A New Class of Versatile Chiral-Bridged Atropisomeric Diphosphine Ligands:  Remarkably Efficient Ligand Syntheses and Their Applications in Highly Enantioselective Hydrogenation Reactions

Abstract

A series of chiral diphosphine ligands denoted as PQ-Phos was prepared by atropdiastereoselective Ullmann coupling and ring-closure reactions. The Ullmann coupling reaction of the biaryl diphosphine dioxides is featured by highly efficient central-to-axial chirality transfer with diastereomeric excess >99%. This substrate-directed diastereomeric biaryl coupling reaction is unprecedented for the preparation of chiral diphosphine dioxides, and our method precludes the tedious resolution procedures usually required for preparing enantiomerically pure diphosphine ligands. The effect of chiral recognition was also revealed in a relevant asymmetric ring-closure reaction. The chiral tether bridging the two aryl units creates a conformationally rigid scaffold essential for enantiofacial differentiation; fine-tuning of the ligand scaffold (e.g., dihedral angles) can be achieved by varying the chain length of the chiral tether. The enantiomerically pure Ru- and Ir-PQ-Phos complexes have been prepared and applied to the catalytic enantioselective hydrogenations of alpha- and beta-ketoesters (C=O bond reduction), 2-(6'-methoxy-2'-naphthyl)propenoic acid, alkyl-substituted beta-dehydroamino acids (C=C bond reduction), and N-heteroaromatic compounds (C=N bond reduction). An excellent level of enantioselection (up to 99.9% ee) has been attained for the catalytic reactions. In addition, the significant ligand dihedral angle effects on the Ir-catalyzed asymmetric hydrogenation of N-heteroaromatic compounds were also revealed.

Adventure in Asymmetric Hydrogenation: Synthesis of Chiral Phosphorus Ligands and Asymmetric Hydrogenation of Heteroaromatics

“…9). Chan and coworkers developed a serial of effective diphosphine ligands, such as axially chiral P-Phos [66], PQ-Phos, [67] phosphinite ligands H 8 -BINAPO [68], and Spiropo [69] with high activity and can be immobilized in DMPEG (poly(ethylene glycol) dimethyl ether) for recycling. Reetz's group found that BINOL-derived diphosphonites linked to an achiral diphenyl ether unit were also effective [70].…”

Ruthenium diphosphine complexes as an efficient hydroamination catalyst

“…Since the 1990s, ruthenium-catalyzed reactions such as [16] olefin metathesis [17], the oxidation of alcohols and amines [18], asymmetric reduction using hydrogen [19], hydroamination and hydroaminomethylation of olefins have attracted a great interest in organic synthesis [20]. Among these complexes, half-sandwich ruthenium(II) arenes are important and widely used organometallic compounds and exhibit a diverse range of coordination chemistry [21][22][23][24].…”

Enantioselective hydrogenation of α-aminomethylacrylates containing a free NH group for the synthesis of β-amino acid derivatives

“…Asymmetric hydrogenation of these substrates 2 is the simplest and most direct route to synthesize 1 because of its inherent efficiency and atom economy. In contrast to the great progress in the synthesis of ␤-substituted ␤-amino acids and derivatives via enantioselective hydrogenations (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38), reports on the synthesis of ␣-substituted ␤-amino acids with this protocol are very limited. To the best of our knowledge, only one exceptional example has been given, very recently by Zheng and coworkers (38), using Rh-monophosphorus catalyst system for the hydrogenation of ␤-phthalimide acrylates.…”

“…The results of using Ru-BINAP (56, 57), Bu-PQ-Phos (35,36), and Rh-Monophos (24) complexes as catalysts were rather disappointing, showing poor reactivities and enantioselectivities (Table 1, entries 1-9). Good improvement occurred by employing Rh-(Me-Duphos) (58) or Rh-Tangphos (59) complex in this reaction.…”