Novel Bicyclic P,S-Heterocycles via Stereoselective hetero-Diels-Alder Reactions of Thiochalcones with 1-Phenyl-4H-phosphinin-4-one 1-Oxide.

Thiochalcones undergo cycloaddition reactions in THF solution at 60 °C with the synthetically unexplored 1-phenyl-4H-phosphinin-4-one 1-oxide in a highly regio- and stereoselective manner, yielding hitherto unknown bicyclic P,S-heterocycles containing fused thiopyran and phosphinine rings. The stereochemical structures of two of the obtained (4+2)-cycloadducts were unambiguously assigned by means of the X-ray single-crystal analysis. Based on these assignments, a concerted mechanism of the hetero-Diels-Alder reaction via the preferred endo approach of the heterodiene from the less hindered P=O side of the phosphininone molecule is postulated to explain the established rac-(4RS,8SR,9SR,10SR)-configured (4+2)-cycloadducts isolated as major products.

(3+2)-Cycloadditions of Levoglucosenone (LGO) with Fluorinated Nitrile Imines Derived from Trifluoroacetonitrile: An Experimental and Computational Study.

The in situ-generated N-aryl nitrile imines derived from trifluoroacetonitrile smoothly undergo (3+2)-cycloadditions onto the enone fragment of the levoglucosenone molecule, yielding the corresponding, five-membered cycloadducts. In contrast to the 'classic' C(Ph),N(Ph) nitrile imine, reactions with fluorinated C(CF3),N(Ar) analogues lead to stable pyrazolines in a chemo- and stereoselective manner. Based on the result of X-ray single crystal diffraction analysis, their structures were established as exo-cycloadducts with the location of the N-Ar terminus of the 1,3-dipole at the α-position of the enone moiety. The DFT computation demonstrated that the observed reaction pathway results from the strong dominance of kinetic control over thermodynamic control.

Hetero-Diels-Alder Reactions of In Situ-Generated Azoalkenes with Thioketones; Experimental and Theoretical Studies.

The hetero-Diels-Alder reactions of in situ-generated azoalkenes with thioketones were shown to offer a straightforward method for an efficient and regioselective synthesis of scarcely known N-substituted 1,3,4-thiadiazine derivatives. The scope of the method was fairly broad, allowing the use of a series of aryl-, ferrocenyl-, and alkyl-substituted thioketones. However, in the case of N-tosyl-substituted cycloadducts derived from 1-thioxo-2,2,4,4-tetramethylcyclobutan-3-one and the structurally analogous 1,3-dithione, a more complicated pathway was observed. By elimination of toluene sulfinic acid, the initially formed cycloadducts afforded 2H-1,3,4-thiadiazines as final products. Advanced DFT calculations revealed that the observed high regioselectivity was due to kinetic reaction control and that the (4 + 2)-cycloadditions of sterically less unhindered thiones occurred via highly unsymmetric transition states with shorter C..S-distances (2.27-2.58 Å) and longer N..C-distances (3.02-3.57 Å). In the extreme case of the sterically very hindered 2,2,4,4-tetramethylcyclobutan-1,3-dione-derived thioketones, a zwitterionic intermediate with a fully formed C‒S bond was detected, which underwent ring closure to the 1,3,4-thiadiazine derivative in a second step. For the hypothetical formation of the regioisomeric 1,2,3-thiadiazine derivatives, the DFT calculations proposed more symmetric transition states with considerably higher energies.

The Fluoride Anion-Catalyzed Sulfurization of Thioketones with Elemental Sulfur Leading to Sulfur-Rich Heterocycles: First Sulfurization of Thiochalcones.

Fluoride anion was demonstrated as a superior activator of elemental sulfur (S8) to perform sulfurization of thioketones leading to diverse sulfur-rich heterocycles. Due to solubility problems, reactions must be carried out either in THF using tetrabutylammonium fluoride (TBAF) or in DMF using cesium fluoride (CsF), respectively. The reactive sulfurizing reagents are in situ generated, nucleophilic fluoropolysulfide anions FS(8-x)-, which react with the C=S bond according to the carbophilic addition mode. Dithiiranes formed thereby, existing in an equilibrium with the ring-opened form (diradicals/zwitterions) are key-intermediates, which undergo either a step-wise dimerization to afford 1,2,4,5-tetrathianes or an intramolecular insertion, leading in the case of thioxo derivatives of 2,2,4,4-tetramethylcyclobutane-1,3-dione to ring enlarged products. In reactions catalyzed by TBAF, water bounded to fluoride anion via H-bridges and forming thereby its stable hydrates is involved in secondary reactions leading, e.g., in the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone to the formation of some unexpected products such as the ring enlarged dithiolactone and ring-opened dithiocarboxylate. In contrast to thioketones, the fluoride anion catalyzed sulfurization of their α,ß-unsaturated analogues, i.e., thiochalcones is slow and inefficient. However, an alternative protocol with triphenylphosphine (PPh3) applied as a catalyst, offers an attractive approach to the synthesis of 3H-1,2-dithioles via 1,5-dipolar electrocyclization of the in situ-generated α,ß-unsaturated thiocabonyl S-sulfides. All reactions occur under mild conditions and can be considered as attractive methods for the preparation of sulfur rich heterocycles with diverse ring-size.

The [4+2]-Cycloaddition of α-Nitrosoalkenes with Thiochalcones as a Prototype of Periselective Hetero-Diels-Alder Reactions-Experimental and Computational Studies.

The [4+2]-cycloadditions of α-nitrosoalkenes with thiochalcones occur with high selectivity at the thioketone moiety of the dienophile providing styryl-substituted 4H-1,5,2-oxathiazines in moderate to good yields. Of the eight conceivable hetero-Diels-Alder adducts only this isomer was observed, thus a prototype of a highly periselective and regioselective cycloaddition has been identified. Analysis of crude product mixtures revealed that the α-nitrosoalkene also adds competitively to the thioketone moiety of the thiochalcone dimer affording bis-heterocyclic [4+2]-cycloadducts. The experiments are supported by high-level DFT calculations that were also extended to related hetero-Diels-Alder reactions of other nitroso compounds and thioketones. These calculations reveal that the title cycloadditions are kinetically controlled processes confirming the role of thioketones as superdienophiles. The computational study was also applied to the experimentally studied thiochalcone dimerization, and showed that the 1,2-dithiin and 2H-thiopyran isomers are in equilibrium with the monomer. Again, the DFT calculations indicate kinetic control of this process.

2-Unsubstituted Imidazole N-Oxides as Novel Precursors of Chiral 3-Alkoxyimidazol-2-ylidenes Derived from trans-1,2-Diaminocyclohexane and Other Chiral Amino Compounds.

'Desymmetrization' of trans-1,2-diaminocyclohexane by treatment with α,ω-dihalogenated alkylation reagents leads to mono-NH2 derivatives ('primary-tertiary diamines'). Upon reaction with formaldehyde, these products formed monomeric formaldimines. Subsequently, reactions of the formaldimines with α-hydroxyiminoketones led to the corresponding 2-unsubstituted imidazole N-oxide derivatives, which were used here as new substrates for the in situ generation of chiral imidazol-2-ylidenes. Upon O-selective benzylation, new chiral imidazolium salts were obtained, which were deprotonated by treatment with triethylamine in the presence of elemental sulfur. Under these conditions, the intermediate imidazol-2-ylidenes were trapped by elemental sulfur, yielding the corresponding chiral non-enolizable imidazole-2-thiones in good yields. Analogous reaction sequences, starting with imidazole N-oxides derived from enantiopure primary amines, amino alcohols, and amino acids, leading to the corresponding 3-alkoxyimidazole-2-thiones were also studied.

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts.

Adamantyloxyamine reacts with formaldehyde to give N-(adamantyloxy)formaldimine as a room-temperature-stable compound that exists in solution in monomeric form. This product was used for reactions with α-hydroxyiminoketones leading to a new class of 2-unsubstituted imidazole 3-oxides bearing the adamantyloxy substituent at N(1). Their reactions with 2,2,4,4-tetramethylcyclobutane-1,3-dithione or with acetic acid anhydride occurred analogously to those of 1-alkylimidazole 3-oxides to give imidazol-2-thiones and imidazol-2-ones, respectively. Treatment of 1-(adamantyloxy)imidazole 3-oxides with Raney-Ni afforded the corresponding imidazole derivatives without cleavage of the N(1)-O bond. Finally, the O-alkylation reactions of the new imidazole N-oxides with 1-bromopentane or 1-bromododecane open access to diversely substituted, non-symmetric 1,3-dialkoxyimidazolium salts. Adamantyloxyamine reacts with glyoxal and formaldehyde in the presence of hydrobromic acid yielding symmetric 1,3-di(adamantyloxy)-1H-imidazolium bromide in good yield. Deprotonation of the latter with triethylamine in the presence of elemental sulfur allows the in situ generation of the corresponding imidazol-2-ylidene, which traps elemental sulfur yielding a 1,3-dihydro-2H-imidazole-2-thione as the final product.

Ammonium-tagged ruthenium-based catalysts for olefin metathesis in aqueous media under ultrasound and microwave irradiation.

The influence of microwave and ultrasonic irradiation on the performance of ammonium-tagged Ru-based catalysts in olefin metathesis transformations in aqueous media was studied. Differences in the catalytic activity in correlation with the nature of the present counter ion and the size of the N-heterocyclic carbene (NHC) ligand were revealed. The presented methodology allows for preparation of a variety of polar and non-polar metathesis products under environmentally friendly conditions.

First thia-Diels-Alder reactions of thiochalcones with 1,4-quinones.

Aryl and hetaryl thiochalcones react smoothly with 1,4-quinones in THF solution at 60 °C yielding the corresponding fused 4H-thiopyrans after spontaneous dehydrogenation of the initially formed [4 + 2] cycloadducts. In general, the yields of the isolated products were high. With 5-chloro-10-hydroxy-1,4-anthraquinone, the thia-Diels-Alder reaction occurred with complete regioselectivity. In the case of the reaction of vitamin K3 (menadione) with diphenylthiochalcone, the initial cycloadduct was isolated in 37% yield.

Dimerization reactions of aryl selenophen-2-yl-substituted thiocarbonyl S-methanides as diradical processes: a computational study.

An intriguing stepwise diradical mechanism of the dimerization of the reactive intermediate (thiocarbonyl S-methanide) appearing in the reaction of phenyl selenophen-2-yl thioketone with diazomethane was studied by means of computational methods. The preferred formation of the unusual macroheterocycle, competitive with the 1,3-ring closure leading to a thiirane and the head-to-head dimerization yielding a 1,4-dithiane derivative, respectively, was explained based on the analysis of the structure of the favored conformer of the intermediate, delocalized diradical species. The influence of selenium as a 'heavy atom' for stabilization of this intermediate has been emphasized.

Nitro-Grela-type complexes containing iodides - robust and selective catalysts for olefin metathesis under challenging conditions.

Iodide-containing nitro-Grela-type catalysts have been synthesized and applied to ring closing metathesis (RCM) and cross metathesis (CM) reactions. These new catalysts have exhibited improved efficiency in the transformation of sterically, non-demanding alkenes. Additional steric hindrance in the vicinity of ruthenium related to the presence of iodides ensures enhanced catalyst stability. The benefits are most apparent under challenging conditions, such as very low reaction concentrations, protic solvents or with the occurrence of impurities.

High-Performance Isocyanide Scavengers for Use in Low-Waste Purification of Olefin Metathesis Products.

Three isocyanides containing a tertiary nitrogen atom were investigated for use as small-molecule ruthenium scavenging agents in the workup of olefin metathesis reactions. The proposed compounds are odorless, easy to obtain, and highly effective in removing metal residues, sometimes bringing the metal content below 0.0015 ppm. The most successful of the tested compounds, II, performs very well, even with challenging polar products. The performance of these scavengers is compared and contrasted with other known techniques, such as silica gel filtration and the use of self-scavenging catalysts. As a result, a new hybrid purification method is devised, which gives better results than using either a self-scavenging catalyst or a scavenger alone. Additionally, isocyanide II is shown to be a deactivating (reaction quenching) agent for olefin metathesis and superior to ethyl vinyl ether.