Ruthenium hydride-catalyzed addition of aldehydes to dienes leading to β,γ-unsaturated ketones

Article abstract of DOI:10.1021/ja806929y

An efficient cross-addition reaction of dienes with aldehydes was developped by using RuHCl(CO)(PPh₃)₃ as a catalyst to give a wide variety of β,γ-unsaturated ketones, where a π-allylruthenium species, derived from hydroruthenation of diene, may be involved as a key intermediate. Copyright

Full text of DOI:10.1021/ja806929y

Published on Web 10/08/2008
Ruthenium Hydride-Catalyzed Addition of Aldehydes to Dienes Leading to
ꢀ,γ-Unsaturated Ketones
Sohei Omura, Takahide Fukuyama, Jiro Horiguchi, Yuji Murakami, and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture UniVersity, Sakai, Osaka 599-8531, Japan
Received June 23, 2008; Revised Manuscript Received September 2, 2008; E-mail: ryu@c.s.osakafu-u.ac.jp
Table 1. Survey of RuH Catalystsa
Transition metal hydrides are involved in a variety of catalytic
transformations, and hydrometalation of such species to unsaturated
bonds provides intermediates having metal-carbon or heteroatom
bonds.1 Ruthenium hydride catalysts have played a large role in
these important transformations.2,3 We recently reported that the
regioselective addition of aldehydes to unsaturated ketones leading
entry
1a (equiv)
catalyst (mol%)
yield of 3a (%)b
to 1,3-diketones can be effectively catalyzed by RuHCl(CO)(PPh3)3
(eq 1).4 If a similarly regioselective hydroacylation takes place in
the reaction between conjugate dienes and aldehydes, ꢀ,γ-unsatur-
ated ketones would be formed (eq 2). A decade ago, employing
Ru(cod)(cot)PPh3 as a catalyst, Kondo, Mitsudo and co-workers5
reported cross-condensation of conjugate dienes and aromatic
aldehydes. Albeit pioneering efforts, their system suffers a narrow
scope, including unavailability of aliphatic aldehydes and harsh
reaction conditions with the use of dienes as a solvent. Considering
the importance of this transformation and relying on the potential
of ruthenium hydride complexes, we embarked on a study to explore
an efficient catalytic system on a synthetically useful level. Herein
we report that ruthenium hydride, RuHCl(CO)(PPh3)3,6 can serve
as an efficient catalyst, providing a general method for the synthesis
of of ꢀ,γ-unsaturated ketones from 1,3-dienes and aldehydes.
1
2
3
4
5
2
2
4
4
4
RuHCl(CO)(PPh3)3 (5)
RuHCl(CO)(PPh3)3 (10)
RuHCl(CO)(PPh3)3 (5)
RuH2(CO)(PPh3)3 (5)
RuHCl(PPh3)3 (5)
65
92
95
11
3
a Conditions: 1a (2 or 4 mmol), 2a (1 mmol), Ru catalyst (5 or 10
mol%), toluene (6 mL). Reaction was carried out in a screw capped test
tube. b GC yields using hexadecane as an internal standard.
Scheme 1. Potential Mechanism
Using the reaction of isoprene (1a) and benzaldehyde (2a) as a
model (Table 1), we surveyed ruthenium hydride catalysts. We were
pleased to find that treatment of a toluene solution of 1a and 2a
with RuHCl(CO)(PPh3)3 (5 mol %) at 90 °C for 24 h gave the
desired cross-addition product, 2,3-dimethyl-1-phenyl-3-buten-1-
one (3a) in 95% yield (entry 3). Other catalysts, such as
RuH2(CO)(PPh3)3 and RuHCl(PPh3)3, gave a smaller amount of
the desired product 3a (entries 4 and 5).
Table 2 illustrates the wide generality and substrate scope of
this transformation. Aryl aldehydes, such as o- and p-tolualdehydes,
gave good yields of ꢀ,γ-unsaturated ketones 3b and 3c, respectively
(entries 2 and 3). Similarly, o-, m-, and p-methoxybenzaldehydes
(2d-2f) gave the corresponding ketones 3d-3f in good yields
(entries 4-6). p-Fluorobenzaldehyde (2g) also reacted with 1a to
give 3g (entry 7). The reaction was effective for heteroaromatic
aldehydes such as 2h (entry 8) and aliphatic and R,ꢀ-unsaturated
aldehydes 2i, 2j, and 2k (entries 9-11). The reaction between 2g
and myrcene (1b), having one more double bond in the molecule,
gave ketone 3l in 53% yield (entry 12). Since the ruthenium hydride
catalyst employed can affect double bond isomerization,4,6a,b,7 we
tested nonconjugate diene 1c, for which double bond migration
would be followed by a cross-coupling reaction. Gratifyingly, 3m
was obtained in good yield via the envisaged alkene-isomerization/
dehydrogenative carbonyl addition sequence (entry 13). In the
reaction of trans-1,3-pentadiene (1d(E)) with 2a, R,ꢀ-unsaturated
ketone 3n was obtained as an E/Z mixture with a ratio of 27/73
(entry 14). Our RuH catalyst system also allows cis isomer 1d(Z)
to react with 2a to give 3n (entry 15).8 The reaction of 4-methyl-
1,3-pentadiene (1e) with 2a gave ketone 3o in 80% yield as a single
product (entry 16). In the case of dialdehyde 2l, cascade-type cross-
condensation took place to give lactone 3p albeit in moderate yield.
A possible mechanism for the present ruthenium hydride
catalyzed reaction is illustrated by the reaction of 1a with 2a in
Scheme 1. Addition of a ruthenium hydride to 1a gives π-allyl-
ruthenium complex A, as confirmed by 1H NMR spectroscopy.9,10
No evidence for regioisomeric B was found in the NMR study,
which may be due to steric considerations. The resulting complex
A would then undergo reaction with aldehyde 2a via a six-
membered transition state so as to place the bulky Ru-portion of
the catalyst at the less hindered methylene carbon. The resulting
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14094 J. AM. CHEM. SOC. 2008, 130, 14094–14095
10.1021/ja806929y CCC: $40.75
2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Synthesis of ꢀ,γ-Unsaturated Ketones by a Ru-H
formed π-allylruthenium intermediate D to more stable Ru-complex
E.11 In a preceding study,5 however, Kondo et al. proposed a
mechanism involving oxidative addition of benzaldehyde to Ru to
form a benzoyl(hydride)ruthenium complex,12 which undergoes the
consecutive hydroruthenation of dienes and reductive elimination.
To determine whether their mechanism is operative in our RuH
system, we carried out a crossover experiment using a mixture of
PhCDO (2a-d) and p-FC6H4CHO (2g) with isoprene 1a. As the
result, we observed nearly equal deuterium scrambling between
products 3a-d and 3g-d. This result demonstrated that the hydrogen
and acyl units that add to the diene do come from different
molecules of aldehydes.13
Catalyzed Cross-Coupling Reaction of Dienes with Aldehydesa
In summary, we have developed an efficient cross-addition
reaction catalyzed by RuHCl(CO)(PPh3)3, which provides entry to
a wide variety of ꢀ,γ-unsaturated ketones starting from the
corresponding aldehydes and dienes. The detailed mechanism of
this reaction as well as further extension of this chemistry is
currently under investigation in this laboratory.
Acknowledgment. We thank JSPS and MEXT, Japan for
financial support of this work and Prof. M. J. Krische for sharing
unpublished results.
Supporting Information Available: Experimental procedure, spec-
trum data of all products, NMR study. This material is available free
of charge via Internet at http://pubs.acs.org.
References
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Org. Chem. 2006, 71, 4255. (b) Krompiec, S.; Kuznik, N.; Urbala, M.;
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He, R. J. Mol. Catal. A: Chem. 2006, 256, 17. (d) Michalak, M.; Wicha,
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(5) Kondo, T.; Hiraishi, N.; Morisaki, Y.; Wada, K.; Watanabe, Y.; Mitsudo,
T. Organometallics 1998, 17, 2131.
(6) For our previous work on the use of RuHCl(CO)(PPh3)3, see: (a) Doi, T.;
Fukuyama, T.; Minamino, S.; Husson, G.; Ryu, I. Chem. Commun. 2006,
1875. (b) Doi, T.; Fukuyama, T.; Horiguchi, J.; Okamura, T.; Ryu, I. Synlett
2006, 721. (c) Doi, T.; Fukuyama, T.; Minamino, S.; Ryu, I. Synlett 2006,
3013.
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double bonds: (a) Wakamatsu, H.; Nishida, M.; Adachi, N.; Mori, M. J.
Org. Chem. 2000, 65, 3966. (b) Krompiec, S.; Pigulla, M.; Szczepankiewicz,
W.; Bieg, T.; Kuznik, N.; Leszczynska-Sejda, K.; Kubicki, M.; Borowiak,
T. Tetrahedron Lett. 2001, 42, 7095. (c) Kuznik, N.; Krompiec, S.; Bieg,
T.; Baj, S.; Skutil, K.; Chrobok, A. J. Organomet. Chem. 2003, 665, 167.
(8) In contrast, the Ru(cod)(cot)-PPh3 system failed to react with 1d(Z); see ref 5.
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(10) For details, see Supporting Information.
(11) For similar isomerization of π-allylruthenium complexes, see ref 9b.
(12) In our experiment, no change of chemical shift of carbonyl carbon was
observed by NMR analysis when the Ru-H complex was treated with
benzaldehyde.
(13) Concurrent with submission of our work, an aligned study was disclosed
by Krische: Shibahara, F.; Bower, J. F.; Krische, M. J. J. Am. Chem. Soc.
2008, 130, in press (http://dx.doi.org/10.1021/ja805356j). We thank
Reviewer 1 for proposing this crossover experiment.
a Conditions: 1 (4 equiv, 2 equiv for entries 4, 5, 6, 12, and 13), 2
(0.5 or 1 mmol), RuHCl(CO)(PPh3)3 (5 mol%), toluene (3 or 6 mL), 90
°C, 24 h. b Isolated yield by chromatography on SiO2. c With 20 mol%
of catalyst. d With 10 mol% catalyst. e NMR yield. f With 5 equiv of 1a.
Isobenzofuranone was obtained in 32% yield.
complex C would then undergo a ꢀ-hydride elimination to give 3a
with liberation of ruthenium hydride. The formation of products
3n and 3o in the case of 1,3-pentadiene (1d (E,Z)) and 4-methyl-
1,3-pentadiene (1e) (Table 2, entries 14, 15, and 16) may be
rationalized by a similar pathway including isomerization of initially
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