A cheap, catalytic, scalable, and environmentally benign method for alkene epoxidations.

Benign Method for Alkene Epoxidations Benjamin S. Lane and Kevin Burgess* Department of Chemistry, Texas A & M UniVersity PO Box 30012, College Station, Texas 77842-3012 ReceiVed NoVember 17, 2000 This paper reports a simple method wherein manganese (2+) salts, for example, MnSO4, catalyze epoxidation of alkenes using 30% aqueous hydrogen peroxide as the terminal oxidant. The reactions are performed by dissolving the substrate and catalyst in DMF or tert-butyl alcohol and then slowly adding a mixture of 30% hydrogen peroxide and aqueous 0.2 M sodium hydrogen carbonate buffer. This method has several desirable attributes with respect to cost, simplicity, and environmental factors. This project emerged from a control experiment performed while screening new, chiral, 1,4,7-triazacyclononane (TACN) complexes as potential asymmetric epoxidation catalysts. High throughput screens in a simple plate apparatus1 indicated simple manganese (2+) salts, without any organic ligand, mediated the epoxidation but only in hydrogen carbonate buffer. There was no epoxidation in buffers based on triethanolamine, 3-[Nmorpholino]propanesulfonic acid (MOPS), phosphate, or borate. Alkenes are epoxidized by hydrogen peroxide/NaHCO3 in H2O (for water soluble alkenes) or in acetonitrile/water mixtures.2,3 We suspected that the transformations in the presence of manganese (2+) salts were fundamentally different because the reaction times reported for the metal-free system3 were significantly longer than those required in the current study. Moreover, the rates of epoxidation in the metal-free system were known to be significantly slower when tert-butyl alcohol was used as the solvent rather than acetonitrile; however, the former solvent was effective in the manganese-containing system. A set of experiments was performed to test for differences between the metal-free and manganese-containing systems. Figure 1 shows a direct comparison of epoxidation of 4-vinylbenzoic acid under exploratory, unrefined conditions (i.e., hydrogen peroxide added all at once at the beginning of the reaction; tertbutyl alcohol solvent). These data showed that the extent of conversion of alkene to epoxide was comparable when 0.1 and 1.0 mol % of manganese sulfate were used. It is less for 0.01 mol % Mn2+, but still much greater than the background conversion that occurred when no metal salt was used. Epoxidation of trans-1,2-diphenylethene was chosen as a model to optimize the conditions. This lypophilic substrate was selected so that solubility issues could be addressed using a relatively difficult case. When the substrate, 10 equiv of 30% hydrogen peroxide, and 1 mol % MnSO4, were mixed in 0.2 M NaHCO3 (pH 8.0) and DMF (1.0:1.4) and the reaction was stirred for 24 h, the yield of the epoxide was only 20%. Precipitation was observed in this experiment, indicating solubility problems. Consequently, slow addition of the aqueous components was investigated to minimize the precipitation, and the yield of product increased. Conversely, increasing the buffer concentration above 0.2 M would be expected to accentuate the insolubility problem, and indeed lower yields were obtained when higher buffer concentrations were used. Finally, a set of conditions were developed wherein a mixture of the buffer and 10 equiv of the peroxide were gradually added over 16 h to a solution of the substrate and catalyst in DMF. These reactions gave 1,2-diphenylethene oxide in 92% isolated yield. Table 1 summarizes the data obtained using various alkenes. 1-Decene was unreactive under these conditions (GC; entry 1). Entries 2, 3, and 16 illustrate that disubstituted aliphatic alkenes were reactive, and an excellent yield of cyclohexene oxide was obtained. Oxidation of the tetrahydroanthraquinone (entry 3) gave a significant amount of the corresponding quinone as a major byproduct. No Baeyer-Villager oxidation was observed for this material or in a control experiment using benzophenone as a substrate (no reaction occurred, data not shown). Entries 4-8 illustrate epoxidations of trisubstituted alkenes. R-Pinene reacted without cyclobutane rupture (entry 4), and citronellal was epoxidized without oxidation of the aldehyde functionality (entry 5; NMR). Similarly, the alcohol functionality of 3-methyl-2-buten1-ol was preserved in the epoxidation process, and no Payne rearrangement product was observed either (entry 6). Entry 7 tested for the generation of radical character adjacent the cyclopropane in the epoxidation, but no cyclopropane opening was observed. Epoxidation of linalool (entry 8) demonstrated that trisubstituted aliphatic alkenes can be selectively epoxidized in the presence of terminal alkenes. This experiment also implies that the allylic hydroxyl does not activate the terminal alkene via a directing effect. Entries 9-12 illustrate that epoxidations of arylsubstituted alkenes proceed smoothly; qualitatively, the rates of these reactions were observed to be appreciably faster than for aliphatic alkenes. The only complication was that a significant amount of trans-3-phenylpropenal was formed in entry 11. Epoxidation of the acid shown in entry 12 was not accompanied by decarboxylation or double bond migration. Some reactions with less catalyst were then attempted since it was evident that aryl alkenes were more reactive than aliphatic ones. Only 0.1 mol % of manganese sulfate was used for the reactions depicted in entries 13-15, and these epoxidations proceeded smoothly. Entries 14 and 15 illustrate that even extremely acidsensitive epoxides can be formed, and the products are stable under the reaction conditions. The last entry in the table was performed on a 1 mol scale; a detailed procedure for preparation and isolation of 84.5 g of cyclooctene oxide is provided here.4 The featured catalytic epoxidation method has numerous attributes. Manganese (2+) salts are cheap, readily available, and relatively nontoxic, and only small amounts (1.0-0.1 mol %) are required. Hydrogen peroxide and sodium hydrogen carbonate are widely used in large-scale production of other chemicals. No halide is involved in the transformation. Slow addition reduces the effective concentration of peroxide and the corresponding risk of explosion. The reaction is run at room temperature in solvents (1) Porte, A. M.; Reibenspies, J.; Burgess, K. J. Am. Chem. Soc. 1998, 120, 9180-9187. (2) Frank, W. C. Tetrahedron Asymmetry 1998, 9, 3745-3749. (3) Yao, H.; Richardson, D. E. J. Am. Chem. Soc. 2000, 122, 3220-3221. Figure 1. Opimization of the number of the hydrogen peroxide/catalyst stoichiometry. Yield determined by HPLC versus an internal standard. Error bars represent the standard deviation of two trials 2933 J. Am. Chem. Soc. 2001, 123, 2933-2934