Synthesis of functionalized α-pyrone and butenolide derivatives by rhodium-catalyzed oxidative coupling of substituted acrylic acids with alkynes and alkenes

Article abstract of DOI:10.1021/jo901077r

(Chemical Equation Presented) The straightforward and efficient synthesis of α-pyrone and butenolide derivatives has been achieved by the rhodium-catalyzed oxidative coupling reactions of substituted acrylic acids with alkynes and alkenes, respectively. Some α-pyrones obtained exhibit solid-state fluorescence.

Full text of DOI:10.1021/jo901077r

pubs.acs.org/joc
On the other hand, transition-metal-catalyzed organic
Synthesis of Functionalized r-Pyrone and Butenolide
Derivatives by Rhodium-Catalyzed Oxidative
Coupling of Substituted Acrylic Acids with Alkynes
and Alkenes
reactions via C-H bond cleavage have been significantly
developed in recent years4 and, in some cases, successfully
substituted for those of the corresponding organic halides.
As one such example, we recently reported the direct oxida-
tive coupling of benzoic acids with alkynes and alkenes, such
as acrylates, under rhodium catalysis involving the cleavage
of their ortho C-H bond (Scheme 1).5 These reactions
provide straightforward pathways to isocoumarin and
phthalide derivatives from widely available benzoic acids.
Satoshi Mochida, Koji Hirano, Tetsuya Satoh,* and
Masahiro Miura*
Department of Applied Chemistry, Faculty of Engineering,
Osaka University, Suita, Osaka 565-0871, Japan
SCHEME 1. Coupling of Benzoic Acids with Alkynes and
Alkenes
satoh@chem.eng.osaka-u.ac.jp; miura@chem.eng.
osaka-u.ac.jp
Received May 21, 2009
Variously substituted acrylic acids are also readily available.
During our further studies of rhodium-catalyzed oxidative
coupling,6,7 it has been found that our catalyst system is
applicable to functionalization of acrylic acids through vinylic
C-H bond cleavage.8 Thus, the corresponding R-pyrone and
butenolide derivatives can be synthesized efficiently by the
oxidative coupling of such acids with alkynes and alkenes,
respectively. Expectedly, some R-pyrones obtained have been
found to show solid-state fluorescence. The results obtained for
the coupling reactions are described herein.
The straightforward and efficient synthesis of R-pyrone
and butenolide derivatives has been achieved by the
rhodium-catalyzed oxidative coupling reactions of sub-
stituted acrylic acids with alkynes and alkenes, respec-
tively. Some R-pyrones obtained exhibit solid-state
fluorescence.
(4) Selected reviews: (a) Kakiuchi, F.; Kochi, T. Synthesis 2008, 3013. (b)
Lewis, J. C.; Bergman, R. G.; Ellman, J. A. Acc. Chem. Res. 2008, 41, 1013.
(c) Ferreira, E. M.; Zhang, H.; Stoltz, B. M. Tetrahedron 2008, 64, 5987. (d)
Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222. (e)
Herrerias, C. I.; Yao, X.; Li, Z.; Li, C.-J. Chem. Rev. 2007, 107, 2546. (f)
Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev. 2007, 107, 174. (g)
Godula, K.; Sames, D. Science 2006, 312, 67. (h) Satoh, T.; Miura, M. J.
Synth. Org. Chem. 2006, 64, 1199. (i) Conley, B. L.; Tenn, W. J. III; Young,
K. J. H.; Ganesh, S. K.; Meier, S. K.; Ziatdinov, V. R.; Mironov, O.;
Oxgaard, J; Gonzales, J.; Goddard, W. A., III; Periana, R. A. J. Mol. Catal.
A 2006, 251, 8. (j) Miura, M.; Satoh, T. Top. Organomet. Chem. 2005, 14, 55.
(k) Kakiuchi, F.; Chatani, N. Adv. Synth. Catal. 2003, 345, 1077. (l) Ritleng,
V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102, 1731. (m) Miura, M.;
Nomura, M. Top. Curr. Chem. 2002, 219, 211. (n) Kakiuchi, F.; Murai, S.
Acc. Chem. Res. 2002, 35, 826. (o) Dyker, G. Angew. Chem., Int. Ed. 1999, 38,
1698. (p) Kakiuchi, F.; Murai, S. Top. Organomet. Chem. 1999, 3, 47. (q)
Shilov, A. E.; Shul’pin, G. B. Chem. Rev. 1997, 97, 2879.
R-Pyrone and butenolide structures are found in various
natural products that exhibit a broad range of interesting
biological properties.1 They are also of interest for their
fluorescence properties.2 One of the useful procedures for
their construction is the palladium-catalyzed annulation by
the coupling of (Z)-β-iodopropenoates with internal alkynes.3
The iodides are, however, prepared in more than four steps.
(5) (a) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. J. Org. Chem. 2009,
74, 3478. (b) Ueura, K.; Satoh, T.; Miura, M. J. Org. Chem. 2007, 72, 5362.
(c) Ueura, K.; Satoh, T.; Miura, M. Org. Lett. 2007, 9, 1407.
(1) For recent examples, see: (a) Inack-Ngi, S; Rahmani, R.; Commeiras,
^
L.; Chouraqui, G.; Thibonnet, J.; Duchene, A.; Abarbri, M. Adv. Synth.
Catal. 2009, 351, 779. (b) Hagimori, M.; Mizuyama, N.; Shigemitsu, Y.;
Wang, B.-C.; Tominaga, Y. Heterocycles 2009, 78, 555. (c) Pozgan, F.;
Kocevar, M. Heterocycles 2009, 77, 657. (d) Kunibobu, Y.; Kawata, A.;
Nishi, M.; Takata, H.; Takai, K. Chem. Commun. 2008, 6360. (e) Virolleaud,
M.-A.; Piva, O. Synlett 2004, 2087. (f) Yao, T.; Larock, R. C. J. Org. Chem.
2003, 68, 5936. (g) Rousset, S.; Abarbri, M.; Thibonnet, J.; Parrain, J.-L.;
(6) (a) Umeda, N.; Tsurugi, H.; Satoh, T.; Miura, M. Angew. Chem., Int.
Ed. 2008, 47, 4019. (b) Shimizu, M.; Tsurugi, H.; Satoh, T.; Miura, M. Chem.
Asian J. 2008, 3, 881. (c) Uto, T.; Shimizu, M.; Ueura, K.; Tsurugi, H.; Satoh,
T.; Miura, M. J. Org. Chem. 2008, 73, 298. (d) Miyamura, S.; Tsurugi, H.;
Satoh, T.; Miura, M. J. Organomet. Chem. 2008, 693, 2438.
(7) More recently, related Rh systems were employed for oxidative
coupling of 2-phenylpyridines and acetanilides: (a) Li, L.; Brennessel, W.
W.; Jones, W. D. J. Am. Chem. Soc. 2008, 130, 12414. (b) Stuart, D. R.;
Bertrand-Laperle, M.; Burgess, K. M. N.; Fagnou, K. J. Am. Chem. Soc.
2008, 130, 16474.
^
Duchene, A. Tetrahedron Lett. 2003, 44, 7633. (h) Shen, Y.-C.; Prakash, C.
V. S.; Kuo, Y.-H. J. Nat. Prod. 2001, 64, 324. (i) Gawronski, J. K.; van
Oeveren, A.; van der Deen, H.; Leung, C. W; Feringa, B. L. J. Org. Chem.
1996, 61, 1513.
(2) (a) Hirano, K.; Minakata, S.; Komatsu, M. Bull. Chem. Soc. Jpn.
2001, 74, 1567. (b) Hirano, K.; Minakata, S.; Komatsu, M.; Mizuguchi, J. J.
Phys. Chem. A 2002, 106, 4868.
(3) (a) Larock, R. C.; Doty, M. J.; Han, X. J. Org. Chem. 1999, 64, 8770.
(b) Larock, R. C.; Han, X.; Doty, M. J. Tetrahedron Lett. 1998, 39, 5713.
(8) For recent examples, see: (a) Shibata, Y.; Otake, Y.; Hirano, M.;
Tanaka, K. Org. Lett. 2009, 11, 689. (b) Giri, R.; Yu, J.-Q. J. Am. Chem. Soc.
2008, 130, 14082. (c) Colby, D. A.; Bergman, R. G.; Ellman, J. A. J. Am.
Chem. Soc. 2008, 130, 3645. (d) Oi, S.; Sakai, K.; Inoue, Y. Org. Lett. 2005, 7,
4009.
DOI: 10.1021/jo901077r
r
Published on Web 07/02/2009
J. Org. Chem. 2009, 74, 6295–6298 6295
2009 American Chemical Society

Mochida et al.
JOCNote
TABLE 1. Reaction of Methacrylic Acid (1a) with Diphenylacetylene
(2a)a
TABLE 2. Reaction of Methacrylic Acid (1a) with Alkynes 2a
entry
oxidant (mmol)
solvent temp (°C) time (h) yield of 3ab
1
2
3
4
5
6
Cu(OAc)2 H2O (1) o-xylene
Cu(OAc)2 H2O (1) DMF
120
120
120
120
100
120
2
4
2
4
6
2
4
25
91 (87)
10
77
3
3
Ag2CO3 (0.5)
Ag2CO3 (0.5)
Ag2CO3 (0.5)
AgOAc (1)
DMF
o-xylene
DMF
DMF
92
aReaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), and solvent (2.5 mL) under N2. bGC yield based on the
amount of 1a used. Value in parentheses indicates yield after purification.
In an initial attempt, methacrylic acid (1a) (0.5 mmol) was
treated with diphenylacetylene (2a) (0.5 mmol) under condi-
tions similar to those employed for the coupling of benzoic
acids with 2a. Under conditions with [Cp*RhCl2]2 (0.005
mmol) and Cu(OAc)2 H2O (1 mmol) in o-xylene (2.5 mL) at
3
120 °C under N2, 3-methyl-5,6-diphenyl-2H-pyran-2-one
(3a) was formed in only 4% yield after 2 h (entry 1 in Table 1,
Cp*=pentamethylcyclopentadienyl). In DMF, the product
yield increased to 25% (entry 2). The use of Ag salts in place
of Cu(OAc)2 as oxidant gave superior results. Thus, in the
presence of Ag2CO3 (0.5 mmol), 3a was obtained in 91%
yield within 2 h (entry 3). Even with the Ag salt, the reaction
was sluggish in o-xylene (entry 4). At 100 °C, the reaction
efficiency somewhat decreased (entry 5). AgOAc could also
be employed as well as Ag2CO3 (entry 6).
aReaction conditions: 1a (0.5 mmol), 2 (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), Ag2CO3 (0.5 mmol), and DMF (2.5 mL) at 120 °C under
N2 for 4 h. bGC yield based on the amount of 1a used. Value in
parentheses indicates yield after purification. cA separable regioisomer
was also isolated in 8% yield (see text).
TABLE 3. Reaction of Acrylic Acids 1 with Diphenylacetylene 2a
The reactions of 1a using various internal alkynes 2b-i in
place of 2a were next examined. Under optimized conditions
in Table 1 (entry 3), methyl- (2b), methoxy- (2c), and chloro-
(2d) substituted diphenylacetylenes underwent the coupling
with 1a to afford the corresponding 5,6-diaryl-3-methylpyr-
an-2-ones 3b-d in good yields (entries 1-3 in Table 2). Bis-
(2-thienyl)acetylene (2e) and dialkylacetylenes such as
4-octyne (2f) and 8-octadecyne (2g) could also be employed
to produce R-pyrones 3e-g in 84-92% yields (entries 4-6).
1-Phenyl-1-propyne (2h) also reacted with 1a to give 3,5-
dimethyl-6-phenyl-2H-pyran-2-one (3h) selectively (entry 7),
and only a trace amount of a regioisomer was detected by
GC-MS. From the reaction of 1-phenyl-1-hexyne (2i) with
1a, 5-butyl-3-methyl-6-phenyl-2H-pyran-2-one (3i) was ob-
tained in 87% yield, along with a minor amount (8%) of a
separable regioisomer, 6-butyl-3-methyl-5-phenyl-2H-pyr-
an-2-one (3i0) (entry 8). 1-Phenyl-2-(trimethylsilyl)acetylene
and phenylacetylene did not couple with 1a at all, and
only an alkyne dimer, diphenylbutadiyne, was detected by
GC-MS as a single major product.
Table 3 summarizes the results for the coupling of a series
of substituted and unsubstituted acrylic acids 1b-j with 2a.
2-Arylacrylic acids 1b-d reacted with 2a smoothly to form
3-aryl-5,6-diphenylpyranones 3j-l (entries 1-3). Commer-
cially available itaconic acid and its derivative, 1e and 1f, also
underwent the reaction with 2a to produce 2-oxo-
5,6-diphenyl-2H-pyran-3-carboxylic acid derivatives 3m
and 3n, respectively (entries 4 and 5). In the reactions of
unsubstituted acrylic acid (1g) as well as 2,3-dimethyl- (1h)
entry
1
R1
R2
time (h)
product, % yieldb
1
2
3
4
1b
1c
1d
1e
1f
1g
1h
1i
Ph
H
H
H
H
H
H
Me
Ph
4
10
10
6
4
4
8
6
6
3j, 84 (77)
3k, 61 (58)
31, 60 (50)
3m, 44 (40)
3n, 81 (77)
3o, 60 (52)
3p, 82 (77)
3q, 22 (22)
3r, 76 (74)
4-MeOC6H4
4-ClC6H4
(HO2C)CH2
(BuO2C)CH2
H
5c
6d
7d
8d
9
Me
Ph
1j
-(CH2)4-
aReaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), [(Cp*RhCl2)2]
(0.005 mmol), Ag2CO3 (0.5 mmol), and DMF (2.5 mL) at 120 °C under
N2. bGC yield based on the amount of 2a used. Value in parentheses
indicates yield after purification. c1 (1 mmol) was used. d[(Cp*RhCl2)2]
(0.01 mmol) was used.
and 2,3-diphenylacrylic acids (1i), increasing the amount of
[Cp*RhCl2]2 to 2 mol % improved the reaction efficiency
(entries 6-8). In contrast, the reaction of 1-cyclohexene-1-
carboxylic acid (1j) proceeded efficiently under standard
conditions with [Cp*RhCl2]2 (1 mol %) to afford a bicyclic
product 3r in 76% yield (entry 9).
Some R-pyrones obtained above showed solid-state fluor-
escence in a range of 460-490 nm (see the Supporting
Information). Notably, 3j exhibited a relatively strong
6296 J. Org. Chem. Vol. 74, No. 16, 2009

Mochida et al.
JOCNote
TABLE 4. Reaction of Acrylic Acids 1 with Acrylates 4a
entry
1
R1 R2
4
R3 conditions time (h) product, % yieldb
1
2
3
4
5
6
7
8
1a Me
1a Me
1a Me
1a Me
1a Me
1h Me Me 4a Bu
1h Me Me 4a Bu
1k Me Ph 4a Bu
H
H
H
H
H
4a Bu
4a Bu
4a Bu
4b Cyd
4c t-Bu
A
Bc
B
B
B
6
6
8
8
8
8
6
10
5a, 50
5a, 54
5a, 65 (63)
5b, 68 (61)
5c, 60 (58)
5d, 11
B
Ae
5d, 75 (72)
5e, 68 (62)
FIGURE 1. Fluorescence spectra of 3j (A) and Alq3 (B) in the solid
state upon excitation at 380 nm.
Ae
aReaction conditions A: 1 (0.5 mmol), 4 (1 mmol), [(Cp*RhCl2)2]
(0.005 mmol), Ag2CO3 (0.5 mmol), and DMF (2.5 mL) at 120 °C under
N2. Conditions B: 1 (0.5 mmol), 4 (1 mmol), [(Cp*RhCl2)2] (0.005
emission compared to a typical emitter, tris(8-hydroxyqui-
nolino)aluminum (Alq3), by a factor of 3.2 (λemis = 474 nm,
A versus B in Figure 1).
mmol), Cu(OAc)2 H2O (1 mmol), and DMF (2.5 mL) at 100 °C under
3
We also examined the oxidative cross-dimerization9 using
acrylic acids with acrylates. When methacrylic acid (1a)
(0.5 mmol) was treated with butyl acrylate (4a) (1 mmol) in
the presence of [Cp*RhCl2]2 (0.005 mmol) and Ag2CO3
(0.5 mmol) in DMF (2.5 mL) at 120 °C under N2 (conditions
A) for 6 h, butyl 2,5-dihydro-4-methyl-5-oxo-2-furanacetate
(5a) was formed in 50% yield (entry 1 in Table 4). Under the
N2. bGC yield based on the amount of 1 used. Value in parentheses
indicates yield after purification. cAt 120 °C. dCy = cyclohexyl. eIn
DMAc (2.5 mL).
SCHEME 2. Plausible Mechanism for the Coupling of
Methacrylic Acid (1a) with Alkynes 2 and Alkenes 4
conditions using Cu(OAc)2 H2O (1 mmol) in place of
3
Ag2CO3 as oxidant at 100 °C (conditions B), the product
yield was improved up to 65% (entry 3). Cyclohexyl- (4b)
and t-butyl acrylates (4c) also underwent the cross-dimeriza-
tion with 1a to afford the corresponding butenolides 5b and
5c, respectively (entries 4 and 5). In contrast, in the reaction
of 2,3-dimethylacrylic acid (1h) with 4a, a better result was
obtained by using Ag2CO3 as oxidant in DMAc compared
with that under conditions B (entry 7 versus entry 6). Under
similar conditions, the reaction of 2-methyl-3-phenylacrylic
acids (1k) with 4a proceeded effectively to produce a bute-
nolide 5e (entry 8).
The reaction of 1a with 2 or 4 seems to proceed via
fundamentally similar steps to those proposed for the oxida-
tive coupling of benzoic acid with 2 or 4 using the
attributed to the interaction of the Rh center with the phenyl
group of alkynes, although the details are not definitive.
In summary, we have demonstrated that the rhodium-
catalyzed oxidative coupling of substituted acrylic acids with
alkynes proceeds efficiently via vinylic C-H bond cleavage
to give the corresponding R-pyrone derivatives. Cross-di-
merization of acrylic acids with acrylate esters can also be
conducted effectively under similar rhodium catalysis to
form butenolides. Acrylic acids are apparently useful build-
ing blocks because of their wide and ready availability.
[Cp*RhCl2]2/Cu(OAc)2 H2O system.5 Thus, as depicted in
3
Scheme 2, coordination of the carboxyl oxygen to Cp*Rh(III)
X2 gives a rhodium(III) carboxylate A, and directed cyclor-
hodation at the 3-position affords a key rhodacycle inter-
mediate B.10 Subsequent alkyne or alkene insertion occurs to
produce the corresponding seven-membered rhodacycle C or
D, which may undergo reductive elimination or β-hydrogen
elimination and nucleophilic cyclization to form 3 or 5,
respectively. In both cases, the resulting Rh(I)X species seem
to be oxidized in the presence of the copper(II) or silver(I) salt
to regenerate a rhodium(III) species.11 The direction of the
insertion of 2h and 2i into the Rh-C bond of B is consistent
with that in our previous work.5,6 This regioselectivity may be
Experimental Section
General Procedure for Reactions of Acrylic Acid 1 with
Alkynes 2. To a 20 mL two-necked flask were added acrylic
acid 1 (0.5 mmol), alkyne 2 (0.5 mmol), [(Cp*RhCl2)2] (0.005
mmol, 3 mg), Ag2CO3 (0.5 mmol, 138 mg), 1-methylnaphtha-
lene (ca. 40 mg) as internal standard, and DMF (2.5 mL). The
resulting mixture was stirred under N2 at 120 °C. GC and
GC-MS analyses of the mixtures confirmed formation of 3.
Then, the reaction mixture was cooled to room temperature and
extracted with Et2O (100 mL). The organic layer was washed by
water (100 mL, three times) and dried over Na2SO4. Product 3
was isolated by column chromatography on silica gel using
hexane/ethyl acetate as eluant.
(9) For recent examples of cross-dimerization of alkenes without direct-
ing groups, see: (a) Xu, Y.-H.; Lu, J.; Loh, T.-P. J. Am. Chem. Soc. 2009, 131,
1372. (b) Lindhardt, A. T.; Mantel, M. L. H.; Skrydstrup, T. Angew. Chem.,
Int. Ed 2008, 47, 2668. (c) Hatamoto, Y.; Sakaguchi, S.; Ishii, Y. Org. Lett.
2004, 6, 4623.
(10) Similar ruthenacycles have been prepared: Kanaya, S.; Komine, N.;
Hirano, M.; Komiya, S. Chem. Lett. 2001, 1284.
(11) The participation of a silver acrylate before the formation of A as
well as some cationic rhodium species under conditions with a Ag salt
oxidant cannot be excluded.
J. Org. Chem. Vol. 74, No. 16, 2009 6297

Mochida et al.
JOCNote
3-Methyl-5,6-diphenyl-2H-pyran-2-one (3a) (entry 3 in Table 1):3a
mp 124-126 °C; 1H NMR (400 MHz, CDCl3) δ 2.19 (d,
J =1.1 Hz, 3H), 7.16-7.35 (m, 11H); 13C NMR (100 MHz,
CDCl3) δ 16.4, 117.9, 123.7, 127.7, 128.0, 128.9, 129.1, 129.2,
129.5, 132.2, 136.6, 144.0, 155.4, 163.1; HRMS m/z calcd for
C18H14O2 (Mþ) 262.0994, found 262.0996.
General Procedure for the Reaction of Acrylic Acids 1 with
Acrylates 4 under Conditions B. To a 20 mL two-necked flask were
added acrylic acid 1(0.5 mmol), acrylate 4(1 mmol), [(Cp*RhCl2)2]
Butyl 2,5-Dihydro-4-methyl-5-oxo-2-furanacetate (5a) (entry
3 in Table 4): oil; 1H NMR (400 MHz, CDCl3) δ 0.94 (t, J=7.3
Hz, 3H), 1.35-1.41 (m, 2H), 1.59-1.66 (m, 2H), 1.92-1.93
(t, J=1.5 Hz, 3H), 2.59 (dd, J = 16.1, 7.0 Hz, 1H), 2.79 (dd, J=
16.1, 7.0 Hz, 1H), 4.13 (t, J=7.0 Hz, 2H), 5.24-5.28 (m, 1H),
7.16-7.28 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 10.5, 13.5,
19.0, 30.5, 38.2, 65.0, 76.7, 130.6, 147.6, 169.1, 173.4; HRMS m/z
calcd for C11H16O4 (Mþ) 212.1049, found 212.1046.
(0.005 mmol, 3 mg), Cu(OAc)2 H2O (1 mmol, 199 mg), 1-methyl-
3
Acknowledgment. This work was partly supported by
Grants-in-Aid from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and the Kurata
Memorial Hitachi Science and Technology Foundation.
naphthalene (ca. 40 mg) as internal standard, and DMF (2.5 mL).
The resulting mixture was stirred under N2 at 100 °C. GC and
GC-MS analyses of the mixtures confirmed formation of 5. Then,
the reaction mixture was cooled to room temperature and ex-
tracted with Et2O (100 mL) and ethylenediamine (2 mL). The
organic layer was washed by water (100 mL, three times) and dried
over Na2SO4. Product 5 was isolated by column chromatography
on silica gel using hexane/ethyl acetate as eluant.
Supporting Information Available: Characterization data of
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
6298 J. Org. Chem. Vol. 74, No. 16, 2009