Iron-catalyzed urea synthesis: Dehydrogenative coupling of methanol and amines

Abstract

Substituted ureas have numerous applications but their synthesis typically requires the use of highly toxic starting materials. Herein we describe the first base-metal catalyst for the selective synthesis of symmetric ureas via the dehydrogenative coupling of methanol with primary amines. Using a pincer supported iron catalyst, a range of ureas was generated with isolated yields of up to 80% (corresponding to a catalytic turnover of up to 160) and with H2 as the sole byproduct. Mechanistic studies indicate a stepwise pathway beginning with methanol dehydrogenation to give formaldehyde, which is trapped by amine to afford a formamide. The formamide is then dehydrogenated to produce a transient isocyanate, which reacts with another equivalent of amine to form a urea. These mechanistic insights enabled the development of an iron-catalyzed method for the synthesis of unsymmetric ureas from amides and amines.