Dedication
Dedicated to our friend, Professor Paul Knochel, on the occasion of his 70th birthday.
Abstract
We report an efficient synthetic route to access 1,2-diazepines from readily available
pyridines through dearomative ring expansion. By initially using previously established
methods to obtain the pyridinium ylide intermediate on multigram scale, the diazepine
was obtained through a 6π electrocyclic ring opening upon irradiation with 370 nm
light. 1,2-Diazepines are among the least common nitrogen heterocycles present in
FDA-approved drugs, likely due to the lack of synthetic pathways that enable access
to these scaffolds rather than a lack of biological significance. While pyridine expansions
are generally multistep procedures, our work has shown promise for a one-pot route
to this expansion product. Taken together, this work provides access to synthetically
difficult drug cores, while also introducing synthetic handles for further derivatization.
Keywords
Skeletal editing - Pyridines - Diazepines - Ring expansion - Pyridinium ylides
