title: A Direct, Concise, and Enantioselective Synthesis of 2-Substituted 4,4,4-Trifluorobutane-1,3-diols Based on the Organocatalytic In Situ Generation of Unstable Trifluoroacetaldehyde.
abstract: A direct, concise, and enantioselective synthesis of 2-substituted 4,4,4-trifluorobutane-1,3-diols based on the organocatalytic asymmetric direct aldol reaction of an ethyl hemiacetal of trifluoroacetaldehyde with various aldehydes was examined. A catalytic amount (30 mol %) of commercially available and inexpensive l-prolinamide is quite effective as an organocatalyst for the catalytic in situ generation of gaseous and unstable trifluoroacetaldehyde from its hemiacetal, and a successive asymmetric direct aldol reaction with various aldehydes in dichloromethane at 0 °C, followed by reduction with sodium borohydride, gives 2-substituted 4,4,4-trifluorobutane-1,3-diols in moderate to good yields (31-84%) with low diastereoselectivities and good to excellent enantioselectivities (64-97% ee).
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan. funabiki@gifu-u.ac.jp.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Funabiki
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Yudai
authors.initials: Y
authors.lastname: Furuno
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yano
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Sakaida
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kubota
authors.affiliation: Department of Chemistry and Biomolecular Science, Gifu University, 1-1 Yanagido, Gifu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Matsui
mesh_terms: D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry; D000447:Aldehydes / Q000737:chemistry; D001894:Borohydrides / Q000737:chemistry; D002072:Butylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D002384:Catalysis; D007659:Ketones / Q000737:chemistry; D008752:Methylene Chloride / Q000737:chemistry; D010084:Oxidation-Reduction; D011392:Proline / Q000031:analogs & derivatives / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D001894:Borohydrides; D002072:Butylene Glycols; D007659:Ketones; D008752:Methylene Chloride; C055298:trifluoroacetaldehyde; C025364:sodium borohydride; C116609:3-hydroxybutanal; D011392:Proline; D000079:Acetaldehyde; C056291:prolinamide
keywords: aldol reaction; asymmetric synthesis; fluorine; organocatalysis; synthesis design