Short Synthesis of Oxetane and Azetidine 3-Aryl-3-carboxylic Acid Derivatives by Selective Furan Oxidative Cleavage
Maryne A. J. Dubois, Milo A. Smith, Andrew J. P. White, Alvin Lee Wei Jie, James J. Mousseau, Chulho Choi, James A. Bull
Abstract
Four-membered rings remain underexplored motifs despite offering attractive physicochemical properties for medicinal chemistry. Arylacetic acids bearing oxetanes, azetidines, and cyclobutanes are prepared in two steps: a catalytic Friedel-Crafts reaction from four-membered ring alcohol substrates, followed by mild oxidative cleavage. The suitability of the products as building blocks is reflected in their facile purification and amenability to derivatization. Examples include heteroaromatics and aryltriflates, as well as oxetane-derived profen drug analogues and a new endomorphin derivative containing an azetidine amino acid residue.