title: Direct catalytic asymmetric Mannich-type reaction of hydroxyketone using a Et2Zn/linked-BINOL complex: synthesis of either anti- or syn-beta-amino alcohols.
abstract: Full details of a direct catalytic asymmetric Mannich-type reaction of a hydroxyketone using a Et2Zn/(S,S)-linked-BINOL complex are described. By choosing the proper protective groups on imine nitrogen, either anti- or syn-beta-amino alcohol was obtained in good diastereomeric ratio, yield, and excellent enantiomeric excess using the same zinc catalysis. N-Diphenylphosphinoyl (Dpp) imine 3 gave anti-beta-amino alcohols in anti/syn = up to >98/2, up to >99% yield, and up to >99.5% ee, while Boc-imine 4 gave syn-beta-amino alcohols in anti/syn = up to 5/95, up to >99% yield, and up to >99.5% ee. The high catalyst turnover number (TON) is also noteworthy. Catalyst loading was successfully reduced to 0.02 mol % (TON = up to 4920) for the anti-selective reaction and 0.05 mol % (TON = up to 1760) for the syn-selective reaction. The Et2Zn/(S,S)-linked-BINOL complex exhibited far better TON than in previous reports of catalytic asymmetric Mannich-type reactions. Mechanistic studies to clarify the reason for the high catalyst efficiency as well as transformations of Mannich adducts are also described.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Matsunaga
authors.forename: Takamasa
authors.initials: T
authors.lastname: Yoshida
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Morimoto
authors.forename: Naoya
authors.initials: N
authors.lastname: Kumagai
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000605:Amino Alcohols / Q000138:chemical synthesis*; D002384:Catalysis; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D009284:Naphthols / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry*
chemical_list: D000605:Amino Alcohols; C406944:BINOL, naphthol; D007659:Ketones; D009284:Naphthols; D009942:Organometallic Compounds; D015032:Zinc