One-Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α-Aryl-α-Trifluoromethyl Alcohols

A novel straightforward one-pot methodology for two successive turbo Grignard reagent (iPrMgCl center dot LiCl) reactions, was developed for a facile synthesis of alpha-aryl-alpha-trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of iPrMgCl center dot LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2-trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one-pot process: the iPrMgCl center dot LiCl-mediated iodine/magnesium-exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2-trifluoroethyl trifluoroacetate; and the reduction of in-situ generated aryl trifluoromethyl ketones with iPrMgCl center dot LiCl, to produce the corresponding alpha-aryl or alpha-heteroaryl-alpha-trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.