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

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.

Visible-Light-Induced Metal- and Photocatalyst-Free Radical Cascade Cyclization of Cinnamamides for Synthesis of Functionalized Dihydroquinolinones.

Visible-light-promoted metal- and photocatalyst-free radical cascade cyclization of cinnamamides with α-oxocarboxylic acids is described for sustainable synthesis of diverse pharmaceutically important dihydroquinolinone scaffolds in one pot under mild conditions. The decarboxylative cascade cyclization proceeded efficiently at room temperature without the need for expensive photocatalysts such as Ir or Ru complexes, which indicates the practicability and environmentally benign nature of this protocol. Preliminary mechanistic studies reveal that the blue LED irradiation efficiently cleaves the I-O bond of the hypervalent iodine reagent PhI(O2CCOAr)2 formed through ligand exchange between iodobenzene diacetate and arylglyoxylic acid to initiate the cascade reaction. The synthetic value of this operationally simple and energy-efficient method is further demonstrated by late-stage functionalization of drug molecules in excellent yields.