Thiolane oxides

A method for the stereospecific synthesis of thiolane oxides involves the pyrolysis of derivatives of 5-t-butylsulfinylpentene (310), and is based on the thermal decomposition of dialkyl sulfoxides to alkenes and alkanesulfenic acids299 (equation 113). This reversible reaction proceeds by a concerted syn-intramolecular mechanism246,300 and thus facilitates the desired stereospecific synthesis301. The stereoelectronic requirements preclude the formation of the other possible isomer or the six-membered ring thiane oxide (equation 114). Bicyclic thiolane oxides can be prepared similarly from a cyclic alkene301. 

A closely related method is the thermolysis of l-allylsulfinyl-2-cyanoethane in alkynes, which leads to the formation of thiolane oxide derivatives via consecutive pericyclic reactions302. The low yield and formation of mixtures are somewhat compensated for by the convenience, but its practicality is as yet rather limited (equation 115). 

Thiolane oxides, Thiolene oxides, Thiophene oxides... 

Thio-Claisen rearrangement 746-748 Thioketene 5-oxides photolysis of 878 reactions of 277 Thiolane dioxides formula of 382 NMR spectra of 460 reactions of 604 synthesis of 461 Thiolane oxides 747 formula of 382 IR spectra of 461 synthesis of 461, 462, 752 Thiolanes, photolysis of 881 Thiolene dioxides formula of 382 NMR spectra of 460 reactions of 464, 465 synthesis of 461 Thiolene oxides formula of 382 synthesis of 461, 746 Thiols... 

IR spectra of thiolane oxides in the solid phase were shown to be most outstandingly different in the sulfoxide region depending on the particular crystalline state/structure a fact which can be used to advantage for conformational analysis. Also, as one could expect, the sulfoxide absorptions indicate strong hydrogen bonding. 

The conversion of cyclic sulfides to sulfones is accompbshed by more energetic oxidations. Perhalogenated thiolanes [106] and 1,3-dithietanes [107] are oxidized to sulfones and disulfones, respectively, by a mixture of chromium trioxide and nitric acid (equation 98) The same reagent converts 2,4-dichloro-2,4-bis(tnfluoromethyl)-l,3-dif/u cto cs to disulfone derivatives [107], whereas trifluoromethaneperoxysulfonic acid converts the starting compound to a sul-fone-sulfoxide derivative [2(equation 99). 

Barbarella and coworkers172 have studied the conformational properties of thiolane-1-oxide (187), its mono- and di-methyl derivatives (188-194) and trans-2-thiahydrindane-2-oxide (195) using force-field calculations and 1H, 13C and 17ONMR. They concluded that the overall conformational preference depends on the substituents and their locations... 

Similarly, the most common method of preparing the substituted, fully unsaturated thiolane system, e.g. thiophene dioxides, is by direct oxidation of the readily available substituted thiophenes with hydrogen peroxide, perbenzoic acid and m-chloroperbenzoic acid280 283. Alternatively, thiophene dioxides are conveniently prepared via the double elimination methodology280 305 illustrated in equation 117. 

Jones and Lewton250 have also demonstrated the utility of the intramolecular addition of sulfenic acids to olefins as a stereospecific method for the synthesis of thiolan 1-oxides. 

It has been noted63 that in competitive reactions of thiolane-1-oxides, the cis sulphoxide, is oxidized somewhat quicker by peracids than the trans isomer (equation 18). This observation is presumably due to the greater accessibility of the electron pair for electrophilic attack in the cis species. 

Subsequently, Paquette and Johnson used LAH reductions to convert strained thietane or thiolane derivatives to their respective sulphides, generally in good yields. Whitney and Cram described the LAH reduction of a chiral derivative of benzothiophene sulphone, as outlined in equation (24). The authors also noted the formation of hydrogen gas and suggested that their results were consistent with those of Bordwell as outlined in equation (22), namely that reduction takes place by the formation of an aluminium oxide and hydrogen gas. In this case, the reduction clearly cannot involve the formation of an a-sulphonyl carbanion and it is unlikely that any C—S bond cleavage and reformation could have occurred. 

Complexation of sodium to the persulfoxide A (Fig. 13B) appears to inhibit intramolecular hydrogen abstraction to form the hydroperoxy sulfonium ylide (B in Fig. 13A) and allows a direct reaction of 12 with the sodium-complexed persulfoxide, (A in Fig. 13B) to compete. Consistent with this suggestion is the observation that the formation of 13CHO that emanates from the hydroperoxy sulfonium ylide by Pummerer rearrangement and subsequent cleavage is completely suppressed during photo-oxidations of thiolane, 13, in NaMBY ... 

The six possible five-membered monocyclic rings containing three oxygen or sulfur atoms in 1,2, and 4 positions are shown in (1) to (6). Examples of each ring system are known, although 1,2,4-trioxolane (1) and 1,2,4-trithiolane (2) are the only parent rings that have been synthesized and characterized. The other systems are found as derivatives of the parent ring, with 1,4,2-dioxa-thiolanes and 1,2,4-oxadithiolanes only reported in the form of S-oxides. 

An interesting reaction related to the ring expansions of penicillin S-oxides (208) was observed in the thermal rearrangement of 2,2,4A-tetramethyl-thiethan-3-one 1-oxide to the five-membered thiolane ring 209. Oxidation attempts of these thermally unstable thietanone oxides led via ring opening to the more stable heterocycle. The reaction mechanism (Scheme 11) was... 

Only a few examples of ring syntheses by transformation of another ring have been published, as exemplified by the preparation of the sultines 168 by ring enlargement of five-membeted thiolane 1-oxides 166 (cf Section 8.10.9.2.3) and the 3,6-dihydro-l,2-dithiins 202 by catalytic transformation of vinylthiiranes 201 (cf Section 8.10.9.4.2). Because possibilities to synthesize six-membered rings with oxygen and/or sulfur as heteroatoms in 1,2-positions are rather limited, these reactions have been covered already in Section 8.10.9 together with alternative syntheses from alicyclic compounds. 

Oxathiane 2-oxides aie fonned by the oxidative ring expansion of 2-alkylthio-2-benzylthiolane 1-oxides brought about by [bis(trifluoroacetoxy)iodo]benzene. That the reaction is only successful with the (lR )-diastereoisomeis is attributed to chelation between the nucleophilic S and O atoms and the hypervalent iodine <99EJ0943>. A diazo-mediated thiolane ring expansion is the key step in a synthesis of the acenaphtho-[U-b][l,4]oxathiine system <99JCS(P2)755>. 

Thiophenes and Tetrahydrothiophenes. Thiophenes (thioles) are subject to aromatic hydroxylation tetrahydrothiophenes (thiolanes) undergo oxidation of the sulfur to give sulfoxides or sulfones. 

Fluorination of tetrachlorothiophene with potassium tetrafluorocobaltate(III) gave 3,4-dichlorotetrafluoro-3-thiolene (156). Similar fluorination of thiophene yielded the 3-thiolene (157) and the thiolan (158) <71JCS(C)346, 72T43). It has been suggested that the fluorination proceeds by initial oxidation of thiophene to the cation-radical by the metal ion, and subsequent quenching of this by atomic fluorine (Scheme 30). 

A similar number of different reaction channels are populated in the photolysis of the related thiolane 1-oxide (tetrahydrothiophene 1-oxide, 4) (80JPC1302). However, in this case also cyclopropane and propene are... 

---