Strain Release Cycloadditions of 2H-Azirines: Access to Polycyclic Heterocycles

A strain release cycloaddition has been developed that exploits intermediate azirines formed via irradiation with blue LEDs. Subsequent cycloaddition with pyrones afforded novel aza-heterocycles (13 examples, 42%→66% yields). A variety of substituents were tolerated. Computational analysis suggests a kinetically favored endo -[4 + 2]cycloaddition that occurs from the least sterically encumbered face of the azirine. Distortion/interaction analysis suggests that the energetic penalty associated with azirine deformation is the primary factor contributing to the observed selectivity.