Synthesis and acid- or base-catalyzed cyclization of various 4-pentyne-1,3-dione derivatives

Article abstract of DOI:10.1246/bcsj.80.780

4-Pentyne-1,3-dione derivatives having various substituents were conveniently synthesized from ynals and silyl enol ethers in two steps. The cyclization behaviors of the obtained 4-pentyne-1,3-diones were studied. γ-Pyrones and 3(2H)-furanones were obtain

Full text of DOI:10.1246/bcsj.80.780

780 Short Articles
Bull. Chem. Soc. Jpn. Vol. 80, No. 4, 780–782 (2007)
R1
R2
R1
O
R2
R1
H
acid or
base(cat.)
O
R2
Synthesis and Acid- or Base-
Catalyzed Cyclization of Various
4-Pentyne-1,3-dione Derivatives
+
O
O
O
O
2
1
3
R1
R2
R1
R2
Ph
n-Bu
Ph
Ph
a
b
t-Bu
c
ꢀ
Ph
n-Bu
t-Bu
d
Hirofumi Kuroda and Hironori Izawa
Scheme 1. Cyclization reaction of 4-pentyne-1,3-dione de-
rivatives 1.
Department of Chemical and Biological Engineering,
Toyama National College of Technology,
13 Hongo-machi, Toyama 939-8630
R2
R1
R1
Received August 31, 2006; E-mail: kuroda@toyama-nct.ac.jp
OSiMe3
R2
5
H
BF3• OEt2 (1.5 mol. amt.)
-78 °C, CH2Cl2
OH
O
O
4
4-Pentyne-1,3-dione derivatives having various sub-
stituents were conveniently synthesized from ynals and silyl
enol ethers in two steps. The cyclization behaviors of the
obtained 4-pentyne-1,3-diones were studied. ꢀ-Pyrones and
3(2H)-furanones were obtained by cyclization in the pres-
ence of an acid or base as a catalyst. The selectivity of the
cyclization was moderately influenced by the substituents
at the acetylenic moiety.
6
R1
R2
Oxidation
O
O
1
Scheme 2. Synthesis of 4-pentyne-1,3-dione derivatives 1.
Table 1. Oxidation of 6 by Using Activated MnO2 or Jones
Reagent
C–C triple bond activated by an electron-withdrawing group
is the one of important reactive functional groups for organic
synthesis and widely used as a key intermediate.1 Previously,
we have reported syntheses of cyclic compounds containing
one oxygen atom, such as furans, by the cyclization of conju-
gated enynones.2 Marei and El-Ghanam synthesized3b phenyl-
pent-4-yne-1,3-dione derivatives having aryl groups conven-
iently by the reaction of ethyl phenylpropynoate with methyl
ketone having a aryl group in the presence of sodium methox-
ide and have reported the syntheses of various heterocycles
containing ꢀ-pyrones and 3(2H)-furanones by using the diones
as a key intermediate.3 However, 4-pentyne-1,3-dione deriva-
tives only having a phenyl group as a substituent on acetylenic
moiety, i.e., 1-aryl-4-phenylpent-4-yne-1,3-diones, were syn-
thesized and used in the studies. Synthesis of 4-pentyne-1,3-
dione derivatives having an aliphatic group on the acetylenic
moiety under basic conditions, such as Marei’s procedure,
may be difficult because of the high anionic reactivity of ace-
tylenic moiety. The target molecules were not obtained due to
complex side-reactions, although we attempted the syntheses
of the diones under basic conditions using various methods in-
volving Marei’s procedure. Moreover, little has been published
about the cyclization conditions and regio selectivity of the cy-
clization of the diones to afford ꢀ-pyrones and 3(2H)-fura-
nones.3 Herein, we wish to describe a new synthetic method
for 4-pentyne-1,3-dione derivatives 1 having various substitu-
ents and its cyclization reaction behavior (Scheme 1).
a)
MnO2
Yc)/% Rd)/%
Jones oxidationb)
No.
R1
R2
Yc)/%
Rd)/%
1
2
3
4
n-Bu
Ph
t-Bu
Ph
Ph
Ph
80
40
61
82
4
48
35
6
70
22
—
—
18
32
—
—
n-Bu t-Bu
a) The oxidation of 6 (2.1 mmol) was carried out in the pres-
ence of activated MnO2 (3.6 g) in hexane (29 mL). b) To a so-
lution of 6 (14.0 mmol) in acetone (140 mL) was added Jones
reagent (14 mmol). c) Isolated yields (column chromatogra-
phy: SiO2, EtOAc/Hex). d) Recovered amount of 5 (column
chromatography: SiO2, EtOAc/Hex).
attempted by using 6a under various conditions (Jones oxida-
tion,5 Collins oxidation,6 Swern oxidation,7 activated manga-
nese dioxide,8 etc.). Oxidation by activated manganese dioxide
or Jones reagent gave relatively favorable results affording 1a
in high yields (70 and 80% yields, respectively). From the re-
sults, the oxidation of 6 was carried out by Jones method or
manganese dioxide (Table 1). Compounds 1a and 1d were ob-
tained in high yield by using manganese dioxide (Nos. 1 and
4). Although various conditions were attempted in the oxida-
tions of 6b and 6c, the starting materials were not completely
consumed (Nos. 2 and 3).
The cyclization of 6a was performed by using various cata-
lysts (0.2 mol amt) (Table 2). When the cyclization was carried
out without a catalyst in dichloromethane under reflux for
2 days, the amount of ꢀ-pyrone 2a was small, and almost of
the starting material was recovered (No. 1). When sulfuric acid
was used as a catalyst in the reaction, 2a was obtained in 77%
yield (No. 2). When n-BuLi was used as a basic catalyst, 2a
4-Pentyne-1,3-dione derivatives were synthesized from
ynals2c 4 and silyl enol ethers4 5 in two steps (Scheme 2).
An acidic Mukaiyama aldol reaction of 4 with 5 was carried
out by the procedure2c reported by us in the presence of boron
trifluoride–diethyl etherate to obtain the corresponding alco-
hols 6 in excellent yields (80–96%). The oxidation of 6 was
Published on the web April 13, 2007; doi:10.1246/bcsj.80.780

Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
Ó 2007 The Chemical Society of Japan
781
Table 2. Cyclization of 1aa) under Various Conditions
R1
O
R2
R1
R1
R2
OH
Et3N
R2
- Et3N+-H
No.
Catalysts Solvent Time/h Yb) of 2/% Rc)/%
O
1
2
3
4d)
5e)
6f)
7
8
9
H2SO4
H2SO4
H2SO4
n-BuLi
NaH
n-Bu3P
DMAP
Et3N
CH2Cl2
CH2Cl2
CH2Cl2
THF
47
18
24
49
20
2
4
71
5
8
77
62
66
48
25
67
94
99
81
20
0
0
0
0
0
0
0
OH
O
O
1
R1
O
R2
R1
O
R2
Et3N-H
- Et3N
THF
CH2Cl2
CH2Cl2
CH2Cl2
THF
2
O
O
R2
R2
R1
O
R1
O
Et3N-H
- Et3N
C
Et3N
H
O
a) The cyclization of 1 (0.943 mmol) was carried out in the
presence of an catalyst (0.189 mol) in a solvent (3 mL) under
reflux. b) Isolated yields (column chromatography: SiO2,
EtOAc/Hex). c) Recovered amount of 1a (column chromatog-
raphy: SiO2, EtOAc/Hex). d) The cyclization was carried out
at 40 ꢃC. e) Oligomeric products were obtained in 36% yield.
f) Oligomeric products were obtained in 61% yield.
O
3
Scheme 3. Plausible mechanism for cyclization reaction of 1.
R1 rather than by R2.
In summary, 4-pentyne-1,3-dione derivatives 1 having var-
ious substituents were conveniently synthesized from ynals
and silyl enol ethers in two steps. The cyclization behavior
of the obtained 4-pentyne-1,3-diones were studied. ꢀ-Pyrones
2 and 3(2H)-furanones 3 were obtained by cyclization in the
presence of acid or base as a catalyst. The selectivity in the cy-
clization reaction was moderately influenced by the substitu-
ents at the acetylenic moiety. Further work on the reactive
characters of 4-pentyne-1,3-dione derivatives 1 is currently be-
ing performed.
Table 3. Cyclization of 1a)
No.
R1
R2
Timeb)/h
Yc) of 2/%
Yc) of 3/%
1
2
3
4
n-Bu
Ph
t-Bu
n-Bu
Ph
Ph
Ph
t-Bu
5
2
6
4
99
49
93
93
0
34
0
0
a) The cyclization of 1 (0.943 mmol) was carried out in the
presence of Et3N (0.175 mmol) in THF (3 mL) under reflux.
b) The time for complete consumption of 1. c) Isolated yields
(column chromatography: SiO2, EtOAc/Hex).
Experimental
Materials and Instruments.
Tetrahydrofuran (THF) was
dried over sodium diphenylketyl and distilled under nitrogen. Di-
chloromethane and triethylamine were dried over calcium hydride
and then purified by distillation. Other commercially available
chemicals were used without purification. Alcohols 6 were synthe-
sized by the procedure described in the previous report.2c Infrared
(IR) spectra were obtained on a JASCO FT/IR 8000 infrared spec-
trometer. 1H and 13C NMR spectra were recorded on a JNM-
AL400 spectrometer, in CDCl3 (using tetramethylsilane as an
internal standard). MS spectra were measured on a JMS-AX500
mass spectrometer.
was obtained in 66% yield (No. 4). When sodium hydride
(No. 5) or tributylphosphine (No. 6) was used, a moderate
amount of oligomeric products formed as by-products. When
N,N-dimethylaminopyridine (DMAP) was used as a basic cat-
alyst, the consumption of 1a was very fast, and 2a was ob-
tained in good yield (No. 7). Although the reaction needed a
long time (71 h) in the case of triethylamine, 2a was obtained
in an almost quantitatively yield (No. 8). Furthermore, when
the reaction was carried out by using THF as a solvent under
reflux to shorten the reaction time, 2a was obtained quantita-
tively in less than 7 h (No. 9).
From the results, the cyclization of 1 having various
substituents was performed by using triethylamine in THF
(Table 3). The influence of substituents R1 and R2 was exam-
ined by using 1a–1d (Nos. 1–4). In the cases of R1 = alkyl
groups, the corresponding ꢀ-pyrones 2a and 2c were obtained
in almost quantitative yields regardless of the size of alkyl
groups (Nos. 1 and 3). In the case of 1b with R1 = phenyl,
ꢀ-pyrones 2b and 3(2H)-furanones 3b9 were obtained in 49
and 34% yields, respectively. The selectivity may be affected
by a difference in the stabilizing ability between the carbonyl
group and R1 for the resulting carbanion. In the case of 1b, 3b
might be obtained due to the stabilizing ability of phenyl group
toward the anion afforded by the addition of an enolate anion
to C–C double bond (Scheme 3). Moreover, 2d was obtained
in almost quantitative yield when R2 was t-butyl (1d) instead
of a phenyl group (No. 4). From these results, it was found that
the selectivity in the cyclization reactions was influenced by
Synthesis of 1. Typical Procedure for Oxidation of Alco-
hols 6 by Using Electrolytic Manganese Dioxide (EMD): To
a suspension of EMD (Tosoh, type H–H, 3.60 g) in hexane
(28.8 mL) was added alcohol 6 (2.10 mmol), and then the mixture
was stirred for 3 h at room temperature under air. The mixture was
filtered, and the filtrate was concentrated under vacuum. The res-
idue was purified by column chromatography on silica gel (hex-
ane/ethyl acetate = 100/1–20/1) to give corresponding dione
1. Typical analytical data for 1. 1a; Rf = 0.53; hexane/ethyl
acetate = 4/1. IR (cmꢁ1, neat) 3065, 2961, 2872, 2834, 2226,
1738, 1599, 1466, 1275, 1203, 1067, 1020, 930, 771, 693.
1H NMR (400 MHz, ꢁ, CDCl3) 0.94 (t, J ¼ 7:2 Hz, 3H, CH3-
CH2–), 1.50 (m, 2H, –CH2–), 1.58 (m, 2H, –CH2–), 2.43 (t, J ¼
6:8 Hz, 2H, –CH2CꢂC–), 6.34 (s, 1H, –CH=C(OH)–), 7.40–
7.60 (m, 3H, –Ph), 7.89 (m, 2H, Ph), 15.77 (bs, 1H, =C(OH)–).
13C NMR (100 MHz, ꢁ, CDCl3) 13.6, 14.2, 19.0, 22.0, 29.9,
78.7, 97.2, 100.7, 127.1, 128.6, 128.7, 132.6, 134.4, 171.1, 184.6.
MS (EI, m=z) 228 (Mþ). 1b; Rf ¼ 0:46; hexane/ethyl acetate =
4/1. IR (cmꢁ1, neat) 3063, 2963, 2921, 2851, 2209, 1599, 1487,
1
1262, 1100, 1022, 801, 772, 689. H NMR (400 MHz, ꢁ, CDCl3)
6.45 (s, 1H, –CH=C(OH)–), 7.40–7.60 (m, 8H, –Ph), 7.89 (m, 2H,

782 H. Kuroda et al.
Bull. Chem. Soc. Jpn. Vol. 80, No. 4 (2007)
Ph), 15.74 (bs, 1H, =C(OH)–). 13C NMR (100 MHz, ꢁ, CDCl3)
86.5, 94.3, 101.7, 120.9, 127.8, 129.2, 129.4, 130.9, 133.2, 133.5,
135.0, 170.9, 186.0. MS (EI, m=z) (Mþ) 248. 1c; Rf ¼ 0:45;
hexane/ethyl acetate = 4/1. IR (cmꢁ1, neat) 3065, 2973, 2930,
2903, 2869, 2216, 1738, 1568, 1252, 1186, 814, 772, 692.
1H NMR (400 MHz, ꢁ, CDCl3) 1.25 (s, 9H, t-Bu–), 6.28 (s, 1H,
–CH=C(OH)–), 7.40–7.60 (m, 3H, –Ph), 7.89 (m, 2H, Ph), 15.73
(bs, 1H, =C(OH)–). 13C NMR (100 MHz, ꢁ, CDCl3) 28.3, 30.4,
101.3, 104.9, 127.7, 129.2, 133.2, 135.0, 172.1, 185.3. MS (EI,
m=z) 228 (Mþ). 1d; Rf = 0.54; hexane/ethyl acetate = 4/1. IR
(cmꢁ1, neat) 2963, 2872, 1591, 1464, 1282, 1221, 1121, 928, 801.
1H NMR (400 MHz, ꢁ, CDCl3) 0.86 (t, J ¼ 7:32 Hz, 3H, CH3–),
1.10 (s, 9H, t-Bu–), 1.37 (m, 2H, –CH2–), 1.51 (m, 2H, –CH2–),
2.33 (t, J ¼ 7:32 Hz, 2H, –CH2CꢂC–), 5.73 (s, 1H, –CH=
C(OH)–), 15.34 (bs, 1H, =C(OH)–). 13C NMR (100 MHz, ꢁ,
CDCl3) 13.7, 19.2, 22.1, 27.3, 30.1, 39.8, 96.8, 100.4, 170.5,
203.0. MS (EI, m=z) 208 (Mþ).
Typical Procedure for Oxidation of 6 by Using Jones
Reagent: To a solution of 6 (14.0 mmol) in acetone (140 mL)
was added Jones reagent (CrO3; 2.50 mol Lꢁ1, 5.60 mL, 14.0
mmol) at 0 ꢃC, and then, the mixture was stirred for 1 h at room
temperature under air. The mixture was diluted with water
(100 mL) and extracted three times with 30 mL of ethyl acetate.
The combined organic solution was washed twice with 20 mL of
saturated aqueous sodium chloride and then dried over magnesium
sulfate. After evaporation, the residue was purified by column
chromatography on silica gel (hexane/ethyl acetate = 100/1–
20/1) to give corresponding dione 1.
J ¼ 1:60 Hz, 1H, >C=CHCO–), 7.42 (m, 3H, Ph–), 7.68 (m,
2H, Ph–). 13C NMR (100 MHz, ꢁ, CDCl3) 13.8, 22.1, 29.0, 33.4,
110.7, 113.4, 125.5, 128.8, 131.0, 131.2, 163.2, 168.7, 180.0.
MS (EI, m=z) 228 (Mþ). 2c; Rf = 0.07; hexane/ethyl acetate =
4/1. IR (cmꢁ1, neat) 3067, 2965, 1651, 1612, 1588, 1455, 1389,
1101, 947, 922, 891, 891, 770, 687. 1H NMR (400 MHz, ꢁ,
CDCl3) 1.29 (s, 9H, t-Bu), 6.20 (t, J ¼ 2:08 Hz, 1H, >C=
CHCO–), 6.62 (d, J ¼ 2:08 Hz, 1H, >C=CHCO–), 7.42 (m, 3H,
Ph–), 7.68 (m, 2H, Ph–). 13C NMR (100 MHz, ꢁ, CDCl3) 28.2,
36.5, 110.8, 110.9, 126.1, 129.5, 131.7, 132.0, 163.8, 176.0,
181.4. MS (EI, m=z) 228 (Mþ). 2d; Rf = 0.04; hexane/ethyl
acetate = 4/1. IR (cmꢁ1, neat) 2963, 2872, 1660, 1622, 1464,
1399, 1111, 924, 866. 1H NMR (400 MHz, ꢁ, CDCl3) 0.88 (t, J ¼
7:33 Hz, 3H, CH3–), 1.19 (s, 9H, t-Bu–), 1.32 (m, 2H, –CH2–),
1.57 (m, 2H, –CH2–), 2.46 (t, J ¼ 7:57 Hz, 2H, –CH2C=C–),
5.99 (d, J ¼ 2:19 Hz, 1H, >C=CHCO–), 6.08 (d, J ¼ 2:19 Hz,
1H, >C=CHCO–). 13C NMR (100 MHz, ꢁ, CDCl3) 13.6, 21.9,
27.7, 28.7, 33.2, 35.9, 110.1, 112.9, 169.5, 176.0, 181.5. MS
(EI, m=z) 208 (Mþ).
References
1
a) E. Winterfeld, in Modern Synthetic Method 1992, ed. by
R. Scheffold, VCH, New York, 1992, p. 103. b) P. Perlmutter,
Conjugate Addition Reactions in Organic Synthesis, Pergamon
Press, Oxford, 1992, p. 339. c) X. Lu, C. Zhang, Z. Xu, Acc.
Chem. Res. 2001, 34, 535.
2
a) H. Kuroda, E. Hanaki, M. Kawakami, Tetrahedron Lett.
Cyclization of 1. A Typical Cyclization Procedure: To a
solution of 1b (0.181 g, 0.730 mmol) in THF (3 mL) was added tri-
ethylamine (16.0 mg, 0.158 mmol). The solution was refluxed for
2 h under nitrogen. After the solvent was evaporated, the residue
was purified by column chromatography (SiO2, hexane/ethyl
acetate = 100/1–20/1) to obtain 2b (0.893 g, 0.360 mmol)
(Rf ¼ 0:29 on TLC, SiO2, hexane/ethyl acetate = 4/1) and 3b
(0.0616 g, 0.248 mmol) (Rf = 0.31 on TLC, SiO2, hexane/ethyl
acetate = 4/1) in 49.3 and 34.0% yields, respectively. 2b; IR
(cmꢁ1, neat) 3061, 2961, 1695, 1641, 1614, 1448, 1386, 1124,
1999, 40, 3753. b) H. Kuroda, I. Tomita, T. Endo, Org. Lett. 2003,
5, 129. c) H. Kuroda, E. Hanaki, H. Izawa, M. Kano, H. Itahashi,
Tetrahedron 2004, 60, 1913.
3
a) M. G. Marei, M. El-Ghanam, Phosphorus, Sulfur,
Silicon Relat. Elem. 1995, 107, 1. b) M. G. Marei, M. El-Ghanam,
Bull. Chem. Soc. Jpn. 1992, 65, 3509. c) M. G. Marei, D. M. Aly,
M. M. Mishrikey, Bull. Chem. Soc. Jpn. 1992, 65, 3419. d) M. G.
Marei, M. M. Mishrikey, I. E. El-Kholy, J. Heterocycl. Chem.
1986, 23, 1849. e) I. E. El-Kholy, M. M. Mishrikey, M. G. Marei,
J. Heterocycl. Chem. 1982, 19, 1421.
1
1060, 931, 761, 692. H NMR (400 MHz, ꢁ, CDCl3) 6.82 (s, 2H,
4
5
P. Brownbridge, Synthesis 1893, 1.
a) K. Bowden, I. M. Heilbron, E. R. H. Jones, B. C. L.
>C=CHCO–), 7.41 (m, 6H, Ph–), 7.74 (m, 4H, Ph-). 13C NMR
(100 MHz, ꢁ, CDCl3) 111.1, 125.6, 128.9, 131.1, 131.2, 162.9,
179.8. MS (EI, m=z) 248 (Mþ), 220. 3b; IR (cmꢁ1, neat) 3063,
2961, 2932, 1697, 1653, 1620, 1449, 1402, 1175, 1060, 961,
Weedon, J. Chem. Soc. 1946, 39. b) A. Bowers, T. G. Halsall,
E. R. H. Jones, A. J. Lemin, J. Chem. Soc. 1953, 2548.
6 J. C Collins, W. W. Hess, F. J. Frank, Tetrahedron Lett.
1968, 9, 3363.
1
766, 698. H NMR (400 MHz, ꢁ, CDCl3) 6.30 (s, 1H, –OC(Ph)=
CHCO–), 6.83 (s, 1H, PhCH=C<), 7.74–7.62 (m, 6H, Ph–), 7.91
(m, 4H, Ph). 13C NMR (100 MHz, ꢁ, CDCl3) 102.4, 112.6, 126.6,
127.5, 128.7, 128.8, 129.7, 131.2, 131.8, 132.4, 146.3, 176.7,
187.0. MS (EI, m=z) 248 (Mþ), 118. 2a; Rf = 0.21; hexane/ethyl
acetate = 4/1. IR (cmꢁ1, neat) 3059, 2959, 2932, 2870, 1659,
1613, 1450, 1399, 1377, 1262, 1157, 885, 769, 693. 1H NMR
(400 MHz, ꢁ, CDCl3) 0.90 (t, J ¼ 7:19 Hz, 3H, CH3–), 1.37 (m,
2H, –CH2–), 1.65 (m, 2H, –CH2–), 2.55 (t, J ¼ 7:59 Hz, 2H,
–CH2C=C–), 6.11 (d, J ¼ 1:60 Hz, 1H, >C=CHCO–), 6.63 (d,
7
b) A. K. Sharma, D. Swern, Tetrahedron Lett. 1974, 15, 1503.
a) K. Omura, D. Swern, Tetrahedron 1978, 34, 1651.
8
Glenat, Bull. Soc. Chim. Fr. 1967, 453.
a) R. M. Evans, Q. Rev. 1959, 13, 61. b) M. Barrelle, R.
1
9
In the H and 13C NMR spectra of 3b, peaks attributed to
the geometric isomer were not observed. The geometry is consid-
ered to be Z-form because a chemical shift of benzylidene proton
in 3b agreed with the analytical data in Marei’s report.3e