Sequential catalytic incorporation of CO and CO2 into 2-ethynylanilines for the one-step multicomponent synthesis of benzoxazinone derivatives

The catalytic incorporation of both carbon oxides into an organic substrate is one of the most difficult targets to achieve in catalysis. So far, a process like this has been realized in only four examples, involving propargylic amines or 2-iodoanilines as the substrates, with formation of oxazolidone, oxazolone or isatoic anhydrides, under either Pd(II) or Pd(0) catalysis. On the other hand, the incorporation of both CO and CO2 onto 2-ethynylanilines for the synthesis of high value added benzoxazinone derivatives has not been achieved so far, in spite of the large number of examples known for either their carbonylation or carboxylative cyclization. Here we show the successful realization of such a process, which is based on the concatenation of two catalytic cycles, the first one corresponding to Pd(II)-catalyzed oxidative carbamoylation of 2-ethynylanilines to give the corresponding 2-ynamide derivatives, and the second one consisting of DBU/Ag(I)-promoted carboxylative cyclization of the 2-ynamide intermediates. In this manner, functionalized benzoxazines are obtained in one synthetic step by the sequential catalytic assembly of several simple building blocks (2-ethynylanilines, CO, amines, O2, and CO2) in a multicomponent fashion.