Asymmetric Conjugate Addition Reactions Of2-Oxindole-3-Carboxylate Esters:Construction Of C~γ-tetrasubstituted α-Amino Acid Derivatives

The amino acids and oxindoles are common structural units in many natural isolates and pharmacological agents. Many of them, especially chiral ones, have good biological activities. The synthsis of these compounds always are the focus of research interests for chemists. Given that spirocyclic oxindoles containing Cγ-tetrasubstituted a-amino acid have a wide range of biological activities, for example, it play an important role in agriculture as pesticides. At the same time, the Michael receptor are mostly limited to3-alkyl,3-aryl,3-isothiocyanato and3-amino substituted oxindoles.2-oxindole-3-carboxylate esters have rarely been used as nucleophiles in asymmetric organocatalytic conjugate addition with only a recent exception from Yao and Liu. We choose2-oxindole-3-carboxylate esters as a nucleophilic reagent. In this thesis, we use2-oxindole-3-carboxylate esters to construct Cγ-tetrasubstituted a-amino acid derivatives. The details are as follows.1. Spirocyclic oxindoles containing Cγ-tetrasubstituted a-amino acid have been established using the organocatalytic asymmetric conjugate addition2-oxindole-3-carboxylate esters to2-phthalimido acrylates. We successively investigated the influence of different bifunctional organocatalysts, solvents, substituent effects, reaction temperature and the amount of catalysts in the reaction. The reaction allows efficient access to a variety of quaternary oxindole based Cγ-tetrasubstituted a-amino acid derivatives in good enantioselectivity (90%ee) with excellent diastereoselectivity (up to93:7dr). The method could efficiently construct quaternary stereocenters of oxindoles at three position. But it is a pity that failed to close ring, only get spirocyclic oxindoles containing Cγ-tetrasubstituted a-amino acid. A possible transition-state model was proposed. At the same time, the products were characterized by NMR, MS and HRMS. The absolute configuration of the product was confimd to be (1S,3S) by X-ray analysis.2. The method can effectively combine the extremely important two kinds of compounds oxindoles and the amino acids. It is worthwhile noting that the opposite enantiomers of the products can also be obtained by changing the configuration of catalyst.