Chiral iridium catalysts

A 2mL glass vial equipped with a magnetic stir bar was filled with 1.72 mg of the chiral iridium catalyst and 19.4 mg of tran -a-methylstilbene. Subsequently, 0.5 mL of dichloromethane were added and the vial placed in the autoclave. 

Table 6.8 Asymmetric hydrogenation of activated pyridines with a chiral iridium catalyst.

Using BARF-modified C02-philic chiral iridium catalysts (Eq. 7), greatly enhanced reaction rates at almost identical ee values were observed for the enantiose-lective hydrogenation of imines upon changing from CH2C12 to scC02 as the solvent. 

The hydrogenation of C=N double bonds is an important synthetic strategy for the synthesis of secondary amines. Chiral iridium catalysts allow the hydrogenation of prochiral imines to be carried out with high enantioselectivity in conventional liquid solvents. Such a process has already found industrial application in the preparation of (S)-metolaclor, a herbicide produced by Novartis in Switzerland [40]. Recent research at the Max Planck Institute for Coal Research has demonstrated that reactions of this type can be carried out in SCCO2 with the same level of enantioselectivity and with enhanced catalyst efficiency [12]. 

Scheme 4.7-4 Asymmetric hydrogenation of imines in SCCO2 using chiral iridium catalysts. Representative results are summarized in Figure 4.7-4.

Figure 4.7-4 Influence of perfluoroalkyl substituents (compounds a or b) and of anions X on the enantiomeric excess in the hydrogenation of imine 8a using chiral iridium catalysts 10-12 [12].

Many organometallic catalysts and especially many chiral catalysts are cationic, and modification of the anion has been found to be very effective for enhancing their solubility in SCCO2 without the requirement for ligand alteration. Tetrakis(3,5-bis(trifluoromethyl)phenyl)borate (BARF) was an early example of such an anion which has proven extremely useful for this purpose [28], and very pronounced anion effects on the activity and selectivity of the catalysts are observed in many other cases [27, 29]. Using the BARF-modified "C02-philic chiral iridium catalyst... 

The chiral iridium catalyst (258) bearing a tridentate spiro aminophosphine ligand catalysed the asymmetric hydrogenation of ketones in EtOH and KOBu with excellent enantioselectivities (up to 99.9% ee) and extremely high turnover numbers. ... 

Shibata and Tsuchikama subsequently developed the enantio- and diastereoselec-tive [2 + 2 + 2] cycloaddition reactions of tetraynes with monoynes. These reactions proceeded in the presence of the same chiral iridium catalyst to give helically chiral quinquearyl compounds, possessing four consecutive axial chiralities, with perfect... 

To date, there is only one example of enantioselective Af-allqvlation by means of hydrogen borrowing. Zhao and co-workers discovered a chiral iridium catalyst/chiral Bronsted acid combination that enables the N-allqv-lation of racemic secondary alcohols with anilines to provide secondary amines, with greater than 90% ee in many cases (Scheme 12.12). Attempts to extend the scope of the amine reactant resulted in poor enantioselectivity. 

More recently, the same type of hgand was used to form chiral iridium complexes, which were used as catalysts in the hydrogenation of ketones. The inclusion of hydrophihc substituents in the aromatic rings of the diphenylethylenediamine (Fig. 23) allowed the use of the corresponding complexes in water or water/alcohol solutions [72]. This method was optimized in order to recover and reuse the aqueous solution of the catalyst after product extraction with pentane. The combination of chiral 1,2-bis(p-methoxyphenyl)-N,M -dimethylethylenediamine and triethyleneglycol monomethyl ether in methanol/water was shown to be the best method, with up to six runs with total acetophenone conversion and 65-68% ee. Only in the seventh run did the yield and the enantioselectivity decrease slightly. 

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. 

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. 

Table 1 Asymmetric hydrogenation of standard substrates with chiral N,P and C,N iridium catalysts...

The treatment of [Cp MCl2]2 (M = Rh and Ir) with (S,S)-TsDPEN gave chiral Cp Rh and Cp Ir complexes (12a and 12b Scheme 5.9). An asymmetric transfer hydrogenation of aromatic ketones using complex 12 was carried out in 2-propanol in the presence of aqueous KOH (1 equiv.) the results obtained are summarized in Table 5.4. In all of the reactions, the (S)-alcohols were obtained with more than 80% enantiomeric excess (ee) and in moderate to excellent yields. The rhodium catalyst 12a was shown to be considerably more active than the iridium catalyst... 

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... 

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