Probing the Diastereoselectivity of Staudinger Reactions Catalyzed by N-Heterocyclic Carbenes

The reaction of ethylphenylketene with 1,3-dimesitylimidazol-2-ylidene (IMes) or 1,3-dimesitylimidazolin-2-ylidene (SIMes) afforded the corresponding azolium enolates in high yields. The two zwitterions were fully characterized by various analytical techniques. Their thermal stabilities were monitored by thermogravimetric analysis and the molecular structure of SIMes.EtPhC=C=O was determined by means of X-ray crystallography. A mechanism was proposed to account for the trans-diastereoselectivity observed in the [2+2] cycloaddition of ketenes and N-protected imines catalyzed by N-heterocyclic carbenes and an extensive catalytic screening was performed to test its validity. The steric bulk of the NHC catalyst markedly affected the cis/trans ratio of the model β-lactam product. The nature of the solvent used to carry out the Staudinger reaction also significantly influenced its diastereoselectivity. Conversely, the nature of the substituent on the N-sulfonated imine reagent and the reaction temperature were less critical parameters. Steric clash: The trans diastereoselectivity observed in the [2+2] cycloaddition of ketenes and N-protected imines catalyzed by N-heterocyclic carbenes was rationalized based on the molecular structure of the zwitterionic imidazolinium enolate derived from 1,3-dimesitylimidazolin-2-ylidene and ethylphenylketene (see scheme).