Hydrogenation is a core technology in chemical synthesis. High rates and selectivities are attainable only by the coordination of structurally well-designed catalysts and suitable reaction conditions. The newly devised [RuCl(2)(phosphane)(2)(1,2-diamine)] complexes are excellent precatalysts for homogeneous hydrogenation of simple ketones which lack any functionality capable of interacting with the metal center. This catalyst system allows for the preferential reduction of a C=O function over a coexisting C=C linkage in a 2-propanol solution containing an alkaline base. The hydrogenation tolerates many substituents including F, Cl, Br, I, CF(3), OCH(3), OCH(2)C(6)H(5), COOCH(CH(3))(2), NO(2), NH(2), and NRCOR as well as various electron-rich and -deficient heterocycles. Furthermore, stereoselectivity is easily controlled by the electronic and steric properties (bulkiness and chirality) of the ligands as well as the reaction conditions. Diastereoselectivities observed in the catalytic hydrogenation of cyclic and acyclic ketones with the standard triphenylphosphane/ethylenediamine combination compare well with the best conventional hydride reductions. The use of appropriate chiral diphosphanes, particularly BINAP compounds, and chiral diamines results in rapid and productive asymmetric hydrogenation of a range of aromatic and heteroaromatic ketones and gives a consistently high enantioselectivity. Certain amino and alkoxy ketones can be used as substrates. Cyclic and acyclic alpha,beta-unsaturated ketones can be converted into chiral allyl alcohols of high enantiomeric purity. Hydrogenation of configurationally labile ketones allows for the dynamic kinetic discrimination of diastereomers, epimers, and enantiomers. This new method shows promise in the practical synthesis of a wide variety of chiral alcohols from achiral and chiral ketone substrates. Its versatility is manifested by the asymmetric synthesis of some biologically significant chiral compounds. The high rate and carbonyl selectivity are based on nonclassical metal-ligand bifunctional catalysis involving an 18-electron amino ruthenium hydride complex and a 16-electron amido ruthenium species.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/1521-3773%2820010105%2940%3A1%3C40%3A%3AAID-ANIE40%3E3.0.CO%3B2-5

Asymmetric Catalysis by Architectural and Functional Molecular Engineering: Practical Chemo‐ and Stereoselective Hydrogenation of Ketones

This account examines double asymmetric induction from theoretical and practical viewpoints. In the context of four major organic reactions-the aldol, Diels-Alder, catalytic hydrogenation, and epoxidation-it is shown that a double asymmetric induction can be analyzed in terms of the single asymmetric reactions of each of the two chiral reactants. A rule which qualitatively relates the results of these single asymmetric reactions with the outcome of the double asymmetric reaction is proposed. A powerful new strategy based on this rule for the predictable creation of new chiral centers is discussed and the use of this strategy for the synthesis of sugars and macrolides is presented.

Double Asymmetric Synthesis and a New Strategy for Stereochemical Control in Organic Synthesis

Laboratory for Advanced Materials and New Catalysis, School of Chemistry and Materials Science, Hubei University, Wuhan 430062, China,Laboratory of Natural Gas Utilization and Applied Catalysis, Dalian Institute of Chemical Physics of Chinese Academy of Sciences, Dalian 116023,China, and Jingmen Technological College, Jingmen 448000, ChinaReceived June 30, 2004

Advances in Homogeneous and Heterogeneous Catalytic Asymmetric Epoxidation

Recent developments in the stereoselective synthesis of α-aminoacids

The Walden memorial at the Technical University in Riga is pictured in the frontispiece to mark the recent centennial of the Walden inversion. This is a rare public monument to key events from the first era of exploration in stereocontrolled synthesis, and may be the only such monument to use the language of organic chemistry expressed at the molecular level. The reaction of racemic substrates with chiral nucleophiles is one of many methods currently known to achieve kinetic resolution, a phenomenon that ranks as the oldest and most general approach for the synthesis of highly enantioenriched substances. The first nonenzymatic kinetic resolutions as well as the original forms of the Walden inversion were studied in the 1890s. All of these investigations were conducted within the first generation following the demonstration that carbon is tetrahedral, and provided abundant evidence that the principles and importance of enantiocontrolled syntheses were understood. However, a reliable, rapid technique to quantify results and guide the optimization process was still lacking. Many decades passed before this problem was solved by the advent of HPLC and GLPC assays on chiral supports, which stimulated explosive growth in the synthesis of nonracemic substances by kinetic resolution. The Walden monument is accessible to passers-by for hands-on inspection as well as for contemplation and learning. In a similar way, kinetic resolution is experimentally accessible and can be thought-provoking at several levels. We follow the story of kinetic resolution from the early discoveries through fascinating historical milestones and conceptual developments, and close with a focus on modern techniques that maximize efficiency.

Efficiency in nonenzymatic kinetic resolution.

Kinetic resolution of racemic allylic alcohols by enantioselective epoxidation. A route to substances of absolute enantiomeric purity

A diverse selection of new synthetic applications of the titaniumcatalyzed asymmetric epoxidation (AE) process is described. These include asymmetric syntheses of (+)_DarvonR Alcohol, (-)-bestatin, (+)-2-methyl bestatin, (-)-propranolol, (-)-u-amino--hydroxybutyric acid, and (_) and (+)_frontalin. The kinetic resolution mode of the AE process was used to prepare chiral insect pheromones in very high (>99% e.e.) optical purity; these include (+)-and (-)-ct-caprolactone, (-)-exobrevicomin, (-)-endobrevicomin, (+)_and (-)-ipsdienol, and (+)-trans-verbenol. A number of unusual kinetic resolutions based on the AE process are presented; these include resolutions of allenic alcohols, n-acetylenic carbinols, -hydroxy sulfides, and a dienol. Almost two years ago we first reported on the titanium-catalyzed asymmetric epoxidation process shown in Scheme 11a In the interim this new chiral catalyst system has rapidly become accepted as one of the best means for synthesizing a great variety of optically pure

Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions

The rate of titanium-tartrate-catalyzed asymmetric epoxidation of allylic alcohols is shown to be first order in substrate and oxidant, and inverse second order in inhibitor alcohol, under pseudo-first-order conditions in catalyst. The rate is slowed by substitution of electron-withdrawing substituents on the olefin and varies slightly with solvent, CH 2 Cl 2 being the solvent of choice. Assymetric induction suffers when the size of the alkyl hydroperoxide is reduced. Kinetic resolution of secondary allylic alcohols is shown to be sensitive to the size of the tartrate ester group and insensitive to the steric nature of inhibitor alcohol. Most importantly, the species containing equimolar amounts to Ti and tartrate is shown to be the most active catalyst in the reaction mixture, mediating reaction at much faster rates than titanium tetraalkoxide alone

Mechanism of asymmetric epoxidation. 1. Kinetics

Stereo and regioselective openings of chiral 2,3‐epoxy alcohols. versatile routes to optically pure natural products and drugs. unusual kinetic resolutions

Scott S. Woodard

Papers

Kinetic resolution of racemic allylic alcohols by enantioselective epoxidation. A route to substances of absolute enantiomeric purity

Stereo and regioselective openings of chiral 2,3-epoxy alcohols. Versatile routes to optically pure natural products and drugs. Unusual kinetic resolutions

Mechanism of asymmetric epoxidation. 1. Kinetics

Stereo and regioselective openings of chiral 2,3‐epoxy alcohols. versatile routes to optically pure natural products and drugs. unusual kinetic resolutions