Oxyfunctionalization

Converting alkanes and aromatics in a controlled way into their oxygenated compounds is of substantial interest. The discovery and development of superacidic 

In recent years, oxyfunctionalization of various natural products (steroids, alkaloids) under superacidic conditions have also been explored. In addition, Nafion resins in combination with various oxidizing agents have also been used in the oxygenations. 

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Raddeanamine (360) is an unusual spirobenzylisoquinoline alkaloid having a tertiary methyl group in five-membered ring. Methylation of the corresponding ketone gave the methyl carbinol with the reverse stereochemistry, namely, the methyl carbinol 361 was obtained from the reaction of the ketone 294 with methyllithium (Scheme 64). Stereoselective synthesis of ( )-raddeanamine was accomplished by an intramolecular oxyfunctionalization via the 8-methyl-8,14-cycloberbine 364 (175). 

Several other miscellaneous heterogeneously catalyzed reactions have been performed in the liquid phase. Hexane was successfully oxyfunctionalized with aqueous hydrogen peroxide by use of the zeolite TS-1 catalyst [50] and microwave-promoted acetalization of a number of aldehydes and ketones with ethylene glycol proceeded readily (2 min) in the presence both of heterogeneous (acidic alumina) and homogeneous (PTSA, Lewis acids) catalysts [51], Scheme 10.7. 

The oxyfunctionalization of alkanes with H2O2 on TS-1 has only been reported very recently [113-114]. Linear or branched alkanes are oxidized to secondary and/or tertiary alcohols and ketones, the latter ones being formed by consecutive oxidation of the secondary alcohols. Primary alcohols are not detected. At 50°C maximum turn-overs of n-hexane of 35 mol/mol Ti were reported... 

In 1992, Hari Prasad Rao and Ramaswamy reported on the oxyfunctionalization of alkanes with H2O2 using a vanadium silicate molecular sieve s . With this catalyst acyclic and cyclic alkanes were oxidized to a mixture of the corresponding alcohols (primary and secondary ones), aldehydes and ketones. Unfortunately, most of the early attempts were of rather limited success due to low turnover frequencies and radical producing side reactions as observed, for example, by Mansuy and coworkers in 1988. ... 

It has already been mentioned (Section III) that the study of the diastereoselection in the electrophilic addition of singlet oxygen to the n face of chiral alkenes is of primary interest for the achievement of a selective oxyfunctionalization reaction. Zeolite confinement and cation- 7r interactions might be expected to affect significantly the diastereoselectivity in the photooxygenation of chiral alkenes. 

With this brief preamble on the more important current theoretical results for the general structural and electronic characteristics of dioxiranes, we shall now examine the computed transition structures of the oxygen transfer in epoxidations, heteroatom oxidations and CFI insertions. Since each reaction type exhibits its individual mechanistic features, these oxyfunctionalizations shall be presented separately. 

Direct insertion into an X—H a bond constitutes the highlight of dioxirane chemistry . Besides the insertion of a dioxirane oxygen atom into an alkane acH bond, for practical purposes a most valuable oxyfunctionalization, also the more facile insertion into the asiH bond is known, a convenient and chemoselective method of preparing silanols. 

For the oxidation of alkanes, the reactivity order follows the sequence primary < secondary < tertiary < benzylic < allylic C—H bonds. The readily accessible and economical DMD is suitable for most substrates, although this oxyfunctionalization may... 

Recently, substantial progress has been registered in regard to the regioselective CH oxidations by dioxiranes. Usually, the regioselectivity of the CH oxidation is mainly governed by the reactivity of the C—H bond for example, in the above-mentioned oxidation of c -decalin , the tertiary C—H bond is selectively oxidized in the presence of the secondary C—H bonds. When the reactivities are similar, the regioselectivity is determined by steric factors. For example, the preferential oxyfunctionalization of the tertiary C—H bond at the C-14 position of the steroid 19 by DMD in the presence of the other tertiary C—H bonds at the C-5, C-8 and C-9 positions is due to steric reasons (equation 30) . ... 

A novel approach to achieve high regioselectivity was recently developed by Yang and coworkers, in which the in-situ-generated dioxirane functionality, contained within the substrate, oxidizes the secondary 5c-h bond rather than the more reactive tertiary yc-H bond, due to a favorable concerted transition state (equation 31). A limitation of this method, however, is that the ketone unit has to be incorporated into the substrate molecule at the appropriate position, normally a rather unpractical and cumbersome task. Moreover, such a process is necessarily stoichiometric in practice and, thereby, it lacks appeal since nowadays catalytic enantioselective oxyfunctionalizations are in vogue ... 

The CH oxidation is also useful in the synthesis of special synthetic targets that are difficult to be achieved by means of conventional oxidants. An early example is the conversion of adamantane to its tetrahydroxy derivative by the exhaustive and selective oxyfnnc-tionalization of all four tertiary C—H bonds, which are contained within the adamantane skeleton. More recently, Curd and coworkers prepared fenestrindane monoalcohol from fenestrindane in good yield by direct TFD oxidation (equation 34), unquestionably a valuable oxyfunctionalization in view of the mild oxidation conditions. ... 

As already briefly mentioned, the oxygen-atom insertion into Si—H bonds of silanes constitutes a selective method for the chemoselective preparation of silanols, which has been much less studied compared to the CH oxidation. This unique oxyfunctionalization of silanes is also highly stereoselective (equation 35) since, like the CH insertions, it proceeds with complete retention of configuration. A novel application of the SiH insertion process is the synthesis of the unusual iron complex with a silanediol functionality, in which selectively both Si—H bonds of the silicon atom proximate to the iron ligand are oxidized in the silane substrate (equation 36). ... 

The oxidation of organic substances by cyclic peroxides has been intensively studied over the last decades , from both the synthetic and mechanistic points of view. The earliest mechanistic studies have been carried out with cyclic peroxides such as phthaloyl peroxide , and more recently with a-methylene S-peroxy lactones and 1,2-dioxetanes . During the last 20 years, the dioxiranes (remarkable three-membered-ring cyclic peroxides) have acquired invaluable importance as powerful and mild oxidants, especially the epoxidation of electron-rich as well as electron-poor alkenes, heteroatom oxidation and CH insertions into alkanes (cf. the chapter by Adam and Zhao in this volume). The broad scope and general applicability of dioxiranes has rendered them as indispensable oxidizing agents in synthetic chemistry this is amply manifested by their intensive use, most prominently in the oxyfunctionalization of olefinic substrates. 

In an interesting paper by Bernini et al., compounds with a flavonoid structure have been selectively oxyfunctionalized at the C-2 carbon atom by dimethyldioxirane (DMD). Products obtained in this way appeared to be useful starting materials to access anthocyani-dins. An example of this route is presented in Scheme 10.1. Here, 2,4-cw-flavane-4-acetate (A) was oxidized by DMD at room temperature, affording the corresponding C-2 hydroxy derivative (B) as the only product (63% yield). Further treatment of B with silica gel eliminated acetic acid to give C quantitatively. Then C was easily transformed into the flavylium salt (D) by simple addition of a 37% solution of HCl in water. 

Through the extensive efforts of the past two decades, the C—H oxyfunctionalization of numerous organic compounds has been accomplished under quite mild reaction conditions, that is, at subambient temperature and in acetone solvent (isolated dioxirane) or in aqueous media (in-situ generation)1. Some of the typical examples are summarized in Scheme 13. 

A new convenient polymer modification for the conversion of the Si—H to Si—OH by the selective oxidation of the Si—H bond by dimethyldioxirane has been described. The oxyfunctionalization of the silane precursor polymers proceeded rapidly and quantitatively and can be applied to the synthesis of a wide variety of novel silanol polymers with specific properties from the corresponding precursor polymers containing Si—H functional groups. Control over the properties of these silanol polymers, such as reactivity and self-association of silanols, was realized through the placement of different substitute groups bonded directly to the silicon atom and by the variation of silanol composition in a copolymer. These novel silanol polymers with a... 

An efficient oxidizing reagent for oxyfunctionalization of saturated hydrocar bons, methyl(trifluoromethyl)dioxirane, can be prepared from aqueous potassium peroxomonosulfale and 1,1,1-tnfluoropropanone [752] The reaction of this reagent with adamantane gives the corresponding tris(hydroxy)adamantane in high yield [755] (equation 80)... 

IRON-PHTHALLOCYANINES ENCAGED IN ZEOLITE Y AND VPI-5 MOLECULAR SIEVE AS CATALYSTS FOR THE OXYFUNCTIONALIZATION OF n-ALKANES... 

In the present work, the construction of a mimic of cytochrome P-450 is attempted by in situ synthesis of iron-phthallocyanines in the supercages of zeolite Y and in the channels of VPI-5. Its catalytic activity and selectivity is tested in the oxyfunctionalization of n-alkanes with tertiary butyl hydroperoxide. 

Oxyfunctionalization reactions of n-alkanes are carried out at room temperature and atmospheric pressure with t.BHP as oxidans and acetone as solvent. Product analysis was done with GC on a 50 m CP Sil-88 capillary column from Chrompack. 

Oxyfunctionalization of lower paraffins such as methane, ethane, propane, and butanes has recently attracted much attention (5, 330, 331, 347-350). Oxidation of -butane to maleic anhydride is an industrial example (346, 351). The oxidation of propane and isobutane with heteropoly catalysts was first reported in 1979 (352). Ai (324a) and Centi et al. (324b, 324c) reported that heteropoly compounds catalyze the oxidation of lower paraffins, especially propane, isobutane, and pentane (324). 

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