(Primary Amido)-ene(amido) Ni(II) Catalysts Containing a P-Chirogenic Substituted Ferrocene Moiety for Highly Enantioselective Asymmetric Transfer Hydrogenation of Ketones

Abstract

Asymmetric transfer hydrogenation (ATH) of ketones is an efficient method for constructing chiral alcohols that are widely used in synthesizing various fine chemicals. Currently, most of the existing catalysts contain precious metals that are highly toxic and scarce, which limits industrial application and sustainability. Therefore, the development of catalysts based on earth-abundant and environmentally friendly 3d metals is an important research topic. We previously reported that amidoene(amido)diphosphine Ni(II) catalysts exhibited promising reactivities. However, the enantioselectivity of the catalytic system was not satisfactory. Here, we report (primary amido)-ene(amido)-Ni(II)diphosphine catalyst 2n containing a P-chirogenic substituted ferrocene moiety in the ligand backbone and its analogue (2m). 2n was used for ATHs of a range of ketones with improved enantioselectivity, affording secondary alcohols of the (S)configuration with up to 98% enantiomeric excess (e.e.). Computational results indicated that in the reaction system of catalyst 2n, the (S)-configuration of the phosphine kept the (S)-planar chiral ferrocene moiety far from the reacting site in the transition state that produced the (S)-configured alcohol. This created space for the aryl ring of the substrate and the ene(amido) moiety of the catalyst to approach each other and form a strong π−π interaction that enhanced the enantioselectivity.