Bis(phosphinite) with C2-Symmetric Axis; Effects on the Ruthenium(II)- Catalyzed Asymmetric Transfer Hydrogenation of Acetophenone Derivatives

Abstract

Chiral ruthenium catalyst systems generated in situ from [Ru(η 6 -p-cymene)(μ-Cl)Cl] 2 complex and chiral C 2 -symmetric bis(phosphinite) ligands based on amino alcohol derivatives were employed in the asymmetric transfer hydrogenation of aromatic ketones to give the corresponding optically active alcohols in high yield. The best results were obtained in the [Ru(η 6 -p-cymene)(μ-Cl)Cl] 2 and (2S)-2- [benzyl(2-{benzyloxy]-3-phenylpropan-2-yl]amino}ethyl)amino]-3-phenylpropyl diphenylphosphinite catalytic systems, which gave enantioselectivities of up to 93% ee and 99% conversion.Asymmetric transfer hydrogenation of ketones has recently emerged as an alternative method to asymmetric hydrogenation for the production of chiral alcohols due to its operational simplicity and ready availability of reductants. 1-3 Chiral alcohols are very important building blocks and synthetic intermediates in organic synthesis and in the pharmaceutical industry. 4,5 Catalytic asymmetric synthesis using chiral metal complexes as catalyst precursors offers an ideal method for reducing ketones to chiral alcohols. 6,7 In general, the most easily designed and the most abundant ligands are C 2 -symmetric bis(phosphines) due to their stereochemical redundancy. Significantly fewer in number are other arrangements, such as bidentate bis(phosphinites) systems. 8,9 Phosphine ligands have found widespread applications in transition-metalcatalyzed asymmetric transformations. 10,11 Phosphinites provide different chemical, electronic, and structural properties compared to phosphines. The metal-phosphorus bond is often stronger for phosphinites compared to the related phosphines due to the presence of the electronwithdrawing P-OR group. In addition, the empty σ*-orbital of the phosphinite P(OR)R 2 is stabilized, making the phosphinite a better electron acceptor. 12 Chiral β-amino alcohols continue to be of importance in modern synthetic chemistry, not least because of their biological properties, 13 but also because of their wide range of synthetic applications. 14,15 Hence, the asymmetric synthesis of enantiomerically enriched amino alcohols has been extensively studied. Especially, catalysts derived from C 2 -symmetric amino alcohols have received much attention and are used in many asymmetric catalytic reactions; furthermore, they have been shown to be powerful tools in the asymmetric reduction of prochiral ketones. 16,17 Because C 2 -symmetric amino alcohols often give high levels of enantioselectivity in asymmetric reactions, as an extension of our ongoing research program, we wanted to synthesize novel C 2 -symmetric bis(phosphinites) based on amino alcohol derivatives and use them with Ru(II) precursors as catalysts in the asymmetric transfer hydrogenation of aromatic ketones with i-PrOH under varying conditions. The synthesis of the ligands was accomplished as illustrated in Scheme 1. First, the synthesis of L-and D-phenylglycinol, and L-and D-phenylalaninol were accomplished in one step from the corresponding phenylglycine or phenylalanine ac...

Ferrocene based chiral binuclear η6‐benzene‐Ru(II)‐phosphinite complexes: Synthesis, characterization and catalytic activity in asymmetric reduction of ketones

“…A small coordination shift was attributed to formation of the corresponding C 2 ‐ symmetric η 6 ‐benzene‐Ru(II)‐phosphinite complexes 5–8. The 1 H NMR and 13 C‐{ 1 H} NMR data for complexes 5–8 are consistent with the formulation of ferrocene based binuclear η 6 ‐benzene‐Ru(II)‐phosphinite and in line with the values previously observed for similar complexes [22, 15c] . Elemental analyses and FT‐IR spectra of complexes 5–8 are also consistent with the expected molecular formulas.…”

“…The signals of the starting materials Ph 2 PCl at δ = 81.0 ppm and i Pr 2 PCl at δ = 133.8 ppm disappeared and new singlets were appeared at δ = 116.76 (Figure S1), 115.66 ppm (Figure S3) and at δ =154.69 (Figure S2), 152.51 ppm (Figure S4) due to the diphenylphosphinite or diisopropylphosphinite moiety, respectively. 31 P–{ 1 H} NMR spectra of the free ligands are in line with the values previously observed for similar compounds and indicate that two phosphorus atoms in the each molecule are equivalent [22, 23, 8b, 15c] . Additionally, 1 H–NMR, 13 C‐{ 1 H} NMR, IR spectra and C, H, N elemental analyses were in agreement with the proposed structures for the new phosphinite ligands.…”

Biological assays and theoretical density functional theory calculations of Rh(I), Ir(III), and Ru(II) complexes of chiral phosphinite ligand

“…Spectral data including 1 H 13 C NMR and infrared spectroscopy supported ring opening. The imidazolium‐based phosphinite ( 2 ) was prepared upon the reaction of 1 with PPh 2 Cl and Et 3 N by a modified literature procedure, [ 38,47,48 ] formation of which was confirmed by 31 P‐{ 1 H} NMR monitoring [ 49–51 ] (Scheme 1). In the 31 P‐{ 1 H} NMR spectrum of (2) a singlet is present at δ 118.49 ppm.…”

Synthesis and Characterization of Half‐Sandwich Ruthenium Complexes Containing Aromatic Sulfonamides Bearing Pyr­id­inyl Rings: Catalysts for Transfer Hydrogenation of Acetophenone Derivatives

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Keywords: Transfer hydrogenation / Sulfonamides / Ruthenium / N ligands benzenesulfonamides 1-6 were successfully synthesized by the reaction of 8-aminoquinoline and various benzenesulfonyl chlorides. [38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] Herein, a series of half-sandwich Ru II complexes containing sulfonamide ligands were synthesized and characterized by various spectroscopic techniques. The synthesized compounds were characterized by NMR and FTIR spectroscopy and elemental analysis, and compounds 8 and 9 were further ana-

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3224 lyzed by X-ray diffraction.

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