Synthesis and Structural Characterization of a Highly Effective Chiral Dipyridylphosphine Ligand and Its Application in the Ru-Catalyzed Asymmetric Hydrogenation of β-Ketoesters

Abstract

Abstract:A new chiral dipyridylphosphine ligand Tol-P-Phos has been synthesized and the structure of the complex of (R)-Tol-PPhos oxide with (-)-dibenzoyl-L-tartaric acid [(-)-DBT] was determined by single crystal X-ray diffraction. The ruthenium complex of Tol-P-Phos, Ru(R-Tol-P-Phos)(C 6 H 6 )Cl 2 , has been found to be a highly active and enantioselective catalyst in the asymmetric hydrogenation of b-ketoesters (up to 98.2% e.e.). The catalyst is also found to be air-stable even in solution.Key words: asymmetric catalysis, hydrogenation, dipyridylphosphine ligands, ruthenium complex, b-ketoesterThe search for new chiral ligands is an ongoing process in the field of asymmetric synthesis.1 Although more than a thousand chiral nonracemic diphosphines have been synthesized and the efficiency of catalysts derived from these ligands have been established, 1,2 the possibility of discovering catalysts with improved utility, activity, and selectivity by designing new ligands remains to be an area of active research.Over the past two decades, tremendous success has been achieved in the use of chiral arylphosphine ligands such as BINAP, BIPHEP, MeO-BIPHEP, and DuPhos, etc. in Rhor Ru-catalyzed asymmetric hydrogenation reactions.1 As an effort to expand the scope of the arylphosphine ligands and their application in homogeneous catalysis, transition-metal complexes containing pydridylphosphine ligands have been synthesized and tested in homogeneous catalysis.3 Unfortunately, the tested complexes were found to be inactive in the homogeneous hydrogenations owing to the pyridyl group which coordinated to the metal center and rendered the complex coordinately saturated. 4 By preventing the coordination of the pyridyl groups via the use of bulky substituents, we found that the resulting rhodium(I) complex was effective for the hydrogenation of aldehydes, olefins, and imines.

A remarkably effective copper(II)-dipyridylphosphine catalyst system for the asymmetric hydrosilylation of ketones in air

“…Our previous studies on catalytic asymmetric hydrogenation reactions demonstrated that the dipyridylphosphine ligands possessed better air stability than that of 2,2Ј-bis(diphenyllphosphino)-1,1Ј-binaphthyl (47,48). In the present air-accelerated system, air is one of the key factors for the enhancement of reaction rates, and consequently, dipyridylphosphines with good air stability exhibited extraordinary advantages to other common diphosphines.…”

“…48) for Ru-catalyzed hydrogenation of a broad scope of simple ketones (17,18). Particularly noteworthy was the observation that the Ru-(P-Phos) catalyst system was highly air-stable even in solution (18,47,48). Capitalizing on this fact, we conjectured that the air stability of P-Phos-type ligands might be especially favorable for the air-accelerated, copper(II)-catalyzed asymmetric hydrosilylations of unfunctional ketones (45).…”

“…1 and ref. 46) and its analogues (47,48) and have established their effectiveness for many catalytic asymmetric hydrogenation reactions (46 -49), especially the utility of 2,2Ј,6,6Ј-tetramethoxy-4,4Ј-bis[di(3,5-dimethylphenyl)phosphino]-3,3Ј-bipyridine (Xyl-P-Phos) (1b, Fig. 1 and ref.…”

P-Phos: A Family of Versatile and Effective Atropisomeric Dipyridylphosphine Ligands in Asymmetric Catalysis

“…Surprisingly, higher temperature (100°C) led to excellent chiral efficiency (97% ee) under 100 atm H 2 pressure. 23 In contrast, the employment of Ru complexes of P-Phos 11b or Tol-P-Phos 12 applied to the practical synthesis of L-carnitine (Scheme 6), an important agent responsible for the transport of long-chain fatty acid through human metabolism. 23 Activity and Air Stability of the Ru-(P-Phos) Catalyst System.…”

Enantioselective Ketone and β‐Keto Ester Hydrogenations (Including Mechanisms)

“…The small dihedral angle of the SEGPHOSRu complex (658) may have a major influence on the high enantioselectivity. MeO-BIPHEP [14 q, 18], Tol-P-Phos [43], 2A [25], ferrocenyl diphosphine 2Bc [44], and the monodentate phosphine 1C [31] also show high enantioselectivity. A Ru complex with the diphosphinite ligand Xylyl-o-BINAPO gives the hydroxy ester in 99% ee [35].…”