Dithianes, substituted

Dithianes substituted at the 2 and 5 positions, and their sulfoxides, are insecticidal agents. Optimum activity was observed for 5-/-butyl derivatives with either 2-phenyl or 2-cyano substituents <92Mi 608-02). The mode of action is thought to be similar to that of the insecticidal 2,6,7-trioxabicyclo[2.2.2]octanes. Investigations of the oxidation, metabolism, and photoactivity of these materials have been carried out <92Mi 608-03,92Mi 608-04,94JMC133). In related work, 2,5-disubstituted-... 

Scheme 11.3 Thermal rearrangement of 1.3-dithiane-substituted VCPs. 

We attributed the difficulties with this otherwise trivial RCM reaction to the close proximity of the dithiane ring to the metal center after catalyst coordination. This could allow a sulfur atom to coordinate to ruthenium, preventing catalyst turnover. A fix to this problem was not obvious as a dithiane was required as the acyl anion equivalent as determined above nevertheless, dithiomethylmethane was briefly investigated as a dithiane substitute, but this resulted in lower yields at various points in the synthesis leading up to the acrylate. Since this work was originally reported, however, more RCM catalysts have become commercially available from various chemical suppliers and those might be able to overcome the difficulties we experienced. 

The possibility of activating the indole nucleus to nucleophilic substitution has been realized by formation of chromium tricarbonyl complexes. For example, the complex from TV-methylindole (215) undergoes nucleophilic substitution with 2-lithio-l,3-dithiane to give a product (216) which can be transformed into l-methylindole-7-carbaldehyde (217) (78CC1076). 

The pivotal step in this sequence is an electrophilic substitution on indole. Although the use of l,3-dithian-2-yl carbanions is well documented, it has been shown only recently that 1,3-dithian-2-yl carbenium ions can be used in a Priedel-Crafts type reaction. This was accomplished initially using 2-methoxy-l,3-dithiane [1,3-Dithiane, 2-methoxy-] or 2-metlioxy-l,3-dithiolane [1,3-Dithiolane, 2-methoxy-] and titanium tetrachloride [Titanate(l —), tetrachloro-] as the Lewis acid catalyst.9 2-Substituted lysergic acid derivatives and 3-substituted indoles have been prepared under these conditions, but the method is limited in scope by the difficulties of preparing substituted 2-methoxy-1,3-dithianes. l,3-Dithian-2-yl carbenium ions have also been prepared by protonation of ketene dithioacetals with trifluoroacetic acid,10 but this reaction cannot be used to introduce 1,3-dithiane moieties into indole. 

However, (—)-(S)-p-tolylthio-(p-tolyl) sulphinylmethane 252 was obtained in 20% e.e. from gem-disulphide 253 using Helmintosporium cultures306 (equation 138). With this culture much higher asymmetric induction was observed when 1,3-dithianes 254 substituted or unsubstituted at carbon 2 were used as substrates (equation 139). Whereas the optical yield of the (— )-(S)-monosulphoxide 255 (X = Y = H) was about 14% only, this... 

Cyclic dithioketals and acetals represent another important class of sulfur containing chiral auxiliaries, which are available in chiral form by biooxidation. Biotransformations were performed on a preparative scale using whole-cells (wild type and recombinant) and isolated enzyme. Again, enantiocomplementary oxidation of unsubstituted dithianes (linear and cyclic, R = H) was observed when using and CPMOcomo (Scheme 9.28) [211,212]. Oxygenation of functionalized substrates (R = substituted alkyl) with gave preferably trans... 

The l,3-dithian-2-ylidene substituted carbene (54), accessible from the tosylhydrazone (53) by a Bamford - Stevens reaction, not only participates in cycloaddition reactions but is also a source of 4,8-dithiaspiro[2.5]oct-l-ene 6JCS(P1)2773>. 

The regeneration of carbonyl compounds from 1,3-dithianes can be achieved using potassium hydrogen persulfate, Oxone , supported on wet alumina <96SL767> and by periodic acid under non-aqueous conditions <96TL4331>. The deprotection of benzyl substituted 1,3-dithianes can be achieved using the one electron oxidant [Fe(phen)3](PF6)3 <96SL315>. 

Both o- and p- substituted bis(methylthio)arylmethylium salts, derived by the 5-methylation of substituted dithiobenzoates, dimerise following deprotonation to give 1,4-dithianes. Only with the former isomer is the quinone methide generated leading to a cyclooctene derivative <96LA1159>. 

Nenajdenko et al. described the first example of addition of a 1,2-dication to C-C mutiple bonds. The only S-S dication found to participate in this reaction was the highly strained dication 115 derived from 1,4-dithiane. The reaction with alkenes 119 proceeded under mild conditions and led to derivatives of dithioniabicyclo[2.2.2]octane 120 as shown in Equation (33) and Table 21 <1998JOC2168>. This reaction was sensitive to steric factors and proceeded only with mono and 1,2-disubstituted ethylenes. Only alkenes conjugated with aromatic or cyclopropane moieties underwent this reaction. For the 1,2-disubstituted alkenes used in this study, the relative configuration of substitutents at the double bond was preserved and only one diastereomer was formed (see entries 2 and 3). 

It has been shown that Lewis acid catalyzed isomerization of thionolactones provides access to thiolactones. For example, exposure of the substrate 22 to catalytic amounts of BF3 OEt2 led to efficient conversion to the thiolactone 23. Such transformations were also found to give minor amounts of lactone or dithiolactone side products <06TL6067>. Substituted tetrahydrothiophene derivatives have also been obtained from 1,4-dithiane-2,5-diol and 2-nitroethyl acetate derivatives by a base induced sequence featuring a Michael addition and a Henry reaction <06TL8087>. 

An abnormal (tele) substitution of chlorine in both 2,3- and 2,6-dichloropyrazines 91, 92 occurred on reaction with dithiane anion, while morpholine gave the normal //wo-substitution <06TL31>. Another paper described the highly selective ipso monosubstitution of the 2,3-dichloro compound by enolates in toluene <06T9919>. 

Further evidence for the above-mentioned mechanism of HOMO elevation by group 14 elements is provided by studies of thioethers. The decrease in oxidation potential of silyl ethers as compared to ethers is not realized in the case of a-silylthioethers whereas a-stannyl substituents in thioethers cause a considerable cathodic shift in oxidation potential. Moreover, the effect is geometry-dependent. Values for substituted cyclic dithianes 15 are summarized in Table 21. The difference between Si and Sn in this case is illustrative. The lone nonbonding pair in the 3p orbital of sulfur is much too low in energy compared to... 

TABLE 22. Peak potentials of oxidation (vs Ag+/AgN03 0.1 M/AN), of substituted 4,6-civ-di methyl-1,3-dithianes (16) ... 

The formation of S-oxides has also been observed when oxidizing a variety of 5-substituted 2-tert-butyl-l,3-dithianes in wet acetonitrile. In an undivided cell, 4-substituted 1,2-dithiolane-l-oxides were oblained (Scheme 25) [113]. A coupled cathodic process, in this case, was the reduction of protons formed in the anodic reaction. 

The phosphine-mediated desulfurization of substituted 1,2-dithianes to the corresponding tetrahydrothiophenes proceeds stereospecifically for the corresponding reactions of cis- and /ra r, 5-dihydroxy-l,2-dithianes 124 and 125/126, three different phosphines R3P (R=Et, Ph, (CH2)2COOH-HCl) were employed <2003H(60)47>. The reaction is pH-dependent under mildly acidic conditions, the thiols 127 and 128 were obtained under neutral or moderately basic conditions, however, the 4-hydroxy-3-mercaptotetrahydrothiophenes 129-131 were formed (Scheme 32). Erom 124 and 125 racemic 129 and 130 were obtained, while for 126 the stereospecific product 131 was isolated the identity of... 

The stability of substituted 1,2-dithianes toward ring-opening polymerization was tested by heating the disulfides with a catalytic amount of sodium methanethiolate <1989T91> none of the 1,2-dithianes were stable with respect to polymerization under these conditions. The thermal polymerization of 1,2-dithiane was also studied in detail <2005POJ512, 2004MM3143>. 

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