Rhenium- and manganese-catalyzed synthesis of aromatic compounds from 1,3-dicarbonyl compounds and alkynes

Article abstract of DOI:10.1021/jo902072q

(Chemical Equation Presented) We have succeeded in the development of three approaches to the synthesis of aromatic compounds from 1,3-dicarbonyl compounds and alkynes. The first approach is a manganese-catalyzed [2+2+2] cycloaddition between 1,3-dicarbonyl compounds, which have no substituents at the active methylene moiety, and terminal alkynes. This reaction proceeds with high regioselectivity when aryl acetylenes are employed as the alkyne component. The second approach is a rhenium- or manganese-catalyzed formal [2+1+2+1] cycloaddition between β-keto esters and two kinds of alkynes. In this reaction, the aromatic compounds are obtained by the following reaction sequence: (1) insertion of the first alkyne into a carbon-carbon single bond of a β-keto ester, (2) formation of 2-pyranones via intramolecular cyclization with the elimination of ethanol, and (3) Diels-Alder reaction between the formed 2-pyranone and the second alkyne. This reaction provides multisubstituted aromatic compounds in a regioselective manner. The third approach is a rheniumcatalyzed formal [2+2+1+1] cycloaddition reaction from two 1,3-diketones and one alkyne. In this reaction, the aromatic skeleton is constructed from three carbons of the first 1,3-diketone, two carbons of the alkyne, and one carbon of the second 1,3-diketone. 2009 American Chemical Society.

Full text of DOI:10.1021/jo902072q

pubs.acs.org/joc
Rhenium- and Manganese-Catalyzed Synthesis of Aromatic Compounds
from 1,3-Dicarbonyl Compounds and Alkynes
Yoichiro Kuninobu,* Mitsumi Nishi, Atsushi Kawata, Hisatsugu Takata,
Yumi Hanatani, Salprima Yudha S., Aya Iwai, and Kazuhiko Takai*
Division of Chemistry and Biochemistry, Graduate School of Natural Science and Technology,
Okayama University, Tsushima, Kita-ku, Okayama 700-8530, Japan
kuninobu@cc.okayama-u.ac.jp; ktakai@cc.okayama-u.ac.jp
Received September 25, 2009
We have succeeded in the development of three approaches to the synthesis of aromatic compounds
from 1,3-dicarbonyl compounds and alkynes. The first approach is a manganese-catalyzed [2þ2þ2]
cycloaddition between 1,3-dicarbonyl compounds, which have no substituents at the active methyl-
ene moiety, and terminal alkynes. This reaction proceeds with high regioselectivity when aryl
acetylenes are employed as the alkyne component. The second approach is a rhenium- or
manganese-catalyzed formal [2þ1þ2þ1] cycloaddition between β-keto esters and two kinds of
alkynes. In this reaction, the aromatic compounds are obtained by the following reaction sequence:
(1) insertion of the first alkyne into a carbon-carbon single bond of a β-keto ester, (2) formation of
2-pyranones via intramolecular cyclization with the elimination of ethanol, and (3) Diels-Alder
reaction between the formed 2-pyranone and the second alkyne. This reaction provides multi-
substituted aromatic compounds in a regioselective manner. The third approach is a rhenium-
catalyzed formal [2þ2þ1þ1] cycloaddition reaction from two 1,3-diketones and one alkyne. In this
reaction, the aromatic skeleton is constructed from three carbons of the first 1,3-diketone, two
carbons of the alkyne, and one carbon of the second 1,3-diketone.
Introduction
on the aromatic skeleton from two or three kinds of alkynes.
Recently, to overcome this limitation, research has focused
on new approaches to the synthesis of multisubstituted
aromatic compounds.2 During our investigations of rhe-
nium- and manganese-catalyzed reactions,3,4 we found that
Aromatic compounds play an important role in organic
chemistry, serving as functional materials and bioactive
compounds. This has led to many reports on the synthesis
of aromatic compounds including transition metal-catalyzed
[2þ2þ2] cycloaddition reactions of alkynes, which are popu-
lar and atom-economical.1 However, due to the low pair-
and regioselectivity of the [2þ2þ2] cycloaddition, it does not
lend itself to the easy introduction of different substituents
(2) (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539.
(b) Saito, S.; Yamamoto, Y. Chem. Rev. 2000, 100, 2901. (c) Mori, N.; Ikeda,
S.; Odashima, K. Chem. Commun. 2001, 181.
(3) For rhenium-catalyzed reactions, see: (a) Kuninobu, Y.; Kawata, A.;
Takai, K. J. Am. Chem. Soc. 2005, 127, 13498. (b) Yudha, S. S.; Kuninobu,
Y.; Takai, K. Org. Lett. 2007, 9, 5609. (c) Kuninobu, Y.; Nishina, Y.;
Matsuki, T.; Takai, K. J. Am. Chem. Soc. 2008, 130, 14062. (d) Yudha, S. S.;
Kuninobu, Y.; Takai, K. Angew. Chem., Int. Ed. 2008, 47, 9318.
(4) For manganese-catalyzed reactions, see: (a) Kuninobu, Y.; Nishina,
Y.; Takeuchi, T.; Takai, K. Angew. Chem., Int. Ed. 2007, 46, 6518.
(b) Kuninobu, Y.; Kikuchi, K.; Takai, K. Chem. Lett. 2008, 37, 740.
(1) (a) Grotjahn, D. B. In Comprehensive Organometallic Chemistry II;
Hegedus, L. S., Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Pergamon:
Oxford, UK, 1995; Vol. 12, pp 741-770. (b) Bonnemann, H.; Brijoux, W. In
Transition Metals for Organic Synthesis; Beller, M., Bolm, C., Eds.; Wiley-
VCH: Weinheim, Germany, 2004; Vol. 1, pp 171-197.
334 J. Org. Chem. 2010, 75, 334–341
Published on Web 12/09/2009
DOI: 10.1021/jo902072q
r
2009 American Chemical Society

Kuninobu et al.
JOCArticle
TABLE 1. Reactions between β-Keto Esters 1 and Alkynes 2a
substituted aromatic compounds could be obtained regio-
selectively from 1,3-dicarbonyl compounds and two alkynes
by changing the catalysts, additives, and/or reaction condi-
tions. In this paper, we report the scope and limitations of the
reactions and their reaction mechanisms.
Results and Discussion
Manganese-Catalyzed Synthesis of Tetra- and Trisubsti-
tuted Aromatic Compounds via [2þ2þ2] Cycloaddition. In
2005, we reported on the addition of 1,3-dicarbonyl com-
pounds to terminal alkynes, where alkenylation of the active
methylene moiety of 1,3-dicarbonyl compounds occurred.5
During the investigation of additives, we found a quite
different reaction accidentally. By adding a catalytic amount
of N,N-dimethylacetoamide (DMA), a tetrasubstituted aro-
matic compound 3a was formed in 50% yield from a β-keto
ester 1a and 2 equiv of phenylacetylene (2a) (eq 1).6
The yield of the tetrasubstituted aromatic compound 3a
was improved by using a manganese complex, MnBr(CO)5,
as a catalyst (Table 1, entry 1).6,7 In this system, DMA was
not necessary to promote the reaction. Tetrasubstituted
aromatic compounds could be synthesized regioselectively
by changing the substituents on the β-keto esters (Table 1,
entries 2 and 3). This reaction is suitable for the synthesis of
p-terphenyl derivatives (Table 1, entries 4-7). Aryl acety-
lenes with either an electron-donating group, 2b and 2c, or a
bromo atom, 2d, provided the corresponding terphenyls
3d-f in good yields (Table 1, entries 4-6). In the case of
2d, side reactions did not occur at the carbon-bromine bond
(entry 6). 1,4-Dinaphthalenylbenzene 3g was also produced
with alkyne 2e (Table 1, entry 7). Although the aryl acet-
ylenes 2a-e afforded only single products, a mixture of two
isomers 3h and 3h0 was generated when alkylacetylene 2f was
used (Table 1, entry 8). This reaction did not proceed with
β-keto esters with a substituent at the active methylene
moiety.8 Also, the reaction did not occur with internal alkynes.
This reaction also proceeded with 1,3-diketones as sub-
strates; however, the products were different (eq 2). Treat-
ment of 1,3-diketone 4a with phenylacetylene (2a) in the
presence of a manganese catalyst, MnBr(CO)5, and mole-
cular sieves in toluene produced tetrasubstituted aceto-
phenone derivative 5 in 69% yield. In this reaction, alkeny-
lated product 7 was formed in 7% yield as a side product.
Interestingly, deacylated aromatic compound 6 was also
obtained in 5% yield. To improve the yield of the trisub-
stituted aromatic compound 6, we investigated the reaction
a1 (1 equiv), 2 (2.5 equiv). bThe ratio between 3h and 3h0.
conditions. As a result, aromatic compound 6 was afforded
in 66% yield when the reaction was carried out at 80 °C in a
mixture of toluene and water (1:1). By using a catalytic
amount of Sc(OTf)3, the yield of 6 increased slightly.
To confirm if the tetra- and trisubstituted aromatic com-
pounds, 5 and 6, are formed from alkenylated product 7 and
phenylacetylene (2a), the reaction shown in eq 3 was carried
out. However, neither of the aromatic compounds was
produced showing that this was not the case.
(5) Kuninobu, Y.; Kawata, A.; Takai, K. Org. Lett. 2005, 7, 4823.
(6) Kuninobu, Y.; Nishi, M.; Yudha, S. S.; Takai, K. Org. Lett. 2008, 10,
3009.
(7) Another group also reported on the similar manganese-catalyzed
reaction. See: Tsuji, H.; Yamagata, K.-i.; Fujimoto, T.; Nakamura, E.
J. Am. Chem. Soc. 2008, 130, 7792.
(8) When β-keto esters with a substituent at the active methylene moiety
were used, insertion of alkynes into a carbon-carbon bond of β-keto esters
occurred, and successive intramolecular cyclization gave 2-pyranones. See:
Kuninobu, Y.; Kawata, A.; Nishi, M.; Takata, H.; Takai, K. Chem. Com-
mun. 2008, 6360.
To explain the formation of the tetrasubstituted aromatic
compounds 3 and their regiochemistry, there are three
J. Org. Chem. Vol. 75, No. 2, 2010 335

Kuninobu et al.
JOCArticle
SCHEME 1. Formation of Tetrasubstituted Aromatic Com-
pounds 3 via a Manganacyclopentadiene Intermediate
nucleophilic addition via the elimination of ethanol, to obtain
the 2-pyranone derivative 8a in 96% yield (eq 4).11,12
SCHEME 2. Formation of Tetrasubstituted Aromatic Com-
pounds 3 via an Alkenyl-Manganese Intermediate
2-Pyranone derivatives are good precursors to synthesize
aromatic compounds via the Diels-Alder reaction.13 Thus,
the reactions in eq 4 could be applied to the synthesis of
multisubstituted aromatic compounds (Table 2). By the
reaction of β-keto ester 1d with diphenylacetylene (2g) in
the presence of [ReBr(CO)3(thf)]2 as a catalyst, followed by
treatment with a catalytic amount of tetrabutylammonium
fluoride (TBAF) and heating with alkyne 9a, an aromatiza-
tion reaction proceeded and hexasubstituted benzene deri-
vative 10a was obtained in 83% yield (entry 1). A β-keto ester
bearing a phenyl group at the β-position, 1e, and without a
substituent at the active methylene moiety, 1a, provided
multisubstituted aromatic compounds, 10b and 10c, in
64% and 84% yields, respectively (entries 2 and 3). When
an internal alkyne was employed, the structure of the pro-
ducts changed dramatically, as can be seen by comparing the
products obtained in eq 1 with those in Table 2, entry 3.
1-Phenyl-1-propyne (2h) and terminal acetylenes, such as
phenylacetylene (2a) and 1-dodecyne (2i), also afforded
polysubstituted aromatic compounds in good to excellent
yields (entries 4-8).14 Interestingly, in the case of terminal
acetylenes, 2a and 2i, the addition of TBAF lowered the
reaction temperature dramatically, and 2-pyranone deriva-
tives 8 were formed under milder conditions (entries 6 and
8).8 Two regioisomers of hexasubstituted aromatic com-
pounds, 10g and 10h, could be synthesized selectively by
exchanging two substituents of the β-keto esters, 1f and 1g
(entries 9 and 10). In this reaction, the regioselective insertion
of alkynes into a carbon-carbon bond is important to
generate 10g and 10h, selectively. Ethyl propiolate (9b) also
afforded pentasubstituted aromatic compounds, 10i and a
mixture of 10j þ 10k, in 86% and 77% (10j:10k = 39:61)
yields, respectively (entries 11 and 12).
SCHEME 3. Formation of Tetrasubstituted Aromatic Com-
pounds 3 via an Alkenyl-Manganese Intermediate
possible reaction pathways (Schemes 1-3). The first is that
the reaction proceeds via the formation of a manganacyclo-
pentadiene intermediate, which suggests that two substitu-
ents are located at the 2- and 5-positions due to the steric
factor (Scheme 1). The second possibility is that the reaction
proceeds via the formation of a metalacyclopentene inter-
mediate, which is produced by a reaction between a 1,
3-dicarbonyl compound and an alkyne (Scheme 2).9 The
third possibility is the formation of an alkenyl-manganese
intermediate via the stepwise insertion of two alkynes in the
opposite orientation to each other (Scheme 3). Very recently,
Nakamura, Tsuji, and co-workers reported on the mechan-
istic study of the [2þ2þ2] cycloaddition.10 In the paper, they
concluded that the reaction proceeds via the route shown in
Scheme 3.
Rhenium-Catalyzed Synthesis of Penta- and Hexasubsiti-
tuted Aromatic Compounds via Carbon-Carbon Bond Clea-
vage of β-Keto Esters. When β-keto esters with a substituent
at the active methylene moiety were employed, the structure
of the products was changed dramatically, as can be seen by
comparing the products obtained in eq 1 with those in eq 4.
Treatment of ethyl 2-methyl-3-oxobutanoate (1d) with diphe-
nylacetylene (2g) in the presence of a catalytic amount of a
rhenium complex, [ReBr(CO)3(thf)]2, and molecular sieves in
toluene at 180 °C for 24 h, resulted in the insertion of 2g into a
carbon-carbon single bond of 1d and successive intramolecular
The regioselective synthesis of a multisubstituted aromatic
compound could also be achieved with use of a manganese
complex, MnBr(CO)5, as a catalyst; however, the yield of
the multisubstituted aromatic compound was lower than
that of the rhenium-catalyzed transformation. For example,
(11) Kuninobu, Y.; Takata, H.; Kawata, A.; Takai, K. Org. Lett. 2008,
10, 3133.
(12) For some representative examples of 2-pyranone synthesis, see:
(a) Cho, S. H.; Liebeskind, L. S. J. Org. Chem. 1987, 52, 2631. (b) Tsuda,
T.; Morikawa, S.; Sumiya, R.; Saegusa, T. J. Org. Chem. 1988, 53, 3140.
(c) Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39, 5713.
(d) Fukuyama, T.; Higashibeppu, Y.; Yamaura, R.; Ryu, I. Org. Lett. 2007,
9, 587.
(13) For the formation of aromatic compounds from 2-pyranones and
acetylenes, see: (a) Tam, T. F.; Coles, P. Synthesis 1988, 383. (b) Afarinkia,
K.; Vinader, V.; Nelson, T. D.; Posner, G. H. Tetrahedron 1992, 48, 9111.
(14) Diels-Alder reactions between 2-pyranone 8b and alkyne 9a were
(9) The intermediate shown in Scheme 2 is thought to be a manganese-
and rhenium-catalyzed ring expansion and carbon-chain extension reaction.
See: Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2006, 128,
11368. See also ref 8.
(10) Nakamura’s group reported on the mechanistic investigations. In the
paper, they claimed that the reaction must proceed via the formation of
alkenyl-magnesium intermediate (Scheme 3). See: Yoshikai, N.; Zhang, S.;
Yamagata, K.-i.; Tsuji, H.; Nakamura, E. J. Am. Chem. Soc. 2009, 131, 4099.
investigated in the presence or absence of a rhenium catalyst,
[ReBr(CO)3(thf)]2, and MS4A to clarify the role of the rhenium catalyst
and MS4A in the Diels-Alder reactions. The yields are as follows: no
catalyst 53%; [ReBr(CO)3(thf)]2 (2.5 mol %) 80%; [ReBr(CO)3(thf)]2 (2.5
mol %) þ MS4A (200 wt%-Re cat.) 64%; and MS4A (200 wt%-Re cat.)
40%. These results show that a rhenium catalyst, [ReBr(CO)3(thf)]2, accel-
erated the Diels-Alder reaction between 8b and 9a, whereas MS4A slightly
inhibited the Diels-Alder reaction.
336 J. Org. Chem. Vol. 75, No. 2, 2010

Kuninobu et al.
JOCArticle
TABLE 2. Rhenium-Catalyzed Synthesis of Multisubstituted Aromatic Compounds 10 from β-Keto Esters 1 and Alkynes 2 and 9a
entry
R1
Me
R2
Me
Me
H
Me
Me
Me
Me
Me
nC5H11
compd no.
R3
Ph
Ph
Ph
Me
H
R4
compd no.
R5
R6
compd no.
% yieldb
1
2
3
4
5
6
7
8
9
1d
1e
1a
1d
1d
1d
1d
1d
1f
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
2g
2g
2g
2h
2ac
2ae
2if
2ie
2j
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
9a
9a
9a
10a 83 (88)
10b 64 (67)
10c 84 (89)
10d 91 (92)
10e 87 (93)
10e 80 (85)
10f 72 (77)
10f 66 (71)
10g þ 10h 85 (89)
[10g:10h = 96:4]g
10g þ 10h 83 (89)
[10g:10h = 6:94]g
10i 86 (89)
Ph
Me
Me
Me
Me
Me
Me
Me
9a
9ad
9ad
9ad
9ad
9a
H
H
H
nC6H13
10
nC5H11
Me
1g
nC6H13
Ph
2j
CO2Et
CO2Et
9a
11
12
Me
Ph
Me
Me
1d
1e
Ph
Ph
Ph
Ph
2g
2g
CO2Et
CO2Et
H
H
9b
9b
10j þ 10k 77 (81)
[10j:10k = 39:61]h
a1 (1 equiv), 2 (1.2 equiv), 9 (2 equiv). bYield determined by 1H NMR is reported in parentheses. c80 °C, 8 h; 180 °C, 16 h. d9a (1 equiv, 3 times) was
added every 8 h. e80 °C, 8 h. Then, TBAF (10 mol %) was added, and the mixture was stirred at 25 °C for 8 h. f48 h. gThe ratio of 10g and 10h is given in
square brackets. hThe ratio of 10j and 10k is given in square brackets.
pentasubstituted aromatic compound 10e was obtained
in 64% yield by the reaction of β-keto ester (1d) with
phenylacetylene (2a) in the presence of a catalytic amount
of MnBr(CO)5 followed by treatment with alkyne 9a (eq 5).15
In this reaction, 2-pyranone 8b, which is an intermediate
of 10e, remained in 23% yield (eq 5). However, 2-pyranones
were not formed when internal alkynes were used instead
of 2a.
applying a rhenium-catalyzed reaction (eq 6). Treatment of
β-keto ester 1d, 1e, or 1g with alkyne 2g in the presence
of a rhenium catalyst, [ReBr(CO)3(thf)]2, produced the
corresponding 2-pyranones 8a, 8c, and 8d. After the for-
mation of the 2-pyranones, a mixture of 2-trimethylsilyl-
phenyl triflate (11) and cesium fluoride was added without
isolation of 8a, 8c, and 8d. As a result, tetrasubstituted
naphthalene derivatives 12a, 12b, and 12c were produced in
83-96% yields.
The differences between rhenium and manganese catalysts
in the formation of 2-pyranones are summarized as follows:
(1) In the case of terminal aryl alkynes, a manganese catalyst,
MnBr(CO)5, shows a higher catalytic activity compared with
a rhenium catalyst, [ReBr(CO)3(thf)]2. (2) In other cases,
such as terminal aliphatic alkynes and internal alkynes, the
rhenium catalyst has a higher catalytic activity (the manga-
nese catalyst promoted the formation of 2-pyranones from
terminal aliphatic alkynes in low yields, and did not produce
2-pyranones when internal alkynes were employed).
Anthracene derivative 14a was also generated in 79%
yield by treatment with a mixture of 2-(trimethylsilyl)-
naphthalen-3-yl trifluoromethanesulfonate (13) and
cesium fluoride instead of 11 and cesium fluoride after
the formation of 2-pyranone 8a (eq 7). When β-keto ester 1f
was treated with diphenylacetylene (2g), the corresponding
Synthesis of naphthalene derivatives 12 could be
achieved in excellent yields under mild conditions by
(15) In the first step of the reaction, 2-pyranone8b was formed in 96% yield.
J. Org. Chem. Vol. 75, No. 2, 2010 337

Kuninobu et al.
JOCArticle
anthracene derivative 14b was produced in 59% yield (eq
7).
SCHEME 4. Proposed Mechanism for the Formation of Mul-
tisubstituted Aromatic Compounds
Intramolecular reaction could also be used to synthesize
multisubstituted bicyclic aromatic compounds. By the reac-
tion of a β-keto ester with an acetylene moiety, 15, using a
rhenium catalyst, [ReBr(CO)3(thf)]2, followed by treatment
with alkyne 9c, tetrahydronaphthalene derivative 16 was
afforded in 84% yield (eq 8). This reactivity is in sharp
contrast to other intramolecular additions of β-keto esters
to alkynes, such as transition metal-catalyzed Conia-ene
reactions.16
Rhenium-Catalyzed Synthesis of Tri-, Tetra-, and Penta-
substituted Aromatic Compounds via Carbon-Carbon Bond
Cleavage. When 1,3-ketones were employed as substrates
instead of the β-keto esters used in eq 4, the products were
changed dramatically. Treatment of 1,3-diketone 4b with
phenylacetylene (2a) in the presence of a catalytic amount of
[ReBr(CO)3(thf)]2 and molecular sieves afforded tetrasub-
stituted aromatic compound 17a in 11% yield (eq 9). Since
there are many side products, the yield of 17a was low. In the
side products, a tetrasubstituted acetophenone derivative 5
and deacylated aromatic compound 6 were detected by GC-
MS. This result shows that the [2þ2þ2] type reaction shown
in eq 2 also proceeded. In this reaction, a rhenium complex,
Re2(CO)10, and manganese complexes, MnBr(CO)5 and
Mn2(CO)10, did not show similar catalytic activities.
The proposed reaction mechanism is as follows (Scheme 4):
(1) formation of a rhenacyclopentene intermediate by a
reaction between a rhenium catalyst, β-keto ester, and alkyne
(in this step, the β-keto ester and alkyne orient
regioselectively); (2, 3) after the formation of the rhenacy-
clopentene intermediate, a δ-keto ester is generated via (2-a
and 3-a) carbon-carbon bond cleavage via a retro-aldol
reaction,17,18 followed by reductive elimination or (2-b and
3-b) a pathway that has a different timing for the reductive
elimination;8,9 (4) isomerization of the olefinic moiety of
the δ-keto ester and cyclization leading to 2-pyranone;19
(5) Diels-Alder reaction between 2-pyranone and the
second alkyne; and (6) decarboxylation.
When p-methoxyphenylacetylene (2b) was used, tetrasub-
stituted aromatic compound 17b was formed in 11% yield
(Table 3, entry 1).20 By the reactions of 1,3-diketone with a
phenyl group, 4c, or without any substituent at the active
methylene moiety, 4a, with p-methoxyphenylacetylene (2b),
biaryl compounds 17c and 17d were provided in 22% and
17% yields, respectively (Table 3, entries 2 and 3). By using
diphenylacetylene (2g), the yield of the aromatic compound
increased, and pentasubstituted aromatic compound 17e was
afforded in 43% yield (Table 3, entry 4). However, the
reaction did not occur with 6-dodecyne.
(16) For examples of transition metal-catalyzed Conia-ene reactions, see:
(a) Kennedy-Smith, J. J.; Staben, S. T.; Toste, F. D. J. Am. Chem. Soc. 2004,
126, 4526. (b) Gao, Q.; Zheng, B.-F.; Li, J.-H.; Yang, D. Org. Lett. 2005, 7,
2185. (c) Tsuji, H.; Yamagata, K.-i.; Itoh, Y.; Endo, K.; Nakamura, M.;
Nakamura, E. Angew. Chem., Int. Ed. 2007, 46, 8060. (d) Deng, C.-L.; Song,
R.-J.; Guo, S.-M.; Wang, Z.-Q.; Li, J.-H. Org. Lett. 2007, 9, 5111. See also
ref 5.
(17) There have been some examples on chemical transformations via
carbon-carbon bond cleavage. See: (a) Murakami, M.; Ito, Y. (Murai, S., Ed.)
Top. Organomet. Chem. 1999, 3, 97. (b) Jun, C.-H. Chem. Soc. Rev. 2004, 33,
610.
If the reaction proceeds between 1 equiv of 1,3-diketones
and 1 equiv of alkynes, then there is one extra carbon
(18) (a) Kochetkov, N. K.; Kudryashov, L. J.; Gottich, B. P. Tetrahedron
1961, 12, 63. (b) Crombie, L.; James, A. W. G. Chem. Commun 1966, 357.
(19) (a) Fried, J.; Elderfield, R. C. J. Org. Chem. 1941, 6, 566. (b) Wiley,
R. H.; Jarboe, C. H.; Hayes, F. N. J. Am. Chem. Soc. 1957, 79, 2602.
(20) The structure of 17b was determined by the comparison with the
spectrum data of 17b, which was prepared by palladium-catalyzed cross-
coupling reaction between 4-methoxyphenylboronic acid and 2,3,5-tri-
methylphenyl trifluoromethanesulfonate.
338 J. Org. Chem. Vol. 75, No. 2, 2010

Kuninobu et al.
JOCArticle
TABLE 3. Reactions between 1,3-Diketones 4 and Alkynes 2a
SCHEME 5. Proposed Mechanism for the Formation of Aro-
matic Compounds 17
a4 (2 equiv), 2 (1 equiv). bYield determined by 1H NMR is reported
d
in parentheses. c4 (1 equiv), 2 (1.2 equiv). MS4A (200 wt %-Re cat.),
150 °C.
atom in the biaryl products. To elucidate the source of the
one carbon atom, we examined the following 13C labeling
experiment.
13C labeled 1,3-dicarbonyl compound 4d-C was employed
(eq 10). Interestingly, biaryl product 17f-C contained two
13C enriched carbon atoms. This result indicates that a
methyl carbon of the 1,3-dicarbonyl compounds (see the
structure of 4d-C) is the source of the additional carbon
atom.
the unsaturated 1,5-diketone and another 1,3-diketone;
(5) dehydration; (6) intramolecular aldol reaction; and
(7) elimination of β-keto carboxylic acid to give multisub-
stituted aromatic compounds.21
Conclusion
We have succeeded in the synthesis of aromatic com-
pounds using three different methods. The first approach is
a manganese-catalyzed [2þ2þ2] cycloaddition between 1,3-
dicarbonyl compounds and 2 equiv of terminal alkynes. In
this reaction, two substituents of the alkynes locate on 1,4-
positions of the formed aromatic skeletons regioselectively.
The second is a rhenium- and manganese-catalyzed formal
[2þ1þ2þ1] cycloaddition reaction of β-keto esters and two
kinds of alkynes. The first alkynes insert into a car-
bon-carbon single bond of β-keto esters regioselectively,
and successive intramolecular cyclization provides 2-pyra-
none derivatives. The 2-pyranones can act as diene compo-
nents, and react with the second alkynes in a Diels-Alder
fashion to give multisubstituted aromatic compounds regio-
selectively. The third approach is a rhenium-catalyzed
formal [2þ2þ1þ1] cycloaddition between 1,3-diketones
and alkynes. In this reaction, aromatic compounds are
derived from 1,3-diketones, alkynes, and a part of another
From the 13C labeling experiments and the positions of
substituents at the substrates and products, the proposed
reaction mechanism is as follows (Scheme 5): (1) formation
of a rhenacyclopentene intermediate from a 1,3-diketone,
alkyne, and rhenium; (2, 3) after the formation of the
rhenacyclopentene intermediate, there are two possible path-
ways, the difference is the timing of reductive elimination:
Path A: (2-a) retro-aldol reaction and (3-a) reductive elim-
ination to give unsaturated 1,5-diketone; Path B: (2-b)
reductive elimination and (3-b) retro-aldol reaction to
give unsaturated 1,5-diketone; (4) aldol reaction between
(21) In Scheme 5, the formation of β-keto acid was not detected by GC.
The β-keto carboxylic acid might be decomposed (Krapcho reaction) or
reacted with a species before decomposition under the reaction conditions.
Therefore, the generation of β-keto carboxylic acid is only speculated.
J. Org. Chem. Vol. 75, No. 2, 2010 339

Kuninobu et al.
JOCArticle
1,3-diketone. Interestingly, aromatic compounds can be
synthesized by three different means whereas these three
reactions employ 7 group transition metal catalysts and
similar substrates, which are 1,3-dicarbonyl compounds
and alkynes. We hope that these methods will become
powerful tools to synthesize multisubstituted aromatic com-
pounds.
chromatography, diethyl 3,6-dimethyl-4,5-diphenylphthalate
(10a) was obtained in 83% yield. 1H NMR (400 MHz, CDCl3)
δ 1.39 (t, J = 7.2 Hz, 6H), 2.08 (s, 6H), 4.38 (q, J = 7.2 Hz, 4H),
6.88 (d, J = 7.8 Hz, 4H), 7.05-7.14 (m, 6H); 13C NMR (100
MHz, CDCl3) δ 14.3, 18.6, 20.7, 126.1, 127.5, 129.4, 130.0,
133.4, 140.2, 144.8, 168.6; IR (Nujol/cm-1) 3060, 3011, 2924,
2855, 1727, 1600, 1568, 1479, 1072, 964, 752, 727, 625.
Anal. Calcd for C26H26O4: C, 77.59; H, 6.51. Found: C, 77.44;
H, 6.54.
Preparation of Naphthalene Derivatives. 1,4-Dimethyl-2,
3-diphenylnaphthalene (12a). A mixture of ethyl 2-methylace-
toacetate (1d, 72.1 mg, 0.500 mmol) and diphenylacetylene (2g,
107 mg, 0.600 mmol) in the presence of [ReBr(CO)3(thf)]2 (10.6
mg, 0.0125 mmol) and powdered MS4A (21.2 mg, 200 wt %-Re
cat.) in toluene (1.0 mL) was heated at 180 °C under argon
atmosphere. After 24 h, 2-(trimethylsilyl)phenyl triflate (11,
223.8 mg, 0.750 mmol), cesium fluoride (228 mg, 1.50 mmol),
and acetonitrile (1.0 mL) were added. The reaction mixture was
stirred at 20 °C for 24 h. After purification by silica gel column
chromatography, 1,4-dimethyl-2,3-diphenylnaphthalene (12a)
was obtained in 91% yield. 1H NMR (400 MHz, CDCl3) δ 2.44
(s, 6H), 6.95-6.98 (m, 4H), 7.07-7.14 (m, 6H), 7.57-7.60 (m,
2H), 8.13-8.16 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 16.9,
125.0, 125.7, 125.8, 127.2, 129.4, 130.4, 132.0, 139.4, 141.7; IR
(Nujol/cm-1) 3055, 3011, 2928, 2860, 1456, 1377, 1070, 916, 851,
750, 702, 599; Anal. Calcd for C24H20: C, 93.46; H, 6.54. Found:
C, 93.23; H, 6.64.
Experimental Section
Synthesis of 30-Methyl[1,10;40,100]terphenyl-20-carboxylic Acid
Ethyl Ester (3a). A mixture of β-keto ester 1a (32.5 mg, 0.250
mmol), phenylacetylene (2a, 63.8 mg, 0.625 mmol), MnBr(CO)5
(3.4 mg, 0.0125 mmol), and molecular sieves 4A (3.9 mg, 115
wt %-Mn cat.) was stirred at 80 °C for 24 h. After the reaction
was quenched with a solution of HCl in ether (0.25 mL), the
solvent was removed in vacuo. The product was isolated by
column chromatography on silica gel (hexane:ethyl acetate =
1
20:1) to give 3a in 85% yield as a white solid. H NMR (400
MHz, CDCl3) δ 0.98 (t, J = 7.2 Hz, 3H), 2.28 (s, 3H), 4.08 (q, J
= 7.2 Hz, 2H), 7.26-7.46 (m, 12H); 13C NMR (100 MHz,
CDCl3) δ 13.7, 17.6, 61.0, 127.0, 127.1, 127.4, 128.17, 128.21,
128.4, 129.3, 130.8, 132.4, 134.4, 139.0, 140.7, 141.1, 141.7,
170.0; IR (Nujol/cm-1) 1719, 1302, 1246, 1173, 1144, 1067,
1007, 835, 766, 721, 700; HR-MS calcd for C22H20O2 (Mþ)
316.1463, found 316.1452.
Selective Synthesis of 5. A mixture of 2,4-pentanedione (4,
25.0 mg, 0.250 mmol), phenylacetylene (2a, 63.8 mg, 0.625
mmol), MnBr(CO)5 (3.4 mg, 0.0125 mmol), molecular sieves
4A (3.9 mg, 115 wt %-Mn cat.), and toluene (0.50 mL) was
stirred at 50 °C for 24 h. After the solvent was removed in vacuo,
the product was isolated by column chromatography on silica
gel (hexane:ethyl acetate = 20:1) to give 5 in 69% yield as a
white solid.
Selective Synthesis of 6. A mixture of 2,4-pentanedione (4,
25.0 mg, 0.250 mmol), phenylacetylene (2a, 63.8 mg, 0.625
mmol), MnBr(CO)5 (3.4 mg, 0.0125 mmol), Sc(OTf)3 (6.2 mg,
0.0125 mmol), toluene (0.25 mL), and water (0.25 mL) was
stirred at 80 °C for 24 h. After the solvent was removed in vacuo,
the product was isolated by column chromatography on silica
gel (hexane:ethyl acetate = 10:1) to give 6 in 68% yield as a
white solid.
Synthesis of 3,6-Dimethyl-4,5-diphenylpyran-2-one (8a). A
mixture of ethyl 2-methylacetoacetate (1d, 72.1 mg, 0.500 mmol)
and diphenylacetylene (2g, 107 mg, 0.600 mmol) in the presence
of [ReBr(CO)3(thf)]2 (10.6 mg, 0.0125 mmol) and powdered
MS4A (21.2 mg, 200 wt %-Re cat.) in toluene (1.0 mL) was
heated at 180 °C for 24 h under argon atmosphere. After
purification by silica gel column chromatography, 3,6-dimeth-
yl-4,5-diphenylpyran-2-one (8a) was obtained in 96% yield. 1H
NMR (400 MHz, CDCl3) δ 1.92 (s, 3H), 2.12 (s, 3H), 6.86-6.90
(m, 4H), 7.12-7.17 (m, 6H); 13C NMR (100 MHz, CDCl3) δ
14.3, 18.5, 119.2, 119.4, 127.1, 127.5, 127.8, 127.9, 128.2, 130.4,
135.2, 136.5, 154.0, 155.6, 164.0; IR (Nujol/cm-1) 3086, 3062,
3027, 2921, 2859, 1733, 1718, 1653, 1457, 1379, 1041, 896.
Anal. Calcd for C19H16O2: C, 82.58; H, 5.84. Found: C, 82.46;
H, 5.90.
Typical Procedure for the Synthesis of Multisubstituted
Benzenes from β-Keto Esters and Two Alkynes. Diethyl 3,6-
Dimethyl-4,5-diphenylphthalate (10a). A mixture of ethyl 2-
methylacetoacetate (72.1 mg, 0.500 mmol) and diphenylacety-
lene (107 mg, 0.600 mmol) in the presence of [ReBr(CO)3(thf)]2
(10.6 mg, 0.0125 mmol) and powdered MS4A (21.2 mg, 200
wt %-Re cat.) in toluene (1.0 mL) was heated at 180 °C under
argon atmosphere. After 24 h, acetylene dicarboxylic acid ethyl
ester (170 mg, 1.00 mmol) was added. The reaction mixture was
stirred at 150 °C for 24 h. After purification by silica gel column
Preparation of Anthracene Derivatives. 1,4-Dimethyl-2,
3-diphenylanthracene (14a). A mixture of ethyl 2-methylacetoa-
cetate (1d, 72.1 mg, 0.500 mmol) and diphenylacetylene (2g, 107
mg, 0.600 mmol) in the presence of [ReBr(CO)3(thf)]2 (10.6 mg,
0.0125 mmol) and powdered MS4A (21.2 mg, 200 wt %-Re cat.)
in toluene (1.0 mL) was heated at 180 °C under argon atmo-
sphere. After 24 h, 2-(trimethylsilyl)naphthalen-3-yl trifluoro-
methanesulfonate (13, 261.3 mg, 0.750 mmol), cesium fluoride
(228 mg, 1.50 mmol), and acetonitrile (1.0 mL) were added. The
reaction mixture was stirred at 80 °C for 12 h. After purification
by silica gel column chromatography, 1,4-dimethyl-2,3-diphe-
nylanthracene (14a) was obtained in 91% yield. 1H NMR (400
MHz, CDCl3) δ 2.66 (s, 6H), 7.09-7.11 (m, 4H), 7.18-7.26 (m,
6H), 7.56-7.59 (m, 2H), 8.13-8.15 (m, 2H), 8.76 (s, 2H); 13C
NMR (100 MHz, CDCl3) δ 17.2, 123.7, 125.4, 125.9, 127.2,
128.3, 130.4, 130.9, 131.5, 138.8, 141.8; IR (Nujol /cm-1) 2723,
1599, 1460, 1376, 1211, 1030, 872, 722, 700, 665. Anal. Calcd for
C28H22: C, 93.81; H, 6.19. Found: C, 93.77; H, 6.28.
Intramolecular Reaction. Dimethyl 3-Methyl-4-phenyl-5,6,7,
8-tetrahydronaphthalene-1,2-dicarboxylate (16). A mixture of
ethyl 2-acetyl-8-phenyloct-7-ynoate (15, 143 mg, 0.500 mmol),
[ReBr(CO)3(thf)]2 (10.6 mg, 0.0125 mmol), and powdered
MS4A (10.6 mg, 100 wt %-Re cat.) in toluene (2.0 mL) was
heated at 150 °C under argon atmosphere for 24 h. Then, an
acetylene dicarboxylic acid methyl ester (9c, 142 mg, 1.00 mmol)
was added and the mixture was stirred at 150 °C. After 24 h, an
additional acetylene dicarboxylic acid methyl ester (9c, 142 mg,
1.00 mmol) was added and the mixture was heated at 150 °C for
24 h. After purification by silica gel column chromatography,
dimethyl 3-methyl-4-phenyl-5,6,7,8-tetrahydronaphthalene-1,
2-dicarboxylate (16) was obtained in 84% yield. 1H NMR
(400 MHz, CDCl3) δ 1.62-1.66 (m, 2H), 1.68-1.74 (m, 2H),
1.98 (s, 3H), 2.29 (t, J = 6.3 Hz, 2H), 2.83 (t, J = 6.3 Hz, 2H),
3.86 (s, 3H), 3.89 (s, 3H), 7.05 (d, J = 6.9 Hz, 2H), 7.34-7.38
(m, 1H), 7.42-7.46 (m, 2H); 13C NMR (100 MHz, CDCl3)
δ 17.94, 22.28, 22.52, 27.30, 29.32, 52.26, 52.28, 127.06, 128.57,
128.77, 129.55, 131.34, 131.75, 132.99, 138.63, 140.08,
144.71, 169.16, 169.20; IR (Nujol/cm-1) 3051, 2930, 2852,
1725, 1568, 1435, 1126, 1028, 958, 846, 794, 731, 704, 609. Anal.
Calcd for C21H22O4: C, 74.54; H, 6.55. Found: C, 74.77; H,
6.60.
340 J. Org. Chem. Vol. 75, No. 2, 2010

Kuninobu et al.
JOCArticle
Typical Procedure for Rhenium-Catalyzed Synthesis of Multi-
substituted Aromatic Compounds from 1,3-Diketones and
Alkynes. 1,3,4-Trimethyl-5-phenylbenzene (17a). A mixture of
3-methyl-2,4-pentanedione (4b, 57.1 mg, 0.500 mmol) and
phenylacetylene (2a, 61.3 mg, 0.600 mmol) in the presence of
[ReBr(CO)3(thf)]2 (10.6 mg, 0.0125 mmol) and powdered MS4A
(21.2 mg, 100 wt %-Re cat.) in toluene (1.0 mL) was heated at
80 °C under argon atmosphere for 24 h. After purification by
silica gel column chromatography, 1,3,4-trimethyl-5-phenyl-
benzene (17a) was obtained in 11% yield. 1H NMR (400
MHz, CDCl3) δ 2.13 (s, 3H), 2.33 (s, 6H), 6.94 (s, 1H), 7.02 (s,
1H), 7.30-7.35 (m, 3H), 7.39-7.43 (m, 2H); 13C NMR (100
MHz, CDCl3) δ 16.5, 20.6, 20.8, 126.5, 127.9, 128.3, 129.4,
129.7, 130.8, 134.5, 137.0, 142.2, 142.7; IR (neat /cm-1) 3028,
2918, 2862, 1601, 1576, 1495, 1474, 1456, 1382, 1072, 1009, 858,
773, 758, 702, 646, 584. Anal. Calcd for C15H16: C, 91.78; H,
8.22. Found: C, 91.94; H, 8.12.
Acknowledgment. Financial support by a Grant-in-Aid for
Scientific Research on Priority Areas (No. 18037049, “Ad-
vanced Molecular Transformations of Carbon Resources”)
from the Ministry of Education, Culture, Sports, Science, and
Technology of Japan, and for Young Scientists (B) (No.
18750088) from the Japan Society for the Promotion of Science.
Supporting Information Available: The general procedure,
product characterization data for 3b-h, 5, 6, 10b-k, 12b,c, 14b,
and 17b-f, and 1H and 13C NMR spectra of 3a-h, 5, 6, 8,
10a-k, 12a-c, 14a,b, 16, and 17a-f. This material is available
free of charge via the Internet at http://pubs.acs.org.
J. Org. Chem. Vol. 75, No. 2, 2010 341