Hydrogenation reactions asymmetric

Jessop and co-workers studied asymmetric hydrogenation reactions with the catalyst complex Ru(OAc)2(tolBINAP) dissolved in [BMIM][PFg]. In both reactions under investigation - the hydrogenation of tiglic acid (Scheme 5.2.10) and the hydrogenation of the precursor of the anti-inflammatory dmg ibuprofen (Scheme 5.2.11) - no CO2 was present during the catalytic transformation. However, SCCO2 was used in both cases to extract the reaction products from the reaction mixture when the reaction was complete. 

The first application involving a catalytic reaction in an ionic liquid and a subsequent extraction step with SCCO2 was reported by Jessop et al. in 2001 [9]. These authors described two different asymmetric hydrogenation reactions using [Ru(OAc)2(tolBINAP)] as catalyst dissolved in the ionic liquid [BMIM][PFg]. In the asymmetric hydrogenation of tiglic acid (Scheme 5.4-1), the reaction was carried out in a [BMIM][PF6]/water biphasic mixture with excellent yield and selectivity. When the reaction was complete, the product was isolated by SCCO2 extraction without contamination either by catalyst or by ionic liquid. 

Scheme 1. First use of P-chirogenic phosphine ligands in asymmetric hydrogenation reaction...

Scheme 22. Examples of Rh-catalyzed asymmetric hydrogenation reactions of dehydroammo esters...

Scheme 25. Rh-catalyzed asymmetric hydrogenation reactions leading to a biologically active compound...

Scheme 27. Example of the Rh-catalyzed asymmetric hydrogenation reaction of ethenephosphonate...

In 2000, these authors also developed a very efficient diphosphine-bithiophene ligand, tetraMe-BITIOP, which is depicted in Scheme 8.29. The ruthenium complex of this electron-rich diphosphine was used as the catalyst in asymmetric hydrogenation reactions of prostereogenic carbonyl functions of a-... 

Recently, Miethchen modified diphosphinite 97 d with a crown-ether linker in the 1,4-positions in order to study the effect on enantioselectivity in Rh-cata-lyzed asymmetric hydrogenation reactions [99]. Introduction of the crown ether in the 1,4-position of the carbohydrate allows the enantioselectivity to be tuned, based on a strong effect of the formation of cryptate species with alkali ions. 

Chapter 2 to 6 have introduced a variety of reactions such as asymmetric C-C bond formations (Chapters 2, 3, and 5), asymmetric oxidation reactions (Chapter 4), and asymmetric reduction reactions (Chapter 6). Such asymmetric reactions have been applied in several industrial processes, such as the asymmetric synthesis of l-DOPA, a drug for the treatment of Parkinson s disease, via Rh(DIPAMP)-catalyzed hydrogenation (Monsanto) the asymmetric synthesis of the cyclopropane component of cilastatin using a copper complex-catalyzed asymmetric cyclopropanation reaction (Sumitomo) and the industrial synthesis of menthol and citronellal through asymmetric isomerization of enamines and asymmetric hydrogenation reactions (Takasago). Now, the side chain of taxol can also be synthesized by several asymmetric approaches. 

Phosphite compounds, which have been discussed in the context of their application in asymmetric hydrogenation reactions (see Section 6.1.2.6), can also be used to effect the copper salt-mediated asymmetric conjugate addition of diethylzinc to enones.74 As shown in Scheme 8-33, in the presence of diphosphite 92 and copper salt [Cu(OTf)2], the asymmetric conjugate addition proceeds smoothly, giving the corresponding addition product with high conversion and ee. In contrast, the monophosphite 93 gave substantially lower ee. 

The term chiral poisoning as a deactivating strategy has been proposed for the asymmetric hydrogenation reaction of dimethyl itaconate catalyzed by CHIRAPHOS-Rh complex (Scheme 8.5). The combination of racemic CHIRAPHOS-Rh complex and (5)-METHOPHOS 6 as a catalyst poison yields the hydrogenated product in 49% ee. (5)-METHOPHOS is believed to bind to the (S. S -CHlRAPHOS-Rh complex preferentially, as the use of enantiopure (R,R)-CHlRAPHOS-Rh complex affords the product with 98% ee. 

When we first ventured into the field of [2.2]paracyclophane ligand synthesis, successful applications of such ligands were relatively rare [2]. The most prominent example was clearly the PHANEPHOS ligand developed by Rossen and Pye [3], who have found several successful applications in asymmetric hydrogenation reactions. A comprehensive survey of [2.2]paracyclophane-based ligands can be found in recent reviews [4, 5]. 

Ferrocene-derived ligand (l ,S)-Josiphos, which is widely used for catalytic asymmetric hydrogenation reactions, is also a good catalyst for the asymmetric copper-catalyzed 1,4-addition. Reaction in f-BuOMe in the presence of 6 mol% of this ligand gives products with up to 98%. ... 

If some of the ligands bonded to the metal atom in a homogeneous catalyst are chiral, then the hydrogenation can, in theory, produce an excess of one enantiomer of the reduction product. One catalyst that has been found to be effective in such an asymmetric hydrogenation reaction is this chiral rhodium complex ... 

Before leaving asymmetric hydrogenation reactions, we should mention one other related process that has acquired immense importance, again because of its industrial application. You have come across cit-ronellol a couple of times in this chapter already the corresponding aldehyde citronellal is even more important because it is an intermediate in the a synthesis of L-menthol by the Japanese chemical company Takasago. Takasago manufacture about 30% of the 3500 ton annual worldwide demand for L-menthol from citronellal by using an intramolecular ene reaction (a cycloaddition you met in Chapter 35). 

The chiral influence can also be present in a catalyst many asymmetric hydrogenation reactions have been carried out. The example shown (47 -> 48) requires differentiation of the enantiofaces of a double bond [66]. 

In recent years the synthesis of chiral and achiral tripodal phosphines and their application in homogeneous catalysis has been studied in more detail [2]. Enantiomerically pure tripodal ligands were synthesized from the corresponding trichloro compounds and chiral, cyclic lithio-phosphanes, e.g. 17, (Scheme 6) [21,22], Using a rhodium(I) complex of ligand 18, an enantiomeric excess of 89 % was obtained in the asymmetric hydrogenation reaction of methyl acetami-docinnamate (19). 

The chiral center can also reside in the phosphine fragment. 2,5-Dimethyl-3,4-bis[(2i, 5i )-2,5-dimethylphospho-lano] thiophene 102 has been synthesized and used as the ligand for Rh and Ru in asymmetric hydrogenation reactions (Scheme 21) <2005JOC5436>. 

Ryoji Noyori shared the 2001 Nobel Prize in Chemistry for developing methods for asymmetric hydrogenation reactions using the chiral BINAP catalyst. 

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