Methoxy is foxy — Recent advances with Ni(COD)2

Aromatic methoxy-groups are peachy. Synthetic chemists can use them as directing groups for regio-selective lithiations, Friedel-Crafts acylations or halogenations, to name a few basic concepts. Medicinal chemists seem to dig methoxy-groups too, because they can pick up new hydrogen-bond interactions, and increase steric bulkiness, pKa and log P.

Yeah… we all love the good ol’ methoxy – until the day arrives when we for some reason need to delete it. It may be one click away in ChemDraw, but synthesis-wise, it’s always been a multi-step pain in the ass.

Until just recently. This changes everything:

“Ni-Catalyzed Reduction of Inert C−O Bonds: A New Strategy for Using Aryl Ethers as Easily Removable Directing Groups” – JACS 2010, 132, 17352–17353. (Available here.)

“Ni(0)-catalyzed Direct Amination of Anisoles Involving the Cleavage of Carbon–Oxygen Bonds” – Chem. Lett. 2009, 7, 710-711. (Available here.)

Do you realize how cool this is?