Double Intramolecular Transacetalization of Polyhydroxy Acetals: Synthesis of Conformationally-Restricted 1,3-Dioxanes with Axially-Oriented Phenyl Moiety.
The synthesis of conformationally-restricted 1,3-dioxanes with a phenyl moiety fixed in an axial orientation at the acetalic center is described. Starting with diethyl 3-hydroxyglutarate (15), benzaldehyde acetal12aand acetophenone ketal12bbearing a protected 1,3,5-trihydroxypentyl side chain in theo-position were prepared. The first acid-catalyzed intramolecular transacetalization gave a mixture of diastereomeric 2-benzofurans18(ratio of diastereomers 2:2:1:1). After OH group deprotection, the second intramolecular transacetalization afforded tricyclic alcohol14a(2-(1,5-epoxy-1,3,4,5-tetrahydro-2-benzoxepin-3-yl]ethan-1-ol). Analogous cyclizations led to the corresponding silyl ether22a(19%) and azide23a(13%). Whereas tricyclic alcohol14awas obtained as a 1:1 mixture of diastereomers, the silyl ether22aand the azide23aafforded only one diastereomer. This observation indicates a faster cyclization of the minor diastereomers providing the thermodynamically-favored compounds with equatorially-oriented substituents in the 3-position of the tricyclic 1,5-epoxy-2-benzoxepine system. In general, acetophenone-derived ketalic compounds (b-series) required very mild reaction conditions and gave lower yields than the corresponding acetalic compounds (a-series).
Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 48, D-48149 Münster, Germany. asn12002@yahoo.com.
Samuel
S
Asare-Nkansah
Institut für Pharmazeutische und Medizinische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 48, D-48149 Münster, Germany. wuensch@uni-muenster.de.|Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, D-48149 Münster, Germany. wuensch@uni-muenster.de.
Bernhard
B
Wünsch
D000080:Acetals / Q000737:chemistry*; D000107:Acetylation; D004146:Dioxanes / Q000138:chemical synthesis* / Q000737:chemistry*
D000080:Acetals; D004146:Dioxanes
1,5-epoxy-2-benzoxepines; axially-oriented phenyl moiety; conformationally-restricted 1,3-dioxanes; double intramolecular transacetalization; polyhydroxy acetals; tricyclic alcohols