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Synlett 2006(8): 1133-1149  
DOI: 10.1055/s-2006-941565
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Asymmetric Synthesis of Hydroxylated Pyrrolidines, Piperidines and Related Bioactive Compounds: From N-Acyliminium Chemistry to N-α-Carbanion Chemistry

Pei-Qiang Huang*
Department of Chemistry and The Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, P. R. of China
e-Mail: pqhuang@xmu.edu.cn;
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Publication History

Received 12 December 2005
Publication Date:
05 May 2006 (online)

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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-
pyrrolidinones, 2-Alkyl-3-pyrrolidinols and 3-Alkyl-isoindolin-1-ones by Stepwise Reductive Alkylation of Protected Malimides

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
for the Asymmetric Syntheses of (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

pyrrolidines - 2-pyrrolidinones - β-hydroxy-γ-amino ­acids - N-acyliminium - piperidines - 2-piperidinones - α-amidoalkyl­ation - sulfones - sulfides - samarium diiodide - N-α-carbanion - isoindolin-1-ones - tetramic acids - tetramates - alkaloids - synthons - building blocks - Umpolung

63

See, for example, ref. 49a.

67

Zheng, X.; Huang, P.-Q. unpublished results.