Enantioselective Synthesis of 2‐(2‐Arylcyclopropyl)glycines: Conformationally Restricted Homophenylalanine Analogs

Starting from simple aromatic aldehydes and acetylfuran, ( E )‐1‐(furan‐2‐yl)‐3‐arylprop‐2‐en‐1‐ones ( 2 ) were synthesized in high yields. Cyclopropanation of the CC bond with trimethylsulfoxonium iodide (Me 3 SO + I − ) furnished (furan‐2‐yl)(2‐arylcyclopropyl)methanones 3 in 90–97% yields. Selective conversion of cyclopropyl ketones to their ( E )‐ and ( Z )‐oxime ethers 5 and oxazaborolidine‐catalyzed stereoselective reduction of the CN bond followed by separation of the formed diastereoisomers, furnished (2‐arylcyclopropyl)(furan‐2‐yl)methanamines 6 in optically pure form and high yield. Oxidation of the furan ring of ( S , S , S )‐, ( S , R , R )‐, ( R , S , S )‐, and ( R , R , R )‐ 6a afforded the four stereoisomers of α ‐(2‐phenylcyclopropyl) glycine ( 1a ).