Facile approach to 4-substituted 2(5H)-furanones

Full text of DOI:10.1021/jo000195t

5
034
J . Org. Chem. 2000, 65, 5034-5036
F a cile Ap p r oa ch to 4-Su bstitu ted
(5H)-F u r a n on es
compounds and the difficult removal of the toxic orga-
notin byproducts. Due to the readily availability and
8
2
environmentally friendly features of boronic acids, the
9
Suzuki coupling reaction came to attract ever-increasing
Min-Liang Yao and Min-Zhi Deng*
attention recently. Because of the readily availability and
the better electrophility of triflates, Suzuki and Miyaura
investigated the palladium-catalyzed cross-coupling reac-
tion of organoboranes and aryl, alkenylboronic acids with
alkenyl, aryl triflates.9 The first Suzuki reaction of
â-tetronic acid triflate with 9-alkyl-9-BBN (yield: 51%)
was adopted by Grigg10 during the total synthesis of (-)-
isoseiridine, and later the reaction of alkenylboronic acid
with â-tetronic acid triflate (yield: 48%) was described
Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Academia Sinica, 354 FengLin Lu,
Shanghai 200032, China
c
dengmz@pub.sioc.ac.cn
Received February 11, 2000
The 2(5H)-furanone moieties are prevalent in a variety
1
11
of natural products and medicinally important com-
by Honda in the preparation of syributin 1. Appearent-
2
pounds. The compounds containing 2(5H)-furanone moi-
ly, the yields of both reactions were unsatisfactory, and
the further study of the coupling condition in detail was
necessary.
ety have been considering as potential insectcides, fun-
3
gicides, antimicrobial and antitumor agents, etc. There-
fore, in recent years, much attention has been paid to
Considering that the â-tetronic acid triflate could be
prepared by the treatment of the readily available
the preparation of various substituted 2(5H)-furanones.
4
The recent patent about the pharmacological effects of
12
â-tetronic acid with triflic anhydride in the presence of
4
-alkyl-2(5H)-furanones in curing gastric ulcer and gas-
10
Hunig’s base, and in connection with our ongoing
tric hypersecretion actuated us to prepare their ana-
logues.
In contrast with the 3-substituted or 5-substituted
projects relating to the cross-coupling reactions of cyclo-
13
propylboronic acids, we felt it significant to introduce
the stereodefined cyclopropyl function into C-4 position
of 2(5H)-furanones via the coupling reaction of â-tetronic
acid triflate with cyclopropylboronic acids, and develop
a convenient method to prepare 4-cyclopropyl-2(5H)-
furanones, the special alkyl-substituted 2(5H)-furanones,
which might have some potential bioactivity. In this
paper, we wish to disclose our recent study in this
research work.
The reaction of trans-pentylcyclopropylboronic acids
with â-tetronic acid triflate was examined under an argon
atmosphere to optimize the reaction conditions(Table 1).
The reaction condition14 established for cyclopropylbo-
ronic acids with activated alkenyl triflates did make the
expected reaction take place, but the yield was poor
2
4
(5H)-furanones, the problem of the preparation of
-substituted 2(5H)-furanones has not been solved sat-
5
isfactorily yet. In the existing limited methods to 4-sub-
stituted 2(5H)-furanones, the transition metal-catalyzed
6
coupling methodologies occupied the overwhelming ma-
jority.7 Among them, the Stille coupling reaction was
adopted frequently;5,7a-e however, its feasibility was
limited due to the annoying preparation of organotin
*
To whom correspondence should be addressed. Fax: 0086-21-
4166128.
1) (a) Miao, S.-C.; Andersen, R. J . J . Org. Chem. 1991, 56, 6275.
b) Wang, T.-Z.; Pinard, E.; Paquette, L. A. J . Am. Chem. Soc. 1996,
6
(
(
1
6
18, 1309. (c) Paquette, L. A.; Ezquerra, J .; He, W. J . Org. Chem. 1995,
0, 1435. (d) Takayama, H.; Kuwajima, T.; Kitajima, M.; Nonato, M.
(
entry 1). Both the use of additive (entry 2), and the
G.; Aimi, N. Heterocycles 1999, 50, 75. (e) Rodriguez, A. D.; Shi, J .-G.;
Huang, S.-D. J . Org. Chem. 1998, 63, 4425. (f) Xu, L.-P.; Gou, D.; Liu,
J .-S.; Zheng, J .-H.; Koike, K.; J ia, Z.-H.; Nikaido, T. Heterocycles 1999,
1
0
adoption of the reaction conditions used by Grigg (entry
11
3
) and Honda (entry 4) could not improve the yield. The
blank test of â-tetronic acid triflate alone in toluene
solvent at 100 °C in the presence of K PO indicated that
â-tetronic acid triflate was sensitive to the strong base
PO . The reaction carried out in the weaker base KF
2 N aqueous solution) afforded only a trace of desired
5
1, 605.
2) (a) Cerri, A.; Mauri, P.; Mauro, M.; Melloni, P. J . Heterocycl.
(
Chem. 1993, 30, 1581. (b) Tan, L.; Chen, C.-Y.; Larsen, R. D.;
Verhoeven, T. R.; Reider, P. J . Tetrahedron Lett. 1998, 39, 3961. (c)
Vallat, J .-N.; Grossi, P.-J .; Boucherle, A.; Simiand, J . Eur. J . Med.
Chem. 1981, 16, 409.
3
4
K
(
3
4
(3) (a) Brima, T. S. U. S.US 4,968, 817 US Appl. 635,338, 1984;
Chem. Abstr. 1991, 114, 185246. (b) Tanabe, A. J pn. Kokai Tokkyo
Koho J P 63, 211, 276[88, 211, 276], 1988; Chem. Abstr. 1989, 110,
product and the massive â-tetronic acid, this fact sug-
gested that the â-tetronic acid triflate was also sensitive
to the water at 100 °C in the presence of the catalyst
9
4978. (c) Ducharme, Y.; Gauthier, J . Y.; Prasit, P.; Leblanc, Y.; Wang,
Z.; Leger, S.; Therien, M. PCT Int. Appl. WO 95 00, 501, 1995; Chem.
Abstr. 1996, 124, 55954.
(
4) Oomura, Y.; Shiraishi, T.; Takeoka, J . J pn. Kokai Tokkyo Koho
J P 07, 196, 491[95, 196, 491], 1995; Chem. Abstr. 1995, 123, 246850.
(8) (a) Piers, E.; J ean, M.; Marrs, P. S. Tetrahedron Lett. 1987, 28,
5075. (b) Fouquet, E.; Pereyre, M.; Rodriguez, A. J . Org. Chem. 1997,
62, 5242.
(
5) Lattmann, E.; Hoffmann, H. M. R. Synthesis 1996, 155.
(6) (a) For a recent review, see: Knight, D. W. Contemp. Org. Synth.
1
3
994, 1, 287. (b) Marshall, J . A.; Wolf, M. A. J . Org. Chem. 1996, 61,
238. (c) Xiao, W.-J .; Alper, H. J . Org. Chem. 1997, 62, 3422. (d)
(9) For recent reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev.
1995, 95, 2457. and (b) Suzuki, A. J . Organomet. Chem. 1999, 576,
147. (c) Ohe, T.; Miyaura, N.; Suzuki, A. J . Org. Chem. 1993, 58, 2201.
(10) Grigg, R.; Kennewell, P.; Savic, V. Tetrahedron 1994, 50, 5489.
(11) Honda, T.; Mizutani, H.; Kanai, K. J . Org. Chem. 1996, 61,
9374.
Marshall, J . A.; Wolf, M. A. J . Org. Chem. 1997, 62, 367. (e) J oh, T.;
Nagata, H.; Takahashi, S. Inorg. Chim. Acta 1994, 220, 45. (f) Forgione,
P.; Wison, P. D.; Fallis, A. G. Tetrahedron Lett. 2000, 41, 17.
(7) (a) Reginato, G.; Capperucci, A.; Degl’Innocenti, A.; Mordini, A.;
Pecchi, S. Tetrahedron 1995, 51, 2129. (b) Hoffmann, H. M. R.; Gerlach,
K.; Lattmann, E. Synthesis 1996, 164. (c) Hollingworth, G. J .; Sweeney,
J . B. Tetrahedron 1992, 33, 7049. (d) Hollingworth, G. J .; Perkins, G.;
Sweeney, J . B. J . Chem. Soc., Perkin Trans. 1 1996, 1913. (e) Maon,
R,; Richecoeur, A. M. E.; Sweeney, J . B. J . Org. Chem. 1999, 64, 328.
(12) (a) Mullholland, T. P. C.; Foster, R.; Haydock, J . Chem. Soc.,
Perkin Trans. 1 1972, 1225. (b) Greenhill, J . V.; Tomassini, T.
Tetrahedron Lett. 1974, 2683. (c) Schmidt, D. G.; Zimmer, H. Synth.
Commun. 1981, 11, 385.
(13) (a) Wang, X.-Z.; Deng, M.-Z. J . Chem. Soc., Perkin. Trans. 1
1996, 2663. (b) Zhou, S.-M.; Yan, Y.-L.; Deng, M.-Z. Synlett 1998, 198.
(c) Ma, H.-R.; Wang, X.-H.; Deng, M.-Z. Synth. Commun. 1999, 29,
2477.
(
f) Ma, S.-M.; Shi, Z.-J . J . Org. Chem. 1998, 63, 6387. (g) Boukouvalas,
J .; Lachance, N.; Ouellet, M.; Trudeau, M. Tetrahedron Lett. 1998, 39,
7
2
665. (h) Ma, S.-M.; Shi, Z.-J .; Yu, Z.-Q. Tetrahedron Lett. 1999, 40,
393.
(14) Yao, M.-L.; Deng, M.-Z. Synthesis accepted, 2000.
1
0.1021/jo000195t CCC: $19.00 © 2000 American Chemical Society
Published on Web 07/19/2000

Notes
J . Org. Chem., Vol. 65, No. 16, 2000 5035
Ta ble 1. Effects of Solven t a n d Ba se on th e Cou p lin g of
Ta ble 2. Cou p lin g Rea ction of Bor on ic Acid s w ith
tr a n s-P en tylcyclop r op ylbor on ic Acid w ith â-Tetr on ic
â-Tetr on ic Acid Tr ifla tea
a
Acid Tr ifla te
yieldb
entry
conditions
(%)
27
25
1
2
3
4
5
6
7
8
9
toluene, K3PO4‚3H2O, Pd(PPh3)4, 100 °C
toluene, K3PO4‚3H2O, NaBr, Pd(PPh3)4, 100 °C
dioxane, K3PO4, Pd(OAc)2, PPh3 (2 equiv), 70 °C 19
THF, K3PO4, Pd(PPh3)2Cl2, 70 °C
toluene, 2N KF, Pd(PPh3)4, 100 °C
toluene, KF, Pd(PPh3)4, 90 °C
toluene, Ag2O, Pd(PPh3)4, 90 °C
toluene, Ag2O, PdCl2(dppf), 90 °C
toluene, Ag2O, Pd(MeCN)2Cl2, AsPh3 (4 equiv),
22
tracec
16
38
13
49
9
0 °C
toluene, Ag2O, Pd(MeCN)2Cl2, AsPh3 (4 equiv),
0 °C
THF, Ag2O, Pd(MeCN)2Cl2, AsPh3 (4 equiv),
0 °C
dioxane, Ag2O, Pd(MeCN)2Cl2, AsPh3 (4 equiv),
0 °C
1
1
1
0
1
2
56
77
62
7
7
7
a
Reactions were carried out using 0.05 mmol of catalyst. trans-
-Pentylcyclopropylboronic acid (1.1 mmol), triflate (1 mmol), and
2
b
base (3 mmol) in 4 mL of solvent for 18 h. Isolated yield based
c
on triflate. â-Tetronic acid was obtained.
and the base (entry 5 vs 6). To circumvent the sensitivity
of â-tetronic acid triflate to both water and strong base,
2
we turn to use the even weaker base Ag O, which was
a
reported to have the characteristic of accelerating the
coupling reaction rate.15 As expected, this modification
enhanced the yield to 38% (entry 7). To evaluate the effect
of the catalysts on the reaction, some catalysts were
examined. The results showed that the catalytic activity
Reactions were carried out at 70 °C using 0.05 mmol of
Pd(MeCN)2Cl2, 0.20 mmol of AsPh3, boronic (1.1 mmol), â-tetronic
b
acid triflate (1.0 mmol), 3 equiv of Ag2O in 4 mL THF. Isolated
c
yields based on â-tetronic acid triflate. ee: 91%, determined by
HPLC(chiralcel OJ ), [R]20D ) -462.5 (c 0.45 in CHCl3). ee: 93%,
d
20
determined by HPLC(chiralcel OJ ), [R] D ) +467.1 (c 0.54 in
of Pd(MeCN)
Pd(PPh and PdCl
of the reaction temperature made the yield increase to
6% (entry 10 vs 9). The investigation of solvent effect
2
Cl
2
/AsPh
3
was more effective than that of
CHCl ).
3
3
)
4
2
(dppf) (entry 9 vs 7, 8). The decrease
Sch em e 1
5
on the reaction indicated that etheral solvent THF and
dioxane were preferred to the nonpolar solvent toluene-
(entries 11, 12 vs 10).
After establishing the optimum reaction conditions
Table 1, entry 11), we evaluated the scope of the coupling
(
reaction by investigating the reaction with various cy-
clopropylboronic acids (Table 2). As shown in Table 2,
the optimized coupling reaction condition is applicable
to both the racemic cyclopropylboronic acids (entry 1-5)
that the chiral cyclopropyl group was not racemized
during the coupling reaction with aryl bromides.
1
6
1
6
and the optical active cyclopropylboronic acids (entries
This coupling reaction condition was also suitable to
the alkenylboronic acids (entries 8, 9), and judging from
1
6
, 7). The H NMR spectrums of the products showed that
1
products were pure trans-isomer, indicating that the
configuration of cyclopropyl group was retained during
the reaction. Together with the fact that the coupling
products 2f and 3 of the same (1R,2R)-2-phenylcyclopro-
pylboronic acid 1f had the same ee value and optical
sense (Scheme 1), suggested that the absolute configu-
ration of cyclopropyl group was retained during the
reaction. As in our previous work it has been confirmed
the H NMR spectrums of the products, the configuration
of alkenyl group was retained during the reaction. The
yields of these cross-coupling products were moderate to
good. Therefore, we have supplied here a better coupling
condition than that of Grigg and Honda.
In summary, we have studied the palladium-catalyzed
cross-coupling condition for â-tetronic acid triflate with
sterodefined cyclopropyl (including the enantiomeric cy-
clopropyl), alkenylboronic acids in detail. The success of
this reaction provides an efficient and convenient ap-
proach to 4-substituted 2(5H)-furanones. For the active
alkenyl and cyclopropyl functions could be further elabo-
rated,17 our reaction procedure might opened a door to
prepare many other types of 4-substituted 2(5H)-fura-
(
15) (a) Uenishi, J .; Beau, J .-M.; Armstrong, R. W.; Kishi, Y. J . Am.
Chem. Soc. 1987, 109, 4156. (b) Gillmann, T.; Weeber, T. Synlett 1994,
49. (c) Gronowitz, S.; Bj o¨ rk, P.; Malm, J .; H o¨ rnfeldt, A. B. J .
Organomet. Chem. 1993, 460(1), 127.
16) (1R,2R)-2-Phenylcyclopropylboronic acid (1f) and (1S,2S)-2-
6
(
phenylcyclopropyl-boronic acid (1g) were prepared via the asymmet-
ricly cyclopropanation of trans-tosylboronic acid ester of (+)-TMTA and
(
-)-TMTA, respectively, according to our previous procedure (see:
Zhou, S.-M.; Deng, M.-Z.; Xia, L.-J .; Tang, M.-H. Angew. Chem., Int.
Ed. Engl. 1998, 37, 2845-2847.)
(17) Delgado, J .; Espin o´ s, A.; J im e´ nez, M. C.; Miranda, M. A.; Roth,
H. D.; Tormos, R. J . Org. Chem. 1999, 64, 6541, and references therein.

5
036 J . Org. Chem., Vol. 65, No. 16, 2000
Notes
nones. The biological activities of these compounds are
being studied.
(100); 43 (43.69); 209 (38.88); 79 (33.97). Anal. Calcd for
13 20 2
C H O : C, 74.96; H, 9.68. Found: C, 75.16; H, 10.07.
-
1
P r od u ct 2d . Liquid. IR νmax/cm : 2935; 1780; 1743; 1631;
1
8
1
(
34. H NMR δ
3H); 1.10-1.20 (m, 1H); 0.86-1.04 (m, 5H). MS (EI) m/z: 94
: C, 75.63;
H
(ppm): 5.63 (s, 1H); 4.67 (s, 2H); 1.27-1.47 (m,
Exp er im en ta l Section
100); 43 (58.17); 223 (45.48). Anal. Calcd for C14
H
22
O
2
All reactions were performed under an argon atmosphere. The
H, 9.97. Found: C, 75.71; H, 9.99.
â-tetronic acid triflate was prepared according to the literature
P r od u ct 2e. Liquid. IR νmax/cm-1: 3030; 1780; 1744; 1627;
1
0 1
3
procedure. HNMR spectra were recorded using CDCl as the
1
1
2
(
604; 699. H NMR δ
H
(ppm): 7.25-7.34 (m, 3H); 7.09-7.12 (m,
solvent with TMS as an internal standard. The ee values were
determined by chiral HPLC on Chiralcel OJ column.
General procedure for the coupling reaction: â-tetronic acid
triflate (232 mg, 1.0 mmol), boronic acid (1.1 mmol), Pd-
H); 5.75 (s, 1H); 4.78 (s, 2H); 2.28-2.34 (ddd, 1H); 1.90-1.97
ddd, 1H); 1.60-1.68 (ddd, 1H); 1.42-1.48 (ddd, 1H). MS (EI)
m/z: 155 (100); 91 (62.70); 154 (54.40). Anal. Calcd for
: C, 77.98; H, 6.04. Found: C, 77.75; H, 5.92.
P r od u ct 2f. ee: 91%, determined by HPLC (chiralcel OJ ).
R]20
) -462.5 (c 0.45 in CHCl ).
P r od u ct 2g. ee: 93%, determined by HPLC (chiralcel OJ ).
13 12 2
C H O
2 2 3 2
(MeCN) Cl (13 mg, 0.05 mmol), AsPh (61 mg, 0.20 mmol), Ag O
(696 mg, 3 mmol) were placed in a flask under argon atmosphere,
[
D
3
then degassed and dried THF (4 mL) was added, the reaction
mixture was stirred at 70 °C and monitored by TLC. On
completion of the reaction, the mixture was diluted with ether
[
R]20
D
3
) +467.1 (c 0.54 in CHCl ).
P r od u ct 2h . Liquid. IR νmax/cm-1: 2934; 1782; 1753; 1649;
(
50 mL), filtered through a short pad of silica gel, and evapo-
rated. Purification of the residue by silica gel chromatography
ethyl acetate/petroleum ) 1:2-7) gave the corresponding
products 2a -i.
P r od u ct 2a . Liquid. IR νmax/cm- : 2934; 1775; 1736; 828. H
NMR δ
(ppm): 5.61 (s, 1H); 4.66 (s, 2H); 1.28-1.44 (m, 9H, 4 ×
CH + H); 1.09-1.18 (m, 1H); 0.86-1.03 (m, 5H, CH + H +
H). MS (EI) m/z: 181 (100); 111 (31.92); 41 (30.34). Anal. Calcd
for C12 : C, 74.19; H, 9.34. Found: C, 74.15; H, 9.51.
P r od u ct 2b. Liquid; IR νmax/cm : 2932; 1778; 1739; 828. H
NMR δ (ppm): 5.62 (s, 1H); 4.66 (s, 2H); 1.28-1.44 (m, 7H);
1
8
88. H NMR δ
H
(ppm): 6.39 (d, 1H, J ) 16.1 Hz); 6.14 (dt, 1H,
J ) 6.9;16.1 Hz); 5.83 (s, 1H); 4.95 (s, 2H); 2.17-2.24 (dt, 2H, J
6.9); 1.34-1.46 (m, 2H); 1.24-1.32 (m, 4H); 0.88-0.93 (t, 3H,
J ) 7.0 Hz). MS (EI) m/z: 111 (100); 67 (35.75); 43 (33.73). Anal.
Calcd for C11 : C, 73.30; H, 8.95. Found: C, 73.20; H, 9.21.
P r od u ct 2i. Liquid. IR νmax/cm : 2934; 1782; 1753; 1649;
(
)
1
1
16 2
H O
H
-
1
2
3
1
8
88. H NMR δ
J ) 6.9;16.1 Hz); 5.83 (s, 1H); 4.95 (s, 2H); 2.19-2.26(dt, 2H, J
6.9); 1.32-1.46 (m, 2H); 1.24-1.31 (m, 6H, 3 × CH ); 0.87-
.92 (t, 3H, J ) 6.8 Hz). MS (EI) m/z: 111 (100); 79 (51.22); 43
38.26); 77 (36.70); 112 (30.99). Anal. Calcd for C12 : C,
H
(ppm): 6.39 (d, 1H, J ) 16.1 Hz); 6.14 (dt, 1H,
18 2
H O
)
0
(
2
-
1
1
H
18 2
H O
1
1
8
.09-1.18 (m, 1H); 0.85-1.04 (m, 5H). MS (EI) m/z: 181 (100);
7
4.19; H, 9.34. Found: C, 74.20; H, 9.58.
82 (16.95); 41 (8.02). Anal. Calcd for C11
.95. Found: C, 73.04; H, 8.87.
16 2
H O : C, 73.30; H,
Ack n ow led gm en t. We thank the National Science
Foundation of China for the financial support.
P r od u ct 2c. Liquid. IR νmax/cm-1: 2934; 1778; 1742; 1628;
1
8
1
29. H NMR δ
H
(ppm): 5.62 (s, 1H); 4.66 (s, 2H); 1.26-1.45 (m,
1H); 1.10-1.19 (m, 1H); 0.86-1.04 (m, 5H). MS (EI) m/z: 111
J O000195T