Synthesis of N-methyl secondary amides via diboronic acid anhydride-catalyzed dehydrative condensation of carboxylic acids with aqueous methylamine†

Abstract

In this study, we present the first catalytic methodology for synthesizing N-methyl secondary amides via dehydrative condensation of hydroxycarboxylic acids with readily available and safe aqueous methylamine, employing diboronic acid anhydride (DBAA) as the catalyst. DBAA catalysis can also be applied to direct amidations using aqueous ethylamine or aqueous dimethylamine. Moreover, we demonstrate the applicability of this catalytic system for the concise synthesis of eight biologically active compounds containing β-amino alcohol motifs, including halostachine, synephrine, longimammine, phenylephrine, metanephrine, normacromerine, etilefrine, and macromerine.