Synthesis of Dihydropyridine Spirocycles by Semi-Pinacol-Driven Dearomatization of Pyridines

The identification of the beneficial pharmacokinetic properties of aza-spirocycles has led to the routine incorporation of these highly rigid and three-dimensional structures in pharmaceut-icals. Herein, we report an operationally simple synthesis of spirocyclic dihydropyridines via an electrophile-induced dearoma-tive semi-pinacol rearrangement of 4-(1 '-hydroxycyclobutyl)-pyridines. The various points for diversification of the spirocycliza-tion precursors, as well as the synthetic utility of the amine and ketone functionalities in the products, provide the potential to rapidly assemble medicinally relevant spirocycles.

Automated summary

Aza-spirocycles, highly rigid and three-dimensional structures, have been incorporated into pharmaceuticals due to their beneficial pharmacokinetic properties. We report a simple synthesis of spirocyclic dihydropyridines through an electrophile-induced dearomatization reaction, which offers the potential for rapid assembly of medicinally relevant spirocycles.