Henri Doucet

trans-[RuCl2(phosphane)2(1,2-diamine)] and Chiraltrans-[RuCl2(diphosphane)(1,2-diamine)]: Shelf-Stable Precatalysts for the Rapid, Productive, and Stereoselective Hydrogenation of Ketones

A turnover number (TON) of 2 400 000 and a turnover frequency (TOF) of 63 s-1 are achieved with the chiral RuII complex 1 (R=p-CH3 C6 H4 ) in the asymmetric hydrogenation of acetophenone. Carbonyl-selective asymmetric hydrogenation of α,β-unsaturated ketones proceeds in the presence of these RuII catalysts, and 4-substituted cyclohexanones are selectively converted into cis alcohols.

Palladium‐Catalyzed C3 or C4 Direct Arylation of Heteroaromatic Compounds with Aryl Halides by CH Bond Activation

In recent years, palladium‐catalyzed direct C2 or C5 arylation of heteroaromatic compounds with aryl halides by CH bond activation has become a popular method for generating carbon–carbon bonds. For this reaction, a wide variety of heteroaromatics, such as furans, thiophenes, pyrroles, thiazoles, oxazoles, imidazoles, pyrazoles, indoles, triazoles, or even pyridines, can be employed. C3 and C4 arylations of heteroaromatics by CH bond activation have also been described. Such reactions initially attracted much less attention than the C2 or C5 arylations due to the lower reactivity of the C3 and C4 positions. How‐ ever, in more recent years, several results from using modified and improved catalysts and reaction conditions have been reported, which permit C3 and C4 arylations in synthetically useful yields. Several intramolecular cyclizations of 2‐substituted heterocycles have been described, with formation of a CC bond on C3 resulting in the formation of five‐ to nine‐membered rings incorporating pyrroles, indoles, thiophenes, furans, isoxazoles, or pyridines. Intermolecular C3 or C4 direct arylations are still quite rare for some heteroaromatics and are in several cases not highly regioselective. For such reactions, the best results have been obtained using pyrroles, thiophenes, or furans. For selected substrates, regioselective arylation at C3 or C4 of the heteroaromatic compounds took place under appropriate reaction conditions. Only a few examples of intermolecular couplings using oxazoles, thiazoles, imidazoles, isoxazoles, pyrazoles, triazoles, or pyridines have been reported. For most of these reactions, aryl iodides or bromides have been used as coupling partners, although a few examples with aryl chlorides are also known. This method allows the synthesis of complex molecules in only a few steps, and will provide access to a very wide variety of new heteroaryl derivatives in the next years.

Greener solvents for ruthenium and palladium-catalysed aromatic C–H bond functionalisation

The formation of carbon-carbon bonds by transition metal-catalysed direct functionalisation of C–H bonds has recently emerged as a greener alternative to traditional cross-coupling reactions. Despite tremendous improvement of the catalytic efficiency allowing reactions under milder conditions or lower catalyst loadings, this type of transformation still suffers from a major limitation with regards to green chemistry concerning the reaction media since the preferred solvents for these transformations are the undesirable and toxic, high boiling point, polar, aprotic, N-methylpyrrolidinone (NMP), dimethylformamide (DMF) or dimethylacetamide (DMAc). Recently, efforts have been made to perform these reactions in greener or more environmentally acceptable media. This review summarises the contributions made in this direction during the past few years.

Phosphine-free palladium-catalyzed direct arylation of imidazo[1,2-a]pyridines with aryl bromides at low catalyst loading.

Ligand-free Pd(OAc)(2) was found to catalyze very efficiently the direct arylation of imidazo[1,2-a]pyridines at C3 under very low catalyst concentration. The reaction can be performed employing as little as 0.1-0.01 mol % catalyst with electron-deficient and some electron-excessive aryl bromides.

trans-[RuCl2(phosphan)2(1,2-diamin)]- und chiraletrans-[RuCl2(diphosphan)(1,2-diamin)]- Komplexe: lagerstabile Katalysatorvorstufen für die schnelle, produktive und stereoselektive Hydrierung von Ketonen

Eine Umsatzzahl (TON) von 2 400 000 und einen Umsatz pro Zeit (TOF) von 63 s−1 ermoglicht der chirale RuII-Komplex 1 (R=p-H3CC6H4) als Katalysator bei der asymmetrischen Hydrierung von Acetophenon. Mit verwandten RuII-Katalysatoren werden α,β-ungesattigte Ketone selektiv an der Carbonylgruppe asymmetrisch hydriert und aus 4-substituierten Cyclohexanonen die entsprechenden cis-Alkohole erhalten.

Ligand-less palladium-catalyzed direct 5-arylation of thiophenes at low catalyst loadings

Ligand-less Pd(OAc)2 provides a very efficient catalyst for the direct 5-arylation of thiophene derivatives. With this catalyst, a low palladium concentration (0.1–0.001 mol%) should be employed in order to obtain high yields of coupling products. At higher concentrations a fast formation of inactive “Pd black” generally occurs. Substrates/catalysts ratios up to 100000 can be employed with the most reactive aryl bromides. A very wide variety of functional groups is tolerated on both coupling partners. The major waste of this reaction is HBr associated with KOAc. Therefore this procedure is more economically and environmentally attractive than the traditional cross-coupling procedures employing organometallic derivatives.

Ligand-free palladium-catalyzed direct arylation of thiazoles at low catalyst loadings.

Ligand-free Pd(OAc)2 was found to catalyze very efficiently the direct arylation of thiazole derivatives under very low catalyst concentration. By using activated aryl bromides, the reaction can be performed employing as little as 0.1-0.001 mol % catalyst. With such substrates, this procedure is economically and environmentally attractive. On the other hand, in the presence of more challenging substrates, such as some strongly deactivated or highly congested aryl bromides, in some cases, disappointing results were obtained.

Aryl triflates: useful coupling partners for the direct arylation of heteroaryl derivatives via Pd-catalyzed C–H activation–functionalization

Aryl triflates were found to be suitable partners for the palladium catalyzed direct arylation of heteroaromatics via C-H activation-functionalization. The reaction conditions and the catalyst have a determining influence on the yields. The system combining PPh3 and Pd(OAc)2 using KOAc as base and DMF as solvent promotes the selective 2- or 5-arylations in moderate to high yields. Several heteroaromatics such as furan, thiophene, thiazole or oxazole derivatives have been employed successfully. The electronic properties of the aryl triflates also have a decisive influence on the yields of the coupling products. Electron-rich aryl triflates gave satisfactory results, whereas the electron-poor ones led to the formation of phenols.

Regioselectivity in palladium-catalysed direct arylation of 5-membered ring heteroaromatics

In recent years, palladium-catalysed arylation of heteroaromatics via C–H bond activation has become a popular method for generating carbon–carbon bonds. For this reaction, a wide variety of heteroaromatics such as (benzo)furans, (benzo)thiophenes, pyrroles, indoles, thiazoles, oxazoles, imidazoles, pyrazoles or triazoles can be employed. In most of these heterocycles, several reactive C–H bonds are present. If specific C–H bonds of such heteroarenes can be coupled with arenes, this becomes one of the most simple methods to access bi(hetero)arenes. In the past few years, several results using modified and improved catalysts and new reaction conditions have been reported permitting better control of the regioselectivity of such arylations. For example, initially only C2- or C5-arylated thiophenes were accessible via palladium-catalysed direct arylation, whereas now regioselective C3- or C4-arylations are possible when appropriate reaction conditions are used. In this review, the influence of the reactants, catalysts and reaction conditions on the regioselectivity of palladium-catalysed arylation of heteroaromatics is reported. The recent progress in the regioselectivity control now allows the synthesis of a wide variety of complex molecules using only a few steps, and will certainly provide simpler access to new heteroaryl derivatives in the next years.

Carbonates: eco-friendly solvents for palladium-catalysed direct arylation of heteroaromatics

The palladium-catalysed direct 2-, 4- or 5-arylation of a wide range of heteroaromatics with aryl halides proceed in moderate to good yields using the eco-friendly solvents carbonates. The best yields were obtained using benzoxazole or thiazole derivatives. The arylation of furan, thiophene, pyrrole, imidazole or isoxazole derivatives was found to require a more elevated reaction temperature.