Electrochemical dual oxidative C(sp3)-H amination: switchable synthesis of imidazo-fused quinazolinones.

An efficient electrochemical dual C(sp3)-H amination was developed under metal-free and chemical oxidant-free conditions. A series of imidazo[1,5-a]quinazolin-5(4H)-ones and 5-oxo-4,5-dihydroimidazo[1,5-a]quinazoline-3-carbonitriles can be obtained in high yields and the product distribution can be modulated by virtue of this method. The reaction mechanism was investigated and the corresponding intermediates were studied. The reaction features a broad substrate scope, regulation of the product distribution, mild conditions and scalable preparation.

A copper-catalyzed asymmetric Friedel-Crafts hydroxyalkylation of pyrazole-4,5-diones with 5-aminoisoxazoles.

An asymmetric Friedel-Crafts hydroxyalkylation reaction of 5-aminoisoxazoles with pyrazole-4,5-diones was developed under the catalysis of 5% chiral copper complexes. This reaction exhibits functional group tolerance and excellent enantioselectivity. Moreover, the reaction can be scaled up and its mechanism was studied.

Switchable Direct Oxygenative Arylation of C(sp3)-H Bonds via Electrophotocatalysis.

A metal-free electrophotochemical C(sp3)-H arylation was developed under mild conditions. This method enables a switchable synthesis of diaryl alcohols and diaryl alkanes from inactive benzylic carbons. More importantly, a cheap and safe mediator N-chlorosuccinimide (NCS) was developed, which was employed for the hydrogen atom transfer (HAT) process of the benzylic C-H bond. In addition, this active radical was captured and identified by electron paramagnetic resonance (EPR).

Construction of chiral N,O-hemiaminals via a copper-catalyzed enantioselective Michael/N-hemiacetalization cascade reaction.

An efficient Michael/N-hemiacetalization cascade reaction of 5-aminoisoxazoles with ß,γ-unsaturated α-ketoesters was developed under the catalysis of a chiral copper complex. A series of optically pure six-membered ring N,O-hemiaminals were obtained with excellent yields (up to 96% yield) and high enantioselectivities (up to 98% ee). The possible transition state was supported by DFT calculations and thereby the corresponding mechanism was proposed.

Construction of a Chiral ß-Fluoroamine by Asymmetric Mannich Reaction of 2-Fluoroindanone with Pyrazolinone Ketimines.

The asymmetric Mannich reaction of 2-fluoroindanone with ketimine was developed under the catalysis of a kind of chiral copper complex, affording a chiral tetrahedral center containing fluorine. A series of ß-fluoroamine derivatives can be obtained in excellent yields (73-94%) with high diastereoselectivities (>99:1 dr) and enantioselectivities (89-99%). The possible transition state was supported by density functional theory calculation.

Construction of spirocyclic oxindole derivatives by copper-catalyzed enantioselective Michael/hemiketalization in aqueous media.

An asymmetric Michael/hemiketalization reaction between isatin-derived ß,γ-unsaturated α-ketoesters and 4-hydroxycoumarins was developed in aqueous media. A series of chiral spirooxindole derivatives with an all-carbon quaternary stereogenic center were obtained in high yields (up to 93%) and excellent enantioselectivities (up to 98%).

Efficient enantioselective synthesis of trisubstituted γ-lactam via the Michael addition reaction of 2,3-dioxopyrrolidine with indole in aqueous media.

An efficient enantioselective Michael addition reaction of 2,3-dioxopyrrolidine with indole in aqueous media was developed by virtue of a chiral copper complex. This reaction features air tolerance, a broad substrate scope and mild reaction conditions. Furthermore, a gram-scale synthesis was conducted to afford the corresponding products with a high yield and excellent enantioselectivity. Moreover, the proposed mechanism was supported by control experiments, XPS investigation and DFT calculations.

Copper-Catalyzed Stereoselective [4 + 2] Cycloaddition of ß,γ-Unsaturated α-Keto Esters and 2-Vinylpyrroles in Water.

An asymmetric [4 + 2] cycloaddition of ß,γ-unsaturated α-keto esters with 2-vinylpyrroles in water was developed under the catalysis of a kind of copper complex with a low loading. A series of optically pure 3,4-dihydro-2H-pyran derivatives could be obtained in excellent yields, with high diastereoselectivities and enantioselectivities. The corresponding mechanism was proposed, which was supported by DFT calculations.

Iodine-mediated oxythiolation of o-vinylanilides with disulfides for the synthesis of benzoxazines.

An efficient iodine-mediated oxythiolation of o-vinylanilides with disulfides was developed. By virtue of this method, a series of thio-tethered benzoxazine derivatives were synthesized in good to excellent yields. The reaction features high yields, is metal-free, and has a wide substrate scope.

Zn-Catalyzed enantioselective allylation and allenylation of isatins by virtue of a proline-derived chiral ligand.

An asymmetric allylation and allenylation of isatins with facile organoboron reagents was developed under the catalysis of a Lewis acid. A series of optically pure 3-allyl-3-hydroxyoxindoles and 3-allenyl-3-hydroxyoxindoles can be obtained in excellent yields (up to 99% yield) and high enantioselectivities (up to 97% ee). The possible transition state was supported by DFT calculation and the corresponding mechanism was proposed. A gram scale experiment and further functionalization of these chiral 3-hydroxyoxindoles are established.

Iodine-mediated electrochemical C(sp3)-H cyclization: the synthesis of quinazolinone-fused N-heterocycles.

An efficient iodine-mediated electrochemical C(sp3)-H cyclization was developed under mild conditions. A variety of functionalized quinazolinone-fused N-heterocycles can be obtained with good to excellent yields by virtue of this method. The reaction features a broad substrate scope and scalability, and is metal-free and chemical oxidant-free.

Stereoselective Copper-Catalyzed Direct Aldol Reaction of ß, γ-Unsaturated α-Ketoesters with Coumaran-3-Ones.

An efficient direct aldol reaction between coumaran-3-ones and ß, γ-unsaturated α-ketoesters by virtue of a chiral copper complex is developed. A series of coumaran-3-one derivatives containing chiral tertiary alcohol structures are obtained in excellent yields and stereoselectivities.

Electrosynthesis of Quinazolines and Quinazolinones via an Anodic Direct Oxidation C(sp3)-H Amination/C-N Cleavage of Tertiary Amine in Aqueous Medium.

An electrochemical synthesis for quinazolines and quinazolinones was developed via a C(sp3)-H amination/C-N cleavage by virtue of the anodic oxidation. The reaction can be carried out in aqueous media under mild conditions to afford the desired products with high yields. The reaction mechanism was proposed after detailed investigation.

A novel chiral surfactant-type metallomicellar catalyst for asymmetric Michael addition in water.

A series of Schiff-based ligands consisting of both tertiary amines and lipophilic groups were designed and synthesized. Using these ligands, a new chiral surfactant-type metallomicellar catalyst was developed in water, and this was identified by SEM/TEM analyses. These metallomicelles can be empolyed in asymmetric Michael addition reactions in water, delivering the corresponding adducts with excellent yields and enantioselectivities.

Iodine-Mediated Electrochemical C(sp2)-H Amination: Switchable Synthesis of Indolines and Indoles.

A metal-free electrochemical intramolecular C(sp2)-H amination using iodine as a mediator was developed. This method enables a switchable synthesis of indoline and indole derivatives, respectively, from easily available 2-vinyl anilines.

Lewis Acid-Catalyzed Enantioselective Friedel-Crafts Alkylation of Pyrrole in Water.

Highly enantioselective Friedel-Crafts alkylation of pyrroles with 2-enoyl-pyridine N-oxides in water/chloroform (10:1) was developed under catalysis of Lewis acid. The Friedel-Crafts alkylation products can be obtained in high yields and excellent enantioselectivities. Moreover, several control experiments were carried out to study the reaction mechanism.

Copper Catalyzed Diastereo- and Enantioselective 1,4-Addition Michael Reaction of 2,3-Dioxopyrrolidines with Nitroalkanes in Aqueous Media.

A good diastereo- and enantioselective 1,4-addition Michael reaction catalyzed by a chiral copper complex was developed in aqueous media. A series of nitro-containing pyrrolidones could be gained in high yields with excellent diastereoselectivities and good ee values by virtue of this developed method. It affords a facile access to construct carbon-carbon bonds with water and air tolerance. Furthermore, the gram scale synthesis was conducted successfully to give rise to the corresponding products.

Electrocatalytic Three-Component Reaction: Synthesis of Cyanide-Functionalization Imidazo-Fused N-Heterocycles.

An electrochemical three-component cyclization was developed under metal-free conditions, which provides a novel and facile approach for the construction of cyanide-functionalization imidazo-fused N-heterocycles. A variety of cyanide-functionalization imidazo-fused N-heterocycles can be obtained from easily available methyl N-heteroaromatics, primary alkylamines, and trimethylsilyl cyanide with good to excellent yields. The reaction features a broad scope of substrates, scalability, and mild conditions.

Copper-catalyzed enantioselective Mukaiyama aldol reaction of silyl enol ethers with isatins.

A highly enantioselective Mukaiyama aldol reaction of silyl enol ethers with isatins catalyzed by chiral copper complexes was developed. A series of chiral 3-substituted 3-hydroxy-2-oxindoles bearing a tetra-substituted center could be obtained exclusively with high yields (up to 95%) and excellent enantioselectivities (up to 99%). In particular, water was essential to improve the diastereoselectivity.

Electrocatalytic Tandem Synthesis of 1,3-Disubstituted Imidazo[1,5- a]quinolines via Sequential Dual Oxidative C(sp3)-H Amination in Aqueous Medium.

An NH4I-mediated tandem electrosynthesis of 1,3-disubstituted imidazo[1,5- a]quinolines was developed from readily available starting materials in aqueous medium, affording a variety of 1,3-disubstituted imidazo[1,5- a]quinolines with good to excellent yields.