title: Strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays based on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides: application to natural product synthesis.
abstract: We describe a new strategy for enantio- and diastereoselective syntheses of all possible stereoisomers of 1,3-polyol arrays. This strategy relies on a highly catalyst-controlled epoxidation of alpha,beta-unsaturated morpholinyl amides promoted by the Sm-BINOL-Ph(3)As[double bond]O (1:1:1) complex, followed by a conversion of morpholinyl amides into ketones and diastereoselective ketone reduction. Highly enantio- (up to >99 % ee) or diastereoselective (up to >99.5:0.5) epoxidation was achieved using 5-10 mol % of the Sm complex to afford synthetically very useful, nearly optically pure alpha,beta-epoxy morpholinyl amides. Stereoselectivity of the epoxidation was controlled by the chirality of BINOL with overwhelming inherent diastereofacial preference for the substrate. Combination with the syn- and anti-selective ketone reduction with the highly catalyst-controlled epoxidation allowed for an iterative strategy for the syntheses of all possible stereoisomers of 1,3-polyol arrays. Eight possible stereoisomers of 1,3,5,7-tetraol arrays were synthesized with high to excellent stereoselectivity. Moreover, the efficiency of the present strategy was successfully demonstrated by enantioselective syntheses of several 1,3-polyol/alpha-pyrone natural products, for example, cryptocaryolone diacetate.
authors.affiliation: Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shin-ya
authors.initials: SY
authors.lastname: Tosaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Nemoto
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohshima
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Shibasaki
mesh_terms: D000438:Alcohols / Q000138:chemical synthesis*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D002384:Catalysis; D004852:Epoxy Compounds / Q000138:chemical synthesis; D007811:Lanthanum / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry*; D011753:Pyrones / Q000138:chemical synthesis; D012493:Samarium / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000438:Alcohols; D000577:Amides; D004852:Epoxy Compounds; D009942:Organometallic Compounds; D011753:Pyrones; D012493:Samarium; D007811:Lanthanum