Diastereoselective Dearomative 1,3-Dipolar Cycloaddition of Bicyclobutanes with Pyridinium Ylides: A Modular Approach to Multisubstituted Azabicyclo[3.1.1]heptanes

We describe a formal 1,3-dipolar cycloaddition between bicyclobutanes and pyridinium ylides to form azabicycloheptanes via diastereoselective pyridine dearomatization. Microscale highthroughput experimentation led to identification of conditions affording high yield and stereoselectivity without the need for catalysis. These reactions proceed using as-received reagents and solvents under ambient atmosphere. The resulting ring-fused azabicyclo[3.1.1]heptanes have diverse synthetic handles for further transformations, making them potentially valuable scaffolds for the design of Csp3-rich drug candidates. We also demonstrate a diastereoselective photochemical skeletal rearrangement to give a 1,1,3,3-tetrasubstitued cyclobutane.