Nucleophiles dioxirane oxidation

Sulfur compounds with divalent sulfur functionalities are much more prone to dioxirane oxidation on account of their higher nucleophilicity compared to the above-presented oxygen-type nucleophiles. Examples of this type of dioxirane oxidation abound in the literature. Such a case is the oxidation of thiols, which may be quite complex and afford a complex mixture of oxidation products, e.g. sulfinic acids, sulfonic acids, disulfides, thiosulfonates and aldehydes , and is, therefore, hardly useful in synthesis. Nevertheless, the oxidation of some 9i/-purine-6-thiols in the presence of an amine nucleophile produces n >( -nucleoside analogs in useful yields (equation 19). This reaction also displays the general chemoselectivity trend that divalent sulfur functionalities are more reactive than trivalent sp -hybridized nitrogen compounds P. 

The relative reactivity of a wide series of nucleophiles towards dioxirane, dimethyidioxirane, carbonyl oxide, and dimethylcarbonyl oxide has been examined at various levels of theory. The general trend in reactivity for oxidation by dioxirane was R2S R2SO, R3P > R3N in the gas phase, and R2S R2SO, R3N R3 (R = Me) in solution. A theoretical study of the first oxidation step of [3.2.1]-bridged bicyclic disulfides highlights a highly oriented reaction path was probably responsible for stereoselective attack on the exo face. ... 

Asymmetric epoxidation of olefins is an effective approach for the synthesis of enan-tiomerically enriched epoxides. A variety of efficient methods have been developed [1, 2], including Sharpless epoxidation of allylic alcohols [3, 4], metal-catalyzed epoxidation of unfunctionalized olefins [5-10], and nucleophilic epoxidation of electron-deficient olefins [11-14], Dioxiranes and oxazirdinium salts have been proven to be effective oxidation reagents [15-21], Chiral dioxiranes [22-28] and oxaziridinium salts [19] generated in situ with Oxone from ketones and iminium salts, respectively, have been extensively investigated in numerous laboratories and have been shown to be useful toward the asymmetric epoxidation of alkenes. In these epoxidation reactions, only a catalytic amount of ketone or iminium salt is required since they are regenerated upon epoxidation of alkenes (Scheme 1). 

Dimesityldioxirane, a crystalline derivative, has been isolated by Sander and colleagues and subjected to X-ray analysis. The microwave and X-ray data both suggest that dioxiranes have an atypically long 0—0 bond in excess of 1.5 A. Those factors that determine the stability of dioxiranes are not yet completely understood but what is known today will be addressed in this review. A series of achiral, and more recently chiral oxygen atom transfer reagents, have been adapted to very selective applications in the preparation of complex epoxides and related products of oxidation. A detailed history and survey of the rather remarkable evolution of dioxirane chemistry and their numerous synthetic applications is presented in Chapter 14 of this volume by Adam and Cong-Gui Zhao. Our objective in this part of the review is to first provide a detailed theoretical description of the electronic nature of dioxiranes and then to describe the nuances of the mechanism of oxygen atom transfer to a variety of nucleophilic substrates. 

Since dioxiranes are electrophilic oxidants, heteroatom functionalities with lone pair electrons are among the most reactive substrates towards oxidation. Among such nucleophilic heteroatom-type substrates, those that contain a nitrogen, sulfur or phosphorus atom, or a C=X functionality (where X is N or S), have been most extensively employed, mainly in view of the usefulness of the resulting oxidation products. Some less studied heteroatoms include oxygen, selenium, halogen and the metal centers in organometallic compounds. These transformations are summarized in Scheme 10. We shall present the substrate classes separately, since the heteroatom oxidation is quite substrate-dependent. 

Trivalent phosphorus compounds are more readily oxidized than the corresponding nitrogen derivatives on account of their higher nucleophilicity however, the oxidation of such highly reactive substrates by dioxiranes has been sparsely studied. Only about a handful of examples are available in the literature, such that little may be said about the general trends in reactivity and selectivity. 

As discussed in Section 10.1, asymmetric epoxidation of C=C double bonds usually requires electrophilic oxygen donors such as dioxiranes or oxaziridinium ions. The oxidants typically used for enone epoxidation are, on the other hand, nucleophilic in nature. A prominent example is the well-known Weitz-Scheffer epoxidation using alkaline hydrogen peroxide or hydroperoxides in the presence of base. Asymmetric epoxidation of enones and enoates has been achieved both with metal-containing catalysts and with metal-free systems [52-55]. In the (metal-based) approaches of Enders [56, 57], Jackson [58, 59], and Shibasaki [60, 61] enantiomeric excesses > 90% have been achieved for a variety of substrate classes. In this field, however, the same is also true for metal-free catalysts. Chiral dioxiranes will be discussed in Section 10.2.1, peptide catalysts in Section 10.2.2, and phase-transfer catalysts in Section 10.2.3. 

In comparison with the diazines, the inductive effects of the extra nitrogen(s) leads to an even greater susceptibility to nucleophilic attack and, as a result, all the parent systems and many derivatives react with water, in acidic or basic solution. Similarly, simple electrophilic substitutions do not occur some apparent electrophilic substitutions, such as the bromination of 1,3,5-triazine, probably take place via bromide nucleophilic addition to an N -Br triazinium salt. Attempted direct A-oxidation of simple tetrazines with the usual reagents generally results in ring cleavage, however it can be achieved satisfactorily with methyl(trifluoromethyl)dioxirane. ... 

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