Chan–Lam N- and O-cyclopropylation (Pfizer collaboration)

Together with a team from Pfizer Medicinal Chemistry Oncology, we report a new method to append cyclopropyl groups to phenols and aza-heterocycles via Chan–Lam coupling in a manuscript appearing today in J. Org. Chem. The transformation exhibits good functional group tolerance with compatibility with functional groups and heterocycles that are commonly encountered in drug discovery. Using computational ADME tools, we also dug into Pfizer’s data to explore the effect of various cyclopropyl-to-alkyl transforms on clearance rates, illustrating the unique properties of the cyclopropyl group in drug discovery. Congrats to the entire team, Joe, Miriam, Matt, Mark, Ryan, Fen, Michelle, Indra, and special thanks to all the folks from Pfizer for a great collaboration! Click here for a link to the paper.


(not pictured: Mark)