Asymmetric Catalysis with Heterobimetallic Compounds

Abstract This review focuses on a new concept in catalytic asymmetric reactions that was first realized for the use of heterobimetallic complexes. As these heterobimetallic complexes function as both a Brønsted base and as a Lewis acid, just like an enzyme, they make possible a variety of efficient catalytic asymmetric reactions. This heterobimetallic concept should prove to be applicable to a variety of new asymmetric catalyses. The first part of this review describes the development of rare‐earth–alkali metal complexes such as LnM 3 tris(binaphthoxide) complexes (LnMB, Ln = rare‐earth metal, M = alkali metal), which are readily prepared from the corresponding rare‐earth trichlorides or rare‐earth isopropoxides, and their application to catalytic asymmetric synthesis. By using a catalytic amount of LnMB complexes several asymmetric reactions proceed efficiently to give the corresponding desired products in up to 98% ee : LnLB‐catalyzed asymmetric nitroaldol reactions (L = Li), LnSB‐catalyzed asymmetric Michael reactions (S  Na), and LnPB‐catalyzed asymmetric hydrophosphonylations of either imines or aldehydes (P  K). Applications of these heterobimetallic catalysts to the syntheses of several biologically and medicinally important compounds are also described. Spectral analyses and computational simulations of the asymmetric reactions catalyzed by the heterobimetallic complexes reveal that the two different metals play different roles to enhance the reactivity of both reaction partners and to position them. From mechanistic considerations, a useful activation of the heterobimetallic catalyses was realized by addition of alkali metal reagents. The second part describes the development of another type of heterobimetallic catalysts featuring Group 13 elements such as Al and Ga as the central metal. Among them, the AlLibis(binaphthoxide) complex (ALB) is an effective catalyst for asymmetric Michael reactions, tandem Michael–aldol reactions, and hydrophosphonylation of aldehydes.