A method for the enantioselective construction of hydrocarbazole skeletons through dearomative [4 + 2] annulation of 3-nitroindoles with Nazarov reagents is reported. The reactions use multiple hydrogen-bonding bifunctional thiourea as catalyst and are highly diastereo- and enantioselective (up to >20:1 dr and >99% ee). The protocol was demonstrated by preparative-scale experiment and the versatile conversion of the products. The multiple hydrogen-bonding in the catalyst plays a pivotal role in the reactivity and stereoselectivity.

A highly organocatalyzed asymmetric Michael addition reaction of pyrazoleamides to β-phthalimidonitroethene has been developed with a chiral bifunctional thiourea-tertiary amine as the catalyst. A wide range of γ-nitro β-amino amides were readily obtained in good to excellent yields with high diastereo- and enantioselectivities (up to 99% yield, 99% ee and >20:1 dr). The large scale experiment and transformation of the product have also been demonstrated.Download high-res image (209KB)Download full-size image

A method for the synthesis of α,α-bisthiofunctionalized butenolide compounds has been successfully developed. The bis-sulfenylation of γ-substituted butenolides at α-position is promoted by using triethylamine as the catalyst and N-(aryl(alkyl)sulfanyl)succinimides or N-(phenylsulfanyl)phthalimides as sulfenylating reagents under mild reaction conditions. A range of α-sulfenylated butenolide derivatives could be smoothly obtained in moderate to excellent yields. A preliminary attempt at the catalytic asymmetric α-sulfenylation of α-methyl-γ-phenyl-substituted butenolide was also conducted and afforded promising enantioselectivity.Download high-res image (184KB)Download full-size image

Catalytic asymmetric Michael addition–lactonization of arylacetyl phosphonates to β,γ-unsaturated α-keto esters by a chiral bifunctional thiourea–tertiary amine was established. Using the developed protocol, a range of optically pure syn-3,4-dihydropyranones were generated in good yields with good to excellent stereoselectivities (up to >20:1 dr and 99% ee). Meanwhile, when stoichiometric diisopropylethylamine and 1,8-diazabicyclo[5.4.0]undec-7-ene were used as the base for the same reaction, a series of 5,6-dihydropyranones could be obtained in moderate to good yields (53–75% yield).

A base-mediated Neber reaction of enaminopyrazolones, which are the tautomers of 4-acyloxime-2-pyrazolin-5-ones, with sulfonyl chlorides was achieved. With this developed approach, a range of spiro-fused 2H-azirine-pyrazolones were obtained in good yields under mild conditions. A preliminary trial of a catalytic asymmetric version of the Neber reaction was conducted and gave promising enantioselectivity.

An organocatalyzed direct asymmetric vinylogous Michael addition reaction of α,β-unsaturated γ-butyrolactam to 2-enoylpyridines has been developed with a chiral bifunctional amine-squaramide as the catalyst. This approach provides easy access to a series of optically active α,β-unsaturated γ-substituted butyrolactams in high yields (up to 99%) with excellent diastereoselectivities (up to >99:1) and enantioselectivities (up to >99% ee).

An unprecedented reaction between indolin-2-ones and α-substituted ketones has been developed. Using this protocol, a wide range of biologically important 3-hydroxy-3-phenacyloxindole derivatives could be obtained in good yield (up to 93%) under mild reaction conditions. A possible mechanism of this reaction was tentatively proposed based on some control experiments and MS spectrometry analysis.

Catalytic asymmetric Michael addition of arylacetyl phosphonates to nitroalkenes was achieved with a chiral bifunctional amine-thiourea bearing a multiple-hydrogen-bond donor as a catalyst. A range of α-substituted carboxylic ester compounds with contiguous tertiary stereocenters could be smoothly obtained in good yields (up to 85%) and with high to excellent diastereo- and enantioselectivities (up to >99:1 dr and 95% ee). The large scale experiment and facile synthesis of a chiral γ-butyrolactam have also been demonstrated.

An organocatalytic asymmetric Michael addition reaction of 3-pyrrolyloxindoles to β-phthalimidonitroethene has been developed with a bifunctional thiourea–tertiary amine as the catalyst. A range of 3,3′-disubstituted oxindoles bearing contiguous 3,α,β-triamino functionality could be obtained in high yields with good diastereoselectivities and high enantioselectivities (up to 99% yield, 99:1 dr, and 98% ee). The higher reactivity of β-phthalimidonitroethene compared to the reactivity of ordinary nitroalkenes in the reaction with 3-pyrrolyloxindoles was demonstrated by contrast experiments.

An unprecedented organocatalytic asymmetric Michael/cyclization cascade reaction of 3-isothiocyanato oxindoles and 3-nitroindoles has been disclosed. A wide range of enantioenriched polycyclic spirooxindoles, containing three contiguous chiral centers with two of them having quaternary stereocenters, could be smoothly obtained with satisfactory results (up to 99% yield, >99:1 dr, and 96% ee). This method is very promising because the reaction is scalable, and the versatile transformations of the products into other spirocyclic oxindoles are also feasible.

The diastereo- and enantioselective direct vinylogous Michael addition reaction of γ-substituted butenolides to 2-enoylpyridines has been achieved. A range of γ,γ-disubstituted butenolide derivatives, bearing two consecutive tri- and tetrasubstituted stereogenic centers, were readily obtained in good yields with excellent stereoselectivities (up to >99:1 dr and >99% ee).

A range of 3-pyrrolyl-3,3′-disubstituted oxindoles were smoothly obtained via the reaction of 3-pyrrolyl-oxindoles with nitroalkenes using an organocatalyst. The usefulness of the protocol was also demonstrated by the versatile conversions of the Michael adducts into other functionalized 3,3′-disubstituted oxindoles, as well as into the analogues of some valuable natural products.

A highly enantioselective Michael addition of 3-monosubstituted oxindoles to α,β-unsaturated acyl phosphonates with chiral squaramides as catalysts is investigated for the first time. A wide range of 3,3′-disubstituted oxindole adducts bearing adjacent quaternary and tertiary stereogenic centres could be smoothly obtained in good yields (up to 98%), diastereo- (up to >99:1 dr) and enantioselectivities (up to 98% ee) with the developed protocols.

A range of structurally diverse chiral spiro[imidazolidine-2-thione-4,3′-oxindole] compounds could be obtained via a domino Mannich-cyclization reaction of 3-isothiocyanato oxindoles and imines with commercial quinine as catalyst under mild conditions. The protocol is significantly characterized by simple process, easily available catalyst, high reactivity, low catalyst loading (1 mol %), and good to excellent diastereo- and enantioselectivity (up to>99:1 dr and 97% ee). A plausible dual activation working model was tentatively proposed to account for the stereochemistry of the domino Mannich-cyclization process.

An efficient and unprecedented organocatalytic asymmetric reaction of 3-pyrrolyl-oxindoles with α,β-unsaturated aldehydes to generate spirocyclic oxindole compounds was developed. The reactions were catalyzed by diphenylprolinol silyl ether and 2-fluorobenzoic acid via an asymmetric Michael/Friedel–Crafts cascade process, followed by dehydration with p-toluenesulfonic acid to afford a wide variety of structurally diverse spiro[5,6-dihydropyrido[1,2-a]pyrrole-3,3′-oxindole] derivatives in high yields (up to 93%) and with high to excellent diastereo- and enantioselectivities (up to >99:1 dr and 97% ee).

Catalytic asymmetric sulfenylation and selenenylation of 3-pyrrolyl-oxindoles for the synthesis of 3,3-disubstituted oxindoles bearing two different heteroatoms at the C3 position have been achieved with commercially available cinchonidine as catalyst. A wide range of optically active 3-thio-3-pyrrolyl-oxindoles and 3-seleno-3-pyrrolyl-oxindoles could be smoothly obtained under mild conditions with satisfactory results. The promising applicability of the protocol was also demonstrated by large-scale production.

Enantioselective Michael/cyclization cascade reactions of 3-hydroxyoxindoles/3-aminooxindoles with α,β-unsaturated acyl phosphonates by using a cinchonine derived squaramide as the catalyst were developed. A broad range of spirocyclic oxindole-γ-lactones/lactams could be obtained in moderate to excellent yields (up to 98%) with good to excellent diastereo- and enantioselectivities (up to >99:1 dr and 97% ee) under mild conditions. This work represents the first example about the α,β-unsaturated acyl phosphonates for the asymmetric construction of spirocyclic oxindoles.

An efficient method for the preparation of 3-sulfonylated 3,3-disubstituted oxindole derivatives has been developed. The protocol involves a base-catalyzed addition of sulfinate salts to 3-halooxindoles, affording a wide range of 3-sulfonylated 3,3-disubstituted oxindoles in good to excellent yields under mild conditions. A preliminary trial of asymmetric catalytic version was conducted and gave promising enantioselectivity. The mechanism for the reaction was tentatively explored with the help of mass spectrometric analysis.

An efficient Diels–Alder reaction of 3-hydroxy-2-pyrone with a wide range of methyleneindolinones has been developed by employing 4-dimethylaminopyridine as a catalyst under mild reaction conditions. This process provides a promising method for the construction of structurally diverse spirocyclic oxindoles containing bicyclic lactone motif with moderate diastereoselectivities and good to excellent yields.

A new methodology was developed for the synthesis of spirocyclic oxindoles bearing polyfunctional dihydropyrrole units via an organocatalytic tandem Michael/cyclization sequence. Products bearing adjacent quaternary–tertiary stereocenters were smoothly obtained in high yields (up to 97% yield) with excellent diastereoselectivities up to >20/1.

An efficient method for the direct construction of two classes of spirocyclic oxindoles by the reactions of 3-hydroxyoxindoles/3-aminooxindoles and (Z)-olefinic azlactones through a tandem Michael addition–ring transformation process has been developed. With DBU as the catalyst, a range of spiro-butyrolactoneoxindoles and spiro-butyrolactamoxindoles, containing an oxygen or a nitrogen heteroatom, respectively, in the spiro stereocenter, were smoothly obtained with good to excellent diastereoselectivities in high yields.

A wide range of structurally diverse 3,3′-thiopyrrolidonyl spirooxindoles bearing three contiguous stereogenic centers can be smoothly obtained via a domino Michael/cyclization reaction between 3-isothiocyanato oxindoles and 3-methyl-4-nitro-5-alkenyl-isoxazoles with commercially available quinine as the catalyst under mild conditions. The protocol is significantly characterized by high reactivity, a low catalyst loading (1 mol %), and an excellent diastereo- and enantioselectivity (up to >99:1 dr and 98% ee).

A novel ruthenium catalyst on the basis of a chiral monophosphorus ligand is efficient for the asymmetric addition of arylboronic acids to aryl aldehydes, providing a series of chiral diarylmethanols in excellent yields and enantioselectivities (up to 92% ee). Preliminary study has shown that this process is catalyzed by a Ru complex with a single monophosphorus ligand.

An enantioselective synthesis of quaternary 3-aminooxindoles with 3-monosubstituted 3-aminooxindoles as nucleophiles is first presented. A Michael addition reaction of 3-monosubstituted 3-aminooxindoles to nitroolefins has been developed with a bifunctional thiourea-tertiary amine as a catalyst to afford a range of 3,3-disubstituted oxindoles bearing adjacent quaternary-tertiary centers in good results (up to 98% yield, >99:1 dr, and 92% ee). We also demonstrate the potential synthetic utility of this methodology by a transformation of the product into a spirocyclic oxindole compound.

α-Isothiocyanato phosphonates are first used as nucleophiles to react with aldehydes for the asymmetric synthesis of β-hydroxy-α-amino phosphonic acid derivatives. The process is catalyzed by a quinine-derived thiourea via cascade aldol/cyclization reaction, affording a wide range of protected β-hydroxy-α-amino phosphonates containing adjacent quaternary-tertiary stereocenters in up to 93% yield, up to 81% ee, and >99:1 dr. This work represents the first example of α-isothiocyanato phosphonates serving as nucleophiles that are used in the catalytic asymmetric synthesis.

An efficient FeCl3-catalyzed stereoselective intramolecular tandem 1,5-hydride transfer/ring closure reaction was developed. The method allows for the formation of structurally diverse spirooxindole tetrahydroquinolines in high yields (up to 98%) with good to excellent levels of diastereoselectivity (up to 99:1 dr). The catalytic enantioselective variant of this process was also investigated preliminarily with a chiral BINOL-derived phosphoric acid.

An efficient and stereoselective reaction between 3-isothiocyanato oxindoles and isatins/isatinimines has been developed to afford structurally diverse dispiro[oxazolidine-2-thione]bisoxindoles and dispiro[imidazolidine-2-thione]bisoxindoles in excellent results under mild conditions. The potential of asymmetric induction by means of a chiral auxiliary was explored. The isomers are separable, and products could be isolated as single diastereomers by column chromatography. Further synthetic transformations of the reaction product were also successfully realized.

The catalytic enantioselective three-component Petasis reaction among salicylaldehydes, amines, and organoboronic acids with a newly designed thiourea-binol catalyst is presented. A broad range of alkylaminophenols can be obtained in good yield (up to 92%) and good to high enantioselectivity (up to 95% ee). A possible reaction pathway for this catalytic enantioselective Petasis reaction is tentatively proposed.

An unprecedented method for the construction of optically active 3,3′-disubstituted oxindoles via an organocatalyzed decarboxylative stereoablation reaction has been developed. We describe the first asymmetric reaction between β-ketoacids and 3-halooxindoles utilizing an organocatalyst. This method allows for the formation of a variety of 3,3′-disubstituted oxindoles bearing a keto-carbonyl group, which are not easily accessible using other methodologies, in moderate to good yields with high enantioselectivities.

A simple and eco-friendly method for the aminomethylation of various 3-substituted oxindoles via three-component Mannich reaction in aqueous media has been established. A variety of oxindoles containing a quaternary carbon center, which comprises an aminomethyl group were obtained smoothly in good yields (up to 93%) with this method. Particularly valuable features, such as employing cheap and readily available formalin as a useful aminomethylation C1 unit and using water as a reaction medium, are embodied in this method.

An enantioselective 1,6-Michael addition reaction of arylthiols to a wide range of 3-methyl-4-nitro-5-alkenyl-isoxazoles catalyzed by readily available Takemoto’s thiourea catalyst has been developed. This reaction provides a useful catalytic method for the synthesis of optically active chiral sulfur compounds bearing a 4-nitroisoxazol-5-yl moiety in high to excellent yields (up to 97%) and high enantioselectivities (up to 91% ee). Significantly, the potential utilities of the protocol had been further demonstrated by gram-scale reaction and the versatile conversions of some resulting products into other functionalized and useful compounds.

An organocatalytic asymmetric Michael addition reaction of 3-substituted oxindoles to protected 2-amino-1-nitroethenes has been developed. The reaction is catalyzed by a simple and readily available amino-indanol derivative and affords the desired products in very high yields (up to 99%) with excellent diastereoselectivities (up to >99:1) and very good enantioselectivities (up to 90%). Significantly, this study provides a general catalytic method for the construction of 3,3′-disubstituted oxindoles bearing α,β-diamino functionality as well as vicinal chiral quaternary/tertiary stereocenters. The potential utility of the protocol also had been demonstrated by gram-scale reaction and the versatile conversion of product. Furthermore, On the basis of the comprehensive experimental results and the absolute configuration of one of the Michael adducts, a work model was also proposed to explain the origin of asymmetric induction.

A highly diastereo- and enantioselective Michael addition reaction with respect to prochiral 3-substituted oxindoles and maleimides by a chiral bifunctional thiourea−tertiary amine catalyst was investigated for the first time. The corresponding adducts, containing a quaternary center at the C3-position of the oxindole as well as a vicinal tertiary center, were generally obtained in good to high yields (up to 92%) with high to excellent diastereo- (up to 99:1 dr) and enantioselectivities (up to 99% ee).

The first enantioselective organocatalytic two- and three-component reactions via a domino Knoevenagel/Michael/cyclization sequence with cupreine as catalyst have been developed. A wide range of optically active spiro[4H-pyran-3,3′-oxindoles] were obtained in excellent yields (up to 99%) with good to excellent enantioselectivities (up to 97%) from simple and readily available starting materials under mild reaction conditions. These heterocyclic spirooxindoles will provide promising candidates for chemical biology and drug discovery.

An efficient one-pot synthetic approach to access a variety of 3-(indol-3-yl)quinoxalin-2-ones from various quinoxalin-2-ones and very wide scope of indoles through TfOH-catalyzed Friedel–Crafts type coupling reaction in DMF has been developed. Only 10 mol % Brønsted acid as a catalyst, air as an oxidizer, and very wide range of substrates are the prominent advantages of this method.

In the presence of molecular sieve (MS) 4 Å in DMF, a catalyst-free aldol condensation of a variety of aromatic and aliphatic ketones with isatins under mild reaction conditions has been developed. This approach may provide access to a wide range of 3-substituted-3-hydroxyindolin-2-ones in good to excellent yields.

A highly bifunctional thiourea-tertiary amine-catalyzed enantioselective Michael addition reaction of anthrone to a wide variety of nitroalkenes has been developed, and the corresponding adducts were obtained smoothly in high yields (up to 97%) and good enantioselectivities (up to 94% ee).9-(2-Nitro-1-phenylethyl)anthracen-10(9H)-oneC22H17NO3Ee = 93%[α]D20=+25.4 (c 0.48, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(4-Chlorophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16ClNO3Ee = 93%[α]D20=+21.7 (c 0.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(4-Methoxyphenyl)-2-nitroethyl)anthracen-10(9H)-oneC23H19NO4Ee = 86%[α]D20=+18.7 (c 0.74, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-p-tolylethyl)anthracen-10(9H)-oneC23H19NO3Ee = 85%[α]D20=+25.4 (c 0.62, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-(4-nitrophenyl)ethyl)anthracen-10(9H)-oneC22H16N2O5Ee = 80%[α]D20=+21.2 (c 0.42, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(4-Bromophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16BrNO3Ee = 91%[α]D20=+15.4 (c 0.54, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)9-(1-(4-Fluorophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16FNO3Ee = 94%[α]D20=+31.0 (c 0.46, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown4-(2-Nitro-1-(9-oxo-9,10-dihydroanthracen-10-yl)ethyl)benzonitrileC23H16N2O3Ee = 91%[α]D20=+22.0 (c 0.62, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(2-Bromophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16BrNO3Ee = 83%[α]D20=+7.1 (c 0.74, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(2-Methoxyphenyl)-2-nitroethyl)anthracen-10(9H)-oneC23H19NO4Ee = 89%[α]D20=-8.6 (c 0.88, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-(2-nitrophenyl)ethyl)anthracen-10(9H)-oneC22H16N2O5Ee = 90%[α]D20=-4.0 (c 0.20, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(2-Chlorophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16ClNO3Ee = 84%[α]D20=-14.8 (c 0.54, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-m-tolylethyl)anthracen-10(9H)-oneC23H19NO3Ee = 91%[α]D20=+33.2 (c 0.60, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-(3-Nitrophenyl)ethyl)anthracen-10(9H)-oneC22H16N2O5Ee = 90%[α]D20=+38.1 (c 0.40, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(3-Bromophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16BrNO3Ee = 90%[α]D20=+31.0 (c 0.58, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-(3-(trifluoromethyl)phenyl)ethyl)anthracen-10(9H)-oneC23H16F3NO3Ee = 91%[α]D20=+26.2 (c 0.44, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(3-Fluorophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H16FNO3Ee = 90%[α]D20=+26.3 (c 0.58, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(2,4-Dichlorophenyl)-2-nitroethyl)anthracen-10(9H)-oneC22H15Cl2NO3Ee = 81%[α]D20=-16.0 (c 0.22, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(Furan-2-yl)-2-nitroethyl)anthracen-10(9H)-oneC20H15NO4Ee = 90%[α]D20=-2.3 (c 0.74, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(2-Nitro-1-(thiophen-2-yl)ethyl)anthracen-10(9H)-oneC20H15NO3SEe = 91%[α]D20=+17.3 (c 0.50, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-(Naphthalen-1-yl)-2-nitroethyl)anthracen-10(9H)-oneC26H19NO3Ee = 60%[α]D20=-36.0 (c 0.60, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(3-Methyl-1-nitrobutan-2-yl)anthracen-10(9H)-oneC19H19NO3Ee = 84%[α]D20=+34.1 (c 0.45, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(4-Methyl-1-nitropentan-2-yl)anthracen-10(9H)-oneC20H21NO3Ee = 86%[α]D20=+24.3 (c 0.64, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown9-(1-Cyclohexyl-2-nitroethyl)anthracen-10(9H)-oneC22H23NO3Ee = 85%[α]D20=+61.0 (c 0.24, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: unknown

A catalytic asymmetric Michael/cyclization cascade reaction of 3-isothiocyanato oxindoles and 3-nitroindoles has been disclosed with a chiral Zn(OTf)2/diphenylamine-linked bis(oxazoline) complex as the catalyst. A range of enantioenriched polycyclic spirooxindole derivatives containing three contiguous stereocenters were efficiently constructed in quantitative yields with excellent diastereo- and enantioselectivities. Importantly, the metal catalytic strategy in this work is significantly superior to the previous organocatalytic method in the diastereo- and enantioselectivities for almost all of the examined cases.

A base-mediated Neber reaction of enaminopyrazolones, which are the tautomers of 4-acyloxime-2-pyrazolin-5-ones, with sulfonyl chlorides was achieved. With this developed approach, a range of spiro-fused 2H-azirine-pyrazolones were obtained in good yields under mild conditions. A preliminary trial of a catalytic asymmetric version of the Neber reaction was conducted and gave promising enantioselectivity.

A range of 3-pyrrolyl-3,3′-disubstituted oxindoles were smoothly obtained via the reaction of 3-pyrrolyl-oxindoles with nitroalkenes using an organocatalyst. The usefulness of the protocol was also demonstrated by the versatile conversions of the Michael adducts into other functionalized 3,3′-disubstituted oxindoles, as well as into the analogues of some valuable natural products.

The diastereo- and enantioselective direct vinylogous Michael addition reaction of γ-substituted butenolides to 2-enoylpyridines has been achieved. A range of γ,γ-disubstituted butenolide derivatives, bearing two consecutive tri- and tetrasubstituted stereogenic centers, were readily obtained in good yields with excellent stereoselectivities (up to >99:1 dr and >99% ee).

An unprecedented reaction between indolin-2-ones and α-substituted ketones has been developed. Using this protocol, a wide range of biologically important 3-hydroxy-3-phenacyloxindole derivatives could be obtained in good yield (up to 93%) under mild reaction conditions. A possible mechanism of this reaction was tentatively proposed based on some control experiments and MS spectrometry analysis.

A highly enantioselective Michael addition of 3-monosubstituted oxindoles to α,β-unsaturated acyl phosphonates with chiral squaramides as catalysts is investigated for the first time. A wide range of 3,3′-disubstituted oxindole adducts bearing adjacent quaternary and tertiary stereogenic centres could be smoothly obtained in good yields (up to 98%), diastereo- (up to >99:1 dr) and enantioselectivities (up to 98% ee) with the developed protocols.

An organocatalyzed direct asymmetric vinylogous Michael addition reaction of α,β-unsaturated γ-butyrolactam to 2-enoylpyridines has been developed with a chiral bifunctional amine-squaramide as the catalyst. This approach provides easy access to a series of optically active α,β-unsaturated γ-substituted butyrolactams in high yields (up to 99%) with excellent diastereoselectivities (up to >99:1) and enantioselectivities (up to >99% ee).