2-Thiazolin-5-thiones, a New Type of Sulfur Heterocycle Synthesis and Reactions

Simple syntheses of 4,4-disubstituted 2-thiazolin-5-thiones, which have so far been difficult to obtain, are described. These compounds are stable and undergo a number of different reactions. The first type of reaction discussed here are cyclosubstitutions, which occur on heating in the presence of electron-deficient acetylenes. 1,3-Dithiafulvenes are thus formed via nitrile elimination. Thiazolinthiones show different chemical behaviour in reactions with ynamines. On warrning, thiazolinylidene-thioamides and -thioketones are formed via a [2+2] cycloaddition, followed by an electrocyclic ring opening reaction. The third reaction type has been observed in the conversion with 1,3-dipolar reagents, In situ generated benzonitriliumbetaines undergo 1,3-dipolar cycloaddition to the exocyclic e,S-double bond and form dithiaspiro [4.4]nonadienes

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

Selected hetaryl and aryl thioketones react with acetylenecarboxylates under thermal conditions in the presence of LiClO4 or, alternatively, under high-pressure conditions (5 kbar) at room temperature yielding thiopyran derivatives. The hetero-Diels–Alder reaction occurs in a chemo- and regioselective manner. The initially formed [4 + 2] cycloadducts rearrange via a 1,3-hydrogen shift sequence to give the final products. The latter were smoothly oxidized by treatment with mCPBA to the corresponding sulfones.The authors thank the National Science Center (Cracow, Poland) for generous financial support (Grant Maestro-3 (Dec- 2012/06/A/ST5/00219). Skilful performance of microanalyses by Ms Hanna Jatczak and Ms Agnieszka Cieślińska (University of Łódź) is gratefully acknowledge

Synthesis of Fluorinated and Fluoroalkylated Heterocycles Containing at Least One Sulfur Atom via Cycloaddition Reactions

Fluorinated heterocycles constitute an important group of organic compounds with a rap- idly growing number of applications in such areas as medicinal chemistry, agrochemicals produc- tion, polymer chemistry, as well as chemistry of advanced materials. In the latter case, fluorinated thiophenes are considered as a lead class of compounds with numerous spectacular applications. On the other hand, cycloaddition reactions offer a superior methodology for stereo-chemically con- trolled synthesis of heterocycles with a diverse ring size and a variable number of heteroatoms. A comprehensive review of methods based on cycloaddition reactions and applied for construction of fluorinated and/or fluoroalkylated S-heterocycles has not yet been published. For this reason, the main goal of the presented review was to fill the existing gap and to summarize the results pub- lished over last six decades. In this context, the [3+2]- and [4+2]-cycloadditions (Huisgen reactions, and Diels–Alder reactions, respectively) are of special importance. Some questions related to the discussed mechanisms of cycloaddition processes observed in reactions with electron deficient, fluorinated substrates (dipolarophiles and dienophiles), and electron-rich sulfur containing counter partners, are of fundamental importance for the development of interpretations of organic reaction mechanisms

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

Synthesis of Z-Protected Aib- and Phe(2Me)-Containing Pentapeptides and Their Crystal Structures

A series of pentapeptide derivatives containing alpha,alpha-disubstituted alpha-amino acids have been prepared by a combination of the 'azirine/oxazolone method' and segment condensations. X-Ray crystal-structure determinations of the molecular structures confirmed the presence of helical conformations stabilized by beta-turns of type III or III’. Pentapeptides containing (R)-Phe(2Me) form a right-handed helix, whereas those containing (S)-Phe(2Me) adopt a left-handed helical structure

Thermal [2+2]-cycloadditions of diphenylketene with aryl- and hetaryl-substituted thioketones

The reaction of diphenylketene (1) with aryl- and hetaryl-substituted thioketones (2) gave the corresponding 3,3,4,4-tetraarylthietan-2-ones (3) in good yields. Remarkably, the reactions with bis-hetaryl-substituted thioketones occurred significantly faster compared with those involving the bis-aryl-substituted thioketones. The structure of compound 3c has been established by X-ray crystallography

An unexpected formation of a 14-membered Cyclodepsipeptide

The treatment of diluted solutions of the hydroxy diamides 6a and 6b in toluene with HCl gas at 100° gave the dimeric, 14-membered cyclodepsipeptide 10 in up to 72% yield (Scheme 3). The same product was formed from the linear dimer of 6b, the depsipeptide 11, under the same conditions (cf. Scheme 4). All attempts to prepare the cyclic seven-membered monomer 9, starting with different precursors and using different lactonization methods failed, and 10 was the only product which was isolated (cf. Scheme 6). For example, the reaction of the ester 20 with NaH in toluene at 80° led exclusively to the cyclodimer 10. On the other hand, the base-catalyzed cyclization of the hydroxy diester 22, which is the 'O-analogue' of 20, yielded neither the seven- membered dilactone, nor the 14-membered tetralactone, but only the known trimer 23 and tetramer 24 of 2,2- dimethylpropano-3-lactone (cf. Scheme 7)

Synthesis of optically active polycyclic N-heterocycles derived from L-prolinamine

The N-Boc-protected (S)-prolinamine reacts readily with formaldehyde and diverse alpha-hydroxyimino ketones to give imidazole N-oxides with an enantiomerically pure N-protected (pyrrolidin-2-yl)methyl substituent. Subsequent deprotection yields the corresponding NH derivatives. Upon treatment of these products with Ac2O at room temperature, a cascade of reactions leads to optically active tricyclic products. In all these processes, the stereogenic center is preserved. In one case, the bis-heterocyclic imidazole N-oxide was transformed into the corresponding optically active imidazole-2-thione via a sulfur-transfer reaction with 2,2,4,4-tetramethylcyclobutane-1,3-dithione

Strong influence of the trifluoromethyl group on the chemoselectivity of [3+2]-cycloadditions of thiocarbonyl S-methanides with α,β-unsaturated ketones

The in situ-generated reactive thiocarbonyl S-methanides were reacted with fluorinated enones. The type of the obtained [3+2]-cycloadduct depends strongly on the location of the activating CF3 group. In the case of enones containing the CF3CH=CH moiety, the [3+2]- cycloaddition occurs chemo- and regioselectively onto the C=C bond to give trifluoromethylated tetrahydrothiophene derivatives. On the other hand, enones containing the CF3–C=O unit react as carbonyl dipolarophiles leading to trifluoromethylated 1,3- oxathiolanes also in a chemo- and regioselective manner. These are the first reported reactions of thiocarbonyl S-methanides with α,β-unsaturated ketones