Zinc or indium-mediated Barbier-type allylation of aldehydes with 3-bromomethyl-5H-furan-2-one in aqueous media: An efficient synthesis method for α-methylene-γ-butyrolactone

Article abstract of DOI:10.1039/c2ob25397f

A zinc or indium-mediated Barbier-type allylation of aldehydes with 3-bromomethyl-5H-furan-2-one in aqueous solvents was developed to provide an efficient route to α-methylene-γ-butyrolactone, which is synthetically very useful. The desired products were

Full text of DOI:10.1039/c2ob25397f

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COMMUNICATION
Zinc or indium-mediated Barbier-type allylation of aldehydes with
3-bromomethyl-5H-furan-2-one in aqueous media: an efficient synthesis
method for α-methylene-γ-butyrolactone†
YuZhe Gao, Xue Wang, LiDong Sun, LongGuan Xie and XiaoHua Xu*
Received 24th February 2012, Accepted 31st March 2012
DOI: 10.1039/c2ob25397f
organic wastes. The development of such reactions offers the
possibility of obtaining environmentally benign reaction con-
ditions. The metals employed therein include magnesium,3 tin,4
indium,5 zinc,6 cadmium,7 manganese,8 antimony9 and
bismuth.10
In our earlier work, it was found that the construction of
α-methylene-γ-butyrolactone can be easily carried out though
Barbier-type reaction of 3-bromomethyl-5H-furan-2-one, and
two natural products were successfully synthesized and
reported,11,12 which proved that this bromolactone is quite a
useful synthon for α-methylene-γ-butyrolactone.
The first reported compound using 3-bromomethyl-5H-furan-
2-one as a synthon was ( )-cedarmycin B,11 which was accom-
plished in a yield of 8%. Then 8-epigrosheimin was successfully
synthesized12 and a final yield of 45% obtained after the route
was improved.13 ( )-Hydroxymatairesinol and ( )-methylenol-
actocin were the latest compounds reported.14
A zinc or indium-mediated Barbier-type allylation of alde-
hydes with 3-bromomethyl-5H-furan-2-one in aqueous sol-
vents was developed to provide an efficient route to
α-methylene-γ-butyrolactone, which is synthetically very
useful. The desired products were obtained in moderate to
high yields in aqueous solvents. Excellent drs were achieved,
among which the best diastereomeric ratios of products were
found when water was used in the indium-mediated reaction,
and THF–NH4Cl (sat, aq) (2 : 1) mixture in the zinc-
mediated reaction. Furthermore, the allylation can be
induced by chiral centers, especially those in the α-position,
as a substrate-controlled reaction to obtain the enantioselec-
tive homoallylation alcohols.
Although it has been used in synthesis for some years, the
study and application of allylation reactions with 3-bromo-
methyl-5H-furan-2-one is still in its infancy and only a little
research has been reported,14 in which the allylation takes place
in organic solvents or is complicated to manipulate, and so the
Introduction
There are about 10% natural products containing the γ-butyrolac-
tone construction that display a broad biological profile which
attracts much attention. In many cases, the α-methylene groups
in the lactone ring lead to their biological activities,1 which is
not easy to build2 (Fig. 1).
On the other hand, carbon–carbon bond formation constitutes
one of the fundamental processes in organic synthesis and a
wide variety of synthetic protocols have been developed to date
for effecting this, amongst which organometallic reactions have
played a major role. It was noticed in the early 1980s that allylic
halides in particular can be used to react with aldehydes in the
presence of metal powder to afford homoallylic alcohols in
aqueous media. This type of allylic carbonyl addition has been
called the Barbier-type allylation. Then there was a surge of
great interest in the Barbier-type allylation. The use of water as
solvent could reduce or eliminate environmental damage by
State Key Laboratory of Elemento-Organic Chemistry, Nankai
University, Tianjin 300071, China. E-mail: xiaohuaxu@nankai.edu.cn;
Fax: +88 22 23504284
†Electronic supplementary information (ESI) available. CCDC reference
numbers 869715 and 869716. For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/c2ob25397f
Fig. 1 Representative α-methylene γ-butyrolactones.
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Table 1 Effect of metal and solvent on the allylation of benzaldehyde
aqueous NH4Cl solution instead of water, the yield of product
increased a little, but the dr dropped (entry 4, Table 1). We also
observed that in a mixture of THF and water (2 : 1) or THF and
saturated aqueous NH4Cl (2 : 1), the reaction can be finished
more quickly but still with a dr of 98 : 2 (entries 5 and 6,
Table 1). Then we found that, with 2.0 equiv of indium, the reac-
tion in water can be accomplished in a yield of 96%, while with
1.5 equiv of indium, the yield decreased to 76% (entries 2 and 3,
Table 1). Thus, conditions A (1.5 equiv of 3-bromomethyl-5H-
furan-2-one, 2 equiv of indium, water, rt) were established as the
optimized reaction conditions. When indium was replaced with
activated zinc powder, the mixture of THF and saturated aqueous
NH4Cl proved to be the best media (entry 9, Table 1, conditions
B), with the best yield and the highest dr. While in water or a
mixture of THF and water (2 : 1), the zinc-mediated reaction
gave worse yields and lower drs.
Then we investigated the Barbier-type reaction of benzal-
dehyde with 3-bromomethyl-5H-furan-2-one in organic media.
The zinc and indium-mediated reaction afforded 86%, 79%
yields with 88 : 12 and 98 : 2 drs in DMF, while the yields
dropped to 35%–54% in DCM, THF and ether when indium was
used, in contrast to no products being observed with zinc. But
the reaction with zinc can take place in THF with BF3·Et2O cata-
lysis, affording 42% yield and 92 : 8 dr. However, both yields
and drs dropped in the indium-mediated reaction with BF3·Et2O
catalysis in organic solvents. This proves aqueous media is much
better for the reaction.
Entry Metal Solvent
Time (h) Yielda (%) drb
1
2
3
4
5
6
In
H2O
H2O
H2O
12
12
12
12
6
87
76
96
88
91
89
99 : 1
99 : 1
99 : 1
98 : 2
98 : 2
98 : 2
Inc
Ind
In
NH4Cl (sat, aq)
THF–H2O = 2 : 1
THF–NH4Cl
(sat, aq) = 2 : 1
H2O
THF–H2O = 2 : 1
THF–NH4Cl
(sat, aq) = 2 : 1
In
In
6
7
8
9
Zn
Zn
Zn
12
6
0.25
82
90
92
85 : 15
95 : 5
96 : 4
1
a Isolated yield. b Determined by H NMR. c 1.5 Equiv of indium were
used. d 2.0 Equiv of indium were used.
full synthetic potential of such reactions is still waiting to be
explored.
Of the metals that have been used in the Barbier-type reaction,
indium and zinc are widely represented. The use of indium metal
as a mediator in the addition of allyl bromides to carbonyl com-
pounds under Barbier-type conditions was first reported in
1988.15 Compared to other metals, indium offers a number of
advantages: indium has the lowest first ionization potential rela-
tive to zinc, tin and magnesium which makes high reactivity in
the absence of external activators and proton sources.16 Mean-
while, it is not sensitive to boiling water or alkali and does not
form oxides in air, which makes indium a promising metal for
Barbier-type allylation. Zinc was first employed in Barbier-type
allylations by Wolinsky and co-workers in 1977, and has like-
wise proved to be a highly useful mediator for the allylation of
various substrates. Zinc offers the greatest potential for industrial
application because of its relatively low cost and ready avail-
ability. In contrast to In-mediated allylations, which commonly
are carried out in water–THF mixtures without additives, the use
of Zn generally requires the application of saturated aqueous
NH4Cl as a proton source together with the organic solvent.
Herein we wish to report our recent studies on Barbier-type
reactions of aldehydes with 3-bromomethyl-5H-furan-2-one
using zinc or indium under aqueous conditions, which is more
convenient and environmentally friendly.
Also, we tried to use tin in the reaction.4 But in water with a
catalytic amount of hydrobromic acid or a 1 : 1 mixture of THF
and saturated aqueous NH4Cl, no reaction occurred.
Subsequently, the scope of the allylation of aromatic alde-
hydes and aliphatic aldehydes was studied, with some typical
results listed (Tables 2 and 3).
We found that the Barbier-type allylation of aromatic alde-
hydes took place smoothly under conditions A or B, giving the
expected homoallylic alcohols in moderate to good yields
(Table 2). Various differently substituted benzaldehydes were
investigated, such as 2-chlorobenzaldehyde (entry 3, Table 2), 3-
chlorobenzaldehyde (entry 2, Table 2), 4-chlorobenzaldehyde
(entry 1, Table 2), 4-methoxybenzalde-hyde (entry 4, Table 2),
4-trifluoromethylbenzaldehyde (entry 5, Table 2), 4-tert-butyl-
benzaldehyde (entry 6, Table 2), 4-cyanobenzaldehyde (entry 7,
Table 2), and the other aromatic aldehydes like β-naphthaldehyde
(entry 8, Table 2), 2-furaldehyde (entry 9, Table 2), 2-thiophenal-
dehyde (entry 10, Table 2). All these reagents afforded the
expected products which indicated the wide scope of the reac-
tion. In all cases, the diastereomeric ratios of the homoallylic
alcohols formed using indium were higher than those formed
using activated zinc, which showed the better stereoselectivity of
the reaction when indium is used.
During the reaction of aliphatic aldehydes with 3-bromo-
methyl-5H-furan-2-one, we investigated regular aldehydes
(entries 1 and 2, Table 3) and aldehydes with a conjugated CvC
bond (entry 3, Table 3), an unconjugated CvC bond (entry 5,
Table 3), a heteroatom (entry 4, Table 3), a group with a large
steric effect (entry 6, Table 3) and a phenyl group (entry 7,
Table 3). Moderate to good yields were achieved in most cases.
Better drs were found with indium compared to the situations
with activated zinc. The indium-mediated reactions yielded
Results and discussion
As a starting point, the Barbier-type addition reaction of benzal-
dehyde was chosen to establish the protocol. Some representative
results are listed in Table 1. From Table 1, it is observed that
with 1.7 equiv indium the reaction of 1.5 equiv of 3-bromo-
methyl-5H-furan-2-one with benzaldehyde in water at room
temperature afford homoallylic alcohol in 88% yield with a dia-
stereomeric ratio of 99 : 1 (entry 1, Table 1). By using saturated
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Table 2 Allylation of aromatic aldehydes using In or Zn
Table 3 Allylation of aldehyde using In or Zn
Yield of 2a
Conditions (%)
Entry Aldehyde
Conditions Yield of 4a (%) drb
Entry Aromatic aldehyde
1
drb
1
2
3
4
5
6
A
B
A
B
A
B
A
B
A
B
A
B
94 (4a)
97 (4a)
93 (4b)
96 (4b)
83 (4c)
95 (4c)
80 (4d)
95 (4d)
91 (4e)
89 (4e)
96 (4f)
92 (4f)
99 : 1
74 : 26
99 : 1
91 : 9
97 : 3
45 : 55
99 : 1
90 : 10
95 : 5
96 : 4
99 : 1
98 : 2
A
B
93 (2a)
90 (2a)
95 : 5
90 : 10
2
3
A
B
90 (2b)
92 (2b)
99 : 1
94 : 6
A
B
96 (2c)
92 (2c)
94 : 6
87 : 13
4
A
B
89 (2d)
93 (2d)
98 : 2
95 : 5
7
A
B
79 (4g)
84 (4g)
99 : 1
96 : 4
5
6
A
B
91 (2e)
91 (2e)
96 : 4
93 : 7
a Isolated yield. b Determined by 1H NMR.
A
B
90 (2f)
88 (2f)
98 : 2
97 : 3
7
8
A
B
87 (2g)
98 (2g)
99 : 1
99 : 1
A
B
89 (2h)
85 (2h)
98 : 2
95 : 5
9
A
B
73 (2i)
94 (2i)
76 : 24
73 : 26
10
A
B
85 (2j)
93 (2j)
97 : 3
83 : 17
a Isolated yield. b Determined by 1H NMR.
diastereomeric ratios of up to 99 : 1 dr, especially when the alde-
hydes were hexanal and trans-2-hexenal. When 4-pentenal was
used, a better dr was achieved in the reaction with zinc (96 : 4),
rather than in the reaction with indium (95 : 5), and we cannot
figure out what factor leads to this result. In addition, it should
be noted that 1,4-addition to the conjugated CvC bond in the
aldehydes was not observed, indicating the excellent chemo-
selectivity of reaction.
Scheme 1 Allylation of 5-isopropenyl-2-methyl-1-en-cyclopentane-
carboxaldehyde and 5-isopropenyl-2-methyl-3-oxo-cyclopentanecarbox-
aldehyde.
aldehyde at the β-position, two isomer products are obtained.
Both of these isomers have anti-configuration as a result of the
stereoselectivity derived from the chiral center. When the alde-
hyde contains two or more chiral centers, especially when the
α-carbon is chiral, it might lead to a unique homoallylic alcohol,
which would provide a quite valuable method for chiral organic
synthesis according to the Barbier-type reaction with 3-bromo-
methyl-5H-furan-2-one.
When we used 5-isopropenyl-2-methyl-1-en-cyclopentane-
carboxaldehyde in the Barbier reaction, two isomer products
were observed, compared to the single 5-isopropenyl-2-methyl-
3-oxo-cyclopentanecarboxaldehyde
allylation
product12
(Scheme 1). If there is no chiral center in the starting aldehyde,
potentially four isomers can be produced in the reaction. The
reaction of 3h in both the In-H2O or Zn-THF-NH4Cl reaction
systems indicated that when there is one chiral center in the
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(2) Synthesis of 4-((3-chlorophenyl)(hydroxy)methyl)-3-
methylenedihydrofuran-2(3H)-one (2b)
The ratio was 63 : 37 (4hII : 4hI) using conditions A and
dropped to 44 : 56 using conditions B. After the two isomers
were separated and both treated with two further steps,12 we
obtained the related compounds which confirmed the absolute
configuration by X-ray crystallographic analysis, proving the
configuration of the two isomers of 4h.17
The reaction of 1b (139 mg, 0.99 mmol), 3-bromomethyl-5H-
furan-2-one (263 mg, 1.49 mmol), indium powder (225 mg,
1.96 mmol) and water (1.0 ml) at rt for 12 h afforded 2b
(212 mg, 90%): oil. 1H NMR (400 MHz, CDCl3) δ 7.35 (s, 1H),
7.29–7.31 (m, 2H), 7.18–7.23 (m, 1H), 6.31 (d, J = 2.2 Hz, 1H),
5.67 (d, J = 1.8, 1H), 4.72 (d, J = 7.1 Hz, 1H), 4.23 (t, J = 9.5
Hz, 1H), 4.12 (dd, J = 9.6, 4.1 Hz, 1H), 3.33–3.40 (m, 1H), 2.91
(s, 1H).
Conclusions
In summary, we have developed a convenient allylation reaction
of aldehydes with 3-bromomethyl-5H-furan-2-one by using
indium or zinc in aqueous media, providing an efficient, environ-
mentally friendly route to α-methylene-γ-butyrolactone. Due to
the synthetic potential of the products and mild reaction con-
ditions, this method may be very useful in organic synthesis.
Further studies on the scope and applications of this reaction
with 3-bromomethyl-5H-furan-2-one are being carried out in our
laboratory.
Discernable data for minor diastereoisomer: 6.22 (d, J = 2.2
Hz, 1H), 5.12 (d, J = 2.1 Hz, 1H), 4.54 (dd, J = 9.6, 3.9 Hz,
1H), 4.34 (t, J = 8.1 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 170.9, 142.8, 134.8, 134.4,
130.0, 128.6, 125.8, 124.8, 67.7, 45.4; IR (neat), ν (cm−1) 3455,
1758, 1659, 1274, 1138, 807; HRMS (ESI): M + Na+ found
261.0289, C12H11ClO3Na requires 261.0297.
The reaction of 1b (140 mg, 1.00 mmol), 3-bromomethyl-5H-
furan-2-one (262 mg, 1.49 mmol), activated zinc powder
(106 mg, 166 mmol), THF (1 ml), and saturated aqueous NH4Cl
(0.5 ml) at rt for 15 min afforded 2b (219 mg, 92%).
Experimental section
(1) Synthesis of 4-((4-chlorophenyl)(hydroxy)methyl)-3-
methylenedihydrofuran-2(3H)-one (2a)
(3) Synthesis of 4-((2-chlorophenyl)(hydroxyl)methyl)-3-
methylenedihydrofuran-2(3H)-one (2c)
Typical procedure for the reaction with indium. To a reaction
vessel were added sequentially 1a (135 mg, 0.96 mmol), 3-bro-
momethyl-5H-furan-2-one (254 mg, 1.44 mmol), water (1.0 ml)
and indium powder (225 mg, 1.97 mmol). The mixture was
stirred vigorously at rt. After 12 h the reaction mixture was
filtered by diatomite, extracted with diethyl ether (20 ml × 3),
washed with brine (20 mL), and dried over anhydrous Na2SO4.
Evaporation and column chromatography on silica gel (pet-
roleum ether–ethyl acetate = 1 : l) afforded 2a (214 mg, 93%):
The reaction of 1c (138 mg, 0.99 mmol), 3-bromomethyl-5H-
furan-2-one (265 mg, 1.51 mmol), indium powder (227 mg,
1.99 mmol) and water (1.0 ml) at rt for 12 h afforded 2c
(226 mg, 96%): white solid, mp: 94–108 °C. 1H NMR
(400 MHz, CDCl3) δ 7.50 (dd, J = 7.5, 1.9 Hz, 1H), 7.40 (dd, J
= 7.5, 1.7 Hz, 1H), 7.26–7.34 (m, 2H), 6.27 (d, J = 2.2 Hz, 1H),
5.28 (d, J = 3.6 Hz, 1H), 5.27 (s, 1H), 4.37 (t, J = 9.3 Hz, 1H),
4.32 (dd, J = 9.4, 3.9 Hz, 1H), 3.46–3.52 (m, 1H), 2.67 (br s,
1H).
1
oil, H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 1.9 Hz, 1H),
Discernable data for minor diastereoisomer: 7.62 (dd, J = 7.7,
1.7 Hz, 1H), 7.14–7.19 (m, 3H), 6.31 (d, J = 2.5 Hz, 1H), 5.59
(s, 1H), 5.46 (d, J = 4.0 Hz, 1H), 4.55 (dd, J = 9.5, 4.1 Hz, 1H),
4.21 (t, J = 8.3 Hz, 1H).
7.35 (t, J = 2.3 Hz, 1H), 7.29 (d, J = 2.0 Hz, 1H), 7.27 (d, J =
4.2 Hz, 1H), 6.32 (d, J = 2.3 Hz, 1H), 5.69 (d, J = 1.8 Hz, 1H),
4.73 (d, J = 7.1 Hz, 1H), 4.21 (dd, J = 8.2, 9.6 Hz, 1H), 4.10
(dd, J = 4.1, 9.6 Hz, 1H), 3.33–3.39 (m, 1H), 2.81 (br s, 1H).
Discernable data for minor diastereoisomer: 6.20 (d, J = 2.4
Hz, 1H), 5.08 (d, J = 2.1 Hz, 1H), 4.54 (dd, J = 9.6, 3.9 Hz,
1H), 4.35 (dd, J = 9.6, 7.9 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 171.1, 138.0, 133.8, 131.9,
129.6, 129.4, 128.5, 127.1, 125.6, 71.9, 68.6, 43.6; IR (neat), ν
(cm−1) 3453, 1742, 1659, 1274, 1141, 768; HRMS (ESI):
M + Na+ found 260.0289, C12H11ClO3Na requires 261.0297.
The reaction of 1c (135 mg, 0.96 mmol), 3-bromomethyl-5H-
furan-2-one (263 mg, 1.49 mmol), activated zinc powder
(107 mg, 1.67 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2c (212 mg, 92%).
13C NMR (100 MHz, CDCl3) δ 170.8, 139.1, 134.5, 134.3,
128.9, 127.9, 125.6, 74.8, 67.6, 45.4; IR (neat), ν (cm−1) 3457,
1759, 1660, 1272, 1132, 822; HRMS (ESI): M + Na+ found
260.0291, C12H11ClO3Na requires 261.0297.
Typical procedure for the reaction with zinc. To a reaction
vessel were added sequentially 1a (141 mg, 1.00 mmol), 3-bro-
momethyl-5H-furan-2-one (260 mg, 1.47 mmol), THF (1 ml),
saturated aqueous NH4Cl (0.5 ml) and activated zinc powder
(110 mg, 1.72 mmol). The mixture was stirred for 15 min at rt
and filtered by diatomite, extracted with diethyl ether
(20 ml × 3), washed with brine (20 ml) and dried over anhydrous
Na2SO4. Evaporation and column chromatography on silica gel
(petroleum ether–ethyl acetate = 1 : 1) afforded 2a (216 mg,
90%).
(4) Synthesis of 4-((4-methoxyphenyl)(hydroxy)methyl)-3-
methylenedihydrofuran-2(3H)-one (2d)
The reaction of 1d (140 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), indium powder (225 mg,
1.97 mmol) and water (1.0 ml) at rt for 12 h afforded 2d
1
(215 mg, 89%): oil, H NMR (400 MHz, CDCl3) δ 7.26 (d, J =
8.2 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 6.36 (d, J = 2.2 Hz, 1H),
5.85 (d, J = 1.6 Hz, 1H), 4.65 (d, J = 7.9 Hz, 1H), 4.16 (dd, J =
8.4, 9.5 Hz, 1H), 4.02 (dd, J = 4.5, 9.6 Hz, 1H), 3.81 (s, 3H),
3.36–3.42 (m, 1H), 2.40 (br s, 1H).
The following Barbier-type products were prepared according
to this procedure.
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Discernable data for minor diastereoisomer: 7.84 (d, J = 8.8
Hz, 2H), 7.02 (d, J = 8.7 Hz, 2H), 6.17 (d, J = 2.4 Hz, 1H), 4.97
(d, J = 2.0 Hz, 1H), 4.40 (dd, J = 9.4, 7.9 Hz, 1H), 4.31 (t, J =
6.7 Hz, 1H), 3.89 (s, 3H).
(106 mg, 1.66 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2f (234 mg, 88%).
13C NMR (100 MHz, CDCl3) δ 170.8, 159.8, 135.2, 132.8,
(7) Synthesis of 4-((4-cyanophenyl)(hydroxy)methyl)-3-
methylenedihydrofuran-2(3H)-one (2g)18
127.8, 125.4, 114.2, 75.3, 67.5, 55.3, 45.5; IR (neat), ν (cm−1
)
3454, 1759, 1658, 1465, 1250, 1120, 819; HRMS (ESI):
M + Na+ found 257.0787, C13H14O4Na required 257.0792.
The reaction of 1d (134 mg, 0.98 mmol), 3-bromomethyl-5H-
furan-2-one (258 mg, 1.47 mmol), activated zinc powder
(106 mg, 1.66 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2d (215 mg, 93%).
The reaction of 1g (134 mg, 1.02 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), indium powder (225 mg,
1.97 mmol) and water (1.0 ml) at rt for 12 h afforded 2g
(204 mg, 87%): white solid, mp: 151–155 °C. 1H NMR
(400 MHz, CDCl3) δ 7.71 (d, J = 8.0 Hz, 2H), 7.51 (d, J = 8.1
Hz, 2H), 6.37 (s, 1H), 5.61 (s, 1H), 4.88 (d, J = 6.6 Hz, 1H),
4.29 (t, J = 9.4 Hz, 1H), 4.19 (dd, J = 3.6, 9.6 Hz, 1H), 3.4 (s,
1H), 2.48 (br s, 1H).
13C NMR (100 MHz, CDCl3) δ 170.0, 145.5, 134.0, 132.5,
127.6, 127.2, 125.7, 118.2, 112.4, 74.8, 67.2, 45.3.
(5) Synthesis of 4-((4-trifluoromethylphenyl)(hydroxy)methyl)-
3-methylenedihydrofuran-2(3H)-one (2e)
The reaction of 1g (129 mg, 0.98 mmol), 3-bromomethyl-5H-
furan-2-one (267 mg, 1.52 mmol), activated zinc powder
(113 mg, 1.77 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2g (221 mg, 98%).
The reaction of 1e (170 mg, 0.98 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), indium powder (228 mg,
2 mmol) and water (1.0 ml) at rt for 12 h afforded 2e (242 mg,
1
91%): solid, mp: 76–90 °C. H NMR (400 MHz, CDCl3) δ 7.67
(d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.1 Hz, 2H), 6.36 (d, J = 2.1
Hz, 1H), 5.67 (d, J = 1.7 Hz, 1H), 4.85 (d, J = 7.0 Hz, 1H), 4.26
(t, J = 9.6 Hz, 1H), 4.16 (dd, J = 9.6, 3.9 Hz, 1H), 3.39–3.43
(m, 1H), 2.59 (br s, 1H).
(8) Synthesis of 4-(hydroxy(naphthalen-3-yl)methyl)-3-
methylenedihydrofuran-2(3H)-one (2h)
The reaction of 1h (160 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (263 mg, 1.49 mmol), indium powder (228 mg,
2 mmol) and water (1.0 ml) at rt for 12 h afforded 2h (232 mg,
Discernable data for minor diastereoisomer: 8.12 (d, J = 7.9
Hz, 2H), 7.77 (d, J = 8.1 Hz, 2H), 6.27 (d, J = 2.4 Hz, 1H), 5.96
(s, 1H), 5.15 (d, J = 2.0 Hz, 1H).
1
13C NMR (100 MHz, CDCl3) δ 170.1, 144.5, 134.4, 127.0,
89%): oil, H NMR (400 MHz, CDCl3) δ 7.83–7.88 (m, 3H),
125.8, 125.77, 125.73, 75.0, 67.5, 45.5; IR (neat), ν (cm−1
)
7.77 (s, 1H), 7.52–7.54 (m, 2H), 7.46 (d, J = 8.4 Hz, 1H), 6.36
(s, 1H), 5.77 (s, 1H), 4.84 (d, J = 7.5 Hz, 1H), 4.17 (t, J = 9.1
Hz, 1H), 4.10 (dd, J = 9.3, 4.1 Hz, 1H), 3.49 (s, 1H), 2.67
(br s, 1H).
Discernable data for minor diastereoisomer: 7.22 (d, J = 8.9
Hz, 1H), 6.16 (d, J = 2.4 Hz, 1H), 4.99 (d, J = 2.1 Hz, 1H), 4.65
(dd, J = 9.7, 4.1 Hz, 1H), 4.41 (dd, J = 9.4, 7.8 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 170.8, 138.0, 134.9, 133.3,
133.0, 128.9, 128.0, 127.7, 126.5, 125.5, 123.9, 75.7, 67.7,
45.3; IR (neat), ν (cm−1) 3443, 1759, 1658, 1273, 1123; HRMS
(ESI): M + Na+ found 277.0828, C16H14O3Na required
277.0841.
3466, 1735, 1662, 1276, 1124, 828; HRMS (ESI): M + Na+
found 295.0546, C13H11O3F3Na required 295.1560.
The reaction of 1e (176 mg, 1.01 mmol), 3-bromomethyl-5H-
furan-2-one (265 mg, 1.51 mmol), activated zinc powder
(111 mg, 1.73 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2e (251 mg, 91%).
(6) Synthesis of 4-((4-tert-butylphenyl)(hydroxy)methyl)-3-
methylenedihydrofuran-2(3H)-one (2f)
The reaction of 1h (153 mg, 0.98 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), activated zinc powder
(113 mg, 1.77 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2h (212 mg, 85%).
The reaction of 1f (161 mg, 0.99 mmol), 3-bromomethyl-5H-
furan-2-one (267 mg, 1.52 mmol), indium powder (231 mg,
2.03 mmol) and water (1.0 ml) at rt for 12 h afforded 2f
1
(233 mg, 90%): oil, H NMR (400 MHz, CDCl3) δ 7.43 (d, J =
8.3 Hz, 2H), 7.29 (d, J = 8.8 Hz, 2H), 6.39 (d, J = 2.0 Hz, 1H),
5.89 (d, J = 1.4 Hz, 1H), 4.68 (d, J = 8.1 Hz, 1H), 4.18 (t, J =
9.5 Hz, 1H), 4.04 (dd, J = 9.6, 4.5 Hz, 1H), 3.41–3.46 (m, 1H),
2.17 (br s, 1H), 1.33 (s, 3H).
(9) Synthesis of 4-(hydroxy(furan-3-yl)methyl)-3-methyl-
enedihydrofuran-2(3H)-one (2i)
Discernable data for minor diastereoisomer: 7.73–7.71
(m, 2H), 7.55 (dd, J = 6.1, 2.9 Hz, 2H), 6.22 (d, J = 2.4 Hz,
1H), 5.84 (d, J = 1.8 Hz, 1H), 5.04 (d, J = 2.0 Hz, 1H), 4.42
(dd, J = 9.4, 8.1 Hz, 1H), 4.33 (t, J = 6.8 Hz, 1H).
The reaction of 1i (101 mg, 1.05 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), indium powder (225 mg,
1.97 mmol) and water (1.0 ml) at rt for 12 h afforded 2i
1
(149 mg, 73%): oil, H NMR (400 MHz, CDCl3) δ 7.41 (d, J =
13C NMR (100 MHz, CDCl3) δ 170.7, 151.9, 137.7, 135.3,
126.4, 125.8, 125.4, 75.5, 67.6, 45.4, 34.7, 31.3; IR (neat),
ν (cm−1) 3305, 1764, 1656, 1286, 1124, 837; HRMS (ESI):
M + Na+ found 283.1309, C16H20O3Na required 283.1310.
The reaction of 1f (176 mg, 1.09 mmol), 3-bromomethyl-5H-
furan-2-one (265 mg, 1.51 mmol), activated zinc powder
1.0 Hz, 1H), 6.36 (d, J = 3.7 Hz, 2H), 6.33 (d, J = 3.3 Hz, 1H),
5.76 (d, J = 2.0 Hz, 1H), 4.77 (d, J = 7.4 Hz, 1H), 4.32 (t, J =
9.5 Hz, 1H), 4.18 (dd, J = 9.6, 4.3 Hz, 1H), 3.56–3.63 (m, 1H),
2.65 (br s, 1H).
Discernable data for minor diastereoisomer: 7.43 (d, J = 1.0
Hz, 1H), 6.26 (d, J = 2.5 Hz, 1H), 5.21 (d, J = 2.2 Hz, 1H), 4.75
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(12) Synthesis of 4-(1-hydroxybutyl)-3-methylenedihydrofuran-
2(3H)-one (4b)
(d, J = 7.6 Hz, 1H), 4.56 (dd, J = 9.6, 4.3 Hz, 1H), 4.47 (t, J =
8.1 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 170.6, 153.2, 142.8, 134.2,
125.7, 110.5, 108.2, 69.2, 67.4, 43.3; IR (neat), ν (cm−1) 3418,
1755, 1660, 1274, 1123; HRMS (ESI): M + Na+ found
217.0470, C10H10O4Na required 2170.477.
The reaction of 3b (80 mg, 1.11 mmol), 3-bromomethyl-5H-
furan-2-one (258 mg, 1.47 mmol), indium powder (230 mg,
2.02 mmol) and water (1.0 ml) at rt for 12 h afforded 4b
1
(176 mg, 93%): oil, H NMR (400 MHz, CDCl3) δ 6.37 (d, J =
The reaction of 1i (98 mg, 1.02 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), activated zinc powder
(110 mg, 1.72 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2i (187 mg, 94%).
2.1 Hz, 1H), 5.81 (d, J = 1.8 Hz, 1H), 4.41 (t, J = 9.2 Hz, 1H),
4.27 (dd, J = 9.4, 3.7 Hz, 1H), 3.67–3.71 (m, 1H), 3.12–3.15
(m, 1H), 2.07 (br s, 1H), 1.33–1.59 (m, 4H), 0.96 (t, J = 7.2 Hz,
3H).
Discernable data for minor diastereoisomer: 5.71 (d, J = 2.0
Hz, 1H), 4.76 (t, J = 9.1 Hz, 1H), 3.85 (dd, J = 10.3, 5.5 Hz,
1H).
(10) Synthesis of 4-(hydroxy(thiophene-3-yl)methyl)-3-methyl-
enedihydrofuran-2(3H)-one (2j)
13C NMR (100 MHz, CDCl3) δ 170.9, 135.1, 124.6, 72.9,
68.1, 44.6, 35.6, 18.9, 13.9; IR (neat), ν (cm−1) 3453, 1761,
1660, 1274, 1123; HRMS (ESI): M + Na+ found 193.0830,
C9H14O3Na required 193.0841.
The reaction of 1j (115 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), indium powder (230 mg,
2.02 mmol) and water (1.0 ml) at rt for 12 h afforded 2j
(184 mg, 85%): oil, 1H NMR (400 MHz, CDCl3) δ 7.32 (dd, J =
4.9, 1.1 Hz, 1H), 6.98–7.02 (m, 2H), 6.39 (d, J = 2.3 Hz, 1H),
5.90 (d, J = 1.8 Hz, 1H), 4.98 (d, J = 7.7 Hz, 1H), 4.28 (t, J =
9.7 Hz, 1H), 4.13 (dd, J = 9.7, 4.4 Hz, 1H), 3.44–3.50 (m, 1H),
2.75 (br s, 1H).
The reaction of 3b (75 mg, 1.04 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), activated zinc powder
(109 mg, 1.70 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4b (170 mg, 96%).
(13) Synthesis of (E)-4-(1-hydroxyhex-2-en-1-yl)-3-methyl-
enedihydrofuran-2(3H)-one (4c)
Discernable data for minor diastereoisomer: 7.25 (d, J = 5.1
Hz, 1H), 6.91 (dd, J = 4.9, 3.6 Hz, 1H), 6.81 (d, J = 2.7 Hz,
1H), 6.26 (d, J = 2.5 Hz, 1H), 5.20 (d, J = 2.1 Hz, 1H), 4.56
(dd, J = 9.8, 4.2 Hz, 1H), 4.45 (t, J = 8.1 Hz, 1H).
The reaction of 3c (97 mg, 0.99 mmol), 3-bromomethyl-5H-
furan-2-one (265 mg, 1.51 mmol), indium powder (230 mg,
2.02 mmol) and water (1.0 ml) at rt for 12 h afforded 4c
13C NMR (100 MHz, CDCl3) δ 170.5, 144.3, 134.6, 127.0,
125.9, 125.3, 71.6, 67.4, 45.9; IR (neat), ν (cm−1) 3443, 1759,
1659, 1276, 1125; HRMS (ESI): M + Na+ found 233.0240,
C10H10O3SNa required 233.0248.
1
(162 mg, 83%): oil, H NMR (400 MHz, CDCl3) δ 6.35 (d, J =
2.2 Hz, 1H), 5.85 (d, J = 1.8 Hz, 1H), 5.72–5.79 (m, 1H), 5.46
(dd, J = 15.4,7.3 Hz, 1H), 4.35 (t, J = 9.4 Hz, 1H), 4.24 (dd, J =
8.5, 4.1 Hz, 1H), 4.17 (t, J = 7.0 Hz, 1H), 3.19–3.23 (m, 1H),
1.98–2.06 (m, 2H), 1.96 (br s, 1H), 1.35–1.43 (m, 2H), 0.91
(t, J = 7.3 Hz, 3H).
The reaction of 1j (113 mg, 1.01 mmol), 3-bromomethyl-5H-
furan-2-one (260 mg, 1.47 mmol), activated zinc powder
(107 mg, 1.67 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 2j (197 mg, 93%).
Discernable data for minor diastereoisomer: 6.38 (d, J = 2.2
Hz, 1H), 5.74 (s, 1H).
13C NMR (100 MHz, CDCl3) δ 170.7, 135.9, 135.2, 128.2,
124.6, 74.6, 67.3, 44.1, 34.3, 22.2, 13.6; IR (neat), ν (cm−1
)
(11) Synthesis of 4-(1-hydroxyhexyl)-3-methylenedihydrofuran-
3454, 1760, 1662, 1274, 1124; HRMS (ESI): M + Na+ found
219.0990, C11H16O3Na 219.0997.
2(3H)-one (4a)18
The reaction of 3c (101 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (267 mg, 1.52 mmol), activated zinc powder
(105 mg, 1.64 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4c (192 mg, 95%).
The reaction of 3a (103 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), indium powder (227 mg,
1.99 mmol) and water (1.0 ml) at rt for 12 h afforded 4a
1
(192 mg, 94%): oil, H NMR (400 MHz, CDCl3) δ 6.38 (d, J =
2.0 Hz, 1H), 5.82 (d, J = 1.6 Hz, 1H), 4.43 (t, J = 9.3 Hz, 1H),
4.27 (dd, J = 9.4, 3.7 Hz, 1H), 3.71 (dd, J = 11.6, 5.9 Hz, 1H),
3.13–3.16 (m, 1H), 1.90 (br s, 1H), 1.44–1.50 (m, 3H),1.31 (s,
5H), 0.92 (t, J = 6.5 Hz, 3H).
(14) Synthesis of 4-(3-methylthio-1-hydroxypropyl)-3-methyl-
enedihydrofuran-2(3H)-one (4d)
Discernable data for minor diastereoisomer: 5.72 (d, J = 0.8
Hz, 1H), 3.81–3.87 (m, 1H).
The reaction of 3d (104 mg, 1 mmol), 3-bromomethyl-5H-furan-
2-one (263 mg, 1.49 mmol), indium powder (227 mg,
1.99 mmol) and water (1.0 ml) at rt for 12 h afforded 4d
13C NMR (100 MHz, CDCl3) δ 170.9, 135.2, 124.6, 73.2,
68.1, 44.5, 33.5, 31.6, 25.4, 22.6, 14.0; IR (neat), ν (cm−1
)
(162 mg, 80%): oil, H NMR (400 MHz, CDCl3) δ 6.38 (d, J =
1
3445, 1765, 1661, 1270, 1129; HRMS (ESI): M + Na+ found
221.1146, C10H18O3Na required 221.1154.
2.1 Hz, 1H), 5.82 (d, J = 1.7 Hz, 1H), 4.43 (t, J = 9.4`Hz, 1H),
4.30 (dd, J = 9.4, 3.6 Hz, 1H), 3.86–3.92 (m, 1H), 3.16–3.20
(m, 1H), 2.70 (t, J = 6.7 Hz, 2H), 2.51 (br s, 1H), 2.11 (s, 3H),
1.69–1.82 (m, 2H).
Discernable data for minor diastereoisomer: 5.75 (d, J = 2.1
Hz, 1H), 3.96–4.01 (m, 1H), 2.33 (br s, 1H).
The reaction of 3a (100 mg, 1 mmol), 3-bromomethyl-5H-
furan-2-one (263 mg, 1.49 mmol), activated zinc powder
(106 mg, 1.66 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4a (193 mg, 97%).
3996 | Org. Biomol. Chem., 2012, 10, 3991–3998
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13C NMR (100 MHz, CDCl3) δ 170.7, 135.0, 124.8, 72.4,
67.8, 44.6, 31.6, 30.9, 15.4; IR (neat), ν (cm−1) 3453, 1762,
1660, 1414, 1279, 1122; HRMS (ESI): M + Na+ found
225.0562, C9H14O3SNa required 225.0561.
The reaction of 3d (107 mg, 1.03 mmol), 3-bromomethyl-5H-
furan-2-one (262 mg, 1.49 mmol), activated zinc powder
(107 mg, 1.67 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4d (198 mg, 95%).
2.04 mmol) and water (1.0 ml) at rt for 12 h afforded 4g
(162 mg, 80%): oil, H NMR (400 MHz, CDCl3) δ 7.33 (t, J =
1
7.3 Hz, 2H), 7.24 (dd, J = 7.2, 11.8 Hz, 3H), 6.37 (d, J = 1.6
Hz, 1H), 5.79 (d, J = 1.0 Hz, 1H), 4.40 (t, J = 8.9 Hz, 1H), 4.24
(dd, J = 3.4, 9.4 Hz, 1H), 3.71 (t, J = 9.2 Hz, 1H), 3.13 (s, 1H),
2.93 (m, 1H), 2.75 (m, 1H), 2.05 (br s, 1H), 1.84 (m, 2H).
Discernable data for minor diastereoisomer: 5.70 (d, J = 1.7
Hz, 1H), 4.40 (t, J = 8.9 Hz, 1H), 4.24 (dd, J = 3.4, 9.4 Hz, 1H),
3.71 (t, J = 9.2 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 170.7, 141.1, 135.0, 128.6,
128.4, 126.3, 124.8, 72.4, 68.0, 44.7, 35.2, 32.0.
The reaction of 3g (130 mg, 0.97 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), activated zinc powder
(113 mg, 1.77 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4g (189 mg, 84%).
(15) Synthesis of 4-(1-hydroxypent-4-en-1-yl)-3-methylenedi-
hydrofuran-2(3H)-one (4e)
The reaction of 3e (90 mg, 1.07 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 2 mmol), indium powder (226 mg,
1.98 mmol) and water (1.0 ml) at rt for 12 h afforded 4e
(177 mg, 91%): oil, 1H NMR (400 MHz, CDCl3) δ; 6.37 (d, J =
1.5 Hz, 1H), 5.76–5.86 (m, 2H), 5.09 (d, J = 17.1 Hz, 1H), 5.02
(d, J = 10.1 Hz, 1H), 4.41 (t, J = 9.2 Hz, 1H), 4.27 (dd, J = 9.4,
3.6 Hz, 1H), 3.69–3.74 (m, 1H), 3.14 (s, 1H), 2.25–2.31 (m,
2H), 2.12–2.21 (m, 1H), 1.54–1.60 (m, 2H).
(18) Synthesis of 4-(hydroxy-(5-isopropenyl-2-methyl-1-en-
cyclopentyl)methyl)-3-methylenedihydrofuran-2(3H)-one (4g)
The reaction of 3g (153 mg, 1.02 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), indium powder (228 mg,
2 mmol) and water (1.0 ml) at rt for 12 h afford 4g (220 mg,
87%): oil.
Discernable data for minor diastereoisomer: 5.72 (d, J = 1.9
Hz, 1H), 3.83–3.88 (m, 1H).
13C NMR (100 MHz, CDCl3) δ 171.4, 138.2, 135.6, 125.3,
116.3, 73.2, 68.6, 45.1, 33.1, 30.6; IR (neat), ν (cm−1) 3444,
1760, 1660, 1271, 1123,; HRMS (ESI): M + Na+ found
182.0940, C10H14O3Na required 182.0943.
4gI (81 mg, 32%): [α]D20 = −150.7 (c = 0.01, EtOH); 1H NMR
(400 MHz, CDCl3) δ 6.34 (s, 1H), 5.93 (s,1H), 4.78 (s, 1H),
4.72 (s, 1H), 4.30 (d, J = 9.4 Hz, 1H), 4.22 (t, J = 8.8 Hz, 1H),
3.97 (dd, J = 9.4, 3.4 Hz, 1H), 3.53 (d, J = 8.6 Hz, 1H), 3.32 (s,
1H), 2.44–2.52 (m, 1H), 2.22–2.28 (t, J = 9.6 Hz, 1H),
2.00–2.10 (m, 1H), 1.93 (s, 1H), 1.81 (s, 3H), 1.66–1.72 (m,
1H), 1.64 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 170.8, 148.5,
141.0, 135.8, 134.7, 125.2, 111.5, 70.3, 67.8, 53.7, 43.4, 38.3,
29.0, 19.1, 14.7; IR (neat) ν (cm−1) 3481, 1766, 1659, 1275,
1119; HRMS (ESI) M + Na+ found 271.1313, C15H20O3Na
required 271.1305.
The reaction of 3e (86 mg, 1.02 mmol), 3-bromomethyl-5H-
furan-2-one (267 mg, 1.52 mmol), activated zinc powder
(108 mg, 1.69 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4e (166 mg, 89%).
(16) Synthesis of 4-(hydroxy(cyclohex-2-yl)methyl)-3-methylenedi-
hydrofuran-2(3H)-one (4f)
4gII (139 mg, 55%): [α]2D0 = +2.8 (c = 0.01, EtOH); 1H NMR
(400 MHz, CDCl3) δ 6.33 (dd, J = 2.4, 0.8 Hz, 1H), 6.04 (dd, J
= 2.2, 0.9 Hz, 1H), 4.85 (s, 1H), 4.78 (t, J = 1.5 Hz, 1H), 4.48
(dd, J = 9.2, 5.9 Hz, 1H), 4.26 (dd, J = 9.4, 8.5 Hz, 1H), 3.86
(dd, J = 9.5, 5.0 Hz, 1H), 3.27–3.33 (m, 1H), 2.41–2.50
(m, 1H), 2.23–2.29 (m, 2H), 1.95–2.06 (m, 1H), 1.76 (s, 3H),
1.64–1.71 (m, 1H); 13C NMR (100 MHz, CDCl3) δ 170.8,
151.3, 141.4, 135.9, 133.7, 125.0, 110.7, 71.0, 67.3, 53.1, 43.6,
37.5, 28.9, 19.7, 14.3; IR (neat) ν (cm−1) 3481, 1766, 1658,
1276, 1121; HRMS (ESI)
C15H20O3Na required 271.1305.
The reaction of 3g (150 mg, 1.0 mmol), 3-bromomethyl-5H-
furan-2-one (264 mg, 1.5 mmol), activated zinc powder
(107 mg, 1.67 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4g (221 mg, 89%).
The reaction of 3f (114 mg, 1.02 mmol), 3-bromomethyl-5H-
furan-2-one (258 mg, 1.47 mmol), indium powder (231 mg,
2.03 mmol) and water (1.0 ml) at rt for 12 h afforded 4f
1
(205 mg, 96%): oil, H NMR (400 MHz, CDCl3) δ 6.39 (d, J =
2.1 Hz, 1H), 5.84 (d, J = 1.6 Hz, 1H), 4.44 (t, J = 8.8 Hz, 1H),
4.22 (dd, J = 9.1, 4.2 Hz, 1H), 3.42 (t, J = 6.1 Hz, 1H),
3.24–3.30 (m, 1H), 1.70–1.83 (m, 6H), 1.42–1.44 (m, 1H),
1.09–1.26 (m, 5H).
Discernable data for minor diastereoisomer: 6.66 (d, J = 2.1
Hz, 1H), 5.57 (d, J = 1.2 Hz, 1H), 4.54 (t, J = 8.9 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ 170.7, 134.8, 124.4, 76.4,
M +
Na+ found 271.1311,
68.3, 40.7, 40.0, 29.7, 26.8, 25.9, 25.8, 25.5; IR (neat), ν (cm−1
)
3490, 1741, 1659, 1265, 1134; HRMS (ESI): M + Na+ found
233.1146, C12H18O3Na required 233.1154.
The reaction of 3f (116 mg, 1.04 mmol), 3-bromomethyl-5H-
furan-2-one (261 mg, 1.48 mmol), activated zinc powder
(113 mg, 1.77 mmol), THF (1 ml), and saturated aqueous
NH4Cl (0.5 ml) at rt for 15 min afforded 4f (194 mg, 79%).
Acknowledgements
Financial support from the National Natural Science Foundation
of China (20872070) is greatly appreciated.
(17) Synthesis of 4-(3-phenyl-1-hydroxypropyl)-3-methylenedi-
hydrofuran-2(3H)-one (4g)18
Notes and references
The reaction of 3g (142 mg, 1.06 mmol), 3-bromomethyl-5H-
furan-2-one (270 mg, 1.53 mmol), indium powder (235 mg,
1 M. Seitz and O. Reiser, Curr. Opin. Chem. Biol., 2005, 9, 285–292.
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 3991–3998 | 3997

View Article Online
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3998 | Org. Biomol. Chem., 2012, 10, 3991–3998
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