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

Asymmetrische Katalyse mit hinsichtlich Struktur und Funktion gezielt entworfenen Molekülen: die chemo‐ und stereoselektive Hydrierung von Ketonen

Recent evidence suggests that blocking aberrant hedgehog pathway signaling may be a promising therapeutic strategy for the treatment of several types of cancer. Cyclopamine, a plant Veratrum alkaloid, is a natural product antagonist of the hedgehog pathway. In a previous report, a seven-membered D-ring semisynthetic analogue of cyclopamine, IPI-269609 (2), was shown to have greater acid stability and better aqueous solubility compared to cyclopamine. Further modifications of the A-ring system generated three series of analogues with improved potency and/or solubility. Lead compounds from each series were characterized in vitro and evaluated in vivo for biological activity and pharmacokinetic properties. These studies led to the discovery of IPI-926 (compound 28), a novel semisynthetic cyclopamine analogue with substantially improved pharmaceutical properties and potency and a favorable pharmacokinetic profile relative to cyclopamine and compound 2. As a result, complete tumor regression was observed in a Hh-dependent medulloblastoma allograft model after daily oral administration of 40 mg/kg of compound 28.

Discovery of a Potent and Orally Active Hedgehog Pathway Antagonist (IPI-926)

Tetrahydrofurfuryl alcohol could be obtained by catalytic hydrogenation of either furfural or furfuryl alcohol using Pd-, Ru-, Rh- and Ni-supported catalysts as well as their mixtures with a Cu-supported catalyst. In the case of furfural hydrogenation, the best results (97 % yield, 100 % conversion, 98 % selectivity) were obtained in the presence of Ni and Cu. However, this catalytic mixture could not be recycled. In the case of furfuryl alcohol hydrogenation, Ni-supported catalysts were the most active. Nickel-onsilica-alumina catalyst containing 59 % of metal lead to the best results (98–99 % yield, selectivity and conversion >99 %). Moreover, it could be recycled. Hydrogenation of furfuryl alcohol in the presence of this catalyst was the best procedure for the production of tetrahydrofurfuryl alcohol.

High selective production of tetrahydrofurfuryl alcohol: Catalytic hydrogenation of furfural and furfuryl alcohol

Phosphine Effects in the Copper(I) Hydride-Catalyzed Hydrogenation of Ketones and Regioselective 1,2-Reduction of α,β-Unsaturated Ketones and Aldehydes. Hydrogenation of Decalin and Steroidal Ketones and Enones

Highly stereoselective hydrogenation of 3-oxo-4-ene and -1,4-diene steroids to 5.beta. compounds with palladium catalyst

Stereochemistry of the Palladium-Catalyzed Hydrogenation of 3-Oxo-4-ene Steroids1

A detailed analysis of the 400 MHz 1H-NMR spectrum of magydardienediol (1), a diterpene isolated from Magydaris panacifolia (Vahl) Lange, has been performed by use of a combination of proton homonuclear spin decoupling, COSY, NOE difference, and NOESY techniques. This 1H-NMR spectral analysis, in conjunction with the mass spectral analysis of some derivatives of 1, revealed that the structure of 1 should be revised to t-6-hydroxymethyl-1,t-3-dimethyl-t-2-(3-methyl-2-butenyl)-3-(4-methyl-3-pentenyl)-γ-1-cyclohexanol.

400 MHz Proton nuclear magnetic resonance study of magydardienediol, a diterpene from Magydaris panacifolia.

Reactions of cycloalkanones in the presence of platinum-metal catalysts and hydrogen

Hydrogenation of unhindered cyclohexanones with rhodium catalyst in isopropyl alcohol or tetrahydrofuran in the presence of hydrochloric acid gives excellent yields of axial alcohols. Steroidal 3,17- and 3,20-diones are selectively hydrogenated at C-3 to give the corresponding 3-axial-hydroxy ketones in high yields.

Michio Shiota

Papers

Highly stereoselective hydrogenation of 3-oxo-4-ene and -1,4-diene steroids to 5.beta. compounds with palladium catalyst

Stereochemistry of the Palladium-Catalyzed Hydrogenation of 3-Oxo-4-ene Steroids1

400 MHz Proton nuclear magnetic resonance study of magydardienediol, a diterpene from Magydaris panacifolia.

Reactions of cycloalkanones in the presence of platinum-metal catalysts and hydrogen

Stereoselective hydrogenation of unhindered cyclohexanones to axial alcohols with rhodium catalyst