Base‐Catalyzed Asymmetric α‐Functionalization of 2‐(Cyanomethyl)azaarene N‐Oxides Leading to Quaternary Stereocenters.

A simple, new strategy for the direct asymmetric α-functionalization of 2-alkyl azaarenes is described. Specifically, a Bronsted base catalyzed conjugate addition of substituted 2-cyanomethylpyridine (and pyrazine) N-oxides to acrylate equivalents to afford hitherto elusive 2-tert-alkyl azaaryl adducts with high enantioselectivity (up to 94% ee) is realized. Extension of the method to the α-amination reaction by using azodicarboxylate esters as electrophiles is also demonstrated. Key for success is the N-oxide functionality of substrates that acts as a removable activating and stereodirecting group. A bifunctional Bronsted base catalyst bearing a squaramide with an attached bulky silyl group is also disclosed.