Asymmetric synthesis of 1,4-disubstituted 3-methylidenedihydroquinolin-2(1H)-ones

A series of enantiomerically pure or highly enriched (R)- or (S)-3-methylidenetetrahydroquinolin-2-ones was readily prepared by highly diastereoselective Michael additions of various Grignard reagents to quinolin-2(1H)-ones, containing an (R,R)- or (S,S)-di(1-phenylethylamino)phosphoryl group as chiral auxiliary, followed by Horner-Wadsworth-Emmons olefination of formaldehyde. An efficient synthesis of the starting (R,R)- and (S,S)-3-({di(1-phenylethyl)amino]}phosphoryl)-1-alkyl-quinolin-2(1H)-ones is also described. The relative and absolute configurations of the intermediate adducts and final methylidenequinolinones were established by NMR and X-ray analysis.