Oxidative dithiolanes

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

Electrolysis 1.5 V, CH3CN, H2O, UCIO4 or Bu4N-"C104, 50-75% yield. " 1,3-Dithiolanes were not cleaved efficiently, by electrolytic oxidation. 

HgCl2, CaC03, THF, H2O, 0°, rapid. These derivatives are less susceptible to oxidation and hydrogenolysis than are the 1,3-dithiane and 1,3-dithiolane precursors. 

The preparation of e/n-difluoro compounds by the oxidative fluorodesul-furization ot 1,3-dithiolanes readily proceeds by treatment with a pyridinium polyhydrogen fluoride-Af-halo compound reagent the latter serves as a bromonium ion source [2], l,3-Dibromo-5,5-dimethylhydantoin is the most effective of several At-halo oxidants. It is believed that /V-halo compounds combine with hydrogen fluoride to generate in situ halogen fluorides, the oxidants. Formation of gem-difluorides from dithiolanes derived from ketones is efficient and rapid, even at -78 °C, whereas the reaction of dithiolanes derived from aldehydes requires higher temperature (0 °C) (equation 4). 

Advances in synthesis and research of oligomeric tetrathiafulvalenes 97MI9. Enantioselective oxidation of 1,3-dithiolanes to corresponding S-oxides and S,S-dioxides by designer yeast 99JHC1533. 

Oxidation of a thiiraneradialene with equimolar amounts of MCPBA in CH2C12 at about 0°C gave the corresponding thiiraneradialene S-oxide 26 in a quantitative yield47 (equation 11). 5-Membered heterocyclic sulphoxides such as 1,3-benzoxathiolane sulphoxide 27, 1,3-benzdithiolane sulphoxide 28 and 1,3-dithiolane sulphoxide 29 were readily obtained from their sulphide precursors by oxidation with MCPBA in dich-loromethane solution48. 

The modified Sharpless reagent was also successfully applied288 for the asymmetric oxidation of a series of 1,3-dithiolanes 248 to their S-monooxides 249 (equation 134). It was observed that the optical induction on sulphur (e.e. from 68 to 83%) is not significantly affected by the substituents R1 and R2. Asymmetric oxidation of a few aryl methyl sulphides by organic hydroperoxides in the presence of a catalytic amount of the optically active Schiff base-oxovanadium(IV) complexes gave the corresponding sulphoxides with e.e. lower than 40%289. 

It is noteworthy that, based on the sulfoxide- sulfenic acid rearrangement, the readily accessible 1,3-dithiolane systems (316) may be utilized (equation 116) as an efficient entry into the 1,4-dithiane series303, including the construction of carbocyclic fused systems304. The oxidation of the dithienes 318 to the corresponding sulfoxides (319 and 320) and sulfones is a simple, straightforward process. 

The substitution of a heteroatom for an a-sulfoxy methylene group substantially increases the preference for an axial orientation of the sulfoxide oxygen320, despite the smaller space requirement of the sulfur with its lone pairs, compared to that of a methylene group321, at least in the case of 1,3-dithiolane oxides. The substituting heteroatom, therefore, should decrease the conformation stability (i.e. lower the barrier to chair-chair interconversion). 

Dithiolane oxides, synthesis of 241 Dithiolanes, asymmetric oxidation of 291 Divinyl sulphones, reactions of 642, 1021 Divinyl sulphoxides reactions of 349, 352, 353, 359 synthesis of 240 Donor-acceptor capacities 387... 

Analogous ring enlargements of S-oxides of benzothiazolium compounds on heating with acetic anhydride have been described elsewhere [19 a] (cf. also Section 8.1.4). S-Oxides of thioketals such as 1189 are converted to the unsaturated 1,3-dithiolanes such as 1190 [21] (Scheme 8.6). 

Reaction of thiolates with the l,2-dithiolan-3-one 1-oxide heterocycle of leinamycin generates the snlfenate intermediate Cyclization of this sulfenate onto... 

The regeneration of carbonyl compounds from dithioacetals and dithiolanes is often done with reagents that oxidize or otherwise activate the sulfur as a leaving... 

Several secondary metabolites are dithiolanes, as for instance the allelochem-icals found in the tropical weed, Sphenoclea zeylanica. Zeylanoxide A is present in two stereoisomeric forms depending on whether the chirality at sulfur is (R) or (5) the latter form is 44 (Scheme 15). Zeylanoxides B are similar but in these cases the oxide function is on the sulfur at the 2 position. These molecules inhibited root growth in rice seedlings as well as the germination of letuce seeds.95... 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

The formation of S-oxides has also been observed when oxidizing a variety of 5-substituted 2-tert-butyl-l,3-dithianes in wet acetonitrile. In an undivided cell, 4-substituted 1,2-dithiolane-l-oxides were oblained (Scheme 25) [113]. A coupled cathodic process, in this case, was the reduction of protons formed in the anodic reaction. 

Scheme 25 Conversion of 1,3-dithianes into 1,2-dithiolane-l-oxides.

The oxidation of dithianes (Scheme 13) leads to a dicationic species that reacts with water affording aldehydes or ketones and 1,2-dithiolane, which undergoes further oxidation to the sulfoxide (20-74% yields) [18]. 

As previously illustrated in Scheme 13, the anodic oxidation of dithianes involves a ring contraction affording 1,2-dithiolane [18]. 

An acyl-transfer and redox coenzyme containing two sulfhydryl groups that form a dithiolane ring in the oxidized (disulfide) form. The redox potential at pH 7 is -0.29 volts. Lipoic acid is attached to the e-amino group of lysyl residues of transacetylases (subunit of a-ketoacid dehydrogenase complexes), thereby permitting acyl... 

V(V), Mo(VI) and Ti(IV) derivatives proved to be both effective and selective in the oxidation of snlfides with alkyl hydroperoxides. As for H2O2, vanadium is at least twofold more efficient than molybdenum in oxidation and much more selective, as proved by the data obtained with the cyclic disulfide 2-aryl-l,3-dithiolane 80. A large predominance of the frawi-S-oxide 81 over the cw-derivative 82 is obtained for all the systems investigated (eqnation 46). However, the diastereoselectivity exhibited by V(V)/TBHP is remarkable . ... 

An interesting synthetic approach to thietanes is the selective desulfurization of cyclic disulfides.The treatment of dithiolanes with a diethyl-aminophosphine results in a ring contraction to thietanes, (Eq. 19). This has been demonstrated with a-lipoic acid, a coenzyme with a dithiolane structure involved in the biological oxidation of pyruvic acid. The reaction is proposed to be initiated by the electrophilic attack of the phosphorus on the ring sulfur atom, resulting in the formation of an acyclic internal phosphonium salt, which by subsequent elimination of a phosphine sulfide, closes to the four-membered ring. °... 

Scheme 1.64). The Ag(I)-mediated cyclization afforded dipole 306 for 1,3-dipolar cycloaddition with methyl vinyl ketone to yield adducts 307 and the C(2) epimer as a 1 1 mixture (48%). Hydrogenolytic N—O cleavage and simultaneous intramolecular reductive amination of the pendant ketone of the former dipolarophile afforded a mixture of alcohol 308 and the C(6) epimer. Oxidation to a single ketone was followed by carbonyl removal by conversion to the dithiolane and desulfurization with Raney nickel to afford the target compound 305 (299). By this methodology, a seven-membered nitrone (309) was prepared for a dipolar cycloaddition reaction with Al-methyl maleimide or styrene (301). 

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