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

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].