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

A chiral
NHC catalyzes the asymmetric formal [2 + 2] cycloaddition
of alkylarylketenes with both electron-deficient benzaldehydes and
2- and 4-pyridinecarboxaldehydes to generate stereodefined β-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 β-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 β-lactone products to be prepared. Derivatization of
these products, either through ring opening into the corresponding
stereodefined β-hydroxy and β-amino acid derivatives without
loss of stereochemical integrity or via cross-coupling, is demonstrated.