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doi:10.1595/147106709X481372
•Platinum Metals Rev., 2010, 54, (1)•
O
O
O
O
O
H 2 N HN–S
H 2 N HN–S
H 2 N HN–S R
S––NH
O
O
O
= poly(ethylene glycol) (PEG)
a R= Me
O
Ph
1 2 3 b R= CF 3
4
NH 2
Ph
NH 2
OH
HO NH 2 HO NHMe
5
6
HO NH 2
7
8
Scheme I. Ligands used for asymmetric transfer hydrogenation in aqueous media described in this review
(shown in Scheme I) which were designed for
organic solvents are also effective for ATH in water
with no need for modification or organic solvents. In
Table I, we summarise the results obtained with various
Ru(II) catalysts, including Ru-1, in the ATH of the
benchmark substrate acetophenone. The catalysts
were usually generated from the ligand and a Ru precursor
at the reaction temperature in water without
adding a base, for example Ru-2 from
[RuCl 2 (p-cymene)] 2 and ligand 2.The structure of Ru-
2 prepared under such conditions has been confirmed
by X-ray diffraction to be the same as the one
obtained in 2-propanol (65,68,122).These precatalysts
show varying solubilities in water. Presumably their
water solubility stems from chloride–water exchange,
resulting in the formation of monoaqua cations.
However,they show much higher solubility in ketones
and alcohols, most of which are insoluble in water.
Hence, we conclude that the reaction is biphasic and
takes place ‘on water’ (in aqueous suspension).
As shown in Table I, the monotosylated diamines
1–4 all served as efficient ligands for the ATH of
ketones in water, with full conversion and up to 97%
ee reached in short reaction times (Entries 3–12,
Table I).Under the given conditions,the ligands 2 and
4 afforded the best enantioselectivity. The reaction
was frequently carried out at an S:C ratio of 100; however,a
high S:C ratio of 10,000 has been demonstrated
to be feasible (Entry 8, Table I). In comparison with
ATH in azeotropic HCOOH-NEt 3 with or without
water, ATH in aqueous HCOONa is much faster
(Entries 3 and 4, Table I).This finding prompted us to
explore factors that might lead to these contrasting
results (65, 73). The clearest difference between the
two systems was found to be the solution pH.
Subsequently, the pH value was proved to be critical
to the reaction rate and enantioselectivity (see
Sections 3.1 and 3.2 of this paper). Indeed, efficient
ATH can be performed with HCOOH-NEt 3 in water,
provided the ratio of HCOOH:NEt 3 is controlled such
that the solution is close to pH neutral (Entries 5–8,
Table I).
Interestingly, while β-aminoalcohol ligands were
believed to be incompatible with formic acid as a
reductant for ATH of ketones (12, 20), the commercially
available simple β-aminoalcohol ligands 5–8
do catalyse the ATH of acetophenone by HCOONa or
HCOOH-NEt 3 in water (70). However, the reduction
rates and enantioselectivities were much lower than
those obtained with the diamine ligands (Entries
13–16, Table I) (70).
The Ru(II)-catalysed ATH has since been applied
to a wide range of aromatic ketones (Scheme II). The
reduction is easy to perform, affording the chiral
alcohols with high ee in a short reaction time for
most of the substrates at S:C ratios from 100:1 to
1000:1. While the substrate ketones are generally
water-insoluble, this does not appear to have a negative
effect on the reaction rates. The reduction of
most ketones proceeded significantly faster in water
than the same transformation in azeotropic HCOOH-
NEt 3 . For example, the reduction of p-methoxyacetophenone,
which is difficult under normal conditions,
gave a conversion of >99% and an ee of 95%
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