Preparation And Application Of Para-alkoxy Substituted MeO-BIPHEP-type Diphosphines In Asymmetric Hydrogenation

Asymmetric hydrogenation has become increasingly popular for producing enantiomerically pure compounds in pharmaceutical and other chemical industries. The demand for new ligands with unique structural features and physical properties continues to grow in order to meet the requirements of a wide range of reactions and substrates. In this paper, a series of new optically active MeO-BIPHEP-type ligands, (S)-6,6`-dimethoxy-2,2`-bis(di-p-alkoxyphenylphosphine)-1,1`-biphenyl ((S)-165c ~ (S)-165f) were prepared and applied in asymmetric hydrogenation.Starting from the commercially available triethyl phosphorite and m-bromoanisole, an optically active (S)-6,6`-dimethoxybiphenyl-2,2`-diyl-bis (phosphonic acid diester) was prepared by an improved method. First, (3-Methoxyphenyl)-phosphonic acid diethyl ester 161 was prepared by the reaction of m-bromoanisole with triethyl phosphorite in the presence of anhydrous NiCl2. Removing of the by-product or microwave assistant synthesis could effectively accelerate the reaction and enhance the yield of product 161. Instead of the the Schmid's method, a new one-pot oxidative home-coupling of 161 catalyzed by anhydrous FeCl3 was used to form rac-6,6`-dimethoxybiphenyl-2,2`-diyl-bis (phosphonic acid diethyl ester) rac-162. The new approach could avoid the preparation and purification of iodide derived from 161 and was much easier to manipulate and more cost-effective. A suitable resolution of rac-162 was studied and...