Iridium asymmetric catalysts

Much like the enol systems discussed in Sect. 6.1, enamines are predictably difficult substrates for most iridium asymmetric hydrogenation catalysts. Both substrate and product contain basic functionahties which may act as inhibitors to the catalyst. Extended aromatic enamines such as indoles may be even more difficult substrates for asymmetric hydrogenation with an additional energetic barrier to overcome. Initial reports by Andersson indicated a very difficult reaction indeed (Table 14) [75]. Higher enantioselectivities were later reported by Baeza and Pfaltz (Table 14) [76]. 

Despite the very low number of examples describing effective iridium-based asymmetric catalysts, there are some which deserve to be mentioned at this point. The preparation of hybrid NHC—oxazoUne ligands, allowed Burgess and coworkers to prepare Ir(l) complexes for the asymmetric hydrogenation of aryl alkenes (Scheme 3.19) [43]. These catalysts are among the most efficient in terms of yield and asymmetric inductions for this reaction. 

Intermolecular asymmetric aminations are at an early stage of development, and consequently much lower turnover frequencies and catalytic yields have been observed at this stage. In the example shown, a key aspect is the activation of the iridium complex catalyst by fluoride ion [111] (Scheme 38). 

Rhodium and iridium catalysts incorporating bisphosphine ligands such as BINAP and derivatives have also been shown to be effective in the asymmetric Pauson—Khand reaction of 1,6-enynes, and some high ees have been obtained with substrates incorporating heteroatoms. As an example, the allylpropargylamine (8.243) is converted into the bicychc product (8.244) with high ee in the presence of an iridium/ToIBINAP catalyst. It has been shown that, in some cases, aldehydes... 

Iridium-Phosphinooxazoline Catalysts. Asymmetric hydrogenation of simple olefins with chiral Rh or Ru catalysts generally shows low reactivity and unsatisfactory enantioselectivity (198,248,249). However, several unfunctionalized olefins can be hydrogenated in high yields and excellent enantioselectivity by using iridium catalysts with chiral phosphinooxazoline ligands (60,186,187, 189,191-194,250) (Fig. 56). To avoid catalyst deactivation, the extremely weakly coordinating anion tetrakis[3,5-bis(trifiuoromethyl)phenyl]borate has to be used (182,251). 

Figure 1.33 Energy scans simulating the approach of the substrate to the corresponding Ir hydrides. The final minima correspond to the completely optimized structures of adducts. (Liu, Y. et al. Mechanism of the asymmetric hydrogenation of exocyclic a, 3-unsaturated carbonyl compounds with an iridium/BiphPhox catalyst NMR and DPT studies. Angew. Chem. Ini. Ed. 2014.53,1901-1905. Copyright Wiley-VCH Verlag GmbH Co. KGa A. Reproduced with permission.)...

Morimoto, T. Achiwa, K. An improved diphosphine-iridium(I) catalyst system for the asymmetric hydrogenation of cyclic imines Phthalimide as an efficient co-catalyst. Tetrahedron Asymmetry 1995, 6,2661-2664. 

Figure 13.4 Iridium-based catalysts for asymmetric hydrogenation reactions.

A method for the asymmetric hydrogenation of seven-membered cyclic imines of benzodiazepinones and benzodiazepines has recently been published. The chiral cyclic amines generated from these reactions make up the cores of many natural products and clinical drugs. Iridium-bisphosphine catalyst systems were investigated and found to give promising enantios-electivities which could be improved upon addition of morpholine tri-fluoroacetate. The optimum conditions, applied to model compound 50, are shown in Scheme 14.19, giving 51 in excellent enantioselectivity and complete conversion. 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

In recent years, the asymmetric hydrogenation of prochiral olefins have been developed in the presence of various chiral sulfur-containing ligands combined with rhodium, iridium or more rarely ruthenium catalysts. The best results have been obtained by using S/P ligands, with enantioselectivities of up to 99% ee in... 

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