High-valent metalloporphyrin, Fe(tpp)OTf, catalyzed rearrangement of α,β-epoxy ketones into 1,2-diketones

Article abstract of DOI:10.1039/b207328e

Iron(III) tetraphenylporphyrin triflate, Fe(tpp)OTf, works as an efficient and characteristic Lewis acid catalyst in the selective rearrangement of α,β-epoxy ketones into 1,2-diketones.

Full text of DOI:10.1039/b207328e

High-valent metalloporphyrin, Fe(tpp)OTf, catalyzed rearrangement of
a,b-epoxy ketones into 1,2-diketones
Kohji Suda,* Kenji Baba, Shin-ichiro Nakajima and Toshikatsu Takanami
Meiji Pharmaceutical University, 2-522-1, Noshio, Kiyose, Tokyo 204-8588, Japan.
E-mail: suda@my-pharm.ac.jp; Fax: +81 (424)-95-8780
Received (in Cambridge, UK) 26th July 2002, Accepted 23rd September 2002
First published as an Advance Article on the web 7th October 2002
Table 1 Iron(III) tetraphenylporphyrin, Fe(tpp)X, catalyzed rearrangement
of trans-3,4-epoxydecan-2-one (1a)
Iron(III) tetraphenylporphyrin triflate, Fe(tpp)OTf, works as
an efficient and characteristic Lewis acid catalyst in the
selective rearrangement of a,b-epoxy ketones into 1,2-di-
ketones.
a,b-Epoxy ketones are an important class of compounds in view
of distinct structural features and high synthetic utility. Both the
ketone and epoxide moieties can be subjected to a wide variety
of further chemical transformations to give potential inter-
mediates and precursors for the synthesis of natural products
and biologically active compounds.1 Since the early work of
House et al. in the 1950s, epoxy ketones have been known to
rearrange into 1,2- and/or 1,3-dicarbonyl compounds with
acids.2 As shown in Scheme 1, the rearrangement involves a
Conditions
Entry
Catalyst/Solvent/Time
Yield of 2a (%)a
cleavage of the C–O bond at the b-position followed by acyl
migration (route A) or hydrogen migration (route B), leading to
1,3- or 1,2-diketones. The acyl migration that gives 1,3-dike-
tones can be achieved with various acids such as BF3·OEt2,
LiClO4 and solid Brønsted acids (zeolites),2–4 and has been
applied to the synthesis of natural products having complex
chemical structures.5 By contrast, fewer examples are docu-
mented on the hydrogen migration that allows access to
1,2-diketones. In particular, none of the catalytic versions of
such a transformation have hitherto been reported.6,7 As part of
our ongoing studies on the development of a novel function and
synthetically useful chemical properties of metalloporphyrins,
we have found that high-valent metalloporphyrins promote
regioselective hydrogen migration in the rearrangement of
epoxides.8 We, therefore, envisioned that these metalloporphyr-
ins would function as a useful catalyst for the rearrangement of
a,b-epoxy ketones. In this communication, we report the first
highly efficient catalytic rearrangement of a,b-epoxy ketones
into 1,2-diketones, which is applicable to a variety of epoxy
ketones.
trans-3,4-Epoxydecan-2-one (1a) was chosen as a model
substrate and the rearrangement with several iron(III) tetra-
phenylporphyrin complexes was investigated (Table 1).† A
catalytic amount (2 mol%) of iron(III) tetraphenylporphyrin
perchlorate, Fe(tpp)ClO4, was added to a solution of 1a (5
mmol) in dioxane (3 ml), and the reaction mixture was refluxed
for 8 h under a nitrogen atmosphere. After concentration in
vacuo, florisil column purification provided decane-2,3-dione
(2a) in 30% yield along with recovered 1a (45%) (entry 1).
Iron(III) tetraphenylporphyrin chloride, Fe(tpp)Cl, instead of
Fe(tpp)ClO4, did not effect the reaction, recovering the starting
1
2
3
4
5
6
7
8
9
Fe(tpp)ClO4 (2 mol%)/dioxane/8 hb
Fe(tpp)Cl (2 mol%)/dioxane/48 hb
Fe(tpp)OTf (2 mol%)/dioxane/1.5 hb
Fe(tpp)OTf (2 mol%)/(CH2)2Cl2/2 hb
Fe(tpp)OTf (2 mol%)/toluene/2 hb
MABR (2 equiv.)/CH2Cl2/48 hef
MABR (2 equiv.)/dioxane/48 heg
BF3OEt2 (1 equiv.)/CH2Cl2/2 hh
BF3OEt2 (1 equiv.)/ether/2 hh
30c
No reactiond
95
50
55
Complex mixture
Complex mixture
Complex mixture
No reactiond
0i
10
MgBr2OEt2 (1 equiv.)/CH2Cl2/1.5 hh
a Isolated yield. b Reflux. c Recovery of 1a (45%). d Recovery of 1a (quant).
e MABR: methylaluminium bis(4-bromo-2,6-di-tert-butylphenoxide).
278 °C to rt. g 220 °C to rt. h 0 °C to rt. i 4-Bromo-3-hydroxydecan-2-one
f
3a (92%) was obtained.
tetraphenylporphyrin triflate, Fe(tpp)OTf, as a catalyst, re-
markably improved the yield of 2a up to 95% and shortened the
reaction time to 1.5 h (entry 3). Although the Fe(tpp)OTf
catalyzed reaction proceeded similarly in other solvents such as
toluene and 1,2-dichloroethane, the yield of 2a decreased to
50% and 55%, respectively (entries 4 and 5). The Lewis acidity
of the metalloporphyrins in the solvents used seems to affect the
reactivity and selectivity of the rearrangement. To evaluate the
aptitude of the Fe(tpp)OTf–dioxane catalyst system, we further
examined the rearrangement of 1a with BF3·OEt2, MgBr2·OEt2
and methylaluminium bis(4-bromo-2,6-di-tert-butylphenoxide)
(MABR),9 which are the most representative and commonly
used Lewis acid reagents in the rearrangement of various kinds
of epoxides. However, all attempts to rearrange 1a with these
Lewis acids under several conditions were unsuccessful,
providing only inseparable complex mixtures, halohydrin
derivative 3a or starting material 1a recovered: neither the
desired product 2a nor the corresponding 1,3-diketone was
detected in the 1H-NMR spectrum of the crude products (entries
6–10). Consequently, the Fe(tpp)OTf–dioxane system depicted
in entry 3 is the most effective metalloporphyrin catalyst system
among those examined, and permits the highly selective
transformation of 1a into 2a at a low catalyst loading without
significant loss of catalytic activity.
material 1a (entry 2). On the other hand, the use of iron(III
)
To explore the generality of the Fe(tpp)OTf–dioxane catalyst
system, the ring-opening rearrangement of various a,b-epoxy
ketones were examined. As shown in Table 2, the Fe(tpp)OTf
Scheme 1
2570
CHEM. COMMUN., 2002, 2570–2571
This journal is © The Royal Society of Chemistry 2002

catalyzed reaction proved to be general and applicable to a
variety of a,b-epoxy ketones.‡ As a whole, a facile and highly
selective conversion of epoxy ketones into 1,2-diketones via
hydrogen migration, viz., route B in Scheme 1, was observed.
Acetylepoxides 1b bearing an alkyl group longer than that of 1a
were easily transformed into the corresponding 1,2-diketone 2b
in 88% yield. In the rearrangement of other acetylepoxides 1c,
1d and 1e, olefinic, cycloalkanoic and aromatic moieties in the
substrates were tolerated well, and the corresponding 1,2-dike-
tones 2c, 2d and 2e were obtained in high yields. Both the yield
and the reaction time are independent of the carbon-chain length
of acyl substituents in the substrates: the reaction of non-
anoylepoxide 1f proceeded smoothly, giving the corresponding
1,2-diketone 2f as a sole isolable product. Phenyl epoxides 1g
and 1h were surprisingly susceptible to the catalytic rearrange-
ment. The rearrangements of these epoxides were completed
within 15 min under the same conditions, affording 1,2-dike-
tones 2g and 2h in high yields. This acceleration in reaction rate
should be ascribed to the presence of the b-phenyl group that
can stabilize the carbonium ion generated by the C–O bond
cleavage at the b-position in the rearrangement.
Notes and references
† Fe(tpp)ClO4 and Fe(tpp)OTf were prepared according to the method
described previously, see ref. 8.
‡ The products 2a–2f gave satisfactory NMR, IR and high-resolution mass
spectra. For example, 1H- and 13C-NMR data of 2a and 2e are as follows.
2a: 1H-NMR (270 MHz, CDCl3) d 0.88 (3H, t, J = 6.6 Hz), 1.18–1.35 (8H,
m), 1.58 (2H, m), 2.33 (3H, s), 2.73 (2H, t, J = 7.4 Hz); 13C-NMR (67.8
MHz, CDCl3) d 14.1, 22.6, 23.1, 23.7, 29.0, 29.1, 31.6, 35.7, 197.6, 199.5.
2e: 1H-NMR (270 MHz, CDCl3) d 1.93 (2H, m), 2.29 (3H, s), 2.64 (2H, t,
J = 7.6 Hz), 2.75 (2H, t, J = 7.3 Hz), 7.15–7.31 (m, 5H); 13C-NMR (67.8
MHz, CDCl3) d 23.7, 24.6, 35.0, 126.1, 128.4, 128.5, 141.3, 197.4, 199.1.
The products 2g10a and 2h6a are compared with the literature data.
1 For a recent review, see: C. Lauret, Tetrahedron: Asymmetry, 2001, 12,
2359.
2 H. O. House, J. Am. Chem. Soc., 1954, 76, 1235; H. O. House and G. D.
Ryerson, J. Am. Chem. Soc., 1961, 83, 979 and references cited
therein.
3 R. D. Bach and J. M. Domagala, J. Org. Chem., 1984, 49, 4181; R. D.
Bach and R. C. Klix, J. Org. Chem., 1985, 50, 5440; F. Kunisch, K.
Horbert and P. Welzel, Tetrahedron Lett., 1985, 26, 6039; R. D. Bach
and R. C. Klix, Tetrahedron Lett., 1985, 26, 985; R. C. Klix and R. D.
Bach, J. Org. Chem., 1987, 52, 580; K. Okada, T. Katsura, H. Tanino,
H. Kakoi and S. Inoue, Chem. Lett., 1994, 157; S. Sankararaman and J.
E. Nesakumar, J. Chem. Soc., Perkin Trans. 1, 1999, 3173; J. A. Elings,
H. E. B. Lempers and R. A. Sheldon, Eur. J. Org. Chem., 2000,
1950.
4 Photo irradiation and a Pd(0) catalyst are also effective for the selective
rearrangement of epoxy ketones into 1,3-diketones: S. P. Pappas, R. M.
Gresham and M. J. Miller, J. Am. Chem. Soc., 1970, 92, 5797; M.
Suzuki, A. Watanabe and R. Noyori, J. Am. Chem. Soc., 1980, 102,
2095.
5 K. Okada, K. Murakami and H. Tanino, Tetrahedron, 1997, 53, 14247;
K. Okada, K. Murakami, H. Tanino, H. Kakoi and S. Inoue,
Heterocycles, 1996, 43, 1735; M. Asaoka, S. Hayashibe, S. Sonoda and
H. Takei, Tetrahedron, 1991, 47, 6967; V. Enev and E. Tsankova,
Tetrahedron Lett., 1988, 29, 1829.
6 Although silica gel and AlCl3 mediated rearrangements of chalcone
epoxides into 1,3-diarylpropane-1,2-diones have been reported, the
substrates exemplified in these reports are strictly restricted to chalcone
epoxide derivatives: (a) T. B. Rao and J. M. Rao, Synth. Commun.,
1993, 23, 1527; (b) O. N. Bubel, I. G. Tishchenko and O. A. Grinkevich,
Khim. Geterotsikl. Soedin., 1985, 1624.
In summary, we have developed the first catalytic version of
the Lewis acid mediated rearrangement of a,b-epoxy ketones
into 1,2-diketones. The rearrangement can easily be promoted
by high-valent metalloporphyrin complexes, especially Fe(tp-
p)OTf, at a low catalyst loading (2 mol%) under very mild
conditions. 1,2-Diketones have been found to be versatile
intermediates in organic synthesis, and their preparation has
been widely investigated.10 As for 1,2-diketone syntheses, the
present catalytic process exceeds or competes with other
methods reported so far in view of the simplicity, high yields,
and availability of starting materials.11 Elucidation of the
precise mechanism and the synthetic applications of the present
metalloporphyrin catalyzed rearrangement are in progress.
We thank Mr N. Eguchi, Miss T. Koseki and Miss A. Ohmae
in the Analytical Center of our university for measurements of
NMR and mass spectral data. This research was supported in
part by a Grant-in-Aid for Scientific Research (No. 11119267)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan and The Science Research Promotion Fund
from Bio Venture Research Center of Meiji Pharmaceutical
University.
7 Sosnovskii et al. have reported that (iPrO)2TiCl2 can promote the
rearrangement. This procedure, however, requires more than a stoichio-
metric amount of (iPrO)2TiCl2: G. M. Sosnovskii and I. V. Astapovich,
Zh. Org. Khim., 1993, 29, 85.
Table 2 Fe(tpp)OTf catalyzed rearrangement of a,b-epoxy ketonesa
8
K Suda, K. Baba, S. Nakajima and T. Takanami, Tetrahedron Lett.,
1999, 40, 7243; T. Takanami, M. Ueno, F. Hino and K. Suda, Chem.
Lett., 1996, 1031.
9 Maruoka et al. have reported that exceptionally bulky, oxygenophilic
organoaluminum reagent, MABR, is among the most effective reagent
for the regio- and stereoselective rearrangement of epoxides into
carbonyl compounds: K. Maruoka, T. Ooi and H. Yamamoto, J. Am.
Chem. Soc., 1989, 111, 6431; K. Maruoka, J. Sato and H. Yamamoto, J.
Am. Chem. Soc., 1991, 113, 5449.
R1
R2
Time
Yield (%)b
10 (a) Z. X. Si, X. Y. Jiao and B. F. Hu, Synthesis, 1990, 509; (b) D.
Seyferth, R. M. Weinstein, R. C. Hui, W. L. Wang and C. M. Archer, J.
Org. Chem., 1991, 56, 5768; (c) F. Babudri, V. Fiandanese, G. Marchese
and A. Punzi, Tetrahedron Lett., 1995, 36, 7305; (d) A. R. Katritzky, Z.
Wang, H. Lang and D. Feng, J. Org. Chem., 1997, 62, 4125; (e) H.
Sakurai, K. Tanabe and K. Narasaka, Chem. Lett., 2000, 168; (f) S.
Antoniotti and E. Duñach, Chem. Commun., 2001, 2566; (g) M. S.
Yusubov, G. A. Zholobova, S. F. Vasilevsky, E. V. Tretyakov and D. W.
Knight, Tetrahedron, 2002, 58, 1607 and references cited therein.
11 Many good methods have been available for the preparation of a,b-
epoxy ketones. For recent reviews, see: M. J. Porter and J. Skidmore,
Chem. Commun., 2000, 1215; T. Nemoto, T. Ohshima and M.
Shibasaki, J. Synth. Org. Chem. Jpn., 2000, 60, 94.
a
b
c
CH3(CH2)5-
CH3(CH2)8-
CH2NCH(CH2)8-
CH3-
CH3-
CH3-
CH3-
1.5 h
1.5 h
2 h
95
88
92
87
d
2.5 h
e
f
g
h
Ph(CH2)2-
CH3(CH2)2-
Ph-
CH3-
CH3(CH2)7-
CH3-
1.5 h
1 h
15 m
15 m
87
91
85
85
Ph-
Ph-
a Conditions: 1 (0.5 mmol), Fe(tpp)OTf (2 mol%), dioxane (3 ml), reflux.
b Isolated yield.
CHEM. COMMUN., 2002, 2570–2571
2571