Once the optimal conditions were established, we applied
them to a set of a,b-unsaturated esters (Table 2). The reaction
outcome seemed to be affected by the substituent volume: while
benzyl crotonate (2) was reduced in 96% yield (entry 1),
benzyl cinnamate (4) was reduced to obtain 5 in 73% yield
(entry 2). Geminally disubstituted olefin such as dimethyl
itaconate (6) led to the corresponding product (7) in a very
good yield (84%) (entry 3). N-Phenyl maleidimide (8) which is
a cis-disubstituted olefin gave compound 9 in 75% yield
(entry 4). Even trisubstituted olefins gave the corresponding
reduction product in good yields (entries 5–7). Interestingly,
fluorocinnamate (14) was also dehalogenated in the same
reaction step to give benzyl 3-phenylpropanoate (5)
(entry 7).12 Finally, an unexpected result came out when we
tried to reduce the triple bond of the benzyl 2-propynyl
succinate 15 (entry 8): a clean and selective deprotection
of the propargyl ester group. After re-esterification with
diazomethane, benzyl methyl succinate (16) was obtained in
91% yield.
Although several mechanisms have been suggested for non-
metathetic reactions of ruthenium–carbene complexes,2c
participation of ruthenium hydride species seems to be the
key to understand not only the olefin reduction but also the
collateral reactions: dehydrosilylation, defluorination and
deprotection of the propargyl ester. Under the conditions
used (MW, 150 1C, 30 min.) formation of the ruthenium
hydride species can be expected during decomposition of
Grubb’s catalyst.13
At this point, we were able to achieve an efficient microwave-
assisted reduction of a,b-unsaturated esters using Et3SiH/
Grubbs’ catalyst combination, so we turned our attention to
the reduction of solid-supported olefins. Since immobilized
a,b-unsaturated esters can be obtained by olefin cross
metathesis,14–16 we decided to perform these reactions back
to back. Although it is possible to carry out a one-pot reaction,
we preferred a sequential process in order to remove the olefin
excess. Thus, an outstanding result was obtained when
immobilized pentenoic acid 17 was subjected to cross
metathesis with benzyl crotonate (2), followed by the
reduction to the saturated ester 18 (Table 3, entry 1). Release
from the solid support afforded the corresponding methyl ester
19 in very high yield for both, the reduction step and the whole
synthetic sequence (93%). A similar result was obtained for the
sequential process with immobilized acrylate 20, which was
reacted under cross metathesis conditions with 4-phenylbut-
1-ene (21) and then reduced to obtain solid-supported
phenylvalerate 22 in 91% yield for the reduction step
(entry 2). Cross metathesis of immobilized vinyl benzoate 24
with benzyl crotonate (2) followed by reduction gave the
saturated ester 25 in 53% yield (entry 3). Besides, we found
that solid-supported a,b-unsaturated amide also underwent
reduction under Et3SiH/Grubbs’ catalyst combination giving
the corresponding butyryl amide 28 in 85% yield (entry 4).
In summary, we have developed microwave-assisted
conditions for the ‘‘hydrogen-free’’ reduction of a,b-
unsaturated esters and amides employing a non-metathetic
behavior of Grubbs’ catalyst. In the homogeneous phase, the
saturated products were obtained in high to excellent yields. It is
interesting to note that benzyl ester moiety is stable to the
reaction conditions; whereas the propargylic ester group
present in 15 was cleaved using the same procedure. This
methodology allows a rapid reduction of the alkene moiety
without contamination from hard-to-remove hydrosilylation
by-products.9 Extrapolation to the solid-phase organic
synthesis was also very effective. A remarkable hint was the
consummation of the sequential cross metathesis/olefin
reduction, which allows a facile construction of sp3–sp3
carbon bonds. Further applications of this methodology
are in progress in our laboratory and will be reported in due
course.
Table
2 Non-immobilized olefin reduction under optimized
conditions employing Et3SiH/Grubbs’ catalysta
Entry Starting material
Product
(%)b
96
1
2
3
73
84
4
75
5
6
82
64
7
61
8
91c
Financial support from Consejo Nacional de Investiga-
ciones Cientı
´
ficas
y
Te
´
cnicas (CONICET), Agencia
fica y Tecnologica, Fundacion
´
a
Reagents and conditions: catalyst 1 (5 mol%), Et3SiH (5 equiv.),
b
Nacional de Promocio
´
n Cientı
´
´
DCM, microwave irradiation, 150 1C (300 W), 30 min. Isolated yield
after column flash chromatography. Reaction product was esterified
by treatment with diazomethane.
Prats, and Universidad Nacional de Rosario from Argentina,
is gratefully acknowledged. AAPP thanks CONICET for
fellowships.
c
c
1566 Chem. Commun., 2011, 47, 1565–1567
This journal is The Royal Society of Chemistry 2011