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.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.