Thietane derivatives

A few special syntheses of thiirane derivatives from four-membered sulfur heterocycles are known. Methylenethiiranes are derived by thermolysis of the tosylhydrazones of thietan-3-ones (Scheme 143) (81TL4815), and 2,2,3,3-tetrakis(trifluoromethyl)thiirane is obtained by thermolysis of 2,2,4,4-tetrakis(trifluoromethyl)-l,3-dithietane 1,1-dioxide with loss of sulfur dioxide. 2,2,3,3-Tetrakis(trifluoromethyl)thiirane 1,1-dioxide is obtained in low yield by heating a mixture of 3,3-bis(trifluoromethyl)-l,2,4-oxadithietane 2,2,4,4-tetroxide and bis(trifluoromethyl)ketene. The mono-episulfide of norbornadiene is obtained from thietane derivative (65 Scheme 144) (73JOC649). 

Other thietane derivatives have been obtained by isomerization of nitrogen-containing heterocycles. The reaction of an acyl isothiocyanate (RCONCS) with diphenyldiazomethane gave 20 and this isomerized in solution to the tetraphenyl-3-thietanone 21 <96BSB253>. Additionally, the isoxazolidine 22 was converted into 23 by the action of trimethylsilyl iodide and zinc iodide <96H1211>. 

Olefins bearing electron-donating substituents yield thietane derivatives 113 ... 

Thietane compounds could occur in space especially when one considers that sulfine, a commonly observed pyrolysis fragmentation product of thietane oxide, has been detected in the interstellar medium by microwave spectroscopy. Thietane derivatives have been isolated from the plant and animal kingdom, and it seems likely that much still remains untapped. In such plants as Tribus Arctotideae, the thioacetylene structure 13 containing a 3-... 

Spectra for most thietanes contain a strong parent ion peak. The four-membered ring is usually fractured into the four possible halves. For example, the cleavage of thietane derivative (43) produces peaks at mje 240, 230, 84, and 74. The parent ion peak is absent at 35°. Similarly, spirothietane 44 splits to give fragments with m/e 162 (77%), 152 (12%), 84 (100%), and 74 (0.6%). Decomposition of the thietane nucleus is also characterized by desulfurization and retro 2-1-2 cycloaddition fragments. 

Radical intramolecular cyclization of ethylene mercaptans leads to thiophene as well as thietane derivatives. ... 

A new approach to the formation of the 2-aryl thietane derivatives 124 includes Friedel-Crafts acylation to give a )9-halo ketone. Following conversion of the ketone to the chloride, cyclization is effected with thiourea ... 

When hexafluoroacetone is treated with thietane (2 1) a concerted addition results in the formation of a six-membered ring (Eq. 51). Here the excited state 205 seems to favor the formation of the six-membered ring structure 207 over the corresponding thietane derivative 206. 

Whereas oxidation leaves the fused thietane derivative 218 intact by giving the corresponding sulfone, reduction produces the 4-isopropyl-l,l-diphenyl-bicyclo[4.1.0]hept-l-ene (219) by extrusion of sulfur (Eq. 58). The general oxidation procedure to convert thietanes to their sulfones comprises refluxing with peracetic acid. 

The susceptibility of the thiete 1,1-dioxides to nucleophilic addition reactions can be utilized to produce 3-substituted thietane derivatives. For example, the thus easily attainable 3-cyano and 3-nitroalkyl-substituted derivatives could be reduced to the 3-aminomethylthietanes ° (Eq. 61). 

In several cases thietane derivatives have been used as ligands in organo-metallic compounds. Stable enolate complexes have been derived from tetra-methyl-3-thietanone and diiron nonacarbonyl. Both compounds were heated in n-hexane at 60°C in an argon atmosphere for longer periods of... 

C-3 in the unsubstituted compound.176,177 However, at the time of these experiments, only C-3 substitution had been observed with 2,3-anhydropentofuranosides, and the results of investigation of this reaction suggest that the amino sugar substituted at C-2 is the major product.184 With thiocyanate ion, substitution also occurs at C-3, leading to the thietane derivative, namely, methyl 3,5-anhydro-3-thio-a-D-xylofuranoside (59) but, as this compound was obtained in only 25% yield, the major pathway may involve 2-substitution, leading to products not characterized.178... 

Certain thietane derivatives such as (54) (67JOC2009), (55) (81JCR(M)1132) and (56) (80JOC2962) are desulfurized on treatment with triarylphosphines. These reactions probably involve initial attack by phosphorus on sulfur. 

Examples of nucleophilic attack by oxygen, sulfur and hydride on the 3-position of thietane derivatives are illustrated for thietanes (67) (72BAU505), (68) (75JCS(P1)2513) and (69) (63JA3236) respectively. 

Table 7 Desulfurization of Thietane Derivatives with Raney Nickel...

One instance of the formation of a thietane derivative from a seven-membered heterocyclic precursor is seen in the photochemical fragmentation of dione (180) (73T2135). 

Only a few papers on the formation of compounds with small rings have been published. One example is the [2 + 2]-cycloaddition of electron-rich enamines to Schiff bases under high pressure (1.4 GPa) (87JOC365). The reaction leads to substituted azetidines (1). Four-membered ring heterocycles, thietane derivatives (4), are formed by interaction of sulfene (2) with enamines (3) (86CB257 93JOC3429). 

Almost all papers describing the synthesis of thietes and thietanes give a variety of spectroscopic data for new obtained compounds including H and 13C NMR, infrared (IR), and mass spectrometry (MS) spectra. Papers cited in the sections concerning the synthesis should therefore be consulted for routine spectroscopic information on thietane derivatives. 

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>. 

Brandsma, Tarasova, and co-workers <2001TL4687, 2003RJ01451> have reported the reaction of 1,3-dilithio-3-phenylpropyne with methyl isothiocyanate in THF-hexane at —90 to —55 °C, followed by the successive treatment of the intermediate product with a proton donor, a superbase, and an alkyl halide, yielding isomeric iminocyclobutenes and iminothietanes 48. The ratio of the products depends on the nature of the proton donor, the base, the co-solvent, and the alkyl halide. The formation of the thietane derivatives proceeded in rather poor yields (Scheme 17). 

Thietanes are also useful as analytical tool for mass spectrometric determination of pheromone 130. This type of pheromone may undergo derivatization with dimethyl disulfide to give the thietane derivative 131, which undergoes... 

The reactivity of substituents attached to ring carbon atoms is of much interest, mainly when it concerns complex fused-ring thietanes linked to naturally occurring compounds. The representative example of such a case is conversion of the thymine-thietane derivative 55 to its flavin derivative 56 in the presence of 1-hydroxybenzotriazole (HOBT) and 2-(l -benzotriazole-l-yl)-l,l,3,3-tetramethyluronium tetrafluoroborate (TBTU) (Equation 12) <20050BC1937>. 

Several articles within the discussed period were devoted to the synthesis of carbohydrates (mono- and disaccharides) with a fused thietane ring. Cubero et al.< 1996CAR145> synthesized a galactose thietane derivative 72 using sodium methoxide as a condensing agent (Equation 21). 

Oxirane taxol derivatives have also been found to be convenient starting materials for the synthesis of taxols fused with a thietane ring. The oxirane-derived taxine B derivatives 118 and 119 have undergone reaction with potassium thioacetate in dimethylformamide (DMF) at 60°C <2000TL4891, 2001JOC5058>, leading to the formation of thietane-derived taxine B derivatives 57 and 121. In the case of the bromine derivative 118, the thietane-taxol 57 was not the exclusive product and the 1,2-dithiolane derivative 120 occurred as the major product (Equations 35 and 36). 

Gunatilaka et al. <1999JOC2694> reported the synthesis of the thietane-derived 5,20-thiapaclitaxel derivative 33 by the action of lithium sulfide on the oxirane-derived paclitaxel derivative 122. This reaction led to the thietane derivative 33 in 56% yield and to minor amounts (13%) of 1,2-dithiolane-derived taxol 123 (Scheme 18). 

For spiro-thietane derivatives, the [2+2] two-fragment cyclization turns out to be the most valuable method. Using this methodology, various spiro-thietanes of complex structure have been synthesized in rather high yields. 

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). 

The preparation of fused thietane derivatives is discussed in . 

The thietane dioxides can be converted into thietes by successive reduction, methyla-tion and Hofmann elimination of the resulting thietane derivatives (equation 2)18. 

Irradiation of thiobenzophenone with 5890 A light does not induce reaction with alkenes containing electron-withdrawing substituents. However, when the reaction components are irradiated with 3660 A light, cycloaddition occurs and results in the formation of thietane derivatives. For example, the reaction of (Z)- and ( )-l,2-dichloroethene and (Z)-butanedi-nitrile affords cis- and /rcw.v-3.4-dichloro-2,2-diphcnylthietane (cis-5 and trans-5) and trans-2,2-diphenyl-3,4-dicyanothietanes (trans-6), respectively47. 

Reaction of 6-sulfanylpurine with 2-chloromethyloxirane and 1 equivalent of aqueous sodium hydroxide gave the dihydrothiazole derivative 20 which could be converted to the thietane derivative 21 in high yield. 

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