NHC-Promoted Asymmetric beta-Lactone Formation from Arylalkylketenes and Electron-Deficient Benzaldehydes or Pyridinecarboxaldehydes

A chiral NHC catalyzes the asymmetric formal [2 + 2] cycloaddition of alkylarylketenes with both electrondeficient benzaldehydes and 2- and 4-pyridinecarboxaldehydes to generate stereodefined beta-lactones. In the benzaldehyde series, optimal product diastereo- and enantiocontrol is observed using 2-nitrobenzaldehyde (up to 93:7 dr (syn:anti) and 93% ee). Substituted 2- and 4-pyridinecarboxaldehydes are also tolerated in this process, generating the corresponding beta-lactones in good yield and enantioselectivity, although the diastereocontrol in these processes is highly dependent upon the aldehyde substitution. These processes are readily scalable, allowing multigram quantities of the beta-lactone products to be prepared Derivatization of these products, either through ring opening into the corresponding stereodefined beta-hydroxy and beta-amino acid derivatives without loss of stereochemical integrity or via cross coupling, is demonstrated.