On the strong difference in reactivity of acyclic and cyclic diazodiketones with thioketones: experimental results and quantum-chemical interpretation

The 1,3-dipolar cycloaddition of acyclic 2-diazo-1,3-dicarbonyl compounds (DDC) and thioketones preferably occurs with Z,Econformers and leads to the formation of transient thiocarbonyl ylides in two stages. The thermodynamically favorable further transformation of C=S ylides bearing at least one acyl group is identified as the 1,5-electrocyclization into 1,3-oxathioles. However, in the case of diazomalonates, the dominating process is 1,3-cyclization into thiiranes followed by their spontaneous desulfurization yielding the corresponding alkenes. Finally, carbocyclic diazodiketones are much less reactive under similar conditions due to the locked cyclic structure and are unfavorable for the 1,3-dipolar cycloaddition due to the Z,Z-conformation of the diazo molecule. This structure results in high, positive values of the Gibbs free energy change for the first stage of the cycloaddition process.A. V. I. thanks the Saint Petersburg State University for financial support of his stay at the University of Łódź with Prof. G. Mloston (order 1831/1; 02.06.2011). A. S. M. acknowledges the Saint Petersburg State University for financial support in the form of a postdoctoral fellowship (No. 12.50.1562.2013). G. M. acknowledges support by the National Science Center (PLCracow) within the Grant Maestro–3 (Dec–2012/06/A/ST5/ 00219). The calculations were performed with the assistance of the Saint Petersburg State University Computer Center and the Chemistry Department of Saint Petersburg State University

Nonbonding pairs in cyclic thioethers: Electrostatic modelling and ab initio calculations for complexes of 2,5-dihydrothiophene, thietane and thiirane with hydrogen fluoride

Electrostatic potential energies V(ϕ) of a non‐perturbing, protonic charge at fixed distances r from the S atom in three cyclic thioethers were examined as functions of the angles ϕ made by the r‐vector with the C2 axis (thiirane and 2,5‐dihydrothiophene) or the local C2 axis (thietane). The electrostatic PE VHF(ϕ) of HF (HF modelled as an extended electric dipole) was also calculated and the results compared with geometries of the thioether⋯HF complexes calculated at the CCSD(T)‐F12c/cc‐pVTZ‐F12 level. The latter reveal angular deviations θ ∼10‐20° of the S⋯H-F nuclei from collinearity in directions suggesting secondary interactions of F with H atom(s) of the rings. Angles ϕ made by the S⋯H hydrogen bond with the C2 (or local C2) axes in the complexes are systematically larger (∼4‐9°) than indicated by the VHF(ϕ) functions. Minima in the simple V(ϕ) versus ϕ functions occur at values smaller (∼5‐10°) than those in the VHF(ϕ) curves

Sulfur-bearing species in molecular clouds

We study several molecules that could help in the solution of the missing sulfur problem in dense clouds and circumstellar regions, as well as in the clarification of the sulfur chemistry in comets. These sulfur molecules are: the trimer (CH2S)3 and the tetramer (CH2S)4 of thioformaldehyde, pentathian S5CH2, hexathiepan S6CH2, thiirane C2H4S, trisulfane HSSSH, and thioacetone (CH3)2CS. Infrared spectra of these species are calculated using density functional theory methods. The majority of calculated bands belong to the mid-infrared, with some of them occurring in the near and far-infrared region. We suggest that some of unidentified spectral features measured by Infrared Space Observatory in several active galactic nuclei and starburst galaxies could be caused by 1,3,5-trithiane ((CH2S)3), 1,3,5,7-tetrathiocane ((CH2S)4), and thiirane (C2H4S). The objects whose unidentified infrared features we compare with calculated bands are: NGC 253, M82, NGC 1068, Circinus, Arp 220, 30 Doradus, Orion KL, and Sgr B2.Comment: accepted for publication in MNRA

N-(Diazoacetyl)oxazolidin-2-thiones as Sulfur Donor Reagents: Asymmetric Synthesis of Thiiranes from Aldehydes

Financial support was provided by the University of the Basque Country UPV/EHU (UFI 11/22), Basque Government (GV grant No IT-291-07), and Ministerio de Ciencia e Innovación (MICINN, Grant CTQ2007-68095-C02), Spain. A. L. thanks MICINN and European Social Foundation for a Ramón y Cajal contract. I. O. thanks MCINN for a fellowship. We also thank SGIker (UPV/EHU) for providing NMR, HRMS, X-Ray, and computational resources

Exploring the functional space of thiiranes as gelatinase inhibitors using click chemistry

A series of 4-[(triazolyl)methoxy]phenyl analogs of the phenoxyphenyl-substituted thiirane SB-3CT 1 was evaluated for its ability to inhibit gelatinases, members of the matrix metalloproteinase family of enzymes. The triazole segment of these inhibitors was assembled using the Meldal-Sharpless copper-catalyzed Huisgen dipolar cycloaddition of an azide and a terminal alkyne. While these triazole derivatives possessed fair activity as gelatinase inhibitors, an intermediate used in the dipolar cycloaddition, 4-(propargyloxy)phenyl derivative 2, showed very good activity (<50% inhibitory activity following a 3 h pre-incubation of 2 at a concentration of 3 μM) as an inhibitor of human matrix metalloproteinase-2.Fil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; ArgentinaFil: Llarrull, Leticia Irene. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; ArgentinaFil: Fisher, Jed F.. University of Notre Dame; Estados UnidosFil: Chang, Mayland. University of Notre Dame; Estados UnidosFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido

Intramoleculer Hydrogen Bonding In Epoxide, Thiirane, Aziridine And Phosphirane Containing Cyclopentanols

A recent computational analysis of the stabilizing intramolecular OH· · · O contact in 1,2-dialkyl-2,3-epoxycyclopentanol diastereomers has been extended to thiiriane, aziridine and phosphirane analogues. Density functional theory (DFT), second-order Møller-Plesset perturbation theory (MP2) and CCSD(T) coupled-cluster computations with simple methyl and ethyl substituents indicate that electronic energies of the cis isomers are lowered by roughly 3 to 4 kcal mol−1 when the OH group of these cyclopentanol systems forms an intramolecular contact with the O, S, N or P atom on the adjacent carbon. The results also suggest that S and P can participate in these stabilizing intramolecular interactions as effectively as O and N in constrained molecular environments. The stabilizing intramolecular OH· · · O, OH· · · S, OH· · · N and OH· · · P contacts also increase the covalent OH bond length and significantly decrease the OH stretching vibrational frequency in every system with shifts typically on the order of −41 cm−1

The X-ray structure of carboxypeptidase a inhibited by a thiirane mechanism-based ihibitor

The three-dimensional X-ray crystal structure of carboxypeptidase A, a zinc-dependent hydrolase, covalently modified by a mechanism-based thiirane inactivator, 2-benzyl-3,4-epithiobutanoic acid, has been solved to 1.38 Å resolution. The interaction of the thiirane moiety of the inhibitor with the active site zinc ion promotes its covalent modification of Glu-270 with the attendant opening of the thiirane ring. The crystal structure determination at high resolution allowed for the clear visualization of the covalent ester bond to the glutamate side chain. The newly generated thiol from the inhibitor binds to the catalytic zinc ion in a monodentate manner, inducing a change in the zinc ion geometry and coordination, while its benzyl group fits into the S1' specificity pocket of the enzyme. The inhibitor molecule is distorted at the position of the carbon atom that is involved in the ester bond linkage on one side and the zinc coordination on the other. This particular type of thiirane-based metalloprotease inhibitor is for the first time analyzed in complex to the target protease at high resolution and may be used as a general model for zinc-dependent proteases.Fil: Fernández, Daniel. Universitat Autònoma de Barcelona; EspañaFil: Testero, Sebastian Andres. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Química Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Química Rosario; Argentina. University of Notre Dame; Estados UnidosFil: Vendrell, Josep. Universitat Autònoma de Barcelona; EspañaFil: Avilés, Francesc X.. Universitat Autònoma de Barcelona; EspañaFil: Mobashery, Shahriar. University of Notre Dame; Estados Unido

Catalyst-Controlled Stereoselective Barton-Kellogg Olefination

Overcrowded alkenes are expeditiously prepared by the versatile Barton-Kellogg olefination and have remarkable applications as functional molecules endowed by their unique stereochemical features. The induced stereodynamics thereby enable the controlled motion of molecular switches and motors while the high configurational stability prevents undesired isomeric scrambling that would impact their essential molecular topology. Bistricyclic aromatic enes are prototypical overcrowded alkenes with outstanding stereochemical properties, but their stereocontrolled preparation is challenging and was thus far only feasible in stereospecific reactions and by the use of chiral auxiliaries. Here, we now report that direct catalyst control is achieved by means of a stereoselective Barton-Kellogg olefination with enantio- and diastereocontrol in the preparation of various bistricyclic aromatic enes. Using Rh2(S-PTAD)4 as catalyst, several diazo compounds were selectively coupled with a thioketone to give one of the four anti -folded overcrowded alkene stereoisomers upon reduction. Moreover, complete stereodivergence was reached by catalyst control in combination with distinct thiirane reductions, providing access to all four stereoisomers with an e.r. of up to 99:1. We envision that the catalyst controlled synthesis of overcrowded alkenes and the possibility for stereodivergence in the Barton-Kellogg olefination will provide a direct and effective route for a broad range of topologically unique overcrowded alkenes for functional molecules, catalysis, energy- and electron transfer, or bioactive compounds

Synthesis of highly substituted alkenes by sulfur-mediated olefination of N-tosylhydrazones

Tetraphenylethylenes (TPEs) are well-known for their aggregation-induced emission properties. The synthesis of TPE derivatives, as well as other highly substituted olefins, generally requires the use of hazardous reagents, such as metalorganic compounds, to overcome the high activation energies caused by the sterically congested double bond. Herein, we present an efficient and metal-free procedure for the synthesis of tetraarylethylenes via alkylidene-homocoupling of N-tosylhydrazones, derived from readily available benzophenones, in excellent yields. The method relies only on cheap and benign additives, i.e. elemental sulfur and potassium carbonate, and easily competes with other established procedures in terms of scope, yield and practicability. A mechanistic study revealed a diazo compound, a thioketone and a thiirane as key intermediates in the pathway of the reaction. Based on this, a modified method, which allows for selective alkylidene-cross-coupling, generating a broader scope of tri- and tetrasubstituted olefins in good yields, is showcased as well