Dimethyldioxirane stereoselectivity

Analyze the following data on the product ratios obtained in the epoxidation of 3-substituted cyclohexenes by dimethyldioxirane. What are the principal factors that determine the stereoselectivity ... 

Two new reactive, very powerful organic peroxides, dimethyldioxirane and methyl(trifluoromethyl)dioxirane (4), have been introduced.81-83 The latter is more reactive and can be used more conveniently.84 85 Acyclic alkanes give a mixture of isomeric ketones on oxidation with methyl(trifluoromethyl)dioxirane,84,85 while cyclohexanone is the sole product in the oxidation of cyclohexane (99% selectivity at 98% conversion).85 With the exception of norbomane, which undergoes oxidation at the secondary C-2 position, highly selective tertiary hydroxylations can be carried out with regioselectivities in the same order of magnitude as in oxidations by peracids.85-87 A similar mild and selective tertiary hydroxylation by perfluorodialkyloxaziridines was also reported.88 Oxidation with dioxiranes is highly stereoselective 85... 

Dimethyldioxirane has also been used as the epoxidizing agent in a key step in the synthesis of A-norsteroids69,70. The reaction occurs in dichloromethane-acetone and is highly regio- and stereoselective as shown in equation 9. Dioxiranes may also be generated in situ, by reaction of potassium monoperoxysulfate (sold commercially as OXONE) and cyclohexanones. In this case, cyclohexene derivatives may be smoothly epoxidized in 40-100% yields (equation 10)71. 

Dimethyloxazolidines have been utilized as chiral auxiliaries for the diastere-oselective functionalization of the optically active tiglic acid derivatives by means of epoxidation with dimethyldioxirane (DMD) or m-CPBA and ene reactions with 02 or 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD). In the DMD and m-CPBA epoxidations, high diastereoselectivities but opposite senses of diastereomer selection was observed. In contrast, the stereochemistry of the 102 and PTAD ene reactions depended on the size of the attacking enophile whereas essentially perfect diastereoselectivity was obtained with PTAD, much lower stereoselection was observed with 02. The stereochemical results for the DMD and m-CPBA epoxidations and the PTAD ene reaction are explained in terms of the energy differences for the corresponding diastereomeric transition states, dictated by steric and electronic effects.200... 

Epoxidation of oxonine 93 with dimethyldioxirane, followed by reduction with diisobutylaluminium hydride (DIBAL-H), resulted in a separable mixture of alcohols 95 and 96, and the side product 94 (Scheme 16). Each of the isomers was submitted to Swern oxidation and sequential stereoselective reduction with L-selectride to achieve desired stereochemistry of the products 97 and 98. Formation of the side product 94 was explained by Lewis acidity of DIBAL-H and confirmed by treatment of oxirane derived from 93 with another Lewis acid, AlMe3, to produce oxocine aldehyde 99 in 35% isolated yield <1997CL665>. Similar oxidative synthetic sequence was utilized for the synthesis of functionalized oxonines as precursors of (-l-)-obtusenyne <1999JOG2616>. 

Oxidative rearrangements of tetrahydrobenzimidazoles 300-304 on treatment with dimethyldioxirane (DM DO) provided spiro-5-imidazolones 305-311 selectively in good yields. Moderate to excellent stereoselectivity was achieved via preferential oxidation at the less sterically hindered face (Scheme 73) <20040L735>. 

Dioxiranes, RR C02 [usually 3,3-dimethyldioxirane and 3-(trifluorome-thyl)-3-methyldioxirane], as efficient reagents for oxyfunctionalization of C-H compounds have been described and investigated (see, for example, reviews [46] and recent original publications [47]). Stereoselective hydroxylation of a steroid compound with 3-(trifluoromethyl)-3-methyldioxirane is shown below [47g] ... 

It is worthy noting that while oxidation of the tetracyclic ring system 7.11 provided the desired p-epoxide 7.12 (see also compound 7.3), Heathcock 145) found that epoxidation of the tricyclic hydrindane derivative 6.4 (Scheme 11) occurred from the a-face either with mCPBA or with VO(acac)2 and BuOOH, or with dimethyldioxirane. It has been suggested that in the case of 6.4 a stereoelectronic effect is responsible for the observed a-stereoselectivity. Regioselective oxidation of diol 25.1 then provided 25.2, a diastereomer of ( )velutinal. 

A further synthesis of hypothemycin (481) was published by the group of Winssinger in 2009 (384). They used a partial solid-phase strategy with a benzylic sulfide linker to build up the resorcylic macrolactone. The applied macrolacto-nization step proceeded extremely efficiently and epoxidation of LL-Zl640-2 (567) with dimethyldioxirane afforded hypothemycin with excellent regio- and stereoselectivity, but in a poor yield. 

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