Two Scalable Syntheses of 3-(Trifluoromethyl)cyclobutane-1-carboxylic Acid

Two efficient synthetic methods for preparation of 3-(trifluoromethyl)cyclobutane-1-carboxylic acid are reported starting from readily available 4-oxocyclobutane precursors. These cyclobutanones can be converted to their CF3 carbinols upon treatment with TMSCF3 and a fluoride source. The bis-carboxylate system 9 was deoxygenated by treatment of Bu3SnH and provided desired compound 1 upon decarboxylation. In the monocarboxylate system 15, the triflate could be efficiently eliminated; subsequent hydrogenation afforded cis-1.