DOI: 10.1002/cctc.201500006
Communications
Ruthenium-Catalyzed Highly Chemoselective
Hydrogenation of Aldehydes
Lucia Bonomo, Laurent Kermorvan, and Philippe Dupau*[a]
The use of a [(ethylenediamine)(dppe)Ru(OCOtBu)2] [dppe=
1,2-bis(diphenylphosphino)ethane] complex under base-free
conditions allowed highly efficient and selective hydrogenation
of aldehydes in the presence of ketones in addition to olefins.
Even in the case of highly sensitive 1,6-ketoaldehydes, the de-
sired ketoalcohols were obtained in high yields with 94–99%
overall selectivity at complete aldehyde conversion with a TON
up to 30000. The lack of requirement for strong basic co-cata-
lysts and polar protic solvents also allowed efficient and highly
chemoselective reduction of aldehydes bearing other function-
al groups, such as epoxides, carboxylic acids, esters, amides,
and nitriles emphasizing the potential synthetic utility of the
catalyst.
aldehydes in the presence of ketones, such a transformation
represents a step further in chemoselectivity. This could be re-
lated to the general requirement for a strongly basic co-cata-
lyst to achieve high catalytic efficiency, such conditions favor-
ing the aldol side reaction. In addition to this, if aldehydes are
known to be more reactive than ketones, some with only
a slight difference in bond energy (about 5 kcalmolÀ1), it is
a true obstacle to achieve high chemoselectivity results at
complete aldehyde conversion. Also, several homogeneous
catalysts, such as [Ir(H3)(PPh3)3], [RuCl2(PPh3)3], [Rh(cod)Cl]2/
TPPTS (cod=1,5-cyclooctadiene; TPPTS=tris(3-sulfophenyl)-
phosphine trisodium salt), developed earlier were reported to
exhibit some decent activity for the hydrogenation of alde-
hydes rather than ketones.[5] However, the hydrogenation reac-
tion in general had been scarcely reported for the selective re-
duction of aldehydes in the presence of ketones. Indeed,
Masson and co-workers[6] described some competitive experi-
ments using a heterogeneous Raney-nickel-type catalyst also
known for efficient C=C bond hydrogenation. Later, Casey and
co-workers[7] reported the use of Shvo-type ruthenium cata-
lysts for selective hydrogenation of benzaldehyde in the pres-
ence of acetophenone. Benzyl alcohol was obtained with high
chemoselectivity (up to >99%), which was achieved by using
relatively high ruthenium loadings (3–4 mol%) and performing
the hydrogenation reaction at incomplete aldehyde conver-
sion. More recently, Breit and co-workers[8] also described a few
examples of such chemoselective transformation by using an
in situ generated rhodium catalyst. Along with the use of addi-
tional carbon monoxide to reach the desired catalytic results
(0.2 mol% Rh loadings) starting from a metal carbonyl precur-
sor, this system also required some excess non-commercially
available supramolecular ligand (10 equiv. Rh).
The search for highly enantioselective chemical processes has
been the main driving force towards the development of new
synthetic catalytic methodologies for many years, probably re-
lated to the ever-growing number of optically pure drugs pro-
duced in the pharmaceutical industry.[1] Nevertheless, if aston-
ishingly high enantiocontrol was achieved for a large number
of chemical transformations, it was quite often done at the ex-
pense of process efficiency in terms of catalyst loadings and re-
action scope. Initially introduced and further developed as
a concept by Trost,[2] chemoselectivity was more recently
claimed by Baran and co-workers[3] to be the key for further
synthetic efficiency, especially to access highly complex mole-
cules. Discovery of new chemoselective transformations should
indeed allow some traditional retrosynthetic approaches to be
reconsidered and avoid some tedious protection/deprotection
sequences. New transformations should also be able to effi-
ciently meet some increasing industrial requirements related
to the environment with the potential to decrease the E-factor.
Research towards highly efficient chemoselective processes
has been nicely illustrated by recent developments in the re-
duction of carbonyl groups into alcohols. Noyori-type catalysts
are widely used for the hydrogenation of ketones in the pres-
ence of olefins, even in the case of achiral transformations,
thanks to their amazingly high catalytic activity.[4] Nevertheless,
such catalysts were never reported for selective reduction of
As a consequence, the use of stoichiometric amounts of haz-
ardous and waste-generating modified metal hydrides[9] still re-
mains the method of choice to perform selective reduction of
aldehyde in the presence of ketones as exemplified in the syn-
thesis of (+)-trienomycins A and F[10] and diterpenoid (À)-cya-
thin B2 antibiotics.[11] In some instances, such levels of chemo-
selectivity were also achieved by using non alumino or borohy-
dride-type waste-generating stoichiometric reducing re-
agents[12] or by slightly more environmentally friendly reducing
methods.[13]
[a] Dr. L. Bonomo, L. Kermorvan, Dr. P. Dupau
R&D Division
In previous studies, we developed some highly efficient
base-free chemoselective hydrogenation of aldehydes in the
presence of olefins by using [(diamine)(diphosphine)Ru-
(OCOR)2] complexes.[14] After screening for further functional
groups tolerance, we are now reporting the use of such ruthe-
nium complexes as efficient catalysts for the highly challenging
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