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

• Published in: Journal of organic chemistry Vol. 68; no. 24; pp. 9433 - 9440
• Main Authors: Adams, Luke A, Aggarwal, Varinder K, Bonnert, Roger V, Bressel, Bettina, Cox, Russell J, Shepherd, Jon, de Vicente, Javier, Walter, Magnus, Whittingham, William G, Winn, Caroline L
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 28.11.2003; Amer Chemical Soc
• Subjects: Alicyclic compounds; Alicyclic compounds, terpenoids, prostaglandins, steroids; Amino Acids - chemical synthesis; Amino Acids - chemistry; Chemistry; Chemistry, Organic; Cyclopropanes - chemical synthesis; Cyclopropanes - chemistry; Diazonium Compounds - chemistry; Exact sciences and technology; Models, Chemical; Molecular Structure; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Stereoisomerism; ALKENES; ENANTIOSELECTIVE SYNTHESIS; TASTE PROPERTIES; CATALYTIC CYCLOPROPANATION; DECOMPOSITION; ASYMMETRIC SYNTHESES; STEREOSELECTIVE-SYNTHESIS; TRANSFORMATIONS; CORONAMIC ACID; METAL CARBENES; 1,3-Dipolar cycloaddition; Cyclopropane derivatives; Selectivity; Thermal reaction; Diastereoselectivity; Cis stereoisomer; Unsaturated compound; Cyclopropanation; Iron complex; Aminoacid; Trans stereoisomer; Reaction mechanism; Aromatic compound; Diazo compound; Metalloporphyrin; Hydrazone; Chemical synthesis
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo035060c

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].