Abstract
This account describes our recent studies on the development of chiral nonracemic cyclic imide-based synthetic methodology and the complementary N -α-carbanion synthon-based synthetic methodology for the asymmetric syntheses of naturally occurring or pharmaceutically interesting hydroxylated pyrrolidines, 2-pyrrolidinones, β-hydroxy-γ-amino acids, and their higher homologous; as well as isoindolin-1-ones; tetramic acid and tetramate derivatives.
1 Introduction
2 Asymmetric Syntheses of (S )-5-Alkyl-4-hydroxy-2-
2.1 Synthesis of (S )- or (R )-Malimides
2.2 Synthesis of (S )-5-Alkyl-4-benzyloxy-2-pyrrolidinones via Reductive Alkylation of Malimides
2.3 Synthetic Application of the Reductive Alkylation of Malimide-Based Synthetic Methodology
3 Asymmetric Syntheses of (S )-6-Alkyl-5-hydroxy-2-piperidinones and 2-Alkyl-3-piperidinols by Stepwise Reductive Alkylation of Protected 3-Hydroxyglutarimides
3.1 Synthesis of Protected (S )- or (R )-3-Hydroxyglutarimides
3.2 Asymmetric Synthesis of Bioactive 2-Alkyl-3-piperidinols via the Reduction-α-Amidoalkylation of Protected (S )- or (R )-3-Hydroxyglutarimides
4 Asymmetric Syntheses of (S )-5-Hydroxyalkyl-4-hydroxy-2-pyrrolidinones, 5-Alkyl-tetramic Acid and 5-Alkyl-tetramate Derivatives and β-Hydroxy-γ-amino Acids via Carbanionic Chemistry
4.1 Studies on the Chiral Nonracemic 3-Pyrrolidinol 2-carbanion Synthon and the Synthesis of trans -(3S ,4S )-3-Substituted 4-Hydroxy-2-pyrrolidinones
4.2 A Formal Reductive 5-Hydroxyalkylation Approach S )-5-Hydroxyalkyl-4-benzyloxy-2-pyrrolidinones
4.3 A Flexible Approach to (S )-5-Alkyl-tetramic Acid Derivatives: Application to the Asymmetric Synthesis of (+)-Preussin and Protected (3S ,4S )-AHPPA
4.4 A Flexible Approach to (S )-5-Alkyl-tetramate Derivatives
4.5 Chemistry of the 3-Pyrrolidinol 2-carbanion
4.6 Chemistry of the 3-Aminopyrrolidine 2-Carbanion and the Asymmetric Synthesis of (+)-Absouline
5 Conclusion
Key words
pyrrolidinesN -acyliminium - piperidines - 2-piperidinones - α-amidoalkylation - sulfones - sulfides - samarium diiodide -
N -α-carbanion - isoindolin-1-ones - tetramic acids - tetramates - alkaloids - synthons - building blocks - Umpolung
