Concomitant monoreduction and hydrogenation of unsaturated cyclic imides to lactams catalyzed by ruthenium compounds

Article abstract of DOI:10.1002/anie.200462996

(Chemical Equation Presented) One for two: [Ru₄H ₆(p-cymene)₄]Cl₂ and [RuCl₂(p- cymene)]₂, [Ru], are efficient catalyst precursors for the selective transformation of cyclic imides into saturated lactams (see scheme). The catalytic systems operate with the same reagent (H₂) to perform two transformations, namely, monoreduction of the carbonyl groups and hydrogenation of C=C bonds, with the release only of water, which is the solvent of the reaction.

Full text of DOI:10.1002/anie.200462996

Angewandte
Chemie
Ruthenium-Catalyzed Reactions
Concomitant Monoreduction and Hydrogenation
of Unsaturated Cyclic Imides to Lactams
Catalyzed by Ruthenium Compounds**
Rimane Aoun, Jean-Luc Renaud, Pierre H. Dixneuf,
and Christian Bruneau*
Catalytic transformations of multifunctional molecules now
offer access to a variety of useful intermediates. However,
there are still some important unsolved problems. This is the
case of the transformation of cyclic imides into lactams
through selective monoreduction of one carbonyl group
which is still a challenge in organic synthesis. Strong reducing
reagents such as LiAlH have been used to perform complete
4
[
1]
reduction with formation of cyclic amines, and only in the
special case of highly substituted cyclic acylureas (hydantoins)
[
2]
was the monoreduction into ureas obtained. The mono-
reduction of phthalimides into isoindolinone derivatives has
been performed in moderate to good yields under acidic
conditions in the presence of stoichiometric amounts of
[
3]
[4]
reducing metals such as Sn or Zn. Their catalytic reduction
in the presence of hydrogen has been carried out with Raney
nickel as catalyst, but under drastic conditions (1808C,
[
5]
1
90 bar H ). In water, under hydrogen pressure at 1008C,
2
N-methylsuccinimide was transformed into 2-pyrrolidinone in
the presence of water-soluble ruthenium precatalysts such as
RuCl ·3H O, [RuCl (dmso) ], or [Ru(dmp)(H O) ](PF )
3
2
2
4
2
2
6 2
(
(
dmp = 2,9-dimethylphenanthroline), but in modest yields
< 28%).
[
6]
Herein we report that the ruthenium precatalysts [RuCl2-
(
p-cymene)] and [Ru H (p-cymene) ]Cl are efficient cata-
2
4
6
4
2
lyst precursors for the monoreduction of cyclic imides in
water under hydrogen pressure. Moreover, they make possi-
ble the concomitant monoreduction and hydrogenation of
unsaturated cyclic imides into saturated lactams (Scheme 1).
Scheme 1. [Ru]=[Ru H (p-cymene) ]Cl and [RuCl (p-cymene)] .
4
6
4
2
2
2
[*] Dr. R. Aoun, Dr. J.-L. Renaud, Prof. P. H. Dixneuf, Dr. C. Bruneau
Institut de Chimie de Rennes
UMR 6509: CNRS-Universitꢀ de Rennes
Organomꢀtalliques et Catalyse
Campus de Beaulieu-35042 Rennes Cedex (France)
Fax: (+33)2-2323-6939
E-mail: christian.bruneau@univ-rennes1.fr
[**] The authors thank ORIL Industrie for financial support.
Angew. Chem. Int. Ed. 2005, 44, 2021 –2023
DOI: 10.1002/anie.200462996
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2021

Communications
This represents a new example of a multifunctional catalytic
(Table 1, entry 4). The saturated imide 7 was also detected
as a minor reaction product. Furthermore, H NMR analyses
and chiral gas-chromatography studies showed that the
hydrogenation was diastereoselective and that the formed
product 5 resulted from a pure cis addition of hydrogen to a
formal junction C=C bond.
[
7]
1
system able to perform two chemical transformations
reduction of carbonyl groups and hydrogenation of double
(
and aromatic bonds) with the same reagent (H ) and with
2
atom economy, to release only water, which is the solvent of
the reaction.
The reaction of succinimide 1 (5 mmol) in distilled water
This ruthenium-based catalytic system tolerated the
presence of functional groups such as primary amines as it
performed the transformation of the 5-aminouracil 8 into the
novel 5-amino tetrahydropyrimidin-2-one 9 through selective
reduction of the acyl carbonyl group of the starting acylurea
structure. The example reported in Table 1,
[
8]
(
(
10 mL) in the presence of [Ru H (p-cymene) ]Cl
4 6 4 2
1 mol%) under hydrogen (60 bar) for 13 h led to its
complete and selective conversion into 2-pyrrolidinone 2,
which was isolated in 87% yield (Table 1, entry 1). No further
entry 6 revealed that the reduction of the
Table 1: Monoreduction/hydrogenation of cyclic imides in the presence of [Ru H (p-cymene) ]Cl and
4
6
4
2
[
a]
[
RuCl (p-cymene)] as catalyst precursors.
carbonyl group was more difficult to per-
form than the hydrogenation of the carbon–
carbon double bond of uracil 10, as after
complete conversion the tetrahydropyrimi-
din-2-one 11 was isolated in only 70% yield
together with only 30% of the saturated
hydantoin 12.
2
2
Entry
Substrate
Product
[Ru H (p-cymene) ]Cl
[RuCl (p-cymene)]
2 2
4
6
4
2
[
b]
t [h]
Isolated Yield [%]
t [h]
Conversion [%]
1
13
87
–
–
[
Ru H (p-cymene) ]Cl was prepared by
4 6 4 2
treatment of [RuCl (p-cymene)] in water at
2
2
[
8]
6
08C under 60 bar of hydrogen pressure,
2
3
4
13
22
24
86
3
100
100
thus under conditions very close to those of
the catalytic conditions described above.
The hypothesis of a common or closely
related intermediates that are active in
catalysis in both the previous catalytic
system and during the stoichiometric trans-
formation of [RuCl (p-cymene)] was eval-
97
15
2
2
7
2
6 (5)
4 (7)
uated. The hydrogenation of the cyclic
imides 3, 4, 6, 8, and 10 in water in the
[
c]
78 (5)
15
presence of [RuCl (p-cymene)]
(1–
2
2
2
mol%) as catalyst precursor at 908C
under hydrogen (60 bar; Table 1) took
place even more efficiently than with
5
6
24
23
66
13
24
100
[
Ru H (p-cymene) ]Cl as precatalyst to
4 6 4 2
give 2, 5, 7, 9, and 11. Indeed, with half the
amount of potentially active ruthenium
sites, complete conversions and transforma-
tions into lactams were reached within
shorter reaction times. For instance, the
complete conversion of the imide 10 into
the sole tetrahydropyrimidin-2-one 11 was
obtained within 24 h which indicates a more
efficient carbonyl-reduction reaction. Note
7
3
0 (11)
0 (12)
100 (11)
[
a] General conditions: imide (1 mmol), [Ru H (p-cymene)]Cl (1 mol%), [RuCl (p-cymene)] (1 mol%),
4 6 2 2 2
water (5–10 mL), hydrogen (60 bar), 908C. [b] Complete conversion. [c] Catalyst (2 mol%).
reduction into the amine was detected. Under similar
conditions, the unsaturated maleimide 3 quantitatively pro-
vided the same lactam 2 in 86% isolated yield, whereas the
unsaturated tetrahydrophtalimide 4 underwent complete
conversion into the bicyclic lactam 5 after 22 h of reaction
that it had already been shown that the binuclear system was
more active than the corresponding hydride cluster for the
simple hydrogenation of aromatic hydrocarbons.
With both catalysts, the hydrogenation of N-substituted
phthalimides and phthalic anhydride only led to the hydro-
genation of the aromatic ring. This shows that the presence of
the NH bond of the cyclic imides plays a crucial role in the
reduction of one carbonyl group.
[
9]
(
Table 1, entry 3). These reactions showed that the catalytic
system operating in water is able to perform the selective
monoreduction of one carbonyl group of a cyclic imide and
the hydrogenation of activated and nonactivated olefinic
bonds. The concomitant reduction and hydrogenation of
aromatic substrates was also attempted and phthalimide 6 was
converted into the aliphatic lactam 5, which was isolated in
A screening of the temperature and H pressure para-
2
meters in the presence of [RuCl (p-cymene)]2 as catalyst
2
precursor indicated that the hydrogenation of the aromatic
ring of phthalimide 6 took place even at low temperature
(508C) and low pressure (10 bar), whereas the reduction of
7
8% yield, after 24 h under similar catalytic conditions
2
022
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.angewandte.org
Angew. Chem. Int. Ed. 2005, 44, 2021 –2023

Angewandte
Chemie
the carbonyl group required high temperatures (Table 2). In
hydrogenation with molecular metal catalysts, the question of
the colloidal or nanoparticle nature relative to the molecular
[7] a) A. Ajamian, J. L. Gleason, Angew. Chem. 2004, 116, 3842;
Angew. Chem. Int. Ed. 2004, 43, 3754; b) D. E. Fogg, E. N.
dos Santos, Coord. Chem. Rev. 2004, 248, 2365.
[8] L. Plasseraud, G. Sꢀss-Fink, J. Organomet. Chem. 1997, 539, 163.
[
10,11]
nature of the active species is raised.
Mercury is known to
[
9] E. Garcia Fidalgo, L. Plasseraud, G. Sꢀss-Fink, J. Mol. Catal. A
998, 132, 5.
10] a) G. Sꢀss-Fink, M. Faure, T. R. Ward, Angew. Chem. 2002, 114,
05; Angew. Chem. Int. Ed. 2002, 41, 99; b) G. Sꢀss-Fink, B.
1
[
[
Table 2: Reaction of phthalimide 6 in the presence of [RuCl (p-cymene)]
2
2
[
a]
1
(
2 mol%).
Therrien, L. Vieille-Petit, M. Tschan, V. B. Romakh, T. R. Ward,
M. Dadras, G. Laurenczy, J. Organomet. Chem. 2004, 689, 1362.
11] J. A. Widegren, M. A. Bennett, R. G. Finke, J. Am. Chem. Soc.
P(H ) [bar]
T [8C]
t [h]
7/5
2
6
3
1
6
6
0
0
0
0
0
90
90
90
50
90
15
23
21
23
15
24:76
20:80
25:75
78:22
2003, 125, 10301.
[
b]
17:83
[
a] 6 (1 mmol), H O (5 mL), complete conversion of 6. [b] Reaction
2
performed in the presence of mercury.
poison heterogeneous catalysts by formation of an amalgam
[
11]
with metals. We have found that the transformation of 6
with a catalytic amount of [RuCl (p-cymene)] in the presence
2
2
of mercury under our most severe conditions (908C, 60 bar)
during 15 h led to quantitative conversion of the phthalimide
6
to form 7 and 5 in the ratio 17:83, which is very close to that
observed in the absence of mercury (Table 2). This result
tends to corroborate the involvement of molecular catalytic
species rather than colloids or nanoparticles in this type of
hydrogenation process under the temperature and hydrogen
pressure conditions used.
We have revealed a new catalytic activity of easy to
prepare or commercially available ruthenium complexes and
solved the problem of selective monoreduction of cyclic
imides into lactams. Moreover, these complexes generate
catalytic systems that are able to promote two catalytic
reactions in one pot: the hydrogenation of carbon–carbon
double bonds, including aromatic structures, and the mono-
reduction of cyclic imides. These catalytic systems might be
very helpful for selective reduction of imides and desymmet-
rization transformations.
Received: December 20, 2004
Published online: February 21, 2005
Keywords: hydrogenation · lactams · reduction · ruthenium
.
[
1] a) K. C. Schreiber, V. P. Fernandez, J. Org. Chem. 1961, 26, 1744;
b) H. Okamura, H. Shimizu, Y. Nakamura, T. Iwagawa, M.
Nakatani, Tetrahedron Lett. 2000, 41, 4147.
[
[
2] F. Marshall, J. Am. Chem. Soc. 1956, 78, 3696.
3] a) M. H. Norman, D. J. Minick, G. C. Rigdon, J. Med. Chem.
1
996, 39, 149; b) S. Cacchi, G. Fabrizi, L. Moro, Synlett 1998, 741.
4] a) S. Feng, C. A. Panetta, D. E. Graves, J. Org. Chem. 2001, 66,
12; b) P. S. Anderson, M. E. Christy, C. D. Colton, W. Halc-
zenco, G. S. Ponticelli, K. L. Shepard, J. Org. Chem. 1979, 44,
519.
5] H. Hennige, R. P. Kreher, M. Konrad, F. Jelitto, Chem. Ber. 1988,
21, 234.
6] D. E. Patton, R. S. Drago, J. Chem. Soc. Perkin Trans. 1 1993,
611.
[
6
1
[
[
1
1
Angew. Chem. Int. Ed. 2005, 44, 2021 –2023
www.angewandte.org
ꢀ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2023