A modular design of ruthenium(II) catalysts with chiral C2-symmetric phosphinite ligands for effective asymmetric transfer hydrogenation of aromatic ketones

Hydrogen-transfer reduction processes are attracting increasing interest from synthetic chemists in view of their operational simplicity. The new chiral C2-symmetric ligands N,N′-bis-[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 1 and N,N′-bis-[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 2 and the corresponding ruthenium complexes 3 and 4 have been prepared and their structures have been elucidated by a combination of multi-nuclear NMR spectroscopy, IR spectroscopy, and elemental analysis. 1H–31P NMR, DEPT, 1H–13C HETCOR, or 1H–1H COSY correlation experiments were used to confirm the spectral assignments. The catalytic activity of complexes 3 and 4 in transfer hydrogenation of acetophenone derivatives by iso-PrOH has also been studied. Under optimized conditions, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer hydrogenation of acetophenone derivatives in iso-PrOH and act as excellent catalysts, giving the corresponding chiral alcohols in 99% yield and up to 75% ee. This transfer hydrogenation is characterized by low reversibility under these conditions.

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N,N′-Bis(1S)-2-hydroxyethyl-1-(S)-sec-butyl]ethaneamide[C14H28N2O4][α]D25=+25.8 (c 1.0 DMSO)Source of chirality: l-isoleucineAbsolute configuration: (S,S,S,S)

N,N′-Bis[(1S)-1-phenyl-2-hydroxyethyl]ethanediamide[C18H20N2O4][α]D25=-35.2 (c 1.0 DMSO)Source of chirality: l-glycineAbsolute configuration: (S,S)

N,N′-Bis-[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethanediamide[C38H46N2O4P2][α]D25=+33.6 (c 1.0 DMSO)Source of chirality: l-isoleucineAbsolute configuration: (S,S,S,S)

N,N′-Bis-[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethanediamide[C42H38N2O4P2][α]D25=-35.2 (c 1.0 DMSO)Source of chirality: l-glycineAbsolute configuration: (S,S)

[Ru{chloro(p-cymene)(N,N′-bis[(1S)-1-sec-butyl-2-O-(diphenylphosphinite)ethyl]ethane diamide)}]chloride[C48H60N2O4P2RuCl2][α]D25=+38.2 (c 1.0 DMSO)Source of chirality: l-isoleucineAbsolute configuration: (S,S,S,S)

[Ru{chloro(p-cymene)(N,N′-bis[(1S)-1-phenyl-2-O-(diphenylphosphinite)ethyl]ethane diamide)}]chloride[C55H52N2O4P2RuCl2][α]D25=-38.0 (c 1.0 DMSO)Source of chirality: l-glycineAbsolute configuration: (S,S)