Epoxidation of Alkenes by Amine Catalyst Precursors:  Implication of Aminium Ion and Radical Cation Intermediates

Abstract

We report herein the discovery of a novel process for epoxidation of alkenes, using Oxone, which, remarkably, is catalyzed by simple amines. This process, which does not rely on transition metal catalysts, utilizes Oxone/NaHCO 3 as the oxidant and simple, cheap, and readily available amines (see Table 1) as catalyst precursors for alkene epoxidation. The standard reaction procedure is illustrated in Scheme 1.Normally, Oxone buffered with NaHCO 3 in MeCN:H 2 O epoxidizes unfunctionalized alkenes only when oxygen-transfer reagents such as ketones, 1 imines, 2 or iminium salts, 3 are present. Aqueous solutions of Oxone at approximately neutral pH are also known to oxidize alkenes to give epoxides but in variable yield. 4,5 At lower pH, mixtures of epoxides and diols are obtained. 4 During our studies on iminium salt-catalyzed epoxidations of alkenes 3b we discovered that simple amines were also capable of epoxidizing our test substrate, 1-phenylcyclohexene and so we tested a broad range of amines (Table 1). In a control experiment, alkene and oxidant were combined in the absence of amine, and essentially no epoxide was obtained (entry 1). Primary amines were not effective (entry 2), but in the presence of secondary and tertiary amines (entries 3, 4, 6-9) rapid epoxidation ensued. Secondary amines gave the highest yields, and within this class, pyrrolidine (entry 6) was optimum. 1,2-Diamines (entry 10) and amides (entry 11) were not effective catalysts. We therefore tested pyrrolidine at loadings of 10 and 5 mol % and discovered that good levels of turnover could be achieved (entries 12-15). Unfortunately, with lower amine loadings (entries 12,14) a significant amount of hydrolysis of the epoxide occurred despite the fact that an excess of NaHCO 3 was present. Although less hydrolysis could be achieved by increasing the ratio of water present, this also resulted in reduced conversion. 6 Attempts to increase the pH of the media with other inorganic bases were unsuccessful but the use of 0.5 equiv of pyridine did largely suppress epoxide hydrolysis 7 (entries 13 and 15). A control experiment showed that pyridine itself was not able to catalyze the epoxidation process (entry 16). Pyrrolidine and a chiral derivative [(S)-2-(diphenylmethyl)pyrrolidine-1 8 ] were tested as catalysts at just 5 mol % loading 9 with a range of alkenes (Table 2) and it was found that good yields of epoxides could be obtained in most cases although the reaction was sensitive to both the structure of the alkene and the amine. The substituted pyrrolidine 1 was a more effective catalyst for a broader range of alkenes than pyrrolidine itself (compare entries 5-7, and 9) and gave up to 57% enantioselectivity with 1-phenylcyclohexene (entry 5). Amine 1 was an effective catalyst for most alkenes; only stilbenes, aliphatic disubstituted and terminal alkenes gave low yields.We have carried out competition experiments with structurally similar alkenes, and found that the amine-catalyzed epoxidation reactions showed much greater selectivity compared ...

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