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Rhodium(I)-Catalyzed Asymmetric Hydrogenation

Tsuneo Imamoto

Chiba University, Faculty of Science, Department of Chemistry, Yayoi-cho, Inage-ku, 263-8522 Chiba, Japan

1.1 Introduction

The asymmetric hydrogenation of prochiral unsaturated compounds, such as alkenes, ketones, and imines, is one of the most straightforward methods for the synthesis of optically active compounds. This method using molecular hydrogen and small amounts of chiral transition-metal complexes is operationally simple, environmentally friendly, and frequently employed in both academia and industry.

During the last five decades, the homogeneous asymmetric hydrogenation by the use of rhodium, ruthenium, iridium, and other transition-metal complexes has remarkably progressed with the developments of thousands of chiral ligands. The catalytic performance of asymmetric hydrogenation is largely affected by the used transition metal, and rhodium-catalyzed hydrogenation has constituted a unique and large research area to provide useful technologies for the production of optically active pharmaceuticals, agrochemicals, and fine chemicals.

Previously, Chi, Tang, and Zhang described an excellent review of Rh-catalyzed asymmetric hydrogenation covering the literatures published until 2003 [1]. This review describes the subsequent advancement of this area, citing the literatures published since 2004.

1.2 Chiral Phosphorus Ligands

Chiral phosphorus ligands play pivotal roles in Rh-catalyzed asymmetric hydrogenation as well as in many other transition-metal-catalyzed asymmetric transformations [2]. Although numerous chiral phosphorus ligands have been designed and synthesized over the past half a century and many of them have been used in both academia and industry, the work to develop more efficient ligands is still actively underway. This section summarizes the chiral phosphorus ligands used for Rh-catalyzed asymmetric hydrogenation that have been reported since 2004. They are largely classified into several types according to their structural variations, electronic properties, and characteristic activities toward prochiral unsaturated substrates.

1.2.1 P-Chirogenic Bisphosphine Ligands

1.2.1.1 Electron-Rich C 2 Symmetric Ligands

BisP*- and MiniPHOS-Based Ligands

BisP* and MiniPHOS are typical P-chirogenic phosphine ligands, possessing a bulky alkyl group and a methyl group at the phosphorus atoms (Figure 1.1). These ligands exhibit excellent enantioselectivities in some representative catalytic asymmetric reactions, but because of their high air sensitivity, they are not widely used, except in the mechanistic study of Rh-catalyzed asymmetric hydrogenation [3]. Further studies to overcome the drawbacks of these ligands, QuinoxP* [4, 5], Ad-QuinoxP* [6], L1 [7], AlkynylP* [8], BenzP* [5, 9], DioxyBenzP* [5], TMB-QuinoxP* [10], and BipheP* [11] have been designed and synthesized (Figure 1.1). Among these ligands, QuinoxP* and BenzP* are air-stable crystalline solids and are frequently used not only in Rh-catalyzed asymmetric hydrogenation but also in many other catalytic asymmetric transformations [12].

Figure 1.1 Electron-rich P-chirogenic phosphine ligands.

Bisphosphacycle Ligands

In 2002, Tang, Zhang, and coworkers reported the synthesis of a P-chirogenic bisphospholane ligand, TangPhos, and its excellent enantioinduction ability and high catalytic activity in Rh-catalyzed asymmetric hydrogenation [13, 14]. The superior catalytic performance of the TangPhos-Rh complex is responsible for its very rigid molecular structure consisting of three fused five-membered rings and the asymmetric environment arising from the tert-butyl groups that effectively shield the two diagonal quadrants. The great success of TangPhos ligand has prompted the synthesis of analogous bisphosphacycle ligands, all of which possess tert-butyl groups at the P-chirogenic phosphorus atoms (Figure 1.2). A seven-membered bisphosphacycle ligand, Binapine, exhibits high enantioinduction ability in the hydrogenation of ß-dehydroamino acids and 2-pyridyl-substituted ketones [15, 16]. DiSquareP* and L2, which contain highly strained four-membered phosphacycles, have their potential utility in Rh-catalyzed asymmetric hydrogenation [17, 18]. In 2005, Liu and Zhang reported DuanPhos ligand composed of two connected benzophospholanes [19]. Both enantiomers of this ligand are commercially available and widely used in Rh-catalyzed asymmetric hydrogenation of various prochiral substrates and often employed in the industrial production of chiral ingredients [20]. ZhangPhos ligand is more rigid and electron-rich than TangPhos and DuanPhos, and it shows exceedingly high enantioselectivities in the hydrogenation of not only standard probing substrates but also N-aryl ß-enamino esters and a-aryl imino esters [21]. Tang and coworkers have developed P-chirogenic bisoxaphospholane ligands BIPOP and WingPhos [22, 23]. These ligands provide unique catalytic performance and have been successfully employed in the hydrogenation that difficultly proceeds with the use of other predecessor ligands [24].

Figure 1.2 C 2 symmetric bisphosphacycle ligands possessing tert-butyl groups at the P-chirogenic centers.

1.2.1.2 Three-Hindered Quadrant Ligands

In 2004, Hoge and coworkers reported a novel C 1 symmetric bisphosphine ligand, di-tert-butylphosphino-tert-butyl(methyl)phosphinomethane named Trichickenfootphos () [25]. This ligand forms a four-membered Rh complex, in which the three tert-butyl groups effectively hinder three quadrants, and its superior catalytic performance was demonstrated by the highly efficient synthesis of a pregabalin precursor [25a]. The three-hindered quadrant motif, apart from the traditional C 2 symmetric design concept, has prompted the synthesis of analogous ligands (L3 [26], MaxPHOS [27], L4 [28], MeO-POP [29], 3H-BenzP* [30a], 3H-QuinoxP* [30]) (Figure 1.3). All of these ligands have proved their high catalytic activities in Rh-catalyzed asymmetric hydrogenations of various substrates.

Figure 1.3 P-Chirogenic three-hindered quadrant ligands.

1.2.1.3 Ligands Bearing Two or Three Aryl Groups at the Phosphorus Atom

DIPAMP synthesized by Knowles and coworkers is a landmark chiral phosphine ligand in the history of Rh-catalyzed asymmetric hydrogenation. Nevertheless, the ligand has not been widely used because of its high but somewhat insufficient enantioselectivities (up to 96% in the hydrogenation of a-dehydroamino acid derivatives) and the inconvenient synthesis with traditional methods. New synthetic methodology using phosphine-boranes as the intermediates has enabled the synthesis of analogous ligands (L5 [31], L6 [32], R-SMS-Phos [33], L7 [34], L8 [35]) (Figure 1.4). Among these ligands, L5 and R-SMS-Phos provide superior enantioselectivities up to >99% in comparison with DIPAMP. Ligands L7 and L8 exhibit unique catalytic performance, arising from the supramolecular component and the large bite angle of the Rh complex.

Figure 1.4 P-Chirogenic ligands bearing two or three aryl groups at the phosphorus atom.

1.2.2 DuPhos, BPE, and Analogous Ligands

DuPhos and BPE possessing chiral phospholanyl cycles are versatile ligands not only for Rh-catalyzed asymmetric hydrogenation but also for many other transition-metal-catalyzed reactions. The great success of DuPhos and BPE provided the opportunity to synthesize ferrocene-based ligands, FerroTANE and Ph-5-Fc, with the chiral phosphacycle motif. Furthermore, several analogous ligands (UlluPHOS [36], Butiphane [37], PhBPM [38], Ph-Quinox [39], Ph-Pyrazine [39], and CatASiumMQF [40]) have been reported since 2004 (Figure 1.5). Among all of these bisphosphacycle ligands, DuPhos is still the most frequently used in Rh-catalyzed asymmetric hydrogenation.

Figure 1.5 DuPhos, BPE, and analogous ligands.

1.2.3 Ferrocene-Based Bisphosphine Ligands

In 1974, Hayashi and coworkers synthesized a chiral ferrocene-based bisphosphine ligand, BPPFA, and demonstrated its high catalytic performance in Rh-catalyzed asymmetric hydrogenation. Since Hayashi's pioneering work, numerous ferrocene-based chiral phosphorus ligands have been synthesized and applied in catalytic asymmetric reactions. Figure 1.6 shows ferrocene-based phosphorus ligands, most of which...