Metal-free synthesis of carbamoylated dihydroquinolinones via cascade radical annulation of cinnamamides with oxamic acids.

Abstract

We report a metal-free procedure for the sustainable synthesis of carbamoylated dihydroquinolinones via tandem addition-cyclization of carbamoyl radicals to cinnamamides. Readily accessible, non-toxic and inexpensive oxamic acids are used as carbamoyl radical precursors. This highly straightforward method provides a mild and environmentally friendly route showing good atom economy and excellent functional group tolerance to obtain diverse medicinally important carbamoylated dihydroquinolinones in one pot. The cascade cyclization is also modular and step-economical with a wide substrate scope and the products were obtained in good to excellent yields. Additionally, the tolerance to air and water, operational simplicity, low cost and scalability enhance the practical value of the proposed synthetic strategy. Preliminary mechanistic studies reveal that cheap and environment-friendly ammonium persulfate acts as a radical initiator in the cascade process and generates carbamoyl radicals from oxamic acids. The synthetic utility of this method is further demonstrated by late stage functionalization of drug molecules with good yields.