C2轴对称樟脑磺酰胺基醇配体催化环己烯乙炔对酮的不对称加成反应

Asymmetric Addition of 1-Ethynylcyclohexene to Ketones Catalyzed by a Chiral C_2-Camphorsulfonamide Ligand

应用C2轴对称的樟脑磺酰胺基醇配体和Cu(OTf)2催化带官能团的环己烯乙炔对酮的不对称加成反应.芳香酮、脂肪酮和杂环酮都适用于此体系,并且在室温下最高e.e.值约为89%,其中脂肪酮首次被应用于此反应,极大地扩展了底物的范围.研究结果表明,脂肪酮的立体位阻对反应的对映选择性起着至关重要的作用.

Addition of terminal alkynes to carbonyls is considered as an effective route for the synthesis of chiral propargyl alcohols and has gained a considerable significance in recent years. For possible further transformations of the alkene group, such as epoxidation, hydroxylation, ozonolysis, addition of carbenes, the asymmetric addition of 1-ethynylcyclohexene to ketones should have more potential applications than phenylacetylene for the synthesis of complex bioactive natural products. In this paper, the development of good enantioselective catalysts involving Cu （OTf） 2 and chiral C2-camphorsulfonamide for the alkynylation of ketones including aromatic, heteroaromatic and aliphatic ketones was described. The reaction proceeded under mild conditions（ toluene, room temperature ） with the available catalyst. The reactions of aliphatic ketones could be completed in less than 12 h to give the products in good yields and enantioselectivities. The best enantioselectivity（up to 89% e. e. ） was obtained in the alkynylation of 3-methylbutan-2-one. Moreover, the hindrance of the aliphatie ketones played a critical role in the control of the enantioselectivities of the corresponding products.