The 50 most-cited articles in The Journal of Organic Chemistry, 2020

The author describes perspectives gained over many years of engagement in the field of organic electrochemistry. The manuscript will hopefully dispel a number of misconceptions and provide a framework for thinking about how electrochemistry can be uniquely applied to solving problems in synthesis and to obtaining mechanistic insights.

With a renewed and growing interest in therapeutic oligonucleotides across the pharmaceutical industry, pressure is increasing on drug developers to take more seriously the sustainability ramifications of this modality. With 12 oligonucleotide drugs reaching the market to date and hundreds more in clinical trials and preclinical development, the current state of the art in oligonucleotide production poses a waste and cost burden to manufacturers. Legacy technologies make use of large volumes of hazardous reagents and solvents, as well as energy-intensive processes in synthesis, purification, and isolation. In 2016, the American Chemical Society (ACS) Green Chemistry Institute Pharmaceutical Roundtable (GCIPR) identified the development of greener processes for oligonucleotide Active Pharmaceutical Ingredients (APIs) as a critical unmet need. As a result, the Roundtable formed a focus team with the remit of identifying green chemistry and engineering improvements that would make oligonucleotide production more sustainable. In this Perspective, we summarize the present challenges in…

In 1864, Hugo Schiff, aged 30, discovered the reaction of aromatic aldehydes with primary amines to give imine derivatives. A C═N imine bond presents the unique properties of being strong, as expected for a covalent double bond, and of being reversible due to a fast hydrolytic process. In view of such features, Schiff base condensations are thermodynamically controlled, which, in the case of reactions involving multifunctional aldehydes and primary amines, allow the formation of complex and sophisticated structures through a trial-and-error mechanism. Back hydrolysis can be prevented by hydrogenating C═N bonds under mild conditions. In such a way, stable rings and cages of varying sizes can be synthesized. Moreover, transition and post-transition metal ions, establishing coordinative interactions with imine nitrogen atoms, can address Schiff base condensations of even more complex molecular systems, whose structure is controlled by the geometrical preferences of the metal. Metal template Schiff base condensations have produced multinuclear metal complexes exhibiting the shape of…

Syringic acid (SA) is a natural phenolic acid found in vegetables, fruits, and other plant-based foods. A range of biological activities were proposed for this compound including anticancer, antimicrobial, anti-inflammation, and anti-diabetic activities, as well as antioxidant and antinitrosant properties. In this study, the focus is on the latter two. The HO •, HOO •, NO, and NO 2 scavenging activities of SA were evaluated in physiological environments by kinetic and thermodynamic calculations. The computed rate constants of the HO • radical scavenging of SA were 4.63 × 10 9 and 9.77 × 10 7 M –1 s –1 in polar and nonpolar solvents, respectively. A comparison with the experimentally determined rate constant in aqueous solution yields a k calculated / k experimental ratio of 0.3, thus the computed kinetic data are reasonably accurate. SA exhibited excellent HOO • and NO 2 scavenging activity in water ( k overall (HOO • ) = 1.53 × 10 8 M –1 s –1 and k overall (NO 2 ) = 1.98 × 10 8 M –1 s –1 ), whereas it did not show NO scavenging activity in any of the studied environments. In lipid…

It is often said that "time is money". This is certainly true in a multistep synthesis when a high-valued product or set of products is needed urgently. Fulfilling this need requires the sensible balancing of atom economy, step economy, and redox economy with the time taken to make the product. In this age of flu-based pandemics, the need for rapid provision of effective therapeutic agents makes the importance of "time economy" particularly clear. In this Perspective, the importance of time economy in total synthesis is described, as well as the general considerations underlining the timely production of desired molecules. As case studies, the syntheses of Tamiflu, Corey lactone, and ibuprofen are discussed, with emphasis on comparing classical and contemporary approaches to a rapid total synthesis. By using modern tactics such as one-pot reaction procedures and versatile synthetic methodologies such as organocatalyst mediated domino reactions coupled with strict-control technologies such as flow chemistry, Tamiflu and Corey lactone can now be synthesized within 60 and 152 min,…

Understanding the degradation mechanisms of organic cations under basic conditions is extremely important for the development of durable alkaline energy conversion devices. Cations are key functional groups in alkaline anion exchange membranes (AAEMs), and AAEMs are critical components to conduct hydroxide anions in alkaline fuel cells. Previously, we have established a standard protocol to evaluate cation alkaline stability within KOH/CD 3 OH solution at 80 °C. Herein, we are using the protocol to compare 26 model compounds, including benzylammonium, tetraalkylammonium, spirocyclicammonium, imidazolium, benzimidazolium, triazolium, pyridinium, guanidinium, and phosphonium cations. The goal is not only to evaluate their degradation rate, but also to identify their degradation pathways and lead to the advancement of cations with improved alkaline stabilities.

The high demand for new and efficient routes toward synthesis of nitrogen-containing heterocyclic scaffolds has inspired organic chemists to discover several methodologies over recent years. This Perspective highlights one standout approach, which involves the use of pyridotriazoles and related compounds in denitrogenative transformations. Readily available pyridotriazoles undergo ring-chain isomerization to produce uniquely reactive α-diazoimines. Such reactivity, enabled by metal catalysts, additives, or visible-light irradiation, can be applied in transannulation, insertion, cyclopropanation, and many other transformations.

The reaction of LH [L = {(ArNH)(ArN)–C=N–C=(NAr)(NHAr)}; Ar =2,6-Et 2 -C 6 H 3 ] with a commercially available alane amine adduct (H 3 Al·NMe 2 Et) in toluene resulted in the formation of a conjugated bis-guanidinate (CBG)-supported aluminum dihydride complex, i.e., LAlH 2 ( 1 ), in good yield. The new complex has been thoroughly characterized by multinuclear magnetic resonance, IR, mass, and elemental analyses, including single-crystal structural studies. Further, we have demonstrated the aluminum-catalyzed hydroboration of a variety of nitriles and alkynes. Moreover, aluminum-catalyzed hydroboration is expanded to more challenging substrates such as alkene, pyridine, imine, carbodiimide, and isocyanides. More importantly, we have shown that the aluminum dihydride catalyzed both intra- and intermolecular chemoselective hydroboration of nitriles and alkynes over other reducible functionalities for the first time.

Dehydrogenative coupling-based reactions have emerged as an efficient route toward the synthesis of a plethora of heterocyclic rings. Herein, we report an efficacious, nickel-catalyzed synthesis of two important heterocycles such as quinoline and quinoxaline. The catalyst is molecularly defined, is phosphine-free, and can operate at a mild reaction temperature of 80 °C. Both the heterocycles can be easily assembled via double dehydrogenative coupling, starting from 2-aminobenzyl alcohol/1-phenylethanol and diamine/diol, respectively, in a shorter span of reaction time. This environmentally benign synthetic protocol employing an inexpensive catalyst can rival many other transition-metal systems that have been developed for the fabrication of two putative heterocycles. Mechanistically, the dehydrogenation of secondary alcohol follows clean pseudo-first-order kinetics and exhibits a sizable kinetic isotope effect. Intriguingly, this catalyst provides an example of storing the trapped hydrogen in the ligand backbone, avoiding metal-hydride formation. Easy regeneration of the oxidized…

Heptamethine cyanines (Cy7) are fluorophores essential for modern bioimaging techniques and chemistry. Here, we systematically evaluated the photochemical and photophysical properties of a library of Cy7 derivatives containing diverse substituents in different positions of the heptamethine chain. A single substitution allows modulation of their absorption maxima in the range of 693-805 nm and photophysical properties, such as quantum yields of singlet-oxygen formation, decomposition, and fluorescence or affinity to singlet oxygen, within 2-3 orders of magnitude. The same substituent in different positions of the chain often exhibits distinctly contradictory effects, demonstrating that both the type and position of the substituent are pivotal for the design of Cy7-based applications. The combination of experimental results with quantum-chemical calculations provides insights into the structure-property relationship, the elucidation of which will accelerate the development of cyanines with properties tailored for specific applications, such as fluorescent probes and sensors,…

π-Conjugated molecules with small highest occupied molecular orbital (HOMO)–lowest unoccupied molecular orbital (LUMO) energy gaps (Δ E H–L ) have been extensively studied because of their unique optoelectronic properties. Although the expansion of π-conjugation is one of the well-known approaches for designing molecules with small Δ E H–L values, such an approach inevitably gives large π-conjugated molecules sometimes suffering from synthetic difficulty and low solubility toward organic solvents. To develop relatively small donor–acceptor molecules with small Δ E H–L values, we have designed and synthesized π-conjugated zwitterions composed of electron-donating anions, such as phenoxide and anthroxide, and electron-accepting cations, such as pyridinium and acridinium. The energy difference between the HOMO of the anion and the LUMO of the cation (Δ E D–A ) and the interplanar angle between them (φ DA ) have a crucial effect on Δ E H–L, and hence, on the electronic structures and optoelectronic properties of these zwitterions. The zwitterions with small Δ E D–A and large φ DA have a…

A K 2 S 2 O 8 -mediated three-component protocol has been developed for the construction of 3-trifluoroalkylated quinoxalin-2(1 H )-ones under metal-free conditions. The present reaction could be accomplished through the trifluoroalkylation of quinoxalin-2(1 H )-ones with unactivated alkenes and Langlois’ reagent (CF 3 SO 2 Na), which provided a highly attractive approach to access a series of biologically important 3-trifluoroalkylated quinoxalin-2(1 H )-ones.

Appending conformationally restraining ring systems to the cyanine chromophore creates exceptionally bright fluorophores in the visible range. Here, we report the application of this strategy in the near-infrared range through the preparation of the first restrained heptamethine indocyanine. Time-resolved absorption spectroscopy and fluorescence correlation spectroscopy verify that, unlike the corresponding parent unrestrained variant, the restrained molecule is not subject to photoisomerization. Notably, however, the room-temperature emission efficiency and the fluorescence lifetime of the restrained cyanine are not extended relative to the parent cyanine, even in viscous solvents. Thus, in contrast to prior reports, the photoisomerization of heptamethine cyanines does not contribute significantly to the excited-state chemistry of these molecules. We also find that the fluorescence lifetime of the restrained heptamethine cyanine is temperature-insensitive and significantly extended at moderately elevated temperatures relative to the parent cyanine. Finally, computational studies…

Indole and indoline rings are important pharmacophoric scaffolds found in marketed drugs, agrochemicals, and biologically active molecules. The [2 + 2] cycloaddition reaction is a versatile strategy for constructing architecturally interesting, sp 3 -rich cyclobutane-fused scaffolds with potential applications in drug discovery programs. A general platform for visible-light mediated intermolecular [2 + 2] cycloaddition of indoles with alkenes has been realized. A substrate-based screening approach led to the discovery of tert -butyloxycarbonyl (Boc)-protected indole-2-carboxyesters as suitable motifs for the intermolecular [2 + 2] cycloaddition reaction. Significantly, the reaction proceeds in good yield with a wide variety of both activated and unactivated alkenes, including those containing free amines and alcohols, and the transformation exhibits excellent regio- and diastereoselectivity. Moreover, the scope of the indole substrate is very broad, extending to previously unexplored azaindole heterocycles that collectively afford fused cyclobutane containing scaffolds that offer…

This study reveals a transition-metal- and external oxidant-free electrochemical method for the C3–H sulfonylation of biologically diverse 2 H -indazoles at room temperature and under ambient air. Using various sulfonyl hydrazides as the sulfonyl precursor, a series of sulfonylated indazole derivatives containing a broad spectrum of functional groups were synthesized in up to 92% yield. Mechanistic studies suggest a precedented radical pathway is operating in the electrochemical process.

The coupling of transition-metal to photoredox catalytic cycles through single-electron transfer steps has become a powerful tool in the development of catalytic processes. In this work, we demonstrated that transition-metal catalysis can be coupled to alternating current (AC) through electron transfer steps that occur periodically at the same electrode. AC-assisted Ni-catalyzed amination, etherification, and esterification of aromatic bromides showed higher yields and selectivity compared to that observed in the control experiments with direct current. Our mechanistic studies suggested the importance of both reduction and oxidation processes in the maintenance of the AC-assisted catalytic reactions. As described in presented examples, the AC assistance should be well-suited for catalytic cycles involving reductive elimination or oxidative addition as a limiting step.

While organic synthesis carried out in most laboratories uses batch methods, there is growing interest in modernizing fine chemical synthesis through continuous-flow processes. As a synthetic method, flow processes have several advantages over batch systems in terms of environmental compatibility, efficiency, and safety, and recent advances have allowed for the synthesis of several complex molecules, including active pharmaceutical ingredients (APIs). Nevertheless, due to several reasons related to the difficulties arising from byproduct formation during the flow process, such as lower yields, poor selectivities, clogging of columns due to poor solubility, catalyst poisoning, etc., successful examples of continuous-flow synthesis of complex organic molecules are still limited. In order to solve this bottleneck, the development of selective and atom-economical continuous-flow organic transformations are needed. This perspective highlights examples of atom-economical addition and condensation reactions with heterogeneous catalysts under continuous-flow conditions and their…

Direct synthesis of N-heterocycles via the acceptorless dehydrogenative coupling is very challenging and scarcely reported under 3d transition-metal catalysis. Here, we have developed an efficient Mn(I)-catalyzed sustainable synthesis of various quinoxalines from 1,2-diaminobenzenes and 1,2-diols via the acceptorless dehydrogenative coupling reaction. Further, this strategy was successfully applied for the unprecedented synthesis of quinazolines by the reaction of 2-aminobenzyl alcohol with primary amides. The present protocol provides an atom-economical and sustainable route for the synthesis of various quinoxaline and quinazoline derivatives by employing an earth-abundant manganese salt and simple phosphine-free NNN-tridentate ligand.

In the last few decades, photocatalytic radical carbonylation strategies have received considerable attention as they are becoming a formidable tool in the toolbox of organic synthesis. These carbonylation strategies involve the incorporation of a carbon monoxide into organic molecules in an atom- and step-economical manner. Mostly, these strategies rely on the generation of an acyl radical as a key intermediate, which would be created via incorporation of CO molecule to an alkyl/aryl radical. The production of alkyl/aryl radical in these methodologies required either the high-intensity light-induced transition-metal (TM)-catalyzed systems or visible-light-induced photocatalytic systems that would be capable of mediating single electron transfer (SET) to the C(sp 3 )- or C(sp 2 )-hybridized coupling partners. Here, in this review, the development in the field of photocatalytic carbonylation is described by compiling the literature of the last 40 years, and their reaction mechanisms have been emphatically discussed. In addition, to aid readers, we have assimilated redox potentials of…

GIAO 13 C NMR calculation plays important roles in structural assignment for small organic molecules. Especially, higher accuracy and confidence are required for the structural assignation of complex organic molecules. In this GIAO 13 C NMR calculation strategy, carbons were sorted according to their type of hybridization, radii of solvation cavity, or solvent interactions. The calculated shielding tensors of carbons in each sorted training set were linear-regressed with experimental data separately, and the obtained linear parameters were used to convert calculated shielding tensors into calculated chemical shifts. This approach shows significantly improved accuracy, especially for sp 2 carbons, compared to conventional GIAO 13 C NMR calculation protocols. A statistic-based probability algorithm was proposed to quantify the reliability of structural assignation. With empirical linear parameters for three commonly used NMR solvents as well as an easy-to-use script and a spreadsheet, this 13 C NMR calculation protocol provides a useful tool for structural validation or assignation of…

A series of asymmetric donor–acceptor (D–A) perylene-based compounds, 3-( N, N -bis(4′-(R)-phenyl)amino)perylene ( Peri – DPA ( R )), were successfully prepared to explore their intramolecular charge transfer (ICT) properties. To induce ICT between the donor and acceptor, diphenylamine (DPA) derivatives (electron donor units) with the same functional groups ( R = CN, F, H, Me, or OMe) at both para positions were linked to the C-3 position of perylene to produce five Peri – DPA derivatives. A steady-state spectroscopy study on Peri – DPA ( R )s exhibited a progressively regulated ICT trend consistent with the substituent effect as it progressed from the electron-withdrawing group to the electron-donating group. In particular, a comparative study using a D–A–D (donor–acceptor–donor) system demonstrated that not only the electron push–pull substituent effect but also subunit combinations influence photophysical and electrochemical properties. The different ICT characters observed in Lippert–Mataga plots of D – A ( CN ) and D – A – D ( CN ) (CN-substituted D – A and D – A – D ) led to…

Photoinduced decarboxylative radical reactions of benzoic acids with electron-deficient alkenes, diborane, and acetonitrile under organic photoredox catalysis conditions and mild heating afforded adducts, arylboronate esters, and the reduction product, respectively. The reaction is thought to involve single-electron transfer promoted the generation of aryl radicals via decarboxylation. A diverse range of benzoic acids were found to be suitable substrates for this photoreaction. Only our two-molecule organic photoredox system can work well for the direct photoinduced decarboxylation of benzoic acids.

A highly sustainable catalytic protocol for the coupling of alcohols and amines for selective monoalkylated amines using Ni(II)–N Λ N Λ O pincer type complexes through the borrowing hydrogen methodology is described. An array of Ni(II) catalysts ( 1–3 ) was synthesized and characterized by various spectral and analytical methods. Furthermore, the distorted square planar geometry of the complexes ( 1 and 2 ) was substantiated with single crystal X-ray diffraction study. The inexpensive nickel-based catalytic methodology displays a broad substrate scope for the N-alkylation of aromatic and heteroaromatic amines using a diverse range of primary alcohols with excellent yields up to 97%. The present approach is environmentally benign, which liberates water as the sole byproduct. A short synthesis of drug intermediates such as mepyramine and chloropyramine illustrates the utility of the present protocol.

Helicenes, chiral members of the family of polyaromatic hydrocarbons, have been increasingly used in a variety of applications in recent years. Despite their intriguing properties, wider utilization is hindered by difficult functionalization of its skeleton, which would provide access to finely tuned derivatives of desired properties. Herein, the recent advancements in the field of helicene functionalization are discussed with an emphasis on different types of transformations, their versatility, and regioselectivity.

/1,10-phenanthroline system-catalyzed synthesis of a series of quinoxalines from both 2-nitroanilines and 1,2-diamines is demonstrated. The reusability test for this system was performed up to the seventh cycle, which afforded good yields of the desired product without losing its reactivity significantly. Notably, during the catalytic reaction, the formation of the heterogeneous Ni-particle was observed, which was characterized by PXRD, XPS, and TEM techniques.

We developed a green method for the synthesis of spiro[4.5]trienones through an electrochemical oxidative halocyclization with N -aryl alkynamides. This reaction was conducted under metal-catalyst- and exogenous-oxidant-free conditions at room temperature. Using readily available LiCl, LiBr, and LiI as the halogen source, a variety of dearomative halo-spirocyclization products were obtained in good to excellent yields with a broad scope and functional group tolerance.

We report the synthesis of C6-substituted isoquinolino[1,2- b ]quinazolinones via rhodium(III)-catalyzed C–H annulation with sulfoxonium ylides and evaluation of the cytotoxic activity of the scaffold. This C–H activation approach enables the most straightforward and convergent synthesis of C6-substituted isoquinolino[1,2- b ]quinazolines reported to date. This operationally simple method is compatible with a wide variety of the sulfoxonium ylide and arene C–H activation coupling partners, permitting access to diverse isoquinolino[1,2- b ]quinazolines. This method shows a high atom economy, generating H 2 O and dimethyl sulfoxide (DMSO) as by-products. This method is scalable and operates with exquisite N-lactam cyclization selectivity, thus enabling expedient access to new heterocyclic analogues featuring promising cytotoxic properties.

Abstract This Perspective goes into the fine details of our laboratory’s quest to answer a longstanding fundamental question: Could any new approach to terpene synthesis, perhaps one patterned on biosynthesis, enable a divergent synthetic approach to the taxane family of natural products? We targeted Taxol, the flagship taxane, as the upper limit of chemical complexity and employed two-phase terpene synthesis logic as the guiding strategy. The first synthesis target was taxadiene, the lowest oxidized member of the taxane family, followed by three site-selective allylic oxidations at C5, C10, and C13, which led to the two-phase synthesis of taxuyunnanine D. Successful C9 oxidation enabled access to a wider range of taxanes, which was demonstrated by the two-phase synthesis of decinnamoyltaxinine E and taxabaccatin III. The final two sp3 C–H oxidations at C1 and C7 were attained by dioxirane-mediated C–H oxidation and an oxidation relay based on judicious substrate design, culminating in a two-phase synthesis of Taxol. The purpose of this Perspective is to articulate strategies and…

High Resolution Image Download MS PowerPoint Slide Quantum mechanical/nuclear magnetic resonance (NMR) approaches are widely used for the configuration assignment of organic compounds generally comparing one cluster of experimentally determined data (e.g., 13 C NMR chemical shifts) with those predicted for all possible theoretical stereoisomers. More than one set of experimental data, each related to a specific stereoisomer, may occur in some cases, and the accurate stereoassignments can be obtained by combining the experimental and computed data. We introduce here a straightforward methodology based on the simultaneous analysis, combination, and comparison of all sets of experimental/calculated 13 C chemical shifts for aiding the correct configuration assignment of groups of stereoisomers. The comparison of the differences between the calculated/experimental chemical shifts instead of the shifts themselves led to the advantage of avoiding errors arising from calibration procedures, reducing systematic errors, and highlighting the most diagnostic differences between calculated and…

An anionic iridium complex [Cp*Ir(2,2'-bpyO)(OH)][Na] was found to be a general and highly efficient catalyst for transfer hydrogenation of ketones and imines with methanol under base-free conditions. Readily reducible or labile substituents, such as nitro, cyano, and ester groups, were tolerated under present reaction conditions. Notably, this study exhibits the unique potential of anionic metal-ligand bifunctional iridium catalysts for transfer hydrogenation with methanol as a hydrogen source.

We report a visible light-mediated flow process for C-N cross-coupling of (hetero)aryl halides with a variety of amine coupling partners through the use of a photoredox/nickel dual catalyst system. Compared to the method in batch, this flow process enables a broader substrate scope, including less-activated (hetero)aryl bromides and electron-deficient (hetero)aryl chlorides, and significantly reduced reaction times (10 to 100 min). Furthermore, scale up of the reaction, demonstrated through the synthesis of tetracaine, is easily achieved, delivering the C-N cross-coupled products in consistently high yield of 84% on up to a 10 mmol scale.

By combining “ N -chlorosuccinimide (NCS)” as the safe chlorine source with “Acr + -Mes” as the photocatalyst, we successfully achieved benzylic C–H bond chlorination under visible light irradiation. Furthermore, benzylic chlorides could be converted to benzylic ethers smoothly in a one-pot manner by adding sodium methoxide. This mild and scalable chlorination method worked effectively for diverse toluene derivatives, especially for electron-deficient substrates. Careful mechanistic studies supported that NCS provided a hydrogen abstractor “ N -centered succinimidyl radical,” which was responsible for the cleavage of the benzylic C–H bond, relying on the reducing ability of Acr • -Mes.

Metal-catalyzed addition of P–H bonds to alkenes, alkynes, and other unsaturated substrates in hydrophosphination and related reactions is an atom-economical approach to valuable organophosphorus compounds. Understanding the mechanisms of these processes may enable synthetic improvements and development of new reactions. The first step in several catalytic cycles is P–H oxidative addition to yield intermediate metal hydride complexes bearing M–P bonds. P–C bond formation may occur via substrate insertion into the M–H bond, followed by P–C reductive elimination, or by insertion into the M–P bond and C–H reductive elimination. In an alternative outer-sphere process, nucleophilic attack of a metal–phosphido (M–PR 2 ) group on an unsaturated substrate and proton transfer involving the metal hydride yields the product. This Perspective reviews the mechanistic possibilities, with a focus on the P–H activation step, and recent progress in developing novel catalytic transformations involving P–C bond formation.

A room-temperature C-H bond functionalization of benzamides has been developed by merging a photocatalyst with a cobalt catalyst for the synthesis of isoindolone spirosuccinimides. The reaction proceeds in aerobic conditions and does not require any sacrificial external oxidants such as Ag(I) or Mn(III) salts. Visible light activates the photocatalyst, and it acts as an electron-transfer reagent and helps in the fundamental organometallic steps by modulating the oxidation state of the cobalt complex. This C-H bond functionalization and spirocyclization showed wide substrate scope and good functional group tolerance. A possible reaction mechanism was proposed from the experimental outcome, showing that C-H bond activation is irreversible and not the rate-determining step.

Organic compounds bearing radioisotopes of iodine are widely used for biological research, diagnostic imaging, and radiotherapy. Early reported synthetic methods for the incorporation of radioiodine have generally involved high temperature reactions or strongly oxidizing conditions. To overcome these limitations and to cope with the demand for novel radioiodinated probes, there has been a surge in the development of new synthetic methodology for radioiodination. This synopsis describes the key transformations developed recently.

A sustainable and transition metal-free approach for C3 chalcogenation and chalcogenocyanation of imidazopyridines with KXCN (X = S or Se) has been developed under mild conditions. Importantly, this reaction was performed in the presence of catalytic iodine in aqueous medium, which afforded either chalcogenated or chalcogenocyanated imidazopyridines under temperature control. The current protocol featured a broad substrate scope, transition metal-free and organic solvent-free conditions, operational convenience, and gram-scale production.

A straightforward and selective reduction of nitroarenes with various alcohols was efficiently developed using an iron catalyst via a hydrogen transfer methodology. This protocol led specifically to imines in 30–91% yields, with a good functional group tolerance. Noticeably, starting from o -nitroaniline derivatives, in the presence of alcohols, benzimidazoles can be obtained in 64–72% yields when the reaction was performed with an additional oxidant, DDQ, and quinoxalines were prepared from 1,2-diols in 28–96% yields. This methodology, unprecedented at iron for imines, also provides a sustainable alternative for the preparation of quinoxalines and benzimidazoles.

An electrochemical method for the C(sp 2 )–H thioetherification of quinoxalin-2(1 H )-ones with primary, secondary, and tertiary thiols has been reported. Various quinoxalin-2(1 H )-ones underwent this thioetherification smoothly under metal- and chemical oxidant-free conditions, affording 3-alkylthiol-substituted quinoxalin-2(1 H )-ones in moderate to good yields.

Abstract A thorough investigation has enabled the optimization of the synthesis of 1,4-dihydro-pyrrolo[3,2-b]pyrroles. Although salts of such metals as vanadium, niobium, cerium, and manganese were found to facilitate the formation of 1,4-dihydro-pyrrolo[3,2-b]pyrroles from amines, aldehydes, and diacetyl, we confirmed that iron salts are the most efficient catalysts. The conditions identified (first step: toluene/AcOH = 1:1, 1 h, 50 °C; second step: toluene/AcOH = 1:1, Fe(ClO4)3·H2O, 16 h, 50 °C) resulted in the formation of tetraarylpyrrolo[3,2-b]pyrroles in a 6–69% yield. For the first time, very electron-rich substituents (4-Me2NC6H4, 3-(OH)C6H4, pyrrol-2-yl) originating from aldehydes and sterically hindered substituents (2-ClC6H4, 2-BrC6H4, 2-CNC6H4, 2-(CO2Me)C6H4, 2-(TMS-C≡C)C6H4) present on anilines can be appended to the pyrrolo[3,2-b]pyrrole core. It is now also possible to prepare 1,4-dihydropyrrolo[3,2-b]pyrroles bearing an ordered arrangement of N-substituents and C-substituents ranging from coumarin, quinoline, phthalimide to truxene. These advances in scope enable…

Although organic-based photocatalysts provide an inexpensive, environmentally friendly alternative, many are incapable of absorption within the visible wavelength range; this ultimately influences their effectiveness. Photocatalytic reactions usually proceed via single electron transfer (SET) or energy transfer (ET) processes from the photoexcited molecules to the various substrates. In our study, the carbohalogenation of olefins was accomplished by combining CBr 4 and 4-Ph-pyridine under irradiation. The atom transfer radical addition reaction of olefins was catalyzed by an in situ-formed photocatalyst via halogen bonding to afford a variety of products in moderate to good yields. Essential to the reaction is the formation of a CT complex with the haloalkene, which triggers charge separation processes and, ultimately, leads to the formation of the C-centered radical. While taking advantage of relatively inexpensive, readily available, and environmentally friendly reagents, the indirect activation of the substrate via the photoexcited catalyst paves the way for more efficient…

The N-methylation of amines with methanol in aqueous solution was proposed and accomplished by using a water-soluble metal–ligand bifunctional dinuclear iridium catalyst. In the presence of [(Cp*IrCl) 2 (thbpym)][Cl] 2 (1 mol %), a range of desirable products were obtained in high yields under environmentally benign conditions. Notably, this research exhibited the potential of transition metal-catalyzed activation of methanol as a C1 source for the construction of the C–N bond in aqueous solution.

Organic dyes that absorb and emit in the near-infrared (NIR) region are potentially noninvasive, high-resolution, and rapid biological imaging materials. Indolizine donor-based cyanine and squaraine dyes with water-solubilizing sulfonate groups were targeted in this study due to strong absorptions and emissions in the NIR region. As previously observed for nonwater-soluble derivatives, the indolizine group with water-solubilizing groups retains a substantial shift toward longer wavelengths for both absorption and emission with squaraines and cyanines relative to classically researched indoline donor analogues. Very high quantum yields (as much as 58%) have been observed with absorption and emission >700 nm in fetal bovine serum. Photostability studies, cell culture cytotoxicity, and cell uptake specificity profiles were all studied for these dyes, demonstrating exceptional biological imaging suitability.

Three new dimeric bis-guanidinate zinc(II) alkyl, halide, and hydride complexes [LZnEt] 2 ( 1 ), [LZnI] 2 ( 2 ) and [LZnH] 2 ( 3 ) were prepared. Compound 3 was successfully employed for the hydrosilylation and hydroboration of a vast number of ketones. The catalytic performance of 3 in the hydroboration of acetophenone exhibits a turnover frequency, reaching up to 5800 h –1, outperforming that of reported zinc hydride catalysts. Notably, both intra- and intermolecular chemoselective hydrosilylation and hydroboration reactions have been investigated.

The iron-catalyzed hydrogen transfer strategy has been applied to the redox condensation of o -hydroxynitrobenzene with alcohol, leading to the formation of benzoxazole derivatives. A wide range of 2-substituted benzoxazoles were synthesized in good to excellent yields without the addition of an external redox agent. A series of control experiments provided a plausible mechanism. Furthermore, the reaction system was successfully extended to the synthesis of benzothiazoles and benzimidazoles.

Development of a visible light-induced and singlet oxygen-mediated green protocol has been accomplished for the first time for the photochemical transformation of 4-hydroxy-α-benzopyrones to a new series of biorelevant 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxamides and 2-hydroxy-3-oxo-2,3-dihydrobenzofuran-2-carboxylates using rose bengal as a triplet photosensitizer at ambient temperature. Metal-free one-pot synthesis, broader substrate scope, good-to-excellent yields, use of cost-effective and eco-friendly starting materials and photosensitizer, and energy efficiency are the salient features of this newly developed method.

This report describes the first example of palladium-catalyzed ortho -C–H glycosylation/ ipso -alkenylation of aryl iodides, and the easily accessible glycosyl chlorides are used as a glycosylation reagent. The reaction is compatible with the functional groups of the substrates, and a series of C-aryl glycosides have been synthesized in good to excellent yield and with excellent diastereoselectivity. It is found that a cheap 5-norbornene-2-carbonitrile as a transient mediator can effectively promote this reaction. In addition, ipso -arylation and cyanation were also realized by the strategy.

Density functional theory calculations have been performed to explore the substituent effect on benzene’s structure and aromaticity upon excitation to the first triplet excited state (T 1 ). Discussion is based on spin density analysis, HOMA (harmonic oscillator model of aromaticity), NICS (nucleus-independent chemical shift), ACID (anisotropy of the induced current density), and monohydrogenation free energies and shows that a large span of aromatic properties, from highly antiaromatic to strongly aromatic, could be achieved by varying the substituent. This opens up a possibility of controlling benzene’s physicochemical behavior in its excited state, while molecular motion, predicted for several derivatives, could be of interest for the development of photomechanical materials.

A ball-milling-enabled zinc-mediated Barbier-type allylation reaction is reported. Notably, running the reaction in this manner renders it effective irrespective of the initial morphology of the zinc metal. The process is operationally simple, does not require inert atmospheres or dry solvents, and is reported over a range of aldehyde and ketone substrates; a gram-scale process is demonstrated.

High Resolution Image Download MS PowerPoint Slide The number of research papers that report photocatalyst-free protocols is currently increasing. Among the different approaches proposed, the conversion of a strong C–X bond of a stable substrate into a photolabile reactive moiety has been recently proposed. In this Synopsis, we introduce the so-dubbed dyedauxiliary group strategy by focusing on arylazo sulfones that are bench stable and visible-light responsive derivatives of anilines that have been exploited as precursors of a wide range of intermediates, including carbon-centered radicals as well as aryl cations.

Although the best-known examples of synthetic polymers are derived from carbon-based monomers, there exists another large and growing family of macromolecules based on the chemistry of phosphorus. These are the poly(organophosphazenes): polymers with a backbone of alternating phosphorus and nitrogen atoms and with two organic side groups attached to each phosphorus. The methods of synthesis of these polymers allow access to property combinations not found in all-organic counterparts, and this provides pathways to new materials that are important in biomedical research, energy generation and storage, aerospace materials, and numerous other specialized applications.