Study On The Catalytic Asymmetric Addition Of 1-ethynylcyclohexene To Ketones Using A Chiral C₂-camphorsulfonamide Ligand

Optically active propargyl alcohols are important and versatile building blocks for the synthesis of a wide range of pharmaceuticals and natural products.Addition of metallated terminal alkynes to carbonyls is considered as an effective route for the synthesis of chiral propargyl alcohols and has gained considerable significance in recent years.Currently,there are lots of reports on the asymmetric alkynylation of aldehydes,showing good to excellent enantioselectivity and high yield.However,due to the inertness of the ketones and the difficulties of controlling the stereoselectivity of the chiral center of the tertiary propargylic alcohols,the reaction of asymmetric alkynylation of ketones is still a chanllenge.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.Moreover, the comparative substituents of the carbonyl leaded to the difficulties of the alkynylations of the aliphatic ketones.There were few reports concerning the alkynylations of the aliphatic ketones.Particularly,the asymmetric addition for the metallated terminal functionalized alkynes to aliphatic ketones has not been reported so far.Here,we mainly discuss design and synthesis of some chiral ligands or catalysts and their application to the asymmetric addition of 1-ethynylcyclohexene to aromatic,heteroaromatic,aliphatic and unsaturated ketones.From commercially available(1S)-(+)-10-Camphorsulfonyl chloride,C₂ camphorsulfonamide ligand was easily prepared in two simple steps and applied in the enantioselective addition of 1-ethynylcyclohexene to ketones.The reactions of aliphatic ketones could complete in less than 12 hours to give the products in good yields and enantioselectivities(up to 89%ee).In the reaction of 1-ethynylcyclohexene addition to aromatic ketones,heteroaromatic ketones and unsaturated ketones,the results obtained are quite promising in terms of yields and enantiomeric excess(up to 83%ee).