Diastereoselective Synthesis of Cyclopropane Amino Acids Using Diazo Compounds Generated in Situ

Luke A. Adams, Varinder K. Aggarwal, Roger V. Bonnert, Bettina Bressel, Russell J. Cox, Jon Shepherd, Javier De Vicente, Magnus Walter, William G. Whittingham, Caroline L. Winn

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Abstract

A simple and high-yielding method for the preparation of cyclopropane amino acids is described. The novel method involves the one-pot cyclopropanation of readily available dehydroamino acids using aryl and unsaturated diazo compounds generated in situ from the corresponding tosylhydrazone salts. It was found that thermal 1,3-dipolar cycloaddition followed by nitrogen extrusion gave the cyclopropane amino acid derivatives with good E selectivity, while reactions in the presence of meso-tetraphenylporphyrin iron chloride gave predominantly the corresponding Z isomers. The synthetic utility of this process was demonstrated in the synthesis of (±)-(Z)-2,3-methanophenylalanine [(±)-(Z)-1], the anti-Parkinson (±)-(E)-2,3-methano-m-tyrosine [(±)-(E)-2], and the natural product (±)-coronamic acid [(±)-3].

Original languageEnglish
Pages (from-to)9433-9440
Number of pages8
JournalThe Journal of Organic Chemistry
Volume68
Issue number24
DOIs
Publication statusPublished - 28 Nov 2003
Externally publishedYes

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