Highly Air‐ and Water‐Stable Fluorinated Ferrocenylphosphine‐Aminophosphine Ligands and their Applications in Asymmetric Hydrogenations

Abstract

Air-and water-stable fluorinated ferrocenylphosphine-aminophosphine ligands have been synthesized and applied to the Rh-catalyzed asymmetric hydrogenation of enamides and a-dehydroamino acid derivatives. These reactions afforded the corresponding products in good to excellent ees (up to 99.7% ee) and nearly quantitative yields. The combination of the remarkable air-and waterstability with excellent catalytic performance makes these catalysts excellent choices for practical applications.Keywords: air-stable ligands; asymmetric hydrogenation; enamides; ferrocenylphosphine-aminophosphine ligands; rhodium Asymmetric catalytic reactions have attracted much attention in recent years because of their great potential in making higher-value-added products. [1] In this respect, the use of chiral ligands has played a very important role.[2] So far many chiral ligands have been prepared and used for Rh-and Ru-catalyzed asymmetric hydrogenation.[3] Although moderate to excellent enantioselectivities have been achieved using these ligands, most of the catalytic reactions needed to be performed with the strict exclusion of oxygen and moisture, thus making them quite inconvenient for general organic synthesis and industrial applications. From a practical standpoint, it is desirable to develop effective, easily prepared chiral ligands and catalysts with high air-and water-stability, so that the associated catalytic reactions can be easily carried out in ordinary laboratory or industrial settings.Chiral ligands with a ferrocenyl backbone have found useful applications in transition metal-catalyzed asymmetric hydrogenations. [1,3,4] Some well known examples include Hayashis (aminoalkyl)ferrocenylphosphine ligands, [5] Tognis Josiphos-type ligands, [6] Burks Ferro-TANE-type ligands, [7] Knochels ferrocenyl ligands with two phosphanyl substituents, [8] Zhangs f-binaphane [9] and Spindlers Walphos-type ligands.[10] Recently, Baoz et al. reported the preparation of phosphinoferrocenylaminophosphines and their application in the rhodium-catalyzed asymmetric hydrogenation with high activities and enantioselectivities.[11] In our quest for highly efficient ligands in asymmetric hydrogenation, [12] we became interested in ferrocene-based ligands with high efficiency and stability. Herein we report the interesting findings of some new fluorinated phosphinoferrocenylaminophosphines in rhodium-catalyzed asymmetric hydrogenation. The distinctly high air-and water-stabilities of the fluorinated ligands as well as their Rh(I) complexes, combined with the high enantioselectivities in asymmetric hydrogenation, make them good choices for practical applications.We first examined ligand 1 (Scheme 1) in hydrogenation of arylenamides, and relatively poor ee values were observed in contrast to the results obtained from the hydrogenation of a-dehydroamino acid derivatives under similar conditions ( > 99% ee).[11] This is not surprising because chiral ligands for asymmetric catalysis usually perform well for specific types of substrates. It is w...

Synthesis of Aminophosphines and Their Applications in Catalysis

“…The majority of early applications of aminophosphines in asymmetric transformations were related to ruthenium-and rhodium-catalyzed asymmetric hydrogenations [81][82][83] and preparation of chiral alcohols and amines with excellent enantioselectivities and yields. An example of enantioselective hydrogenation of unsaturated carboxylic acids without any additional functional groups using rhodium complexes with aminophosphine ligands is shown in Scheme 36 [84].…”

Bidentate Ligands for Enantioselective Enamide Reduction

“…However, this ligand class is inefficient in the hydrogenation of enamides in terms of the enantioselectivity, and gave relatively poor ee values ($70% ee). A subsequent investigation on the optimization of ligand structure, performed by Chan [43], discovered that the introduction of a CF 3 group (39b) into the phenyl rings of aminophosphino moiety could significantly improve the enantioselectivity of the rhodium-catalyzed asymmetric hydrogenation of enamides (Figure 9.9). With this catalytic system, a variety of a-arylenamides were quantitatively converted to the corresponding chiral products in ee values ranging 92.1-99.7%.…”

Recent Applications of Chiral Ferrocene Ligands in Asymmetric Catalysis

“…The phosphinite ligand 3 , with the 3,5‐bis(trifluoromethyl)phenyl substitution, and the phosphoramidite ligand ( R c , S p , S a )‐ 4 , derived from ( S )‐Binol, afforded the best results in the hydrogenation of dehydro‐α‐amino acids (up to 99.6 % ee ; Scheme 4 B and C). The same research group has also prepared some phosphine–aminophosphine ferrocene ligands (for example, BoPhoz‐type ligand 1 b ), which are very efficient in the hydrogenation of α‐aryl enamides (Scheme 5) 55…”