Youming Wang

Highly enantio- and diastereoselective Michael addition of cyclohexanone to nitroolefins catalyzed by a chiral glucose-based bifunctional secondary amine-thiourea catalyst

A novel bifunctional thiourea bearing a saccharide-scaffold and a secondary amino group was synthesized, and was proven to be an effective organocatalyst for the asymmetric Michael reaction of cyclohexanone to both aryl and alkyl nitroolefins. The corresponding adducts were obtained with excellent diastereo- (up to >99/1 dr) and enantioselectivities (up to 97% ee).

Enantioselective Synthesis of trans-Dihydrobenzofurans via Primary Amine-Thiourea Organocatalyzed Intramolecular Michael Addition

A primary amine-thiourea organocatalyzed intramolecular Michael addition access was developed for the synthesis of trans-dihydrobenzofurans. Under the catalysis of an (R,R)-1,2-diphenylethylamine derived primary amine-thiourea bearing a glucosyl scaffold, the corresponding trans-dihydrobenzofurans were obtained in high yields with excellent level of enantioselectivities (94 to >99% ee). Moreover, an in situ isomerization occurring at high temperature gave good to excellent trans/cis ratios as well (trans/cis: 84/16-96/4).

A Recyclable Organocatalyst for Asymmetric Michael Addition of Acetone to Nitroolefins

Based on different chiral diamine skeletons, a series of bifunctional primary amine-thiophosphoramides were synthesized and screened as the catalysts for the asymmetric Michael addition of acetone to both aromatic and aliphatic nitroolefins. Under the catalysis of a thiophosphoramide derived from 1,2-diphenylethane-1,2-diamine, the corresponding adducts were obtained in high yields (up to >99%) with excellent enantioselectivities (97-99% ee) under mild reaction conditions. Moreover, the catalyst could be recovered via simple phase separation and reused at least five times without any loss of both catalytic activity and stereocontrol.

Organocatalyzed Enantioselective Michael Addition of 2-Hydroxy-1,4-naphthoquinone to β,γ-Unsaturated α-Ketophosphonatesθ

By employing a cinchonine-based thiourea as catalyst, highly enantioselective Michael addition reactions of 2-hydroxy-1,4-naphthoquinone to β,γ-unsaturated α-ketophosphonates were realized. The reaction afforded the corresponding β-substituted carboxylates in excellent yields with high levels of enantioselectivities (94->99% ee) upon quenching the generated parent structures with DBU and MeOH as a second nucleophile.

Stereocontrolled Construction of Tetrahydropyrano[2,3-c]pyrazole Scaffold via an Organocatalyzed Formal [3 + 3] Annulation

A bifunctional squaramide catalyzed enantioselective formal [3 + 3] annulation reaction with pyrazolin-5-ones and nitroallylic acetates has been developed. Densely substituted tetrahydropyrano[2,3-c]pyrazoles with two adjacent stereogenic centers are obtained in a highly stereocontrolled manner. Representative transformation of the annulation product to a biologically important fused dihydroisoquinoline is achieved without any appreciable loss in the diastereo- and enantioselectivity.

Enantioselective organocatalytic domino Michael/aldol reactions: an efficient procedure for the stereocontrolled construction of 2H-thiopyrano[2,3-b]quinoline scaffolds.

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.

Organocatalyzed Highly Diastereo‐ and Enantioselective Tandem Sulfa‐Michael–Mannich Reaction of 2‐Mercaptoquinoline‐3‐carbaldimines with Maleimides

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).

Organocatalyzed asymmetric tandem Michael-cyclization reaction of 4-benzylidene-3-methylpyrazol-5-ones and malononitrile: stereocontrolled construction of pyrano[2,3-c]pyrazole scaffold

An efficient approach for the stereocontrolled construction of pyrano[2,3-c]pyrazole scaffold has been developed. Under the catalysis of a bifunctional squaramide derived from (1R,2R)-1,2-diphenylethane-1,2-diamine, the asymmetric tandem Michael addition/cyclization reaction of 4-benzylidenepyrazol-5(4H)-ones and malononitrile proceeded efficiently to furnish the desired pyrano[2,3-c]pyrazoles in satisfactory yields with high levels of enantioselectivity (up to 99% ee).

Stereoselective Synthesis of Highly Functionalized Nitrocyclopropanes through the Organocatalyic Michael‐Addition‐Initiated Cyclization of Bromonitromethane and β,γ‐Unsaturated α‐Ketoesters

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.

Chiral Bifunctional Squaramide‐Catalyzed Highly Enantioselective Michael Addition of Allomaltol to β,γ‐Unsaturated α‐Ketoesters

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.