Nickel-Catalyzed Reaction of C-H Bonds in Amides with I2: ortho-Iodination via the Cleavage of C(sp2)-H Bonds and Oxidative Cyclization to β-Lactams via the Cleavage of C(sp3)-H Bonds

The first example of the nickel(II)-catalyzed reaction of amides using inexpensive and milder molecular iodine (I-2) as an iodinating reagent is reported. The reaction of aromatic amides having an 8-amino-5-choloroquinoline as a directing group with I-2 resulted in the production of ortho-iodination products. Deuterium labeling experiments indicate that the cleavage of C-H bonds is irreversible and is likely the rate-determining step, which is in sharp contrast to the previously reported transformation using the same Ni(II) catalyst/8-aminoquinoline chelation system. The reaction is applicable to the synthesis of beta-lactams from aliphatic amides as the substrate, in which C(sp(3))-H bonds are activated. The results of deuterium labeling experiments indicate that the cleavage of C(sp(3))-H bonds is also irreversible.