DAST-mediated Preparation of N-substituted 3-Alkoxyisoindolinones

3-Alkoxy-2-phenylethylisoindolinones are conveniently prepared by reacting the corresponding hydroxylactams with diethylaminosulfur trifluoride (DAST) in the presence of a range of alcohols. The DAST-mediated reaction did not result in any reactant fluorination but smooth installation of the alkoxy group derived from the reactant alcohol on the benzylic position of the heterocycle. The central starting hydroxylactam substrate was prepared from the corresponding chiral phthalimide, 2-((S)-1-phenylethyl)-isoindoline-1,3-dione, by selective reduction using either aluminum amalgam or sodium borohydride. The resultant diasteriomeric mixture of hydroxylactams were used in the DAST alkoxylation reaction and were compared with a more conventional method of alkoxylation using the protic acid camphorsulfonic acid. [GRAPHICS] .