The 50 most-cited articles in The Journal of Organic Chemistry, 2018

The use of combined Heck carbometalation and cross-coupling remains one of the most powerful ways for the difunctionalization of unactivated olefins with organometallic reagents and organohalides. This synopsis will provide an overview of this reaction developed in the last three and a half decades. Herein, both the three-component and the two-component cyclization/cross-coupling processes will be reviewed with a focus on strategies utilized to overcome the complications of β-hydride elimination from Heck C(sp 3 )-[M] intermediates, which usually functions as a major side reaction.

Herein, we present a selective synthesis of 2-substituted and 1,2-disubstituted benzimidazoles by acceptorless dehydrogenative coupling of aromatic diamine with primary alcohols. The reaction is catalyzed by a phosphine-free tridentate NNS ligand-derived manganese(I) complex.

An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.

This study reports a nickel-catalyzed sustainable synthesis of polysubstituted quinolines from α-2-aminoaryl alcohols by a sequential dehydrogenation and condensation process that offers the advantages of a low catalyst loading and wide substrate scope. In contrast to earlier reported methods, this strategy allows the use of both primary as well as secondary α-2-aminoaryl alcohols in combination with either ketones or secondary alcohols for desired product formation. Using this methodology, 30 substituted quinoline derivatives were synthesized with up to 93% isolated yields.

The transition metal-catalyzed allylic substitution reaction is a particularly versatile method for the construction of carbon-carbon and carbon-heteroatom bonds. In this regard, the rhodium-catalyzed variant has emerged as a powerful method for the regioselective and stereospecific allylic substitution of chiral nonracemic secondary and tertiary allylic carbonates with a variety of carbon- and heteroatom-based nucleophiles. In addition, recent developments have made the analogous enantioselective process possible using prochiral nucleophiles with achiral allylic electrophiles, which represents a significant advance in this area. In this Perspective, the discovery, development and applications of these conceptually orthogonal strategies to target-directed synthesis are discussed, with a particular emphasis given to those methods developed in our laboratory.

The zw-type [3 + 2] cycloaddition (32CA) reactions of C,N-dialkyl nitrones with a series of ethylenes of increased electrophilic character have been studied within the Molecular Electron Density Theory (MEDT) at the MPWB1K/6-311G(d,p) computational level. Both, reactivity and selectivities are rationalized depending on the polar character of the reaction. Due to the strong nucleophilic character of C,N-dialkyl nitrones, the corresponding zw-type 32CA reactions are accelerated with the increased electrophilic character of the ethylene, which also plays a crucial role in the reaction mechanism, thus determining the regio- and stereoselectivities experimentally observed. While, in the 32CA reactions with nucleophilic ethylenes, the reaction begins with the formation of the C-C single bond, determining the ortho regioselectivity, in the 32CA reactions with strong electrophilic ethylenes, the reaction begins with the formation of the C-O single bond involving the β-conjugated carbon of the ethylene, determining the meta regioselectivity. The present MEDT study also provides an…

Two environmentally benign methods for the synthesis of quinazolines via acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol (Path A) and 2-aminobenzylalcohol with benzonitrile (Path B), catalyzed by cheap, earth abundant and easy to prepare nickel catalysts, containing tetraaza macrocyclic ligands (tetramethyltetraaza[14]annulene (MeTAA) or 6,15-dimethyl-8,17-diphenyltetraaza[14]annulene (MePhTAA)) are reported. A wide variety of substituted quinazolines were synthesized in moderate to high yields starting from cheap and easily available starting precursors. A few control reactions were performed to understand the mechanism and to establish the acceptorless dehydrogenative nature of the catalytic reactions.

We report herein an effective method for the halogenation of imidazo-fused heterocycles using readily available sodium salts (NaCl/NaBr/NaI) as halogen source and K 2 S 2 O 8 (or) oxone as promoter. A variety of C-3 halogenated imidazo[1,2- a ]pyridines and benzo[d]imidazo[2,1- b ]thiazoles were obtained in good to excellent yields. The present method of halogenation has been also extended to 2-aminopyridines, 2-aminopyrimidine, indole, and isoquinoline with moderate to excellent yields.

A modular autonomous flow reactor combining monitoring technologies with a feedback algorithm is presented for the synthesis of the natural product carpanone. The autonomous self-optimizing system, controlled via MATLAB, was designed as a flexible platform enabling an adaptation of the experimental setup to the specificity of the chemical transformation to be optimized. The reaction monitoring uses either online high pressure liquid chromatography (HPLC) or in-line benchtop nuclear magnetic resonance (NMR) spectroscopy. The custom-made optimization algorithm derived from the Nelder-Mead and golden section search methods performs constrained optimizations of black-box functions in a multidimensional search domain, thereby assuming no a priori knowledge of the chemical reactions. This autonomous self-optimizing system allowed fast and efficient optimizations of the chemical steps leading to carpanone. This contribution is the first example of a multistep synthesis where all discrete steps were optimized with an autonomous flow reactor.

) was readily prepared from the sweet additive Saccharin in two steps with a 71% overall yield. By applying this new reagent to diverse nucleophiles such as benzothiophenes, indoles, oxindoles, aromatic amines, phenols, β-keto carbonyl compounds, and aromatic ketones, a novel electrophilic thiocyanation reaction was achieved with high yields (up to 99%). The potential recycling of Saccharin, the wide scope of substrates, and the mild reaction conditions made this protocol much more practical.

The problem of deriving atomic charges from the results of ab Initio MO calculations has been studied by the use of several reported methods: Mulliken population analysis, the minimal basis set (MBS) procedure, the natural population analysis (NPA), two electrostatic potential fitting methods, M-K and ChelpG, the Hirshfeld population analysis, and CM5 (charge model 5), which is related to the Hirshfeld method. The first set of studies were concerned with hydrogen charges. It was found that the MBS charges were linearly related to the Hirshfeld charges. The Hirshfeld, CM5, and MBS methods, but not the others, provided an excellent correlation for H atomic charge with the H-C-H bond angle, and with calculated gas-phase acidity. The two methods that were linearly related and gave hydrogen charges in agreement with an experimental study of partially deuterated methanes are MBS and Hirshfeld. In order to see which of the two methods is the more satisfactory, the methanol dimer was examined. The calculated H bond energy was 6.2 kcal/mol, which was in good agreement with studies of…

Azides are building blocks of increasing importance in synthetic chemistry, chemical biology, and materials science. Azidobenziodoxolone (ABX, Zhdankin reagent) is a valuable azide source, but its safety profile has not been thoroughly established. Herein, we report a safety study of ABX, which shows its hazardous nature. We introduce two derivatives, tBu-ABX and ABZ (azidobenziodazolone), with a better safety profile, and use them in established photoredox- and metal-mediated azidations, and in a new ring-expansion of silylated cyclobutanols to give azidated cyclopentanones.

) cross-dehydrogenative coupling between tetrahydroisoquinoline and imidazo[1,2- a]pyridine has been developed to afford 3-substituted imidazopyridines using a catalytic amount of rose bengal as photosensitizer under aerobic conditions. The present methodology is also applicable to imidazo[1,2- a]pyrimidine, indolizine, indole, and pyrrole as well as N, N-dimethyl aniline. Wide substrates scope, use of organo photocatalyst, metal-free, and mild reaction conditions are the attractive features of this methodology.

The rhodium(III)-catalyzed C-H functionalization followed by intramolecular annulation reactions between azobenzenes and sulfoxonium ylides is described. This protocol leads to the efficient formation of 3-acyl (2 H)-indazoles with a range of substrate scope. A high level of chemoselectivity and functional group tolerance of this transformation were also observed.

A practical synthesis of 2,4-methanopyrrolidines was elaborated. The key synthetic step was an intramolecular photochemical [2 + 2]-cycloaddition of an acrylic acid derivative in flow. In spite of a higher molecular weight, 2,4-methanopyrrolidines were shown to have higher solubility in water and lower lipophilicity than pyrrolidines, important characteristics of bioactive molecules in drug design.

A metal-free visible-light-induced phosphonylation of 2 H-indazoles with diphenylphosphine oxide has been developed using rose bengal as an organophotoredox catalyst under ambient air at room temperature. A library of diphenyl(2-phenyl-2 H-indazol-3-yl)phosphine oxide with broad functionalities has been synthesized in high yields. The experimental result suggests the radical pathway of the reaction.

The first catalytic asymmetric dearomative [3 + 2] cycloaddition of 3-nitroindoles with vinylcyclopropanes has been established, which constructed chiral cyclopenta[b]indoline scaffolds in generally high enantioselectivities (up to 97% ee). This reaction also represents the first application of all-carbon 1,3-dipoles in catalytic asymmetric dearomative [3 + 2] cycloadditions of 3-nitroindoles. This approach will not only advance the catalytic asymmetric dearomatization reactions of electron-deficient indoles but also provide an efficient method for constructing chiral cyclopenta[b]indoline scaffolds.

The electronic and steric effects of aryl substituents and the influence of hydrogen bonding in Z-isomer stability of phenylazopyrazole derivatives have been investigated. In this regard, 38 substituted phenylazopyrazole derivatives and 6 N-methyl phenylazopyrazoles (with meta substitutions) have been synthesized. Their photoswitching behavior, photostationary states (PSS), and kinetics of thermal reverse isomerization were evaluated experimentally using UV-vis and NMR spectroscopic techniques. Furthermore, density functional theory (DFT) computations have been performed for more detailed insights. Despite the presence of substantial substituent effects inferred through Taft and Hammett relationships, the concentration dependency in controlling the isomerization rates has also been observed. Kinetics studies at different concentrations, solvent effects, and computations have confirmed the decisive role of hydrogen bonding and solvent-assisted tautomerism in this regard. Through this study, a complex interplay of steric, electronic effects and hydrogen bonding as factors in dictating…

Asymmetric dearomative [3 + 2] cycloaddition reactions of 3-nitroindoles with vinyl aziridine and vinyl cyclopropanes have been respectively successfully developed in the presence of a chiral box/Pd(0) complex. A series of enantiomerically enriched 3a-nitro-hexahydropyrrolo[2,3-b]indole and 8b-nitrohexahydrocyclopenta[b]indole derivatives containing three contiguous chiral centers are smoothly obtained in high yields with satisfactory regio-, chemo-, and enantioselectivity. Remarkably, the synthetic utility of this process was demonstrated through direct reductive amination and functionalization of the carbon-carbon double bond of the desired products.

A novel silver-catalyzed ring-opening acylation of cyclopropanols and cyclobutanols is described. The reaction proceeds under mild and neutral conditions and provides a facile access to nonsymmetric 1,4- and 1,5-diketones in promising yields with broad substrate scope. Mechanistic studies including DFT calculations suggest the involvement of an uncommon water-assisted 1,2-HAT process, which is strongly exothermic and thus promotes addition of carbon radicals to aldehydes. In contrast to traditional reductive radical addition protocols, this work represents the first example of the intermolecular oxidative radical addition to aldehydes, thus offering a novel strategy for the direct synthesis of acyclic ketones from readily accessible aldehydes.

A series of novel ruthenium(II) complexes supported by a symmetrical NNN ligand were prepared and fully characterized. These complexes exhibited good performance in transfer hydrogenation to form new C-C bonds using alcohols as the alkylating agents, generating water as the only byproduct. A broad range of substrates, including (hetero)aryl- or alkyl-ketones and alcohols, were well tolerated under the optimized conditions. Notably, α-substituted methylene ketones were also investigated, which afforded α-branched steric hindrance products. A potential application of α-alkylation of methylene acetone to synthesize donepezil was demonstrated, which provided the desired product in 83% yield. Finally, this catalytic system could be applied to a one-pot double alkylation procedure with sequential addition of two different alcohols. The current protocol is featured with several characteristics, including a broad substrate scope, low catalyst (0.50 mol %) loadings, and environmental benignity.

A novel synthetic methodology for the preparation of 1,3-disubstituted pyrazoles from in situ generated nitrile imines and acetylene is reported. The reactions are performed in a simple two-chamber reactor. One part of the reactor is loaded with hydrazonoyl chloride precursors of active nitrile imine species and a base. The other part is used to generate acetylene from CaC 2 and water. Partitioning of the reactants improves the yields of desired pyrazoles up to 99% and simplifies their isolation to a simple procedure of solvent evaporation. The approach requires no complex equipment and utilizes inexpensive, safe, and easy to handle calcium carbide as a starting material. A model deuterium incorporation is carried out according to the developed methodology, producing a series of novel 4,5-dideuteropyrazoles with excellent deuterium enrichment. Theoretical calculations on reaction mechanism and characterization of possible intermediate structures were performed.

A highly effective and green procedure for the formation of α-alkylated ketones has been disclosed via the reaction of primary alcohols with secondary alcohols and ketones by using [IrCl(COD)(NHC)] complexes as a catalyst. Various α-alkylated ketones were obtained in high yields from the alkylation of alcohol with alcohol and ketone with alcohol through a borrowing hydrogen reaction by using 0.05-0.5 mol % iridium(I) and a catalytic amount of KOH (5-10 mol %) as the base under air atmosphere and within very short reaction times.

The first cyclization of para-quinone methide derivatives with alkynes was established by utilizing the [4 + 2] reaction of ortho-hydroxyphenyl-substituted para-quinone methides with ynones or benzyne, which efficiently constructed the scaffolds of chromene and xanthene in high yields (up to 88%). This protocol has not only fulfilled the task of developing cyclization reactions of para-quinone methide derivatives but also provided an efficient method for constructing chromene and xanthene scaffolds.

At the early stages of the drug development process, thousands of compounds are synthesized in order to attain the best possible potency and pharmacokinetic properties. Once successful scaffolds are identified, large libraries of analogues are made, which is a challenging and time-consuming task. Recently, late stage functionalization (LSF) has become increasingly prominent since these reactions selectively functionalize C-H bonds, allowing to quickly produce analogues. Classical electrophilic aromatic halogenations are a powerful type of reaction in the LSF toolkit. However, the introduction of an electrophile in a regioselective manner on a drug-like molecule is a challenging task. Herein we present a machine learning model able to predict the reactive site of an electrophilic aromatic substitution with an accuracy of 93% (internal validation set). The model takes as input a SMILES of a compound and uses six quantum mechanics descriptors to identify its reactive site(s). On an external validation set, 90% of all molecules were correctly predicted.

The preparation of nitriles from primary amides or aldoximes was achieved by using oxalyl chloride with a catalytic amount of dimethyl sulfoxide in the presence of Et 3 N. The reactions were complete within 1 h after addition at room temperature. A diverse range of cyano compounds were obtained in good to excellent yields, including aromatic, heteroaromatic, cyclic, and acyclic aliphatic species.

Highly effective hydroboration precatalyst is developed based on a cobalt(II)-terpyridine coordination polymer (CP). The hydroboration of ketones, aldehydes, and imines with pinacolborane (HBpin) has been achieved using the recyclable CP catalyst in the presence of an air-stable activator. A wide range of substrates containing polar C═O or C═N bonds have been hydroborated selectively in excellent yields under ambient conditions.

The origin of the anomeric effect has been reexamined in a coordinated experimental and computational investigation. The results of these studies implicate a number of different, but correlated, interactions that in the aggregate are responsible for the anomeric effect. No single factor is uniquely responsible for the axial preference of a substituent that is the hallmark of the anomeric effect. A CH···G nonbonded attraction between a polar axial substituent (G) and the syn-axial hydrogen(s) in the heterocycle has been demonstrated experimentally. The hyperconjugation model involving electron transfer from a ring heteroatom to an excited state of an axial C-G bond was shown to be, at most, a minor contributor because of the very small changes in charge density at the ring heteroatom(s): the main charge transfer is from hydrogen to G in the H-C-G unit. This appears to result from lengthening the C-G bond to minimize repulsion with the ring atom lone pair(s) and the advantage of having a more positive hydrogen that leads to a stabilizing Coulombic interaction with the ring…

In this manuscript, we report the first synthesis of an organic monomolecular emitter, which behaves as a circularly polarized luminescence (CPL)-based ratiometric probe. The enantiopure helical ortho-oligo(phenylene)ethynylene ( o-OPE) core has been prepared by a new and efficient macrocyclization reaction. The combination of such o-OPE helical skeleton and a pyrene couple leads to two different CPL emission features in a single structure whose ratio linearly responds to silver(I) concentration.

The molecular architectures and potent bioactivities of diazo-containing natural products have attracted the interest of synthetic and biological chemists. Despite this attention, the biosynthetic enzymes involved in diazo group construction have not been identified. Here, we show that the ATP-dependent enzyme CreM installs the diazo group in cremeomycin via late-stage N-N bond formation using nitrite. This finding should inspire efforts to use diazo-forming enzymes in biocatalysis and synthetic biology as well as enable genome-based discovery of new diazo-containing metabolites.

Diaporindenes A–D ( 1 – 4 ), four unusual 2,3-dihydro-1 H -indene isomers, a novel isoprenylisobenzofuran A ( 5 ), two new isoprenylisoindole alkaloids diaporisoindoles D and E ( 6 and 7 ), and a new benzophenone derivative tenellone D ( 11 ), together with four known biogenetic agents ( 8 – 10 and 12 ), were all separated from the endophytic fungus Diaporthe sp. SYSU-HQ3 guided by ultraperformance liquid chromatography high-resolution mass spectrometry. The absolute configurations of 1 – 7 and 11 were defined by X-ray diffraction, quantum chemical calculations, and spectroscopic analysis. Diaporindenes A–D ( 1 – 4 ) possessed an unprecedented chemical skeleton featuring a 2,3-dihydro-1 H -indene ring and a 1,4-benzodioxan moiety. All of the isolates ( 1 – 12 ) were tested for their inhibitory effects on the production of nitric oxide in lipopolysaccharide-induced microglial cells (RAW 264.7 cells). Compounds 1 – 5, 8, and 9 were found to exhibit significant inhibitory effects against nitric oxide production with IC 50 values from 4.2 to 9.0 μM and SI values from 3.5 to 6.9. In…

Herein, we report an enantioselective synthesis of azepinones via the N-heterocyclic carbene (NHC) catalyzed [3+4] annulation reaction of isatin-derived enals and aurone-derived azadienes. The corresponding spirocyclic oxindole-benzofuroazepinones were obtained in good yields, with excellent diastereo- and enantioselectivities. The resulted azepinones were evaluated for their in vitro cytotoxic activities against six human tumor cell lines, with two compounds showing significant inhibitory activity comparable with that of cisplatin.

This work reports a cobalt(II)/ N-hydroxyphthalimide (NHPI)-catalyzed cross-dehydrogenative oxidative coupling of N-aryl tetrahydroisoquinolines with various pro-nucleophiles, such as indoles, nitroalkanes, and trialkylphosphites, active methylene compounds, and other nucleophiles, such as cyanide (ethyl cyanoformate), at room temperature under aerobic conditions. The present protocol is operationally simple and can be carried out without photoirradiation and under peroxide-free conditions, even on a gram scale, to afford the products in good to excellent yields. On the basis of mass spectrometry and control experiments, a catalytic reaction pathway has been proposed.

O)] was found to be a highly efficient and general catalyst for transfer hydrogenation of aldehydes and chemoselective transfer hydrogenation of unsaturated aldehydes with isopropanol under neutral conditions. It was noteworthy that many readily reducible or labile functional groups such as nitro, cyano, ester, and halide did not undergo any change under the reaction conditions. Furthermore, this catalytic system exhibited high activity for transfer hydrogenation of ketones with isopropanol. Notably, this research exhibited new potential of metal-ligand bifunctional catalysts for transfer hydrogenation.

A novel visible-light-mediated ipso-carboacylation of N-(p-methoxyaryl)propiolamides with acyl chloride has been established for the synthesis of diverse 3-acylspiro[4,5]trienones with high selectivity and efficiency. This method represents a new difunctionalization of alkynes through cross coupling of the acyl chloride C-Cl bonds with an ipso-aromatic carbon by simultaneously forming two new carbon-carbon bonds and one carbon-oxygen double bond.

Carbon radicals are reactive species useful in various organic transformations. The C-X bond cleavage of organohalides by photoirradiation is a common method to generate carbon radicals in a controlled fashion. The use of organochloride substrates is still a formidable challenge due to the low reduction potential and the high dissociation energy of the C-Cl bond. In this report, we address these issues by using a nonmetal organic molecule with a relatively simple structure as a photocatalyst. In this catalyst (bis(dimethylamino)carbazole), the amino groups increase both the HOMO and LUMO energy levels, especially in the former. As a result, compared to the parent molecule, the new catalyst shows experimentally red-shifted absorption in the visible region and forms an excited state with better reducing capability. This photocatalyst was used in the reduction of unactivated aryl chlorides and alkyl chlorides in the presence of hydrogen atom donor at room temperature. The catalytic system can also be applied to the coupling of aryl chlorides with electron-rich arene and heteroarenes to…

Novel scorpionate-type organocatalysts capable of effectively coupling carbon dioxide and epoxides under mild conditions to afford cyclic propylene carbonates were developed. On the basis of a combined experimental and computational study, a precise mechanistic proposal was developed and rational optimization strategies were identified. The epoxide ring-opening, which requires an iodide as a nucleophile, was enhanced by utilizing an immonium functionality that can form an ion pair with iodide, making the ring-opening process intramolecular. The CO 2 activation and cyclic carbonate formation were catalyzed by the concerted action of two hydrogen bonds originating from two phenolic groups placed at the claw positions of the scorpionate scaffold. Electronic tuning of the hydrogen bond donors allowed to identify a new catalyst that can deliver >90% yield for a variety of epoxide substrates within 7 h at room temperature under a CO 2 pressure of only 10 bar, and is highly recyclable.

Organosulfides have great significance and value in synthetic and biological chemistry. To establish a versatile and green methodology for C–S bond generation, we successfully developed a new aerobic cross-dehydrogenative coupling of C–H and S–H to synthesize aryl sulfides in water, utilizing CoPcS as the catalyst and O 2 as the oxidant. This protocol shows great tolerance of a wide range of substrates. A large variety of organosulfur compounds were produced in modest to excellent yields.

An effective radical cascade cyclization strategy was developed, by which a wide range of 2-phosphoryl-substituted quinoxalines were prepared in one pot via reaction of ortho -diisocyanoarenes with diarylphosphine oxides in the presence of AgNO 3 under mild reaction conditions.

A one-pot route for the regioselective synthesis of 3-formylpyrazolo[1,5- a]pyrimidines 4a-k in good yields through a microwave-assisted process is provided. The synthesis proceeds via a cyclocondensation reaction between β-enaminones 1 with NH-3-aminopyrazoles 2, followed by formylation with an iminium salt moiety (Vilsmeyer-Haack reagent). These N-heteroaryl aldehydes 4 were successfully used as strategic intermediates for the preparation of novel functional fluorophores with yields up to 98%. The structures of the products obtained and regioselectivity of the reactions were determined on the basis of NMR measurements and X-ray diffraction analysis. Since pyrazolo[1,5- a]pyrimidines (PPs) 3 have shown an important fluorescence, photophysical properties of four 2-methylderivatives substituted at position 7 with different acceptor (A) or donor (D) groups were investigated. The compounds evaluated exhibited large Stokes shift in different solvents, but only the substituted p-methoxyphenyl (4-An) showed a strong fluorescence intensity with quantum yields up to 44% due to its greater…

An efficient copper-catalyzed radical cascade cyclization strategy was developed, by which a wide variety of 3-sulfonyl substituted indenones were prepared in one pot via reaction of 2-alkynylbenzonitriles with sulfonyl hydrazides in the presence of TBHP and CuI under mild reaction conditions. Much more importantly, the 3-sulfonyl indenones, synthesized through our newly developed copper-catalyzed radical cascade cyclization strategy, were found to own typical aggregation-induced emission (AIE) properties, showing orange to red emission with large Stokes shift (more than 135 nm). In addition, such newly found AIEgens could be successfully used in live cell imaging, exhibiting excellent biocompatibility and application potential.

A simple and efficient tert-butyl hydroperoxide-mediated direct trifluoromethylation of indazoles using sodium trifluoromethanesulfinate has been developed under metal-free conditions. A library of trifluoromethylated products with broad functionalities has been synthesized with moderate to good yields. A radical mechanistic pathway has been proposed for the present protocol.

Hemoproteins have recently emerged as promising biocatalysts for promoting a variety of carbene transfer reactions including cyclopropanation and Y-H insertion (Y = N, S, Si, B). For these and synthetic carbene transfer catalysts alike, achieving high chemoselectivity toward cyclopropanation in olefin substrates bearing unprotected Y-H groups has proven remarkably challenging due to competition from the more facile carbene Y-H insertion reaction. In this report, we describe the development of a novel artificial metalloenzyme based on an engineered myoglobin incorporating a serine-ligated Co-porphyrin cofactor that is capable of offering high selectivity toward olefin cyclopropanation over N-H and Si-H insertion. Intramolecular competition experiments revealed a distinct and dramatically altered chemoselectivity of the Mb(H64V,V68A,H93S)[Co(ppIX)] variant in carbene transfer reactions compared to myoglobin-based variants containing the native histidine-ligated heme cofactor or other metal/proximal ligand substitutions. These studies highlight the functional plasticity of myoglobin as…

The synthesis of 1-methylphenoxazine via CO 2 -directed lithiation chemistry is reported. This electron donor was coupled with 2,8-dibromodibenzothiophene- S, S -dioxide with Buchwald–Hartwig chemistry to give a new donor–acceptor–donor charge-transfer fluorescent molecule 1b . X-ray crystal structures and calculations show that the phenoxazinyl groups are coplanar and equatorial (eq) to the acceptor plane in nonmethylated 1a but are pyramidal and axial (ax) in 1b . The bond rotation energy barriers between donor and acceptor groups for 1a and 1b are only 0.13 and 0.19 eV, respectively, from hybrid-DFT computations at the CAM-B3LYP/6-31G(d) level. Many possible conformers are present in solutions and in zeonex. In zeonex, the methyl groups in 1b shift the emission band 0.13 eV higher in energy compared to 1a . Excited state eq–eq and ax–ax geometries were identified with DFT calculations with charge transfer (CT) emission assigned as 1 CT(eq) and 1 CT(ax) dominating. The lower energy 1 CT(eq) contributes to thermally activated delayed fluorescence, whereas the higher energy 1 CT(ax)…

A green, aerobic sulfenylation of imidazo[1,2- a ]pyridines was performed using thiols, a flavin-and-iodine dual catalytic system, and environmentally benign molecular oxygen as the only sacrificial reagent. The dual metal-free catalysts smoothly promote a unique stepwise tandem process, beginning with the aerobic oxidation of a thiol to afford a disulfide that is utilized in the oxidative sulfenylation of the imidazo[1,2- a ]pyridine. This process has afforded diverse 3-sulfenylimidazo[1,2- a ]pyridines of biological interest and is environmentally friendly, as benign H 2 O is the only byproduct.

We report a highly efficient method to construct 3-trifluoromethyl coumarins using CF 3 SO 2 Cl as the trifluoromethyl radical source with ester 3-arylpropiolates. The reaction incorporated a cascade cyclization/dearomatization/ester migration/oxidization/rearomatization process to afford various 3-trifluoromethyl coumarins under visible light irradiation in good to excellent yields.

Herein we report a novel C–S bond cleavage and reconstruction strategy for the synthesis of thiocyanates through direct photocatalytic S–H bond cyanation from thiols and inorganic thiocyanate salts. In our strategy, the unprecedented example of cutting off C–S bond of SCN – to deliver the green “CN” sources is demonstrated. This transformation features nontoxic and inexpensive “CN” sources, available starting materials, metal-/base-/ligand-/peroxide-free, high step economy and mild conditions. It leads to the construction of various thiocyanates and some medicinally and biologically active thiocyanate-containing molecules.

A visible-light-mediated decarboxylative cyclization of N-acyloxylphthalimides with vinyl azides has been developed under metal-free conditions. This protocol features mild conditions, a broad substrate scope, and an excellent functional group tolerance, thus providing a facile and efficient access to substituted phenanthridines. Control experiments revealed that the reaction proceeded via a radical process.

An efficient, three-component strategy for Rh(III)-catalyzed annulation of readily available 3-aminopyrazoles, aldehydes, and sulfoxonium ylides to give diverse pyrazolo[1,5- a]pyrimidines is disclosed. The reactions were performed under straightforward benchtop conditions using microwave heating with short reaction times. Good yields were obtained for many substituted aminopyrazoles and a very large variety of aromatic and heteroaromatic aldehydes, including those incorporating electron-withdrawing, electron-donating, basic nitrogen, halide and acidic functionality. Ester and methoxy functionalities could also be directly installed on the pyrimidine ring by employing ethyl glyoxylate and trimethyl orthoformate in place of the aldehyde, respectively. In addition, a range of sulfoxonium ylides provided products in good yields to establish that aryl, heteroaryl, and branched and unbranched alkyl substituents can be introduced with this reagent. Finally, the first use of a formyl sulfoxonium ylide in a chemical transformation enabled the preparation of products with only a single…

A series of air-stable, easily accessible tridentate ferrocene-based diamine-phosphine sulfonamide (f-diaphos) ligands were successfully developed for iridium-catalyzed asymmetric hydrogenation of ketones. The f-diaphos ligands exhibited excellent enantioselectivity and superb reactivity in Ir-catalyzed asymmetric hydrogenation of ketones (for arylalkyl ketones, ( S)-selectivity, up to 99.4% ee, and 100 000 TON; for diaryl ketones, ( R)-selectivity, up to 98.2% ee, and 10 000 TON). This protocol could be easily conducted on gram scale, thereby providing a chance to various drugs.