title: NHC-promoted asymmetric β-lactone formation from arylalkylketenes and electron-deficient benzaldehydes or pyridinecarboxaldehydes.
abstract: 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.
authors: EaStCHEM, School of Chemistry, University of St Andrews, North Haugh, St Andrews KY16 9ST, UK.
authors: James
authors: J
authors: Douglas
authors: James E
authors: JE
authors: Taylor
authors: Gwydion
authors: G
authors: Churchill
authors: Alexandra M Z
authors: AM
authors: Slawin
authors: Andrew D
authors: AD
authors: Smith
mesh_terms: D001547:Benzaldehydes / Q000737:chemistry*; D002384:Catalysis; D004583:Electrons; D007783:Lactones / Q000737:chemistry*; D015394:Molecular Structure; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001547:Benzaldehydes; D007783:Lactones; D011725:Pyridines; C051439:pyridinecarboxaldehyde