Fluoride-assisted regioselective conversion of functionalized furans to α-substituted γ-hydroxybutenolides using singlet oxygen

Article abstract of DOI:10.1021/jo070666c

(Chemical Equation Presented) A facile synthesis of α-substituted γ-hydroxybutenolides from 3-furfural was achieved using a Baylis-Hillman reaction followed by singlet oxygen oxidation. The regioselectivity of this conversion was controlled by using TBAF.

Full text of DOI:10.1021/jo070666c

SCHEME 1
Fluoride-Assisted Regioselective Conversion of
Functionalized Furans to r-Substituted
γ-Hydroxybutenolides Using Singlet Oxygen
Santoshkumar N. Patil and Fei Liu*
Department of Chemistry and Biomolecular Sciences,
Macquarie UniVersity, Sydney, New South Wales, 2109
Australia
fliu@alchemist.chem.mq.edu.au
ReceiVed April 1, 2007
droxybutenolide has met with considerable challenges. Most
recently, Aquino and co-workers reported the first example of
a regioselective conversion of a bromo-furan to the R-substituted
γ-hydroxybutenolide using DBU (eq 1).3f This method, however,
resulted in complex mixtures of products when we applied it
to more functionalized furans such as 3a (eq 2).
We have previously reported using the Baylis-Hillman
reaction for synthesizing 3-hydroxyacrylate furans, from 3-fur-
A facile synthesis of R-substituted γ-hydroxybutenolides
from 3-furfural was achieved using a Baylis-Hillman
reaction followed by singlet oxygen oxidation. The regiose-
lectivity of this conversion was controlled by using TBAF.
The γ-hydroxybutenolide moiety is frequently observed in
bioactive natural products. The R-substituted γ-hydroxybuteno-
lides have found utility as antimicrobial compounds, while the
â-substituted γ-hydroxybutenolides are known to have antican-
cer or anti-inflammatory properties.1 This has prompted ongoing
interest in the development of facile and selective synthetic
methods for rapidly accessing diverse and highly functionalized
analogues of this class of structures.2 Photooxidative conversion
of furans to R- or â-substituted γ-hydroxybutenolides (Scheme
1), among other transformations amenable to practical combi-
natorial synthesis, has in particular received significant attention
due to the mild and green nature of this transformation from
readily available starting materials.3 The use of a simple alkyl
amine base to confer regioselectivity for the â-substituted
γ-hydroxybutenolides in this transformation is an established
strategy;3d however, the selectivity for the R-substituted γ-hy-
fural and a range of acrylates, and their subsequent conversion
selectively to the â-substituted γ-hydroxybutenolides using
Hu¨nig’s base.4 Herein, we report a regioselective conversion
of these highly functionalized furans to R-substituted γ-hy-
droxybutenolide by simply switching the base to TBAF during
the photooxidation reaction. Nucleophilic halides have been
shown to catalyze the alkylation of butenolides masked as
alkoxyfurans.5 In this Note, the use of a fluoride anion is
proposed to exert its effect on the regioselectivity for R-sub-
stituted γ-hydroxybutenolide through H-bonding to the 3′-
hydroxy group in close proximity.
The Baylis-Hillman reaction was found to be an economic
and mild method for synthesizing 3-hydroxyacrylate furans with
moderate yields between 30 and 70% (unreacted starting
materials recovered).4 From our previous mechanistic studies
of the photooxidation reaction of the 3-hydroxyacrylate furans
in the presence of Hu¨nig’s base, the key intermediate observed
by NMR was a salt, 5, formed between the ammonium cation
and an open-ring, butenolide anion (Scheme 2). The formation
of the final butenolide required protonation as a separate step.
This led us to examine the effect of quaternary ammonium salts
in the photooxidation reaction. It was hypothesized that different
salts may prefer different pathways of the endoperoxide opening.
* Corresponding author. Tel.: (02) 9850 8312; fax: (02) 9850 8313.
(1) For recent examples of R- or â-substituted bioactive butenolides found
in nature, see: (a) Wright, A. D.; Nys, R. D.; Angerhofer, C. K.; Pezzuto,
J. M.; Gurrath, M. J. Nat. Prod. 2006, 69, 1180-1187. (b) Keyzers, R. A.;
Davies-Coleman, M. T. Chem. Soc. ReV. 2005, 34, 355-365. (c) Charan,
R. D.; McKee, T. C.; Boyd, M. R. J. Org. Chem. 2001, 64, 661-663.
(2) For recent reviews of synthetic routes to butenolides, see: (a)
Bru¨ckner, R. Curr. Org. Chem. 2001, 5, 679-718. (b) Carter, N. B.; Nadany,
A. E.; Sweeney, J. B. J. Chem. Soc., Perkin Trans. 1 2002, 2324-2342.
(3) For initial work in photooxidative conversion of furans to γ-hy-
droxybutenolides, see: (a) Grimminger, W.; Kraus, W. Lieb. Ann. Chem.
1979, 10, 1571-1576. (b) Brownbridge, P.; Chan, T. H. Tetrahedron Lett.
1980, 21, 3431-3434. (c) Katsumura, S.; Hori, K.; Fugiwara, S.; Isoe, S.
Tetrahedron Lett. 1985, 26, 4625-4628. (d) Kernan, M. R.; Faulkner, D.
J. J. Org. Chem. 1988, 53, 2773-2776. For a recent summary of the use
of singlet oxygen in biomimetic syntheses, see: (e) Margaros, I.; Montagnon,
T.; Tofi, M.; Pavlakos, E.; Vassilikogiannakis, G. Tetrahedron 2006, 62,
5308-5317. For a very recent example of regioselective synthesis of
γ-hydroxybutenolides, see: (f) Aquino, M.; Bruno, I.; Riccio, R.; Gomez-
Paloma, L. Org. Lett. 2006, 8, 4831-4834.
(4) Patil, S. N.; Liu, F. Org. Lett. 2007, 9, 195-198.
(5) Ma, S.; Lu, L.; Lu, P. J. Org. Chem. 2005, 70, 1063-1065.
10.1021/jo070666c CCC: $37.00 © 2007 American Chemical Society
Published on Web 07/13/2007
J. Org. Chem. 2007, 72, 6305-6308
6305

TABLE 2. TBAF-Assisted Regioselective Conversion of 3 to 4 and
6
SCHEME 2
entry
furan
R
%yielda 4/6
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
Me
Et
Butyl
dodecyl
2-chloroethyl
Allyl
benzyl
cinnamyl
84:12
86:11
95:0
91:3
92:3
87:11
89:0
90:4
TABLE 1. Effects of Quaternary Ammonium Salts and Solvents
on the Conversion of 3a to 4a and 6a
3g
3h
a Isolated yields.
only in the ester group of the hydroxy acrylate side chain
attached to the furan core. The side chain variation on the furan
core was influential on the regioselectivity of the photooxidation.
The bulkiness of the side chain seemed to somewhat enhance
the regioselectivity ratio for the R-isomer, even though the
deprotonation site leading to the R-isomer must be at the
sterically more hindered proton. For example, the regioselec-
tivity ratio for 3a (entry 1, Table 2) was 7:1, while that for 3h,
which has a larger cinnamyl side chain (entry 8, Table 2), was
23-25:1. In the case of 3g (entry 7, Table 2), the R-isomer
was the sole γ-hydroxybutenolide isolated.
Initially, the isolated yields of butenolides 4a-h from this
transformation were only moderate between 30 and 60%. This
was inconsistent with the proton NMR spectra of the crude
mixtures of the reactions that indicated nearly quantitative
deprotonation of the endoperoxide to reach the salt intermediate.
It was hypothesized that the subsequent protonation step may
not have proceeded efficiently. Optimization of the purification
step revealed that DOWEX acidic resins would suffice in
protonating the salt intermediate and furnish the desired
butenolides in high yields without aqueous workup. The utility
of these resins in TBAF workup was also highlighted by a recent
report on the synthesis of halichondrin.6
entry
quaternary ammonium salta
solvent
ratio 4a/6ab
0:1
1:13
5:1
complex mixture
complex mixture
3:1
7:1
1
2
3
4
5
6
7
TBAH in MeOHc
TBAC
MeOH
MeOH
MeOH
THF
THF
THF
TBAF in THFc
TBAI
TBAC
TBAF in THF
TBAF in THF
DCM
a Abbreviations: tetrabutylammonium hydroxide (TBAH), tetrabutyl-
ammonium iodide (TBAI), tetrabutylammonium chloride (TBAC), and
tetrabutylammonium fluoride (TBAF). b Ratio was determined by NMR.
c These reagents were commercially available as solutions.
When a series of tetrabutylammonium salts was applied (Table
1), the usual regioselectivity for the â-substituted γ-hydroxy-
butenolide was observed for TBAH and TBAC in methanol,
while this selectivity was reversed with TBAF, which provided,
interestingly, R-substituted γ-hydroxybutenolide as the major
isomer.
As this preference for the R-isomer of γ-hydroxybutenolide
controlled by a salt in singlet oxygen oxidation is unprecedented,
we sought to examine the role of TBAF in this reaction further.
A panel of quaternary ammonium fluorides, including tetra-
ethylammonium fluoride (TEAF), tetrahexylammonium fluoride
(THAF), and TBAF, was applied to the photooxidation reaction
of 3a in dichloromethane. The selectivity for the R-isomer of
γ-hydroxybutenolide was consistently observed for all three
fluorides, with the regioselectivity ratio reduced to around 2 or
4:1 in the TEAF or THAF case. This suggested that the
regioselectivity was dependent on the fluoride anion and that
the bulkiness of the alkyl ammonium cation had only a minor
effect in determining the deprotonation pathway of the endo-
peroxide.
This fluoride-based regioselectivity prompted us to investigate
further the possible mechanism behind this preferred deproto-
nation path in opening the endoperoxide intermediate. It was
postulated that the secondary hydroxy group could guide the
incoming fluoride through H-bonding toward the H2 proton for
deprotonation, which would lead to the regioselective formation
of the R-substituted γ-hydroxybutenolides. To test this hypoth-
esis, the hydroxy group of 3a was protected as an acetate to
provide 7, which was then subjected to the photooxidation in
the presence of TBAF (Scheme 3). The regioselectivity for the
R-isomer, 8, was in this case lost, in the absence of this
We then investigated the scope and substrate effect of this
fluoride-assisted, regioselective conversion of furans to buteno-
lides with TBAF as the fluoride source. A group of highly
functionalized furans, 3a-h, synthesized as the BH adducts of
3-furfural with a variety of acrylates, was subjected to this
reaction in the presence of 1.2 equiv of TBAF in dichlo-
romethane (Table 2). These substrates differed from one another
(6) Kaburagi, Y.; Kishi, Y. Org. Lett. 2007, 9, 723-726.
6306 J. Org. Chem., Vol. 72, No. 16, 2007

SCHEME 3
Butyl 2-(Furan-3-yl(hydroxy)methyl)acrylate (3c). Yield: 49%;
1H NMR (400 MHz, CDCl3) δ 0.91-0.94 (m, 3H), 1.41-1.36 (m,
2H), 1.67-1.60 (m, 2H), 3.09 (d, J ) 6.3 Hz, 1H), 4.17 (t, J ) 6.6
Hz, 2H), 5.51 (d, J ) 6.3 Hz, 1H), 5.85 (s, 1H), 6.30 (s, 1H), 6.36
(d, J ) 0.8 Hz, 1H), 7.37 (s, 1H), 7.38 (d, J ) 0.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 14.1, 19.6, 31.0, 65.4, 67.4, 109.5,
126.2, 127.2, 140.3, 142.0, 143.8, 166.9; IR (thin film/NaCl) 1719
cm-1; ESI [M + Na+]: 247.095717, calcd for (C12H16O4Na)+:
247.094629.
Dodecyl 2-(Furan-3-yl(hydroxy)methyl)acrylate (3d). Yield:
1
40%; H NMR (400 MHz, CDCl3) δ 0.88 (t, J ) 6.6 Hz, 3H),
1.26 (s, 18H), 1.66-1.54 (m, 2H), 3.12 (d, J ) 6.3 Hz, 1H), 4.15
(t, J ) 6.6 Hz, 2H), 5.51 (d, J ) 6.1 Hz, 1H), 5.85 (s, 1H), 6.29
(s, 1H), 6.36 (s, 1H), 7.38-7.37 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 14.6, 23.2, 26.2, 26.4, 29.0, 29.7, 29.8, 29.9, 30.0, 30.1,
32.4, 65.7, 67.3, 109.6, 126.1, 127.2, 140.3, 142.1, 143.7, 166.9;
IR (thin film/NaCl) 2929, 2855, 1718 cm-1; ESI [M + Na+]:
359.219551, calcd for (C20H32O4Na)+: 359.219830.
H-bonding group, and the â-substituted γ-hydroxybutenolide,
9, became the predominant isomer. Presumably, in the absence
of the H-bond donor, the preferred deprotonation site would be
the less hindered H5, as seen in our previous study with a bulky
Hu¨nig’s base, to form the â-substituted butenolide.4 The
relationship seen in the 3a-h series between the bulkiness of
the side chain and the regioselectivity ratio for the R-isomer
through the more hindered deprotonation pathway supports
indirectly this postulate, as the transition state could be more
conformationally rigidified in the presence of a bulkier side
chain to facilitate a stronger H-bonding interaction between the
fluoride anion and the 3′-hydroxy group.
In conclusion, this work illustrates the utility of using a simple
reagent, TBAF, to control the regioselective formation of
R-substituted γ-hydroxybutenolides from highly functionalized
3′-hydroxyacrylate furans using singlet oxygen. The role of
TBAF in conferring the regioselectivity is attributed to the
H-bonding interaction between the fluoride anion and the OH
group in close proximity to bias one of the two deprotonation
pathways from the key endoperoxide intermediate formed upon
photooxidation. This selective and facile synthesis presents an
efficient entry to functionalized butenolides as useful synthons
for further transformations.
Benzyl 2-(Furan-3-yl(hydroxy)methyl)acrylate (3g). Yield:
1
47%; H NMR (400 MHz, CDCl3) δ 4.70 (s, 1H), 5.20 (s, 2H),
5.54 (s, 1H), 5.90 (s, 1H), 6.36-6.34 (m, 2H), 7.38-7.28 (m, 7H);
13C NMR (100 MHz, CDCl3) δ 65.9, 67.3, 109.5, 126.7, 127.5,
128.2, 128.6, 128.9, 129.1, 135.9, 140.4, 141.8, 143.8, 166.6; IR
(thin film/NaCl) 3055, 2985, 1717 cm-1; ESI [M + Na+]:
281.078810, calcd for (C15H14O4Na)+: 281.078979.
General Procedure for Singlet Oxygen Oxidation Reaction.
To a mixture of a Baylis-Hillman adduct (0.30 mmol) and Rose
Bengal (3 mg, 0.003 mmol) in anhydrous dichloromethane (70 mL)
was added tetrabutylammonium fluoride, 1.0 M solution in tet-
rahydrofuran (0.36 mmol). The reaction mixture was then exposed
to singlet oxygen (generated from air with a 150 W flood light) at
-78 °C for 1 h. The reaction mixture was then warmed to -20
°C, and the solvent was removed under vacuum at room temper-
ature. The crude mixture as solution in acetonitrile (2 mL) was
then passed through Poly Prep columns containing a prefilled
AG50W-X8 (H+) resin of ion exchange capacity 3.4 (nominal
mequiv/2 mL of resin) using 8 mL of acetonitrile. The residue,
after the protonation step, was filtered through silica gel to remove
trace impurities (silica gel, 60 Å, 0.06-0.2 mm, 70-230 mesh)
and further purified by flash column chromatography to afford the
butenolide as a colorless oil.
Methyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
methyl)acrylate (4a). Yield: 84%; H NMR (400 MHz, CDCl3)
Experimental Section
1
δ 3.79 (s, 3H), 5.33 (s, 1H), 6.05 (s, 1H), 6.14 (s, 1H), 6.43 (s,
1H), 7.12 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 55.8, 66.7, 97.7,
129.0, 138.1, 138.3, 146.4, 166.8, 170.5; IR (thin film/NaCl) 3421,
1759, 1715 cm-1; ESI [M + Na+]: 237.037562, calcd for (C9H10O6-
Na)+: 237.037508.
General Procedure for the Preparation of Baylis-Hillman
Adducts. DBU (475 mg, 3.12 mmol) was added to a stirred solution
of an acrylate (3.75 mmol) and 3-furfural (300 mg, 3.12 mmol) at
0 °C. The reaction mixture was allowed to warm to room tempera-
ture and stirred under nitrogen at room temperature for 2 days. Upon
finishing, dichloromethane (15 mL) was added to the reaction mix-
ture and neutralized with 1 N HCl, followed by washing with water
and brine. The organic layer thus obtained was dried over Na2SO4,
filtered, and evaporated to provide a crude mixture for further puri-
fication by column chromatography (petroleum ether/ethyl acetate
2:1) to afford the Baylis-Hillman adduct as a colorless oil.
Ethyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
1
methyl)acrylate (4b). Yield: 86%; H NMR (400 MHz, CDCl3)
δ 1.30 (t, J ) 7.1 Hz, 3H), 4.22 (q, J ) 7.1 Hz, 2H), 5.31 (s, 1H),
6.03 (bs, 1H), 6.12 (s, 1H), 6.42 (s, 1H), 7.11 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 14.5, 62.0, 66.4, 66.5, 97.8, 128.5, 128.8,
138.1, 138.6, 146.6, 166.4, 170.7; IR (thin film/NaCl) 1766, 1712
cm-1; ESI [M + Na+]: 251.053500, calcd for (C10H12O6Na)+:
251.053158.
Methyl 2-(Furan-3yl(hydroxy)methyl)acrylate (3a). Yield:
1
66%; H NMR (400 MHz, CDCl3) δ 3.06 (d, J ) 4.0 Hz, 1H),
3.76 (s, 3H), 5.50 (d, J ) 4.0 Hz, 1H), 5.87 (s, 1H), 6.30 (s, 1H),
6.35 (s, 1H), 7.37-7.38 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
52.6, 66.2, 109.5, 126.4, 127.0, 140.3, 141.7, 144.1, 167.8; IR (thin
film/NaCl) 1719 cm-1; ESI [M + Na+]: 205.047658, calcd for
(C9H10O4Na)+: 205.047679.
Butyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
1
methyl)acrylate (4c). Yield: 95%; H NMR (400 MHz, CDCl3)
δ 0.94 (t, J ) 7.4 Hz, 3H), 1.44-1.34 (m, 2H), 1.69-1.62 (m,
2H), 4.0-3.9 (bs, 1H), 4.17 (t, J ) 6.6 Hz, 2H), 4.9-4.7 (bs, 1H),
5.31 (s, 1H), 6.02 (s, 1H), 6.13 (s, 1H), 7.11 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 14.1, 19.6, 30.9, 65.8, 66.6, 97.8, 128.6, 138.2,
Ethyl 2-(Furan-3-yl(hydroxy)methyl)acrylate (3b). Yield: 51%;
1H NMR (400 MHz, CDCl3) δ 1.27 (t, J ) 7.1 Hz, 2H), 3.12 (bs,
1H), 4.22 (q, J ) 7.1 Hz, 2H), 5.50 (s, 1H), 5.85 (s, 1H), 6.30 (s,
1H), 6.36-6.35 (m, 1H), 7.39-7.37 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 14.6, 61.5, 67.3, 109.5, 126.1, 127.2, 140.3, 142.0, 143.8,
166.9; IR (thin film/NaCl) 3411, 1712 cm-1; ESI [M + Na+]:
219.062522, calcd for (C10H12O4Na)+: 219.063329.
138.6, 146.4, 166.5, 170.6; IR (thin film/NaCl) 1767, 1709 cm-1
ESI [M
279.084458.
;
+
Na+]: 279.086116, calcd for (C12H16O6Na)+:
Dodecyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
1
methyl)acrylate (4d). Yield: 91%; H NMR (400 MHz, CDCl3)
δ 0.88 (t, J ) 6.8 Hz, 3H), 1.4-1.2 (m, 18 H), 1.8-1.5 (m, 2H),
J. Org. Chem, Vol. 72, No. 16, 2007 6307

3.9-3.7 (bs, 1H), 4.16 (t, J ) 6.74 Hz, 2H), 5.32 (s, 1H), 6.02 (s,
1H), 6.13 (s, 1H), 6.41 (s, 1H), 7.12 (s, 1H); 13C NMR (100 MHz,
CDCl3) δ 14.6, 23.2, 26.4, 28.9, 29.7, 29.8, 29.98, 30.05, 30.1,
32.4, 66.1, 65.0, 97.7, 128.6, 138.4, 138.5, 146.0, 166.5, 170.2; IR
(thin film/NaCl) 1765, 1717 cm-1; ESI [M + Na+]: 319.209785,
calcd for (C20H32O6Na)+: 319.209659.
6.28 (dt, J ) 15.4, 6.6 Hz, 1H), 6.48 (s, 1H), 6.67 (d, J ) 15.8 Hz,
1H), 7.11 (s, 1H), 7.38-7.23 (m, 5H); 13C NMR (100 MHz, CDCl3)
δ 60.0, 66.4, 98.5, 122.8, 127.1, 128.7, 128.9, 129.1, 135.3, 136.4,
138.0, 138.7, 146.9, 166.1, 170.9; IR (thin film/NaCl) 1769, 1709
cm-1; ESI [M + Na+]: 339.084760, calcd for (C17H16O6Na)+:
339.084458.
2-Chloroethyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-
3-yl)methyl)acrylate (4e). Yield: 92%; 1H NMR (400 MHz, CDCl3)
δ 3.73 (t, J ) 5.6 Hz, 2H), 4.43-4.40 (m, 2H), 5.36 (s, 1H), 6.10
(s, 1H), 6.16 (s, 1H), 6.51 (s, 1H), 7.12 (s, 1H); 13C NMR (100
MHz, CDCl3) δ 42.0, 65.1, 66.6, 98.1, 129.7, 138.2, 146.0, 165.7,
170.3; IR (thin film/NaCl) 3409, 1764, 1710 cm-1; ESI [M + Na+]:
287.010534, calcd for (C10H11O6ClNa)+: 287.011236.
Allyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
methyl)acrylate (4f). Yield: 87%; 1H NMR (400 MHz, CDCl3) δ
4.67 (dt, J ) 5.8, 1.3 Hz, 2H), 5.36-5.27 (m, 3H), 5.93 (ddt, J )
17.2, 10.4, 5.9 Hz, 1H), 6.06 (s, 1H), 6.12 (s, 1H), 6.46 (s, 1H),
7.10 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 66.4, 66.8, 97.7, 119.5,
129.0, 132.0, 138.1, 138.4, 146.3, 166.0, 170.4; IR (thin film/NaCl)
1767, 1718 cm-1; ESI [M + Na+]: 263.052578, calcd for
(C11H12O6Na)+: 263.053158.
Methyl 2-(Acetoxy(furan-3-yl)methyl)acrylate (7). Yield: 30%;
1H NMR (400 MHz, CDCl3) δ 2.10 (s, 2H), 3.75 (s, 1H), 5.92 (s,
1H), 6.36 (s, 1H), 6.38 (s, 1H), 6.66 (s, 1H), 7.36 (s, 1H), 7.42-
7.41 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 21.5, 52.6, 66.4,
109.9, 123.7, 126.2, 139.6, 141.7, 143.8, 165.9, 169.9; ESI [M +
Na+]: 247.057789, calcd for (C11H12O5Na)+: 247.058243.
Methyl 2-(Acetoxy(2-hydroxy-5-oxo-2,5-dihydrofuran-3-yl)-
methyl)acrylate (9). Yield: 79%; 1H NMR (400 MHz, CDCl3) δ
2.16 (s, 1H), 3.81 (s, 1H), 6.04 (s, 1H), 6.11 (s, 1H), 6.30 (s, 1H),
6.52 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 21.2, 53.2, 66.4, 68.2,
98.8, 120.5, 121.7, 128.7, 130.3, 169.8; ESI [M + Na+]: 279.047662,
calcd for (C11H12O7Na)+: 279.048073.
Acknowledgment. This work was supported by an Austra-
lian Research Council Discovery Grant to F.L. (ARC-
DP055068). S.N.P. is supported by a pre-doctoral research
fellowship from Macquarie University.
Benzyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-yl)-
1
methyl)acrylate (4g). Yield: 89%; H NMR (400 MHz, CDCl3)
δ 5.19 (d, J ) 4.2 Hz, 2H), 5.33 (s, 1H), 6.03 (s, 1H), 6.05 (s, 1H),
6.46 (s, 1H), 7.02 (s, 1H), 7.30-7.36 (m, 5H); 13C NMR (100 MHz,
CDCl3) δ 66.4, 67.5, 97.7, 128.7, 128.8, 129.0, 129.1, 129.2, 135.6,
Supporting Information Available: NMR spectra of 3a-h,
1
4a-h, 7, and 9 and H NMR spectra of the product mixtures of
138.4, 146.5, 166.0, 170.5; IR (thin film/NaCl) 1767, 1709 cm-1
;
the singlet oxygen oxidation of furans after ion exchange and
filtering. This material is available free of charge via the Internet
at http://pubs.acs.org.
ESI [M + Na+]: 313.069581, calcd for (C15H14O6Na)+: 313.068808.
Cinnamyl 2-(Hydroxy(5-hydroxy-2-oxo-2,5-dihydrofuran-3-
yl)methyl)acrylate (4h). Yield: 90%; 1H NMR (400 MHz, CDCl3)
δ 4.83 (d, J ) 5.5 Hz, 2H), 5.34 (s, 1H), 6.06 (s, 1H), 6.10 (s, 1H),
JO070666C
6308 J. Org. Chem., Vol. 72, No. 16, 2007