Dimethyl Carbonate as a Sacrificial Molecule for the Synthesis of 5-MemeberedN- andO-Heterocycles

In the last twenty years DMC has been employed as an efficient methylating and methoxycarbonylating agent with several monodentate and bidentate nucleophiles, showing great selectivity and unexpected results. In this short review we report on yet another application of DMC chemistry i.e. the synthesis of 5-membered N- and O-heterocycles. In these reactions DMC acts as a sacrificial molecule since it is not present in the final products, but only in the reaction intermediates as an halogen-free leaving group. This DMC-based synthesis of heterocycles resulted of general application, as it is effective for aliphatic and aromatic 1,4-diols, incorporating several functionalities (primary, secondary, tertiary, allylic, phenolic), as well as, for bifunctional compounds i.e. 4-amino-1-butanol. This synthetic procedure was also employed for industrially relevant compounds such as (-)-norlabdane oxide and isosorbide showing to maintain the chiral integrity of the substrate. In one case intramolecular cyclisation of isosorbide was also observed to achieve a strained tricyclic derivative. Comparing this reaction methodology with a chlorine based procedure, the DMC-mediated pathway is quantitative, occurs in one step, does not require any chlorine-based chemical or strong acid and does not produce any chlorinated waste material.