The first organocatalytic diastereo-and enantioselective Michael addition reaction of 4-substituted-pyrazolin-5-ones to nitroolefins has been developed with a chiral bifunctional thiourea as organocatalyst. A wide variety of desired multi-substituted pyrazolin-5-one derivatives with contiguous quaternary and tertiary stereocenters are smoothly obtained in very good yields (up to 98%) with excellent enantioselectivities (up to > 99% ee) and acceptable diastereoselectivities (up to 80:20). This experimentally simple process facilitates the access to various enantioenriched, multiply substituted pyrazolin-5-one derivatives, potential biologically active molecules, starting from readily available starting materials.

A bifunctional thiourea-tertiary amine-catalyzed asymmetric hydroxymethylation of 3-substituted oxindoles using paraformaldehyde as the C1 unit was developed. A wide scope of oxindoles, bearing C3 sterically congested quaternary carbon centers, were smoothly obtained in good to excellent yields (up to 99%) and high enantioselectivities (up to 91% ee) under mild reaction conditions. A more significant feature of this approach employs cheap and readily available paraformaldehyde as a hydroxymethylation C1 unit, which is activated by chiral bifunctional thiourea organocatalysts. Chiral 3,3-disubstituted 2-oxindole substructures are present in many biologically active natural products and pharmaceutical compounds.1,2 Recently, some progress has been described in the development of efficient methods to construct functionalized chiral 3,3-disubstituted 2-oxindole scaffolds. 3,4 In this regard, various electrophiles have been investigated for the asymmetric reactions with prochiral 3-substituted oxindoles as donors. However, to the best of our knowledge, only a single example, reported by Feng and co-workers, describes a direct asymmetric aldol-type reaction of 3-substituted oxindoles with aldehyde (phenylglyoxal derivatives) using N,N 0 -dioxide-Sc(OTf) 3 complex as catalyst. 3k Thus, it is evident that there remains further need for synthetic approaches of oxindoles with aldehydes to access diversely structured 3,3-disubstituted 2-oxindoles.Enantioselective hydroxymethylation of carbonyl compounds at their R-position with formaldehyde as the C1 unit is one useful method for constructing chiral building blocks in organic synthesis, and some progress has been obtained (6) For direct aldol reactions involving formaldehyde with organocatalysts, see: (a) Torii, H.; Nakadai, M.; Ishihara, K.; Saito, S.; Yamamoto, H.

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.

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3‐Substituted oxindoles as electrophilic partners: An unprecedented method for the construction of hydroxylated 3‐substituted oxindoles in high yields and excellent enantioselectivities through stereoablative hydroxylation of 3‐halooxindoles with an organocatalyst has been developed. This process not only differs from the common convention of using 3‐substituted oxindoles as nucleophiles, but also provides a viable entry to optically active 3‐substituted 3‐hydroxy‐2‐oxindoles (see scheme).

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).Stereoselective construction of vicinal quaternary-tertiary carbon centers not only is one of the most difficult challenges in asymmetric catalysis, but also belongs to one of the key issues that is encountered during the synthesis of complex molecules.1 Significant effort has been directed toward to this area over the past decades. 1,2 The addition of 3-substituted oxindoles to appropriate electrophiles provides a very straightforward approach to access oxindole derivatives bearing a C3-quaternary center. In addition, chiral 3,3-disubstituted oxindoles are ubiquitous in nature and have † Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences.