Synthesis of chiral C/N-functionalized morpholine alcohols: study of their catalytic ability as ligand in asymmetric diethylzinc addition to aldehyde
| Autor: | Rajesh Dave, N. André Sasaki |
|---|---|
| Přispěvatelé: | Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| Rok vydání: | 2006 |
| Předmět: |
chemistry.chemical_classification
Addition reaction [CHIM.ORGA]Chemical Sciences/Organic chemistry 010405 organic chemistry Stereochemistry Organic Chemistry Enantioselective synthesis General Medicine Diethylzinc 010402 general chemistry Medicinal chemistry 01 natural sciences Aldehyde Catalysis 0104 chemical sciences Inorganic Chemistry Benzaldehyde chemistry.chemical_compound chemistry Morpholine Hydroxymethyl Stereoselectivity Physical and Theoretical Chemistry Enantiomer |
| Zdroj: | Tetrahedron: Asymmetry Tetrahedron: Asymmetry, Elsevier, 2006, 17(3), pp.388-401. ⟨10.1016/j.tetasy.2005.12.027⟩ |
| ISSN: | 0957-4166 |
| DOI: | 10.1016/j.tetasy.2005.12.027 |
| Popis: | A broad variety of chiral C/N-functionalized morpholine alcohols sharing a common structural motif in the 3-(hydroxymethyl)morpholine 6 were prepared from enantiomerically pure serine for the purpose of studying their catalytic ligand properties. The asymmetric addition of diethylzinc to benzaldehyde in the presence of 10 mol % of chiral C/N-functionalized morpholine alcohols gave 1-phenyl-1-propanol in 59–81% yield with 10–30% ee. The addition of 10 mol % of n -butyl lithium to the reaction mixture resulted in a significant enhancement of the stereoselectivity in the case of ligands bearing the two geminal phenyl substituents on the backbone. In the presence of n -butyl lithium and using ( S )-3-(hydroxydiphenylmethyl)morpholine ( S )- 19 as the chiral promoter, ( S )-1-phenyl-1-propanol was obtained in 81% yield with 76% ee. The geminal diphenyl-class of morpholine ligands was examined for the diethylzinc addition to four different aldehydes in the presence of n -butyl lithium. ( S )- N -Benzyl-3-(hydroxydiphenylmethyl)morpholine ( S )- 27 was found to be most enantioselective in the case of 4-methoxybenzaldehyde to give ( R )-alcohol in 87% yield with 80% ee. Catalysts ( S )- 19 and its N -methyl derivative ( S )- 26 gave alcohols with an ( S )-absolute configuration while the N-benzylated derivative ( S )- 27 gave the opposite enantiomeric products. The tentative transition state models to account for the observed product stereoselectivity with morpholine ligands holding the geminal diphenyl group on the β-amino alcohol segment are proposed. |
| Databáze: | OpenAIRE |
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