Catalytic asymmetric alkylations of ketoimines. Enantioselective synthesis of N-substituted quaternary carbon stereogenic centers by Zr-catalyzed additions of dialkylzinc reagents to aryl-, alkyl-, and trifluoroalkyl-substituted ketoimines.
Catalytic enantioselective alkylations of three classes of ketoimines are reported. Reactions are promoted in the presence 0.5-10 mol % of a Zr salt and a chiral ligand that contains two inexpensive amino acids (valine and phenylalanine) and involve Me2Zn or Et2Zn as alkylating agents. Requisite aryl- and alkyl-substituted alpha-ketoimine esters, accessed readily and in >80% yield on gram scale through a two-step sequence from the corresponding ketones, undergo alkylation to afford quaternary alpha-amino esters in 79-97% ee. Aryl-substituted trifluoroketoimines are converted to the corresponding amines by reactions with Me2Zn, catalyzed by a chiral complex that bears a modified N-terminus. The utility of the catalytic asymmetric protocols is illustrated through conversion of the enantiomerically enriched alkylation products to a range of cyclic and acyclic compounds bearing an N-substituted quaternary carbon stereogenic center.
Fu
Peng
P
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
Snapper
Marc L
ML
Hoveyda
Amir H
AH
D000473:Alkanes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D000478:Alkylation; D002384:Catalysis; D006845:Hydrocarbons, Fluorinated / Q000737:chemistry*; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D008956:Models, Chemical; D009942:Organometallic Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
D000473:Alkanes; D000475:Alkenes; D006845:Hydrocarbons, Fluorinated; D007097:Imines; D007659:Ketones; D009942:Organometallic Compounds; D015032:Zinc