A novel one-pot 1,3-dipolar cycloaddition of indolenines, 3-aminooxindoles, and aldehydes is reported. The reaction provides indolenine-substituted spiro[pyrrolidin-2,3′-oxindoles] containing four contiguous stereogenic centers in high yields (up to 99%) and excellent diastereoselectivities (up to >20:1 dr) under mild conditions. Remarkably, the inversion of diastereoselectivity could be readily achieved through slightly modifying the reaction conditions.

An organocatalytic asymmetric [3+2] cycloaddition of 3-amino oxindole-based azomethine ylides and α,β-ynones has been developed. This reaction afforded spiro[dihydropyrrole-2,3′-oxindole] products in high chemical yields with excellent stereoselectivities (up to 99% yields, >20 : 1 dr and >99% ee). Notably, a series of important spiro[pyrrole-oxindole] derivatives were readily obtained via oxidation of the cycloadducts, thus extending the diversity of the products.

•A facile and expeditious approach to 1H-pyrazoles is developed.•Starting materials are α,β-unsaturated ketones/aldehydes and sulfonyl hydrazide.•The reaction is catalyzed by as low as 2 mol % I2.•The process features simple conditions, high yield, and broad substrate scope.A facile and expeditious method for the synthesis of 1H-pyrazoles by the reaction of α,β-unsaturated aldehydes/ketones and sulfonyl hydrazide catalyzed by as low as 2 mol % I2 has been demonstrated. This synthetic system features simple operation and mild reaction conditions, and displays a broad functional group tolerance furnishing good to excellent yields.

An asymmetric fluorination process of 4-substituted pyrazolones catalyzed by quinine is revealed. The reaction afforded a wide range of 4-fluorinated pyrazol-5-ones with excellent yields (up to 98%) and moderate to good enantioselectivities (up to 81% ee).4-Benzyl-4-fluoro-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H17FN2O51% ee[α]D22 = −51.6 (c 0.28, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(4-fluorobenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H16F2N2O40% ee[α]D22 = −45.0 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-1,3-diphenyl-4-(4-(trifluoromethyl)benzyl)-1H-pyrazol-5(4H)-oneC23H16F4N2O41% ee[α]D22 = −51.1 (c 0.36, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(2-nitrobenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC22H16FN3O342% ee[α]D22 = −37.4 (c 0.56, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(3-methylbenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O71% ee[α]D26 = −95.2 (c 0.46, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(4-methoxybenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O267% ee[α]D25 = −65.8 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(2-methylbenzyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC23H19FN2O68% ee[α]D25 = −75.4 (c 0.50, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(furan-2-ylmethyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC20H15FN2O257% ee[α]D22 = −69.0 (c 0.45, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-1,3-diphenyl-4-(thiophen-2-ylmethyl)-1H-pyrazol-5(4H)-oneC20H15FN2OS45% ee[α]D22 = −76.0 (c 0.58, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-4-(naphthalen-1-ylmethyl)-1,3-diphenyl-1H-pyrazol-5(4H)-oneC26H19FN2O81% ee[α]D26 = −89.8 (c 0.55, CH2Cl2)Source of chirality: asymmetric fluorination4-Allyl-4-fluoro-1,3-diphenyl-1H-pyrazol-5(4H)-oneC18H15FN2O35% ee[α]D26 = −43.5 (c 0.47, CH2Cl2)Source of chirality: asymmetric fluorination4-Fluoro-1,3-diphenyl-4-(prop-2-ynyl)-1H-pyrazol-5(4H)-oneC18H13FN2O40% ee[α]D21 = −35.7 (c 0.45, CH2Cl2)Source of chirality: asymmetric fluorination4-Benzyl-3-(4-bromophenyl)-4-methyl-1-phenyl-1H-pyrazol-5(4H)-oneC23H19BrN2O37% ee[α]D26 = −19.4 (c 0.66, CH2Cl2)Source of chirality: asymmetric fluorination4-Benzyl-4-fluoro-1-phenyl-3-p-tolyl-1H-pyrazol-5(4H)-oneC23H19FN2O51% ee[α]D26 = −43.5 (c 0.53, CH2Cl2)Source of chirality: asymmetric fluorination4-Benzyl-4-fluoro-3-(4-methoxyphenyl)-1-phenyl-1H-pyrazol-5(4H)-oneC23H19FN2O253% ee[α]D26 = −28.1 (c 0.46, CH2Cl2)Source of chirality: asymmetric fluorination

A highly efficient and practical one-pot sequential process, consisting of an organocatalytic enantioselective Friedel–Crafts-type addition of 4-nonsubstituted pyrazolones to isatin-derived N-Boc ketimines and a subsequent diastereoselective fluorination of the pyrazolone moiety, is developed. This reaction sequence delivers novel oxindole–pyrazolone adducts featuring vicinal tetrasubstituted stereocenters with a 0.5 mol % catalyst loading in high yield with excellent enantio- and diastereocontrol. Notably, chloro, bromo, and thioether functionalities can be readily incorporated, rendering a broad diversity of the product.

The selective hydrogenation of 3-hydroxypyridinium salts has been achieved using a homogeneous iridium catalyst, providing a direct access to 2- and 4-substituted piperidin-3-one derivatives with high yields, which are important organic synthetic intermediates and the prevalent structural motifs in pharmaceutical agents. Mild reaction conditions, high chemoselectivity, and easy scalability make this reaction highly practical for the synthesis of piperidin-3-ones.

The catalytic asymmetric three-component 1,3-dipolar cycloaddition of 3-amino oxindoles with aldehydes and nitroolefins under the catalysis of a chiral phosphoric acid is reported. The reaction provides a facile approach to synthesize a diverse array of spiro[pyrrolidine-2,3′-oxindoles] in high yields with excellent diastereo- and enantioselectivities under mild conditions.

A zinc chloride catalyzed tandem 1,5-hydride shift/cyclization process to form spiropyrazolone terahydroquinoline derivatives is developed. A series of new spiropyrazolone derivatives were obtained in good to high yields with good to excellent diastereoselectivities (up to 95% yield, >95:5 dr). Additionally, the spiropyrazolone derivatives could be converted into the corresponding novel spriopyrazolines.

By employing a natural cinchona alkaloid as a catalyst, the enantioselective tandem Michael addition/oxidation of 4-substituted pyrazol-5-ones with p-benzoquinones was realized. The reaction afforded a wide range of 4,4-disubstituted pyrazol-5-ones with moderate to good yields (up to 72%) and moderate to good enantioselectivities (up to 99%).2-(4-Ethyl-5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC23H18N2O380% ee[α]D20 = +70.45 (c 0.19, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Allyl-5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC24H18N2O399% ee[α]D20 = +90.5 (c 0.26, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(5-Oxo-1,3-diphenyl-4-(prop-2-yn-1-yl)-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC24H16N2O399% ee[α]D20 = +92.7 (c 0.26, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC28H20N2O392% ee[α]D20 = +92.6 (c 0.26, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-(4-Fluorobenzyl)-5-oxo-1,3-diphenyl-4,5-dihydro-1H pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC28H19FN2O397% ee[α]D20 = +110.9 (c 0.27, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-(4-Methylbenzyl)-5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC29H22N2O366% ee[α]D20 = +70.45 (c 0.19, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-(4-Methoxybenzyl)-5-oxo-1,3-diphenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC29H22N2O469% ee[α]D20 = +34.6 (c 0.28, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(5-Oxo-1,3-diphenyl-4-(thiophen-2-ylmethyl)-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC26H18N2O3S92% ee[α]D20 = +99.1 (c 0.30, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-3-(4-bromophenyl)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC28H19BrN2O350% ee[α]D20 = +74.8 (c 0.36, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-3-(4-methoxyphenyl)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC29H22N2O484% ee[α]D20 = +92.95 (c 0.31, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-5-oxo-1-phenyl-3-(p-tolyl)-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC29H22N2O397% ee[α]D20 = +127.9 (c 0.24, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-3-(naphthalen-1-yl)-5-oxo-1-phenyl-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC32H22N2O392% ee[α]D20 = +115.3 (c 0.30, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined2-(4-Benzyl-5-oxo-1-phenyl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-4-yl)cyclohexa-2,5-diene-1,4-dioneC26H18N2O3S84% ee[α]D20 = +86.5 (c 0.12, CH2Cl2)Source of chirality: Asymmetric tandem Michael addition/oxidation processAbsolute configuration: not determined

A versatile method for the synthesis of mono- and bis-arylthioindoles via I2 catalysed direct oxidative sulfenylation of indoles with thiophenols (especially mercaptobenzoic acids) has been presented. This system features environmental friendliness, easy operation, and mild reaction conditions, and shows a broad functional group tolerance furnishing good to excellent yields.

The Michael addition of 3-substituted oxindoles to nitroolefins was catalyzed by a novel tartrate-derived guanidine in high yield with excellent diastereo- and enantioselectivity. This method showed an extraordinarily broad substrate scope in terms of both reaction partners.

We report a highly efficient approach to constructing chiral N,S-acetals using 5-substituted rhodanines as sulfur-bound pronucleophiles catalyzed by natural cinchona alkaloids quinine or quinidine. This α-amination reaction has a broad substrate scope, and the products featuring both rhodanine and N,S-acetal structural motifs were obtained in high yields and excellent enantioselectivities.

A novel library of chiral guanidines featuring a tartaric acid skeleton was developed from diethyl l-tartrate. These guanidines are easily accessed with tunable steric and electronic properties. The utilities of the guanidines were highlighted by their ability to catalyze the α-hydroxylation of β-ketoesters and β-diketones with remarkable efficiency and excellent enantioselectivity.

A natural quinidine-catalyzed asymmetric chlorination of 4-substituted pyrazolones is developed, affording products with a quaternary chiral chlorine-attached carbon centre in high yield with excellent enantioselectivity. The low catalyst loading (1 mol%), broad substrate scope, and facile and valuable transformation of the product highlight the practical utility of this process.

An organocatalytic asymmetric [3+2] cycloaddition of 3-amino oxindole-based azomethine ylides and α,β-ynones has been developed. This reaction afforded spiro[dihydropyrrole-2,3′-oxindole] products in high chemical yields with excellent stereoselectivities (up to 99% yields, >20:1 dr and >99% ee). Notably, a series of important spiro[pyrrole-oxindole] derivatives were readily obtained via oxidation of the cycloadducts, thus extending the diversity of the products.

We report a highly efficient approach to constructing chiral N,S-acetals using 5-substituted rhodanines as sulfur-bound pronucleophiles catalyzed by natural cinchona alkaloids quinine or quinidine. This α-amination reaction has a broad substrate scope, and the products featuring both rhodanine and N,S-acetal structural motifs were obtained in high yields and excellent enantioselectivities.

The Michael addition of 3-substituted oxindoles to nitroolefins was catalyzed by a novel tartrate-derived guanidine in high yield with excellent diastereo- and enantioselectivity. This method showed an extraordinarily broad substrate scope in terms of both reaction partners.

The catalytic asymmetric three-component 1,3-dipolar cycloaddition of 3-amino oxindoles with aldehydes and nitroolefins under the catalysis of a chiral phosphoric acid is reported. The reaction provides a facile approach to synthesize a diverse array of spiro[pyrrolidine-2,3′-oxindoles] in high yields with excellent diastereo- and enantioselectivities under mild conditions.