Toward Efficient Asymmetric Hydrogenation: Architectural and Functional Engineering of Chiral Molecular Catalysts

Abstract

Asymmetric hydrogenation uses inexpensive, clean hydrogen gas and a very small amount of a chiral molecular catalyst, providing the most powerful way to produce a wide array of enantio-enriched compounds in a large quantity without forming any waste. The recent revolutionary advances in this field have entirely changed the synthetic approach to producing performance chemicals that require a high degree of structural precision. The means of developing efficient asymmetric hydrogenations is discussed from a mechanistic point of view.A symmetric catalysis lies outside the realm of traditional organic synthesis. It is a pervasive, global endeavor involving synthetic organic chemistry, catalytic chemistry, structural chemistry, inorganic and coordination chemistry, physical chemistry, and theoretical chemistry, as well as chemical engineering. Chiral Molecular Catalysts:Beyond the Shape Asymmetric catalysis is four-dimensional chemistry (1). High efficiency can be achieved only by using a combination of both an ideal 3D structure (x, y, z) and suitable kinetics (t). Currently, efficient asymmetric catalysis primarily uses a molecular catalyst that consists of a metallic element and chiral organic ligand(s) (2). Fig. 1 illustrates a typical (but not general) catalytic scheme. Under reaction conditions, the initially used precatalyst 1 is converted to the true catalyst 2 (induction process) that activates achiral molecules A and B and transforms them to the chiral product A-B (catalytic cycle). Although the ligand must create a distinct enantio-differentiating environment in transition metal-based complexes, such an architectural design does not suffice to achieve asymmetric catalysis. Some of the steps in the multistep transformation are reversible, whereas the first irreversible step, for example 334, kinetically determines the absolute stereochemistry of A-B. Efficient asymmetric catalysis requires a high turnover number and high turnover frequency, but the best way to generate high catalytic activity is not immediately apparent. First, the induction process of converting 1 to 2 is often not straightforward. Furthermore, to obtain a high turnover frequency, all of the transition metal-based entities 2-4 in this cycle must be neither very unstable nor very stable, avoiding substrate and͞or product inhibition. Instead, 2-4 are required to interconvert one another smoothly by means of a low kinetic barrier, and without any destructive side reactions. The reaction conditions strongly influence the stability and reactivity of 1-4. In general, both suitable architectural and functional engineering are crucial for obtaining sufficient catalytic efficiency. ''Molecular catalysis'' can cope with such requirements, because any molecules, by definition, can be designed and synthesized at will.This perspective deals largely with the intrinsic mechanistic aspects of asymmetric hydrogenation developed in our laboratories (3-5). Although HOH bonds are readily cleaved by transition metal complexes, truly useful asymmetric hydrogena...

Purification, immobilization and stabilization of a highly enantioselective alcohol dehydrogenase from Thermus thermophilus HB27 cloned in E. coli

“…This extremely stable and selective biocatalyst seems to present very good prospects as industrial catalyst in asymmetric reductions [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15].…”

“…The asymmetric reductions of ketones [1][2][3][4][5][6][7][8] or double bonds [9] are examples of these interesting reactions. Stereoselective reduction of ketones to form chiral alcohols is one of the most useful reactions in organic synthesis [10][11][12]. Chiral alcohols are precursors of many high value compounds (e.g., pharmaceuticals) and dehydrogenases are a very good alternative to catalyze the asymmetric ketone reduction processes.…”

Iron-, Cobalt-, and Nickel-Catalyzed Asymmetric Transfer Hydrogenation and Asymmetric Hydrogenation of Ketones

“…46 13 When iron precatalysts containing unsymmetrical P−N−P′ pincer ligands were used, the hydrogenation of ketones proceeded at TOF up to 2000 h −1 and with up to 85% ee. Notably, the catalyst system must be activated by treatment with LiAlH 4 and then with alcohol.…”

(Benzoylamino)methyl 4-Hydroxybenzoate

“…In this paper, we present the synthesis of a new paraben compound, i.e., -benzamidomethylparaben‖ [(benzoylamino)methyl 4-hydroxybenzoate]. The benzamidomethyl group can be found in many molecules with biological activity or it intermediates within the synthesis of different biologically active compounds [21][22][23][24][25] such as the 2-benzamidomethyl-3-oxybutanoates, which are used as intermediates in the preparation of (2R,3S)-2-benzamidomethyl-3hydroxybutanoates [26][27][28] as chiral building blocks for the synthesis of biologically active carbapenems [29][30][31].…”