, published 15
, doi: 10.1098/rsta.2004.1536
2005 Phil. Trans. R. Soc. A
Ryoji Noyori, Christian A Sandoval, Kilian Muñiz and Takeshi Ohkuma
ligand bifunctional catalysis for asymmetric
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Metal–ligand bifunctional catalysis
for asymmetric hydrogenation
BY RYOJI NOYORI, CHRISTIAN A. SANDOVAL, KILIAN MUN ˜IZ
AND TAKESHI OHKUMA
Department of Chemistry and Research Center for Materials Science,
Nagoya University, Chikusa, Nagoya 464-8602, Japan
Chiral diphosphine/1,2-diamine–Ru(II) complexes catalyse the rapid, productive and
enantioselective hydrogenation of simple ketones. The carbonyl-selective hydrogenation
takes place via a non-classical metal–ligand bifunctional mechanism. The reduction of
the CaO function occurs in the outer coordination sphere of an 18e trans-
RuH2(diphosphine)(diamine) complex without interaction between the unsaturated
moiety and the metallic centre. The Ru atom donates a hydride and the NH2ligand
delivers a proton through a pericyclic six-membered transition state, directly giving an
alcoholic product without metal alkoxide formation. The enantiofaces of prochiral
ketones are differentiated on the chiral molecular surface of the saturated RuH2species.
This asymmetric catalysis manifests the significance of ‘kinetic’ supramolecular
Keywords: asymmetric hydrogenation; 2,20-bis(diphenylphosphino)-1,10-binaphthyl;
chiral alcohols; chiral diamines; ketones; ruthenium complexes
Although H2 is the smallest molecule, it has enormous potential from both
scientific and technical perspectives. Asymmetric hydrogenation provides the
most powerful way to produce a wide range of enantio-enriched compounds
without forming any waste (Noyori 1994a, 2002; Ohkuma & Noyori 1998, 1999;
Ohkuma et al. 2000; Noyori et al. 2004). Earlier, we reported that BINAP–RuX2
complexes (BINAPZ2,20-bis(diphenylphosphino)-1,10-binaphthyl; XZhalogen;
polymeric form) efficiently catalyse the asymmetric hydrogenation of various
functionalized ketones to give chiral alcohols in high enantiomeric excess (ee), as
shown in figure 1 (Noyori 1989, 1990, 1994b, 1996; Noyori & Kitamura 1989).
This asymmetric method is now widely practiced in research laboratories and
even at the industrial level (Akutagawa 1992; Noyori 2002). b-Keto esters are
hydrogenated in an alcoholic solvent with a substrate to catalyst molar ratio
(S/C) of up to 10 000, thus giving chiral b-hydroxy esters in greater than 99% ee
(Kitamura et al. 1993). As illustrated in figure 2, the actual catalyst is the RuHCl
species formed by the heterolysis of H2by the RuCl2precatalyst. Both H2and
the ketonic substrate are activated in the BINAP–Ru template and,
Phil. Trans. R. Soc. A (2005) 363, 901–912
Published online 12 April 2005
One contribution of 19 to a Discussion Meeting ‘Catalysis in chemistry and biochemistry’.
q 2005 The Royal Society
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reduction. Here the enantiofaces of the aromatic ketone 1 are differentiated on
the molecular surface of the 18e complex (S,SS)-11. As is clearly illustrated in
figure 10, TSRleading to (R)-2 is favoured over TSS, which suffers significant
non-bonded repulsion between the axial P-tolyl ring and the phenyl substituent
Other chiral diphosphine/diamine complexes such as 5 and 6 (figure 4) also
act as excellent precatalysts (Noyori & Ohkuma 2001). The asymmetric
hydrogenation of 1 occurs in 2-propanol with at least two or one equivalents of
a strong base, giving (R)-2 in the same 82% ee. Although the activation of these
halide-containing complexes is considerably more complicated, the reaction
involves the same catalytic cycles I and II.
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