A new three-component reaction, namely condensation–anti-Michael addition–aromatization, enabling the construction of benzylic compounds is disclosed. This reaction can not only act as an alternative approach to regioselective Csp2–H trifluoromethylation of arenes through an “aromatic to be” strategy, but also provides a simple, convenient, step-economic, and practical strategy for the in situ generation of electrophilic p-(trifluoromethyl)benzyl species under extremely mild conditions.

AbstractThe C−C bond formation via C−S bond activation (disclosed in 2000) has received increasing attention. However, stoichiometric amounts of exogenous thiophilic reagents are generally required as thiolate scavengers. Herein, a new model for the synthesis of 4-aminoquinolines, the copper(II)-catalyzed aerobic oxidative desulfitative 6π cyclization of the readily available N-arylimino ketene N,S-acetals is described. The reaction can proceed efficiently under mild conditions without any exogeneous thiolate scavengers (due to the formation of disulfide as the by-product) to afford diverse 4-aminoquinolines, a privileged structure motif displaying antimalarial activity, with a wide range of functional groups at the C-2 to C-8 positions.

Acid-catalyzed electrophilic aromatic substitution for C–C bond formation, commonly referred to as the Friedel–Crafts reaction in recognition of its discoverers, has been one of the most useful reactions in organic chemistry for over a century. However, the Friedel–Crafts reaction cannot occur on a benzene ring having a strongly electron withdrawing group, such as an acyl group, which deactivates the aromatic ring toward electrophilic substitutions and remains a major challenge. Herein, the synthesis of naphthoquinones and 1,3-indandiones, bearing two acyl groups at positions ortho to each other on a benzene ring, are demonstrated by means of copper-catalyzed intramolecular aerobic oxidative acylation of benzoylacetone derivative precursors. This unusual Friedel–Crafts reaction reveals a new activation mode for the in situ polarity reverse of an electron-deficient aromatic ring to a reactive, electron-rich ring tuned by remote electronic effects.

We reveal here the unique reactivity of α-(alkylideneamino)nitriles toward molecular oxygen. Thus, α-(alkylideneamino)nitriles can serve as the imide building block for the efficient synthesis of imides in the absence of transition metals under extremely mild conditions.

The first formal [3+2] cycloaddition using α-trifluoromethyl-(indol-3-yl)methanols as the trifluoromethylated C3 1,3-dipoles for the construction of the five-membered carbocycle of 1-trifluoromethylated cyclopenta[b]indole alkaloids is described. An unprecedented step-wise dehydrative alkenylation of α-trifluoromethyl alcohols was revealed as the crucial transformation.

The polarity reversible nature of azomethine imines as the crucial transformation enables the tandem Michael addition/imine isomerization/[3+2] cycloaddition to proceed under mild, transition-metal-free conditions to form cyclohepta[b]pyrroles in a single operation starting from readily available acyclic precursors with a broad substrate scope.

The selective construction of a diverse array of five-membered aromatic heterocycles from common starting materials is an attractive and challenging task. We report here that 5-alkylthio-pyrroles, 4-alkylthiocarbonyl-pyrroles and 2-alkylthio-4-tosyl-furans can be prepared, selectively, in a single operation using the readily available α-formyl ketene dithioacetals as common precursors, through their regiodivergent heterocyclization with α-acidic isocyanides controlled by the choice of suitable catalysts/promoters.

A new strategy, the 1,3-carbothiolation/aromatization, for the synthesis of functionalized (trifluoromethyl)arenes has been developed that enables the regioselective introduction of two different functional groups onto an “aromatic ring” in the meta-position to each other in a single step.

The synthetic methods of trifluoromethylated cyclopentadienes/fulvenes/norbornenes have been developed using 3-CF3-1,4-dien-3-ols as the synthons, which can be easily prepared by the regiospecific 1,2-addition of the Ruppert–Prakash reagent (TMSCF3) to divinyl ketones. All the reactions are carried out under mild, metal-free conditions to afford the corresponding products in high to excellent yields.

We describe here a single-step synthesis of substituted 1-pyrrolines from N-(4-chlorobenzylidene)-glycine methyl ester and enones which combines conversion of the Michael adducts to 1-pyrrolines with separation between the products on silica gel column chromatography.

The selective construction of a diverse array of five-membered aromatic heterocycles from common starting materials is an attractive and challenging task. We report here that 5-alkylthio-pyrroles, 4-alkylthiocarbonyl-pyrroles and 2-alkylthio-4-tosyl-furans can be prepared, selectively, in a single operation using the readily available α-formyl ketene dithioacetals as common precursors, through their regiodivergent heterocyclization with α-acidic isocyanides controlled by the choice of suitable catalysts/promoters.

The first formal [3+2] cycloaddition using α-trifluoromethyl-(indol-3-yl)methanols as the trifluoromethylated C3 1,3-dipoles for the construction of the five-membered carbocycle of 1-trifluoromethylated cyclopenta[b]indole alkaloids is described. An unprecedented step-wise dehydrative alkenylation of α-trifluoromethyl alcohols was revealed as the crucial transformation.

The polarity reversible nature of azomethine imines as the crucial transformation enables the tandem Michael addition/imine isomerization/[3+2] cycloaddition to proceed under mild, transition-metal-free conditions to form cyclohepta[b]pyrroles in a single operation starting from readily available acyclic precursors with a broad substrate scope.

The synthetic methods of trifluoromethylated cyclopentadienes/fulvenes/norbornenes have been developed using 3-CF3-1,4-dien-3-ols as the synthons, which can be easily prepared by the regiospecific 1,2-addition of the Ruppert–Prakash reagent (TMSCF3) to divinyl ketones. All the reactions are carried out under mild, metal-free conditions to afford the corresponding products in high to excellent yields.

We reveal here the unique reactivity of α-(alkylideneamino)nitriles toward molecular oxygen. Thus, α-(alkylideneamino)nitriles can serve as the imide building block for the efficient synthesis of imides in the absence of transition metals under extremely mild conditions.

A new three-component reaction, namely condensation–anti-Michael addition–aromatization, enabling the construction of benzylic compounds is disclosed. This reaction can not only act as an alternative approach to regioselective Csp2–H trifluoromethylation of arenes through an “aromatic to be” strategy, but also provides a simple, convenient, step-economic, and practical strategy for the in situ generation of electrophilic p-(trifluoromethyl)benzyl species under extremely mild conditions.