The application of readily available optically active 4-substituted 5-nitropentan-2-ones as chiral building blocks in the stereocontrolled construction of spiro-pyrazolone scaffolds was investigated. In the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (1 equiv.) optically active 4-substituted 5-nitropentan-4-ones exhibited excellent chiral inducing abilities in the diastereoselective cascade Michael/aldol reaction with a wide range of unsaturated pyrazolones to generate the corresponding biologically significant spiro-pyrazolone derivatives with five contiguous stereocenters in acceptable to good yield with high levels of diastereoselectivity.

Multisubstituted 2-oxopyran-6-carboxylic acid derivatives were synthesized under mild reaction conditions through a base-promoted reaction between 3,4-dihydro-3-nitrochromen-2-ones and β,γ-unsaturated α-oxo esters to give products in excellent yields. The reaction is believed to proceed through a cascade Michael–intramolecular transesterification–elimination process.

An efficient approach for the stereocontrolled construction of the 3,4-dihydrothiacarbazol-2(9H)-one skeleton has been developed. In the presence of a bifunctional squaramide catalyst that was derived from L-tert-leucine, the asymmetric tandem Michael/thiolysis reactions of 9-methylindoline-2-thiones and N-alkynoylphthalimides proceeded efficiently to furnish the desired 3,4-dihydrothiacarbazol-2(9H)-one derivatives in satisfactory yields with high levels of enantioselectivity (up to 98 % ee).

A highly diastereo- and enantioselective organocatalyzed domino sulfa-Michael–Mannich reaction of 2-mercaptoquinoline-3-carbaldimines with maleimides has been developed. This approach provides a convenient and efficient access to multifuntionalized tetracyclic quinoline derivatives with three contiguous stereocenters in high yield with excellent stereoselectivity (up to >99:1 dr and >99 % ee).

A highly enantioselective Michael addition of allomaltol (5-hydroxy-2-methyl-4H-pyran-4-one) to both aromatic and aliphatic β,γ-unsaturated α-ketoesters has been realized. Under the catalysis of a chiral bifunctional tertiary amine-squaramide that bears a (1R,2R)-1,2-diphenylethane-1,2-diamine scaffold, the reaction proceeded smoothly with high levels of enantioselectivity to give the desired products in acceptable yields with 86–>99 % enantiomeric excess. This methodology provided an efficient process for the enantioselective synthesis of optically active kojic acid derivatives.

Optically active 2H-thiopyrano[2,3-b]quinolines with three contiguous stereocenters have been synthesized via a chiral bifunctional squaramide-catalyzed tandem Michael–Henry reaction between 2-mercaptoquinoline-3-carbaldehydes and nitroolefins. The reactions proceed with excellent diastereo- and enantioselectivity to give the title compounds in high yields with high levels of diastereo- and enantioselectivity (up to >99/1 dr and >99% ee, respectively).

The organocatalytic asymmetric, one-pot, sequential Michael addition/dearomative bromination reaction of pyrazol-5-ones to nitro olefins and N-bromosuccinimide (NBS) has been developed. Under the catalysis of a chiral bifunctional squaramide, a wide variety of chiral brominated pyrazol-5-one derivatives with contiguous quaternary and tertiary stereocenters was obtained in high yields (up to >99 %) with good to excellent diastereoselectivities (62:38–99:1 dr) and uniformly high levels of enantioselectivity (92 to >99 % ee). This experimentally simple process facilitates access to various enantioenriched, multiply substituted pyrazolin-5-one derivatives, potential biologically active molecules, starting from readily available starting materials.

A highly diasterero- and enantioselective intramolecular Michael addition of keto-enones has been realized. By using the (R,R)-1,2-diphenylethane-1,2-diamine-based bifunctional primary amine-squaramide catalyst, the reaction proceeded smoothly to generate the corresponding trans-2,3-disubstituted dihydrobenzofuran derivatives in excellent yields with good to excellent diastereo- and enantioselectivities (up to 97:3 dr, up to >99 % ee).

A bifunctional squaramide based on (R,R)-11,12-diamino-9,10-ethylene-9,10-dihydroanthracene has been developed, and it has demonstrated great advantages over previously reported organocatalysts in the asymmetric Michael addition of 4-hydroxycoumarins to β,γ-unsaturated α-oxophosphonates. Upon quenching the generated β-4-hydroxy-2-oxo-2H-chromen-3-yl-substituted acylphosphonate intermediates with DBU and an alcohol or amine as a second nucleophile, the corresponding β-substituted carboxylates or amides were obtained in acceptable to excellent yields and with high levels of enantioselectivity (80–97 % ee) in a one-pot fashion.

A highly diastereo- and enantioselective cyclopropanation of β,γ-unsaturated α-ketoesters with bromonitromethane has been successfully developed through a domino Michael-addition/intramolecular-alkylation strategy. Acceptable yields (up to 89 %) and enantioselectivities (up to 96 % ee) have been obtained.

An efficient procedure for the stereocontrolled construction of 2H-thiopyrano[2,3-b]quinoline scaffolds has been developed, starting from simple compounds. The domino Michael/aldol reactions between 2-mercaptobenzaldehydes and enals, promoted by chiral diphenylprolinol TMS ether, proceed with excellent chemo- and enantioselectivity to give the corresponding synthetically useful and pharmaceutically valuable 2H-thiopyrano[2,3-b]quinolines in high yields with 90–99 % ee.

β-Oxo phosphonates have been proven to be alternative Michael donors in Michael addition reactions to nitro olefins in the presence of cinchonine-based bifunctional thiourea, affording a direct and atom-economic approach to the efficient construction of synthetically and biologically valuable chiral acyclic α-substituted β-oxo phosphonates with high levels of enantioselectivity (up to 98 % ee).

3,3′-Triphenylsilyl-substituted (S)-BINOL-based (1,1′-bi-2-naphthol) phosphoric acid has proven to be an effective organocatalyst for the asymmetric Friedel–Crafts alkylation of indoles with 3-substituted 3-hydroxyisoindolin-1-ones, affording the corresponding quaternary carbon-containing 3,3-disubstituted isoindolin-1-ones in good yields (up to 99 %) with good to excellent enantioselectivities (up to 95 % ee). The optical purity of the product was further improved after a single recrystallization. This protocol provides a convenient method for the catalytic asymmetric synthesis of valuable 3,3-disubstituted isoindolin-1-ones in high yields and enantioselectivities.

Chiral phosphoric acids have been proven to be effective organocatalysts for the asymmetric Friedel–Crafts alkylation of indoles with 3-hydroxyisoindolin-1-ones. The corresponding products were obtained in excellent chemical yields (up to 99 %) with moderate to excellent enantioselectivities (up to >99 % ee after a single recrystallization). This is the first example of the catalytic asymmetric synthesis of valuable 3-substituted isoindolin-1-ones in high yields and enantioselectivities.

Chirality transfer from (S)-2-(aminomethyl)pyrrolidine to the tropos biphenyl skeleton has been observed in the preparation of a chirally flexible biphenol-derived novel chiral thiophosphoramide to afford exclusively the thermodynamically favoured diastereomer. This novel secondary amine–thiophosphoramide has proven to be an effective bifunctional organocatalyst for the asymmetric Michael addition of cyclohexanone to both aryl- and alkyl-substituted nitro olefins. The corresponding adducts were obtained with excellent diastereo- (up to >99:1 dr) and enantioselectivities (up to >99 % ee).

A novel type of pyrrolidine-based chiral (thio)phosphoramidates was synthesized. Among them, compound (S,aR)-3d was proven to be an effective bifunctional organocatalyst for the asymmetric Michael addition of ketones to nitro olefins. The corresponding adducts were obtained in good to excellent chemical yields with high levels of diastereo- and enantioselectivities (up to >99:1 dr and 99 % ee).

A series of bifunctional primary amine-thiophosphoramides were synthesized, which proven to be effective organocatalysts for the asymmetric Michael reaction of acetone to both aryl and alkyl nitro olefins in the presence of phenol as a protic additive. The corresponding adducts were obtained in excellent chemical yields (up to >99 %) with excellent enantioselectivities (up to 97 % ee).

A bifunctional chiral thiourea organocatalyst bearing a glycosyl scaffold and a tertiary amino group proved to be an effective organocatalyst for the asymmetric Michael addition of acetylacetone to nitroolefins. The corresponding adducts were obtained in good to excellent yields with excellent enantioselectivities (up to 96 % ee). (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A novel chiral (salen)Al^III complex was synthesized through the reaction of Et₂AlCl and salen (R,R)-1 derived from (R,R)-11,12-diamino-9,10-dihydro-9,10-ethanoanthracene. This complex is an efficient catalyst for the asymmetric trimethylsilylcyanation of aldehydes in the presence of tributylphosphane oxide as an additive. The use of 1 mol-% of the complex led to the corresponding cyanohydrins in high yields (85–94 %) with good-to-excellent enantioselectivities (42–92 % ee).(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Asymmetric Michael-type Friedel–Crafts (F-C) alkylations of indoles with nonchelating α,β-unsaturated aromatic ketones catalyzed by a chiral H₈-BINOL-based phosphoric acid were investigated. The reactions took place smoothly in the presence of only 2 mol-% of catalyst at room temperature to afford the desired F-C alkylation products in good yields and with moderate enantioselectivities.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Four types of chiral amines have been synthesized starting from readily available chiral sources. These chiral amines in combination with L-proline have been found to be efficient cocatalysts for the asymmetric Morita–Baylis–Hillman (MBH) reaction between methyl vinyl ketone (MVK) and aromatic aldehydes. The corresponding adducts were formed in reasonable chemical yields and with good enantioselectivities (up to 83 % ee). Moreover, parallel cocatalytic reactions with the two enantiomers of chiral amine 4 and L-proline revealed that it is the proline stereochemistry that determines the configuration of the newly formed chiral center. In addition, the existence of the free hydroxy group in amine 4a enhanced the enantioselectivity of the reaction. Based on these findings, a plausible mechanism for this cocatalytic MBH reaction has been proposed.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

A convenient and practical method for the preparation of N-thiophosphoryl imines was developed through the thermal condensation of acetals with different thiophosphoramides at 120–160°C. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:238–244, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20412