Ru-Catalysed Hydrogenation

1 Alkenes. There are only a few reports about enantioseleetive hydrogenation of alkenes with ruthenium complexes bearing / -stereogenic ligands. The substrates are the same as those used in rhodium-catalysed hydrogenations. Most of the results are Ksted in Table 7.7. 

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Deuterium labeling experiments, kinetic studies, and rate law analysis have indicated that the (S )-BINAP-Ru-catalysed hydrogenation of 2-formyl-1-methylene-6,7-dimethoxy-l,2,3,4-tetrahydroisoquinoline proceeds via a monohydride-unsaturated mechanism whereby the two protiums at the a- and j3-positions of the enamide substrate are derived from two different hydrogen molecules. The overall rate is limited by the hydrogenolysis step.333... 

Table 7.7 Results of enantioselective Ru-catalysed hydrogenation of alkenes. 

The mathematical expression makes it possible for the organic synthetic chemist to evaluate a DKR process using a simple set of experiments, thereby providing a guideline for improving efficiency. The validity of this approach is demonstrated by a correlation of the experimental and simulated results in the BINAP-Ru-catalysed hydrogenation of stereochemicaUy labile ketonic substrates [4a, 141]. More detailed quantification of a variety of DKR or DKR-related systems have been reported elsewhere [142]. 

The proposed mechanism (Scheme 17) involves the initial sp C-H bond oxidative addition to ruthenium(O) followed by aryl transmetallation and reductive elimination. It was suggested by Sames [11] that the role of the ketone was to insert into the Ru-H bond to favour traiw-arylation with the phenylboronate ester. Later on it was shown by Maes that pinacolyl alcohol was formed via Ru-catalysed hydrogenation of pinacolone rather than through a Ru-alkoxide intermediate [12]. 

Similarly, reactions which are substantially enhanced by the use of PTC can be carried out even with reduced use of PTC with substantial enhanced rates of reaction as has been demonstrated by Sivakumar and Pandit (2000) in the case of conversion of benzamide to benzonitrile. In the case of A-alkylation of diphenylamine with benzyl bromide, in the presence of KOH as the anion source and PEG methyl ether as the PTC, some improvement in the rate has been observed. (Cains et al., 1998). Metal catalysed hydrogenations, such as those based on Ni, Pd/C, and Ru/C also benefit from ultra-sound. 

The seven-membered ring containing chiral bisphosphine 121 (n = 1) was made as part of a series of bisphosphines (n = 1-6) to study the influence of ligand dihedral angles on the enantioselectivity of Ru-catalysed asymmetric hydrogenation of p-ketoesters . 

Ru(II)-TPPTS to the corresponding unsaturated alcohols in biphasic mode. If one compares the reaction times until full conversion, it becomes clear that the reaction rate correlates with the solubility of the substrate in the aqueous phase, as expected. The latter decreases with increasing chain length or branching of the chain at the C3-atom. In contrast to heterogeneously catalysed hydrogenations of o , d-unsaturated aldehydes, the steric hindrance of substituents at the C3-atom only plays a minor role in the coordination mode of the substrate at the metal centre, since selectivity differences from croton-aldehyde to citral are marginal. 

Sturm, T., Weissensteiner, W. and Spindler, F. A Novel Class of Eerrocenyl-aryl-based Diphosphine Ligands for Rh- and Ru-catalysed Enantioselective Hydrogenation. Adv. Synth. Catal. 2003, 345, 160-164. 

For examples of Ru-catalyzed hydrogenation of N-(3.4-dihydro-2-naphthalenyl)-acetamide see (a) Renaud. J.L., Dupau, P., Hay. A.-E.. Guingouain. M., Dixneuf P.H. and Brtmeau. C. (2003) Ruthenium-catalysed enantioselective hydrogenation of trisubstituted enamides derived from 2-tetralone and 3-chromanone Influence of substitution on the amide ai m and the aromatic ring. Adv. Synth. Catal.. 345. 230-238. 

Some 1,6- and 1,7-enynes undergo interesting Pd, Pt and Ru-catalysed cyclizations, which are regarded as Alder-ene reaction and metathesis. These reactions offer a useful method for the construction of polycyclic compounds [132]. These cyclizations can be understood by the following two mechanisms as shown by Scheme 7.3. As the first possibility, the oxidative cyclization of 1,6-enyne 320 generates the palladacy-clopentene 321. Elimination of two different /1-hydrogens from 321 yields either 322 or 323, which undergoes reductive elimination to produce the 1,4-diene 324 as the Alder-ene product, and the 1,3-diene 325 [133]. Of course, the 1,4-diene is the expected product of the thermal ene reaction. 

As another example of the reaction via the ruthenacyclopentene, 1,4-diketones are formed by the Ru-catalysed reaction of terminal alkynes with vinyl ketones in aqueous DMF in the presence of NH4PF6 and InCl3. The reaction is explained by the generation of the ruthenacyclopentene 422, followed by addition of H2O to the double bond. Elimination of /5-hydrogen and reductiuve elimination afford 1,5-diketones [165a],... 

Asymmetric hydrogen transfer from 2-propanol to aromatic ketones such as acetophenone (99) has been achieved by using the same chiral Ru complex in 2-propanol containing KOH at room temperature, and (S)-1 -phenylethanol (100) with 98% ee was obtained [68,69]. Similarly, efficient Ru-catalysed transfer hydrogenation of aromatic ketones using the cyclic amino alcohol [(I. S, 3R,4i )-2-azanorbomylmetha-nol] (110) [70] and bis(oxazolinylmethyl) amine (111) [71] was reported. 

Modern variations include the in situ, and thus catalytic, use of this high-valent selective reagent, not only for alcohols but also for ethers (see later). Ru(VII) (perruthenate) in the compounds tetra-n-butylammonium perruthenate (TBAP) and tetra-n-propylammonium perruthenate (TPAP) has found wide application in alcohol oxidation. Ru-oxo complexes with valence states of IV to VI are key intermediates in, for example, the selective oxygen transfer to alkenes, leading to epoxides. On the other hand 16-electron Ru(II) complexes can be used to catalyse hydrogen transfer thus these are excellent catalysts for oxidative dehydrogenation of alcohols. A separate section is included to describe the different mechanisms in more detail. 

Although more limited in scope than the BINAP-Ru(II)-catalysed hydrogenations, rhodium-catalysed hydrogenations are of enormous commercial importance because of the demand for both natural and unnatural amino acids on a vast scale. It is even economical for the more expensive of the natural amino acids to be made synthetically rather than isolated from natural sources—phenylalanine, for example, of industrial importance as a component of the artificial sweetener aspartame, is manufactured by enantiosfelective hydrogenation. 

Details about ILs properties are covered in this book in the contributions by Seddon, Chiappe and Scott. However, two features deserve a comment for their possible consequences on reactivity and catalysis. First, depending on a delicate balance of entropie and enthalpic factors, including the polarity of the transition state structures with respect to regents, a reaction can be either speeded up or decelerated when carried out in an ionic liquid medium compared to a molecular solvent. An elegant study by Welton shows that in S-,2 reactions, primary, secondary and tertiary amines are more reactive as nucleophiles in ionic liquids, while halides react faster in conventional molecular solvents such as CH2CI2. In particular in a series of [Bmim] salts the order of nucleophilicity of halides is determined by the anion partner. To the same direction moves a kinetic study by Dyson on a cationic Ru(II) complex-catalysed hydrogenation of styrene in ILs, where it is clearly demonstrated that both the cation and the anion of the IL can inhibit or accelerate the formation of the active catalytic species. ... 

Copolymer of PEG, (R)-5,5 -diamino-BINAP, and terephthaloyl chloride =0.05 H20 ,Me0H =, ethylene glycol", Et0Ac/H20" Ru-catalysed asymmetric hydrogenation of a,p unsaturated carhoxyhc acids (-t) Precipitation (ether) [145]... 

Ru-catalysed asymmetric hydrogenation of unsaturated carboxylic acids... 

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