Electron-withdrawing-group Stetter reactions

Unfettered by the bounds of common Michael acceptors with electron-withdrawing groups, the Glorius group have impressively demonstrated the Stetter reaction of aldehydes with tethered unactivated 1,1-disubstituted alkenes. The cyclization reaction generally proceeds smoothly to afford cyclic ketones with quaternary stereocenters in excellent yields with high enantioselectivity. Based on detailed DFT calculations, they proposed a concerted mechanism for this reaction the proton migration and C—C bond formation between the Breslow enolate and the alkene occur simultaneously (Scheme 7.23). 

In the same year, Glorius and coworkers successfully introduced dehydroamino ester 47 as the Michael acceptor for the Stetter reaction. Aromatic aldehydes 21 with an electron-withdrawing group worked well. However, electron-rich aromatic aldehydes did not (Scheme 20.23). 

In 2011, the enantioseleetive intramolecular Stetter reaction of unactivated olefins was reported by the Glorius group. Under the catalysis of NHC H3 derived from r-phenylalaninol, chromanone derivatives 31 containing a newly formed quaternary stereocentre were obtained in good yield with up to 99% enantiomeric excess. Both electron-donating substituents and electron-withdrawing substituents worked well (Scheme 20.15). 

---