An organophotocatalytic late-stage N-CH 3 oxidation of trialkylamines to N -formamides with O 2 in continuous flow.

We report an organophotocatalytic, N-CH 3 -selective oxidation of trialkylamines in continuous flow. Based on the 9,10-dicyanoanthracene (DCA) core, a new catalyst (DCAS) was designed with solubilizing groups for flow processing. This allowed O 2 to be harnessed as a sustainable oxidant for late-stage photocatalytic N-CH 3 oxidations of complex natural products and active pharmaceutical ingredients bearing functional groups not tolerated by previous methods. The organophotocatalytic gas-liquid flow process affords cleaner reactions than in batch mode, in short residence times of 13.5 min and productivities of up to 0.65 g per day. Spectroscopic and computational mechanistic studies showed that catalyst derivatization not only enhanced solubility of the new catalyst compared to poorly-soluble DCA, but profoundly diverted the photocatalytic mechanism from singlet electron transfer (SET) reductive quenching with amines toward energy transfer (E n T) with O 2 .