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Synlett 2011(4): 535-538  
DOI: 10.1055/s-0030-1259535
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Asymmetric Synthesis of Di- and Trisubstituted Cyclopropanes through an Intramolecular Ring Closure

Jeffrey M. Kallemeyn*, Mathew M. Mulhern, Yi-Yin Ku
Chemical Process Research and Development, R450, Global Pharmaceutical Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA
Fax: +1(847)9385932; e-Mail: Jeff.Kallemeyn@abbott.com;
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Publication History

Received 21 November 2010
Publication Date:
08 February 2011 (online)

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Abstract

An asymmetric synthesis of di- and trisubstituted cyclopropanes proceeding through an intramolecular ring closure of activated chiral benzyl alcohols has been developed. The chiral alcohol intermediates are obtained from asymmetric reduction of readily available 1,4-keto esters and undergo a one-pot activation and ring closure to provide the ester-functionalized cyclopropanes in high enantio- and diastereomeric purity. This methodology avoids the use of hazardous diazo and alkyl zinc reagents commonly employed in cyclopropanation reactions.

Key words

cyclopropane - ring closure - asymmetric synthesis - asymmetric reduction - stereoselectivity

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