Thiocarbonyl Derivatives Research Articles

Redox-Active Thiocarbonyl Auxiliaries in Ni-Catalyzed Cross-Couplings of Aliphatic Alcohols.

ConspectusThe Barton-McCombie deoxygenation reaction first established the use of O-alkyl thiocarbonyl derivatives as powerful redox-active agents for C(sp3)-O reduction. In recent years, first-row transition metals capable of engaging with alkyl radical intermediates generated from O-alkyl thiocarbonyl derivatives using alternative stoichiometric radical precursors have been developed. Given the ability of select Ni catalysts to both participate in single-electron oxidative addition pathways and intercept alkyl radical intermediates, our group has investigated the use of O-alkyl thiocarbonyl derivatives as electrophiles in novel cross-coupling reactions. After describing related work in this area, this Account will first summarize our entry point into this field. Here, we used the cyclopropane ring as a reporter of leaving group reactivity to aid in the design and optimization of a novel redox-active O-thiocarbamate leaving group for C(sp3)-O arylation. Motivation for this pursuit was driven by the propensity of the cyclopropane ring to undergo ring opening under polar (2e) oxidative addition pathways or to be maintained under single-electron (1e) conditions. Using these guiding principles, we developed a method for the deoxygenative arylation of cyclopropanol derivatives using a Ni catalyst without the need for a stoichiometric external reductant or photocatalyst. We next summarize our evaluation of an alternative redox-active O-thiocarbonyl imidazole auxiliary in a related deoxygenative cross-coupling. This work demonstrated an extension of our initial approach to the deoxygenative arylation of primary and secondary aliphatic alcohol derivatives. A brief mechanistic investigation revealed that this reaction likely proceeds via a distinct mechanism involving direct homolytic C(sp3)-O bond cleavage. We conclude this Account with a summary of work aimed toward a unique approach for thiocarboxylic acid derivative synthesis. This project was inspired by the efficiency of thionoester generation under most of the reaction conditions evaluated in our prior investigations. Using alcohol, amine, or thiol starting materials, which were activated with convenient thiocarbonyl sources in a single step, we optimized for a Ni-catalyzed cross-coupling capable of providing access to a range of thionoester, thioamide, or dithioester products. In summary, our work has revealed the potential of redox-active thiocarbonyl auxiliaries in Ni-catalyzed cross-couplings with C(sp3)-O electrophiles. We anticipate that the continued investigation of aliphatic thiocarbonyl derivatives as radical precursors with alternative single-electron inputs will be an area of continued growth in the years to come.

Thiocarbonyl Derivatives of Natural Chlorins: Synthesis Using Lawesson's Reagent and a Study of Their Properties.

The development of sulfur-containing pharmaceutical compounds is important in the advancement of medicinal chemistry. Photosensitizers (PS) that acquire new properties upon incorporation of sulfur-containing groups or individual sulfur atoms into their structure are not neglected, either. In this work, a synthesis of sulfur-containing derivatives of natural chlorophyll a using Lawesson's reagent was optimized. Thiocarbonyl chlorins were shown to have a significant bathochromic shift in the absorption and fluorescence bands. The feasibility of functionalizing the thiocarbonyl group at the macrocycle periphery by formation of a Pt(II) metal complex in the chemotherapeutic agent cisplatin was shown. The chemical stability of the resulting conjugate in aqueous solution was studied, and it was found to possess a high cytotoxic activity against sarcoma S37 tumor cells that results from the combined photodynamic and chemotherapeutic effect on these cells.

Tuning Photoenolization-Driven Cycloadditions Using Theory and Spectroscopy.

The first broad spectrum investigation into the photoenolization/Diels-Alder (PEDA) sequence was carried out using M06-2X/6-31+G(d,p) in conjunction with SMD solvation and supported by experimental UV-vis spectroscopy. A test set of 20 prodienes was chosen to examine the role of the H atom acceptor group (substituted and unsubstituted carbonyl, thiocarbonyl, and imine), the H atom donor group, and bystander ring substituents. As reaction partners for the photogenerated dienes, a diverse test set of 20 dienophiles was examined, comprising electron rich, electron poor, neutral, strain activated, hydrocarbon, and heteroatom-containing molecules including CO2 and CO. A key finding of this work is the demonstration that the PEDA sequence of carbonyl based prodienes is tolerant of most substitution patterns. Another is that thiocarbonyl derivatives should behave analogously to the carbonyls but are likely to do so much more slowly, due to an inefficient intersystem crossing, an endothermic 1,5-hydrogen atom transfer (HAT) step, and a [1,5] sigmatropic H shift to regenerate the starting material that outcompetes the [4 + 2]cycloaddition. In contrast, the T1 state of the ortho-alkyl imines displays the incorrect orbital symmetry for 1,5-HAT and is correspondingly accompanied by higher barriers, even in the excited state. However, provided these barriers can be overcome, the remaining steps in the PEDA sequence are predicted to be facile. The Diels-Alder reaction is predicted to be of much broader scope than reported synthetic literature: while electron poor dienophiles are expected to be the most reactive partners, ethylene and electron rich alkenes should react at a synthetically useful rate. CO is predicted to undergo a facile (4 + 1)cheletropic addition instead of the normal [4 + 2]cycloaddition pathway. This unique photoenolization/cheletropic addition (PECA) sequence could provide metal-free access to benzannelated cyclopentanones.

Microbiological versus Chemical Reductive Sulfidation: An Experimental and Theoretical Study.

Microbiological reductive sulfidation (RS) has rarely been documented, although it represents an efficient strategy for thiol formation. In this work, we reported on the sulfate-respiring bacterium Desulfovibrio sp.86 that has previously demonstrated RS activity toward the pesticide chlordecone. The purpose of this study was to assess its substrate versatility using a set of 28 carbonyls, to compare with chemical RS and to rationalize the observed trends using a dual experimental and theoretical approach. The chemical RS generally proceeds in two steps (S/O exchange using a sulfur donor like P4S10, reduction of the thione intermediate). Intriguingly, chlordecone was found to be converted into chlordecthiol following the first step. Hence, we designed a protocol and applied it to the 28 substrates to assess their propensity to be directly converted into thiols with the P4S10 treatment alone. Finally, we performed density functional theory calculations on these carbonyls and their thiocarbonyl derivatives to build a set of structural, electronic, and thermodynamic parameters. The results showed that chemical and microbiological RS probably involved two distinct mechanisms. Chemically, we observed that several carbonyls, possessing electron-withdrawing groups and/or aromatic rings, were directly transformed into thiols in the presence of P4S10. The correlation obtained with the electron affinity of the thiones led us to conclude that a probable single-electron reductive transfer occurred during the first step. We also found that Desulfovibrio sp.86 transformed a variety of aldehydes and ketones, without ever detecting thiones. No significant correlation was observed with the calculated parameters, but a relationship between aldehyde RS biotransformation and bacterial growth was observed. Differences in selectivity with chemical RS open the way for further applications in organic synthesis.

Torsional Potentials of Glyoxal, Oxalyl Halides, and Their Thiocarbonyl Derivatives: Challenges for Popular Density Functional Approximations.

The reliability of popular density functionals was studied for the description of torsional profiles of 36 molecules: glyoxal, oxalyl halides, and their thiocarbonyl derivatives. HF and 18 functionals of varying complexity, from local density to range-separated hybrid approximations and double-hybrid, have been considered and benchmarked against CCSD(T)-level rotational profiles. For molecules containing heavy halogens, most functionals fail to reproduce barrier heights accurately and a number of functionals introduce spurious minima. Dispersion corrections show no improvement. Calibrated torsion-corrected atom-centered potentials rectify the shortcomings of PBE and also improve on σ-hole based intermolecular binding in dimers and crystals.

Synthesis and Characterization of Sodium Diphenylcarbamodithioate Ligand [L] and its Cobalt, Nickel, and Copper Complexes

A correlation of the infrared spectra of thiocarbonyl derivatives based on the literature data has been carried out. Assignments have also been made in some new systems. Sodium Diphenylcarbamodithioate ligand and its monomeric complexes were synthesized at room temperature and stirring condition. The ligand and its complexes of the general formula [M(L) 2 ] (where M= Co +2 , Ni +2 and Cu +2 ) were characterized by spectroscopic methods (IR and ultraviolet-visible), elemental analysis (C.H.N. and S) metal content, magnetic susceptibility measurement, and biological activity (an antibacterial activity of the complex was studied by agar disc diffusion method and minimum inhibitory concentration strain against Staphylococcus aureus and Bacillus subtilis). The complex exhibited significant activities against S. aureus and B. subtilis, thin-layer chromatography, mass spectrometry, X-ray powder diffraction, and molar conductance. Our study revealed the formation of four-coordinate square planar complexes around Coп, Niп, and Cuп metal ions.

Computational Mechanistic Study of Thionation of Carbonyl Compounds with Lawesson's Reagent.

The thionation reaction of carbonyl compounds with Lawesson's reagent (LR) has been studied using density functional theory methods and topological analyses. After dissociation of LR, the reaction takes place through a two-step mechanism involving (i) a concerted cycloaddition between one monomer and the carbonyl compound to form a four-membered intermediate and (ii) a cycloreversion leading to the thiocarbonyl derivative and phenyl(thioxo)phosphine oxide. Topological analyses confirmed the concertedness and asynchronicity of the process. The second step is the rate-limiting one, and the whole process resembles the currently accepted mechanism for the lithium salt-free Wittig reaction. No zwitterionic intermediates are formed during the reaction, although stabilizing electrostatic interactions are present in initial stages. Phenyl(thioxo)phosphine oxide formed in the thionation reaction is capable of performing a second thionation, although with energy barriers higher than the first one. The driving force of the thionation reactions is the formation of trimers from the resulting monomers. In agreement with experimental observations, the amides are the most reactive when compared with esters, aldehydes, and ketones and the reaction is slightly influenced by the polarity of the solvent. Whereas for amides and esters substituents have little effect, aldehydes and ketones are influenced by both steric and electronic effects.

TiCl4-Mediated Preparation of Thiophthalide Derivatives via Formal Thio-Passerini Reactions.

By the formal extension of the Passerini reaction to thiocarbonyl derivatives, the straightforward preparation of thiophthalides is disclosed. This method involves the intermediate formation of a sulfanyl-phthalide and a titanium tetrachloride mediated isocyanide insertion reaction. When tert-butyl thiol is used, thanks to the deprotection of the tert-butyl group, a thiophthalide resulting from a 1,5-Mumm rearrangement is isolated. Owing to the multifaceted activity of TiCl4, all steps may conveniently be performed in one pot, starting directly from 2-formylbenzoic acids, tert-butyl thiol, and various isocyanides.

DFT studies of imino and thiocarbonyl ligands with the pentaaqua Mg2+ cation: affinity and associated parameters

The affinity of the pentaaqua Mg(2+) cation for a set of para-substituted imino [HN = CHC₆H₄(R)] and thiocarbonyl [S = CHC₆H₄(R)] ligands (R = H, F, Cl, Br, OH, OCH₃, CH₃, CN, NH₂ and NO₂) was analyzed with DFT (B3LYP/6-31+G(d)) and semi-empirical (PM6-DH2) methods. The interaction enthalpy was calculated to quantify the affinity of the Mg(2+) cation for the ligands. Additionally, geometric and electronic parameters were correlated with the intensity of the metal-ligand interaction. The imino ligands have stronger interaction with the pentaaqua Mg(2+) cation than the thiocarbonyl derivatives. The electronic nature of the substituent is the main parameter that determines the interaction enthalpy. Ligands with electron donor substituents have more exothermic interaction enthalpies than those with electron withdrawing groups. The HSBA analysis showed that the interaction between the Mg(2+) cation and hard bases (imino ligands) is stronger than with soft bases (thiocarbonyl derivatives). The EDA analysis showed that the electrostatic, covalent and repulsion components of the interaction are the most affected by the substituent, whereas the dispersion and exchange components are almost constant.

Coaxial versus perpendicular structures for a range of binuclear cyclopentadienylpalladium derivatives

Binuclear palladium complexes of planar hydrocarbon ligands are of particular interest since both the coaxial structure (η5-Me5C5)2Pd2(μ-CO)2 and the perpendicular structure (μ-C6H6)2Pd2(Al2Cl7)2 have been synthesized as stable compounds. Here we report theoretical studies on a family of related compounds. For the formal Pd(II) derivatives Cp2Pd2X2 (Cp = η5-C5H5; X = F, Cl, CN) the perpendicular structures with direct Pd–Pd bonds are predicted to lie in energy below the isomeric coaxial structures. These coaxial structures have long Pd⋯Pd distances indicating the absence of palladium–palladium bonds. The lowest energy perpendicular Cp2Pd2X2 structures (X = F, CN) and a higher energy similar Cp2Pd2Cl2 structure contain a substituted η4-C5H5X cyclopentadiene ligand obtained by the addition of X to one of the Cp ligands. For the formal Pd(I) complexes Cp2Pd2L2 (L = CO and CS) the coaxial structures lie in energy below the isomeric perpendicular structures with a particularly large energy separation of ∼19 kcal mol−1 for the thiocarbonyl derivatives. However, for Cp2Pd2(CNCH3)2 the coaxial and perpendicular isomers have essentially the same energies.

Unsaturation in binuclear cyclopentadienyliron carbonyl thiocarbonyls: Four-electron donor bridging thiocarbonyl groups versus metal–metal multiple bonds

Theoretical studies on the binuclear cyclopentadienyliron carbonyl thiocarbonyl derivatives Cp2Fe2(CO)2(μ-CS)(μ-CO) and Cp2Fe2(CO)2(μ-CS)2 indicate that the trans and cis isomers are nearly degenerate in energy, consistent with experiment. Structures with bridging CS groups are of lower energy than corresponding structures with bridging CO groups. The corresponding unbridged Cp2Fe2(CS)(CO)3 and Cp2Fe2(CS)2(CO)2 isomers are predicted to lie 11 and 16kcal/mol, respectively, above their global minima, indicating increasing activation energies for the cis/trans interconversion as bridging CO groups are replaced by bridging CS groups. The unsaturated species Cp2Fe2(μ-CS)(μ-CO)2 and Cp2Fe2(μ-CS)2(μ-CO) are predicted to have triply bridged triplet spin state structures with FeFe double bonds of lengths 2.26Å, analogous to the experimentally known triplet (Me5C5)2Fe2(μ-CO)3. However, low-lying singlet Cp2Fe2(CS)(CO)2 and Cp2Fe2(CS)2(CO) structures with four-electron donor bridging η2-μ-CS groups and formal Fe–Fe single bonds are also found. The lowest lying Cp2Fe2(CS)(CO) and Cp2Fe2(CS)2 structures have two bridging groups and very short FeFe distances of ∼2.14Å, suggesting formal triple bonds. Several higher energy four-electron donor η2-μ-CS bridged structures are also found for Cp2Fe2(CS)(CO) and Cp2Fe2(CS)2. In addition, singlet and triplet structures are found for Cp2Fe2(CS)2 in which the two CS ligands have coupled to form a bridging SCCS group with a carbon–carbon bond. Only a η2-μ-CS bridged singlet structure is predicted for Cp2Fe2(CS), rather than the normal bridged structure with a FeFe quadruple bond such as that predicted for the carbonyl analog Cp2Fe2(CO).

Synthesis and in vitro activity of novel 1,2,4-triazolo[4,3-a]pyrimidine oxazolidinone antibacterial agents

The synthesis and antibacterial activity of 3-(4-([1,2,4]triazolo[4,3-a]pyrimidin-3-yl)phenyl)oxazolidin-2-ones is reported. Thiocarbonyl derivatives were found to be potent inhibitors of gram-positive pathogens and compound 4l was two to fourfold more potent than Linezolid.

ChemInform Abstract: On the Mechanism of Deoxygenation of Secondary Alcohols by Tin Hydride Reduction of Methyl Xanthates and Other Thiocarbonyl Derivatives.

ChemInform Abstract: On the Mechanism of Deoxygenation of Secondary Alcohols by Tin Hydride Reduction of Methyl Xanthates and Other Thiocarbonyl Derivatives.

ChemInform Abstract: Recyclization of Enamino Carbonyl and Enamino Thiocarbonyl Derivatives of Imidazolidine into Pyrrolines.

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ChemInform Abstract: Thiocyanohydrins, a New Class of Compounds, Precursors of Unstabilized Thiocarbonyl Derivatives.

Abstract Mono- and dialkylated thiocyanohydrins are prepared by alkylation of the parent compound 2 (NCCH2SH) under mild conditions. Some examples of the reactivity of this new class of compounds are also given.

ChemInform Abstract: Silicon-Assisted Synthesis of Thiocarbonyl Derivatives and Reactivity of Dienophilic Thioaldehydes.

Treatment of bis(trimethylsilyl) sulfide with CoCl 2 .6H 2 0 in the presence of aldehydes affords the coresponding thiocarbonyl analogues which can be trapped to avoid polymerization.

Axially Extended Perylene Dyes

AbstractPerylenecarboxylic anhydride imides were condensed with semicarbazide and thiosemicarbazide to form perylene dyes extended by triazoline rings and bathochromically shifted UV/Vis absorption and fluorescence. The thiocarbonyl derivative reacts with diazo compounds to cause a further extension with spiro‐arranged thiirane rings. Applications in analytics are discussed.

Different pathways for the deoxygenation of the A-ring of natural triterpene compounds

Some deoxygenation pathways were tested to remove the hydroxyl groups of the natural triterpenes oleanolic acid and maslinic acid to obtain a practical starting material for the semisynthesis of other interesting organic synthons. Different deoxygenation processes were carried out starting from these triterpenic acids or from several derivatives such as methyl esters and epoxy derivatives. The hydroxyl groups were transformed into some intermediate compounds including xanthyl, thiocarbonyl or tosyl derivatives. The opening of the oxirane ring between C-2 and C-3 was also achieved through different methods using deoxygenating reagents such as Me3SiCl/NaI, WCl4/n-BuLi and Cp2TiCl.

Site-selective catalysis of phenyl thionoformate transfer as a tool for regioselective deoxygenation of polyols.

We report the application of peptide-embedded imidazoles as catalysts for the site-selective delivery of the phenyl thionoformate unit as a prelude to deoxygenation reactions of polyols. Methodology was developed that allows for the synthesis of thiocarbonyl derivatives based on a combination of additives that include N-alkylimidazoles and FeCl3 as co-catalysts. The use of this reagent combination leads to increased reaction rates and efficient yields relative to those of simple base-mediated reactions. In terms of controlling regioselectivity during the course of polyol modification, we found that histidine-containing peptides, in combination with FeCl3, could lead to modulation of the product distribution. Through screening of peptides and control of reaction conditions, products could be observed that reflected both the inherent preference of substrates and also reversal of inherent selectivity.

A quantitative prediction of the electronic spectra of thiocarbonyl chromophores: TD-DFT versus SAC-CI

In this contribution, we set up a SAC-CI methodology to evaluate the n → π* and π → π* vertical transition energies of a series of thiocarbonyl derivatives. We show that Frozen-Core SAC-CI provides accurate vertical excitations energies. Nevertheless, in order to obtain converged results, the R2S2 unliked integrals have to be taken into account in L3-SAC-CI calculations. In addition, we present the comparative performances of three computational procedures, INDO/S, TD-DFT, and SAC-CI, for the calculation of valence excited states energies and it turns out that: (1) no tuning of the exact exchange (α) included in TD-DFT allows to consistently reproduce the SAC-CI results; (2) SAC-CI and TD-B3LYP both evaluate the n → π*, as well as the π → π* transition energies, with a similar accuracy.