New domino radical synthesis of aminoalcohols promoted by TiCl4–Zn/t-BuOOH system: selective hydroxyalkylation of amines in alcohol or in cyclic ether cosolvents

Abstract

We report a new and fast domino synthesis of aminoalcohols under mild conditions. The free-radical reaction of aliphatic and aromatic amines with alcohol cosolvents is promoted by means of the TiCl₄–Zn/t-BuOOH system. According to the proposed mechanism, the amine reacts with two molecules of alcohol in an electrophilic–nucleophilic cascade process. This procedure, if compared with the TiCl₃/t-BuOOH-mediated protocol previously reported, appears to be more selective, of more general applicability and affords the desired products in higher yields. Besides, with the same catalytic system it was possible to promote the reaction of primary arylamines with two molecules of cyclic ether, leading to the formation of a wider range of functionalized aminoalcohols.