98 Chapter 3 was more active (2 turnovers/h). Similar but water soluble tungsten and molybdenum complexes are known [223-226] which would allow the use of water as solvent for such reactions. It is noteworthy, though, that ionic hydrogenation of ketones by dihydrogen complexes has so far been observed only in non-aqueous solutions [223,227]; perhaps the coordination of a ketone is disfavoured in water due to competition by 3.4 HYDROGENATION OF MISCELLANEOUS ORGANIC SUBSTRATES 3.4.1 Hydrogenation of nitro compounds and imines Amines are extremely important intermediates and end products of the chemical industry and are often obtained by hydrogenation of the corresponding nitro compounds or imines. A search of the literature reveals, that hydrogenation of nitro compounds catalyzed by well-defined molecular complexes in aqueous solutions is rare. One reason may line in the fact, that reduction of the function proceeds in one-electron steps, while many soluble hydrogenation catalysts act in the “oxidative addition of elimination of the product” cycles in which the central metal ion (formally) looses or gains two electrons at a time. It is not surprising therefore, that the catalysts of nitro-hidrogenations are either metal centered radicals themselves or are capable of delocalizing the temporary surplus of electron(s) on their large conjugated system or on a cluster framework Catalysts, operating through formation of intermediate monohydrides, which does not require the change of the oxidation state of the metal, are good candidates of nitro- reduction (see also 3.8.2) on reductions with ). Unfortunately, other functional groups in a molecule are usually even more reactive towards hydrogenation than the nitro functionality - therefore selective Hydrogenations of nitro compounds catalyzed by are briefly mentioned in 3.1.1.2. Some other hydrogenation catalysts with Pt(II), Pd(II) or Rh(III) central ions contain ligands with extended conjugated such as 1-phenyl-azo-2-naphtol [228], indigosulfonic acid [229] and the sodium salts of 1,2-dioxy-9,10-anthraquinone-3-sulfonic acid (Alizarin red, QS) [73,74]. It was established by EPR and NMR investigations [73,74], that with the Pd(II) complex of Alizarin red, activation of dihydrogen takes place at the metal ion but the ligand also takes important part in the redox reaction: it is reduced to a reduction of groups is not an easy task. Previous Page Hydrogenation 99 semiquinone radical. Such radicals are rapidly oxidized by nitro compounds, and, indeed, this complex is an active catalyst for hydrogenation of nitro groups at room temperature and 1 bar Other characteristics of reductions involving i.e. the very slight temperature dependence of the rate, hydrogenolysis of carbon-halogen bonds, and sensitivity to radical scavangers, are also in accord with the formation of radicals during the hydrogenation process. In addition of being capable of reduction of groups, is also a very effective catalyst for hydrogenations at low temperatures and this property made it the catalyst of choice for the hydrogenation of many model- and biomembranes (see 3.7). Catalytic hydrogenation of chloro-nitroaromatics is usually accompanied by dehalogenation. However, the water-soluble complex prepared from and TPPTS in DMSO-containing water reduced 5-chloro-2- nitrophenol to 2-amino-5-chlorophenol with high selectivity [231] (Scheme 3.25). The selectivity of the hydrogenation halo-nitro aromatic compounds can be influenced by cyclodextrins, as additives, or by using cyclodextrin- derived catalysts [232] (see Ch .10). Asymmetric hydrogenation of imines was studied in aqueous/organic biphasic systems and presented a puzzle which is still not solved completely. It was first discovered by Bakos et al. [233], that acetophenone benzylimines were hydrogenated to the corresponding amines with unprecedented enantioselectivity up to 96% under very mild conditions with the Rh- complexes of sulfonated BDPP, 36 , provided the degree of sulfonation of BDPP was close to 1 (in fact it was 1.41-1.65) (Scheme 3.26). With increasing number of sulfonate substituents in 36 the enantioselectivity decreased sharply. 100 Chapter 3 This “monosulfonation effect” was investigated in detail by de Vries et al. [234,235], who isolated the sulfonated BDPP with one, two, three and four sulfonate groups (each phenyl ring carries only one). In hydrogenation of acetophenone benzylimine it was confirmed, that indeed, the highest enantioselectivity (94 %) could be achieved by using monosulfonated BDPP as ligand in the in situ prepared Rh-catalyst, whereas with the bissulfonated ligand a practically racemic product (2 % e.e.) was obtained Note, that monosulfonated BDPP is chiral at one of the phosphorus atoms, and it was determined by HPLC that it contained a 1:1 ratio of the two epimers. Now the puzzle is in that how can a ligand, which is a 1:1 mixture of two diastereomers, induce such outstandingly high enantioselectivity what was found with the Rh-complex of monosulfonated BDPP in the hydrogenation of imines. It is also important to add, that under comparable conditions, the enantiomeric excess of the hydrogenation of acid and its methyl ester decreased monotonously with increasing degree of sulfonation (from 87 % to 65 % and from 74 % to 45 %, respectively). However, in case of itaconic acid there was a slight “monosulfonation effect” (Table 3.9). It is clear from Table 3.9, that the effect is not related to the difference in electron density on the two phosphorus atoms since this should be the same with and Still the catalyst with trisulfonated BDPP gave Hydrogenation 101 miserable enantioselectivity with both substrates. It is also important, that the Rh-complex with the monosulfonated BDPP is well soluble in ethyl acetate and moves completely to the organic phase during hydrogenation, while the other three sulfonated BDPP-s yield exclusively water soluble complexes. Presumably, one of the sulfonate groups acts as the anion of the cationic rhodium center and in case of the monosulfonated BDPP this gives an organosoluble 1:1 zwitter-ionic product (Scheme 3.27). Coordination of the group of the ligand to the rhodium may, indeed, be important in the observed effect. It was found by Buriak and Osborn [146,147] that in microemulsions, prepared with the surfactant AOT (Scheme 3.11) the sulfonate group of AOT did coordinate to rhodium in the complex. It was suggested that this led to an easier example in case of (Scheme 3.28), i.e. to a switch from a dihydride route of hydrogenation to a monohydride pathway. How this would lead to high enantioselection still remains elusive. Nevertheless, these studies nicely emphasized the warning of the authors of [146]: “ large changes in enantioselectivity result from small energy differences (well below 5 kcal/mol) which can arise from apparently minor effects which are difficult to evaluate, such as solvation energies”. Solvation deprotonation of an intermediate dihydride species in case of than for 102 Chapter 3 is so much different in water than in most organic solvents that one should always keep this warning in mind. 3.5 TRANSFER HYDROGENATION AND HYDROGENOLYSIS Transfer hydrogenation is a reaction in which hydrogen is catalytically transferred from a suitable hydrogen donor to a reducible substrate (S) yielding the hydrogenated product and the oxidized form of the donor molecule (D) [236-238]. Several of the most common hydrogen donors, such as formic acid and formates, ascorbic acid, EDTA or 2-propanol are well or at least sufficiently soluble in water. In addition, itself can serve as a source of hydrogen. Frequently, hydrogenation of unsaturated substrates is achieved by using mixtures; such reactions are discussed in 3.8. As written in eq. (3.11) the hydrogen transfer reaction is often reversible, an obvious example being the reduction of ketones using 2-propanol as donor. Reductions with hydrogen transfer are attractive for at least two reasons. First, the concentration of in the reaction mixture can be much higher than that of under high pressure (cf. for example and in water at 1 bar pressure). This may be beneficial for a faster reaction. Second, the use of a soluble or liquid hydrogen donor also eliminates the safety hazard of handling high pressure hydrogen. Formic acid and formates were among the most effective donors used for the reduction of olefins with or catalysts in non-aqueous systems [239-241]. No wonder, the water soluble analogues of these catalysts became widely used in aqueous solutions. In a series of investigations [242-245] with Ru/TPPMS and Rh/TPPMS catalysts olefins (such as 1-heptene) were hydrogenated in mixtures of HCOOH/HCOONa. Crotonaldehyde was selectively reduced to butyraldehyde by the catalyst [245]. It was also established that (unfiltered) ultraviolet irradiation accelerated the reactions [245]. Dimethyl itaconate was reduced by hydrogen transfer from aqueous sodium formate under mild conditions (Scheme 3.29). This reaction served also as one of the model processes in development of new reactors, such as the centrifugal partition chromatograph, for high throughput catalyst testing [246-248]. Hydrogenation 103 Based on isotope labelling experiments in and mixtures it was suggested, that the reaction mechanism involved a rhodacyclobutane intermediate (Scheme 3.30). In this respect the reaction pathway differs substantially from those of hydrogenations with Water-soluble Rh(I) complexes containing TPPTS catalyzed the transfer hydrogenation of itaconic, mesaconic, citraconic and tiglic acids as well as that of and acids from HCOOM [235]. The reactions were run at 50 °C for 15-67 h, during which 48-100 % conversions were achieved. Use of the chiral tetrasulfonated cyclobutanediop, 37 , led to an enantiomeric excess of up to 43 %, which is close to the value obtained in biphasic hydrogenations catalyzed by the same rhodium complex [100]. Aqueous sodium formate served as hydrogen donor in the reduction of aldehydes catalyzed by [202]. Since in this case both the catalyst and the substrate reside in the organic phase, a phase transfer agent was necessary to carry from the aqueous into the organic phase; were applied for this purpose. An important feature of the reaction is the strong substrate inhibition which does not allow the reduction of e.g. benzaldehyde in solutions with higher than 0.8 M aldehyde concentration. The precise nature of this substrate inhibition is not clear; it may be due to formation of catalytically unreactive intermediates either via or coordination of the substrate aldehydes. The same reaction was investigated in a reverse experimental setup, i.e. having the water-soluble catalyst excess TPPMS, and the hydrogen donor HCOONa in the aqueous phase and the substrate aldehyde together with the products in the organic (chlorobenzene) phase [249,250]. Unsaturated aldehydes, such as cinnamaldehyde (Scheme 3.18) 104 Chapter 3 and citral (Scheme 3.31) were reduced to the corresponding unsaturated alcohols with high selectivity. No cis-trans isomerization was observed around the double bond. It is important to note, that in this arrangement of an aqueous/organic biphasic reaction the substrate inhibition discussed above was hardly observable. Although the aldehydes are sufficiently soluble in water to allow a fast reaction, still most of the substrate is found in the organic phase at all times. Therefore the concentration of the aldehydes in the catalyst- containing aqueous phase is not high enough to cause efficient inhibition of catalysis [250]. Under comparable conditions, Ru(II) and Rh(I) complexes of PTA behaved very similar to their TPPMS-containing analogues in that led to exclusive formation of unsaturated alcohols [27,204] while catalysis by selectively produced saturated aldehydes in reduction of unsaturated aldehydes with [27,28,204]. In contrast to the case of the water soluble complexes (P = PTA, TPPMS or TPPTS) which did not promote the reduction of function in aldehydes or ketones in biphasic systems, was found an active catalyst for reduction of ketones with aqueous HCOONa (Scheme 3.32). The reaction was aided by phase transfer catalysis using Aliquat-336 and required a large excess of to prevent reduction of rhodium into inactive metal. Substrates like acetophenone, butyrophenone, cyclohexanone and dibenzyl-ketone were reduced to the corresponding secondary carbinols with turnover frequencies of [251]. Hydrogenation 105 It is not easy to rationalize this difference in the selectivity provided by dissolved in the organic phase and by in the aqueous phase. One reason may be in that when a solution of in a water-immiscible organic solvent is stirred with an aqueous solution of a mild base (HCOONa in this case), formation of can be assisted by extraction of chloride into the aqueous phase (Scheme 3.33). Although there is no evidence for this process taking place in the reduction of ketones with hydrogen transfer from formate [251], in a related system the rate of hydrogenation of acetophenone, catalyzed by the same catalyst in the presence of was substantially increased upon mixing the 106 Chapter 3 organic solution with water (Figure 3.4) [252]. Most of the chloride was found in the aqueous phase which means that the equilibrium depicted on Scheme 3.33 was largely shifted to the right. This is supported by the finding that when a 0.5 M aqueous was added instead of a solution, the reaction proceeded with the original low rate. On the other The water-soluble iridiurn(III) complex, was found a suitable catalyst precursor for reduction of aldehydes and ketones by hydrogen transfer from aqueous formate [254]. Under the conditions of Scheme 3.34 turnover frequencies in the range of were determined. Of the several water-soluble substrates the cyclic cyclopropanecarboxaldehyde reacted faster than the straight-chain butyraldehyde, and aldehydes were in general more reactive than the only simple ketone studied (2-butanone). While glyoxylic acid was reduced fast, pyruvic acid did not react at all. The reaction rate of the reduction of these carbonyl compounds showed a sharp maximum at pH 3.2, which coincides with the value of HCOOH in the studied concentration, and there was no reaction above pH 5. The lack of reactivity at higher pH can be attributed to the formation of the catalytically inactive hydroxide-bridged trimer, which, however, is in equilibrium with the starting catalyst precursor at the optimum pH of the reaction. The active form of the catalyst is most probably the dimeric which happens to form to the hand, is known to be a good catalyst for ketone hydrogenation in the presence of amines [253]. It is instructive to see, that in biphasic aqueous organometallic catalysis a seemingly minor change (dissolving the catalyst in the aqueous or, contrary, in the organic phase) may lead to major changes in the rate and/or the selectivity of the catalyzed reaction under otherwise identical conditions. Hydrogenation 107 highest extent at pH 3.2; the compound was characterized in solution and in isolated from, as well. It is supposed that reduction of the carbonyl compounds takes place on this dimer (Scheme 3.35). [...]... metallocarboxylic 118 acid (via “abnormal insertion” [279] of on Scheme 3.45 Chapter 3 into the Ru-H bond), as shown Water-soluble rhodium complexes, such as or the ones prepared in situ from and TPPTS and from and TPPTS were succesfully used by Leitner et al [282,295] for the hydrogenation of in aqueous solutions in the presence of amines or aminoalkanols In this system no other products of carbon dioxide... and 40 bar total pressure a was observed For this reaction an overall activation barrier was determined Interestingly, under the same conditions the ruthenium complex, proved much inferior to the Rh-TPPTS catalysts with a TOF of only In the supposed catalytic cycle key role was assigned to a monohydrido-rhodium complex (Scheme 3.46) which at that time could not be supported by spectroscopic methods . accompanied by dehalogenation. However, the water-soluble complex prepared from and TPPTS in DMSO-containing water reduced 5-chloro-2- nitrophenol to 2-amino-5-chlorophenol. from those of hydrogenations with Water-soluble Rh(I) complexes containing TPPTS catalyzed the transfer hydrogenation of itaconic, mesaconic, citraconic