Transition metal-catalyzed enantioselective hydrogenation of enamides and enamines is one of the most important methods for the preparation of optically active amines. This review describes the recent developments of highly efficient catalytic asymmetric hydrogenation of enamides, and enamines. It specifically focuses on the substrates because hydrogenation of enamides and enamines is highly dependent on the substrates although the chiral metal catalysts play a significant role.

Transition Metal-Catalyzed Enantioselective Hydrogenation of Enamines and Imines

Asymmetric hydrogenation of heteroarenes and arenes.

Advances in the chemistry of tetrahydroquinolines.

Recent Developments in the Application of Oxazoline-Containing Ligands in Asymmetric Catalysis

Asymmetric hydrogenation of heteroaromatic compounds has emerged as a promising new route to saturated or partially saturated chiral heterocyclic compounds. In this Account, we outline recent advances in asymmetric hydrogenation of heteroaromatic compounds, including indole, quinoline, isoquinoline, furan, and pyridine derivatives, using chiral organometallic catalysts and organocatalysts.

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Asymmetric Hydrogenation of Heteroaromatic Compounds

Iridium complexes with chiral N,P ligands have established themselves as efficient catalysts for the asymmetric hydrogenation of olefins, with largely complementary scope to Rh and Ru diphosphane complexes. In contrast to Rh and Ru catalysts, they do not require a coordinating polar group next to the C=C bond. Initial experiments with cationic phosphanyloxazoline (phox) complexes ([Ir(1)(cod)]X ) (cod= cyclooctadiene) showed that these catalysts are highly active in the hydrogenation of unfunctionalized triand even tetrasubstituted olefins. In this respect, they resemble Crabtree)s catalyst, [(Cy3P)(pyridine)Ir(cod)]PF6 (Cy= cyclohexyl), which provided the stimulus for the development of these catalysts. In these studies, we also found that the choice of solvent and anion is crucial as only in weakly coordinating solvents like dichloromethane or toluene with a virtually non-coordinating anion such as BArF (tetrakis[bis3,5-(trifluoromethyl)phenyl]borate) could high turnover numbers (> 5000) be obtained. Although high enantioselectivities were obtained in the hydrogenation of certain trisubstituted aryl alkenes such as (E)-methylstilbene, the application range of Ir-phox catalysts proved to be limited. However, subsequent work has led to new classes of N,P ligands, which have broadened the scope of Ir-catalyzed hydrogenation considerably. 7] Among the many structures we investigated, oxazolinephosphinites such as 3 and certain imidazoline analogues proved to be particularly efficient, giving high enantiomeric excesses with a wide range of unfunctionalized as well as certain functionalized olefins. With the intention of mimicking the coordination sphere of the Crabtree catalysts more closely, we also examined a series of pyridineand quinoline-derived ligands 4 and 5. As the results were quite encouraging, we decided to extend our studies to bicyclic analogues of type 6 because we thought that the more rigid conformation imposed by the additional ring could result in even higher enantioselectivities. Here we report the syntheses of a series of pyridyl–phosphinites 6 and their evaluation as ligands for Ir-catalyzed asymmetric hydrogenation. As shown in the schemes below, ligands of this type are readily accessible from simple, commercially available starting materials via the corresponding pyridyl alcohols. By changing the substituents at the pyridine ring and the P atom, or altering the size of the carbocyclic ring, the steric and electronic properties of these ligands and the coordination geometry can be optimized for a specific substrate. Ligands with unsubstituted backbones (6, R=H) were synthesized from commercially available precursors 12–14 via pyridyl alcohols 7–9 (Scheme 1). Oxidation to the corre-

Iridium Catalysts with Bicyclic Pyridine–Phosphinite Ligands: Asymmetric Hydrogenation of Olefins and Furan Derivatives

Synthesis of Versatile Chiral N,P Ligands Derived from Pyridine and Quinoline

Heterocyclic phosphino oxazolines derived from thiophene and benzo[b]thiophene (HetPHOX) form highly active iridium complexes for the enantioselective hydrogenation of olefins and imines.

Iridium-HetPHOX Complexes for the Catalytic Asymmetric Hydrogenation of Olefins and Imines

Anionic boron-bridged bisoxazolines (borabox ligands) have been synthesized and characterized in their protonated forms. The ligands are tuneable over a wide range, allowing either alkyl or aryl substituents at the oxazoline rings and the central bridging boron atom. The structural parameters of this new ligand type have been investigated by X-ray analyses of palladium and copper complexes. Electronic properties have been studied by (13)C NMR spectroscopy and by DFT calculations on palladium allyl complexes and compared to those of analogous bisoxazoline (box) complexes. Borabox complexes are more electron-rich at the metal center than their neutral box congeners, and as a consequence of the longer bonds between the bridging atom and the oxazoline rings, their bite angles are larger. Palladium(II) complexes bearing an unsubstituted allyl ligand and homoleptic copper(II) complexes each possess an almost flat chelate ring. NMR analysis of a (1,3-diphenylallyl)(borabox)palladium complex showed a 92:8 mixture of (syn,syn) and (anti,syn) allyl isomers, in contrast with a previously reported box analogue that existed exclusively in the (syn,syn) form. Comparison of the corresponding crystal structures revealed that the distance between the bisoxazoline and the allyl ligand in the borabox complex is shorter. In the copper-catalyzed allylic oxidation of cyclohexene and cyclopentene with tert-butyl perbenzoate, borabox ligands gave results similar-and in some cases superior-to those obtained with analogous box ligands.

https://www.wiley-vch.de/contents/jc_2111/2008/f800822_s.pdf

Stefan Kaiser

Papers

Iridium Catalysts with Bicyclic Pyridine–Phosphinite Ligands: Asymmetric Hydrogenation of Olefins and Furan Derivatives

Synthesis of Versatile Chiral N,P Ligands Derived from Pyridine and Quinoline

Iridium-HetPHOX Complexes for the Catalytic Asymmetric Hydrogenation of Olefins and Imines

Chiral boron-bridged bisoxazoline (borabox) ligands: structures and reactivities of Pd and Cu complexes.

Iridium Catalysts with Bicyclic Pyridine—Phosphinite Ligands: Asymmetric Hydrogenation of Olefins and Furan Derivatives.