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Synlett 2005(18): 2701-2719  
DOI: 10.1055/s-2005-918950
ACCOUNT
© Georg Thieme Verlag Stuttgart · New York

Development and Applications of Amino Acid Derived Organometallics

Ian Rilatt, Lorenzo Caggiano, Richard F. W. Jackson*
Department of Chemistry, Dainton Building, University of Sheffield, Brook Hill, Sheffield, S3 7HF, UK
Fax: +44(114)2229303; e-Mail: r.f.w.jackson@sheffield.ac.uk;
Further Information

Publication History

Received 9 August 2005
Publication Date:
12 October 2005 (online)

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Abstract

This Account describes the discovery and development of a family of organometallic reagents derived from naturally occurring α-amino acids that have found widespread use in the stereocontrolled synthesis of non-natural analogues of proteinogenic amino acids. The general approach that we have taken involves the conversion of the side chain of enantiomerically pure naturally occurring amino acids, such as serine, aspartic acid and glutamic acid, into the corresponding primary alkyl iodide, followed by conversion into the corresponding organozinc reagents. Subsequent palladium- or copper-catalysed reactions of these reagents allow the synthesis of a wide variety of functionalised α-, β- and γ-amino acid derivatives, without loss of stereochemical integrity. Insights gained from ­spectroscopic and kinetic studies into the stability of functionalised organozinc reagents are included.

  • 1 Introduction

  • 2 Preparation and Applications of α-Amino Acid Derived
    Zinc Organometallics

  • 2.1 Synthesis of Phenylalanine Derivatives

  • 2.2 Preparation of β-Heteroaryl Alanine Derivatives

  • 3 Cross-Couplings with Aryl Triflates, Bromides and
    ­Chlorides

  • 4 Cross-Couplings with Vinyl Triflates and Iodides

  • 5 Preparation of Keto Amino Acids

  • 6 Preparation and Applications of α-Amino Acid Derived
    Zinc/Copper Organometallics

  • 7 Preparation of Homologous Amino Acid Derived
    ­Organometallics

  • 8 Stability and Reactivity Studies of β- and γ-Amidozinc
    ­Reagents

  • 9 Conclusions

Key words

amino acids - copper - cross-coupling - palladium - zinc