Iridium catalysts hydrogenation

Hydrogenation of substrates having a polar multiple C-heteroatom bond such as ketones or aldehydes has attracted significant attention because the alcohols obtained by this hydrogenation are important building blocks. Usually ruthenium, rhodium, and iridium catalysts are used in these reactions [32-36]. Nowadays, it is expected that an iron catalyst is becoming an alternative material to these precious-metal catalysts. 

As expected initial examination of the hydrogenation of this substrate revealed its relatively low activity compared to dehydroamino acids that provide 3-aryl-a-amino acids. By carrying out the hydrogenation at an elevated temperature, however, the inherent low activity could be overcome. A screen of the Dowpharma catalyst collection at S/C 100 revealed that several rhodium catalysts provided good conversion and enantioselectivity while low activity and selectivity was observed with several ruthenium and iridium catalysts. Examination of rate data identified [(l )-PhanePhos Rh (COD)]Bp4 as the most active catalyst with a rate approximately... 

The stereochemistry of reduction by homogeneous catalysts is often controlled by functional groups in the reactant. Delivery of hydrogen occurs cis to a polar functional group. This behavior has been found to be particularly characteristic of an iridium-based catalyst that contains cyclooctadiene, pyridine, and tricyclohexylphosphine as ligands, known as the Crabtree catalyst 6 Homogeneous iridium catalysts have been found to be influenced not only by hydroxy groups, but also by amide, ester, and ether substituents.17... 

Presumably, the stereoselectivity in these cases is the result of coordination of iridium by the functional group. The crucial property required for a catalyst to be stereodirective is that it be able to coordinate with both the directive group and the double bond and still accommodate the metal hydride bonds necessary for hydrogenation. In the iridium catalyst illustrated above, the cyclooctadiene ligand (COD) in the catalysts is released by hydrogenation, permitting coordination of the reactant and reaction with hydrogen. 

Fig. 5.5. Suggested basis of enantioselectivity in hydrogenation of a-methylstilbene by a phosphinoaryl oxazoline-iridium catalyst. Reproduced from Chem. Eur. J., 9, 339 (2003), by permission of Wiley-VCH.

The magnitudes of the rate constants for the iridium catalyst were close to those obtained for rhodium 3 and osmium 5 based catalyst systems at similar conditions. However, the unusual dependence on catalyst concentration affects its general utility in comparison to other homogeneous catalysts for the hydrogenation of NBR. 

According to the proposed mechanism, the hydrogenation of olefin by iridium catalyst should conform to the following rate expression,... 

The catalyst powders were compressed to thin disks under a pressure of about 50 kg/cm2, with the exception of the alumina-supported catalysts which required a pressure of 1500 kg/cm2 to obtain reasonable transmittance. The samples were reduced in a stream of hydrogen supplied at a rate of 10 1 hr-1 (SV 30,000 hr-1). The temperatures of reduction were 350°-450°C for the nickel samples, 475°C for the palladium samples, and 425°C for the iridium catalysts. 

Scheme 8.4. Catalytic hydrogenation of imines using cationic iridium catalysts with the C02-philic BARF anion...

Asymmetric hydrogenation of nitrones in an iridium catalyst system, prepared from [IrCl(cod)]2, (S)-BINAP, NBu 4 BH4, gives with high enantioselectivity the corresponding A-hydroxylamines which are important biologically active compounds and precursors of amines (480). Further reduction of hydroxylamines to secondary amines or imines can be realized upon treatment with Fe/AcOH (479), or anhydrous titanium trichloride in tetrahydrofuran (THF) at room temperature (481). 

The reversal of hydrogenation is also possible, as evidenced by the many iridium catalysts for alkane dehydrogenation to alkenes or arenes, though to date this area is of mainly academic interest rather than practical importance [19]. 

In these reactions, the major diastereomer is formed by the addition of hydrogen syn to the hydroxyl group in the substrate. The cationic iridium catalyst [Ir(PCy3)(py)(nbd)]+ is very effective in hydroxy-directive hydrogenation of cyclic alcohols to afford high diastereoselectivity, even in the case of bishomoallyl alcohols (Table 21.4, entries 10-13) [5, 34, 35]. An intermediary dihydride species is not observed in the case of rhodium complexes, but iridium dihydride species are observed and the interaction of the hydroxyl unit of an unsaturated alcohol with iridium is detected spectrometrically through the presence of diastereotopic hydrides using NMR spectroscopy [21]. 

Cationic iridium and rhodium catalysts are also effective for the hydrogenation of exocyclic olefmic alcohols (see Table 21.5), except for 2-exomethylenecy-clohexanol and 2-methylenecyclohexanemethanol (entries 2 and 3). In entry 4, a cationic rhodium catalyst gave a single product whilst a cationic iridium catalyst induced only modest selectivity (72 28). 

The amide group shows a prominent directivity in the hydrogenation of cyclic unsaturated amides by a cationic iridium catalyst, and much higher diastereo-selectivity is realized than in the corresponding ester substrates (Table 21.7). In the case of / ,y-unsaturated bicyclic amide (entry 3), the stereoselectivity surpasses 1000 1 [41]. An increase of the distance between the amide carbonyl and olefmic bond causes little decrease in the selectivity (d, -unsaturated amide, entry 6) compared with the case of the less-basic ester functionality (Table 21.6, entry 5). 

Another series of achiral iridium catalysts containing phosphine and heterocyclic carbenes have also been tested in the hydrogenation of unfunctionalized alkenes [38]. These showed similar activity to the Crabtree catalyst, with one analogue giving improved conversion in the hydrogenation of 11. 

Aided by these developments, the past five years has seen a rapid growth in this area. A breakthrough was the introduction of iridium catalysts with chiral P,N ligands. A large number of new P,N and other ligands have been synthesized and applied to the hydrogenation of unfunctionalized alkenes. This chapter details the catalysts, conditions and substrates used in the enantiomeric hydrogenation of unfunctionalized alkenes. 

Tetrasubstituted alkenes are challenging substrates for enantioselective hydrogenation because of their inherently low reactivity. Crabtree showed that it was possible to hydrogenate unfunctionalized tetrasubstituted alkenes with iridium catalysts [46]. Among the iridium catalysts described in the previous section, several were found to be sufficiently reactive to achieve full conversion with al-kene 77 (Table 30.14). However, the enantioselectivities were significantly lower than with trisubstituted olefins, and higher catalyst loadings were necessary. 

Scheme 39.6 Enantiomeric hydrogenation of imine 22 in an IL/ scC02 biphasic system using an in-situ-activated iridium catalyst.

The formation of dimers and trimers is a major issue in hydrogenations with iridium catalysts. In the context of developing an industrial process to produce (S)-metolachlor via an enantioselective imine hydrogenation (see Chapters 34 and 37), Blaser et al. investigated the causes of catalyst deactivation in the iri-dium/bisphosphine-catalyzed hydrogenation of DMA imine (Scheme 44.11) [84]. 

P. Schnider, G. Koch, R. Pr etot, G. Wang, F. M. Bohnen, C. Kruger, A. Pfaltz, Enantioselective Hydrogenation of Imines with Chiral (Phospanodihydrooxazole)iridium Catalysts, Chem. Eur. J. 1997, 3, 887-892. 

A similar system based on rhodium has been studied (123) and was found to be less active than the equivalent iridium catalysts. Selective hydrogenation of acetylenes to olefins and dienes to monoolefins can be performed using the rhodium system, and the authors note that although propan-2-ol is an effective source of hydrogen (via oxidation to acetone), mild pressures of hydrogen gas can also be employed. 

An iridium catalyst was used in the selective hydrogenation of a steroid compound, where the exocyclic double bond was saturated in the presence of an endocyclic one (equation 67)161. 

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