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

Abstract

The first example of the nickel(II)-catalyzed reaction of amides using inexpensive and milder molecular iodine (I2) as an iodinating reagent is reported. The reaction of aromatic amides having an 8-amino-5-choloroquinoline as a directing group with I2 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 β-lactams from aliphatic amides as the substrate, in which C(sp3)–H bonds are activated. The results of deuterium labeling experiments indicate that the cleavage of C(sp3)–H bonds is also irreversible.