Palladium-Catalyzed Direct Arylation of C(sp³)–H Bonds of α-Cyano Aliphatic Amides

Pd(OAc)2-catalyzed arylation of C(sp(3))-H bonds in α-cyano-α-methyl aliphatic amides is achieved in the presence of 8-aminoquinoline, as a removable directing group, using Mn(OAc)2 and Na2CO3. The current strategy enables the placement of an aryl/heteroaryl group at the β-position of α-cyano aliphatic acids for the first time. Wide functional group tolerance and easily accessible starting materials provide an efficient protocol for the synthesis of arylated α-cyano amides. Furthermore, the synthetic utility of the products has been demonstrated by their efficient conversions to medicinally important α,α-dialkylated acid and β-amino acid derivatives.