Unexpected course of the attempted conversions of ferrocenyl(hetaryl)methanols into thiols using Lawesson’s reagent

A series of secondary methanols bearing ferrocenyl and a hetaryl substituent was tested in reactions with Lawesson’s reagent (LR) aimed at the preparation of respective methanethiols. The study showed that in boiling toluene after only few minutes the starting alcohols were consumed and unexpectedly, depending on the type of hetaryl substituent, tetra-substituted ethane or disubstituted methane derivatives were obtained in good to excellent yields. The presence of the ferrocene moiety is crucial for the observed reaction courses

Efficient synthesis of ferrocifens and other ferrocenyl-substituted ethylenes via a ‘sulfur approach’

Stable and non-odorous alkyl ferrocenyl thioketones react with bis(4-methoxyphenyl)diazomethane according to the ‘two-fold extrusion’ reaction principles, and tetrasubstituted ethylenes obtained thereby can be demethylated to give (Fc,2OH)-ferrocifens in good yields. The method offers an alternative approach to this class of medically relevant compounds. A similar protocol with alkyl ferrocenyl thioketones and selected diaryldiazomethanes leads to ferrocenyl-substituted ethylenes including dibenzofulvenes. These products are of potential interest for electrochemical and photophysical studies

Synthesis of ferrocenyl- and hetaryl-substituted 2,2,2-trifluoroethanols and their conversion into 2,2,2-trifluoroethanethiols using Lawesson’s reagent

Ferrocenyl- and hetaryl-substituted ketones react smoothly with the Ruppert-Prakash reagent and, after desilylation of the intermediate adduct, gave the corresponding tertiary 2,2,2-trifluoroethanols. Similarly, ferrocenyl carbaldehyde was converted into 1-ferrocenyl-2,2,2-trifluoroethanol via nucleophilic trifluoromethylation. Some of the obtained fluorinated alcohols were transformed into thiols by treatment with Lawesson’s reagent or P2S5·2C5H5N complex. Remarkably, the obtained thiols are non-odorous compounds

Silylated thiocarbonyl S-methanides as key intermediates in one-pot olefination reactions leading to ferrocenyl-substituted ethenes and dibenzofulvenes

(Trimethylsilyl)diazomethane (TMS-CHN2) reacts smoothly with cycloaliphatic thioketones as well as with fluorene-9-thione at low temperature to give the corresponding 1,3,4-thiadiazole derivatives as product of a regioselective [3+2]-cycloaddition. In the first case, the obtained cycloadducts are relatively stable and eliminate N2 upon heating at 40ºC. In the second case, N2-extrusion occurs already at –40ºC. The silylated thiocarbonyl S-methanides generated thereby can be trapped regioselectively with ferrocenyl hetaryl thioketones to give the sterically crowded 2-silylated 4,4,5,5-tetrasubstituted 1,3-dithiolanes. Without isolation, these products are desilylated with TBAF and tetrasubstituted ethenes or dibenzofulvenes are obtained as final products via cycloelimination (‘[3+2]-cycloreversion’) of the intermediate 1,3-dithiolane carbanion

First synthesis of ferrocenyl-substituted thiochalcones and their [4+2]-cycloadditions with acetylenic dienophiles

Ferrocenyl methyl ketone reacts with aromatic aldehydes yielding 1-ferrocenyl-3-aryl-propenones (chalcones), which upon treatment with Lawesson’s reagent (LR) are converted to the corresponding thiochalcones. The latter enter the thia-Diels–Alder reaction with acetylenic dienophiles (DMAD and methyl propiolate) to give ferrocenyl-substituted 4H-thiopyrans. In the case of methyl propiolate, the formation of the six-membered ring occurs with complete regioselectivity

A novel application of 2-silylated 1,3-dithiolanes for the synthesis of aryl/hetaryl-substituted ethenes and dibenzofulvenes

Trimethylsilyldiazomethane (TMS-CHN2) reacts readily with hetaryl thioketones to give sterically crowded 2-trimethylsilyl-4,4,5,5-tetrahetaryl-1,3-dithiolanes with complete regioselectivity at −75 °C as well as at rt. Thiofluorenone, a relatively stable and highly reactive aryl thioketone, yields upon treatment with TMS-CHN2 at −60 °C the corresponding 1,3,4-thiadiazoline. This unstable cycloadduct undergoes decomposition at ca. −45 °C and the silylated thiocarbonyl S-methanide generated thereby is trapped with complete regioselectivity by aryl or hetaryl thioketones forming also sterically crowded 2-trimethylsilyl-1,3-dithiolanes. The obtained 1,3-dithiolanes, by treatment with an equimolar amount of TBAF in a one-pot procedure, are converted in high yields into hetaryl/aryl-substituted ethenes or dibenzofulvenes, respectively, via a cycloreversion reaction of the intermediate 1,3-dithiolane carbanion. The presented protocol offers a new, highly efficient approach to tetrasubstituted ethenes and dibenzofulvenes bearing aryl and/or hetaryl substituents

The unusual influence of hetaryl groups on the direct conversion of some secondary alcohols into thiols with Lawesson’s reagent: elucidation of the reaction mechanism

A series of hetaryl-substituted methanols were used for direct conversion into the corresponding thiols by treatment with Lawesson’s reagent in boiling toluene. Unexpectedly, the respective sulfides were formed exclusively. In the case of chiral alcohols, the sulfides were obtained as 1:1-mixtures of meso- and dl-diastereoisomers. In contrast to hetaryl-substituted alcohols, the analogous protocol applied for benzhydryl alcohol led to a mixture of the expected secondary thiol and a bis(diphenylmethyl) trithiophosphonate. Finally, the analogous reactions with ferrocenyl(phenyl)methanol and diferrocenylmethanol, respectively, led to the corresponding thiols in good yield

A convenient access to 1,2-diferrocenyl-substituted ethylenes via [3 + 2]-cycloelimination of 2-silylated 4,4,5,5-tetrasubstituted 1,3-dithiolanes

Ferrocenyl thioketones bearing a hetaryl, phenyl or alkyl group as the second substituent react with (trimethylsilyl)diazomethane at ca. −30°C in THF solution without formation of a stable [3+2]-cycloadduct. After the spontaneous evolution of N2, the corresponding sterically crowded 4,4,5,5-tetrasubstituted 2-silylated 1,3-dithiolanes are formed as products of the second [3 + 2]-cycloaddition of the intermediate thiocarbonyl S-methanide with the starting thioketone. After desilylation by treatment with TBAF, they are converted into the corresponding carbanions, which display different stability depending on the type of substituent. The presence of hetaryl and phenyl groups results in the exclusive formation of 1,2- diferrocenyl ethylenes. In contrast, the presence of methyl groups significantly enhances the stability of the carbanion, which by protonation yields trans-4,5-diferrocenyl-4,5-dimethyl-1,3-dithiolane

Dialkyl dicyanofumarates as oxidizing reagents for the conversion of thiols into disulfides and selenols into diselenides

Aliphatic and aromatic thiols react smoothly with dialkyl dicyanofumarates in CH2Cl2 at room temperature to give the corresponding disulfides in excellent yields. Aliphatic 1,2-, 1,3-, and 1,4-dithiols afford cyclic disulfides. Analogous reaction courses were observed starting with selenols, and the required diselenides were also formed in nearly quantitative yields. In all of the reactions, dialkyl dicyanosuccinates formed as a 1:1-mixture of diastereoisomers as the only other product. Cysteamine (2-mercaptoethylamine) behaved differently; the Michael addition of the primary amine group led to complete consumption of the dicyanofumarate, and the formation of the disulfide containing the enamine moiety occurred without the formation of dicyanosuccinate

Microwave-assisted reactions of α\alpha-diazoketones with hetaryl and ferrocenyl thioketones

Differently substituted hetaryl thioketones react with less reactive diazoketones under MW irradiation in toluene solution. After only 2 min, the reactions were complete and, depending on the type of the used diazoketone, α,β-unsaturated ketones, acyl substituted thiiranes or 1,3-oxathiols were obtained as final products. In the case of azibenzil and di(thiophen-2-yl) thioketone, a new type of 1,5-dipolar electrocyclization of the intermediate thiocarbonyl ylide involving a thiophene ring led to a fused sulfur heterocycle. In contrast to hetaryl thioketones, the ferrocenyl analogues decompose under MW irradiation. Alternatively they react with diazopropanone and 2-diazo-1-phenylethanone in boiling THF in the presence of LiClO4 to give α,β-unsaturated ketones as sole products. In these cases, the reactions require long reaction times