Hydroruthenation triggered catalytic conversion of dialdehydes and keto aldehydes to lactones

Article abstract of DOI:10.1039/b912850f

Lactonization of dialdehydes and keto aldehydes was effectively catalyzed by RuHCl(CO)(PPh₃)₃. A cascade lactonization sequence accompanied by cross-coupling with enones was also attained.

Full text of DOI:10.1039/b912850f

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Hydroruthenation triggered catalytic conversion of dialdehydes
and keto aldehydes to lactonesw
Sohei Omura, Takahide Fukuyama, Yuji Murakami, Hiromi Okamoto and Ilhyong Ryu*
Received (in Cambridge, UK) 30th June 2009, Accepted 6th October 2009
First published as an Advance Article on the web 19th October 2009
DOI: 10.1039/b912850f
Lactonization of dialdehydes and keto aldehydes was effectively
catalyzed by RuHCl(CO)(PPh3)3. A cascade lactonization
sequence accompanied by cross-coupling with enones was also
attained.
Lactones are important frameworks found in a variety of
biologically active compounds including antibiotics, antifungal
compounds, pheromones, lignans, and flavor components.1
ð1Þ
Using phthalaldehyde (1a) as a model compound, we surveyed
a variety of ruthenium hydride complexes (Table 1). When a
toluene solution of 1a was treated with RuHCl(CO)(PPh3)3
(0.5 mol%) at 90 1C for 5 h, 1-(3H)-isobenzofuranone (2a), the
envisaged lactone, was obtained in 94% yield (entry 1). The
yield of 2a became nearly quantitative when 1 mol% of
RuHCl(CO)(PPh3)3 was used (entry 2). Other ruthenium
hydride complexes, such as RuH2(PPh3)4, RuH2(CO)(PPh3)3,
and RuH(NO)(PPh3)3, were found to be less effective in giving
2a (entries 3–5).
Typically, lactones are prepared by the dehydration reaction
of o-hydroxy carboxylic acids with acid catalyst or stoichiometric
coupling reagents such as DCC/DMAP, Mukaiyama–Corey’s
reagent and Yamaguchi’s reagent.2 On the other hand, the
direct conversion of dialdehydes to lactones represents a
different approach, which is generally termed as an intra-
molecular Tishchenko reaction.2,3 Three decades ago, Yamamoto
and coworkers reported that group 8 metal hydrides, such as
RuH2(PPh3)4, affect Tishchenko dimerization of aldehydes.4
Inspired by this work, Grigg and coworkers subsequently
attained the intramolecular version of the Tishchenko reaction,
in which RhH(CO)(PPh3)3 was used for the conversion
of dialdehydes to lactones.5 Later, the Bosnich group
demonstrated the utility of cationic rhodium diphosphine
complexes for the dialdehyde–lactone conversion, in which
acylrhodium hydride, formed in situ by oxidative addition of
the starting aldehydes, plays a key role.6 With a few recent
exceptions,7 the Tishchenko type lactonization reactions have
been pursued in a variety of ways other than using transition
metal hydrides.8 During the course of our study on the
development of novel catalytic transformations we found that
a ruthenium hydride complex, RuHCl(CO)(PPh3)3, can serve
as an excellent catalyst for a variety of atom-economical
transformations with aldehydes.9 This led us to consider the
potential of ruthenium hydrides for an hydroruthenation–
intramolecular alkoxy-ruthenation sequence (eqn (1)), which
would lead to an intramolecular Tishchenko type lactonization
reaction. Herein we report that lactonizations of both
dialdehydes and keto aldehydes were affected by using
RuHCl(CO)(PPh3)3 as the catalyst. We also report that in
the presence of enones cascade lactonization accompanied by
cross-coupling with enones is possible.
We then examined the generality of the reaction, using a
variety of dialdehydes 1a–1d, 1f–1h, the results for which are
summarized in Table 2. The reaction of 2,3-naphthalene
dicarboxaldehyde (1b) gave lactone 2b in good yield (entry 2).
The reaction also worked well for the synthesis of the seven-
membered ring lactone 2c (entry 3). In the case of
unsymmetrical dialdehyde 1d, no differentiation of the
conjugated and unconjugated formyl groups was observed,
thereby giving two products, 2d and 2d0, as a 1.1 : 1 mixture
(entry 4). Aliphatic dialdehydes 1f, 1g, and 1h also worked
well to give the corresponding five to seven membered ring
lactones 2f–2h, the yields are moderate to good (entries 6–8).10
The catalytic lactonization reaction was also effective for
Table 1 Survey of ruthenium hydride catalystsa
Entry
Ru–H catalyst
mol%
2a (%)b
1a (%)b
1
2
3
4
5
RuHCl(CO)(PPh3)3
RuHCl(CO)(PPh3)3
RuH2(PPh3)4
RuH2(CO)(PPh3)3
RuH(NO)(PPh3)3
0.5
1.0
0.5
0.5
0.5
94
99
5
1
19
6
trace
95
95
Department of Chemistry, Graduate School of Science,
Osaka Prefecture University, Sakai, Osaka 599-8531, Japan.
E-mail: ryu@c.s.osakafu-u.ac.jp; Fax: +82-72-254-9695;
Tel: +82-72-254-9695
w Electronic supplementary information (ESI) available: Experimental
details. See DOI: 10.1039/b912850f
76
a
Conditions: 1a (0.25 mmol), toluene (1.5 mL), catalyst (0.5 or 1 mol%),
b
90 1C, 5 h. Yield based on 1H NMR analysis using Cl2CHCHCl2 as an
internal standard.
ꢀc
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Chem. Commun., 2009, 6741–6743 | 6741

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Table 2 Ruthenium hydride catalyzed lactonization of dialdehydes and keto aldehydes
Entry
Aldehydes 1
Conditions
Lactones 2 and 4
Yield (%)a
99
1 mol%
0.17 M, 90 1C, 5 h
1
2 mol%
0.17 M, 110 1C, 5 h
2
3
94
97
1 mol%
0.1 M, 110 1C, 5 h
5 mol%
0.1 M, 90 1C, 5 h
4
99 (1.1 : 1)b
5 mol%
0.1 M, 120 1C, 40 h
5
6
7
91
1 mol%
0.1 M, 110 1C, 5 h
40c
70c
49c
5 mol%
0.1 M, 90 1C, 10 h
10 mol%
0.05 M, 110 1C, 20 h
8
9
10 mol%
0.1 M, 120 1C, 40 h
32
55
10 mol%
0.25 M, 90 1C, 5 h
ethyl vinyl ketone
(3a) 5 equiv.
10
11
1a
1a
79 (dr = 2 : 1)b
10 mol%
45 (dr = 4.4 : 1)b
0.25 M, 90 1C, 5 h
cyclohexenone
(3b) 10 equiv.
10 mol%
0.25 M, 90 1C, 5 h
3a 5 equiv.
12
13
1b
1b
1c
43 (dr = 1.9 : 1)b
60 (dr = 3.6 : 1)b
44 (dr = 2.8 : 1)b
10 mol%
0.25 M, 90 1C, 5 h
3b 5 equiv.
10 mol%
0.25 M, 90 1C, 5 h
3b 5 equiv.
14
a
b
c
Isolated yield after flash chromatography on SiO2. The ratio was determined by 1H NMR. Yield based on 1H NMR analysis using
Cl2CHCHCl2 as an internal standard.
keto aldehyde 1e, which gave lactone 2e having a methyl group at
the oxycarbon in 91% yield (entry 5). In the case of aliphatic keto
aldehyde 1i, lactone 2i was obtained in rather low yield (entry 9),
due to a competing Tishchenko reaction leading to ester 2i0.
A likely reaction mechanism is proposed with an example of
a keto aldehyde, 1e (Scheme 1). The hydroruthenation gives
two types of acetal-type Ru complex, B and D. Ru complex D,
which arises from hydroruthenation to an aldehyde group,
ꢀc
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is being performed to extend the hydroruthenation-based
methodology for atom-economical cyclization chemistry.
I.R. and T.F. acknowledge a Grant-in-Aid for Scientific
Research from MEXT Japan and JSPS.
Notes and references
1 (a) S. S. C. Koch and A. R. Chamberlin, Stud. Nat. Prod. Chem.,
1995, 16, 687; (b) Y. Wache, M. Aguedo, J.-M. Nicaud and
J.-M. Belin, Appl. Microbiol. Biotechnol., 2003, 61, 393;
(c) M. I. Konaklieva and B. J. Plotkin, Mini-Rev. Mrd. Chem.,
2005, 5, 73.
Scheme 1 Proposed mechanism for lactonization of the keto aldehyde.
2 Synthesis of lactones and lactams, ed. M. A. Ogliaruso, J. F. Wolfe,
P. Saul and R. Zvi, John Wiley & Sons, Chichester, 1993.
3 For a review on the Tishchenko reaction, see: O. P. Tormakanges
and A. M. P. Koshinen, Recent Res. Dev. Org. Chem., 2002, 5, 225.
4 RuH2(PPh3)4: (a) H. Horino, T. Ito and A. Yamamoto, Chem.
Lett., 1978, 17; (b) T. Ito, H. Horino, Y. Koshiro and
A. Yamamoto, Bull. Chem. Soc. Jpn., 1982, 55, 504; (c) see also:
S. I. Murahashi, T. Naota, K. Ito, Y. Maeda and H. Taki, J. Org.
Chem., 1987, 52, 4319.
5 RhH(CO)(PPh3)3: (a) R. Grigg, T. R. B. Mitchell and
S. Sutthivaiyakit, Tetrahedron, 1981, 37, 4313 RhH(PPh3)4:
(b) M. Massoui, D. Beaupere, L. Nadjo and R. Uzan,
J. Organomet. Chem., 1983, 259, 345 HM (Cr, Mo, W):
(c) T. Fuchikami, Y. Ubukata and Y. Tanaka, Tetrahedron Lett.,
1991, 32, 1199.
6 Rh(diphosphine)(CO)2
B. Bosnich, Organometallics, 1990, 9, 566.
+
: S. H. Bergens, D. P. Fairlie and
7 For a Rh catalyzed enantioselective intramolecular Tishchenko
reaction, see: (a) Z. Shen, H. A. Khan and V. M. Dong, J. Am.
Chem. Soc., 2008, 130, 2916. Ir catalyzed reaction; (b) T. Suzuki,
T. Yamada, K. Watanabe and T. Katoh, Bioorg. Med. Chem.
Lett., 2005, 15, 2583.
Scheme 2 Cascade reaction leading to the substituted lactone.
cannot undergo b-hydride elimination, hence back to A via 1e.
Eventually, the Ru-complex B arising from the hydroruthenation
of a ketone carbonyl undergoes cyclization and b-elimination
to give lactone 2e.
8 For selected examples, see: aluminium catalyzed reaction:
(a) T. Ooi, T. Miura, K. Takaya and K. Maruoka, Tetrahedron
Lett., 1999, 40, 7695. Alkaline earth metal catalyzed reaction;
(b) T. Seki and H. Hattori, Chem. Commun., 2001, 2510;
(c) T. Seki, H. Tachikawa, T. Yamada and H. Hattori, J. Catal.,
2003, 217, 117; (d) M. R. Crimmin, A. G. M. Barrett, M. S. Hill
and P. A. Procopiou, Org. Lett., 2007, 9, 331. Sm-amide catalyzed
reaction: (e) Y. Chen, Z. Zhu, J. Zhang, J. Shen and X. Zhou,
J. Organomet. Chem., 2005, 690, 3783. N-Heterocyclic carbene
catalyzed reaction; (f) A. Chan and K. A. Scheidt, J. Am. Chem.
Soc., 2006, 128, 4558. SmI2 i-PrSH; (g) J. L. Hsu, C.- T. Chen and
J.- M. Fang, Org. Lett., 1999, 1, 1989. SmI2(OBu-t); (h) J. Uenishi,
S. Masuda and S. Wakabayashi, Tetrahedron Lett., 1991, 32, 5097.
Lanthanoide (La, Nd); (i) S. Onozawa, T. Sakakura, M. Tanaka
and S. Motoo, Tetrahedron, 1996, 52, 4291; (j) G. L. Lange and
M. G. Organ, Synlett, 1991, 665.
9 For our recent work on RuHCl(CO)(PPh3)3 catalyzed transformation,
see: (a) S. Omura, T. Fukuyama, J. Horiguchi, Y. Murakami and
I. Ryu, J. Am. Chem. Soc., 2008, 130, 14094; (b) T. Fukuyama, T. Doi,
S. Minamino, S. Omura and I. Ryu, Angew. Chem. Int. Ed., 2007, 46,
5559; (c) T. Doi, T. Fukuyama, S. Minamino, G. Husson and I. Ryu,
Chem. Commun., 2006, 1875; (d) T. Doi, T. Fukuyama, S. Minamino
and I. Ryu, Synlett, 2006, 3013; (e) T. Doi, T. Fukuyama,
J. Horiguchi, T. Okamura and I. Ryu, Synlett, 2006, 721.
10 The reaction of heptanedial gave a mixture of the envisaged
8-membered lactone (7%) and dimeric cyclic esters (13%).
11 In Bosnich’s Rh catalyzed lactonization,11 it was proposed that the
first event is the oxidative addition of an aldehyde to a rhodium
complex to generate an acylrhodium hydride complex. Thus, two
reaction mechanisms were proposed starting from the complex: (i)
intramolecular acylrhodation and reductive elimination, and (ii)
hydrorhodation and reductive elimination.
12 For examples of catalytic transformations based on ruthenium
enolates, see: (a) I. Matsuda, M. Shibata and S. Sato,
J. Organomet. Chem., 1988, 340, C5; (b) S.-I. Murahashi,
T. Naota, H. Taki, M. Mizuno, H. Takaya, S. Komiya,
Y. Mizuho, N. Oyasato, M. Hiraoka, M. Hirano and A. Fukuoka,
J. Am. Chem. Soc., 1995, 117, 12436; (c) B. M. Trost and
A. B. Pinkerton, J. Am. Chem. Soc., 2000, 122, 8081; (d) S. Chang,
Y. Na, E. Choi and S. Kim, Org. Lett., 2001, 3, 2089.
As we were curious of the formation and behavior of
alkoxyruthenium intermediate F, which would be expected
to form via a Ru-aldol reaction of ethyl vinyl ketone (3a) and
dialdehyde 1a (Scheme 2), we examined the RuH-catalyzed
cross-coupling reaction of ethyl vinyl ketone (3a) with
dialdehyde 1a in detail. To suppress the formation of lactone
2a, we used enones in excess amounts. Thus, treatment of five
molar excess amounts of 3a with 1a in the presence of
10 mol% of RuHCl(CO)(PPh3)3 at 90 1C for 5 h gave the
envisaged cross-coupling product 3-(1-methyl-2-oxobutyl)-
1(3H)-isobenzofuranone (4a) in 79% yield (Table 2, entry
10). The cross-coupling reaction of 1a with 2-cyclohexenone
(3b) gave the corresponding coupling product 4b in 45% yield
(entry 11). In a similar procedure keto lactones 4c–4e were
obtained (entries 12–14). A proposed reaction mechanism for
this cascade reaction is also shown in Scheme 2.11 Thus,
nucleophilic attack of the ruthenium enolate complex12 to
one formyl group of 1a would give an alkoxyruthenium
complex F, which is analogous to A, then undergoes nucleophilic
addition to give G. The subsequent b-hydride elimination of G
would give keto lactone 4a.
In summary, we have reported that a ruthenium hydride
complex, RuHCl(CO)(PPh3)3, is an efficient catalyst for
lactonization of both aromatic and aliphatic dialdehydes.
The ruthenium hydride also catalyzed lactonization of keto
aldehydes. Cross-coupling reaction of dialdehydes with enones,
followed by lactonization was also attained. The intramolecular
addition of alkoxy-ruthenium complex to a carbonyl group is
considered to be a key step in the lactonization. Ongoing work
ꢀc
This journal is The Royal Society of Chemistry 2009
Chem. Commun., 2009, 6741–6743 | 6743