We previously reported on enantioselective aldol reactions of acetone and some aldehydes catalyzed by chiral Zn(2+) complexes of L-prolyl-pendant [12]aneN(4) (L-ZnL(1)) and L-valyl-pendant [12]aneN(4) (L-ZnL(2)) in aqueous solution. Here, we report on the one-pot chemoenzymatic synthesis of chiral 1,3-diols in an aqueous solvent system at room temperature by a combination of enantioselective aldol reactions catalyzed by Zn(2+) complexes of L- and D-phenylalanyl-pendant [12]aneN(4) (L-ZnL(3) and D-ZnL(3) ) and the successive enantioselective reduction of the aldol products using oxidoreductases with the regeneration of the NADH (reduced form of nicotinamine adenine dinucleotide) cofactor. The findings indicate that all four stereoisomers of 1,3-diols can be produced by appropriate selection of a chiral Zn(2+)-complex and an oxidoreductase commercially available from the "Chiralscreen OH" kit.

Extending carbon frameworks via a series of C–C bond forming reactions is essential for the synthesis of natural products, pharmaceutically active compounds, active agrochemical ingredients, and a variety of functional materials. The application of stereoselective C–C bond forming reactions to the one-pot synthesis of biorelevant compounds is now emerging as a challenging and powerful strategy for improving the efficiency of a chemical reaction, in which some of the reactants are subjected to successive chemical reactions in just one reactor. However, organic reactions are generally conducted in organic solvents, as many organic molecules, reagents, and intermediates are not stable or soluble in water. In contrast, enzymatic reactions in living systems proceed in aqueous solvents, as most of enzymes generally function only within a narrow range of temperature and pH and are not so stable in less polar organic environments, which makes it difficult to conduct chemoenzymatic reactions in organic solvents. In this review, we describe the design and synthesis of chiral metal complexes with Zn2+ ions as a catalytic factor that mimic aldolases in stereoselective C–C bond forming reactions, especially for enantioselective aldol reactions. Their application to chemoenzymatic reactions in aqueous solution is also presented.

We previously reported that chiral Zn(2+) complexes that were designed to mimic the actions of class-I and class-II aldolases catalyzed the enantioselective aldol reactions of acetone and its analogues thereof with benzaldehyde derivatives. Herein, we report the synthesis of new chiral Zn(2+) complexes that contain Zn(2+)-tetraazacyclododecane (Zn(2+)-[12]aneN4) moieties and amino acids that contain aliphatic, aromatic, anionic, cationic, and dipeptide side chains. The chemical and optical yields of the aldol reaction were improved (up to 96 % ee) by using ZnL complexes of L-decanylglycyl-pendant [12]aneN4 (L-ZnL(7)), L-naphthylalanyl-pendant [12]aneN4 (L-ZnL(10)), L-biphenylalanyl-pendant [12]aneN4 (L-ZnL(11)), and L-phenylethylglycyl-pendant [12]aneN4 ligands (L-ZnL(12)). UV/Vis and circular dichroism (CD) titrations of acetylacetone (acac) with ZnL complexes confirmed that a ZnL-(acac)(-) complex was exclusively formed and not the enaminone of ZnL and acac, as we had previously proposed. Moreover, the results of stopped-flow experiments indicated that the complexation of (acac)(-) with ZnL was complete within milliseconds, whereas the formation of an enaminone required several hours. X-ray crystal-structure analysis of L-ZnL(10) and the ZnL complex of L-diphenylalanyl-pendant [12]aneN4 (L-ZnL(13)) shows that the NH2 groups of the amino-acid side chains of these ligands are coordinated to the Zn(2+) center as the fourth coordination site, in addition to three nitrogen atoms of the [12]aneN4 rings. The reaction mechanism of these aldol reactions is discussed and some corrections are made to our previous mechanistic hypothesis.

We previously reported on enantioselective aldol reactions of acetone and cyclic ketones with benzaldehyde derivatives catalyzed by chiral Zn 2+ complexes that mimic class II aldolases. The results and mechanistic studies indicated that the catalytic activity of Zn 2+ complexes is dependent not only on the coordination numbers of Zn 2+ but also on its coordination structure. In this study, we report on shape measures (abbreviated as S values in this manuscript) of such Zn 2+ complexes with respect to the 5-coordination structure based on calculations with continuous shape measures (CShM) using their crystal structures. The S values of Zn 2+ ions in Zn 2+ complexes for trigonal bipyramidal (D 3h ) or square pyramidal (C 4v ) [a]

Asymmetric Aldol Reactions Between Acetone and Benzaldehydes Catalyzed by Chiral Zn 2+ Complexes of Aminoacyl 1,4,7,10-Tetraazacyclododecane: Fine-Tuning of the Amino-Acid Side Chains and a Revised Reaction Mechanism. -The yields and enantioselectivities of the reaction are improved compared to the known methods. The reaction mechanism is discussed and the previously proposed mechanism is corrected. -(ITOH, S.; TOKUNAGA, T.; SONOIKE, S.; KITAMURA, M.; YAMANO, A.; AOKI*, S.; Chem. -Asian J. 8 (2013) 9, 2125-2135, http://dx.