Asymmetric conjugate addition to enones catalyzed by novel bisisoquinoline/transition metal complexes

Abstract

Novel bisisoquinoline-based ligands have been synthesized and used in various asymmetric reactions by Mr. Gao Qi in our lab. Good yields of up to 92% and moderate ee of up to 35% were obtained for the enantioselective conjugate addition of Grignard reagents to cyclohexenones to obtain the desired 1,4 – adducts. It was proposed to extend this investigation to the more challenging cyclopentenone substrates.

Using cyclopentenone as a model substrate, various reaction parameters were optimized. These parameters include: Grignard reagent, chiral ligands, metal salts, solvent system, reaction temperature, catalyst loading and other components (such as molecular sieves and co-ligands) used. NMR was used to confirm the identity of the products while Gas Chromatography was used to determine the enantioselectivities of the desired products.

Under the optimized reaction conditions investigated, the best ee of 28% was obtained for the reaction of 2-cyclopentenone with isopropylmagnesium chloride using 15 mol% of a complex between basic ligand M1 and copper (II) triflate in dry THF at -90 °C for 15 minutes in the presence of Drierite.