羰基到氮原子交换实现富sp³骨架中的氮扫描

Zining Zhang, Zhehan Liang, Rong Ye, Guangbin Dong* Medicinal chemistry campaigns routinely require access to series of saturated nitrogen heterocycle (SNH)–based analogs that place nitrogen at different positions to probe structure- activity relationships. However, systematic preparation of N-positional variants remains synthetically burdensome. In this work, we report a strategy for nitrogen scanning in sp3-rich scaffolds enabled by the exchange of a carbonyl group with an amine moiety, formally achieving a carbonyl-to-nitrogen (CO-to-N) atom swap. Because ketone positional isomers can be readily obtained through carbonyl transposition or carbon- hydrogen oxidation from a common carbocyclic precursor, the CO-to-N atom swap greatly streamlines the preparation of SNH positional analogs and obviates the need for multiple de novo syntheses. …