Pd-catalyzed gamma-c(sp3)-h arylation / heteroarylation of free amines

A method for Pd(II)-catalyzed g-C(sp3)-H arylation or heteroarylation of a primary amine having a γ-hydrogen atom, using an effective amount of a catalytic transient directing group of formula TDG

• wherein Y is N or CX4;
• and
• X1, X2, X3, and X4 each independently is alkyl, aryl, haloalkyl, alkylamino, or alkoxyl;
• or wherein any single pair of X1 and X2, of X2 and X3, and of X3 and X4 when present, together with the ring to which they are bonded, forms a fused 5-, 6-, or 7-membered cycloalkyl ring;
• the method comprising contacting a primary amino compound of formula (I)
• wherein R1, R2, R3, and R4 each independently is hydrogen or alkyl, or wherein R2 and R4 together with the atoms to which they are bonded form a cycloalkyl,
• and an aryl iodide (ArI) or a heteroaryl iodide (HetArI), respectively, which can be unsubstituted or can be substituted with one or more independently selected aryl, alkyl, halo, nitro, haloalkyl, alkoxyl, alkoxycarbonyl, or carboxaldehyde groups;
• in a reaction milieu comprising the presence of an effective amount of palladium(II) acetate, Pd(II)(OAc)2, and in the presence of an effective amount of transient directing group TDG, to provide a product of formula (II)
• wherein AH signifies an aryl or a heteroaryl group.