Theoretical investigation on cobalt-catalyzed hydroacylation reaction: Mechanism and origin of stereoselectivity

In the present study, the mechanism of a cobalt-catalyzed hydroacylation reaction between aldehydes and 1,6-enynes and the origin of its stereoselectivity have been systematically investigated using the DFT calculational method. Two possible reaction mechanisms have been investigated: one that starts with oxidative addition of the aldehyde (aldehyde-first) or one that starts with oxidative cyclization of the 1,6-enyne (enyne-first). The computational results show that the aldehyde-first mechanism is energetically more favorable than is the enyne-first mechanism. The aldehyde-first mechanism contains several steps: oxidative addition, acyl migratory insertion, alkene insertion, and reductive elimination. Based on the calculations, the alkene insertion is the stereoselectivity-determining step, generating the S-configured product preferentially. The key to inducing the observed stereoselectivity is the lesser distortion of the structure of the lower-energy transition state that leads to the S-configured product.