Iridium Catalyst enantioselective

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... 

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.

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). 

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. 

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. 

In spite of the success of asymmetric iridium catalysts for the direct hydrogenation of alkenes, there has been very limited research into the use of alternative hydrogen donors. Carreira and coworkers have reported an enantioselective reduction of nitroalkenes in water using formic acid and the iridium aqua complex 69 [66]. For example, the reduction of nitroalkene 70 led to the formation of the product 71 in good yield and enantioselectivity (Scheme 17). The use of other aryl substrates afforded similar levels of enantioselectivity. 

This chapter describes the development of iridium-catalyzed, enantioselective allylic substitution. It is organized to focus on how modifications to the catalyst, combined with mechanistic insights, have provided the foundation for a steady... 

Reactions of allylic electrophiles with stabilized carbon nucleophiles were shown by Helmchen and coworkers to occur in the presence of iridium-phosphoramidite catalysts containing LI (Scheme 10) [66,69], but alkylations of linear allylic acetates with salts of dimethylmalonate occurred with variable yield, branched-to-linear selectivity, and enantioselectivity. Although selectivities were improved by the addition of lithium chloride, enantioselectivities still ranged from 82-94%, and branched selectivities from 55-91%. Reactions catalyzed by complexes of phosphoramidite ligands derived from primary amines resulted in the formation of alkylation products with higher branched-to-linear ratios but lower enantioselectivities. These selectivities were improved by the development of metalacyclic iridium catalysts discussed in the next section and salt-free reaction conditions described later in this chapter. 

Mononuclear oxazolines are among the most effective ligands for enantioselective hydrogenation of nonfunctionalized alkenes." " The styrene substrate 597 is one of the most studied nonfunctionahzed alkenes used to evaluate the efficiency of new chiral ligands (Scheme 8.185). Selected examples of enatioselective hydrogenation of 597 using iridium catalysts are shown in Table g jg 359,425,426,457-459... 

Only one paper has reported on catalytic asymmetric hydrogenation. In this study by Corma et al., the neutral dimeric duphos-gold(I)complex 332 was used to catalyze the asymmetric hydrogenation of alkenes and imines. The use of the gold complex increased the enantioselectivity achieved with other platinum or iridium catalysts and activity was very high in the reaction tested [195] (Figure 8.5). 

An exciting development has come from work with an iridium catalyst. The use of the complex derived from phosphinoaryloxazoline ligand 149 leads to an efficient alkylation of E-cinnamyl acetate (Eq. 8E.32) [217], It is of note that electron-withdrawing substituents on the phosphorus atom, which are known to be required to give a good regioselectivity in general [218], also increased the enantioselectivity dramatically. 

In the past, this field has been dominated by ruthenium, rhodium and iridium catalysts with extraordinary activities and furthermore superior enantioselectivities however, some investigations were carried out with iron catalysts. Early efforts were reported on the successful use of hydridocarbonyliron complexes HFcm(CO) as reducing reagent for a, P-unsaturated carbonyl compounds, dienes and C=N double bonds, albeit complexes were used in stoichiometric amounts [7]. The first catalytic approach was presented by Marko et al. on the reduction of acetone in the presence of Fe3(CO)12 or Fe(CO)5 [8]. In this reaction, the hydrogen is delivered by water under more drastic reaction conditions (100 bar, 100 °C). Addition of NEt3 as co-catalyst was necessary to obtain reasonable yields. The authors assumed a reaction of Fe(CO)5 with hydroxide ions to yield H Fe(CO)4 with liberation of carbon dioxide since basic conditions are present and exclude the formation of molecular hydrogen via the water gas shift reaction. H Fe(CO)4 is believed to be the active catalyst, which transfers the hydride to the acceptor. The catalyst presented displayed activity in the reduction of several ketones and aldehydes (Scheme 4.1) [9]. 

The C2-symmetric diphosphinite and CVsymmetric phosphinite-phosphate ligands, based on a carbohydrate scaffold, and iridium complexes give catalyst precursors that are active in the hydrogenation of imines. Cationic iridium complexes gave rise to catalytic systems that were more active than the neutral iridium complexes. Enantioselectivities up to 76% were obtained.347... 

The catalytic asymmetric hydroboration reaction can also be applied to OTei o-bicyclic hydrazines. The resulting alcohols are of great synthetic interest and can lead to cyclopentanic diamino alcohols with good enantiomeric purity (equation 14). Interestingly, a reversal of enantioselectivity is observed between reactions employing rhodium and iridium catalysts. ... 

In the work with asymmetric hydrogenation in SC-CO2, Kainz et al. used modified iridium catalysts to hydrogenate imines. The presence of BARF as a counterion provided the best results in CO2. In comparison to dichloromethane, CO2 gave up to double the turnover frequency (TOF = TON/time) but enantioselectivities were lower by 10%. Again yield and selectivity were substrate specific. Lange et al. developed a chiral rhodium diphosphinite catalyst... 

---