Chemo-selective control of Ritter-type reaction by coordinatively unsaturated inorganic salt hydrates

Abstract

The Ritter-type reaction, without relying on a pre-installed functional group, is a highly efficient tool for the construction of amides. However, the intrinsic chemo-selectivity that determines the generation of amides or byproducts limits the efficiency and yield of the reaction. From 68 different types of hydrates, we found that a coordinatively unsaturated inorganic salt hydrate, MgSO₄·2H₂O, controlled chemo-selectivity and eliminated the shortcomings of other synthesis approaches. To rationalize the differences in selectivity of inorganic salt hydrates, we analyzed their corresponding water content, alkalinity, anions, and cations. MgSO₄·2H₂O was used with diverse scaffolds and C–H oxygenations, which demonstrated its generality in synthetic utility. Because it is readily available and it significantly improves yield, we expect that MgSO₄·2H₂O will have broad application for Ritter-type reactions.