantity of the copper chloride‚Phen complex did not impair the oxidation of the benzylic alcohol. Although the reaction took longer to reach completion, quantitative formation of p-chlorobenzaldehyde could be accomplished using as little as 0.05 equiv of the catalyst. Unfortunately, this initial catalytic system proved, among other things, to be severely restricted to benzylic alcohols. On the basis of previous work in the biochemistry of hemocyanins and tyrosinases,7 a reasonable mechanism for this aerobic oxidation could be envisioned in which the µ2-peroxide 6 occupies a cardinal position (Figure 4). This intermediate 6 can be formed by two different pathways: (1) either by the displacement of the chloride ion in complex 3 by the alcohol nucleophile,13 (13) The preparation of copper(I) alkoxides and their reactivity toward O2 has been reported in the literature. See, for example: Capdevielle, P.; Audebert, P.; Maumy, M. Tetrahedron Lett. 1984, 25, 4397-4400.
Efficient Oxidation of Alcohols
J. Org. Chem., Vol. 64, No. 7, 1999 2435
Table 1. Effect of the Hydrazine Additives
Table 2. Copper-Catalyzed Aerobic Oxidation of Alcohols Using DEAD-H2
conversion (%) entry
additive
15 min
30 min
1 2 3 4 5 6 7
Me2NNH2 (MeO2CNH-)2 (EtO2CNH-)2 (DEAD-H2) (iPrO2CNH-)2 (DIAD-H2) (MeCONH-)2 (PhCONH-)2 phthalhydrazide
10 31 98 70 5
