Iridium-catalyzed asymmetric hydrogenation of 3-substituted unsaturated oxindoles to prepare C3-mono substituted oxindoles

An efficient and enantioselective hydrogenation of 3-substituted unsaturated oxindoles has been developed by an iridium complex of tropos phosphine-oxazoline ligands. It is the first example to prepare chiral C3-mono substituted oxindoles via asymmetric catalysis. And the reaction provides instant access to this kind of compounds with excellent conversion and enantioselectivities (up to 93% ee).     

Diastereo- and enantioselective conjugate addition of 3-substituted oxindoles to enones via bifunctional catalysts

This paper presents a synthetically challenging vicinal quaternary-tertiary C–C forming reaction of 3-substituted oxindoles and chalcones by a simple aryl substituted bifunctional thiourea catalyst. The reactions work with a broad range of chalcones, giving chiral 3,3′-substituted oxindoles type compounds with adjacent quaternary-tertiary stereocenters in high yields (up to 99%), very good dr (up to >98:2) and very good ee (up to 96%).     

Enantioselective organocatalyzed sulfenylation of 3-substituted oxindoles

A highly enantioselective sulfenylation reaction with respect to 3-substituted oxindoles and electrophilic sulfur reagents by a quinidine catalyst was investigated.     

Chiral phosphine-catalyzed asymmetric allylic alkylation of 3-substituted benzofuran-2(3H)-ones or oxindoles with Morita-Baylis-Hillman carbonates

An efficient chiral phosphine-catalyzed asymmetric substitution reaction of MBH carbonates with 3-substituted benzofuran-2(3H)-ones or 3-substituted oxindoles has been described in this context, giving the corresponding allylic alkylation products bearing adjacent quaternary and tertiary stereogenic centers in high yields, moderate diastereoselectivities and high enantioselectivities under mild conditions.     

A novel and efficient synthesis of 3-fluorooxindoles from indoles mediated by Selectfluor

[reaction: see text] Treatment of several 3-substituted indoles, including derivatives of tryptophan and serotonin, with commercially available Selectfluor in acetonitrile/water furnished 3-substituted 3-fluorooxindoles in good to high yields. Since 3-fluorooxindoles obtained are sterically similar to both oxindoles and 3-hydroxyoxindoles, they should be useful as probes for investigating the enzymatic mechanism of indole biosynthesis and metabolism.     

Construction of chiral 3-alkenyl-3-substituted oxindoles by stereoselective direct alkenylation of isatin derivatives and 3-vinylindoles

An efficient asymmetric alkenylation between 3-vinylindoles and isatin derivatives was developed under catalysis of a chiral copper complex. A series of optically active 3-alkenyl-3-substituted oxindoles were obtained in excellent yields and stereoselectivities. The reaction mechanism was proposed and supported by DFT calculation.     

Vinylogous N,N-dimethylaminomethylenation of 3-[(1-substituted)ethylidene]-oxindoles with N,N-dimethylformamide dimethylacetal

An efficient stereoselective synthesis of various 3-(3-dimethylaminoprop-2-enylidene)oxindoles has been disclosed. The compounds were synthesized via a vinylogous N,N-dimethylaminomethylenation at the γ-position of 3-[(1-substituted)ethylidene]oxindoles with DMF-DMA.     

Catalytic asymmetric sulfenylation of unprotected 3-substituted oxindoles

Catalytic asymmetric sulfenylation of unprotected 3-substituted oxindoles has been developed via cooperative catalysis of a chiral N,N'-dioxide-Sc(OTf)(3) complex and a Br?nsted base. Utilizing readily available N-(phenylthio)phthalimide as the sulfur source, a wide range of optically active 3-phenylthiooxindoles were obtained in excellent yields with excellent enantioselectivities under mild reaction conditions.     

A simple and eco-friendly method for the aminomethylation of 3-substituted oxindoles via three-component Mannich reaction in aqueous media

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.     

Squaramide-catalyzed diastereo- and enantioselective Michael addition of 3-substituted oxindoles to nitroalkenes

An efficient diastereo- and enantioselective Michael addition of 3-substituted oxindoles onto nitroalkenes catalyzed by a bifunctional chiral squaramide catalyst has been developed. This organocatalytic reaction with 2 mol % of catalyst proceeded smoothly to afford 3,3-disubstituted oxindoles in high yields with good diastereoselectivities and enantioselectivities (up to 98:2 dr, 88% ee).     

Enantioselective direct Mannich reactions of 3-substituted oxindoles catalyzed by chiral phosphine via dual-reagent catalysis

A combination of an amino acid-derived chiral phosphine catalyst and methyl acrylate to catalyze the direct Mannich reaction of 3-substituted oxindoles and imines has been reported to afford 3-tetrasubstituted oxindole derivatives which are key structures for biological activities. The products are formed with a quaternary carbon and featured with two adjacent chiral centers. Various N-EDG(electron-donating group) and N-EWG(electron-withdrawing group) protected oxindoles, including 3-aryl and 3-alkyl substituted ones, have been evaluated with aromatic and aliphatic imines under this catalytic system, smoothly giving desired products in good yields as well as excellent diastereo- and enantioselectivities.     

Regio- and enantioselective conjugate addition of β-nitro α,β-unsaturated carbonyls to construct 3-alkenyl disubstituted oxindoles

Reversal of regioselectivity in the catalytic asymmetric conjugate additions of 3-substituted oxindoles to β-nitroenones or β-nitroacrylates was established with chiral scandium catalysts. It enabled the construction of functionalized 3,3-disubstituted oxindoles, including terminal and internal vinyl groups in excellent yields and ee values.     

Chiral calcium VAPOL phosphate mediated asymmetric chlorination and Michael reactions of 3-substituted oxindoles

We disclose a novel high yielding and highly enantioselective chiral calcium VAPOL phosphate-catalyzed chlorination of 3-substituted oxindoles with N-chlorosuccinimide (NCS). The reaction conditions are also shown to be effective for the catalytic enantioselective Michael addition of 3-aryloxindoles to methyl vinyl ketone.     

Organocatalytic stereoselective mannich reaction of 3-substituted oxindoles

The asymmetric Mannich reaction of 3-substituted oxindoles and N-Boc imines was investigated for the first time, employing bifunctional thiourea-tertiary amine organocatalysts based on DPEN scaffold. The novel transformations exhibited high diastereoselectivities, and the Mannich adducts bearing adjacent quaternary and tertiary chiral centers were generally obtained in good to excellent enantioselectivities (up to 95% ee).     

Chiral iminophosphoranes organocatalyzed asymmetric hydroxylation of 3-substituted oxindoles with oxaziridines

Enantioselective hydroxylation of N-protected 3-substituted oxindoles has been developed via chiral iminophosphorane catalysis with oxaziridines as oxidants. As such, a variety of optically active 3-substituted-3-hydroxy-2-oxindoles were obtained in excellent yields (91–99%) and moderate to excellent level of enantiomeric excess (up to 94% ee).     

Photochemical Deracemization of 3-Substituted Oxindoles

Racemic 3-substituted oxindoles were successfully converted into enantiomerically pure or enriched material (up to 99 % ee) upon irradiation at λ=366 nm in the presence of a chiral benzophenone catalyst (10 mol %). The photochemical deracemization process allows predictable editing of the stereogenic center at carbon atom C3. Light energy compensates for the associated loss of entropy and enables the decoupling of potentially reversible reactions, i.e. a hydrogen atom transfer to (photochemical) and from (thermal) the carbonyl group of the catalyst. The major enantiomer is continuously enriched in several catalytic cycles. The obtained oxindoles were shown to be valuable intermediates for further transformations, which proceeded with complete retention at the stereogenic center.     

A novel acid-catalyzed C5-alkylation of oxindoles using alcohols

A novel C5-alkylation of oxindoles using alcohols as alkylating agents under acid catalysis is described for the first time. The reactions of various benzylic, allylic and propargylic alcohols are studied to obtain the corresponding 5-substituted oxindoles in good yields.     

Enantioselective organocatalytic oxyamination of unprotected 3-substituted oxindoles

An enantioselective α-oxyamination of unprotected 3-substituted oxindoles with nitrosobenzene catalyzed by tertiary amine-thiourea bifunctional organocatalysts has been developed and affords the corresponding 3-amino-2-oxindole derivatives in good yields and with moderate to excellent enantioselectivities (up to > 99.9?:?0.1 er when the product is isolated by direct filtration from the reaction mixture). The absolute configuration of the major enantiomers of the products has been established both by chemical correlation and by comparison between the theoretically calculated and the experimental ECD.     

Pd/Cu-Catalyzed Enantioselective Sequential Heck/Sonogashira Coupling: Asymmetric Synthesis of Oxindoles Containing Trifluoromethylated Quaternary Stereogenic Centers

An asymmetric palladium and copper co-catalyzed Heck/Sonogashira reaction between o-iodoacrylanilides and terminal alkynes to synthesize chiral oxindoles was developed. In particular, a wide range of CF₃-substituted o-iodoacrylanilides reacted with terminal alkynes, affording the corresponding chiral oxindoles containing trifluoromethylated quaternary stereogenic centers in high yields with excellent enantioselectivities (94–98 % ee). This asymmetric Heck/Sonogashira reaction provides a general approach to access oxindole derivatives containing quaternary stereogenic centers including CF₃-substituted ones.     

Assembly of spirooxindole derivatives containing four consecutive stereocenters via organocatalytic Michael-Henry cascade reactions

A novel organocatalytic strategy for the synthesis of highly substituted spirocyclopentaneoxindoles was developed employing simple nitrostyrenes and 3-substituted oxindoles as starting materials. Michael-Henry cascade reactions, enabled through cinchona alkaloid organocatalysis, provided products in high yield and excellent enantioselectivity in a single step.