Iridium-Catalyzed Ionic Hydrogenation of Multi-Aza Heterocycles

Nitrogen-containing-heterocycles are a cornerstone of biologically active molecules, natural products, and pharmaceuticals. Saturated heterocycles can lead to improved clinical success of drugs over their aromatic counterpart and sp³-rich three-dimensional molecules cover a much broader and complex chemical space. In this respect, increasing the number of nitrogen atoms in saturated heterocycles open up a wide range of isomeric structures with defined conformations. However, hydrogenation technology of complex heterocycles as efficient access strategy to these entities is still not general and straightforward. Herein, we report an ionic iridium-catalyzed hydrogenation platform of diverse multi-aza arenes to (partially)saturated heteroarenes. With a readily available iridium(III)-complex, we devised a robust system for the selective hydrogenation of 14 different heteroaromatic cores with a unified approach, mild reaction conditions preserving typical reduction-sensitive functional groups such as halides. The hydrogenation operates with low loadings of 0.5 mol%, is amenable to multigram scales without adaption. For instance, all three isomeric diazines cores were reduced to useful piperazines, tetrahydropyrimidines as well as elusive piperidazines with its fragile N─N bonds. Additional heterocycles containing up to four nitrogen atoms comprise isomeric [6,6]-naphthyridines, pyridopyrazines, pyrazolopyridines, pyrazolopyrimidines, and triazolopyrazines.