The 50 most-cited articles in The Journal of Organic Chemistry, 2022

Electron donor-acceptor (EDA) complexes provide a means to initiate radical reactions under visible light irradiation using substrates that do not absorb visible light individually. Catalytic approaches to complex formation are vital for advancing this synthetic strategy as it decouples the complexation and photogeneration of radicals from substrate functionalization, a limitation inherent to stoichiometric approaches that restricts structural diversity. This Synopsis highlights recent developments in EDA complex photochemistry in which either the donor or acceptor are employed catalytically.

In this study, we developed a metal-free and highly chemoselective method for the reduction of aromatic nitro compounds. This reduction was performed using tetrahydroxydiboron [B 2 (OH) 4 ] as the reductant and 4,4′-bipyridine as the organocatalyst and could be completed within 5 min at room temperature. Under optimal conditions, nitroarenes with sensitive functional groups, such as vinyl, ethynyl, carbonyl, and halogen, were converted into the corresponding anilines with excellent selectivity while avoiding the undesirable reduction of the sensitive functional groups.

High Resolution Image Download MS PowerPoint Slide The use of water in organic synthesis draws attention to its green chemistry features and its unique ability to unveil unconventional reactivities. Herein, literature about the use of water as a reaction medium under visible-light photocatalytic conditions is summarized in order to highlight challenges and opportunities. Accordingly, this Synopsis has been divided into four different sections focused on (1) the unconventional role of water in photocatalytic reactions, (2) in -/ on- water reactions, (3) water-soluble photocatalysts, and (4) photomicellar catalytic systems.

Compared to metal–organic complexes and transition-metal halides, group I metal halides are attractive catalysts for the crucial cycloaddition reaction of CO 2 to epoxides as they are ubiquitously available and inexpensive, have a low molecular weight, and are not based on (potentially) endangered metals, especially for the case of sodium and potassium. Nevertheless, given their low intrinsic catalytic efficiency, they require the assistance of additional catalytic moieties. In this work, we show that by exploiting the high nucleophilicity of opportunely designed aminopyridines, catalytic systems based on alkaline metals can be formed, which allow the cycloaddition of CO 2 to epoxides to proceed under atmospheric pressure at moderate temperatures. Importantly, the aminopyridine nucleophiles can be applied in their heterogenized form, leading to a recyclable catalytic system. An investigation of the reaction mechanism by density functional theory calculations shows that metal halide complexes and nucleophilic pyridines can work as a dual cooperative catalytic system where the use of…

ADVERTISEMENT RETURN TO ISSUEEditorialNEXTHow Dangerous Is Too Dangerous? A Perspective on Azide ChemistryDaniel S. Treitler*Daniel S. TreitlerChemical Process Development, Bristol Myers Squibb, New Brunswick, New Jersey 08903, United States*Email: [email protected]More by Daniel S. Treitlerhttps://orcid.org/0000-0001-5375-4920 and Simon LeungSimon LeungChemical Process Development, Bristol Myers Squibb, New Brunswick, New Jersey 08903, United StatesMore by Simon LeungCite this: J. Org. Chem. 2022, 87, 17, 11293–11295Publication Date (Web):September 2, 2022Publication History Received14 June 2022Published online2 September 2022Published inissue 2 September 2022https://pubs.acs.org/doi/10.1021/acs.joc.2c01402https://doi.org/10.1021/acs.joc.2c01402editorialACS PublicationsCopyright © Published 2022 by American Chemical Society. This publication is available under these Terms of Use. Request reuse permissions This publication is free to access through this site. Learn MoreArticle Views32231Altmetric-Citations7LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full…

A photoredox-catalyzed direct arylation of quinoxalin-2-(1 H )-ones using diaryliodonium triflates as the convenient, stable, and cheap aryl source is described. A broad variety of quinoxalin-2-(1 H )-ones are shown to react with structurally and electronically diverse diaryliodonium triflates, allowing efficient access to a wide variety of pharmaceutically important 3-arylquinoxalin-2-(1 H )-ones. The presented method is attractive with regard to operational simplicity, mild conditions, broad scope, scalability, and high functional group tolerance.

Herein, we report a simple, phosphine-free, and inexpensive catalytic system based on a manganese(II) complex for synthesizing different important N-heterocycles such as quinolines, pyrroles, and pyridines from amino alcohols and ketones. Several control experiments, kinetic studies, and DFT calculations were carried out to support the plausible reaction mechanism. We also detected two potential intermediates in the catalytic cycle using ESI-MS analysis. Based on these studies, a metal-ligand cooperative mechanism was proposed.

H nuclear magnetic resonance (NMR) titrations, in conjunction with those from DFT calculations, indicate that this could be explained in terms of the additional energy required for the rotation of the phenyl ring in the diphenyliodonium cation during ligation of the substrate.

An axially chiral indolyl-pyrroloindole scaffold, a new member of axially chiral indole-based scaffolds, has been designed, and the catalytic asymmetric construction of this scaffold has been established by the strategy of organocatalytic asymmetric (2 + 3) cycloaddition of 3,3′-bisindoles with isoindolinone-based propargylic alcohols. By this approach, a series of indolyl-pyrroloindole derivatives bearing both axial chirality and central chirality were synthesized in high yields with excellent diastereo- and enantioselectivities (up to 95% yield, 91:9 dr, 99% ee). This reaction not only realizes the first catalytic asymmetric (2 + n ) cycloaddition of 3,3′-bisindoles as 1,2-dinucleophiles but also provides a new strategy for atroposelective construction of axially chiral indole-based scaffolds bearing five–five-membered rings, thus solving the challenges in constructing this class of axially chiral indole-based scaffolds.

Ground-state destabilization of the N–C(O) linkage represents a powerful tool to functionalize the historically inert amide bond. This burgeoning reaction manifold relies on the availability of amide bond precursors that participate in weakening of the n N → π* C=O conjugation through N–C twisting, N pyramidalization, and n N electronic delocalization. Since 2015, acyl N–C amide bond activation through ground-state destabilization of the amide bond has been achieved by transition-metal-catalyzed oxidative addition of the N–C(O) bond, generation of acyl radicals, and transition-metal-free acyl addition. This Perspective summarizes contributions of our laboratory in the development of new ground-state-destabilized amide precursors enabled by twist and electronic activation of the amide bond and synthetic utility of ground-state-destabilized amides in cross-coupling reactions and acyl addition reactions. The use of ground-state-destabilized amides as electrophiles enables a plethora of previously unknown transformations of the amide bond, such as acyl coupling, decarbonylative…

We present a convenient and efficient protocol to synthesize quinolines and quinazolines in one pot under mild conditions. A variety of substituted quinolines were synthesized in good to excellent yields (up to 97% yield) from the dehydrogenative cyclizations of 2-aminoaryl alcohols and ketones catalyzed by readily available Co(OAc) 2 ·4H 2 O. This cobalt catalytic system also showed high activity in the reactions of 2-aminobenzyl alcohols with nitriles, affording various quinazoline derivatives (up to 95% yield). The present protocol offers an environmentally benign approach for the synthesis of N-heterocycles by employing an earth-abundant cobalt salt under ligand-free conditions.

Machine learning (ML) profoundly improves the accuracy of the fast DU8+ hybrid density functional theory/parametric computations of nuclear magnetic resonance spectra, allowing for high throughput in silico validation and revision of complex alkaloids and other natural products. Of nearly 170 alkaloids surveyed, 35 structures are revised with the next-generation ML-augmented DU8 method, termed DU8ML.

-fluoro-azobenzenes are a class of photoswitches useful for the construction of visible-light-controlled molecular systems. They can be used to achieve spatio-temporal control over the properties of a chosen bioactive molecule. However, the introduction of different substituents to the tetra-fluoro-azobenzene core can significantly affect the photochemical properties of the switch and compromise biocompatibility. Herein, we explored the effect of useful substituents, such as functionalization points, attachment handles, and water-solubilizing groups, on the photochemical properties of this photochromic system. In general, all the tested fluorinated azobenzenes exhibited favorable photochemical properties, such as high photostationary state distribution and long half-lives, both in organic solvents and in water. One of the azobenzene building blocks was functionalized with a trehalose group to enable the uptake of the photoswitch into mycobacteria. Following metabolic uptake and incorporation of the trehalose-based azobenzene in the mycobacterial cell wall, we demonstrated…

Herein, we demonstrated Mn-catalyzed selective C-3 functionalization of indoles with alcohols. The developed catalyst can also furnish bis(indolyl)methanes from the same set of substrates under slightly modified reaction conditions. Mechanistic studies reveal that the C-3 functionalization of indoles is going via a borrowing hydrogen pathway. To highlight the practical utility, a diverse range of substrates including nine structurally important drug molecules are synthesized. Furthermore, we also introduced a one-pot cascade strategy for synthesizing C-3 functionalized indoles directly from 2-aminophenyl ethanol and alcohol.

, are used as the electron source in these reactions. Although heterogeneous reductants are highly practical for preparative-scale batch reactions, they can lead to complications in performing reactions on process scale and are not easily compatible with modern applications, such as flow chemistry. In principle, homogeneous organic reductants can address some of the challenges associated with heterogeneous reductants and also provide greater control of the reductant strength, which can lead to new reactivity. Nevertheless, homogeneous organic reductants have rarely been used in XEC. In this Perspective, we summarize recent progress in the use of homogeneous organic electron donors in Ni-catalyzed XEC and related reactions, discuss potential synthetic and mechanistic benefits, describe the limitations that inhibit their implementation, and outline challenges that need to be solved in order for homogeneous organic reductants to be widely utilized in synthetic chemistry. Although our focus is on XEC, our discussion of the strengths and weaknesses of different methods for introducing…

The Buchwald-Hartwig C-N coupling reaction has been ranked as one of the 20 most frequently used reactions in medicinal chemistry. Owing to its much lower cost and higher reactivity toward less reactive aryl chlorides than palladium, the C-N coupling reaction catalyzed by Ni-based catalysts has received a great deal of attention. However, there appear to be no universal, practical Ni catalytic systems so far that could enable the coupling of electron-rich and electron-poor aryl halides with both primary and secondary alkyl amines. In this study, it is reported that a Ni(II)-bipyridine complex catalyzes efficient C-N coupling of aryl chlorides and bromides with various primary and secondary alkyl amines under direct excitation with light. Intramolecular C-N coupling is also demonstrated. The feasibility and applicability of the protocol in organic synthesis is attested by more than 200 examples.

Herein, we report an efficient photoinduced radical tandem trifluoromethylation/cyclization reaction of N -cyanamide alkenes for the synthesis of functionalized quinazolinones. Importantly, the reaction is carried out under mild conditions without any additional photosensitizer, metal, or extra additives. A series of trifluoromethyl quinazolinones were prepared efficiently with good yields and excellent functional group tolerance. Preliminary mechanistic experiments were conducted to indicate that the transformation proceeds via a possible mechanism involving photoexcited EDA complex and chain propagation.

In this manuscript, we portrayed a stereospecific synthesis of C 2 - and C 1 -symmetric pyrene-fused [7]helicene compounds 1 and 2, respectively. Compounds 1 and 2 were synthesized via a one-pot Suzuki coupling–C–H activation and two-step Suzuki coupling–Scholl reaction, respectively, with complete retention of configuration. The synthesized molecules differ in the fusing mode of [7]helicene units with pyrene via six- and seven-membered rings for 1 and 2, respectively. There was a significant difference in the functional properties and enantiomerization barrier of both compounds because of their distinct molecular symmetry as well as fusing mode to pyrene moiety. The heptagon-containing molecule 2 showed remarkable photophysical and chiroptical properties with commendable configurational stability compared to 1 and pristine [7]helicene as well as its [5]helicene congener.

-aryl dibenzoselenophenium triflates, were found to exhibit remarkable catalytic activity in the model Groebke-Blackburn-Bienaymé reaction. Kinetic analysis and density functional theory (DFT) calculations indicated that their catalytic effect is induced by the ligation of the reaction substrates to the σ-holes on the S or Se atom of the cations. The experimental data indicated that although 10-fold excess of the chloride totally inhibits the catalytic activity of the sulfonium salts, the selenonium salt remains catalytically active, which can be explained by the experimentally found lower binding constant of the selenonium derivative to chloride in comparison with the sulfonium analogue. Both types of salts exhibit lower catalytic activity in the model reaction than dibenziodolium species.

-heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.

The stability of a photocatalyst under irradiation is important in photoredox applications. In this work, we investigated the stability of a thermally activated delayed fluorescence (TADF) photocatalyst {3DPAFIPN [2,4,6-tris(diphenylamino)-5-fluoroisophthalonitrile]}, recently employed in photoredox-mediated processes, discovering that in the absence of quenchers the chromophore is unstable and is efficiently converted by irradiation with visible light into another species based on the carbazole-1,3-dicarbonitrile moiety. The new species obtained is itself a TADF emitter and finds useful applications in photoredox transformations. At the excited state, it is a strong reductant and was efficiently applied to cobalt-mediated allylation of aldehydes, whereas other TADFs (4CzIPN and 3DPAFIPN) failed to promote efficient photocatalytic cycles.

Many synthetic methods that use fluorinated alcohols as solvents have been reported, and the fluorinated alcohols have been found to be crucial to the success of these methods. In addition, there have been reports indicating that adding a weakly coordinated fluorine-containing anion, such as BF 4 –, PF 6 –, or SbF 6 –, to fluorinated alcohols can improve yields. The boosting effect of fluorinated alcohols is attributed mainly to hydrogen bond activation. A few studies have suggested that the very polar fluorinated alcohols can stabilize cationic reaction intermediates. However, how they do so and why weakly coordinated fluorine-containing anions improve yields have not been studied in depth. Here, we used quaternary ammonium cations, a quaternary phosphonium cation, and a triaryl-substituted carbocation as models for short-lived cationic intermediates and studied the possible interactions of these cations with fluorinated alcohols and BF 4 –, PF 6 –, or SbF 6 – . On the basis of the results, we propose that the C–F dipoles of fluorinated alcohols and the E–F dipoles (where E is B,…

High Resolution Image Download MS PowerPoint Slide Azobenzenes are among the best-studied molecular photoswitches and play a key role in the search for red-shifted photoresponsive materials for extended applications. Currently, most approaches deal with aromatic substitution patterns to achieve visible light application, on occasion paired with protonation to yield red-shifted absorption of the azonium species. Appropriate substitution patterns are essential to stabilize the latter approach, as conventional acids are known to induce a fast Z - to E -conversion. Here, we show that steady-state protonation of the azo-bridge instead is possible in simple azobenzenes when the p K a of the acid is low enough, yielding both the Z - and E -azonium as supported by UV–vis- and 1 H NMR spectroscopy as well as density functional theory calculations. Moreover, the steady-state protonation of para -methoxyazobenzene, specifically, yields photoisomerizable azonium ions in which the direction of switching is essentially reversed, that is, visible light produces the out-of-equilibrium Z -azonium.…

Glycerophospholipids are major components of cellular membranes and provide important signaling molecules. Besides shaping membrane properties, some bind to specific receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening of a phosphate triester epoxide with carboxylic acids catalyzed by Jacobsen's Co(salen) complex. We show that this method can be applied to a variety of commercially available fatty acids, photoswitchable fatty acids, and other carboxylic acids to provide the corresponding glycerophosphate derivatives.

Carbon dioxide (CO 2 ) is the major greenhouse gas and also an abundant and renewable carbon resource. Therefore, its chemical conversion and utilization are of great attraction for sustainable development. Especially, reductive conversion of CO 2 with energy input has become a current hotspot due to its ability to access fuels and various important chemicals. Nowadays, the controllable CO 2 hydrogenation to formic acid and alcohols using sustainable H 2 resources has been regarded as an appealing solution to hydrogen storage and CO 2 accumulation. In addition, photocatalytic CO 2 reduction to CO also provides a potential way to utilize this greenhouse gas efficiently. Besides direct CO 2 hydrogenation, CO 2 reductive functionalization integrates CO 2 reduction with subsequent C–X (X = N, S, C, O) bond formation and indirect transformation strategies, enlarging the diverse products derived from CO 2 and promoting CO 2 reductive conversion into a new stage. In this Perspective, the progress and challenges of CO 2 reductive conversion, including hydrogenation, reductive…

An efficient synthesis of a variety of [1,2,3]triazolo-[1,5- a ]quinoxalin-4(5 H )-ones via a [3 + 2] cyclization reaction by photoredox catalysis between quinoxalinones and hypervalent iodine(III) reagents is reported. A range of quinoxalinones and hypervalent iodine(III) reagents were tolerated well. This cyclization reaction allows access to structurally diverse [1,2,3]triazolo-[1,5- a ]quinoxalin-4(5 H )-ones in moderate to good yields.

High Resolution Image Download MS PowerPoint Slide We report a copper-catalyzed cycloaddition of hydrogen azide (hydrazoic acid, HN 3 ) with terminal alkynes to form 4-substituted-1 H -1,2,3-triazoles in a sustainable manner. Hydrazoic acid was formed in situ from sodium azide under acidic conditions to react with terminal alkynes in a copper-catalyzed reaction. Using polydentate N-donor chelating ligands and mild organic acids, the reactions were realized to proceed at room temperature under aerobic conditions in a methanol–water mixture and with 5 mol % catalyst loadings to afford 4-substituted-1,2,3-triazoles in high yields. This method is amenable on a wide range of alkyne substrates, including unprotected peptides, showing diverse functional group tolerance. It is applicable for late-stage functionalization synthetic strategies, as demonstrated in the synthesis of the triazole analogue of losartan. The preparation of orthogonally protected azahistidine from Fmoc- l -propargylglycine was realized on a gram scale. The hazardous nature of hydrazoic acid has been diminished as it…

Using readily available preallylated aldehydes, we report a simple and divergent synthesis of cyclic (alkyl)(amino)carbene (CAAC) iminium precursors. Using a combination of crystallographic data and steric maps, we further elaborate on the specific steric properties of CAAC ligands with respect to state-of-the-art phosphine and carbene ligands.

Chiral sulfoximines have recently been considered as promising bioisosteres in medicinal chemistry. However, methods for preparing chiral sulfoximines in a stereoselective manner are underdeveloped. Herein, we demonstrate an asymmetric synthesis of chiral sulfoximines through a stereospecific S -alkylation of readily accessible chiral sulfinamides under practical conditions. A key to establishing the practical conditions was the identification of the intermediate structure in our previously reported S -alkylation by X-ray crystallographic analysis.

)-H functionalization in the presence of visible light and Rose Bengal as an organophotocatalyst. The reaction of amino pyrazole/iosothiazole/isoxazole or amino uracils with 0.5 equivalent of diphenyl/dibenzyl/diethyl diselenides in the presence of visible light in acetonitrile medium and a catalytic amount of Rose Bengal provided the corresponding phenyl, benzyl, or ethyl selenoethers in good to very good yields. We have also utilized some of the selenylated aminopyrazoles for the preparation of pyrazole-fused dihydropyrimidines tethered with arylselenoethers by a catalyst-free one-pot three-component reaction. The notable features of this methodology are metal-free reaction conditions, good to very good yields, use of an organic photocatalyst, and wide substrate scope; it is also applicable to gram-scale synthesis and provides selenoethers of medicinally important heterocycles such amio-pyrazole, isoxazole, isothiazole, and uracils.

We report a sustainable and eco-friendly approach for selective N -alkylation of various amines by alcohols, catalyzed by a well-defined Zn(II)-catalyst, Zn( L a )Cl 2 ( 1a ), bearing a tridentate arylazo scaffold. A total of 57 N -alkylated amines were prepared in good to excellent yields, out of which 17 examples are new. The Zn(II)-catalyst shows wide functional group tolerance, is compatible with the synthesis of dialkylated amines via double N -alkylation of diamines, and produces the precursors in high yields for the marketed drugs tripelennamine and thonzonium bromide in gram-scale reactions. Control reactions and DFT studies indicate that electron transfer events occur at the azo-chromophore throughout the catalytic process, which shuttles between neutral azo, one-electron reduced azo-anion radical, and two-electron reduced hydrazo forms acting both as electron and hydrogen reservoir, enabling the Zn(II)-catalyst for N -alkylation reaction.

An efficient and convenient method to synthesize 6-oxyalkylated 1,2,4-triazine-3,5(2 H, 4 H )-diones has been developed via visible-light-induced cross-dehydrogenative coupling reaction between 1,2,4-triazine-3,5(2 H, 4 H )-diones and ethers with a wide range of functional group tolerance. The present transformation employs the cheap and low-toxic 2- tert -butylanthraquinone as a metal-free photocatalyst and air as a green oxidant at room temperature. Moreover, this reaction can also be driven by sunlight as a clean energy resource. The synthetic utility of this method is further demonstrated by gram-scale reaction and application in the preparation of key intermediates of bioactive molecules.

Carbazolyl dicyanobenzene (CDCB) derivates exhibiting thermally activated delayed fluorescence (TADF) have shown themselves to be excellent photocatalysts over recent years, particularly 4CzIPN, although investigation into organic TADF compounds as photocatalysts outside of the CDCB group has been limited. Herein, we report an alternative donor–acceptor TADF structure, 9,9′-(sulfonylbis(pyrimidine-5,2-diyl))bis(3,6-di-tert-butyl-9H-carbazole), pDTCz-DPmS, for use as a photocatalyst (PC). A comparison of the electrochemical and photophysical properties of pDTCz-DPmS with 4CzIPN in a range of solvents identifies the former as a better ground state reducing agent and photoreductant, while both exhibit similar oxidation capabilities in the ground and excited state. The increased conjugation of pDTCz-DPmS relative to 4CzIPN presents a more intense CT band in the UV–vis absorption spectrum, aiding in the light absorption of this molecule. Prompt and delayed emission lifetimes are observed for pDTCz-DPmS, confirming the TADF nature, both of which are sufficiently long-lived to participate…

Electron donor–acceptor (EDA) complex-mediated single-electron transfer (SET) is a crucial method for generating carbon radicals. Hydrogen atom transfer (HAT) enables the direct generation of alkyl radicals from alkanes. We report a dual-role EDA-SET/HAT photoreaction system for carbon–carbon bond formation using a phenol catalyst and aryl iodide. This system facilitates a Minisci-type addition of alkyl radicals to arenes. Mechanistic studies revealed that EDA complex formation is mediated by halogen bonding between phenoxide and aryl iodide. Irradiation of the EDA complex with visible light generates an aryl radical, which abstracts a hydrogen atom from an alkane to form an alkyl radical.

Multicomponent synthesis of biologically relevant S -benzyl dithiocarbamates from para -quinone methides, amines, and carbon disulfide are described under catalyst and additive-free conditions. The reactions proceeded at room temperature in a short span of time with excellent yields. One of the synthesized compounds, 3e showed considerable acetylcholinesterase (AChE) inhibitory (51.70 + 5.63% at 20 μm) and antioxidant (63.52 ± 1.15 at 20 μm) activities.

A practical and scalable protocol for electrochemical arylation of quinoxalin(on)es with arylhydrazine hydrochlorides under mild conditions has been developed. This method exhibits high efficiency, easy scalability, and broad functional group tolerance. Various quinoxalin(on)es and arylhydrazines underwent this transformation smoothly in an undivided cell, providing the corresponding aryl-substituted quinoxalin(on)es in moderate to good yields. A radical mechanism is involved in this arylation reaction.

A mild and facile photo-induced cascade radical addition/cyclization of unactivated alkenes has been reported, through which a variety of biologically valuable phosphine-containing quinazolinones could be obtained in moderate to good yields. The protocol was characterized by mild conditions, broad substrate scope, and high atomic economy.

-alkyl indole, into the substrates used in formal [2+2] cycloaddition-retroelectrocyclizations has significant potential to overcome the limited donor-substituted substrate scope problem of CA-RE reactions.

Reported herein is a photoredox-catalyzed amination of o- hydroxyarylenaminones with tert -butyl ((perfluoropyridin-4-yl)oxy)carbamate, a versatile amidyl-radical precursor developed in our laboratory. This work establishes a new cascade pathway for the assembly of a range of 3-aminochromones under mild conditions. Downstream transformations of the obtained 3-aminochromones to construct diverse amino pyrimidines greatly broaden the applications of this photocatalyzed protocol.

A visible-light-induced persulfate-promoted cascade phosphorylation/cyclization reaction to access various phosphorylated pyrrolo[1,2- a ]indolediones under mild conditions was developed. Notably, the transformation was carried out with diethyl carbonate/H 2 O as a green medium at room temperature. More impressively, traditional metal catalysts and photocatalysts could be effectively avoided. The reactions are simple to operate, easy to scale up, and have good functional group tolerance.

Visible light photocatalytic reactions of NH 2 -enaminones and ammonium thiocyanate for chemoselective α-C–H thiocyanation have been realized for the first time, providing a sustainable route for the synthesis of thiocyanated NH 2 -enaminones. In addition, the thiocyanated enaminone products can be flexibly transformed into 2-aminothiazoles and 2-thiazolinones via a simple operation.

A transition metal- and hydride-free protocol has been developed for the chemoselective reduction of α-keto esters and α-keto amides using rongalite as a reducing agent. Here, rongalite acts as a hydride-free reducing agent via a radical mechanism. This protocol offers the synthesis of a wide range of α-hydroxy esters and α-hydroxy amides with 85–98% yields. This chemoselective method is compatible with other reducible functionalities such as halides, alkenes, amides, and nitriles. The use of inexpensive rongalite ( ca. $0.03/1 g), mild reaction conditions, and gram-scale synthesis are some of the key features of this methodology. Also, cyclandelate, a vasodilator drug, has been synthesized in gram scale with 79% yield.

Currently, the construction of new carbon-carbon bonds and value-added structures in an atom- and step economical manner has become a continuous pursuit in the synthetic chemistry community. Since the first transition-metal-catalyzed hydroformylation of ethylene was reported by Otto Roelen in the 1930s, impressive progress has been achieved in the carbonylative functionalization of unsaturated C-C bonds. In contrast to alkenes, the carbonylative functionalization of alkynes offers tremendous potential for the construction of multisubstituted carbonyl-containing derivatives because of their two independently addressable π-systems. This review provides a timely and necessary investigation of transition-metal-catalyzed carbonylative mutifunctionalization of alkynes with the exclusion of carbonylative hydrofunctionalizations. Different transition metals including palladium, rhodium, iridium, ruthenium, iron, copper, etc. were applied to the development of novel carbonylative transformation. Various C-C, C-N, C-O, C-S, C-B, C-Si, and carbon-halogen bonds were formed efficiently and give…

Phenyl boronic acids are valuable for medical diagnostics and biochemistry studies due to their ability to readily bind with carbohydrates in water. Incorporated in carbohydrates are 1,2-diols, which react with boronic acids through a reversible covalent condensation pathway. A wide variety of boronic acids have been employed for diol binding with differing substitution of the phenyl ring, with the goals of simplifying their synthesis and altering their thermodynamics of complexation. One method for monitoring their p K a ’s and binding is 11 B NMR spectroscopy. Herein, we report a comprehensive study employing 11 B NMR spectroscopy to determine the p K a of the most commonly used phenyl boronic acids and their binding with catechol or d, l -hydrobenzoin as prototypical diols. The chemical shift of the boronic acid transforming into the boronate ester was monitored at pHs ranging from 2 to 10. With each boronic acid, the results confirm (1) the necessity to use pHs above their p K a ’s to induce complexation, (2) that the p K a ’s change in the presence of diols, and (3) that 11 B…

An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible and air-stable [Ph 3 PCF 2 H] + Br – as the difluoromethylation reagent, has been established. A range of CF 2 H-substituted chroman-4-one skeletons and their derivatives, such as 2,3-dihydroquinolin-4(1 H )-ones, chroman, 3,4-dihydronaphthalen-1(2 H )-one, 2,3-dihydrobenzofuran, and 2,3-dihydro-1 H -inden-1-one, are efficiently produced in moderate to good yields with excellent chemoselectivity under mild reaction conditions.

Hydrogen bonds not only play a crucial role in the life sciences but also endow molecules with fantastic physical and chemical properties, which help in the realization of their high-tech applications. This work presents an efficient strategy for achieving highly efficient solid-state dual-emission blue emitters with mechanical force-induced enhanced emission properties via intermolecular hydrogen bonds via novel pyrene-based intermediates, namely, 1,3,6,8-tetrabromo-2,7-dihydroxypyrene ( 1 ) and 1,3,6,8-tetrabromo-2-hydroxypyrene ( 2 ), prepared via hydroxylation and bromination of pyrene in high yields. Moreover, further use of a classical Pd-catalyzed coupling reaction affords new pyrene-based luminescent materials 3–5, which display high thermal stability (in range of 336–447 °C), blue emission (<463 nm), and high quantum yields in solution. Interestingly, with the monosubstituted hydroxyl (OH) or methoxy (OMe) group located at position 2 of pyrene, compounds 4a and 5 display exciting dual emission with mechanical force-induced enhanced emission properties, due to the presence…

An electrochemical dearomatizing spirocyclization of alkynes with dimethyl 2-benzylmalonates for the preparation of spiro[4.5]deca-trienones has been developed. This approach adopts ferrocene (Cp 2 Fe) as an electrocatalyst to produce carbon-centered radical intermediates from C–H-based malonates, which obviates the forthputting of noble-metal reagents, sacrificial chemical oxidants and 2-bromomalonates. A wide variety of spiro compounds are efficiently prepared with satisfactory results under mild conditions.

Reactions of acceptor-substituted aryl iodides and bromides with potassium thiocarboxylates under white light irradiation allow for the preparation of S -aryl thioesters including synthetically versatile S -aryl thioacetates. This transition-metal and external photocatalyst-free method features extremely mild reaction conditions compared with those used in transition-metal-catalyzed protocols. Reactions proceed via the initial formation of an electron donor–acceptor (EDA) complex in the ground state, which was supported by UV–vis spectra. Electron paramagnetic resonance (EPR) spin-trapping experiments using phenyl- N - tert -butylnitrone ( PBN ) have revealed the radical nature of the reaction.

A novel and efficient three-component reaction with two C–N bonds and one C–F bond formation has been reported, which provides a straightforward route to a variety of fluorinated pyrimido[1,2- b ]indazole derivatives. This transformation has the advantage of excellent functional group compatibility, including aliphatic and aromatic substituents enaminones. Moreover, metal and additives are not necessary for this reaction, which is of great significance for the synthesis and application of fluorinated heterocycles.

Copper-catalyzed [3 + 2] cycloadditions of N -tosylcyclopropylamine with alkynes and alkenes have been accomplished under visible light irradiation. The developed approach is compatible with a range of functionalities and allows the synthesis of diversified aminated cyclopentene and cyclopentane derivatives being relevant for drug synthesis. The protocol is operationally simple and economically affordable as it does not require any ligand, base, or additives. As the key step, the one-electron oxidation of the N -tosyl moiety by visible light-induced homolysis of a transient Cu(II)-tosylamide complex is proposed, providing a facile entry for N -centered radicals.