Thietane oxides reactions

The preparation and investigation of the thietane oxide system (5a) is largely associated with stereochemical and conformational studies . The investigation of the thietane dioxides (5b) is substantially related to the chemistry of sulfenes , the [2 -I- 2] cycloaddition of which with enamines is probably the method of choice for the synthesis of 5b . The study of the thiete dioxide system (6) evolved, at least in part, from the recognition that the unstable thiete system 183 can be uniquely stabilized when the sulfur in the system is transformed into the corresponding sulfone , and that the thiete dioxide system is very useful in cycloadditions and thermolytic reactions. The main interest in the dithietane oxides and dioxides (7) appears to lie in the synthetic challenge associated with their preparation, as well as in their unique structural features and chemical behavior under thermolytic conditions . ... 

The oxides of thiete and benzothiete have been prepared from halogenated thietane oxides by elimination reactions. (Eqs. 25 and 26)... 

The principal method of synthesis of thietane 1-oxides is by oxidation of thietanes, a reaction discussed in Section II.5.C. Reagents used for oxidation are hydrogen peroxide, hydrogen peroxide-acetic... 

A method of thietan (207) formation that promises to be widely applicable concerns the reaction of chalcones, which are available with a tremendous variety of substituents, and diethyl hydrogen phosphodithioate. A possible drawback is that cis/trans mixtures are obtained. There are very few examples of additions to non-activated alkynes an intramolecular example has now been shown to lead to thietan oxides (208) as well as larger sulphur heterocycles. 

Although sodium sulphide reacts readily with haloalkanes [2] and activated aryl halides (see Chapter 2) [e.g. 3-5] in the presence of a quaternary ammonium catalyst to form symmetrical thioethers (Table 4.1), a major side reaction results in the formation of disulphides owing to the oxidation of the intermediate thiols under the basic conditions. Consequently, little use has been made of this procedure for the synthesis of thioethers [3, 6], but the corresponding reaction of the a,(0-dihaloalkanes to yield cyclic thioethers has proved to be a valuable procedure for the synthesis of thietanes [7] (Table 4.2). The ring closure with the secondary dihaloalkanes is considerably more difficult to effect than is the reaction of the primary dihaloalkanes. 1,3-Dihydrobenzo[c]thiophene (89%) is produced in the reaction of 1,2-bis(bromomethyl)benzene with sodium sulphide (Scheme 4.1) [8]. The direct... 

The reaction of Af,Af-dimethyl-( )-styrylamine (73) with a halogen-substituted methanesulfonyl chloride allowed the first stereoselective formation of the halogenated thietane 1,1-dioxide 74, which then could be converted to the corresponding thiete sulfone 75 via a Cope elimination of the corresponding AT-oxide. ... 

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. °... 

Flash vacuum pyrolysis (FVP) represents a special method for inducing decomposition of thietane compounds. Block et al. succeeded for the first time in the preparation of methylene sulfine in the gas phase, applying this method to thietane 1-oxide. The reaction starting at 600°C was followed by mass and microwave spectroscopy. 

Scheme 1 summarizes some of the common electron-impact induced fragmentation pathways available to thietanes, thietes and their 5-oxides. Major processes include retro-2 + 2 fragmentation for thietanes, thiolactones and iminothietanes, loss of sulfur oxides for thietane 5-oxides, and loss of an a-hydrogen atom from thietes and benzothietes. Certain of these processes, considered to involve electron-impact induced pathways, may actually involve thermolytic reactions occurring in the source region of the mass spectrometer (78JHC421,71JA676). 

Oxygen can be introduced into the a-positions of thietanes by treatment of the thietane with lead tetraacetate as in the formation of (204) (75JOC3046). Thietanones can be prepared by hydrolysis of thiete enamines such as (205) (65LA(684)103) or by oxidation of 3-thietanol with DMSO/benzoic anhydride (78PS(4)167>. Thietanones can be converted into various ring-substituted sulfur derivatives as already illustrated in reactions of (68) and preparation of (199). 

Treatment of 3-hydroxythietanes 21b-g with aqueous sodium hydroxide led to retro-aldol ring cleavage to produce the carbonyl derivatives 23b-g (Table 1) <1997J(P2)425>. It was proven that the rate of the reaction was determined by the nature of the substituent at the 3-position and by the oxidation state of sulfur. 3-Phenylthietane-3-ol 21b underwent retro-aldol reaction to give sulfide ketone 23b. Thietane-l-oxide-3-ol 21c-e or thietane-l,l-dioxide-3-ol 2 If and 21g derivatives underwent retro-aldol reaction to produce carbonyl sulfoxides 23c-e and carbonyl sulfones 23f and 23g (Table 1) <1997J(P2)425>. 

The Pummerer reaction of 3,3-dibenzoyloxyethyl-thietane 1-oxide 32a with thymine in the presence of trimethyl-silyl triflate (TMSOTf), triethylamine, and Znl2 in dichloromethane allowed the synthesis of the thietane-derived thymidine 33a in 70% yield <1996TL7569>. The treatment of thietane-1-oxide derivative 32b under similar conditions but in toluene resulted in the modified nucleoside 33b in 30% yield (Scheme 9) <1996TL7569>. 

The Pummerer reaction of 2,3-di(benzoyloxymethyl)-thietane-l-oxide 34 with 6-chloropurine in the presence of TMSOTf in toluene led to the modified thietanyl chloropurine 35 (Equation 8) <1999TL7385>, which after the subsequent action of ammonia resulted in a modified adenosine. 

The reaction of. 9-acetyl azidoarabinofuranoside derivative 135 with sodium bicarbonate in methanol gave bicyclic thietane derived azidolyxofuranoside 136, which was subsequently oxidized with hydrogen peroxide to a sulfoxide derivative 137 <2006PS1249> (Scheme 22). 

Chlorinolysis is another reaction mode observed in some sulphides, in which sulphur retains its oxidation state. For example, phenyl trityl sulphide and benzyl trityl sulphide were converted into trityl chloride and sulphenyl chlorides [26]. Thiirane and thietane reacted similarly with 3-(dichloroiodo)pyridine to afford chlorinated disulphides [25] ... 

Thietane A-oxides undergo Pummerer reactions which allow the introduction of groups at C(2), as illustrated in Scheme 88 <1996TL7569, 1997SL1247>. 

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