Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles.

Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-ß-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Enantioselective synthesis of 3a-azido-pyrroloindolines by copper-catalyzed asymmetric dearomative azidation of tryptamines.

Copper-catalyzed asymmetric dearomative azidation of tryptamines using azidobenziodoxolone as an azidating reagent was developed, which affords a variety of 3a-azido-pyrroloindolines in good to high enantioselectivities under mild reaction conditions. The azides could be readily transformed into the corresponding 3a-amino-pyrroloindolines via reduction and 1,2,3-triazole derivatives via a click reaction.

Azidobenziodazolones as Azido Sources for the Enantioselective Copper-Catalyzed Azidation of N-Unprotected 3-Trifluoromethylated Oxindoles.

Both azido (N3) and trifluoromethyl (CF3) groups are key moieties of numerous valuable molecules that are extensively applied in drug discovery, chemical biology, and synthetic chemistry. However, the asymmetric construction of chiral quaternary stereocenters bearing both N3 and CF3 groups is still unexplored. Herein, we report a kind of bench-stable and easily adjustable benziodazolone-based azidating reagents. These reagents were used to achieve an enantioselective copper-catalyzed azidation of N-unprotected 3-trifluoromethylated oxindoles to provide diverse enantioenriched 3-N3-3-CF3 oxindoles.

Simple and Versatile Nitrooxylation: Noncyclic Hypervalent Iodine Nitrooxylating Reagent.

Organic nitrates are broadly applied as pharmaceuticals (acting as efficient nitric oxide donor), energetic materials, building blocks in organic synthesis, etc. However, practical and direct methods to access organic nitrates efficiently are still rare, mainly due to the lack of powerful nitrooxylating reagents. Herein, we report bench-stable and highly reactive noncyclic hypervalent iodine nitrooxylating reagents, oxybis(aryl-λ3 -iodanediyl) dinitrates (OAIDNs, 2), which are prepared just by using aryliodine diacetate and HNO3 . The reagents are used to achieve a mild and operationally simple protocol to access diverse organic nitrates. By employing of 2, zinc-catalyzed regioselective nitrooxylation of cyclopropyl silyl ethers is realized efficiently to access the corresponding ß-nitrooxy ketones with high functional-group tolerance. Moreover, a series of direct and catalyst-free nitrooxylations of enolizable C-H bonds are carried out smoothly to afford the desired organic nitrates within minutes by just mixing the substrates with 2 in dichloromethane.

Mechanical and Microcrack Evolution Characteristics of Roof Rock of Coal Seam with Different Angle of Defects Based on Particle Flow Code.

The creation of the natural ceiling rock of the coal seam is rife with fractures, holes, and other flaws. The angle of the defects has a significant influence on the mechanical characteristics and crack evolution of coal seam roof rock. Multi-scale numerical simulation software PFC2D gets adapted to realize the crack propagation and coalescence process in the roof rock of a coal seam with different angles of defects under uniaxial compression. The effect of flaw angles on the micro and macro mechanical characteristics of rock is also discovered. The results show that: (1) the defect angle has influence on the stress-strain, elastic modulus, peak strength, peak strain, acoustic emission (AE) and strain energy of roof rock of coal seam. When the defect angles are different, the starting position of the roof rock in a coal seam fracture is different. The quantity of microcracks firstly reduces with an increase in defect angles before gradually increasing. At the same fault angle, the cracks are mostly tensile ones and only a few shear ones. (2) When the defect angle is less than 90°, tensile and shear fractures are mostly localized at the defect's two tips and propagate along the loading direction. When the defect angle is 90°, the tensile and shear cracks are not concentrated at the tip of the defect. (3) As the defect angles increase, the elastic strain energy rises initially and then falls, and the dissipated energy and total input energy both increase continuously. The elastic strain energy is greatest at the highest strength. The study provides a certain reference for the use of various analysis methods in practical engineering to evaluate the safety and stability of rock samples with pre-existing defects.

Acid-Free Copper-Catalyzed Electrophilic Nitration of Electron-Rich Arenes with Guanidine Nitrate.

A practical copper-catalyzed nitration of electron-rich arenes with trimethylsilyl chloride and guanidine nitrate is reported. A variety of nitrated products were generated in moderate to excellent yields (32-99%) at ambient temperature under acid-free, open-flask, and operationally simple conditions.

Tailoring Sensors and Solvents for Optimal Analysis of Complex Mixtures Via Discriminative 19F NMR Chemosensing.

Separation-free analytic techniques capable of providing precise and real-time component information are in high demand. 19F NMR-based chemosensing, where the reversible binding between analytes and a 19F-labeled sensor produces chromatogram-like output, has emerged as a valuable tool for the rapid analysis of complex mixtures. However, the potential overlap of the 19F NMR signals still limits the number of analytes that can be effectively differentiated. In this study, we systematically investigated the influence of the sensor structure and NMR solvents on the resolution of structurally similar analytes. The substituents adjacent and distal to the 19F labels are both important to the resolving ability of the 19F-labeled sensors. More pronounced separation between 19F NMR peaks was observed in nonpolar and aromatic solvents. By using a proper sensor and solvent combination, more than 20 biologically relevant analytes can be simultaneously identified.

Expanding the Boxmi Ligand Family: Synthesis and Application of NON and NSN Ligands.

Two synthetic strategies for a new family of neutral NON ligands featuring a "bis(oxazolinylmethylidene)isobenzofuran" framework (boxman) are reported. A Pd-mediated cyclization reaction forming the isobenzofuran core constitutes the key reaction in the eight-step synthetic route to the nonbackbone-methylated target compound H,Rboxman. In contrast, the introduction of two additional methyl groups provides stereochemical control during backbone construction and thereby access to the methylated derivative Me,Rboxman, which was synthesized in five steps and improved yields. In addition, the synthetic sequence was transferred to the thio analogue, providing access to the NSN ligand H,Rboxmene. Subsequent complexation experiments with iron and cobalt chloride precursors afforded the four-coordinated chlorido complexes Me,RboxmanMCl2 (R = Ph, iPr; M = Fe, Co) and established the boxman family as trans-chelating, bidentate bis(oxazoline) ligands. Application of the latter in the nickel(II)- and zinc(II)-catalyzed α-fluorination of ß-ketoesters and oxindoles (up to 98% yield and 94% ee) demonstrated their suitability for enantioselective catalysis.

The Enrichment Process of Groundwater Fluorine in Sea Water Intrusion Area of Gaomi City, China.

A typical area, Gaomi City in China, was chosen to discuss the enrichment process of groundwater fluorine in sea water intrusion area. The groundwater had fluorine levels of 0.09-10.99 mg/L, with an average concentration of 1.38 mg/L. The high-fluorine groundwater was mainly distributed in the unconsolidated Quaternary sediments, where concentrations in 83.6% of the samples exceeded the national limit of 1.0 mg/L. The groundwater in the Quaternary sediments also had higher levels of Cl- , TDS, Mg2+ , and pH and lower levels of Ca2+ , Co, Ni, and Cu than that in the bedrock. The groundwater fluorine levels in the Quaternary sediments are positively correlated with Cl- , TDS, Mg2+ , pH, and negatively correlated with Ca2+ , γCa2+ /γMg2+ , Co, Ni, Cu. Geochemical indices of Cl- and TDS indicate sea water intrusion in the Quaternary high-fluorine groundwater area (F- > 1.0 mg/L), while they do not indicate any intrusion in the bedrock area. The chemical weathering of minerals was intensified with the intrusion of sea water. Cation exchange was confirmed to occur in the Quaternary sediments and was promoted by sea water intrusion. Cation exchange consumes part of groundwater Ca2+ and permits more F- dissolving. Consequently, in the Quaternary sediments, the groundwater was supersaturated with CaF2 minerals and undersaturated with MgF2 minerals when F- > 1.0 mg/L, while CaF2 and MgF2 minerals both are undersaturated when F- < 1.0 mg/L. Thus, the chemical weathering of minerals and cation exchange caused by sea water intrusion are the crucial processes controlling the groundwater fluorine levels, which should be considered when the groundwater fluorine enrichment mechanism is discussed along coastal zones.

The Enrichment Process of Groundwater Fluorine in Seawater Intrusion Area of Gaomi City, China.

A typical area, Gaomi City in China, was chosen to discuss the enrichment process of groundwater fluorine in seawater intrusion area. The groundwater had fluorine levels of 0.09-10.99 mg/L, with an average concentration of 1.38 mg/L. The high-fluorine groundwater was mainly distributed in the unconsolidated Quaternary sediments, where concentrations in 83.6% of the samples exceeded the national limit of 1.0 mg/L. The groundwater in the Quaternary sediments also had higher levels of Cl- , TDS, Mg2+ , pH and lower levels of Ca2+ , Co, Ni, Cu than that in the bedrock. The groundwater fluorine levels in the Quaternary sediments are positively correlated with Cl- , TDS, Mg2+ , pH, and negatively correlated with Ca2+ , γCa2+ /γMg2+ , Co, Ni, Cu. Geochemical indexes of Cl- and TDS indicate seawater intrusion in the Quaternary high-fluorine groundwater area (F- > 1.0 mg/L), while they do not in the bedrock area. The chemical weathering of minerals was intensified with the intrusion of seawater. Cation exchange was confirmed to occur in the Quaternary sediments, and was promoted by seawater intrusion. Cation exchange consumes part of groundwater Ca2+ and permits more F- dissolving. Consequently, in the Quaternary sediments, the groundwater was super-saturated with CaF2 minerals and under-saturated with MgF2 minerals when F- > 1.0 mg/L, while CaF2 and MgF2 minerals both are under-saturated when F- < 1.0 mg/L. Thus, the chemical weathering of minerals and cation exchange caused by seawater intrusion are the crucial processes controlling the groundwater fluorine levels, which should be considered when the groundwater fluorine enrichment mechanism is discussed along coastal zones. This article is protected by copyright. All rights reserved.

Rhodium-Catalyzed Successive C-H Bond Functionalizations To Synthesize Complex Indenols Bearing a Benzofuran Unit.

An efficient rhodium-catalyzed redox-neutral annulations of N-phenoxyacetamides and ynones via successive double C-H bond activations has been developed. A series of novel and complex indenols bearing a benzofuran unit were generated with moderate to excellent regioselecetivities under mild conditions. Adding N-ethylcyclohexanamine (CyNHEt) could restrict the formation of the mono C-H bond activation byproduct, which is not the intermediate of the reaction demonstrated via the mechanistic investigations.

Iron-Catalyzed Nitrene Transfer Reaction of 4-Hydroxystilbenes with Aryl Azides: Synthesis of Imines via C═C Bond Cleavage.

C═C bond breaking to access the C═N bond remains an underdeveloped area. A new protocol for C═C bond cleavage of alkenes under nonoxidative conditions to produce imines via an iron-catalyzed nitrene transfer reaction of 4-hydroxystilbenes with aryl azides is reported. The success of various sequential one-pot reactions reveals that the good compatibility of this method makes it very attractive for synthetic applications. On the basis of experimental observations, a plausible reaction mechanism is also proposed.

Enantioselective Copper-Catalyzed Electrophilic Dearomative Azidation of ß-Naphthols.

The first example of copper-catalyzed enantioselective dearomative azidation of ß-naphthols using a readily available N3-transfer reagent is reported. A series of 2-hydroxy-1-naphthamides bearing a complex N-substituent were converted to the corresponding products in high yields with up to 96% ee, and chiral 1-azido-2-hydroxy-1-naphthoates were obtained with up to 90% ee under mild reaction conditions. The azides could be further transformed into the corresponding 1,2,3-triazoles smoothly via "click" reaction.

Electron-Deficient Alkynes as Dipolarophile in Pd-Catalyzed Enantioselective (3 + 2) Cycloaddition Reaction with Vinyl Cyclopropanes.

The activated alkynes have been used successfully for the first time as the dipolarophile in the palladium-catalyzed asymmetric (3 + 2) cycloaddition, affording highly functionalized cyclopentenes in good to high yields with high chemoselectivities and good to high enantioselectivities. The introduction of an additional carbonyl group at the α-position of the alkynyl esters is the key to activating the carbon-carbon triple bond. The reaction process was investigated, and an inverse process of Pd-catalyzed (3 + 2) cycloaddition was observed.

Nucleophilic Substitution of gem-Difluoroalkenes with TMSNu Promoted by Catalytic Amounts of Cs2CO3.

The efficient and practical nucleophilic cyanation and trifluoromethylation with appropriate trimethylsilyl nucleophiles were developed. Catalytic amounts of cheap and nontoxic Cs2CO3 were used to maintain a sufficiently high concentration of nucleophilic anion (CN- or CF3-) which could begin the catalytic cycle. The present methodologies provide diverse functionalized monofluoroalkenes bearing a cyano and trifluoromethyl group with excellent to moderate stereoselectivities.

Difluorocarbene-derived trifluoromethylselenolation of benzyl halides.

Cu-Promoted difluorocarbene-derived trifluoromethylselenolation of benzyl halides with the Ph3P+CF2CO2-/Se/F- system is described. Three new carbon-heteroatom bonds, a Se-CF2 bond, SeCF2-F bond, and C-SeCF3 bond, were sequentially formed in the reaction. This work represents the first trifluoromethylselenolation protocol involving an external fluoride for the generation of the key intermediate, CF3Se- anion.

Synthesis of ß-Alkyl 2-Hydroxychalcones by Rhodium-Catalyzed Coupling of N-Phenoxyacetamides and Nonterminal Propargyl Alcohols.

An efficient rhodium-catalyzed coupling of N-phenoxyacetamides and nonterminal propargyl alcohols has been developed. A series of ß-Alkyl 2-hydroxychalcones bearing diverse functional groups were obtained with excellent regio- and stereoselectivity, and the desired chalcones could then be converted to triazole and chromene smoothly.

Radical Changes in Lewis Acid Catalysis: Matching Metal and Substrate.

Whereas the stereochemical rigidity of the coordination sphere of boxmi/Cu(II) catalysts is key to achieving high enantioselectivity in the electrophilic alkylation of ß-ketoesters, this pathway is outperformed by a radical process for the corresponding catalytic transformation of oxindoles, giving rise to racemic products. For the corresponding Zn(II) catalysts, the selectivity in the latter process is outstanding despite the greater plasticity of the coordination shell. This reaction was thus developed into a highly useful synthetic method, which enabled the conversion of wide range of substrates with high yields and enantioselectivities.

Anionic chiral tridentate N-donor pincer ligands in asymmetric catalysis.

Tridentate monoanionic ligands known as "pincers" have gained a prominent place as ligands for transition metals and, more recently, for main-group metals and lanthanides. They have been widely employed as ancillary ligands for metal complexes studied inter alia in bond activation steps relevant to catalytic processes. The central formally anionic aryl or heteroaryl unit acts as an "anchor" in the coordination to the metal, which kinetically stabilizes the resulting complexes. Their stability, activity, and reactivity can be tuned by subtle modifications of substitution patterns on the pincer ligand or by modifying the donor atoms. The challenges in pincer ligand design for enantioselective catalysis have been met by their assembly from rigid heterocycles and chiral ligating units in the "wingtip" positions, which generally contain the stereochemical information. The resulting well-defined geometry and shape of the reactive sector of the molecular catalyst favor orientational control of the substrates. On the other hand, the kinetic stability allows reduced catalyst loadings. Recently, a new generation of tridentate anionic N(∧)N(∧)N pincer ligands has been developed which give rise to highly enantioselective transformations. Their applications in asymmetric catalysis have focused primarily on the asymmetric Nozaki-Hiyama-Kishi coupling of aldehydes with halogenated hydrocarbons as well as Lewis acid catalysis involving enantioselective electrophilic attack onto metal-activated ß-keto esters, oxindoles, and related substrates. These include highly selective protocols for Friedel-Crafts alkylations with Michael acceptors, electrophilic fluorinations, trifluoromethylations, azidations, and alkylations and subsequent transformations. Increasingly, these stereodirecting ligands are being employed in other types of transformations, including hydrosilylations, cyclopropanations, and epoxidations. The stability and well-defined nature of the molecular catalysts have made them attractive targets for mechanistic studies into a wide range of these transformations, thus providing the type of insight required for a more rational approach to catalyst development. This Account reviews work performed by us and other groups in the field and places it into perspective in relation to general research efforts in enantioselective catalysis.

Copper-boxmi complexes as highly enantioselective catalysts for electrophilic trifluoromethylthiolations.

The enantioselective trifluoromethylthiolation of ß-ketoesters using chiral copper-boxmi complexes as catalysts is reported. A number of α-SCF3-substituted ß-ketoesters have been obtained with up to >99% enantiomeric excess (ee), and the trifluoromethylthiolated products were then transformed diastereoselectively to α-SCF3-ß-hydroxyesters with two adjacent quaternary stereocenters.