Asymmetric hydrogenation ferrocenyl phosphine

Rh complexes with ChiraPhos, PyrPhos, or ferrocenyl phosphines lacking amino alkyl side chains (such as BPPFA) are much less active toward tetrasubstituted olefins. Table 6-1 shows that in asymmetric hydrogenations catalyzed by 5a-d, the coordinated Rh complex exerts high selectivity on various substrates. It is postulated that the terminal amino group in the ligand forms an ammonium carboxylate with the olefinic substrates and attracts the substrate to the coordination site of the catalyst to facilitate the hydrogenation. 

Many attempts have been made to develop novel nonracemic ferrocenyl phosphine derivatives as asymmetric hydrogenation catalysts. Interested readers will find the design and synthesis of these chiral ferrocenyl phosphine ligands in a recent review by Richards and Locke.286... 

Phosphines ligands that have chirality from ferrocenes have been implemented in the iridium-catalyzed asymmetric hydrogenation of imine with moderate enantioselectivities for Novartis s manufacture of metolachlor. Electronic modifications of these ferrocenyl ligands have increased the enantioselectivity and catalyst reactivity for Lonza s asymmetric hydrogenation processes of biotin and 2-substituted piperazines, intermediates for several pharmaceutical drugs. 

Chiral Rh complexes of hydroxyalkyl ferrocenyl phosphine BppfOH catalyze the asymmetric hydrogenation of aminomethyl aryl ketones to 2-amino-1-aryl ethanols. Both occur in high chemical and optical yield ... 

Asymmetric hydrogenation of a-amidoacrylic acids and related olefins has been reported to proceed with high enantioselectivity in the presence of chiral ferrocenyl-phosphine-rhodium catalysts. Both ferrocenylmonophosphines [21, 24, 58] and ferrocenylbisphosphines [17, 59, 60] can produce A -acetylphenylalanine with >80 /o ee in the rhodium-catalyzed hydrogenation of a-acetoaminocinnamic acid or its esters (Scheme 2-42). The high selectivity is ascribed mainly to a characteristic structure of the olefinic substrate that has an amido group at the proper position... 

Scheme 4. Industrial applications of chiral ferrocenyl phosphines in the asymmetric hydrogenation of C=C and C=N double bonds.

Enantioselective transfer hydrogenation (from propan-2-ol) of some ketones catalysed by iridium(i) complexes with chiral Schifl-base ligands has been reported, giving product alcohol of up to 33% e.e. with propiophenone as substrate. Other new reductive routes to chiral secondary alcohols involve the asymmetric hydrogenation of enol phosphinates (21) catalysed by chiral ferrocenyl-rhodium... 

Cullen, W. R., and E-Shan Yeh Asymmetric Hydrogenation Using Ferrocenyl-phosphine Rhodium(I) Cationic Complexes. J. Organomet. 139, C13 (1977). 

Abstract Chiral ferrocenyl phosphine ligands are certainly one of the most developed and successful classes of chiral ligands used in asymmetric catalysis. The literature describing their synthetic and coordination chemistry, as well as their metal-mediated applications in the field of catalysis, is extremely rich and varied. Moreover, they represent a rare example in which enantioselective chemical catalysts were used in industrial processes. The present chapter provides an account of the planar-chiral ferrocene ligands developed in the Authors laboratory, including their coordination chemistry with various metals as well as their use in different asymmetric catalytic reactions (allylic substitution, Suzuki coupling, methoxycarbonylation of alkenes, hydrogenation of ketones). 

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