Oxidation dioxirane-mediated

It should finally be pointed out that the mild reaction conditions typically employed in dioxirane-mediated oxidations enable the asymmetric epoxidation of enol ethers and enol esters. With the silyl ethers, work-up provides enantiomeri-cally enriched a-hydroxy ketones. As summarized in Table 10.1, quite significant enantiomeric excesses were achieved by use of catalyst 10 at loadings ranging from 30 [30] to 300 mol% [31]. Enol esters afford the intact acyloxyepoxides enantiomeric purities are, again, quite remarkable. 

Denmark has developed a practical dioxirane-mediated protocol for the catalytic epoxidation of alkenes, which uses Oxone as a terminal oxidant. The olefins studied were epoxidized in 83-96% yield. Of the many reaction parameters examined in this biphasic system, the most influential were found to be the reaction pH, the lipophilicity of the phase-transfer catalyst, and the counterion present. In general, optimal conditions feature 10 mol% of the catalyst l-dodecyl-l-methyl-4-oxopiperidinium triflate (30) and a pH 7.5-8.0 aqueous-methylene chloride biphasic solvent system [95JOC1391]. 

Acetonitrile is the solvent of choice for in-situ C-H oxidation. Although ethereal solvents, for example dimethoxymethane, 1,2-dimethoxyethane, 1,4-dioxane, and mixtures thereof, have been successfully used for dioxirane-mediated catalytic asymmetric epoxidations, their application in in-situ C-H oxidation has not been vigorously established. 

Excellent reviews on dioxirane-mediated oxidations have appeared. One of the most eharacteristic points is that dioxiranes can be applied to the epoxidation of labile olefins such as enol ethers, enol acrylates, allenes and others. Dioxiranes have also been utilized for phenolic oxidation, but in relatively rare cases. Oxidation of simple phenols and anisoles with dimethyldioxirane (544) provided only a complex mixture, so that hindered phenols are more favorable. On treatment with dimethyldioxirane (4 equiv.) in acetone, 2,4-di(terf-butyl)phenol (216) was oxidized to afford in 79% yield the corresponding o-benzoquinone 220, which reacted with 544 and aq. NaHS03 to give catechol 545. Dimethyldioxirane-promoted oxidation of 545 provided again a quantitative yield of 220. Further oxidation of 220 produced a 52% yield of two epoxides 546 and 547 in a ratio of 1 20. Oxidation of thymol (548) was effected with dimethyldioxirane in acetone to afford fhe four oxidation producfs 549-552 in 10, 20, 10 and 10% yields, respectively (Scheme 102). ... 

Epoxidation of allylic phosphonates is achieved wilh success at room temperature witli MeCOjH in Et O, CF3CO3H in CHCI3, MCPBA in ( HT I- or MOO5/HMPA complex in CH2CI2 to give the corresponding 2,3-epoxyalkylphosphonates as a mixture of diastereomers. s- Allylic phosphonates may also be converted into 2,3-epoxyphosphonates via the 1,1,1-trifluorodimethyl-dioxirane-mediated oxidation. Dimethyldioxirane (DMD) in acetone at room temperature or methyl(trifluoromethyl)dioxirane (TED) in CHjClj at low temperature can be used instead of MCPBA. Because the reaction is quantitative, evaporation of acetone and excess of DMD allow the direct isolation of the pure product. 2,i55... 

A breakthrough in dioxirane-mediated epoxidation was achieved by Shi in the late 1990s. He reported excellent ees for a wide variety of snbstrates nsing the frnctose-derived ketone 10 [32], This catalyst is easily prepared in two steps, and typical enantioselectivities range from 80% to 95% ee. However, the chiral ketone decomposes under the reaction conditions (pH 7-8), presnmably throngh Baeyer-VUliger oxidation, and initially a large excess of the mediator had to be nsed (3 equivalents, with respect to the snbstrate) (Scheme 1.12). 

The vast majority of organocatalytic reactions proceeds via covalent formation of the catalyst-substrate adduct to form an activated complex. Amine-based reactions are typical examples, in which amino acids, peptides, alkaloids and synthetic nitrogen-containing molecules are used as chiral catalysts. The main body of reactions includes reactions of the so-called generalized enamine cycle and charge accelerated reactions via the formation of iminium intermediates (see Chapters 2 and 3). Also, Morita-Baylis-Hillman reactions (see Chapter 5), carbene-mediated reactions (see Chapter 9), as well as asymmetric ylide reactions including epoxidation, cyclopropanation, and aziridination (see Chapter 10), and oxidation with the in situ generation of chiral dioxirane or oxaziridine catalysts (see Chapter 12), are typical examples. 

Oxone sulfoxidations can show appreciable diastereoselectiv-ity in appropriate cases, as demonstrated in eq 26. Enantio-selective oxidations of sulfides to sulfoxides have been achieved by buffered aqueous Oxone solutions containing bovine serum albumin (BSA) as a chiral mediator (eq 27). As little as 0.05 equiv of BSA is required and its presence discourages further oxidation of the sulfoxide to the sulfone. Oxone can be the active oxidant or reaction can be performed in the presence of acetone, trifluoroacetone, or other ketones, in which case an intermediate dioxirane is probably the actual oxidizing agent. The level of optical induction depends on structure of the sulfide and that of any added ketone. Sulfoxide products show ee values ranging from 1% to 89%, but in most examples the ee is greater than 50%. 

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