Integrated chemical process: One-pot aromatization of cyclic enones by the double elimination methodology

Article abstract of DOI:10.1002/(SICI)1521-3773(19990802)38:15<2267::AID-ANIE2267>3.0.CO;2-3

A variety of aromatic hydrocarbons bearing multiple alkyl substituents are accessible with perfect regiocontrol in a one-pot reaction starting from cyclo-hexenones and their aromatic analogues [Eq. (1)]. The present methodology can be further extended to the synthesis of polycyclic aromatic hydrocarbons. The drawbacks encountered in the Friedel-Crafts reaction are resolved since the reaction proceeds under basic conditions.

Full text of DOI:10.1002/(SICI)1521-3773(19990802)38:15<2267::AID-ANIE2267>3.0.CO;2-3

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this procedure: 1) the addition of a-sulfonyl carbanions
should be specific to provide the 1,2-adducts without 1,4-
adducts, 2) the tertiary alcohol in the resulting aldolates
should be efficiently trapped with a protecting group, and
3) the double elimination of the sterically demanding b-
substituted sulfones should proceed smoothly. We report here
that these problems can be readily overcome and thus a new,
practical version of aromatization is advanced that consists of
simple manipulations only.
Integrated Chemical Process: One-Pot
Aromatization of Cyclic Enones by the Double
Elimination Methodology**
Akihiro Orita, Jayamma Yaruva, and Junzo Otera*
The aromatization of non-benzenoid compounds has at-
tracted a great deal of attention for a long time. Although
dehydrogenation of cyclic alkanes or alkenes is the most
common way, this method requires severe reaction conditions
and yields are not always satisfactory.[1] Trimerization of
ketones, which is of synthetic interest in terms of the
availability of starting materials, also suffers from low yields.[2]
In contrast to these classical technologies, the recent progress
in organometallic chemistry has given rise to a great deal of
innovation. Trimerization of acetylenes proved to be versa-
tile[3] although the regiochemistry is not easy to control in the
intramolecular versions.[4] The [4‡2] cycloaddition was widely
employed as well for constructing benzene frameworks. The
reaction of cyclopentadienones with acetylenes is the oldest,
but still quite popular, method.[5] More recently the cyclo-
addition of cyclopentadienones[6] or furans[7] with olefins
followed by oxidation was put forth. The reaction of 1,3-
dienes with quinone also led to aromatic compounds after
oxidation of the cycloadducts.[8] A number of intramolecular
[4‡2] cycloaddition protocols that use a,b,g,d-unsaturated
heterocumulenes appeared.[9] Moreover, the intermolecular
version between vinylallenes and acetylenes was reported to
furnish regiocontrolled alkylbenzenes.[10] Despite these so-
phisticated technologies there still exists a strong need for
practical methods.
The operation is quite simple (see experimental section).
Sequential treatment of sulfone 2 with BuLi, enone 1,
PhCOCl, and tBuOK (5 equivalents) furnishes the desired
aromatic compounds 3 in good yields (Table 1). In addition to
simple alkyl groups such as methyl, ethyl, and n-hexyl, those
bearing an acid-sensitive group can also be incorporated
(entries 1 ± 7). Notably, crotyl sulfone 2d also works to afford
1-butenylbenzene, though the yield is modest (entry 8). A
variety of cyclohexenones undergo smooth aromatization. a-
Tetralones and their higher homologues can also be employed
to arrive at polycyclic aromatic hydrocarbons (entries 9 ± 14).
It should be noted that the primary alkyl groups are
incorporated on the aromatic rings with complete regiocon-
trol, which is a great advantage over the Friedel ± Crafts
reaction. The Friedel ± Crafts reaction exhibits poor regiose-
lectivity, and alkyl groups are incorporated in branched forms
even if primary alkyl halides were subjected to the reaction.
More seriously, the degree of alkylation is difficult to control:
polyalkylation predominates over monoalkylation because
the alkylation products are more reactive than their precur-
sors. Our method is entirely free from such problems and thus
allowed us to prepare various new polyalkylated aromatic
compounds that are not easy to obtain by conventional
methods.[12]
We earlier disclosed a one-pot procedure for arriving at
dienes and acetylenes under the concept ªintegrated chemical
processº.[11] In this procedure the dienic or acetylenic moieties
are generated in one pot through the aldol-type coupling of
sulfones with aldehydes followed by a double elimination
reaction. The present study stemmed from the idea of using
cyclohexenones as the carbonyl substrates as depicted in
Scheme 1. The following problems had to be solved to realize
Next, we were intrigued by the development of a procedure
for polycyclic aromatic hydrocarbons, which are the targets of
current interest as new materials.[13] The use of w-carboxy
sulfones leads to a-tetralones or their higher homologues and
the iteration of this procedure, in principle, results in annula-
tion of aromatic skeletons (Scheme 2). First, we employed
SO2Ph
R
PhSO2
R
O
PrO
O
PhSO2
R
+
PhSO2
COOH
COOH
PhSO2
R
R
R
O
higher homologues
O
Scheme 1. Concept for the aromatization of cyclohexenones.
Scheme 2. Synthetic route to polycyclic aromatic compounds.
[*] Prof. Dr. J. Otera, Dr. A. Orita, Dr. J. Yaruva
Department of Applied Chemistry
Okayama University of Science
Ridai-cho, Okayama 700-0005 (Japan)
Fax: (‡81)86-256-4292
sulfones with a carboxyl or its ester group at the g-position but
the reaction of their anions with ketones failed to give the
desired aldol products. However, we found an alternative,
convenient procedure with regard to w-acetal sulfones 4.
Treatment of 4 with 1 as described above accomplished the
one-pot aromatization to give 5 (Table 2). Then, treatment of
5 with OXONE (potassium peroxomonosulfate) in THF/H2O
resulted in both deprotection and oxidation of the acetal to
E-mail: otera@high.ous.ac.jp
[**] This work was supported by the Japan Society for the Promotion of
Science under the ªResearch for the Futureº Program (JSPS-
PFTF96P00303).
Supporting information for this article is available on the WWW
under http://www.wiley-vch.de/home/angewandte/ or from the author.
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Table 1. One-pot synthesis of aromatic compounds from cyclic enones.[a]
O
(CH2)nX
R1
R1
R2
BuLi/PhCOCl/tBuOK
+
PhSO2(CH2)nX
R2
R3
R3
2
3
1
Entry
1
1
2
3
Yield [%]
75
O
(CH2)5CH3
(1a)
(1b)
(1c)
(1d)
PhSO2(CH2)5CH3 (2a)
(3a)
(3b)
(3c)
(3d)
(3e)
O
(CH2)5CH3
(CH2)5CH3
(CH2)5CH3
(CH2)5CH3
2
3
4
5
2a
2a
2a
2a
72
69
84
79
O
O
O
(1e)
O
O
PhSO2
O
(2b)
1b
6
(3 f)
78
O
(CH2)6OTBS
7
8
9
1d
1a
PhSO2(CH2)6OSiMe2tBu (2c)
(3g)
(3h)
(3i)
72
59
82
(2d)
PhSO2
O
(CH2)5CH3
(1 f)
(1g)
1g
2a[c]
(CH2)5CH3
O
10
11
12
2a
(3j)
(3k)
(3l)
74
76
79
MeO
MeO
MeO
PhSO2CH3
(CH2)5CH3
O
MeO
MeO
MeO
MeO
(1h)
2a
O
CH3(CH2)5
13
14
(1i)
(1j)
2a[d]
(3m)
(3n)
78
88
O
(CH2)5CH3
2a
[a] Reaction conditions: a) 2 (1.2 mmol), BuLi (1.1 mmol), THF, 788C, 30 min; b) 1 (1 mmol), PhCOCl (1.5 mmol), 788C !RT, 3 h; c) tBuOK (5 mmol),
reflux, 3 h. [b] Yield of isolated product after column chromatography. [c] 2a (1.4 mmol), BuLi (1.2 mmol). [d] 2a (1.3 mmol), BuLi (1.2 mmol).
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Table 2. One-pot synthesis of aromatic compounds substituted by an
acetal-bearing alkyl chain.[a]
trol in one pot starting from cyclohexenones and their
aromatic analogues. The present methodology can be further
extended to the synthesis of polycyclic aromatic hydrocar-
bons. The drawbacks encountered in the Friedel ± Crafts
reaction are completely cleared up since the reaction pro-
ceeds under basic conditions. A somewhat similar strategy
was put forth with regard to the Reformatsky reaction of a-
tetralones.[15] This procedure, however, involves dehydrogen-
ation under drastic conditions, and results in modest yields.
Obviously, the double elimination enables the generation of
the carbon ± carbon double bonds more easily. Each reaction
in the respective three steps (aldol-type coupling, benzoyla-
tion, and double elimination) demands no special or drastic
conditions. As a result of the mildness and practicality, the
present protocol will find wide applications for the synthesis
of aromatic compounds that are otherwise difficult to obtain.
R1
R1
R2
O
R2
O
O
n
BuLi/PhCOCl/tBuOK
PhSO2
+
O
O
n
R3
R3
4
5
1
Entry
1
4
n
5
R1
R2
R3
Yield [%][b]
1
2
3
4
5
6
7
8
9
1a
1b
1d
1 f
1a
1b
1d
1 f
1a
4a
4a
4a
4a[c]
4b
4b
4b
4b[c]
4c
3
3
3
3
2
2
2
2
4
5a
5b
5c
5d
5e
5 f[d]
5g
5h
5i
H
H
H
H
Me
Me
(CH)4
H
Me
Me
(CH)4
H
H
H
Me
H
H
H
Me
H
92
83
83
55
78
78
67
60
62
H
H
H
H
H
[a] Reaction conditions are identical to those described in Table 1. [b] Yield
of isolated product after column chromatography. [c] 4a (1.4 mmol), BuLi
(1.2 mmol). [d] 5 f ˆ 3 f in Table 1.
Experimental Section
BuLi (690 mL, 1.6m solution in hexanes, 1.1 mmol) was added to a solution
of 4a (307 mg, 1.2 mmol) in THF (5 mL) at 788C. The solution was
stirred for 30 min, and then 1a (96 mg, 1.0 mmol) and PhCOCl (174 mL,
1.5 mmol) were added. The reaction mixture was warmed up to room
temperature and stirred for 3 h. Then, tBuOK (562 mg, 5 mmol) was added
and the reaction mixture was heated under reflux for 3 h. The reaction was
quenched with aqueous ammonium chloride. The mixture was extracted
with diethyl ether and the organic layer was dried (Na2SO4). Evaporation
and column chromatography of the residue on silica gel (hexane/EtOAc 95/
5) furnished 5a (177 mg, 92%).
directly furnish carboxylic acids 6 (Table 3).[14] Exposure of 6
to trifluoromethanesulfonic acid (TfOH) provided the desired
ketones 7 in quantitative yields (Table 3). Methyl-substituted
derivatives as well as nonsubstituted aromatics are smoothly
obtained (Table 3, entries 1 ± 4). Further synthetic utility is
apparent from the synthesis of five- and seven-membered
ketones (Table 3, entries 5 ± 9) besides the six-membered
ones. Notably, no regioisomer was detected in the six-
membered ketone of the monomethyl compound (Table 3,
entry 2) whereas two regioisomers emerged with the five-
membered ketones (Table 3, entry 6). The similar difference
of the selectivity was observed in the cyclization of the
naphthalene derivatives (Table 3, entries 4 and 8).
A suspension of OXONE (6.46 g, 10.5 mmol) in H2O (10 mL) was added to
a solution of 5a (672 mg, 3.5 mmol) in THF (10 mL) at 08C. The mixture
was stirred at room temperature for 12 h and then a mixture of H2O/EtOAc
added. The organic layer was washed with brine and dried (Na2SO4). The
residue obtained by evaporation was subjected to column chromatography
on silica gel (hexane/EtOAc 70/30) to furnish 6a (564 mg, 98%).
A solution of 6a (164 mg, 1 mmol) in TfOH (1 mL) was stirred at
58C !room temperature over 2 h. Crushed ice was added slowly and the
reaction mixture was extracted with diethyl ether. The organic layer was
In summary, a variety of aromatic hydrocarbons bearing
multiple alkyl substituents is accessible with perfect regiocon-
Table 3. Cyclization of 5.
R1
R1
R1
R2
R2
R2
O
COOH
b
a
n
n
n-1
O
R3
R3
O
R3
5
6
7
Entry
5
n
6
Yield [%][c]
7
R1
R2
R3
Yield [%][c]
1
2
3
4
5
5a
5b
5c
5d
5 f
3
3
3
3
2
6a
6b
6c
6d
6 f
98
97
94
95
96
7a
7b
7c
7d
7e
H
H
H
H
Me
Me
H
H
Me
H
H
98
97
99
99
99
(CH)4
H
H
H
H
O
6
7
8
9
5g
5h
5i
2
2
2
4
6g
6h
6i
93
82
98
79
7 f‡7 f'
7g
(7 f)
(7h)
(7 f')
(7h')
99[d]
94
O
Me
Me
H
O
O
7h‡7h'
7i
97[e]
5j
6j
H
93
[a] OXONE (3 equiv), THF/H2O, 08C !RT, 12 h. [b] In TfOH, 58C !RT, 2 h. [c] Yield of isolated product after column chromatography. [d] 7 f:7 f' ˆ 1:1.
[e] 7h:7h' ˆ 5:1.
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washed sequentially with aqueous NaHCO3, water, and brine, and dried
(Na2SO4). The residue obtained by evaporation was subjected to column
chromatography on silica gel (hexane/EtOAc 90/10) to furnish 7a (144 mg,
98%).
Electronic Communication in C4-Bridged
Binuclear Complexes with Paramagnetic
Bisphosphane Manganese End Groups
Sohrab Kheradmandan, Katja Heinze,
Helmut W. Schmalle, and Heinz Berke*
Received: February 9, 1999 [Z13018IE]
German version: Angew. Chem. 1999, 111, 2397 ± 2400
Dedicated to Professor Helmut Werner
on the occasion of his 65th birthday
Keywords: arenes
chemical process ´ one-pot reaction
´ eliminations ´ enones ´ integrated
Binuclear metal complexes [LnMCxMLn] bridged by linear
unsaturated carbon chains are of exceptional interest as
building blocks for new one-dimensional materials.[1] Elec-
tronic and optical properties of the molecular precursors, such
as metal ± metal interactions in mixed-valent compounds and
electron delocalization and conjugation within the carbon
chain, are important for the prediction and optimization of
bulk properties of polymeric materials, such as nonlinear
optical (NLO) properties,[2] electrical conductivity,[3] or coop-
erative magnetic effects.[4] Most complexes found in the
literature possess an even number of carbon atoms in the
chain (x ˆ 2,[5] 4,[6] ꢀ 6[7]), a few also an uneven number (n ˆ
3,[8] 5[9]). The metal centers usually have a d8/d8, d6/d6, d5/d6, or
d5/d5 electron configuration.[10] Paramagnetic complexes are
supposed to be more polarizable, as their SOMO/LUMO gaps
are usually smallÐan important prerequisite, for example, for
NLO properties.[2] We report the syntheses, properties, and
solid-state structures of the paramagnetic binuclear MnII
[1] a) L. F. Fieser, M. Fieser, Reagents for Organic Synthesis, Vol. 1, Wiley,
New York, 1967, p. 778; b) R. D. Haworth, J. Chem. Soc. 1932, 1125;
c) G. Haberland, Chem. Ber. 1936, 69, 1380; d) W. E. Bachmann, A. L.
Wilds, J. Am. Chem. Soc. 1938, 60, 624; e) V. C. Burnop, G. H. Elliott,
R. P. Linstead, J. Chem. Soc. 1940, 727.
[2] a) R. Adams, R. W. Hufferd, Org. Synth. 1941, I, 341; b) R. L. Frank,
R. H. Varland, Org. Synth. 1955, III, 829; c) C. M. Buess, D. D.
Lawson, Chem. Rev. 1960, 60, 313.
[3] a) C. W. Bard, Transition Metal Intermediates for Organic Synthesis,
Logos, London, 1967, p. 1; b) H. Bönnemann, W. Brijoux in Transition
Metals for Organic Synthesis, Vol. 1 (Eds.: M. Beller, C. Bolm),
WILEY-VCH, Weinheim, 1998, p. 114; c) L. Tong, H. Lau, D. M. Ho,
R. A. Pascal, Jr., J. Am. Chem. Soc. 1998, 120, 6000; d) V. S. Iyer, K.
Yoshimura, V. Enkelmann, R. Epsch, J. P. Rabe, K. Müllen, Angew.
Chem. 1998, 110, 2843; Angew. Chem. Int. Ed. 1998, 37, 2696.
[4] For a recent study on regioselective trimerization of acetylenes, see
a) A. Takeda, A. Ono, I. Kadota, V. Gevorgyan, Y. Yamamoto, J. Am.
Chem. Soc. 1997, 119, 4547; b) V. Gevorgyan, L. G. Quan, Y.
Yamamoto, J. Org. Chem. 1998, 63, 1244.
[5] L. F. Fieser, Organic Synthesis, Collect. Vol. 5, Wiley, New York, 1973,
p. 604.
[6] A.-D. Schlüter, M. Löffler, V. Enkelmann, Nature 1994, 368, 831.
[7] M. Löffler, A.-D. Schlüter, K. Gessler, W. Saenger, J.-M. Toussaint,
compound
1
(dmpe ˆ 1,2-bis(dimethylphosphanyl)ethane)
‡
and of its one- and two-electron oxidation products 1 and
12‡, respectively.
Â
J.-L. Bredas, Angew. Chem. 1994, 106, 2281; Angew. Chem. Int. Ed.
Engl. 1994, 33, 2209.
ꢁ
ꢁ
[I(dmpe)2Mn C C C C Mn(dmpe)2I]
1
[8] A. D. Thomas, L. L. Miller, J. Org. Chem. 1986, 51, 4160.
[9] a) H. W. Moore, O. H. W. Decker, Chem. Rev. 1986, 86, 821; b) S. L.
Xu, H. W. Moore, J. Org. Chem. 1992, 57, 326; c) L. Sun, L. S.
Liebeskind, J Org. Chem. 1995, 60, 8194; d) C. A. Merlic, M. E. Pauly,
J. Am. Chem. Soc. 1996, 118, 11319.
[10] M. Murakami, M. Ubukata, K. Itami, Y. Ito, Angew. Chem. 1998, 110,
2362; Angew. Chem. Int. Ed. 1998, 37, 2248.
[11] a) A. Orita, Y. Yamashita, A. Toh, J. Otera, Angew. Chem. 1997, 109,
804; Angew. Chem. Int. Ed. Engl. 1997, 36, 779; b) A. Orita, N.
Yoshioka, J. Otera, Chem. Lett. 1997, 1023.
[12] All new compounds obtained in this study were fully characterized by
spectroscopic and elemental analyses, see the supporting information.
[13] M. Müller, C. Kübel, K. Müllen, Chem. Eur. J. 1998, 4, 2099.
[14] According to this procedure the acetal group serves as a protecting
group for the carboxylic group. Since the base-tolerant protection of
this group is not easy, the acetal protocol offers a useful method.
[15] a) G. Stork, J. Am. Chem. Soc. 1947, 69, 2936; b) M. S. Newman, A. S.
Hussey, J. Am. Chem. Soc. 1947, 69, 3023.
According to Scheme 1 the green d5 low-spin MnII complex
1 is obtained from [MeCpMn(dmpe)I][18a] and half an equiv-
alent of bis(trimethylstannyl)-1,3-butadiyne in the presence of
DMPE in 70% yield. The low-spin character of 1 is shown by
1H PNMR spectroscopy: the resonances of the methyl and
methylene protons of the DMPE ligand appear in a typical
region for low-spin [MnII(dmpe)2] complexes (Figure 1).[11]
The linear dependence of the signal positions on the temper-
ature points to Curie±Weiss behavior in the measured temper-
ature range from 908C to 258C. As theoretically predicted
ꢁ
ꢁ
for the isolobal complex [Cp(CO)2Mn C C C C Mn(CO)2-
Cp][12] and confirmed by our density functional theory (DFT)
calculations on the model complex [I(PH3)4Mn C C C C
Mn(PH3)4I], 1 has a triplet ground state (Figure 2).[13]
ꢁ
ꢁ
[*] Prof. Dr. H. Berke, S. Kheradmandan, Dr. K. Heinze,
Dr. H. W. Schmalle
Department of Inorganic Chemistry
University of Zürich
Winterthurerstrasse 190, CH-8057 Zürich (Switzerland)
Fax: (‡41)1-635-6802
E-mail: hberke@aci.unizh.ch
[**] This work was supported by the Swiss National Science Foundation
(SNSF). We thank Dr. Vassily V. Krivykh for some synthetic
explorations.
Supporting information for this article is available on the WWW
under http://www.wiley-vch.de/home/angewandte/ or from the author.
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