A direct catalytic asymmetric Mannich-type reaction via a dinuclear zinc catalyst: synthesis of either anti- or syn-alpha-hydroxy-beta-amino ketones.
The use of imines bearing a hydrolyzable nitrogen substituent in direct asymmetric Mannich reactions with alpha-hydroxyketones is developed. Previous work focused on the use of N-arylimines or nonenolizable imines, and the latter with only methoxy-substituted alpha-hydroxyacetophenones. Using a dinuclear catalyst devised from 2,6-di-(S)-2'-diphenylhydroxymethylpyrrolidino-N-methyl)-4-methylphenol and diethylzinc, a broad array of hydroxyacetylated aromatics, including phenyl, 2-furyl, 1-naphthyl, and 2-naphthyl, react well. In addition, the reactions focused on the use of enolizable imines. With the N-diphenylphosphinoyl, the reactions are anti selective with enantiomeric excesses ranging from 83 to 99%, except for the reaction of the 2-methoxy-2'-hydroxyacetylbenzene. With the N-Boc-imines, the reactions were syn selective with enantiomeric excesses from 90 to 94%. The dependence of the diastereoselectivity on the nature of the N-substituent presumably arises from the steric demands of the diphenylphosphinoyl group.
Trost
Barry M
BM
Department of Chemistry, Stanford University, Stanford, CA 94305-5080, USA. bmtrost@stanford.edu
Jaratjaroonphong
Jaray
J
Reutrakul
Vichai
V
D000605:Amino Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D007097:Imines / Q000737:chemistry; D007659:Ketones / Q000138:chemical synthesis*; D009284:Naphthols / Q000737:chemistry; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
D000605:Amino Alcohols; C406944:BINOL, naphthol; D007097:Imines; D007659:Ketones; D009284:Naphthols; D009942:Organometallic Compounds; D015032:Zinc