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The rhenium(I)-catalyzed generation of α,β-unsaturated carbene complex intermediates from easily available propargyl ethers was achieved for the concise construction of cycloheptadiene derivatives through the formal [4+3] cycloaddition reaction with siloxydienes.

The transformation of a single C−F bond of trifluoromethylarenes bearing a hydrosilyl group at the ortho position was achieved. The activation of the hydrosilyl group with a trityl cation in the presence of nucleophiles allowed for selective C−F bond functionalization, for example, by allylation, carboxylation, or chlorination. Further derivatization of the resulting fluorosilylarenes afforded various aromatic difluoromethylene compounds.

We have achieved a facile and convenient synthesis of a variety of 3,5-dioxopentanoates (3,5-diketo esters) and 3-amino-5-oxopent-3-enoates by a zinc-mediated condensation of readily available 3-oxopropanenitriles (α-cyano ketones) with ethyl bromoacetate. The reaction is a variation on the classical Blaise reaction, tuned to the synthesis of trifunctional compounds having 3,5-diketo ester or 3-enamino 5-keto ester functional groups. Our studies revealed that the Blaise reaction on the nitrile occurs in preference to the Reformatsky reaction on the neighboring ketone when the two functional groups are in a geminal relationship, as found in α-cyano ketones, possibly due to zinc complexation leading to increased electrophilicity of the nitrile.

The enantioselective conjugate alkynylation of β-aryl-β-trifluoromethyl enones has been carried out using terminal alkynes and diethylzinc in the presence of 3,3′-bis(perfluorophenyl)BINOL as the chiral ligand to give the corresponding ketones bearing a trifluoromethylated propargylic quaternary stereocenter with fair to good enantioselectivities. Enones bearing a bulky 2-naphthyl attached to the carbonyl group provided the best enantioselectivities. The synthetic applicability of the resulting products has been demonstrated with their iodocyclization to form 4H-pyrans.

Theoretical reactivity indices based on the conceptual Density Functional Theory (DFT) have become a powerful tool for the semiquantitative study of organic reactivity. A large number of reactivity indices have been proposed in the literature. Herein, global quantities like the electronic chemical potential μ, the electrophilicity ω and the nucleophilicity N indices, and local condensed indices like the electrophilic P k + and nucleophilic P k − Parr functions, as the most relevant indices for the study of organic reactivity, are discussed.

Recent advances in the field of ring-expansion chemistry, involving 1-azoniabicyclo[n.1.0]alkane scaffolds (bicyclic aziridinium ions) as key transient intermediates, have made it possible to efficiently construct a broad variety of medium- and large-sized functionalized nitrogen-containing heterocycles. In this tutorial review, a comprehensive survey of all pathways leading to the generation of 1-azoniabicyclo[n.1.0]alkanes is provided, as well as a discussion on their subsequent ring expansions to relevant azaheterocycles governed by ring size, substitution pattern, and/or nature of applied nucleophiles.

The present text discussed about the recent developments and applications of the Ullmann reaction in respect of the C–C bond formation. The major drawback of the Ullmann reaction, i.e., harsh reaction condition has recently been overcome with the development of various synthetic methodologies. Green synthetic methodologies such as metal-, ligand-, and additive free conditions, recyclable heterogenous catalysts, microwave- and ultrasound-assisted synthesis, etc. have got special importance in this field. This text lucidly describes all these recently developed synthetic methodologies which make the century old Ullmann reaction much efficient, effective, economical and attractive in the field of synthetic organic chemistry. On-surface Ullmann coupling for the C–C bond formation, i.e., invoking C–C coupling reactions on a reactive surface has been discussed. All such developments of the Ullmann C–C coupling facilitate its application in the synthesis of bio-active heterocycles, drug-like molecules and natural products which has also been discussed in this text.

Three phosphates MPb4(PO4)3 (M = K, Rb, Cs) have been synthesized by the high temperature melt method. The single-crystal X-ray structural analyses reveal that all of them belong to apatite-type phases and crystallize in the same space group, P63/m (no. 176). They exhibit a three dimensional (3D) structure that is composed of two kinds of channels constructed by [Pb(1)O6] and [PO4]. And the [Pb(2)|K(1)] ([Pb(2)|Rb(1)], [Pb(2)|Cs(1)]) atoms are located in the small channels. Detailed structural comparison indicates that the cations effect on the framework geometry is less obvious among the title compounds and the reported lead apatite-type phosphates, however, although MPb4(PO4)3 (M = K, Rb, Cs) have the similar stoichiometry with MM'4(BO3)3, the different coordination of the B and P atoms, as well as the cations effect make MPb4(PO4)3 and MM'4(BO3)3 crystallize in various space groups. The IR spectra were used to verify the validity of their structure. The TG-DSC analysis results indicate that KPb4(PO4)3 and RbPb4(PO4)3 melt congruently. The UV–Vis–NIR diffuse reflectance spectra indicate that they have no obvious absorption from 300 to 2500 nm. Optical properties as well as band structure calculations have been also performed based on density functional theory methods.

The novel and one-pot synthesis of 5-hydroxyl hydantoins from Ugi five-component condensation procedures is reported. The transformation was promoted via a microwave heating method and provided 5-hydroxyl hydantoins in workable yields, representing a direct approach to this synthetically challenging and biologically interesting pharmacophore.

A consolidated review on the emergent supramolecules of thiacalixarenes in crystal engineering and molecular recognition contributed from our group is presented. Our simple synthetic method of thiacalixarenes offered improved yields of larger macrocyclic thiacalix[6/8]arenes by carefully adjusting NaOH concentration, temperature, and reaction time. In crystallographic analysis, complexes of thiacalixarenes with alkali metals and rare earth metals build up fascinating assemblies, such as dimeric formations, hetero-alkali metallic thiacalixarenes, one-dimensional ‘ladder-type’ coordination polymers, and one-dimensional hydrogen-bonded polymers. In addition, halogenated thiacalixarenes having various alkyl ethers assemble each other via three halogen interactions of halogen bonding, halogen–halogen interactions, and halogen-π interactions. Liquid–liquid extraction studies using ligand-functionalized thiacalixarene-based extractants developed for separation of precious metals from the last 10 years are discussed.

This review first outlines general considerations on phosphinic acids and derivatives as bioisosteric groups. The next sections present key aspects of phosphinic acid-based molecules and include a brief description of the biological pathways involved for their activities. The synthetic aspects and the biological activities of such compounds reported in the literature between 2008 and 2013 are also described.

Although acylammonium salts are well-studied, chiral α,β-unsaturated acylammonium salts have received much less attention. While these intermediates are convenient synthons, which are readily available from several commodity unsaturated acids and acid chlorides, and possess three reactive sites, their application in organic synthesis has been limited because of the lack of appropriate chiral Lewis bases for their generation. In recent years, the utility of chiral, unsaturated acylammonium salts has expanded considerably, thus demonstrating the unique reactivity of this intermediate leading to the development of a diverse array of catalytic, asymmetric transformations including organocascade processes. This Minireview highlights the recent and growing interest in these intermediates which might spark further research into their untapped potential for asymmetric organocascade catalysis. A cursory comparison is made to related unsaturated iminium and acylazolium intermediates.

ConspectusSingle-molecule magnets (SMMs) can retain their magnetization status preferentially after removal of the magnetic field below a certain temperature. The unique property, magnetic bistable status, enables the molecule-scale SMM to become the next-generation high-density information storage medium. SMMs’ new applications are also involved in high-speed quantum computation and molecular spintronics. The development of coordination chemistry, especially in transition metal (3d) and lanthanide (4f) complexes, diversifies SMMs by introducing new ones. In both 3d and 4f SMMs, the ligands play a fundamental role in determining the SMMs’ magnetic properties. The strategies for rationally designing and synthesizing high-performance SMMs require a comprehensive understanding of the effects of a crystal field.In this Account, we focus mainly on the magneto-structural correlations of 4f or 3d single-ion magnets (SIMs), within which there is only one spin carrier. These one-spin carrier complexes benefit from...

The first utility of praseodymium as a mediating metal in the Barbier reaction of carbonyl compounds with allyl halides was reported in this paper. In contrast to the traditional metal-mediated or catalyzed Barbier reactions, exclusive α-adducts were obtained in this one-pot reaction with a broad scope of substrates and feasible reaction conditions.

Reaction of 3-alkyl-1,2,4-triazolo[1,5-a]benzimidazoles with butylmagnesium bromide follows two hetarylotropic rearrangements to afford 1,2-bis(1H-benzimidazol-2-yl)-1,3-dialkylguanidines and 2-(1’H-1,2’-dibenzimidazol-2-yl)-1,3-dialkylguanidines.

The synthesis of α-amino carbonyl/carboxyl compounds is a contemporary challenge in organic synthesis. Herein, we present a stereoselective α-amination of amides employing simple azides that proceeds under mild conditions with release of nitrogen gas. The amide is used as the limiting reagent, and through simple variation of the azide pattern, various differently substituted aminated products can be obtained. The reaction is fully chemoselective for amides even in the presence of esters or ketones and lends itself to preparation of optically enriched products.

Two new C-glucosyl chromones named aloeverasides A (1) and B (2) were isolated from the resin of Aloe vera (L.) Burm.f. The structures of the two new natural products were elucidated based on 1D- (1H- and 13C-NMR) and 2D-NMR (COSY, HSQC, and HMBC) spectroscopic techniques and mass spectrometry (ESI-MS). Aloeverasides A (1) and B (2) were evaluated for their anticancer activity, and both induced a 76.4 and 70.5% growth inhibition of the breast cancer cell line (MDA-MB-231) at a concentration of 100 μm. Both compounds were also evaluated for their 1,1-diphenyl-2-picryl-hydrazyl antioxidant, urease enzyme, and α-glucosidase enzyme inhibition activities. Aloeverasides A (1) and B (2) displayed good urease enzyme inhibition activities (62 and 55%, resp.), as well as antioxidant activity in which aloeveraside A (1) had a value of 60% inhibition, while aloeveraside B (2) demonstrated a more potent antioxidant activity with 80% inhibition.

Stilbenes react with the hypervalent iodine compound (II) as nitrogen source to give intermediate imines which undergo iron catalyzed conversion into various benzamides in the presence of air.

Asymmetric epoxidation of electron-deficient olefins catalyzed by a biomimetic iron complex in a continuous-flow microreactor is described. The reaction conducted in the microreactor is characterized by rapid (

An efficient, four-component, one-pot condensation reaction of phthalimide or phthalic anhydride, aromatic aldehydes, and ethyl cyanoacetate for the synthesis of 1H-pyrazolo[1,2-b]phthalazine-5,10-dione derivatives mediated by L-proline in excellent yields is reported.

This mini-review summarizes the progress in the asymmetric epoxidation of olefins in the presence of manganese aminopyridine complexes, achieved in the last decade. The major breakthroughs in catalyst design, that eventually led to the emergence of highly enantioselective (> 99% ee ) and efficient (> 1000 TON) catalysts, are discussed. The mechanistic studies carried out in recent years are given particular attention.

A novel rearrangement of 2-vinyl aziridine 2-carboxylates to unusual chiral cyclic sulfoximines is described herein. The method allows the synthesis of substituted cyclic sulfoximines in high yields with complete stereocontrol, and tolerates a wide substrate scope. A one-pot process starting directly from sulfinimines provides access to complex chiral sulfoximines in only two steps from commercially available aldehydes. A mechanistic hypothesis and synthetic application in the formal synthesis of trachelanthamidine, by transformation of a cyclic sulfoximine into a pyrroline, is also disclosed.

Study of the intramolecular aza-Michael addition reaction from an aminofluorovinylsulfone opens a new route for the synthesis of pyrrolidine derivatives. An unexpected diastereoselective cyclization reaction was observed, leading preferentially to the anti-N-benzylpyrrolidine sulfone. The resulting sulfone was reacted with aldehydes to access β-substituted α-fluoroalkenyl pyrrolidines in one step.

In this new Ag(I)-promoted reaction between N-arylacrylamides and ethyl trimethylsilyldifluoroacetate, the corresponding 3-(2-ethoxycarbonyl-2,2-difluoroethyl)-2-oxo-2,3-dihydro-1H-indoles have been prepared in good yields.

Intramolecular oxidative carbonylation reaction is an efficient approach for constructing heterocycles. However, stoichiometric amount of hypervalent metal salts is usually required in this transformation. Here we show an aerobic intramolecular oxidative carbonylation of enamides by combining palladium and photoredox catalysis. The dual catalytic system enables oxygen directly as oxidant, which provides a mild and environmentally friendly method for the synthesis of 1,3-oxazin-6-ones.

The gold(I)-catalyzed domino-cyclization of 1,6-Diynes with a t-butylcarbonate group in the propargylic position affords α-hydroxycyclohexenones.

This paper discloses the first example of photocatalytic direct decarboxylative hydroxylation of carboxylic acids. It enables the conversion of a variety of readily available carboxylic acids to alcohols in moderate to high yields. This unprecedented protocol is accomplished under extremely mild reaction conditions using molecular oxygen (O2) as a green oxidant and using visible light as a driving force.

A convenient method has been developed for the Pechmann reaction of phenols and β-keto esters catalyzed by meglumine sulfate. Solvent-free conditions, inexpensive catalyst, short reaction times, high yield, and ease of purification of the products are the advantages of this protocol. This novel catalytic system is expected to contribute to the development of more benign Pechmann condensation reactions of phenols with β-keto esters.

The exploitation of peptides in the development of smart nanomaterials is gaining increasing attention in the last few years. Amino acids are indeed able to drive the self-assembly and the self-organization at the molecular level. By using non-standard amino acids, it is possible to expand the scope of the possible applications, ranging from biomaterials, biosensors to drug delivery systems. In this digest, the recent advances in this field are presented.

A branching double-annulation cascade (BDAC) strategy for diverse and complex fused THIQ scaffolds via a highly reactive iminium-induced one-pot double-cyclization sequence involving Pictect–Spengler-type cyclization has been developed for the first time. The salient features of this protocol are that it allows direct and rapid access to unprecedented diverse fused THIQ skeletons, is metal/catalyst free, has a cleaner reaction profile, provides good to excellent yields, and is a convenient approach. This catalyst-free domino process facilitates the double annulation with a variety of scaffold building agents via two C–N and one C–X (X = C, N, O) bond formation in a single step under uniform reaction conditions. Furthermore, we reveal an unusual dual BDAC sequence leading to N–N-linked isoquinoline dimer.

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium-activated alcohols as intermediates. The novel method, which can be even performed under solvent-free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste-balance (E-factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one-pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac-Clopidogrel and S-Fendiline.

A highly efficient metal and protection-free approach for the regioselective synthesis of C-3-functionalized quinolines from azadienes (in situ generated from 2-aminobenzyl alcohol) and terminal alkynes through [4 + 2] cycloaddition has been developed. An unprecedented reaction of 2-aminobenzyl alcohol with 1,3- and 1,4-diethynylbenzene provided the C-3 tolylquinolines via [4 + 2] HDA and oxidative decarboxylation. The −NH2 group directed mechanistic approach was well supported by the control experiments and deuterium-labeling studies and by isolating the azadiene intermediate. The reactivity and selectivity of unprotected azadiene in metal-free base-assisted hetero-Diels-Alder reaction is exploited to quickly assemble an important class of C-3-functionalized quinolines, which are difficult to access.

Chromium can exist as both trivalent Cr(III) and hexavalent Cr(VI) in typical drinking water conditions, with Cr(VI) being of particular concern due to its high toxicity and new regulatory perspectives. This study critically reviewed the occurrence and speciation of chromium in drinking water distribution systems in the U.S., based on a detailed analysis of the up-to-date EPA Unregulated Contaminant Monitoring Rule (UCMR) database. Data show that the nationwide Cr(VI) levels in drinking water ranged from non-detectable to 97 μg L−1 at the entry point to drinking water distribution systems, and between non-detectable and 67 μg L−1 at the maximal residence time of distribution systems. Geographic distributions show that higher drinking water Cr(VI) concentrations were observed in Southwest U.S. and were closely associated with the dependence on groundwater as a drinking water source. While Cr(VI) and total chromium concentrations showed either an increase or a decrease between the entry point and the maximal residence time of drinking water distribution systems, they suggested complex physicochemical processes that can act as both sources and sinks of chromium in distribution systems, including the oxidation of Cr(III)-containing solids by residual disinfectants and the adsorption of Cr(VI) by corrosion scales. Time-dependent data analysis revealed that a considerable fraction of Cr(III) at the entry point to distribution systems was inadvertently converted to Cr(VI) by the time the drinking water reached the maximal residence time of distribution systems, and this conversion was positively correlated with the presence of residual disinfectants. Data analyses suggest that the reactivity of downstream water distribution should be managed to control chromium in tap water.

The reactivity of the azomethine ylides in cycloaddition reactions is improved by the presence of electron-deficient aromatic rings as well as the presence of ortho substituents relative to the aminomethyl group.

The first example of Cu-promoted cyclization of α-amino nitrile-tethered enynes incorporating an electron-deficient alkene component is described. A wide range of functionalized 3-azabicyclo[4.1.0]hepta-2,4-dienes and 4,5-dihydro-3H-azepines were prepared efficiently in a controllable manner. Moreover, the diverse cascade process enables efficient incorporation of tertiary amine moieties under mild reaction conditions. A possible reaction pathway is proposed on the basis of a series of control experiments.

The design and preparation of recyclable catalysts are of great economic and environmental importance in the chemical and medicinal industries. Immobilization of homogeneous catalysts on various in...

A formal extension of the Passerini reaction to thiocarbonyls leads to thiophthalides via intermediate formation of a sulfanyl-phthalide followed by insertion of isocyanide.

A simple yet effective method for the formation of thiophene-fused π-systems is reported. When arylethynyl-substituted polycyclic arenes were heated in DMF in the presence of elemental sulfur, the corresponding thiophene-fused polycyclic arenes were obtained via cleavage of the ortho-C–H bond. Thus, arylethynylated naphthalenes, fluoranthenes, pyrenes, corannulenes, chrysenes, and benzo[c]naphtho[2,1-p]chrysenes were effectively converted into the corresponding thiophene-fused π-systems. Apart from polycyclic hydrocarbons, thiophene derivatives are also susceptible to this reaction. The practical utility of this reaction is demonstrated by preparations on the decagram scale, one-pot two-step reaction sequences, and multiple thiophene annulations.

Exploration of scope of an optimized one-pot sequential procedure for preparing of 2,4-di- and 2,4,5-tri-substituted thiazoles has been accomplished. The synthesis was performed by the initial formation of a β-keto-thioester intermediate from nucleophilic substitution of α-bromoketones with thioacid potassium salts, followed by treatment with ammonium acetate and one equivalent of acetic acid in toluene to form imine intermediate eventually leading to cyclization yielding thiazoles. This procedure should be highlighted with a flexible way to control the substitution pattern around thiazole ring by choosing appropriately substituted α-bromoketones even containing acid labile functionality and thioacid potassium salts, and thus its applicability is very wide.

Lingzhifuran A (1) and lingzhilactones D–F (2–4), four new phenolic meroterpenoids were isolated from the fruiting bodies of Ganoderma lucidum. Their structures were identified by spectroscopic data. Chiral HPLC analysis indicates the racemic nature of 2–4. Chiral separation followed by X-ray diffraction analysis discloses the absolute configuration of (−)-2. Compounds 1 and 2 could selectively inhibit TGF-β1-induced Smad3 phosphorylation in rat renal tubular epithelial cells, representing novel scaffolds of selective Smad3 activation inhibitors. Total synthesis accompanied by in vivo rodent experiments reveals antifibrotic activities of 1 against kidney fibrosis. Finally, a plausible biosynthetic pathway for 1 was proposed.

The approach is based on the reaction of cyclic anhydrides with guanidinium hydrochloride as the nitrogen source.