From Regioselective Condensation to Regioselective N-Alkylation: A Novel and Environmentally Benign Strategy for the Synthesis of N,N-Alkyl Aryl Ureas and N,N-Dialkyl Ureas

A protocol for the synthesis of N,N-alkyl aryl ureas and N,N-dialkyl ureas by transition metal-catalyzed regioselective N3-alkylation of the N-monosubstituted ureas with alcohols was proposed and accomplished. In the presence of an iridium/base system, the desired N,N-alkyl aryl ureas and N,N-dialkyl ureas were obtained with 70-93% yields, and no isomeric N1-alkylated and N3-dialkylated products were formed in all cases. From both synthetic and environmental point of views, the reaction is highly attractive because of easily available starting materials, high atom efficiency and the formation of water as the only side product. Apparently, the research opens up the design of regioselective N-alkylation of amines with alcohols based on the regioselective condensation of amines with aldehydes, facilitating the progress of the hydrogen autotransfer (or hydrogen-borrowing) process.