Palladium-catalyzed asymmetric hydrogenation of simple ketones activated by Brønsted acids

Homogeneous Pd(OCOCF₃)₂/(R)-C₄-TunePhos has been successfully applied in the asymmetric hydrogenation of simple ketones activated by catalytic amount of Brønsted acid with up to 88% ee.     

Palladium-catalyzed asymmetric hydrogenation of dibenzo[b,f][1,4]thiazepines activated by Brønsted acid

An efficient and facile route to chiral dihydrodibenzothiazepines has been successfully developed via palladium-catalyzed asymmetric hydrogenation of the dibenzothiazepines with Brønsted acid as activator with up to 94% ee.     

Chiral phosphoric acid-catalyzed asymmetric transfer hydrogenation of quinazolinones

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Palladium-catalyzed direct allylation of fluorinated benzothiadiazoles with allyl chlorides

A palladium catalyzed cross-coupling of fluorinated benzothiadiazoles (FBTs) with allyl chlorides is reported. The significant feature of this method is synthetic simplicity, providing a straightforward access to unsymmetrical and symmetrical alkylated FBT derivatives that are of interest in organic electronic and optoelectronic materials.     

Manganese catalyzed asymmetric transfer hydrogenation of ketones

The asymmetric transfer hydrogenation (ATH) of a wide range of ketones catalyzed by manganese complex as well as chiral P_xN_y-type ligand under mild conditions was investigated. Using 2-propanol as hydrogen source, various ketones could be enantioselectively hydrogenated by combining cheap, readily available [MnBr(CO)₅] with chiral, 22-membered macrocyclic ligand (R,R,R',R')-CyP₂N₄ (L5) with 2 mol% of catalyst loading, affording highly valuable chiral alcohols with up to 95% ee.     

Synthesis of antidepressant duloxetine via asymmetric transfer hydrogenation

Antidepressant duloxetine （1） was prepared via asymmetric transfer hydrogenation of 3-（dimethylamino）-1-（thiophen-2- yl）propan-1-one （3）. The Ru（Ⅱ）, Rh（Ⅲ） and Ir（Ⅲ） complexes of several chiral ligands were examined as the catalyst and （S,S）-N-tosyl-1,2-diphenyl ethylenediamine （TsDPEN）-Ru（Ⅱ） complex was found to provide good yield and excellent enantioselectivity. 2007 Ming Yan. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Chiral rhodium carboxylates as asymmetric hydrogenation catalysts

The comparative catalytic activities of a few chiral rhodium carboxylato complexes in combination with chiral and achiral phosphines are described. In the hydrogenation of α-acetamidocinnamic acid and its methyl ester, differences are observed in turnover numbers and enantioselectivities. Diastereomeric interactions between chiral carboxylato and chiral phosphine moieties resulting in different rates are clearly seen. Arrhenius plots of (+) and (-) DIOP [DIOP = 2,3 isopropylidene 2,3 dihydroxy-1,4bis (diphenylphosphino) butane] with rhodium (-) mandalato complex give markedly different activation energies.     

Polymer-supported monodentate phosphite ligands for asymmetric hydrogenation

Several new polymer-supported monophosphite ligands have been developed and the rhodium complexes were shown to be highly efficient, highly enantioselective and easily separable catalysts for asymmetric hydrogenation of itaconates, enamides, α-dehydroamino acid derivatives and β-dehydroamino acid derivatives.     

Palladium-catalyzed tandem cyclization of fluorinated imidoyl chlorides with 2-bromophenylboronic acid: Synthesis of 6-fluoroalkyl-phenanthridines

An efficient method has been developed to synthesize 6-fluoroalkyl-phenanthridines via the palladium-catalyzed tandem cyclization of fluorinated imidoyl chlorides with 2-bromophenylboronic acid. This methodology facilitates the rapid synthesis of 6-fluoroalkyl-phenanthridines through dual C–C bond formation in an oxidant-free one-pot manner.     

Metal-free asymmetric hydrogenation and hydrosilylation catalyzed by frustrated Lewis pairs

The activation of H₂ for the catalytic hydrogenation of unsaturated compounds is one of the most useful reactions in both academia and chemical industry, which has long been predominated by the transition-metal catalysis. However, metal-free hydrogen activation represents a formidable challenge, and has been less developed. The recent emerging chemistry of frustrated Lewis pairs (FLPs) with a combination of sterically encumbered Lewis acids and Lewis bases provides a promising approach for metal-free hydrogenation due to their amazing abilities for the challenging H₂ activation. In the past several years, the hydrogenation of a wide range of unsaturated compounds using FLP catalysts has been successfully developed. Despite these advances, the corresponding asymmetric hydrogenation is just in its start-up step. Similar to the mode of HH bond activation, SiH bond can also be activated by FLPs for the hydrosilylation of ketones and imines. But its asymmetric version is also not well-solved. This Letter will outline the recent important progress of metal-free catalytic asymmetric hydrogenation and hydrosilylation using FLP catalysts.     

Cu(I)-catalyzed coupling reactions of fluorinated imidoyl halides with terminal alkynes: Convenient synthesis of fluorinated alkynyl imines

The first example of coupling reactions of fluorinated imidoyl halides with terminal alkynes catalyzed by CuI is presented. Each reaction needed no ligand, and fluorinated alkynyl imines were obtained with excellent yields.     

Palladium-catalyzed, asymmetric Baeyer-Villiger oxidation of prochiral cyclobutanones with PHOX ligands

Described in this report is a general method for the conversion of prochiral 3-substituted cyclobutanones to enantioenriched γ-lactones through a palladium-catalyzed Baeyer-Villiger oxidation using phosphinooxazoline ligands in up to 99% yield and 81% ee. Lactones of enantiopurity ≥93% could be obtained through a single recrystallization step. Importantly, 3,3-disubtituted cyclobutanones produced enantioenriched lactones containing a β-quaternary center.     

Recent topics in catalytic asymmetric hydrogenation of ketones

Asymmetric hydrogenation of ketones (AHK) was revolutionized in 1987 and again in 1995 when Ru(CH₃COO)₂(binap)/HCl and RuCl₂(binap)/diamine, respectively, were developed. Since then, the number of reports on Ru-catalyzed AHK has increased exponentially, and the utility of other precious metals (Os, Rh, Ir, and Pd) has also been shown. The utilization of inexpensive base metals (Fe, Co, Ni, and Cu) has been a recent trend. This digest summarizes the key advances in AHK in the past decade by categorizing the chiral ligands into six types: (i) diphosphines, (ii) diphosphines/diamines, (iii) tridentate or tetradentate phosphine amines, (iv) diamines, (v) tetradentate amines, and (vi) tetradentate thioether amines.     

Catalytic asymmetric hydrogenation to access spiroindane dimethyl acetic acid

Asymmetric hydrogenation of achiral spiroindene dimethyl acetic acid 2 with 4% of Ru(II)-Mandyphos in acetone produced (S)-spiroindane dimethyl acetic acid 1 in 86% isolated yield and 96.8:3.2 enantiomeric ratio.     

Palladium-catalyzed asymmetric allylic alkylation using chiral hydrazone ligands with ferrocene skeleton

Palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenyl-2-propenyl acetate (4) with a dimethyl malonate-BSA-LiOAc system has been successfully carried out in the presence of chiral phosphine-hydrazone ligands such as 3a in good yields with good enantioselectivities (up to 84% ee).     

Iridium-catalyzed asymmetric hydrogenation of 2-substituted 1,4-benzodioxines

An Ir-catalyzed asymmetric hydrogenation of 2-substituted 1,4-benzodioxines was developed for the preparation of chiral 1,4-benzodioxanes, which are present in numerous biologically active compounds and natural products. Our tropos biphenyl phosphine-oxazoline ligand is essential for obtaining good ee. A broad range of substrates were tolerable to the reaction conditions and gave the corresponding hydrogenation products in excellent yields and with moderate to good enantioselectivities using the Ir-complex of our tropos phosphine-oxazoline ligand.     

Synthesis of fluorinated allylic amines: Reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides with fluorinated imines

A new synthesis of fluorinated allylamines through the reaction of 2-(trimethylsilyl)ethyl sulfones and sulfoxides (as vinyl anion equivalents) with imines and imino esters has been described. The process includes a TBAF-mediated fragmentation of 2-(trimethylsilyl)ethyl sulfones to afford the desired allylic amines. When the reaction is performed with the corresponding sulfoxides, the fragmentation takes place under the addition conditions, affording the final products in a single step.     

Palladium-catalyzed Heck coupling reactions using different fluorinated phosphine ligands in compressed carbon dioxide and conventional organic solvents

Palladium-catalyzed Heck reaction of iodobenzene and styrene was investigated in compressed CO₂ using different fluorinated phosphine compounds as ligands at a temperature of 70 °C. The reaction mixture is a single phase at 12 MPa but biphasic at 8 MPa, a little higher than the critical pressure of pure CO₂ under the reaction conditions used. Although the solubility of fluorinated ligands is very high in dense CO₂, they have marginal improvements in Heck conversion in this medium compared with a non-fluorinated ligand of triphenylphosphine. The activity of palladium complexes strongly depends on the kind of phosphine compound used, in the order of bis(pentafluorophenyl)phenylphosphine (III)>triphenylphosphine (I), tris(pentafluorophenyl)phosphine (IV)>diphenyl(pentafluorophenyl)phosphine (II), tris(p-fluorophenyl)phosphine (V)>tris(p-trifluoromethyl phenyl)phosphine (VI), 1,2-bis[bis(pentafluorophenyl)phosphino]ethane (VII), for the homogeneous reaction at 12 MPa. This order of effectiveness of these ligands is different from those obtained in conventional organic solvents. Hexane, toluene, ethanol, and N-methylpyrrolidone (NMP) showed maximum conversions with the ligands VI, IV, V and VII, respectively. The conversion in CO₂ with the ligand III is comparable with those in polar solvents of ethanol and NMP, and larger than those in hexane and toluene in the presence of the best ligands. The dense CO₂ may affect the specific activity of palladium complex catalysts and/or the reactivity of reacting species. Small quantities of fluorinated products were observed to form at high pressure of CO₂ and this is direct evidence of P–C bond cleavage during Heck reaction in dense CO₂. The activity of palladium complexes with those ligands is higher in more polar solvent.     

Palladium-catalyzed asymmetric hydrogenation of functionalized ketones

[reaction: see text]. A novel catalytic system for asymmetric hydrogenation of functionalized ketones has been developed using a Pd/bisphosphine complex as the catalyst in 2,2,2-trifluoroethanol. The reaction exhibits high enantioselectivity, and up to 92.2% ee was obtained.     

Novel recoverable catalysts for asymmetric transfer hydrogenation

9-Amino(9-deoxy)epiquinine and 9-amino(9-deoxy)epicinchonine were applied in asymmetric transfer hydrogenation of aromatic ketones in both iridium and rhodium catalytic systems using i-propanol as the hydrogen source. Good to excellent conversions and enantioselectivities were observed with a variety of aromatic ketones. Moreover, the Ir complex and Rh complex of 9-amino(9-deoxy)cinchonine were recovered in high yields with dilute hydrochloric acid. The enantioselectivity of 1-phenylethanol was nearly maintained after six cycles.