Chromium-Catalyzed Diastereoselective Synthesis of Conformationally Constrained Spirotetrahydroquinolines

We report the diastereoselective cyclization of anilineswith cyclobutanonesand congeners by chromium catalysis. This reaction can link two strainedfour-membered rings with tetrahydroquinolines by forming four bondsin a diastereocontrolled manner, forming medicinally interesting cyclobutane-fusedand constrained spirotetrahydroquinolines (STHQs) and complex multiplespiro carbon-containing polyazacycles. The constrained STHQs havebeen used as versatile feedstocks to derive a range of oxygen-, nitrogen-,and thio-substituted spiro analogues, and dioxygen-incorporated spiroazacycles.

Automated summary

We describe the selective cyclization of anilines with cyclobutanones and congeners using chromium catalysis. This reaction enables the formation of diastereoselective tetrahydroquinolines by linking two strained four-membered rings, leading to the synthesis of cyclobutane-fused and constrained spirotetrahydroquinolines (STHQs) and complex multiple spiro carbon-containing polyazacycles. The constrained STHQs have been utilized as versatile precursors for the synthesis of oxygen-, nitrogen-, and thio-substituted spiro analogues, as well as dioxygen-incorporated spiroazacycles.