Table 4 Optimisation studies using Ru pre-catalyst 1 and para-
fluorobenzoic acid methyl ester 9a
that have been shown to be active catalysts for a range of
aromatic esters. Both the catalysts and the method for generating
them should prove useful for those interested in
applying Noyori-type catalysts. Secondly, we have identified a
simple tridentate phosphine–diamine system that gives a catalyst
(1 in Scheme 1) that gives competitive levels of activity and
enables a range of esters to be reduced at reasonably low catalyst
loadings and at near ambient temperatures in the presence
of base.
The authors would like to thank the EPSRC for funding this
project. The authors also thank Washington and Lee University
for a Lenfest grant (MBF) and R. E. Lee Research Fellowships
(SCE, MTK). We also thank Scott Phillips (MLC group PhD
(2011) who donated some of the catalysts, and acknowledge all
the technical staff in the School of Chemistry for their hard
work.
Temperature
Entry Base : catalyst Time (h) (°C)
Catalyst
(%)
Product
(%)
1
2
3
4
5
6
7
8
9
10
50
50
50
50
30
30
30
50
50
50
16
16
16
16
16
16
16
16
64
100
50
50
50
50
50
50
100
30
30
30
0.4
0.3
0.2
0.1
0.5
0.3
0.3
0.5
0.5
0.5
>99
>99
>99
0
93
0
0
5
69
>99
a Unless otherwise stated, the reactions were carried out using 0.5 mol%
Ru precatalyst 1, at an initial pressure of 50 bar using 0.4 mmol of
distilled para-fluorobenzoic acid methyl ester in 3 ml of Me-THF.
of the St Andrews P,N,N systems in asymmetric ketone hydro-
genation5 is a tolerance of heterocycles that can have an inhibi-
tory effect on Ru catalysts, but clearly these benefits are not
transferred to ester hydrogenation catalysis. Two reactions were
set up in which the hydrogenation of ester 9 was carried out
(50 °C, 50 bar H2, 0.5% cat, 25% base) in the presence of
20 mol% of either ester 17 or 2-pyridyl-CH2OH. The reactions
only gave 23 and 9% conversions respectively compared to full
conversion without these additives. This is therefore consistent
with the product acting as an inhibitor.
Notes and references
§Screening experiments show that ethyl-6-methyl-pyridyl-3-carboxylate
and 4-pyridyl carboxylic acid ethyl ester (ethyl isonicotinate) were also
hydrogenated by catalyst 7 at 100 °C with complete conversion in
25 hours at S/C of 200 (as detectable by GCMS and H NMR); this is
also consistent with inhibition by an N,O chelate as opposed to a general
intolerance of pyridyl groups or ortho-substitution.
1
1 (a) S. Nishimura, Handbook of Heterogeneous Catalytic Hydrogenation
for Organic Synthesis, John Wiley and Sons, New York, 2001, p. 392;
(b) A. B. Hungria, R. Raja, S. D. Adams, B. Captain, J. Meurig Thomas,
P. A. Midgley, V. Golovko and B. F. G. Johnson, Angew. Chem., Int. Ed.,
2006, 45, 4782–4785 and ref. therein.
While our efforts were mainly directed towards the hydrogen-
ation of aromatic esters, the hydrogenation of the alkyl ester,
ethyl 3-phenylpropionate could also be accomplished with full
conversion (50 °C, 50 bar H2, 0.5% cat 1, 25% base). However a
few preliminary experiments using more highly substituted esters
were not successful. This, together with the observations in
Table 3, suggests that ester hydrogenation can be rather substrate
specific and a full evaluation of substrate scope and relative reac-
tivity using the arsenal of catalysts now available would be a
useful topic of research. A few studies aimed at establishing the
reactivity of catalyst 1 (Table 4) show that this catalyst works
well at 50 °C and a S/C of 500 under non-optimised conditions.
In a separate experiment, catalyst 1 was found to give 74% con-
version of methyl benzoate to benzyl alcohol at S/C of 200 at
50 °C in 60 min, thus suggesting the reactions in Table 4 are
likely to be complete in significantly shorter reaction times. It is
also noteworthy that the catalyst can still fully reduce ester 9 at
temperatures as low as 30 °C, albeit with impractically long reac-
tion times. These results show that in terms of the promoting the
individual steps of the catalytic cycle, the tridentate systems
operate at amongst the lowest temperatures examined in ester
hydrogenation and in quite a contrast to the temperatures of
100–250 °C commonly employed in early studies. However,
neither very low catalyst loadings below S/C 500 or lower base/
catalysts ratios are possible under these mild conditions. Thus,
either an improvement in catalyst or reaction protocol or an
engineering solution such as continuous flow operation would be
needed to be operable at large scale.
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In summary, this paper reports on a convenient method for
generating hydrogenation catalysts of type [RuCl2(P^P)(N^N)]
Dalton Trans.
This journal is © The Royal Society of Chemistry 2012