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Synlett 2009(19): 3053-3064  
DOI: 10.1055/s-0029-1218299
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Azetidines: New Tools for the Synthesis of Nitrogen Heterocycles

François Couty*, Gwilherm Evano*
Universud Paris, Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin en Yvelines, 45 Avenue des Etats-Unis, 78035 Versailles Cedex, France
Fax: +33(1)39254452; e-Mail: couty@chimie.uvsq.fr; e-Mail: evano@chimie.uvsq.fr;
Further Information

Publication History

Received 19 January 2009
Publication Date:
21 October 2009 (online)

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Abstract

Compared to other nitrogen heterocycles such as aziridines, pyrrolidines, or piperidines, the chemistry of azetidines is much less developed, probably because of their limited availability. In this account, recent synthetic routes to these strained heterocycles starting from readily available enantiomerically pure starting compounds will be detailed. The ring strain in these heterocycles makes them excellent candidates for nucleophilic ring-opening or ring-expansion reactions yielding higher ring systems or highly substituted acyclic amines. These useful transformations will be described in the second section of this account.

1 Introduction

1.1 Synthesis of Azetidines from β-Amino Alcohols

2 Synthetic Transformation of 2-Cyanoazetidines

3 Ring Expansion of Functionalized Azetidines

3.1 Ring Expansion to Pyrrolidines

3.2 Ring Expansion to Azepanes

4 Ring Opening of Azetidines and Azetidinium Ions

5 Reactivity of Azetidinium Ylides

6 Synthetic Applications

7 Concluding Remarks

Key words

azetidines - nitrogen heterocycles - ring expansion - ring opening - chirality

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For a recent review on l-Aze, see ref. 2g