| Summary: | 碩士 === 國立中興大學 === 化學系所 === 98 === Alcohols are important intermediate in the synthesis of many functional groups transformation, and in many drugs and natural products, the optically active secondary alcohols are often part of the structure. So construction of optically active secondary alcohols in the synthesis is very important. We hope that the development of catalysts and obtain high yield and high enantioselectivity for secondary alcohols by asymmetric addition of diethylzinc to aldehydes.
An efficient and practical method for the preparation of optically active secondary alcohols via enantioselective addition of diethylzinc catalyzed by chiral ligands has been developed. Chiral ligands 19 and 20 have been prepared from (1S)-(-)-alpha-pinene in 50% and 37% respectively over 5 steps. The synthetic precursor, alpha-hydroxyketone 16, was synthesized from pinene through asymmetric dihydroxylation by OsO4 followed by oxidation of the secondary alcohol by Parikh-Döering Oxidation in 84% yield over 2 steps. Oxime formation with hydroxylamine hydrochloride, reduction of oxime group followed by N-alkylation with dibromide afforded β-amino alcohols 19 and 20.
β-Amino alcohols were utilized as chiral ligands for diethylzinc asymmetric addition to the carbonyl group of aldehydes (aldehyde : diethylzinc : amino alcohol = 1.0 : 2.0 : 0.05) to provide the corresponding chiral secondary alcohols in up to 96% ee value and 99% chemical yield. In the research, the synthesis of chiral catalysts in the process has encountered some problems, but that are smooth to resolve by finding relational literature, and also discover separate conditions of enantiomer by HPLC.
In this study, Starting from alpha-pinene, a cheap and readily available chemical and using simple synthetic methods to furnish effective chiral catalysts 19 and 20 for the asymmetric addition of diethylzinc to aldehydes. This will be a useful and practical protocol for preparing chiral secondary alcohols in high chemical yield and optical purities.
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