Diastereoselective construction of trans-fused octalone framework via ruthenium-porphyrin-catalyzed cycloaddition

Article abstract of DOI:10.1021/ol500625r

Lewis acid catalyzed cycloaddition of cyclohexenone and butadiene affords trans-fused octalone with high regio- and diastereoselectivity. The use of the ruthenium porphyrin complex as the Lewis acid catalyst is key to the reaction. The cycloaddition proce

Full text of DOI:10.1021/ol500625r

Letter
pubs.acs.org/OrgLett
Diastereoselective Construction of Trans-Fused Octalone Framework
via Ruthenium-Porphyrin-Catalyzed Cycloaddition
Takuma Terada,† Takuya Kurahashi,*,†,‡ and Seijiro Matsubara*,†
†Department of Material Chemistry, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan
‡JST, ACT-C, 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan
S
* Supporting Information
ABSTRACT: Lewis acid catalyzed cycloaddition of cyclo-
hexenone and butadiene affords trans-fused octalone with high
regio- and diastereoselectivity. The use of the ruthenium
porphyrin complex as the Lewis acid catalyst is key to the
reaction. The cycloaddition proceeds in toluene with 1 mol %
of the ruthenium catalyst at 25 °C.
ctalones are among the most versatile building blocks for
the synthesis of various natural products such as
polycyclic sesquiterpenes and triterpenes. The [4 + 2]
cycloaddition of cyclohexenones with butadienes, namely, the
Diels−Alder reaction, would be one of the most straightforward
synthetic routes to octalones with a cis-fused framework
(Scheme 1a). This reaction appears to be simple and facile;
complexes show Lewis acidity toward carbonyl compounds
and thus efficiently catalyze Diels−Alder-type reactions. To test
the hypothesis, we examined the cycloadditions of carbonyl
compounds with carbon−carbon unsaturated compounds12
and found that ruthenium porphyrin complex [Ru(TBPP)-
(CO)]SbF6 (TBPP: meso-tetrakis(4-tert-butylphenyl)por-
phyrinate, Figure 1) catalyzed the [4 + 2] cycloaddition of
O
Scheme 1. Cycloaddition To Afford Octalone
however, as a matter of fact it is rather difficult to accomplish
due to the low reactivity as a dienophile. Hence, the
development of efficient catalysts for the reaction remains a
research topic of great interest.1 Efforts have also been devoted
to preparing octalones with a trans-fused framework by
cycloaddition.2,3 Herein, we report that the intermolecular
reaction of cyclohexenones with 1,3-butadienes affords trans-
fused octalones in a single step (Scheme 1b); ruthenium
porphyrin was found to catalyze the [4 + 2] cycloaddition and
isomerization at ambient temperature.4−7
Porphyrins have emerged as useful ligands for transition-
metal catalysts in organic synthesis in cases where the use of
other ligands is infeasible.8,9 Recently, we developed the iron-
porphyrin-catalyzed [4 + 2] cycloaddition of aldehydes with
1,3-butadienes to afford dihydropyranes.10 During the course of
our study on metalloporphyrin-catalyzed reactions,11 we
postulated that ruthenium porphyrin also catalyzes the
cycloaddition of carbonyl compounds with carbon−carbon
unsaturated compounds, since both iron and ruthenium
Figure 1. Ruthenium porphyrin complexes.
cyclohexenone with 1,3-butadiene to afford trans-fused octalone
diastereoselectively in 74% yield regioselectively (Table 1, entry
1).13−15 We also examined the effect of counteranions, which
would act as axial ligands, on the reactivity of the Ru center.
When the triflate anion (TfO−) was used, 3aa was obtained in
35% yield (entry 2) along with the diastereomer 3aa′.
Ruthenium porphyrin [Ru(TBPP)(CO)] did not catalyze the
reaction (entry 3).16
The use of the ruthenium porphyrin [Ru(TMP)(CO)]SbF6
(TMP: meso-tetrakis(2,4,6-trimethylphenyl) porphyrinate),
which has a sterically hindered meso-aryl group near ruthenium,
provided octalone 3aa in 60% yield (entry 4). However, the
Received: February 27, 2014
Published: April 30, 2014
© 2014 American Chemical Society
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Organic Letters
Letter
Table 1. [4 + 2] Cycloaddition of Cyclohexenone 1a and 1,3-
Butadiene 2a To Afford Trans-Fused Octalone 3aa
Scheme 2. [4 + 2] Cycloaddition of Cyclohexenone and 1,3-
Butadiene To Afford Trans-Fused Octalone
a
a
bc
,
entry
catalyst
yield (%)
d
1
[Ru(TBPP)(CO)]SbF6
74 (99/1)
35 (6/1)
d
2
[Ru(TBPP)(CO)]OTf
d
3
[Ru(TBPP)(CO)]
<1 (−/−)
60 (99/1)
<1 (−/−)
<1 (−/−)
<1 (−/−)
<1 (−/−)
<5 (−/−)
<1 (−/−)
<1 (−/−)
<1 (−/−)
e
4
[Ru(TMP)(CO)]SbF6
RuCl3
5
6
AlCl3
7
BF3·Et2O
f
8
MAD
9
AgSbF6
10
11
12
TfOH
[Fe(TPP)]SbF6
[Co(TPP)]SbF6
a
Reaction conditions: catalyst (1 mol %), cyclohexenone 1a (0.2
mmol), and butadiene 2a (0.8 mmol) in 0.1 mL of toluene for 12 h.
b
c
d
GC yields are given. Ratio of diastereomers (3aa/3aa′). TBPP:
e
meso-tetrakis(4-tert-butylphenyl)porphyrinate. TMP: meso-tetrakis-
(2,4,6-trimethylphenyl)porphyrinate. MAD: methylaluminum bis-
f
(2,6-di-tert-butyl-4-methylphenoxide).
desired product 3aa was not obtained when using other Lewis
acid catalysts such as RuCl3, AlCl3, BF3·Et2O, methylaluminum
bis(2,6-di-tert-butyl-4-methylphenoxide) (MAD), and AgSbF6
or when using the Brønsted acid TfOH (entries 5−10).
Moreover, nonruthenium metalloporphyrin complexes having
iron and cobalt atoms did not show any catalytic activity
(entries 11 and 12).
With the optimized reaction conditions in hand, we briefly
examined the [Ru(TBPP)]SbF6-catalyzed [4 + 2] cycloaddition
to afford trans-fused octalones 3. The results are summarized in
Scheme 2. Not only the symmetrically substituted 1,3-
butadiene 2a but also unsymmetrically substituted 1,3-dienes
such as isoprene 2b, 2-benzyl-1,3-butadiene 2c, and myrcene
2d participated in the reaction with cyclohexenone to afford the
correspondingly substituted octalones 3ab, 3ac, and 3ad in
good to moderate yields with high regio- and diastereoselec-
tivity. Aryl-substituted 1,3-butadienes, which tend to oligo-
merize in the presence of a strong Lewis acid or Brønsted acid,
also reacted with cyclohexenone to provide the corresponding
octalones. For examples, phenyl- and tolyl-substituted 1,3-
butadienes 3e and 3f reacted with cyclohexenone to afford the
correspondingly substituted otcalones 3ae and 3af in 65% and
64% yields, respectively. Aryl-substituted 1,3-butadienes having
electron-withdrawing groups such as chloride, fluoride, and
trifluoromethyl also participated in the cycloaddition to give
3ag, 3ah, and 3ai in moderate yields. However, aryl-substituted
1,3-diene possessing an electron-donating methoxy group failed
to react with cyclohexenone because it underwent rapid
oligomerization. Butadiene 2j possessing an acetyl group also
participated in the reaction to give 3aj in 27% isolated yield,
along with the dimer of 2j. However, cyclohexenones 1b and 1c
did not participate in the reaction with 2a. The molecular
structures of trans-fused octalones 3aa and 3ag were confirmed
through X-ray crystal structure analysis (Figure 2).
a
Reaction conditions: catalyst (1 mol %), cyclohexenone 1 (0.2
mmol), and butadiene 2 (0.8 mmol) in 0.1 mL of toluene for 12 h.
Isolated yields are given. bReaction time, 24 h. cButadiene (0.4 mmol).
dReaction temperature, 50 °C. cis-3ca′ was isolated in 55% yield.
e
Figure 2. ORTEP drawings of 3aa and 3ag.
reaction time (30 min) afforded cis-fused octalone 3aa′ in 11%
yield (Scheme 3). Furthermore, epimerization of cis-fused
octalone 3aa′ to trans-fused octalone 3aa was efficiently
catalyzed by the ruthenium porphyrin, within 4 h (Scheme
4). These results indicated that the ruthenium-porphyrin-
catalyzed cycloaddition proceeded to initially afford a cis-fused
octalone, which underwent epimerization to the trans-fused
octalone.17
In summary, we have demonstrated the ruthenium-
porphyrin-catalyzed reaction of cyclohexenones with 1,3-
butadienes to afford trans-fused octalones regio- and stereo-
selectively. The ruthenium porphyrin effectively catalyzed (1)
the [4 + 2] cycloaddition to provide cis-octalones and
The cycloaddition of cyclohexenone 1a with 2a provided
trans-fused octalone 3aa in 74% yield after 12 h, while a shorter
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Organic Letters
Letter
(5) (a) Peng, F.; Grote, R. E.; Danishefsky, S. J. Tetrahedron Lett.
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(6) For some examples of a photochemical reaction that provides
trans-fused Diels−Alder products, see (a) Nikolai, J.; Loe, Ø.;
Dominiak, P. M.; Gerlitz, O. O.; Autschbach, J.; Davies, H. M. L. J.
Am. Chem. Soc. 2007, 129, 10763. (b) Ghosh, S.; Roy, S. S.; Saha, G.
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Soc. 1965, 87, 2051.
Scheme 3. Ruthenium-Porphyrin-Catalyzed [4 + 2]
Cycloaddition of Cyclohexenone 1a and Butadiene 2a
(7) For the epimerization of cis-fused Diels−Alder products to trans
Diels−Alder products, see: Fringuelli, F.; Pizzo, F.; Taticchi, A.; Halls,
T. D. J.; Wenkert, E. J. Org. Chem. 1982, 47, 5056.
(8) For some representative examples, see: (a) Liu, W.; Huang, X.;
Cheng, M.-J.; Nielsen, R. J.; Goddard, W. A., III; Grove, J. T. Science
2012, 337, 1322. (b) Morandi, B.; Carreira, E. M. Science 2012, 335,
1471. (c) Breslow, R.; Huang, Y.; Zhang, X.; Yang, J. Proc. Natl. Acad.
Sci. U.S.A. 1997, 94, 11156.
Scheme 4. Ruthenium-Porphyrin-Catalyzed Epimerization
of cis-3aa′ to trans-3aa
(9) For some examples of the use of metalloporphyrins in
nonoxidative bond formation, see: (a) Suda, K.; Baba, K.; Nakajima,
S.-I.; Takanami, T. Chem. Commun. 2002, 2570. (b) Suda, K.;
Kikkawa, T.; Nakajima, S.-I.; Takanami, T. J. Am. Chem. Soc. 2004,
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A. R.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127,
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K.-C.; Zhou, C.-Y.; Che, C.-M. Org. Biomol. Chem. 2012, 10, 9165.
(10) Fujiwara, K.; Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc.
2012, 134, 5512.
(11) (a) Wakabayashi, R.; Kurahashi, T.; Matsubara, S. Org. Lett.
2012, 14, 4794. (b) Ozawa, T.; Kurahashi, T.; Matsubara, S. Org. Lett.
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(12) The attempted cycloaddition of aldehyde and a diene with the
ruthenium porphyrin [Ru(TBPP)(CO)]SbF6 catalyst afforded a
cycloadduct in 62% yield, which is lower than that obtained with
the iron porphyrin [Fe(TPP)]SbF6 catalyst.
subsequent (2) epimerization to the trans-isomer. Detailed
studies to elucidate the mechanism underlying the unique
reactivity of the ruthenium porphyrin catalyst and efforts to
improve the scope of the reaction are underway.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures including spectroscopic and analytical
data of new compounds (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
*E-mail: kurahashi.takuya.2c@kyoto-u.ac.jp.
*E-mail: matsubara.seijiro.2e@kyoto-u.ac.jp.
Notes
(13) (a) Young, R. C.; Nagle, J. K.; Meyer, T. J.; Whitten, D. G. J.
Am. Chem. Soc. 1978, 100, 4773. (b) Higuchi, T.; Satake, C.; Hirobe,
M. J. Am. Chem. Soc. 1995, 117, 8879. (c) Jiang, G.; Chen, J.; Thu, H.-
Y.; Huang, J.-S.; Zhu, N.; Che, C.-M. Angew. Chem., Int. Ed. 2008, 47,
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W.; Ibers, J. A. Inorg. Chem. 1991, 30, 4766. (e) Hu, W.-X.; Li, P.-R.;
Jiang, G.; Che, C.-M.; Chen, J. Adv. Synth. Catal. 2010, 352, 3190.
(f) Huang, Y.; Vanover, E.; Zhang, R. Chem. Commun. 2010, 46, 3776.
(g) Gallo, E.; Caselli, A.; Ragaini, F.; Fantauzzi, S.; Masciocchi, N.;
Sironi, A.; Cenini, S. Inorg. Chem. 2005, 44, 2039. (h) Lai, T.-S.;
Kwong, H.-L.; Zhang, R.; Che, C.-M. J. Chem. Soc., Dalton Trans. 1998,
3559. (i) Ito, R.; Umezawa, N.; Higuchi, T. J. Am. Chem. Soc. 2005,
127, 834. (j) Ohtake, H.; Higuchi, T.; Hirobe, M. J. Am. Chem. Soc.
1992, 114, 10660.
(14) The cationic ruthenium complex [Ru(TBPP)(CO)]SbF6 was
prepared following the reported procedure: [Ru(TBPP)(CO)] (290
mg, 0.30 mmol) and AgSbF6 (98 mg, 0.29 mmol) was dissolved in dry
CH2Cl2 (10 mL) and stirred for 6 h in a dry box. The reaction mixture
was filtered to remove Ag(0) and concentrated to dryness. The
complex was used without further purification. ESI-MS and IR
spectroscopy revealed that CO still remains coordinated to the Ru
atom upon oxidation by AgSbF6.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by JST, ACT-C and Grants-in-Aid
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan. T.K. acknowledges the Asahi Glass
Foundation, the Uehara Memorial Foundation, Tokuyama
Science Foundation, and Kurata Memorial Hitachi Science and
Technology Foundation. We thank Rigaku Corporation for the
valuable help in X-ray crystal structural analysis.
REFERENCES
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(15) The high regioselectivity can be explained in terms of the
reaction mechanism; the ruthenium-catalyzed cycloaddition of cyclo-
hexenone with dienes proceeds to afford initial cis-fused octalone
through an asynchronous stepwise mechanism, which consists of the
formation of a cationic intermediate.
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(16) Even though [Ru(TBPP)(CO)]SbF6 could be reduced to
[Ru(TBPP)(CO)] under certain conditions, we observed that
[Ru(TBPP)(CO)] is inactive for the catalyst. Furthermore, the results
of the time course experiment with the [Ru(TBPP)(CO)]SbF6
catalyst indicate that there is no induction period for the reaction
(Supporting Information, Figure S1). Based on these results, we
proposed that [Ru(TBPP)(CO)]SbF6 is not reduced to [Ru(TBPP)
(CO)] under the catalytic reaction conditions and [Ru(TBPP)(CO)]
SbF6 is the active catalyst for the reaction.
(17) The time-dependent changes in cis-trans-isomers also indicated
that the ruthenium-porphyrin-catalyzed cycloaddition proceeded along
with epimerization of the cis-fused octalone to trans-fused octalone
(Supporting Information, Figure S1).
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