Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,2-bis(propiolyl)benzenes with monoalkynes leading to substituted anthraquinones

Article abstract of DOI:10.1039/b301762a

[2 + 2 + 2] cycloadditions of 1,2-bis(propiolyl)benzenes with monoalkynes were effectively catalysed by Cp*RuCl(cod) under mild conditions to give substituted anthraquinones in moderate to high yields.

Full text of DOI:10.1039/b301762a

Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,2-bis(propiolyl)benzenes
with monoalkynes leading to substituted anthraquinones†
Yoshihiko Yamamoto,*a Koichi Hata,b Takayasu Arakawab and Kenji Itohb
a Department of Applied Chemistry, Graduate School of Engineering, Nagoya University, Chiksa, Nagoya
464-8603, Japan. E-mail: yamamoto@apchem.nagoya-u.ac.jp; Fax: 81 52 789 3209; Tel: 81 52 789 3337
b Department of Molecular Design and Engineering, Graduate School of Engineering, Nagoya University,
Chiksa, Nagoya 464-8603, Japan. E-mail: itohk@apchem.nagoya-u.ac.jp; Fax: 81 52 789 3205; Tel: 81 52
789 5112
Received (in Cambridge, UK) 14th February 2003, Accepted 4th April 2003
First published as an Advance Article on the web 2nd May 2003
[2 + 2 + 2] cycloadditions of 1,2-bis(propiolyl)benzenes with
monoalkynes were effectively catalysed by Cp*RuCl(cod)
under mild conditions to give substituted anthraquinones in
moderate to high yields.
tives 1 as diyne components. Initially, a terminal diketodiyne
substrate 1a was reacted with 1-hexyne 2a (2 equiv.) in the
presence of 1 mol% Cp*RuCl(cod) in 1,2-dichloroethane
(DCE) at room temperature. After stirring the solution for 4 h,
complete consumption of 1a was observed by TLC analysis.
Concentration of the reaction mixture followed by silica gel
column chromatography afforded the desired anthraquinone
3aa in 71% yield (Scheme 1). The cycloaddition completed for
1.5 h with increased amounts of both the catalyst (2 mol%) and
2a (4 equiv.), and the yield was improved to 90% (Table 1, run
1).‡ The present ruthenium catalysis proved compatible with
various functional groups on the monoalkyne components. In a
similar manner to run 1, propargyl methyl ether 2b, 5-chloro-
1-pentyne 2c, methyl 5-hexynoate 2d, and N-propargyl phthali-
mide 2e gave anthraquinones possessing a functionalised side
chain in high yields (runs 2–5). Interestingly, the reaction rate
was increased for the latter two monoalkynes, indicating that
coordination of the ester or imide carbonyl groups to the
ruthenium centre facilitated the cycloaddition. On the other
hand, the ruthenium catalysis is quite sensitive to the steric bulk
of the monoalkyne components. Sterically demanding tert-
butylacetylene 2f reacted more slowly than the above monoalk-
ynes 2a–e (run 6). Consequently, the yield of the expected
quinone 3af is moderate probably due to the competitive
dimerization of 1a. Phenylacetylene 2g also exhibited low
reactivity, requiring an increased catalyst loading of 5 mol% to
ensure the complete conversion of 1a (run 7). In striking
contrast, upon stirring with the 2 mol% precatalyst under an
acetylene atmosphere, 1a was efficiently converted into 3ah
within 0.5 h in 92% yield (run 8).
The transition-metal mediated [2 + 2 + 2] cycloaddition1 of a
1,2-bis(propiolyl)benzene 1 with a monoalkyne is a convergent
and straightforward route to substituted anthraquinone frame-
works (Scheme 1). Such a potentially useful anthraquinone
annulation was first realized by means of the reaction of isolated
naphthoquinone-fused rhodacyclopentadiene complexes with
monoalkynes,2 and direct coupling of diketodiyne 1c and
monoalkynes was independently achieved using highly toxic
Ni(CO)4 in large excess.3 From the viewpoint of environmental
safety, an alternative catalytic protocol is, however, highly
desirable. In this context, some research groups reported
catalytic versions of anthraquinone annulations. Müller and
Meier et al. extended their own works to a catalytic protocol
utilizing 5–25 mol% Ni(PPh3)2(CO)2 as a precatalyst at 60–130
°C.4 Thereafter, Vollhardt’s group applied their CpCo(CO)2-
catalyzed method to two diketodiyne substrates to result in low
yields of around 20%.5 More recently, McDonald and co-
workers reported the cycloaddition of a diketodiyne 1b with
alkynylglycals using 20 mol% ClRh(PPh3)3 in refluxing EtOH,
in which interesting C-arylglycosides were obtained in 35–58%
yields.6 These existing examples, however, have some disad-
vantages which need to be improved: (1) sub-stoichiometric
amounts of precatalysts (20–33 mol%) or reaction temperatures
above 60 °C are required, (2) the diyne substrate was almost
completely confined to the internal diketodiynes 1b and 1c, and
(3) the product yields were not higher than 80%.
In addition to the above terminal monoalkynes, internal
alkynes can be employed for our protocol, although relatively
higher catalyst loadings are required. The reaction of 1a with
3-hexyne 2i for 20 h gave rise to a disubstituted anthraquinone
3ai in 33% yield (run 9). Such a low yield was again ascribed to
the competitive dimerization of 1a. An internal diketodiyne 1b
possessing methyl substituents at both alkyne termini was
We have previously revealed that a ruthenium(II) complex,
Cp*RuCl(cod) (Cp* = pentamethylcyclopentadienyl, cod =
1,5-cyclooctadiene), catalysed the cycloaddition of 1,6-diynes
with monoalkynes at ambient temperature to chemo- and regio-
selectively give bicyclic benzene derivatives in good yields.7 To
extend the ruthenium catalysis, we investigated the ruthenium-
catalysed cycloaddition of 1,2-bis(propiolyl)benzene deriva-
Table 1 Ruthenium-catalysed cycloadditions of 1 and monoalkynes
Catalyst
(mol%) Time
Yielda
(%)
Run
R1
R2
R3
1
2
3
4
5
6
7
8
9
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Et
Et
H
Ph
n-Bu
CH2OMe
(CH2)3Cl
(CH2)3CO2Me
CH2NPhthalb
t-Bu
Ph
Hc
Et
Et
n-Bu
Ph
2
1
2
2
1
2
5
2
5
1.5 h
3 h
1 h
0.5 h
10 min
6 h
3aa 90
3ab 84
3ac 81
3ad 84
3ae 76
3af 65
3ag 65
3ah 92
3ai 33
3bi 66
3ba 80
3bj 90
3 h
0.5 h
20 h
4 h
20 h
1 h
H
Scheme 1
10
11
12
Me
Me
Me
10
10
5
† Electronic supplementary information (ESI) available: experimental
procedures and analytical data. See http://www.rsc.org/suppdata/cc/b3/
b301762a/
a Isolated yields. b NPhthal = phthalimide. c 1 atm.
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CHEM. COMMUN., 2003, 1290–1291
This journal is © The Royal Society of Chemistry 2003

expected to be less prone to self-dimerization. Actually, upon
reacting with 2i in the presence of the 10 mol% precatalyst, 1b
afforded the desired tetrasubstituted anthraquinone 3bi in an
improved yield of 66% (run 10). The terminal alkyne 2a, also
reacted with 1b without difficulty to furnish a trisubstituted
product 3ba in 80% yield (run 11). As already described, phenyl
acetylene 2g was found less reactive compared to other terminal
monoalkynes, but, surprisingly, diphenylacetylene 2j reacted
with 1b with less precatalyst and a shorter reaction time to
afford 3bj in excellent yield (run 12). The reason for such a
striking difference in reactivity between 2g and 2j is not clear at
this stage.
bond distances [1.990(2) and 2.009(2) Å] are intermediate
between those of the ruthenacyclopentatriene complexes [I:
1.942(6), II: 1.969(4) Å] and a ruthenacyclopentadiene(phos-
phine) complex III11 [2.059(5) and 2.092(4) Å], indicative of
these bonds having partial double bond character. Actually, the
13C NMR spectrum (75 MHz, CDCl3) showed the characteristic
carbene resonance of C1 and C4 at d 263.89 ppm. The length of
the C2–C3 bond incorporated with the naphthoquinone ring is
also longer than those in I and II [1.430 vs. 1.377(12) or 1.37(1)
Å]. The isolated 4 never gave a cycloadduct upon exposure with
acetylene, diphenylacetylene, and dimethyl acetylenedicar-
boxylate.
The phenyl terminal groups on a diyne component gave a
deteriorative effect on the cycloaddition ability. No cycloadduct
was obtained from the reaction of 1c with both diphenyl
acetylene and acetylene. As previously proposed for the
ruthenium-catalyzed cycloaddition of 1,6-diynes and monoalk-
ynes, the present anthraquinone annulation probably proceeds
via bicyclic ruthenacycle intermediate.7,8 If this is the case, the
terminal phenyl groups on the diketodiyne might stabilize the
ruthenium–carbon bonds and thus reduce the reactivity of the
expected ruthenacycle 4. In good agreement with these
analyses, 4 was formed by simply stirring the solution of
Cp*RuCl(cod) and a slight excess of 1c in DCE at room
temperature for 0.5 h. Recrystallization from CHCl3/ether
afforded 4·CHCl3 in 79% yield as single crystals (Scheme 2).
The obtained single crystal was further submitted to X-ray
diffraction study.§
We gratefully acknowledge financial support (12450360)
from the Ministry of Education, Culture, Sports, Science and
Technology, Japan.
Notes and references
‡ Typical procedure—Synthesis of 3aa: To
a degassed solution of
Cp*RuCl(cod) (2.4 mg, 0.006 mmol) and 1-hexyne (98.7 mg, 1.2 mmol) in
1,2-dichloroethane (1 mL) was added a degassed solution of 1,2-bis(propio-
lyl)benzene 1a (55.4 mg, 0.30 mmol) in 1,2-dichloroethane (4 mL) by a
syringe for 20 min under Ar at room temperature. The solution was stirred
for 1.5 h, and concentrated in vacuo. The residue was purified by silica gel
flush column chromatography (hexane–AcOEt 25 : 1) to afford 3aa (72.3
mg, 90%) as colorless solids.
§ Crystallographic data: Intensity data were collected at 173 K on a Bruker
SMART APEX diffractometor with Mo-Ka radiation (0.71073 Å) and
graphite monochromator. The structure was solved by direct methods and
refined by full-matrix least-squares on F2 (SHELXTL). 4·CHCl3
[C35H30Cl4O2Ru, Mw = 725.46]; space group P21/n, monoclinic; a =
11.6335(6), b = 18.8471(10), c = 15.0128(8) Å, b = 111.8490(10)°, V =
3055.2(3) Å3; Z = 4, Dcalc = 1.577 g cm23; 23271 total reflections were
Scheme 2
As shown in Fig. 1, 4 has the expected naphthoquinone-fused
ruthenacyclic framework. The ruthenacycle core structure is
very similar to the precedent ruthenacyclopentatriene com-
plexes I9 and II10 formed from two phenyl acetylene molecules
and CpRuBr(cod) or Cp*RuCl(cod). The Ru–C1 and Ru–C4
measured of which 8153 were independent [R(int) = 0.0236]; final R1
0.0380, wR2 = 0.1072 [I > 2s(I)], and GOF = 1.060 (for all data, R1
=
=
0.0427, wR2 = 0.1103). CCDC reference number 203734. See http://
www.rsc.org/suppdata/cc/b3/b301762a/ for crystallographic data in CIF or
other electronic format.
1 For a review of transition-metal mediated cyclotrimerizations see: D. B.
Grotjahn, in Comprehensive Organometallic Chemistry II, ed. L. S.
Hegedus, E. W. Abel, F. G. A. Stone and G. Wilkinson, Pergamon,
Oxford, 1995 vol. 12, p. 741; N. E. Shore, in Comprehensive Organic
Synthesis, ed. B. M. Trost and I. Fleming, Pergamon, Oxford, 1991, vol.
5, p. 1037; S. Saito and Y. Yamamoto, Chem. Rev., 2000, 100, 2901.
2 E. Müller, Synthesis, 1974, 761.
3 F. Wagner and H. Meier, Tetrahedron, 1974, 30, 773.
4 E. Müller, A. Scheller, W. Winter, F. Wagner and H. Meier, Chem.-Ztg.,
1975, 99, 155.
5 R. L. Hillard III and K. P. C. Vollhardt, J. Am. Chem. Soc., 1977, 99,
4058.
6 F. E. McDonald, H. Y. H. Zhu and C. R. Holmquist, J. Am. Chem. Soc.,
1995, 117, 6605.
7 Y. Yamamoto, R. Ogawa and K. Itoh, Chem. Commun., 2000, 549.
8 Crystal structure for the corresponding rhodacycle: E. Müller, E.
Langer, H. Jäkle, H. Muhn, W. Hoppe, R. Graziani, A. Gieren and F.
Brandl, Z. Naturforsch., Teil B, 1971, 26, 305.
9 M. O. Albers, D. J. A. de Waal, D. C. Liles, D. J. Robinson, E. Singleton
and M. B. Wiege, J. Chem. Soc., Chem. Commun., 1986, 1680.
10 C. Ernst, O. Walter and E. Dinjus, J. Prakt. Chem., 1999, 341, 801.
11 C. S. Yi, J. R. Torres-Lubian, N. Liu, A. L. Rheingold and I. A. Guzei,
Organometallics, 1998, 17, 1257.
Fig. 1 ORTEP diagram of 4. Ellipsoids are shown at the 50% probability
level. All hydrogen atoms are omitted for clarity. Selected bond distances
(Å) and angles (°): Ru–Cl 2.3279(6), Ru–C1 1.990(2), Ru–C4 2.009(2),
C1–C2 1.395(3), C2–C3 1.430(3), C3–C4 1.400(3); Ru–C1–C2 118.08(15),
Ru–C4–C3 117.18(15), C1–Ru–C4 78.43(8), C1–C2–C3 113.11(19), C2–
C3–C4 113.11(19).
CHEM. COMMUN., 2003, 1290–1291
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