Dithiolans and 1,3-Dithians

3- Dithiolans and 1,3-Dithians.—Phenylacetonitrile and (CHgSClSOa gave 2-cyano-2-phenyl-l,3-dithiolan in 45% yield under phase-transfer conditions.  

The dithiolanylium salts (78 X = Br) were formed in very high yield and with complete exclusion of (79) upon bromination of (80), even when R = Ph. In contrast, cyclization of (80), using a proton acid as catalyst, gave (79 X = C104 ) when R = H, a mixture of (78) and (79) when R = Me, and exclusively 

2-acyl-dithians, e.g. (83), were prepared from 1,3-diketones and (TsSCH2)2CH2 in methanolic base, presumably via a diacyl-dithian intermediate (82).  

The first example of a stable thio-analogue of a Meisenheimer complex has been isolated. The salt (84) (red crystals m.p. 157 °C) was obtained by treatment of 2-(picrylthio)ethanethiol with NaOMe, followed by careful precipitation with toluene. The existence of the trimethylene analogue of (84) was inferred from spectroscopic measurements, but this material could not be isolated. 

Keten thioacetals such as (85) have been prepared by two routes. The first gives yields of 50—70% n = 2), and involves the reaction of bis(dimethyl-alumino)propane-l,3-dithiolate with esters it is patterned after the reaction earlier described, involving the analogous ethane-1,2-dithiolate. In the second method, a Grignard reagent is condensed with CS2, the product is converted into its lithium salt, allowed to react with Br(CHa) Cl, and then cyclized.  

3- Ditliiolans and 1,3-INdiians.—Synthesis. The synthesis of 1,3-dithiolans and 1,3-dithians, which were intended for use as reagents, will be referred to in the section on Reactions, especially if the method used differs substantially from the well-known procedures. 

Only a few syntheses of this class of heterocycle have been reported when the compounds were not intended for immediate further synthetic utilization. A simple preparation of l,3-dithiolan-2-one involved the reaction of ethanedithiol with phosgene in the presence of pyridine at 0 C. The same authors also reported the synthesis of mercaptothioacetic acid and its reaction with aldehydes to form, via loss of H2O or H2S from the intermediate (86), 2-substituted l,3-dithiolan-4-ones (87a) and 2-substituted 

3- oxathiolan-5-ones (87b). The yields were in the range 25—40% for (87a) RCHSCHjCOSH 

Bailey and R. L. Hinrichs, Polymer Preprints Amer. Chem. Soc., Div. Polymer Chan., 1970,11, 598 (Chem. Abs., 1972, 77, 20050j). 

The S=0 bond in 1,3-dithian 1-oxide (92) showed a considerable equatorial preference, in contrast to a marked axial preference in 

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Secondary alkyl selenides are reduced by (TMS)3SiH, as expected in view of the affinity of silyl radicals for selenium-containing substrates (Table 4.3) [40]. Reaction (4.23) shows the phenylseleno group removal from the 2 position of nucleoside [50]. Similarly to 1,3-dithiolanes and 1,3-dithianes, five- and six-membered cyclic selenoacetals can be monoreduced to the corresponding selenides in the presence of (TMS)3SiH [51]. The silicon hydride preferentially approached from the less hindered equatorial position to give transicis ratios of 30/70 and 25/75 for the five-membered (Reaction 4.24) and six-membered cyclic selenoacetals, respectively. 

BnPh3PHS05 was used for deprotection of oximes and semicarbazones to their parent carbonyl compounds under microwave irradiation. Similarly, dethioacetalization of 1,3-dithiolanes and 1,3-dithianes by BnPhsPHSOs in aprotic solvents was also reported . In both these reactions a catalytic amount of bismuth chloride was necessary. 

The stoichiometric equivalents of halofluorides have been recently applied to transform alkylene dithioacetals into gcm-difluorides.70-71 Dithioacetals such as 1,3-dithiolanes and 1,3-dithianes arc readily obtained from the corresponding carbonyl compounds by the reaction with ethane-1,2-dithiol or propane-1,3-dithiol in the presence of the complexes boron trifluoride-bis(acetic acid) or boron trifluoride-diethyl ether. Using a two-step procedure, a range of aldehydes and ketones can be converted into gem-difluorides under mild conditions. 

Ring-expansion substitution reactions of 1,3-dithiolanes and 1,3-dithianes with N-halo- and IV-cyano-succinimide give mono-halo- and -cyano-l,4-dithiins and -1,4-dithiepins (Scheme 19). With NBS and BU4NN3 and NBS and NH4SCN, the azido and thiocyanato analogues are formed, respectively.35... 

Open chain and cyclic thioacetals 1,3-Dithiolane and 1,3-dithiane derivatives are versatile intermediates in the synthesis and interconversion of monocarbonyl and 1,2-dicarbonyl compounds. Protection of carbonyl groups as their open-chain and cyclic thioacetals is an important method in the synthesis of organic molecules. Thioacetals are stable... 

Regeneration of ketones from 1,3-dithiolanes and 1,3-dithianes. Treatment of 1,3-dithiolanes or 1,3-dithianes in 75% aqueous acetonitrile with CAN at room temperature for 3 min. gives the parent carbonyl compounds in 70-87% yield."... 

Cyclopropanecarbaldehydes, 1,1-dialkoxy-l-cyclopropylalkanes and cyclopropyl ketones reacted readily with ethanedithiol " " " and propanedithioP to give the corresponding 1,3-dithiolanes and 1,3-dithianes, respectively, in excellent yield. Boron trifluoride diethyl ether complex, in the presence or absence of acetic acid, has generally been used as the catalyst, but hydrogen chloride has also been utilized.An example of this reaction is the formation of the dithioacetal of cyclopropanecarbaldehyde 3. ... 

Coupled with the fact that the proportion of trace metal contaminants detected within continuous flow reaction products is inherently low, due to reduced catalyst degradation, the use of a scavenger cartridge at the end of a reaction sequence represents a relatively long-term solution to this problem. Other examples of the use of solid-supported scavengers have been reported by Ley and co-workers [65], where in one example, two scavenger modules, comprising QuadraPure TU (126) and phosphane resin, were used in the synthesis of 1,4-disubstituted-l,2,3-triazoles [66], and by Watts and co-workers [67], where silica-supported copper sulfate was used for the removal of residual dithiol (ppb) in the synthesis of 1,3-dithiolanes and 1,3-dithianes. 

The reaction of dithioacetals including 1,3-dithiolanes and 1,3-dithianes with CAN provides a convenient procedure for the generation of the corresponding carbonyl group. The rapid reaction is serviceable in many systems and superior to other methods, e.g. in the synthesis of acylsilanes. In a series of compounds in which the dithiolane group is sterically hindered, the reaction led to enones, i.e. dehydrogenation accompanied the deprotection (eq 11). ... 

Dithiolanes and 1,3-dithianes can also be cleaved by Oxone on wet alumina to give the parent carbonyl compounds in high yields (eq 89). The combination of BnPhsPHSOs and BiCl3 has also been applied successfully to the deprotection of 1,3-dithiolanes and 1,3-dithianes under nonaqueous conditions. ... 

Early workers reacted the ketone with an excess of the thiol in the presence of an acid catalyst such as zinc chloride , hydrogen chloride or />-toluenesulphonic acid to prepare dithioacetals. The results were erratic and the yields often disappointing. The use of boron trifluoride etherate has led to consistently better results . This method is particularly effective when the thiol is used for the solvent of the ketone as the boron trifluoride etherate is added. Ethanedithiol and propanedithiol are usually the thiols of choice forming 1,3-dithiolanes and 1,3-dithianes respectively. For example, the 1,3-dithiolane of cholestane-3-one (equation 1) can be prepared in high yield by this method . Occasionally the choice... 

The use of a mild oxidizing agent such as 1-chlorobenzotriazole with 1,3-dithiolanes and 1,3-dithianes leads to the formation of disulphoxides. 

Ring cleavage of 1,3-dithiolans and 1,3-dithians by methylthiolation, and of s-trithian by treatment with bromine or with Na in liquid has been reported. 

Recently, Sc(OTf)3 has been widely used in many protection reactions such as methoxymethylation [69], tetrahydropyranylation [70], O-glycosidation [71], acylation [72, 73], esterification of alcohols [74], and thioglycosidation of glycols [75]. Scandium salts such as Sc(OTf)3 and SCCI3 were also found to be efficient and recyclable catalysts for conversion of carbonyl compounds to 1,3-oxathiolanes, 1,3-dithiolanes, and 1,3-dithianes [76, 77]. By employing this protocol, chemose-lective oxathioactalization of aldehydes in the presence of ketones was achieved (Scheme 12.34) [78]. 

Corey and Hase have found that 1,3-dithiolans and 1,3-dithians can be converted in good yields into dimethyl acetals, cyclic acetals, or thioacetals (or thioketals) upon reaction of the mono-5-methylated derivatives with methanol, ethylene glycol, and mercaptoethanol, respectively. These interchanges do not appear to involve the free carbonyl compound. The disulphonium salt prepared by the reaction of triethyloxonium tetrafluoroborate with 2-phenyl-l,3-dithiolan can be used to prepare benzylidene derivatives of 1,2-, 1,3-, and 1,4-diols (30— 80%) under basic conditions. This reaction appears to have considerable potential as a route to benzylidenated sugars. 

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