Alkoxyisoindolinones are both versatile and easily-accessible synthons in heterocyclic chemistry, ranging in application scope from natural products to medicinal candidate synthesis. During part of our studies directed at the examination of alkoxyisoindolinones as chiral auxiliaries, we required a series of 3-alkoxy-2-phenylethylisoindolinones. The 3-alkoxy-2-phenylethylisoindolinones were conveniently prepared by reacting the corresponding hydroxylactams with diethylaminosulfur trifluoride in the presence of a range of alcohols. Interestingly, 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-((<i>S</i>)-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 protic acids. A complete array of DAST-mediated alkoxylation products complete with diasteriomeric distribution and comparison with established acid mediation will be presented.

DAST-mediated preparation of <i>N</i>-substituted 3-alkoxyisoindolinones

2019 Spring National Meeting

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DAST-mediated preparation of N-substituted 3-alkoxyisoindolinones