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 Brernsted 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,tris(binaphthoxide) complexes (LnMB, Ln = rareearth metal, M = alkali metal), which are readily prepared from the corresponding rare-earth trichlorides or rareearth 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), LnSBcatalyzed 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 A1 and Ga as the central metal. Among them, the AILibis(binaphthoxide) complex (ALB) is an effective catalyst for asymmetric Michael reactions, tandem Michael -aldol reactions, and hydrophosphonylation of aldehydes.

No abstract

The optically active lanthanum-sodium-BINOL complex (LSB), prepared from La(0-i-Pr)3, (R)-BINOL (3 mol equiv), and NaO-f-Bu (3 mol equiv), is quite effective as an asymmetric catalyst for various Michael reactions to give adducts in up to 92% ee. X-ray crystallographic analysis of LSB shows that this catalyst consists of LaNasCsoFLfiOfi^THF'ILO, in which three BINOL molecules, three sodium atoms, and one water molecule surround a lanthanum atom and two THF molecules coordinate to the each sodium atom. 'H-NMR study indicates the coordination of cyclohexenone, acts as a Michael acceptor, to the lanthanum atom in LSB. Furthermore, Rappe's universal force field calculation of the LSB catalyzed reaction of cyclohexenone with dimethyl malonate supports that this basic LSB complex also acts as a Lewis acid to control the direction of the carbonyl function and enhance the reactivity of the enone. This is the first example of a multifunctional heterobimetallic asymmetric catalyst (chemzyme) in which two different metals play different roles.

Systematic and quantitative measurements of the roles of stereochemistry and skeleton-dependent conformational restriction were made using multidimensional screening. We first used diversity-oriented synthesis to synthesize the same number (122) of [10.4.0] bicyclic products (B) and their corresponding monocyclic precursors (M). We measured the ability of these compounds to modulate a broad swath of biology using 40 parallel cell-based assays. We analyzed the results using statistical methods that revealed illuminating relationships between stereochemistry, ring number, and assay outcomes. Conformational restriction by ring-closing metathesis increased the specificity of responses among active compounds and was the dominant factor in global activity patterns. Hierarchical clustering also revealed that stereochemistry was a second dominant factor; whereas the stereochemistry of macrocyclic appendages was a determinant for bicyclic compounds, the stereochemistry of the carbohydrates was a determinant for the monocyclic compounds of global activity patterns. These studies illustrate a quantitative method for measuring stereochemical and skeletal diversity of small molecules and their cellular consequences.

No abstract

Heterobimetallic asymmetric catalysts, such as the lanthanum-lithium-binaphthol complex (LaLi-BINOL), the aluminum -lithium -binaphthol complex (AlLi-BINOL), and a newly prepared gallium -sodium -binaphthol complex (Ga Na -BINOL), have been selfassembled with reactive nucleophiles, such as lithium nitronates and sodium malonates, to generate more efficient catalysts than the parent heterobimetallic catalysts. For example, by the combined use of LaLi-BINOL (1 mol%; contains one H,O molecule) and BuLi (0.9 mol%) as the catalyst system, asymmetric nitroaldo1 reactions are greatly accelerated in all cases without a decrease in the optical purity of the nitroaldol products. Kinetic analyses have also been carried out on the Ga Na -BINOL-catalyzed Michael reaction of dibenzyl malonate with cyclohexenone, with or without NaOtBu. The calculated rate constants show that the combined use of GaNa-BINOL and NaOtBu as the catalyst gives reaction rates that are about 50 times faster than with GaNa-BINOL alone. This activation method should be useful for other asymmetric reactions catalyzed by heterobimetallic complexes.

No abstract

Two types of metal are essential for some reactions! The first efficient catalyst for asymmetric tandem Michael – aldol reactions is the heter‐obimetallic complex 1, which is easily prepared from LiAlH4 and (R)‐ 2,2′‐dihydroxy‐1,1′‐binaphthyl. The cascade reaction of diethyl methylmalonate, cyclopentenone, and 3‐phenylpropanal affords the three‐component adduct 2 in 64% yield and 91 % ee.