Synthesis from 1,2-dithiolanes

Synthesis.—From 1,2-Dithiolans (Type C). The general synthesis of isothiazoles from 1,2-dithiolans (see Organic Compounds of Sulphur, Selenium, and Tellurium, volumes 2, 3, 4, and 5 ) continues to be exploited. The 1,2-dithiolyIium-4-olates (1) are cleaved by ammonia and subsequently cyclize to give isothiazol-4-ols (2 X = OH). Methylation in HCIO4 gives (3), which are convertible into (4) by base. ... 

In Kiyooka s approach to acetate aldols by use of a stoichiometric amount of 3f, the enantiomeric excess obtained in the reaction with silyl ketene acetals derived from a-unsubstituted acetates was much lower (ca 10-20 %) than that obtained in the reaction with l-ethoxy-2-methyl-l-(trimethylsiloxy)-l-propene (> 98 % ee). Introduction of an removable substituent, e.g., a methylthio or bromo substituent, after aldol reaction at the a-position of chiral esters, resolved this problem [43e], Asymmetric synthesis of dithiolane aldols was achieved in good yield by using the silyl ketene acetal derived from l,3-dithiolane-2-carboxylate in the 3f-promoted aldol reaction, and desulfurization of the dithiolane aldols resulted in production of the acetate aldols in high enantiomeric purity (Eq. 56). 

Kiyooka et al. have reported that stoichiometric use of chiral oxazaborolidines (e.g. (S)-47), derived from sulfonamides of a-amino acids and borane, is highly effective in enantioselective aldol reactions of ketene TMS acetals such as 48 and 49 (Scheme 10.39) [117]. The use of TMS enolate 49 achieves highly enantioselective synthesis of dithiolane aldols, which can be readily converted into acetate aldols without epimerization. The chiral borane 47-promoted aldol reaction proceeds with high levels of reagent-control (Scheme 10.40) [118] - the absolute configuration of a newly formed stereogenic center depends on that of the promoter used and not that of the substrate. 

The unsubstituted l,3-dithiole-2-thione (245) can be accessed, however, by the reaction of dimethyl acetylenedicarboxylate with l,3-dithiolane-2-thione (Scheme 50) <74JOC2456>, from the reaction of sodium acetylide with carbon disulfide and elemental sulfur <64CB1298>, or by a two-step synthesis from the 1,2-dichloroethyl ethylether (246) and potassium trithiocarbonate. The intermediary 4-ethoxy-l,3-dithiolone-2-thione (247) affords, upon reaction with p-toluene sulfonic acid with concomitant loss of ethanol, the unsubstituted derivative (245) <76CC920>. 

In the synthesis of l,3-dithiolan-2-ones from spirocyclic intermediates, via episulfides, substituted tetrathiacyclododecane and the related pentathiacyclopentadecane were isolated in good yields <96JCS(P1)289>. Preparation and molecular dynamics studies of 2,5,8,17,20,23-hexathia[9.9]-p-cyclophane have been reported <96P4203>. The syntheses and properties of thiocrowned l,3-dithiole-2-thiones and their conversion to tetrathiafiilvenes via treatment with triethylphosphine have been described <96LA551>. 

The synthesis of 1,3-dithiolanes (284) which contain a 2-dimethylamino group results from the reaction of ethanedithiol with amide acetals of type (283) (69BSF332). 

Dithiolanes are efficiently synthesized by the oxidative cyclization of 1,3-dithiols , as illustrated by the preparation of 1,2-dithiolane 77 in quantitative yield from 1,3-propanethiol 76 by oxidation with iodine in the presence of 2-methyl-2-butene (Scheme 44) <20000L369> and a similar synthesis of the l,2-dithiol-3-one 78 (Scheme 45) <2004TL4307, 2006JME5626>. 

Derivatives of 1,2,3-frithiane as well as 1,2-dithiolane are known for their biological activity. Two naturally occurring frithiane derivatives are shown in Table 6. 5-Methylthio-l,2,3-trithiane has been isolated by gas-phase isopentane extraction from the green alga Chara globulares and identified by GC/MS, H-MR and UV spectra. Its synthesis is straightforward. The second natural frithiane... 

A slight variation of the [3-I-2] cycloaddition approach <1977ICA(25)165> has also been employed for the diastereoselective synthesis of the corresponding anti- and ry -iron-substituted 1,2-dithiolane 1-oxides 243 from 237, as a source of electrophilic disulfur monoxide, and 7] -allyl iron complex 242 (Scheme 39). The method was also tested with cyclopentadienyl iron dicarbonyl crotonyl complex 244 when four diastereomers 245-248 were generated in modest yields (35%) <19980M5534>. 

The example in Scheme 60 provides a nice illustration of the efficient synthesis of a 1,2-dithiolane analogue of leucine, of interest in medicinal chemistry due to the biological activity of the heterocyclic ring. Thus, the stereo-controlled synthesis of N- and C-protected derivative of (A)-amino-3-(l,2-dithiolan-4-yl)propionic acid 326 and its reduced 1,2-dithiolic form from /< /t-butyl (A)-A - /t-butoxycarbonylpyroglutamate 322 as a precursor were reported <20020L1139>. 

Heating several thietanes with sulfur or selenium yields 1,2-dithiolanes and a 2-selenathiolane, for example, 107 from 19, respectively. The reaction of 108 with sulfur provides a synthesis of thioctic acid. ° A somewhat similar reaction involves heating thietane with aluminum oxide whereby 1,2-dithiolane and hydrogen sulfide are produced, but the dithiolane yield is very low. A photochemical ring-expansion of 99 has been described in Section 11.5.1. ° Treatment of thietane with hexafluoroacetone gives a six-membered cyclic sulfenate. ... 

The synthesis of the five-membered cyclic dithioate 65 is shown in Scheme 16 [52,53]. The parent y-dithiolactone (3,4,5-trihydrothiophene-2-thione) (146) is prepared by thionation of the corresponding thiolactone 147, as shown in Eq. 32 [74]. Preparations for the l,3-dithiolane-4-thione derivatives 148 have been reported [75,76] (Scheme 32). It was proposed that the adamantanespiro compound 148a was formed by a reaction of the thiocarbonyl ylide, generated from 149 by extrusion of N2, with carbon disulfide [75]. 

A facile synthesis of 5-(2-thioxo-l,3-dithiolan-4-yl)methyl dialkylcarbamothioates and 5-thiiran-2-ylmethyl dialkylcarbamothioate from reaction of 5-(chloromethyl)-l,3-oxathiolane-2-thione with sodium dialkylcarbamodithioate and dialkylamine, respectively, has been reported to co-occur via intermolecular 0-S rearrangement (Scheme 81). " ... 

Rapid, selective thioacetalisation of a variety of aldehydes in the presence of ketones can be achieved with 1,2-ethanedithiol using silica treated with sulfuryl chloride as a catalyst [167]. The reaction is carried out at room temperature within 5 h to give yields of more than 90% of the corresponding 1,3-dithiolanes. Acid-treated montmorillonite KSF has been used to catalyse the synthesis of thioenol ethers from cyclic ketones and butanethiol (e.g. equation 4.46) [168]. 

Cyclic Disulphides and Cyclic Diselenides.—Formation. No fundamentally new methods of synthesis of this class of compounds have been reported in the past two years. For l,2>dithiolan the oxidation of l,3>dithiols remains a favoured method, the use of iodine in the presence of triethylamine leading smoothly to 1,2-dithiolans without attendant polymerization. cis- and tra/ -l,2-Dithiolan-3,5-dicarboxylic acids were prepared from a diastereo-isomeric mixture of dimethyl 2,4-dibromoglutarates by sequential treatment with potassium thioacetate and potassium hydroxide in the presence of iodine,and jyn-2,3-dithiabicyclo[3,2,l]octan-8-ol was formed from 2,6-dibromocyclohexanone by successive treatment with potassium thiocyanate, lithium aluminium hydride, and iodine. The stereoselective formation of the less thermodynamically stable alcohol in this case was attributed partly to the formation of chelates with sulphur-aluminium bonds. 2,2-Dimethyl-l,3-dibromopropane was converted into 4,4-dimethyl-l,2-diselenolan on treatment with potassium selenocyanate at 175 °C, but at 140 °C the product was 3,3-dimethylselenetan. Reductive debenzylation of 2-alkylamino-l,3-bis(benzylthio)propanes with lithium in liquid ammonia and oxidation of the resultant dithiols with air afforded 4-dialkylamino-l,2-dithiolans, whilst treatment of a-bromomethyl-chalcone with sodium hydrosulphide gave, as minor product, trans-3 phenyl-4-benzoyl-l,2-dithiolan. Among the many products of thermal decomposition of /ra/ -2,4-diphenylthietan was l,4,5,7-tetraphenyl-2,3-dithiabicyclo [2,2,2]octane. ... 

The conversion of active-methylene compounds into 2-alkylidene derivatives of 1,3-dithiolans by base-catalysed condensation with carbon disulphide followed by treatment with 1,2-dihalogenoalkanes has been further exemplified, and extended to the synthesis of substituted alkyl-idene derivatives of 1,3-diselenolans and 1,3-diselenans. With dimethyl malonate, carbon diselenide, and either 1,2-dibromoethane or 1,3-dibromo-propane, for example, the compounds (142) and (143), respectively, were formed. Analogously, the dithiolate anion obtained from deoxybenzoin... 

---