Asymmetric Alkylation of N-Toluenesulfonylimines with Dialkylzinc Reagents Catalyzed by Copper−Chiral Amidophosphine

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Abstract
The synthetic procedure of a chiral amidophosphine ligand 5 bearing two bulky substituents, 2,4,6-trimethylphenylmethyl or 2,4,6-triisopropylphenylmethyl groups, on the pyrrolidine ring was improved by employing the borane−THF reduction of the lactam−alcohol intermediate 8. The resulting amino alcohol was selectively acylated to give an amide−alcohol 11, which was then converted to the chloride 12 in 55−73% yields by the treatment with methanesulfonyl chloride in collidine. The reaction of the chloride 12 with NaPPh2 in dioxane−THF gave an amidophosphine 5 in an acceptably high 82−83% yields. Addition of a hexane solution of dialkylzinc reagent to a mixture of catalytic amount of an amidophosphine 5, copper species, and N-toluenesulfonylimine 1a of benzaldehyde in toluene provided a solution which gave the alkylated amide 3 in high yield and enantioselectivity up to 96%. A survey of copper sources and solvents concluded that copper(II) ditriflate and copper(I) triflate−benzene complex as good copper sources and toluene as a choice of solvent. N-Toluenesulfonylimines 1a−e of arylaldehydes, furfural, and alkanals were successfully ethylated with diethylzinc to give the corresponding N-toluenesulfonylamides 3aE−eE in satisfactorily good 69−97% yields and high 86−96% enantioselectivities.

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