Atom-Economic Catalytic Direct Substitution of N,O-Acetals with Simple Ketones.

A general and powerful catalytic protocol for the direct amidoalkylation of simple enolizable ketones is described, with use of the Lewis superacid Sn(NTf₂)₄ as a catalyst under thermal conditions. A complete and rational study directed towards the development of efficient conditions for the coupling of a wide range of reaction partner combinations, including the most recalcitrant ones, is presented. The synthetic potential of the reaction is demonstrated through the use of a large set of both carbonyl and N,O-acetalic substrates, providing the corresponding amidoalkylated ketones in 49-99 % yield, by using very low catalyst loadings (≤ 1 mol-%). [ABSTRACT FROM AUTHOR]