Benzyl Sulfoxides Research Articles

The insertion of thiazolo[5,4-d]thiazole unit in covalent triazine framework for boosting the photocatalytic capacities in both selective aerobic oxidation of sulfides and amines

Recently, covalent triazine frameworks (CTFs) have realized versatile applications in the field of photocatalysis. Herein, two CTFs photocatalysts were designed and synthesized with or without thiazolo[5,4-d]thiazole (TzTz), an electron deficient unit, to highlight the introduction of an additional acceptor unit on the photocatalytic aerobic oxidation reaction of triazine based CTFs. Specifically, CTF-TZDA was prepared by a condensation reaction between terephthalimidamide and 4,4′-(thiazolo[5,4-d]thiazole-2,5-diyl) dibenzaldehyde (TzTz aldehyde), and similarly, CTF-FPBA was prepared between terephthalimidamide and [1,1′-biphenyl]-4,4′-dicarbaldehyde. CTF-TZDA showed high photocatalytic activities towards aerobic oxidation of both benzyl sulfides and benzyl amines to benzyl sulfoxides and benzyl imines, respectively, and the reaction was powered by blue light. A wide range of substrates can be aerobically oxidized with high yield (about 99%) and high selectivity over CTF-TZDA photocatalyst. The insertion of the TzTz unit lowered that band gap, accelerated the delocalization of π electrons, and elevated the LUMO levels of CTF-TZDA, which are beneficial to extend the light absorption range, and to promote the separation and transfer of photo-induced charge carriers. This work indicates that the insertion of an additional electron deficient unit rich in heteroatoms is considered as a feasible approach towards enhancing the photocatalytic activity of CTFs.

Nickel-Catalyzed Reductive Arylation of α-Bromo Sulfoxide.

A nickel-catalyzed cross-electrophile coupling of aryl iodides with α-bromo sulfoxide to access a diverse array of aryl benzyl sulfoxides has been discovered. These reactions occurred under mild conditions with excellent functional group tolerance so that optically enriched sulfoxides could be coupled with aryl iodides, generating corresponding sulfoxides with excellent stereochemical integrity. Furthermore, the scalability of this transformation was demonstrated. Initial mechanistic studies revealed that the reaction undergoes a radical pathway.

Operando FTIR-ATR with molecular dynamic simulations to understand the diffusion mechanism of waste tire-derived pyrolytic oil for asphalt self-healing

Recent research proves that pyrolytic oils from waste tires are effective in restoring the chemical and rheological properties of aged asphalt binders. Nonetheless, the role of oil-binder molecular interactions and bindeŕs aging degree on the diffusional behavior of the pyro-oils is still unclear. In this study, authors propose integrating operando Fourier Transformed Infrared Spectroscopy (FTIR) measurements with molecular dynamics (MD) simulations as a novel approach to unravel the diffusion mechanisms of pyro-oils in asphalt binders with self-healing purposes. The produced pyro-oils contains aliphatic and single-ring alkyl aromatic compounds as the most abundant species (ca. 80%). The operando FTIR measurements were correlated by a Fickian model, resulting in diffusion coefficients (D0) between 10-12 and 10-11 m2s−1. Moreover, MD simulations, with a molecular model of aged asphalt containing benzylic rings, sulfoxides, and hydroxyl functional groups, demonstrated that interactions of functional groups in the pyro-oil with the binder, hinder the diffusion behavior of the pyro-oil. The D0 estimated from the MD simulations agreed with those calculated from experimental data and previous reports for petro- and bio-derived rejuvenators. The predictive performance of the MD simulations developed in this study confirms to design of more resilient self-healing asphalt binders using a bottom-up strategy.

A combined theoretical and crystallographic investigation of racemic and enantiopure aryl benzyl sulfoxides

A combined theoretical and crystallographic investigation of racemic and enantiopure aryl benzyl sulfoxides

Sulfenate Anion Catalyzed Diastereoselective Synthesis of Aziridines.

Aziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis of trans-aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO- ) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron-rich and electron-poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans : cis >20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring-opening reactions, with a cyclobutyl-substituted norephedrine derivative obtained through a four-step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the high trans-diastereoselectivity.

Sulfenate Anion Catalyzed Diastereoselective Synthesis of Aziridines

AbstractAziridines are highly valued synthetic targets in organic and medicinal chemistry. The organocatalytic synthesis of such structures with broad substrate scope and good diastereoselectivity, however, is rare. Herein, we report a broadly applicable and diastereoselective synthetic method for the synthesis of trans‐aziridines from imines and benzylic or alkyl halides utilizing sulfenate anions (PhSO–) as the catalyst. Substrates bearing heterocyclic aromatic groups, alkyl, and electron‐rich and electron‐poor aryl groups were shown to be compatible with this method (33 examples), giving good yields and high diastereoselectivities (trans : cis >20 : 1). Further functionalization of aziridines containing cyclopropyl or cyclobutyl groups was achieved through ring‐opening reactions, with a cyclobutyl‐substituted norephedrine derivative obtained through a four‐step synthesis. We offer a mechanistic proposal involving reversible addition of the deprotonated benzyl sulfoxide to the imine to explain the high trans‐diastereoselectivity.

The generation and reactions of sulfenate anions. An update

Sulfenate anions (RSO-) represent the conjugate base of sulfenic acids (RSOH) and are known predominately for their S-nucleophilicity. In the early stages of sulfenate research this often meant the formation of a benzyl or methyl sulfoxide, often to confirm the intermediacy of a sulfenate. Many recent contributions have demonstrated the diversity of functionalization of sulfenates, and those new investigations form the basis of this review. This synopsis begins by describing the predominant methods to generate sulfenates and aspects of their structure. The sections addressing sulfenate reaction chemistry focus on stereoselective S-functionalization chemistry, transition metal catalyzed S–C bond formation (cross-coupling) and bond cleavage, and the discovery of particularly novel reactions and applications. This latter area includes a description of the organocatalytic roles played by sulfenates and some new metal-free sulfenate coupling chemistry. The literature is covered to early 2022.

Localized Partitioning of Enantiomers in Solid Samples of Sulfoxides: Importance of Sampling Method in Determination of Enantiopurity.

Localized partitioning of amorphous enantioenriched aryl benzyl sulfoxides in the solid state can lead to substantial variation in enantiopurities, even for sulfoxides which do not show detectable levels of self-disproportionation of enantiomers (SDE) during chromatography on an achiral stationary phase. The importance of preparation of representative samples of enantioenriched sulfoxides for chiral HPLC to enable reproducible results is clear.

Nickel-Catalyzed Oxidative Coupling Reaction of Phenyl Benzyl Sulfoxides

A novel method to produce disulfoxides diastereoselectively from phenyl benzyl sulfoxides is reported. The Ni(PnBu3)2Cl2]/NIXANTPHOS catalyst system successfully promotes an oxidative coupling reaction of aryl benzylic sulfoxides to disulfoxides. An intermediate aldehyde, produced from the elimination of α-hydroxy sulfoxides, is proposed to generate the key sulfenate anion, enabling the formation of the disulfoxide product. A range of disulfoxides was produced in moderate to high yields (30–83%) and diastereoselectivity (rac/meso ranging from 3:1 to >20:1).

Design, Synthesis and Preliminary Biological Evaluation of Novel Benzyl Sulfoxide 2-Indolinone Derivatives as Anticancer Agents.

In this work, a series of novel benzyl sulfoxide 2-indolinone derivatives was designed and synthesized as potent anticancer agents. Tyrosine kinase inhibitory activity assay indicated that most of the compounds showed significant activity. The in vitro antiproliferative activity of these compounds was further investigated against five human cancer cell lines (HeLa, HepG2, MCF-7, SCC-15, and A549). Several compounds exhibited evident activities. Among them, (Z)-3-(((4-bromobenzyl)sulfinyl)methylene)indolin-2-one (6j) and (Z)-3-((benzylsulfinyl)methylene)-5-bromoindolin-2-one (6o) were found to be effective tyrosine kinase inhibitors (IC50 = 1.34 and 2.69 μM, respectively) in addition to having noteworthy antitumor potential (the average IC50 value of 6j or 6o was less than 40 μM). This class of novel derivatives has promising potential for further development as anticancer agents.

Palladium-Catalyzed Enantioselective Arylation of Aryl Sulfenate Anions: A Combined Experimental and Computational Study.

A novel approach to produce chiral diaryl sulfoxides from aryl benzyl sulfoxides and aryl bromides via an enantioselective arylation of aryl sulfenate anions is reported. A (JosiPhos)Pd-based catalyst successfully promotes the asymmetric arylation reaction with good functional group compatibility. A wide range of enantioenriched diaryl, aryl heteroaryl, and even diheteroaryl sulfoxides were generated. Many of the sulfoxides prepared herein would be difficult to prepare via classic enantioselective oxidation of sulfides, including Ph(Ph-d5)SO (90% ee, 95% yield). A DFT-based computational study suggested that chiral induction originates from two primary factors: (i) both a kinetic and a thermodynamic preference for oxidative addition that places the bromide trans to the JosiPhos-diarylphosphine moiety and (ii) Curtin-Hammett-type control over the interconversion between O- and S-bound isomers of palladium sulfenate species following rapid interconversion between re- and si-bound transmetalation products, re/si-Pd-OSPh (re/si-PdO-trans).

ChemInform Abstract: Versatile C(sp2)—C(sp3) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes.

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross-couplings, and circumvents common issues associated with proto-demetalation and β-hydride elimination.

Versatile C(sp(2) )-C(sp(3) ) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes.

The reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron-deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross-couplings, and circumvents common issues associated with proto-demetalation and β-hydride elimination.

Versatile C(sp2)−C(sp3) Ligand Couplings of Sulfoxides for the Enantioselective Synthesis of Diarylalkanes

AbstractThe reaction of chiral (hetero)aryl benzyl sulfoxides with Grignard reagents affords enantiomerically pure diarylalkanes in up to 98 % yield and greater than 99.5 % enantiomeric excess. This ligand coupling reaction is tolerant to multiple substitution patterns and provides access to diverse areas of chemical space in three operationally simple steps from commercially available reagents. This strategy provides orthogonal access to electron‐deficient heteroaromatic compounds, which are traditionally synthesized by transition metal catalyzed cross‐couplings, and circumvents common issues associated with proto‐demetalation and β‐hydride elimination.

Circular Dichroism and TDDFT Investigation of Chiral Fluorinated Aryl Benzyl Sulfoxides

AbstractA series of ten chiral aryl benzyl sulfoxides with perfluorinated aryl or benzyl rings, obtained by enantioselective oxidation of sulfides, has been investigated by means of electronic circular dichroism (ECD) spectroscopy and time‐dependent DFT (TDDFT) calculations. The (per)fluorination of the aromatic rings has a large impact on the conformer population, the molecular orbitals shape, and the character of electronic transitions. In this series, the transition responsible for the “sulfoxide primary” CD band has a large charge transfer (CT) character, as demonstrated by the CT metric index ΓNTO. As a consequence, global DFT hybrids such as B3LYP are largely inaccurate in the prediction of excited states; nevertheless, a correct simulation of CD spectra may be achieved by using range‐separated functionals such as CAM‐B3LYP. The use of the empirical Mislow's rule for assigning the absolute configuration is strongly discouraged for this class of compounds.

ChemInform Abstract: Palladium Catalyzed Diaryl Sulfoxide Generation from Aryl Benzyl Sulfoxides and Aryl Chlorides.

Diaryl sulfoxides are synthesized from aryl benzyl sulfoxides and aryl chlorides via three sequential catalytic cycles all promoted by a NiXantPhos-based palladium catalyst. The key step is S-arylation of a sulfenate anion. An air- and moisture-stable precatalyst derived from NiXantPhos efficiently facilitates the transformation. Various functional groups, including those with acidic protons, were tolerated. This method can also be extended to methyl and dibenzyl sulfoxides substrates.

Palladium catalyzed diaryl sulfoxide generation from aryl benzyl sulfoxides and aryl chlorides.

Diaryl sulfoxides are synthesized from aryl benzyl sulfoxides and aryl chlorides via three sequential catalytic cycles all promoted by a NiXantPhos-based palladium catalyst. The key step is S-arylation of a sulfenate anion. An air- and moisture-stable precatalyst derived from NiXantPhos efficiently facilitates the transformation. Various functional groups, including those with acidic protons, were tolerated. This method can also be extended to methyl and dibenzyl sulfoxides substrates.

Photosensitized oxidation of aryl benzyl sulfoxides. Evidence for nucleophilic assistance to the C-s bond cleavage of aryl benzyl sulfoxide radical cations.

The radical cations of a series of aryl benzyl sulfoxides (4-X-C6H4CH2SOC6H4Y(+•)) have been generated by photochemical oxidation of the parent sulfoxides sensitized by 3-cyano-N-methylquinolinium perchlorate (3-CN-NMQ(+)ClO4(-)). Steady-state photolysis experiments showed the prevailing formation of benzylic products deriving from the C-S fragmentation in the radical cations, together with sulfur-containing products. Formation of sulfoxide radical cations was unequivocally established by laser flash photolysis experiments showing the absorption bands of 3-CN-NMQ(•) (λmax = 390 nm) and of the radical cations (λmax = 500-620 nm). The decay rate constants of radical cations, determined by LFP experiments, decrease by increasing the electron-donating power of the arylsulfinyl Y substituent and to a smaller extent by increasing the electron-withdrawing power of the benzylic X substituent. A solvent nucleophilic assistance to the C-S bond cleavage has been suggested, supported by the comparison of substituent effects on the same process occurring in aryl tert-butyl sulfoxide radical cations. DFT calculations, performed to determine the bond dissociation free energy in the radical cations, the transition state energies associated with the unimolecular C-S bond cleavage, and the charge and spin delocalized on their structures, were also useful to endorse the nucleophilic assistance to the C-S scission.

Structural Motifs in Enantiopure Halogenated Aryl Benzyl Sulfoxides: Effect of Fluorine Substitution

A series of enantiopure crystalline aryl benzyl sulfoxides, bearing different substituents on both the aryl groups, were synthesized by an enantioselective oxidation of the corresponding sulfides. Structural investigations, achieved by means of single-crystal X-ray diffraction, allowed us to recognize the main assembling interactions. The same procedure was repeated for some corresponding fluorinated aryl benzyl sulfoxides. The synthesis of the enantiomers of a new fluorinated compound, which shows unusual structural patterns, prompted us to compare the structural motifs of the two families of sulfoxides (fluorinated and unfluorinated) and to investigate the changes due to the fluorine substitution. Some short contacts involving the fluorine atom were discussed in more details, taking into account the recent interest in these sometimes controversial interactions.

ChemInform Abstract: Diaryl Sulfoxides from Aryl Benzyl Sulfoxides: A Single Palladium‐Catalyzed Triple Relay Process.

AbstractA wide range of aryl benzyl sulfoxides as well as alkyl benzyl sulfoxides react with various (hetero)aryl bromides in good to excellent yields.