Diastereoselective dearomative cycloaddition of bicyclobutanes with pyridinium ylides: a modular approach to multisubstituted azabicyclo[3.1.1]heptanes

Diastereoselective (3+3) cycloaddition between bicyclobutanes and pyridinium ylides forms azabicyclo[3.1.1]heptanes via pyridine dearomatization. These reactions proceed under ambient conditions with no need for photochemistry or catalysis, and tolerate a wide range of functional gorups. The resulting multicyclic ring systems have diverse synthetic handles for further transformations, making them potentially valuable for the design of Csp 3 -rich drug candidates. These include semi-reduction of the dihydropyridine, and diastereoselective photochemical skeletal rearrangement to give a tetrasubstituted cyclobutane. Structurally-dense and stereochemically-defined tricyclic heterocycles are easily accessed by (3+3) cycloaddition, leading to versatile Csp 3 -rich scaffolds.