Theoretical Studies on Nickel-Catalyzed Cycloaddition of 3-Azetidinone with Alkynes

With the aid of DFT calculations, we have examined the mechanism of the Ni-catalyzed cycloaddition of 3-azetidinone with alkynes. Our DFT results did not support the originally proposed mechanism, which involves a ring expansion through β-carbon elimination. Instead, our calculations supported a mechanism which involves oxidative addition of 1-Boc-3-azetidinone to a Ni(0) center to form an intermediate having both Ni–C(O) and Ni–C(sp 3 ) bonds, then alkyne insertion into either the Ni–C(O) or Ni–C(sp 3 ) bond depending on the alkyne substrates being studied, and finally reductive elimination to give the cycloaddition products. The nature of insertion of alkynes into a Ni–C bond was also discussed. When an alkyne substrate inserts into the Ni–C(O) bond, we found that the alkyne acts as a nucleophile to attack the electron-deficient, metal-bonded C═O carbon center. When an alkyne substrate inserts into the Ni–C(sp 3 ) bond, the alkyne acts as an electrophile to interact with the Ni–C(sp 3 ) bond.