The Study Towards the Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Camphor-based Chiral Ligand

• Main Authors: Shu-Ming Chang, 張書銘
• Other Authors: Ta-Jung Lu
• Format: Others
• Language: zh-TW
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/20034134840040601316

碩士 === 國立中興大學 === 化學系所 === 101 === Optically active secondary alcohols are an important intermediate in organic synthesis and appear in the structures of natural products and drugs. The hydroxyl group can be readily transformed into many different important synthetic intermediates. The purpose of this research is to develop new camphor-based chiral ligands and study their reactivity and enantioselectivity for the addition of diethylzinc to aldehydes to prepare chiral secondary alcohols. The chiral tridentate ligands were envisioned to be prepared from camphor in four steps. First, camphorquinone was synthesized from camphor by selenium dioxide oxidation, which was followed by reacting with hydroxylamine hydrochloride to give camphorquinone oxime. The amino alcohol was obtained by reduction of the oxime with lithium aluminum hydride which was then reacted with different aldehydes to form imines which were reduced by sodium borohydride to give the corresponding chiral tridentate ligands 25a-25i, in 42-84% overall yield over 4 steps. These chiral tridentate ligands catalyzed diethylzinc addition to aldehydes to give secondary alcohols in high yields (48-95%) and enantioselectivities (43-95%). The reaction required 2.5 equivalent of diethylzinc to the aldehyde, and was completed in 2.5 hour at ambient temperature. The catalytic system affords higher enantioselectivities and yields to aromatic aldehydes then those of aliphatic aldehydes. In conclusion, we have developed a simple and practical synthetic method to furnish camphor-based chiral tridentate ligands. The ligands were successfully utilized in the preparation of chiral secondary alcohols by asymmetric addition of diethylzinc to aldehyde. This will be a useful and practical protocol for chiral second alcohols in high optical purities and chemical yield.