DuPHOS ligand, catalytic enantioselective

As a test reaction for the catalytic activity the hydrogenation of dimethylitaconate was employed. No reaction takes place in the blank test, when the carrier Al-MCM-41 itself is used as catalyst. The immobilised rhodium complexes give enantioselectivities up to 92 % ee of dimethyl-(R)-methylsuccinate with a turn over number of 4000 for the S,S-Me-Duphos ligand. The corresponding supported catalysts with R,R-Diop and S,S-Chiraphos ligands lead to enantioselectivities of 34 % ee and 47 % ee with lower activities. With the (+)-Norphos ligand the favoured enantiomer is dimethyl-(S)-succinate which is formed with 47 % ee. 

Copper(II) salts combined with DuPhos ligands proved to be active catalysts for the enantioselective allylboration of ketones (300). Copper(I) triflate with Me-DuPhos hemioxide has been used as an active catalytic system for the enantioselective addition of dialkylzinc to jS-nitroalkenes (301). 

Chiral ligand 78, bearing structural features similar to those of DuPhos, has also been synthesized and gives moderate to high enantioselectivity in the catalytic asymmetric hydrogenation of functionalized carbonyl groups. High levels... 

The rhodium complexes of 71 and 80 show high catalytic activities but only moderate enantioselectivities (up to 90% ee) compared to the very high optical yields of analogous phospholane-based DuPHOS and BPE ligands. 

Several other palladium complexes Pd(L )(Ph)(I)] and Pd(L )(trans-stil-bene)] with different chiral diphosphine ligands L were also employed as catalyst precursors. The yield and enantioselectivity of the product are strongly dependent on the diphosphine. It was found that the DuPhos series (Me/Et/f-Pr-DuPhos) produces results similar to those listed in Table 6.6. In contrast, changing to the more flexible (R,R)-Me-BPE gives a very active catalytic system but with a disappointing 18% ee. With DuXantphos a very slow system results, with the formation of by-products. Ferrocenyl phosphines (Me-FerroLANE, Et- FerroTANE, Josiphos, BoPhoz) were also employed but were found to be inferior to DuPhos. Finally, with several Ni(Me-DuPhos) catalyst precursors, reactions do not reach completion and formation of by-products is observed. 

Numerous complexes for the hydrogenation of imines have been screened in this study, among them DIOP (2,3-D-isopropylidene-2,3-dihydoxy-l,4-bis-(diphenyl-phosphino)butane), BINAP (2,2 -bis(diphenylphosphino)-l,l -binaphtyl), DuPHOS (1,2-bis(2,5-diisopropylphospholano)benzene) and many others. AU of them afforded (—)-(R)-sitagliptin 24 with substantially lower e.e., usually below 30 %. This outcome nicely illustrates how dilficult the rational design of the structure of the chiral ligand for the catalytic complex is, which is highly enantioselective with the specific substrate. 

Other procedures for carbonyl hydrosilylation of aldehydes and ketones are using [bis(imino)pyridine]iron dinitrogen and dialkyl complexes as precatalysts. Only 0.1-1.0 mol% catalyst are required to achieve this transformation. The reductants are either phenylsilane or diphenylsilane in this case. A number of enantioselective versions of the hydrosilylation reaction is described. This includes the application of 1,2-bis[(25, 55)-2,5-dimethylphospholano]benzene [(S,5)-Me-DuPhos] (Scheme 4-328) as chiral ligand, iron(II) acetate as a precatalyst and polymethylhydrosiloxane as hydride source. A large variety of ketones can be transformed into the corresponding alcohols in excellent yield and up to 99% enantiomeric excess. Catalytic ketone hydrosilylation is also achieved with the dialkyliron complexes (S,S)-... 

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