Intramolecular nitrogen insertion of oxime ester to access aminated N-heterocycles

Abstract

The synthesis of aminated N-heterocycles is a critical area in synthetic organic chemistry. But some issues need to be addressed for traditional amination of N-heterocycles, such as the need for halogenated precursors or organometallic compounds, as well as catalyst deactivation due to nitrogen-containing substrates. These methods generate excessive waste, resulting in poor atom- and step-economy, which contradicts the principles of green chemistry. Herein, we leverage the rearrangement of ketoxime esters to develop a synthetic methodology for accessing aminated N-heterocycles, including phenanthraline, dibenzo[b,f][1,4]thiazepine, dibenzo[b,f][1,4]oxazepane, and dibenzo[b,e][1,4]diazepine derivatives. This strategy features broad functional group tolerance and high regioselectivity, and enables the synthesis of quetiapine fumarate, minimizing waste and improving overall efficiency in line with green chemistry principles.