Copper-catalyzed tandem reaction of 2-alkynylanilines with benzoquinones: efficient access to 3-indolylquinones

A simple, mild, catalytic and efficient method for the straightforward synthesis of an interesting class of 2-aryl/alkyl-substituted-3-indolyl quinones in good to high yields is reported for the first time. This atom-efficient method proceeds via copper-catalyzed one-pot sequential intramolecular hydroamination (C–N bond formation) of 2-alkynylanilines followed by oxidative C–C coupling with benzoquinones.

Copper-catalyzed domino cyclization of 2-alkynylanilines followed by C–C bond formation with quinones is an efficient method of accessing 3-indolyl quinones.     

Copper-mediated construction of benzothieno[3,2-b]benzofurans by intramolecular dehydrogenative C–O coupling reaction

An efficient method to synthesize benzothieno[3,2-b]benzofurans via intramolecular dehydrogenative C–H/O–H coupling has been developed. Good to excellent yields (64–91%) could be obtained no matter if the substituted group is electron-donating or electron-withdrawing. Notably, three-to-six fused ring thienofuran compounds could be constructed using this method. A reaction mechanism study showed that 1,1-diphenylethylene can completely inhibit the reaction. Therefore, it is a radical pathway initiated by single electron transfer between the hydroxyl of the substrate and the copper catalyst.

The construction of benzothieno[3,2-b]benzofurans via novel dehydrogenative C–H/O–H coupling reaction has been developed with excellent yields. Furthermore, three-to-six fused ring thienofuran compounds could be constructed.     

Direct C–H functionalization of difluoroboron dipyrromethenes (BODIPYs) at β-position by iodonium salts

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed, which provides facile access to a variety of mono-substituted BODIPY dyes. Interestingly, β-styryl BODIPY compound 9b exhibits apparent cytotoxicity after laser irradiation, which has great potential for photodynamic therapy.

A copper-catalyzed direct C–H arylation or vinylation of BODIPYs at the β-position by iodonium salts has been developed and β-styryl BODIPY 9b has great potential for photodynamic therapy.     

Metal-free oxidative coupling of arylmethylamines with indoles: a simple,environmentally benign approach for the synthesis of 3,3′-bis(indolyl)methanes

The efficient metal-free oxidative coupling of arylmethylamines with indoles has been developed using molecular oxygen as a green oxidant. The present reaction provides a novel route towards the synthesis of 3,3′-bis(indolyl)methanes in excellent yields of up to 95% via C–C and C–N bond formation. This attractive and environmentally friendly one-pot protocol is a simple procedure that features inexpensive acetic acid as the catalyst and molecular oxygen as the sole oxidant, and it supports a wide substrate scope with the good tolerance of functional groups.

The efficient metal-free oxidative coupling of arylmethylamines with indoles has been developed using molecular oxygen as a green oxidant towards a novel rout of 3,3′-bis(indolyl)methanes (BIMs) synthesis.     

Oxone promoted dehydrogenative Povarov cyclization of N-aryl glycine derivatives: an approach towards quinoline fused lactones and lactams

Oxone promoted intramolecular dehydrogenative imino Diels–Alder reaction (Povarov cyclization) of alkyne tethered N-aryl glycine esters and amides has been explored, thus affording biologically significant quinoline fused lactones and lactams. The reaction is simple, scalable, and high yielding (up to 88%). The method was further extended to prepare biologically important luotonin-A analogues and the quinoline core of uncialamycin.

Oxone promoted intramolecular dehydrogenative imino Diels–Alder reaction (Povarov cyclization) of alkyne tethered N-aryl glycine esters and amides has been explored, thus affording biologically significant quinoline fused lactones and lactams.     

A novel 3D Cd(ii) coordination polymer generated via in situ ligand synthesis involving C–O ester bond formation

A novel 3D Cd(ii) coordination polymer {[Cd(ddpa)(2,2′-bpy)]·H₂O}_n (1) (H₂ddpa = 5,10-dioxo-5,10-dihydro-4,9-dioxapyrene-2,7-dicarboxylic acid, 2,2′-bpy = 2,2′-bipyridine) is hydrothermally synthesized in situ, and the influencing factors and mechanism for the in situ reaction are briefly discussed. The synthesis of 1 requires the formation of a new C–O ester bond. This current study confirms that metal ions and N-donor ligands play important roles in the domination of the in situ ligand from 6,6′-dinitro-2,2′,4,4′-biphenyltetracarboxylic acid (H₄dbta). Furthermore, the structure, thermal stability and photoluminescent property of 1 are also investigated.

A 3D Cd(ii) coordination polymer comprising ligand molecules not included in the original reaction mixtures but instead formed via in situ ligand synthesis involving a C–O ester bond.     

Iron catalyzed C–C dehydrogenative coupling reaction: synthesis of arylquinones from quinones/hydroquinones

An atom-economical approach for the synthesis of arylquinones was achieved successfully via direct oxidative C–C dehydrogenative coupling reaction of quinones/hydroquinones with electron-rich arenes using an inexpensive Fe–I₂–(NH₄)₂S₂O₈ system. The efficiency of this catalytic approach was established with a broad scope of substrates involving quinones and hydroquinones to give high yields (60–89%) of several arylated quinones. The present protocol is simple, practical, and shows good functional group tolerance.

The synthesis of arylquinones was achieved via direct oxidative C–H/C–H cross-coupling of quinones/hydroquinones with electron-rich arenes using Fe–I₂–(NH₄)₂S₂O₈ system involving quinones/hydroquinones to give high yields (60–89%) of arylquinones.     

Palladium mediated domino reaction: synthesis of isochromenes under aqueous medium

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes. Notably, this domino process is feasible by using the green solvent, water. The protocol exhibited a broad substrate scope and afforded various isochromenes.

Isochromenes have been synthesized using palladium-catalyzed C–C and C–O bond forming reactions starting from ortho-bromo tertiary benzylic alcohols and internal acetylenes.     

Tracking intramolecular energy redistribution dynamics in aryl halides: the effect of halide mass

Selective excitation of C–H, C–C, CX¹ and CX² stretching vibrational modes in an orderly manner, detection of intramolecular energy redistribution and vibrational coupling in the electronic ground state of aryl halides are performed by time- and frequency-resolved Coherent Anti-Stokes Raman Scattering (CARS) spectroscopy. Intramolecular energy flow from parent modes to daughter modes is observed in the experiment. According to the experimental results, it is found that the up-hill vibrational energy flow from lower frequency modes to higher frequency ones is counterintuitive and energy redistribution efficiencies are controlled by the mass of the halide. The selectivity and directionality of energy flow are also discussed in view of vibrational symmetry.

Selective excitation of C–H, C–C, CX¹ and CX² modes in an orderly manner, detection of intramolecular energy redistribution in aryl halides are performed by time- and frequency-resolved Coherent Anti-Stokes Raman Scattering (CARS) spectroscopy.     

Elucidating the intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid-solid interface

Star-shaped 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules self-assemble at the solid–liquid interface into a compact hexagonal nanoarchitecture on graphite. High resolution scanning tunneling microscopy (STM) images of the molecules reveal intramolecular features. Comparison of the experimental data with calculated molecular charge density contours shows that the molecular features in the STM images correspond to molecular LUMO+2.

Intramolecular contrast in the STM images of 2,4,6-tris(4′,4′′,4′′′-trimethylphenyl)-1,3,5-triazine molecules recorded at room-temperature and at the liquid–solid interface.     

Efficient synthesis of ether phosphonates using trichloroacetimidate and acetate coupling methods

A series of ether phosphonates have been prepared by trichloroacetimidate and acetate coupling methods. Trichloroacetimidates or acetates were treated with primary and secondary alcohols as O-nucleophiles in the presence of catalytic TMSOTf to afford 21 examples of diethyl alkyloxy(substitutedphenyl)methyl phosphonates via C–O bond formation in 55–90% yields and short reaction time.

An efficient method for the synthesis of various ether phosphonates by trichloroacetimidate and acetate coupling methods is described.     

The synthesis of N,N′-disulfanediyl-bis(N′-((E)-benzylidene)acetohydrazide) from (E)-N′-benzylideneacetohydrazide and S8

Herein we report an oxidative coupling reaction for N–S/S–S bond formation from (E)-N′-benzylideneacetohydrazide and S₈ to furnish substituted N,N′-disulfanediyl-bis(N′-((E)-benzylidene) acetohydrazide). It provides a direct approach for the synthesis of disulfides with good yields.

Herein we report an oxidative coupling reaction for N–S/S–S bond formation substituted N,N′-disulfanediyl bis(N′-((E)-benzylidene)acetohydrazide). It provides a direct approach for the synthesis of disulfides with good yields.     

Oxidative radical coupling of hydroquinones and thiols using chromic acid: one-pot synthesis of quinonyl alkyl/aryl thioethers

An efficient, simple and practical protocol for one-pot sequential oxidative radical C–H/S–H cross-coupling of thiols with hydroquinones (HQs) and oxidation leading to the formation of quinonyl alkyl/aryl thioethers using H₂CrO₄ was developed. This cross-coupling of thiyl and aryl radicals offers mono thioethers in good to moderate yield and works well with a wide variety of thiols. Similarly, this method works well for coupling of 2-amino thiophenol and HQs to form phenothiazine-3-ones 5a–c. C–S bond formation via thioether synthesis was observed using a chromium reagent for the first time. Theoretical studies on the pharmacokinetic properties of compounds 5a–c revealed that due to drug-like properties, compound 5b strongly binds with Alzheimer''s disease (AD) associated AChE target sites.

Oxidative radical C–H/S–H cross coupling of hydroquinones and thiols and oxidation to quinone using a H₂CrO₄ system was developed.     

Gold(iii) promoted formation of dihydroquinazolinones: double X–H activation by gold

An efficient 2-furyl gold–carbene promoted synthetic method was developed for the formation of dihydroquinazolinones from enynones by dual insertion of anthranilamides. In this organic transformation a new C–O and two C–N bond formations occurred and dihydroquinazolinones were obtained with a quaternary centre in moderate to very good yields in one-pot synthesis.

An efficient 2-furyl gold–carbene promoted synthetic method was developed for the formation of dihydroquinazolinones from enynones by dual insertion of anthranilamides in very good yields.     

One-pot copper-catalyzed three-component reaction: a modular approach to functionalized 2-quinolones

A copper-catalyzed three-component annulation for the synthesis of functionalized 2-quinolones was developed. Three reactions including an S_N2, a Knoevenagel, and finally C–N bond formation are involved in the designed cascade reaction using 2-bromoacylarenes, 2-iodoacetamide, and nucleophiles as the three components. A new catalytic system was discovered during the study and this modular approach is highly efficient to access functionalized 2-quinolone derivatives, compatible with a broad range of functional groups, scalable, and step-economic. Further derivatization of the obtained product demonstrates the synthetic utility of this method.

A copper-catalyzed three-component annulation for the synthesis of functionalized 2-quinolones was developed.     

The molecular mechanism of P450-catalyzed amination of the pyrrolidine derivative of lidocaine: insights from multiscale simulations

Nitrogen heterocycles are key and prevalent motifs in drugs. Evolved variants of cytochrome P450_BM3 (CYP102A1) from Bacillus megaterium employ high-valent oxo-iron(iv) species to catalyze the synthesis of imidazolidine-4-ones via an intramolecular C–H amination. Herein, we use multi-scale simulations, including classical molecular dynamics (MD) simulations, quantum mechanical/molecular mechanical (QM/MM) calculations and QM calculations, to reveal the molecular mechanism of the intramolecular C–H amination of the pyrrolidine derivative of lidocaine bearing cyclic amino moieties catalyzed by the variant RP/FV/EV of P450_BM3, which bears five mutations compared to wild type. Our calculations show that overall catalysis includes both the enzymatic transformation in P450 and non-enzymatic transformation in water solution. The enzymatic transformation involves the exclusive hydroxylation of the C–H bond of the pyrrolidine derivative of lidocaine, leading to the hydroxylated intermediate, during which the substrate radical would be bypassed. The following dehydration and C–N coupling reactions are found to be much favored in aqueous situation compared to that in the non-polar protein environment. The present findings expand our understanding of the P450-catalyzed C(sp₃)–H amination reaction.

Nitrogen heterocycles are key and prevalent motifs in drugs.     

Catalytic,selective, and stereocontrolled construction of C4 quaternary and homobenzylic dihydroisoquinolones by sp3 C–H benzylation

C1 benzylated isoquinoline derivatives constitute the core of benzylisoquinoline alkaloids (BIAs). However, their C4 congeners remain elusive. Here, we describe a diastereoselective, catalytic, and modular C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds of readily affordable vicinally functionalized dihydroisoquinolones are replaced by sp³ C–benzyl bonds. The method provides expedient access to C4 quaternary and homobenzylic dihydroisoquinolones, which are attractive fragments for potential drug discovery.

A diastereoselective and catalytic C(sp³)–C(sp³) coupling protocol wherein β-amino sp³ C–H bonds are replaced by sp³ C–benzyl bonds, leading to C4 quaternary and homobenzylic dihydroisoquinolones, is described.     

Cu/TEMPO catalyzed dehydrogenative 1,3-dipolar cycloaddition in the synthesis of spirooxindoles as potential antidiabetic agents

A series of spiro-[indoline-3,3′-pyrrolizin/pyrrolidin]-2-ones, 4, 5 and 6 were synthesized in a sequential manner from Cu–TEMPO catalyzed dehydrogenation of alkylated ketones, 1 followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation of isatin, 2 and l-proline/sarcosine, 3 in high regioselectivities and yields. The detailed mechanistic studies were performed to identify the reaction intermediates, which revealed that the reaction proceeds via dehydrogenative cycloaddition. Additionally, the regio and stereochemistry of the synthesized derivatives were affirmed by 2D NMR spectroscopic studies. The synthesized derivatives were explored further with molecular docking, in vitro antioxidant, and anti-diabetic activities.

A series of spiro-[indoline-3,3′-pyrrolizin/pyrrolidin]-2-ones were synthesized from Cu–TEMPO catalyzed dehydrogenation followed by 1,3-dipolar cycloaddition of azomethine ylides via decarboxylative condensation, resulting in high regioselectivities and yields.     

Nickel(ii)-catalyzed reductive silylation of alkenyl methyl ethers for the synthesis of alkyl silanes

A new one pot protocol has been developed for the reductive silylation of alkenyl methyl ethers using Et₃Si–BPin and HSiEt₃ with nickel(ii) catalyst. Styrene type methyl ethers, multi-substituted vinyl methyl ethers, heterocycles and unconjugated vinyl ethers are all tolerated to form alkyl silanes. Mechanistic study reveals that it is a cascade of a C–O bond silylation and vinyl double bond hydrogenation process. Internal nucleophilic substitution or oxidative addition pathways were both acceptable for C–O bond cleavage. The acquired intermediate alkenyl silanes then proceeded through an unconventional reduction process thus providing alkyl silanes.

A Ni(ii)-catalyzed tandem reaction including vinyl C–O bond silylation and olefin hydrogenation has been developed providing structurally diversified alkyl silanes.