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A copper-catalyzed and microwave-assisted synthesis of fully substituted pyrroles has been developed. A series of pentasubstituted pyrroles, especially α-arylpyrroles, could be obtained in moderate to good yields (up to 93%) through a tandem propargylation/alkyne azacyclization/isomerization sequence from readily available β-enamino compounds and propargyl acetates.

The development of concise methods for the synthesis of functionalized small molecules is important in the search for new bioactive molecules. To contribute to this, we have developed oxa-hetero-Diels–Alder reactions of enones with isatins catalyzed by amine-based catalyst systems. Various spirooxindole tetrahydropyranones were synthesized either in enantiomerically enriched forms or as racemic forms depending on the catalyst system. The reaction products were further transformed at the ketone carbonyl group and the indole nitrogen. Using these reactions, functionalized spirooxindole tetrahydropyran derivatives with functional groups in four directions in a three-dimensional space were concisely obtained. From these synthesized compounds, an inhibitor of human ion channel Nav1.7 with μM-level activity was identified, indicating that the developed reaction methods are useful for providing molecules for the discovery of new biofunctional molecules.

A novel copper-catalyzed microwave-promoted propargyl­ation/alkyne oxacyclization/isomerization cascade for the synthesis of 2-methylfuro[3,2-c]coumarins has been developed. This reaction provides furo[3,2-c]coumarins in moderate to good yields (≤82%) from readily available 4-hydroxycoumarins and terminal propargyl acetates as starting materials. Interestingly, by changing the solvent from dimethyl sulfoxide to 1,2-dichloroethane, the isomeric series of 2-meth­ylene-2,3-dihydrofuro[3,2-c]coumarins were obtained in good to acceptable yields (≤85%).

An efficient method for the one-pot synthesis of polysubstituted 3-acylpyrroles by cascade reactions of readily available unsaturated ketones and N-substituted propargylated amines is developed using the cooperative catalysis of pyrrolidine and a copper salt.

Spirooxindoles are important compounds as they are often found in bioactive molecules. Thus, the development of new spirooxindoles and of synthetic routes to spirooxindoles is a great interest to discover new biofunctional molecules and therapeutic leads. We developed a concise method for the synthesis of spirooxindoles bearing a furanose unit. 1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU) was used for an aldol reaction of a pyruvic aldehyde derivative with isatin; reduction of the ketone group was followed by treatment with acid to generate the spirofuranose unit. A set of furanose spirooxindoles were obtained in good to high yields.

Fluorogenic aldehydes or probes for monitoring of the progress of aldol reactions have been developed. Fluorescence of benzaldehydes conjugated with aryl groups via a double or triple bond and of their aldol products was evaluated in aqueous solutions. Based on the fluorescence, fluorogenic aldol reaction substrates and retro-aldol reaction substrates were identified. Use of the probe system with optimal fluorescence properties for aldol reactions was demonstrated in assays with purified protein catalysts and with overproduced crude protein catalysts in cell lysates.

An atom-economical, highly diastereo- and enantioselective organocatalytic hetero Diels—Alder reaction of enones with isatins is presented.

The first allylic alkylation of indene derivatives with Morita—Baylis—Hillman carbonates (I) is catalyzed by (DHQD)2-AQN to give the desired products with high enantioselectivities but only moderate yields.

In addition to propargyl sulfones, some activated olefins can also be used for the generation of spirocyclic oxindoles.

The in situ generation of the tert-butoxy anion as a strong Broensted base by reaction of the amine catalyst with the Morita—Baylis—Hillman carbonates is crucial for generation of the hard nucleophiles.

The first chemoselective asymmetric N-allylic alkylation of enamides (I) and (IV) with Morita—Baylis—Hillman carbonates (II) by the metal-free catalysis of modified cinchona alkaloids is described.

A number of enantioenriched natural-product-like or drug-like molecules with fused bi-, tri-, and polycyclic structures are constructed by synthetic transformations of some prepared Michael-adducts.

A Lewis base-catalyzed asymmetric allylic alkylation of Morita−Baylis−Hillman carbonates derived from isatins has been investigated, which provides an electrophilic pathway to access oxindoles bearing C3-quaternary stereocenters. Excellent diastereoselectivity and high enantioselectivity have been obtained in the vinylogous functionalization of α,α-dicyanoolefin nucleophiles, giving multifunctional products with vicinal quaternary and tertiary chiral carbon centers.

A variety of substrates, obtained by allylic—allylic alkylation of α,α-dicyanoalkenes and Morita—Baylis—Hillman carbonates, smoothly undergoes intramolecular radical cyclization.

The direct asymmetric allylic alkylation of β,γ-butenolides with MBH carbonates to access γ,γ-disubstituted butenolides containing adjacent quaternary and tertiary chiral centers has been presented in excellent stereoselectivities (86−96% ee, dr >95:5) and moderate to good yield (50−83%). Their synthetic utility has been well demonstrated by the facile construction of bicyclic lactones bearing 4−5 stereogenic centers.

The peroxy-asymmetric allylic alkylation of hydroperoxyalkanes with Morita–Baylis–Hillman carbonates was catalysed by modified cinchona alkaloids (up to 93% ee), from which chiral α-methylene-β-hydroxy esters could be efficiently derived.

The organic Lewis base-catalysed asymmetric allylic alkylation of 3-substituted oxindoles with Morita–Baylis–Hillman carbonates is reported, affording multifunctional oxindoles with adjacent quaternary and tertiary chiral centres (dr up to 92 : 8, 86–97% ee).

α,α-Dicyanoalkenes are electron-deficient alkenes and inherently behave as electrophiles. Over the past five years some significant progress has been achieved by using α,α-dicyanoalkenes as vinylogous donors in C–C bond forming and other functionalisation reactions, especially for the construction of multifunctional products. In this feature article we will present the successful development of vinylogous reactions of α,α-dicyanoalkenes by our group and other groups.

The first highly enantioselective allylic-allylic alkylation of alpha,alpha-dicyanoalkenes and Morita-Baylis-Hillman carbonates by dual catalysis of (DHQD)(2)AQN and (S)-BINOL has been investigated. Excellent stereoselectivities have been achieved for a broad spectrum of substrates (d.r. > 99:1, up to 99 % ee). The multifunctional allylic products could be efficiently converted to a range of complex chiral cyclic frameworks. EWG = electron-withdrawing group, (DHQD)(2)AQN = hydroquinidine (anthraquinone-1,4-diyl) diether, (S)-BINOL = (S)-(-)-1,1'-bi-2-naphthol.