NHCs promote the efficient chlorination of unsymmetrical disubstituted ketenes with a range of chlorinating agents; chiral NHCs display promising levels of asymmetric induction

N-heterocyclic carbene (NHC)-catalyzed redox asymmetric hetero-Diels-Alder reactions of α-aroyloxyaldehydes with β-trifluoromethyl enones generates synthetically useful dihydropyranones containing a stereogenic trifluoromethyl substituent in good yields (up to 81%) and excellent diastereoselectivity and enantioselectivity (up to >95:5 dr and >99% ee). The process is stereospecific, with use of either (E)- or (Z)-β-trifluoromethyl enones forming syn- or anti-dihydropyranone products, respectively. Mechanistic studies through in situ kinetic analysis of the reaction reveal key differences in reactivity between chiral NHC precursor 1 and an achiral NHC precursor.

Rhodium complexes based upon chiral sulfinamide-alkene, TADDOL-derived phosphoramidite, or diene ligands catalyze cyclizations of arylboron compounds onto ketones, generating a variety of products containing five-, six-, or seven-membered rings with good yields and high enantioselectivities.

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.