Waste minimized synthesis of pharmaceutically active compounds: Via heterogeneous manganese catalysed C-H oxidation in flow

Herein, we present our results on the development of a continuous flow protocol enabling the waste minimised synthesis of relevant pharmaceuticals and natural compounds. Heterogeneous manganese catalytic systems have been used in combination with molecular oxygen to promote the C-H oxidative coupling of 2-aminophenols, benzenetriols and o-phenylenediamines to access a variety of 2-aminophenoxazin-3-ones (2a-i) and related diaminophenazines (2j-k) and purpurogallin (2l) with minimal metal contamination. Making use of safe and green cyclopentyl methyl ether (CPME), this methodology allowed a fast synthesis of fully decorated molecular entities, preserving the stability of the heterogeneous catalyst which showed minimal metal leaching, with minimal waste production (low E-factor)