Stereoselective synthesis of (Z)-α-phenoxymethylene-γ-butyrolactone and its sulfur analogues from 2-propynyloxy- or 2-propynylthiobenzene

Article abstract of DOI:10.3987/COM-00-8964

The preparations of (Z)-α-phenoxymethylene-γ-butyrolactone, α-phenoxymethyl-γ-butyrolactone, (Z)-α-phenylthiomethylene-γ-butyrolactone, and α-phenylthiomethyl-γ-butyrolactone derivatives from 2-propynyloxy-benzene and 2-propynylthiobenzene were described.

Full text of DOI:10.3987/COM-00-8964

HETEROCYCLES, Vol. 53, No. 9, 2000, pp. 2055 - 2066, Received, 31st May, 2000
STEREOSELECTIVE SYNTHESIS OF (Z)-α-PHENOXYMETHYLENE-
γ-BUTYROLACTONE AND ITS SULFUR ANALOGUES FROM 2-
PROPYNYLOXY- OR 2-PROPYNYLTHIOBENZENE
*
Fen-Tair Luo, ,a Sheng-Li Ko,b Lijun Liu,a and Hui Chenb
a Institute of Chemistry, Academia Sinica, Nankang, Taipei, Taiwan 115, R.O.C.
b
Department of Chemical Engineering, National Central University, Chung Li,
Taoyuan, Taiwan 320, R.O.C.
Abstract – The preparations of (Z)-α-phenoxymethylene-γ-butyrolactone, α-
phenoxymethyl-γ-butyrolactone, (Z)-α-phenylthiomethylene-γ-butyrolactone,
and α-phenylthiomethyl-γ-butyrolactone derivatives from 2-propynyloxy-
benzene and 2-propynylthiobenzene were described.
Recently, we have developed an efficient method for the preparation of (Z)-α-alkylidene-γ-
butyrolactone from 2-alkyn-1-one via a deconjugated hydroiodination process.1 The stereo- selective
synthesis of (Z)-α-alkylidene-γ-butyrolactone has become attractive since these compounds can be used
as a plant growth regulator,2 or as an important intermediate to the synthesis of obtusilactone isolated
from Lindela obtusiloba, a cytotoxic natural product.3 Although several methods have been reported for
the introduction of an alkylidene group at the α-position of a γ-butyrolactone with (E)- or
(Z)-configuration,4 there is no general procedure being reported in the literature for the stereoselective
synthesis of the α-exocyclic double bond of γ-butyrolactone with phenoxy or phenylthio group on the
exocyclic double bond.5 In addition, the sulfonate functionalized on the α-exocyclic double bond of
γ-butyrolactone has been reported to enhance a Michael-type nucleophilic addition-elimination more
rapidly than simple enones so that it may become a possible irreversible alkylation agents for cellular
nucleophiles and may be employed as a cancer chemoterapeutic agents.6 In view of the leaving group
property of either phenoxy or phenylthio group substituted on the β-position of the α-exocyclic double
bond of γ-butyrolactone and their potential application as the alkylating agents for DNA cleavage, we
now report the synthesis of (Z)-α-phenoxymethylene-γ-butyrolactone and (Z)-α-phenylthio-
methylene-γ-butyrolactone derivatives from 2-propynyloxybenzene and 2-propynylthiobenzene,
respectively, as shown in Scheme 1.
The preparation of (Z)-5-methyl-3-phenoxymethylene-4,5-dihydrofuran-2-one (8a) from 2-propynyl-
oxybenzene (1a) was representative as follows. Thus, 1a, obtained in 94% yield from phenol and

Scheme 1. Preparation of α-Phenoxymethylene or Phenoxymethyl-
Substituted γ-Butyrolactones and Their Sulfur Analagues.
1. EtMgBr
2. RCHO
K2CO3
X
Y
X
Y
+
acetone
50oC
Br
1a: X = H, Y = O
1b: X =F, Y = O
1c: X =H, Y =S
X = H, F
Y = OH, SH
CrO3
NaI, TMSCl
H2O, MeCN
X
Y
R
O
H2SO4
X
Y
R
acetone
H2O
OH
2a: X = H, Y = O, R = Me
2b: X = F, Y = O, R = Me
2c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
2d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
2e: X = H, Y = S, R = Me
3a: X = H, Y = O, R = Me
3b: X = F, Y = O, R = Me
3c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
3d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
3e: X = H, Y = S, R = Me
X
Y
I
+
X
Y
I
O
R
O
R
(Z/E = 5/1)
4a: X = H, Y = O, R = Me
4b: X = F, Y = O, R = Me
4c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
4d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
4e: X = H, Y = S, R = Me
5a: X = H, Y = O, R = Me
5b: X = F, Y = O, R = Me
5c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
5d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
5e: X = H, Y = S, R = Me
NaBH
NaBH
4
MeOH
4
MeOH
X
Y
I
X
Y
I
OH
R
OH
R
7a: X = H, Y = O, R = Me
7b: X = F, Y = O, R = Me
6a: X = H, Y = O, R = Me
6b: X = F, Y = O, R = Me
6c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
6d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
6e: X = H, Y = S, R = Me
7c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
7d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
7e: X = H, Y = S, R = Me
Pd(PPh ) cat.
Pd(PPh ) cat.
3 4
3 4
Et N, CO, toluene
Et N, CO, toluene
3
3
O
O
X
Y
X
Y
O
O
R
R
8a: X = H, Y = O, R = Me
8b: X = F, Y = O, R = Me
8c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
8d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
8e: X = H, Y = S, R = Me
9a: X = H, Y = O, R = Me
9b: X = F, Y = O, R = Me
9c: X = H, Y = O, R = 3,4,5-trimethoxyphenyl
9d: X = F, Y = O, R = 3,4,5-trimethoxyphenyl
9e: X = H, Y = S, R = Me

propargyl bromide in the presence of potassium carbonate in acetone at 50°C, was treated with
ethylmagnesium bromide under nitrogen at 0°C and followed by the addition of acetaldehyde at 0°C to
give 5-phenoxypent-3-yn-2-ol (2a) in 90% yield. Jones oxidation of 2a could give the corresponding
conjugated ynone (3a) in 92% yield. Treatment of the conjugated ynone (3a) with sodium iodide,
trimethylsilyl chloride, and water in acetonitrile1,7 at room temperature gave deconjugated
(4Z)-4-iodo-5-phenoxypent-4-en-2-one (4a), conjugated (3Z)-4-iodo-5-phenoxypent-3-en-2-one (5a),
and conjugated (3E)-4-iodo-5-phenoxypent-3-en-2-one in 65, 15, and 3% yields, respectively. Their
1
stereochemistry were determined by 2D NOESY H NMR spectral analyses. It is noteworthy that
treatment of 5a with catalytic amount of trimethylsilyl chloride could transform 5a into deconjugated
iodo enone (4a) in 96% yield as we have reported in the literature.8 Reduction of 4a with sodium
borohydride in methanol at room temperature gave (Z)-3-iodo-3-en-1-ol (6a) in 93% yield with no loss
1
of stereochemistry as judged by H NMR spectral analyses. In the presence of tetrakis(triphenyl-
phosphine)palladium catalyst, triethylamine, and carbon monoxide in toluene, the cyclization of 6a
afforded (Z)-5-methyl-3-phenoxymethylene-4,5-dihydrofuran-2-one (8a) in 18 h and in 84% yield. In
order to test the feasibility and difference of the Michael-type nucleophilic addition-elimination of
γ-butyrolactones with either exocyclic or endocyclic conjugated double bond, we also synthesize
5-methyl-3-phenoxymethyl-5-hydrofuran-2-one (9a) from the conjugated iodo enone (5a) intermediate
with (Z)-configuration. Thus, treatment of 5a with sodium borohydride in methanol at room temperature
1
gave (Z)-3-iodo-2-en-1-ol (7a) in 94% yield without loss of stereochemistry as judged by H NMR
spectral analyses. The cyclization of 7a in the presence of tetrakis(triphenylphosphine)palladiumcatalyst,
triethylamine, and carbon monoxide in toluene could afford 9a in 87% yield. The fluoro- and/or
3,4,5-trimethoxyphenyl substituted, and sulfur-containing analogues of the above mentioned compounds
are prepared similarly to the above described procedures. Thus, (Z)-5-methyl-3-phenylthiomethylene-
4,5-dihydrofuran-2-one (8e) and 5-methyl-3-phenylthio-methyl-5-hydrofuran-2-one (9e) are prepared
from 2-propynylthiobenzene (1c) in a total yields of 30 and 15%, respectively, in five steps. Similarly,
8b-8d and 9b-9d can be prepared in reasonable yields from 1a and 1b. We have attempted to prepare
6-(4-hydroxyphenyl)-hex-3-yn-2-one and 4-(5-oxohex-3-ynyl)phenyl acetate, i.e. 3a with hydroxy or
acetyloxy group at the p-position, via various kinds of oxidation conditions to the corresponding
propargyl alcohols, but only isolated 1,4-benzoquinone as the major product under these oxidation
conditions.
EXPERIMENTAL
Precoated silica gel 60F-254 on aluminum plates made by EM chemical company was used for
thin-layer chromatography. Purification by column chromatography was carried out with EM silica gel
60 (70-230 mesh ASTM). HPLC separation was performed at a flow rate of 0.7 mL/min by the use of

two Chemco-Pak 10 x 250 column packed with Chemcosorb 5-ODS-H. GLC analysis were performed
by a 3.2 x 3.1 column packed with SE-30 (5% on Chemcosorb W). The purity of each compounds was
1
13
judged to be > 95% by GLC, H-NMR or C-NMR spectral analyses. Reactions of organometallic
compounds were undertaken in oven- and/or flame-dried glassware. Tetrakis(triphenylphosphine)-
palladium catalyst was prepared by published method.9 All other materials were used without further
purification. IR spectra were recorded on a Perkin-Elmer Paragon 1000 or 882 infrared
1
13
spectrophotometer. H and C NMR spectra were recorded on a Bruker AC200, AC300, or AMX400
spectrometer, chemical shifts were reported in ppm down field from TMS. MS spectra were obtained on
HP 5971, Fisons MD800 GC/MS or VG 70-250S spectrometers. HRMS was recorded on VG 70-250S
or VG Autospec double focusing high-resolution mass spectrometer. Elemental analyses were performed
on Perkin Elmer EA-2400.
Preparation of 1-fluoro-4-prop-2-ynyloxybenzene (1b) as the representative procedure for the
synthesis of phenyl propargyl ethers or sulfide: To a solution of 4-fluorophenol (1.12 g, 10 mmol) in
15 mL of dry acetone were added anhydrous potassium carbonate (1.38 g, 10 mmol) and propargyl
bromide (1.19 g, 10 mmol). The resultant mixture was stirred at 50°C for 18 h, then the mixture was
cooled and the solvent was removed under reduced pressure. The residue was treated with 15 mL of
water and extracted with ethyl acetate. The combined organic phases were washed with water, brine and
dried over anhydrous magnesium sulfate and evaporated in vacuum. The residue was purified by column
1
chromatography (silica gel, hexane/ethyl acetate = 15/1) to give a colorless oil 1b (1.31 g, 87%): H
NMR (CDCl3, TMS) δ 2.51 (t, J = 2.4 Hz, 1 H), 4.63 (d, J = 2.4 Hz, 2 H), 6.85-7.05 (m, 4 H) ppm ; 13C
NMR (CDCl3, TMS) δ 56.36, 75.57, 78.40, 115.79 (d, J = 48 Hz), 116.02, 154.43 (d, J = 131 Hz),
160.06 ppm; IR (CHCl3) ν 3287, 2124, 1504, 1206, 1027, 827 cm-1; MS m/z 150 (M+), 149, 148, 122,
121, 111, 83. HRMS calcd for C9H7OF 150.0481, found 150.0489.
Prop-2-ynyloxybenzene (1a)10: colorless oil; 94% yield; 1H NMR (CDCl3, TMS) δ 2.49 (t, J = 2.4 Hz, 1
H), 4.66 (d, J = 2.4 Hz, 2 H), 6.9-7.0 (m, 3 H), 7.25-7.35 (m, 2 H) ppm; MS m/z 132 (M+), 131, 130,
103.
Prop-2-ynylthiobenzene (1c)11: colorless oil; 83% yield; 1H NMR (CDCl3, TMS) δ 2.21 (t, J = 2.4 Hz,
1 H), 3.59 (d, J = 2.4 Hz, 2 H), 7.15-7.35 (m, 3 H), 7.4-7.5 (m, 2 H) ppm; MS m/z 148 (M+), 147, 115,
109.
Preparation of 5-phenoxypent-3-yn-2-ol (2a) as the representative procedure for the synthesis of
propargy alcohols: To a stirred solution of phenyl propargyl ether (1a) (1.32 g, 10 mmol) in THF (4 mL)
was added ethylmagnesium bromide (1.1 equiv, 11 mmol) under nitrogen at 0°C. The mixture was
stirred at 0°C for 3 h, then allowed to react with acetaldehyde at 0°C for 4 h and quenched by the
addition of saturated solution of NH4Cl (5 mL). The aqueous layer was extracted with ethyl acetate. The
combined organic layer was dried over magnesium sulfate and was concentrated under reduced pressure.

The resultant crude product was purified by flash chromatography (silica gel, ethyl acetate/hexane = 1/8)
1
to give 2a12 (1.59 g, 90%) as a colorless oil: H NMR (CDCl3, TMS) δ 1.33 (d, J = 4.5 Hz, 3 H), 2.32
(br s, 1 H), 4.43 (q, J = 4.5 Hz, 1 H), 4.60 (s, 2 H), 6.85-6.9 (m, 3 H), 7.2-7.25 (m, 2 H) ppm; 13C NMR
(CDCl3, TMS) δ 23.99, 56.01, 58.24, 78.85, 89.20, 114.88, 121.45, 129.42, 157.62 ppm; IR (CDCl3) ν
3403, 2357, 1594, 1241 cm-1; MS m/z 176 (M+), 158, 131, 103, 94.
5-(4-Fluorophenoxy)pent-3-yn-2-ol (2b): colorless oil; 84% yield; 1H NMR (CDCl3, TMS) δ 1.42 (d, J
13
= 6.5 Hz, 3 H), 2.32 (br s, 1 H), 4.55 (q, J = 6.5 Hz, 1 H), 4.66 (s, 2 H), 6.8-7.05 (m, 4 H) ppm; C
NMR (CDCl3, TMS) δ 23.96, 56.44, 58.14, 78.59, 89.38, 115.88 (d, J = 49 Hz) 116.03 , 154.46 (d, J =
122 Hz), 160.03 ppm; IR (CHCl3) ν 3373, 1505, 1452, 1203, 1019 cm-1; MS m/z 194 (M+), 176, 149,
122, 121, 112. Anal. Calcd for C11H11O2F: C, 68.03; H, 5.71. Found: C, 68.22; H, 5.92.
1
4-Phenoxy-1-(3,4,5-trimethoxyphenyl)but-2-yn-1-ol (2c): colorless oil; 90% yield; H NMR (CDCl3,
TMS) δ 2.90 (br s, 1 H), 3.66 (s, 6 H), 3.80 (s, 3H), 5.26 (s, 1 H), 4.75 (s, 2 H), 5.41 (s, 1 H), 6.68 (s, 2
H), 6.9-7.0 (m, 3 H), 7.2-7.3 (m, 2 H) ppm; 13C NMR (CDCl3, TMS) δ 55.77, 55.88, 60.67, 64.41, 81.47,
86.93, 103.59, 114.70, 121.40, 129.38, 135.70, 137.73, 153.11, 157.42 ppm; IR (CHCl3) ν 3438, 1597,
1495, 1221, 1123, 1010, 755 cm-1; FAB MS: 328 (M+). Anal. Calcd for C19H20O5: C, 69.50; H, 6.14.
Found: C, 69.68; H, 6.21.
1
4-(4-Fluorophenoxy)-1-(3,4,5-trimethoxyphenyl)but-2-yn-1-ol (2d): colorless oil; 85% yield; H
NMR (CDCl3, TMS) δ 2.62 (br s, 1 H), 3.77 (s, 6 H), 3.84 (s, 3 H), 4.73 (s, 2 H) , 5.42 (s, 1 H), 6.69 (s,
2 H), 6.9-7.0 (m, 4 H) ppm; 13C NMR (CDCl3, TMS) δ 55.97, 55.60, 60.73, 64.52, 81.32, 87.11, 103.65,
115.87 (d, J = 33 Hz) , 115.98, 135.66, 137.93, 153.23, 154.81 (d, J =185 Hz), 159.23 ppm; IR (CHCl3)
ν 3454, 1594, 1506, 1463, 1232, 1200, 1007, 829 cm-1; FAB MS: 346 (M+); HRFABMS calcd for
C19H20O5F 347.1295 (MH+), found 347.1285.
1
5-Phenylthiopent-3-yn-2-ol (2e)13: colorless oil; 83% yield; H NMR (CDCl3 TMS) δ 1.36 (d, J = 6.7
13
Hz, 3 H), 2.14 (br s, 1 H), 3.62 (s, 2 H), 4.47 (q, J = 6.7 Hz, 1 H), 7.2-7.45 (m, 5 H) ppm; C NMR
(CDCl3, TMS) δ 22.85, 24.14, 58.20, 79.72, 85.53, 126.87, 128.83, 130.25, 134.97 ppm; IR (CHCl3 ) ν
3390, 1480, 1438, 1155, 1077, 1002, 891 cm-1; MS m/z 192 (M+), 174, 147, 110, 109.
Preparation of 5-phenoxypent-3-yn-2-one (3a) as the representative procedure for the synthesis of
conjugated ynones: To a solution of 2a (0.53 g, 3 mmol) in acetone (3 mL) was added dropwise Jones
reagent (1.2 equiv), while keeping the temperature between 0-5°C, the mixture was stirred at rt for 2 h. It
was diluted with 5 mL of water and extracted with ethyl acetate. The organic layer was washed by water,
brine, and dried over magnesium sulfate. The solvent was removed under reduced pressure. The residue
was purified by chromatography (silica gel, ethyl acetate/hexane = 1/8) to give 3a14 (0.48 g, 92%) as a
colorless oil: 1H NMR (CDCl3, TMS) δ 2.31 (s, 3 H), 4.81 (s, 2 H), 6.9-7.0 (m, 3H), 7.25-7.35 (m, 2 H)
13
ppm; C NMR (CDCl3, TMS) δ 22.54, 32.39, 55.50, 85.80, 85.88, 114.80, 121.90, 129.14, 129.51,
157.20, 183.60 ppm; IR (CHCl3) ν 2218, 1681, 1598, 1495, 1360, 1212, 1047, 755 cm-1; MS m/z 174

(M+), 159, 131, 103.
5-(4-Fluorophenoxy)pent-3-yn-2-one (3b): colorless oil; 85% yield ; 1H NMR (CDCl3, TMS) δ 2.32 (s,
3 H), 4.79 (s, 2 H), 6.85-7.05 (m, 4 H) ppm; 13C NMR (CDCl3, TMS) δ 32.29, 56.26, 85.45, 85.95,
115.97 (d, J = 47 Hz), 116.12, 154.38 (d , J = 164 Hz), 160.24, 183.46 ppm; IR (CHCl3) ν 2217, 1686,
1504, 1360, 1221, 1045, 830 cm-1; MS m/z 192 (M+), 177, 149, 121, 111, 83. Anal. Calcd for C11H9O2F:
C, 68.74; H, 4.72. Found: C, 68.91; H, 4.85.
4-Phenoxy-1-(3,4,5-trimethoxyphenyl)but-2-yn-1-one (3c): mp 79-80°C (EtOAc/EtOH); 94% yield;
1H NMR (CDCl3, TMS) δ 3.69 (s, 6 H) , 3.89 (s, 3 H), 4.98 (s, 2 H), 7.01 (d, J = 5.2 Hz, 3 H), 7.28 (s, 2
H), 7.3-7.35 (m, 2 H) ppm; 13 C NMR (CDCl3, TMS) δ 55.23, 55.87, 60.81, 84.66, 88.46, 106.71, 114.57,
121.79, 129.57, 131.27, 143.63, 152.92, 157.02, 175.79 ppm; IR (CHCl3) ν 2230, 1650, 1588, 1457,
1331, 1209, 1127, 1041 cm-1; FAB MS: 327 (M+ + 1). HRMS calcd for C19H18O5 326.1154; found
326.1162.
4-(4-Fluorophenoxy)-1-(3,4,5-trimethoxyphenyl)but-2-yn-1-one (3d): mp 125-126°C (EtOAc/EtOH);
92% yield; 1H NMR (CDCl3, TMS) δ 3.76 (s, 6 H), 3.91 (s, 3 H), 4.96 (s, 2 H), 6.95-7.05 (m, 4 H), 7.28
(s, 2 H) ppm; 13C NMR (CDCl3, TMS) δ 55.87, 56.00, 60.80, 84.67, 87.94, 106.74, 115.78 , 115.99 (d, J
= 16 Hz), 131.15, 143.74, 152.90, 154.60 (d , J = 229 Hz), 159.34, 175.69 ppm; IR (CHCl3) ν 2233,
1645, 1591, 1506, 1469, 1417, 1334, 1221, 1129, 994, 825 cm-1; MS m/z 344 (M+), 205, 172;
HRFABMS calcd for C19H18O5F 345.1138 (MH+); found 345.1041.
1
5-Phenylthiopent-3-yn-2-one (3e): colorless oil; 82% yield; H NMR (CDCl3, TMS) δ 2.25 (s, 3 H),
3.70 (s, 2 H), 7.25-7.4 (m, 3 H), 7.45-7.5 (m, 2 H) ppm; 13C NMR (CDCl3, TMS) δ 23.00, 32.51, 82.74,
87.86, 127.60, 129.03, 131.06, 133.78, 183.97 ppm; IR (CHCl3) ν 2210, 1674, 1358, 1223, 740 cm-1;
MS m/z 190 (M+), 176, 155, 136. HRMS calcd for C11H10OS 190.0452; found 190.0461.
Preparation of (4Z)-4-iodo-5-phenoxypent-4-en-2-one (4a) as the representative procedure for the
synthesis of deconjugated iodo enones: To a solution of anhydrous sodium iodide (0.68 g, 4.5 mmol)
in MeCN (3 mL) in a dry flask under nitrogen atmosphere was added TMSCl (0.46 mL, 3.6 mmol) and
the mixture was stirred at rt for 20 min followed by the addition of 0.5 equiv of water (27 µL, 1.5 mmol).
After stirring for another 10 min at rt, 1 equiv of 3a (0.52 g, 3 mmol) was added quickly into the flask.
After stirring for another 4 h, the reaction mixture was quenched with saturated solution of sodium
thiosulfate and extracted with ethyl acetate (10 mL x 3). The organic layer was dried over magnesium
sulfate followed by filtration and concentration. The crude product was purified by column
1
chromatography (silica gel, ethyl acetate/hexane = 1/10) to give 4a (0.59 g, 65%) as a colorless oil: H
13
NMR (CDCl3, TMS) δ 2.21 (s, 3 H), 3.65 (s, 2 H), 6.73 (s, 1 H), 7.0-7.4 (m, 5 H) ppm; C NMR
(CDCl3, TMS) δ 29.29, 51.78, 73.37, 116.75, 123.68, 129.61, 146.39, 156.04, 204.70 ppm; IR (CHCl3) ν
1716, 1590, 1490, 1226, 1162, 1126, 755 cm-1; MS m/z 302 (M+), 259, 132, 131, 105, 104, 103. HRMS
calcd for C11H11O2I 301.9804; found 301.9822.

1
(3Z)-4-Iodo-5-phenoxypent-3-en-2-one (5a): colorless oil; 15% yield; H NMR (CDCl3, TMS) δ 2.26
(s, 3 H), 4.75 9 (s, 2 H), 6.88 (d, J = 7.4, 2 H), 7.01 (t, J = 7.4 Hz, 1 H), 7.14 (t, J = 1.5 Hz, 1 H), 7.30 (t,
J = 7.4 Hz, 2 H) ppm; 13C NMR (CDCl3, TMS) δ 31.58, 76.85, 109.26, 114.80, 121.87, 129.52, 129.65,
–1
157.21, 195.76 ppm; IR (CHCl3) ν 1755, 1684, 1594, 1491, 1235, 1209, 1177, 754 cm ; MS m/z 302
(M+), 259, 175, 132, 131, 94. Anal. Calcd for C11H11O2I: C, 43.73; H, 3.67. Found: C, 43.85; H, 3.78.
1
(4Z)-5-(4-Fluorophenoxy)-4-iodopent-4-en-2-one (4b): colorless oil; 61% yield; H NMR (CDCl3,
13
TMS) δ 2.24 (s, 3 H), 3.67 (s, 2 H), 6.67 (s, 1 H), 7.0-7.05 (m, 4 H) ppm; C NMR (CDCl3, TMS) δ
29.51, 51.88, 73.37, 116.28 (d, J = 23 Hz), 118.32, 146.81, 152.36, 159.03 (d, J = 241 Hz), 204.48 ppm;
IR (CHCl3) ν 1716, 1652, 1498, 1241, 1203, 831 cm-1; MS m/z 320 (M+) 277, 150, 122, 83. HRMS
calcd for C11H10O2FI 319.9710; found 319.9722.
1
(3Z)-5-(4-Fluorophenoxy)-4-iodopent-3-en-2-one (5b): colorless oil; 18% yield; H NMR (CDCl3,
13
TMS) δ 2.42 (s, 3 H), 4.86 (s, 2 H), 6.95-7.2 (m, 4 H), 7.27 (s, 1 H) ppm; C NMR (CDCl3, TMS) δ
31.57, 77.58, 108.93, 115.90 (d, J = 6 Hz), 116.22 (d, J = 16 Hz), 129.71, 154.40 (d, J = 152 Hz), 160.18,
195.80 ppm; IR (CHCl3) ν 1697, 1504, 1434, 1196, 1023 cm-1; MS m/z 320 (M+), 277, 193, 150, 112.
Anal. Calcd for C11H10O2FI: C, 41.27; H, 3.15. Found: C, 41.40; H, 3.33.
(3Z)-3-Iodo-4-phenoxy-1-(3,4,5-trimethoxyphenyl)but-3-en-1-one (4c): pale yellow oil; 62% yield;
1H NMR (CDCl3, TMS) δ 3.92 (s, 6 H), 3.93 (s, 3 H), 4.20 (s, 2 H), 6.74 (s, 1 H), 7.03 (d, J = 7 Hz, 2 H),
13
7.10 (t, J = 7 Hz, 1 H), 7.33 (t , J = 7 Hz, 2 H) ppm. C NMR (CDCl3, TMS) δ 46.90, 56.36, 60.95,
73.76, 105.66, 106.07, 115.26, 116.94, 123.74, 129.73, 131.44, 146.55, 153.11, 156.33, 194.72 ppm; IR
(CHCl3) ν 1678, 1581, 1491, 1337, 1228, 1126, 754 cm-1; MS m/z 454 (M+), 328, 235, 196. HRMS
calcd for C19H19O5I 454.0277; found 454.0285.
1
(2Z)-3-Iodo-4-phenoxy-1-(3,4,5-trimethoxyphenyl)but-2-en-1-one (5c): colorless oil; 17% yield; H
NMR (CDCl3, TMS) δ 3.77 (s, 6 H), 3.92 (s, 3 H), 4.86 (s, 2 H), 6.95-7.4 (m, 5 H), 7.59 (s, 2 H) ppm;
13C NMR (CDCl3, TMS) δ 56.04, 60.80, 76.24, 105.64, 109.86, 114.65, 121.74, 128.63, 129.70, 131.63,
142.92, 152.99, 157.10, 188.72 ppm; IR (CHCl3) ν 1658, 1581, 1491, 1453, 1408, 1331, 1228, 1163,
1127, 1001, 757 cm-1; MS m/z 454 (M+), 328, 290, 235, 196, 155. HRMS calcd for C19H19O5I 454.0277;
found 454.0282.
(3Z)-4-(4-Fluorophenoxy)-3-iodo-1-(3,4,5-trimethoxyphenyl)but-3-en-1-one (4d): colorless oil; 64%
yield; 1H NMR (CDCl3, TMS) δ 3.93 (s, 9 H), 4.20 (s, 2 H), 6.68 (s, 1 H), 7.01 (d, J = 6.2 Hz, 4 H), 7.26
13
(s, 2 H) ppm; C NMR (CDCl3, TMS) δ 44.28, 56.39, 61.31, 62.53, 112.89, 115.47 (d, J = 26 Hz),
118.68 (d, J = 8 Hz), 135.19, 142.64, 143.25, 153.19, 155.67, 157.41 (d, J = 280 Hz), 192.74 ppm; IR
(CDCl3) ν 1670, 1581, 1500, 1337, 1201, 1120, 833 cm-1; MS m/z 472 (M+), 344, 234, 219, 206, 195,
191; HRMS calcd for C19H18O5FI 472.0183, found 472.0179.
(2Z)-4-(4-Fluorophenoxy)-3-iodo-1-(3,4,5-trimethoxyphenyl)but-2-en-1-one (5d): colorless oil; 13%
yield; 1H NMR (CDCl3, TMS) δ 3.81 (s, 6 H), 3.90 (s, 3 H), 4.85 (s, 2 H), 6.9-7.0 (m, 4 H), 7.08 (s, 2 H),

7.58 (s, 1 H) ppm; 13C NMR (CDCl3, TMS) δ 56.43, 61.25, 76.38, 112.34, 114.64 (d, J = 28 Hz), 117.25
(d, J = 8 Hz), 135.69, 139.68, 144.39, 153.97, 154.63, 157.29 (d, J = 272 Hz), 186.37 ppm; IR (CHCl3)
ν 1664, 1575, 1504, 1331, 1203, 1126, 830 cm-1; HRFABMS calcd for C19H19O5FI 473.0261 (MH+),
found: 473.0240.
1
(4Z)-4-Iodo-5-phenylthiopent-4-en-2-one (4e): colorless oil; 53% yield; H NMR (CDCl3, TMS) δ
13
2.20 (s, 3 H), 3.74 (s, 2 H), 6.84(s, 1 H), 7.25-7.45 (m, 5 H) ppm; C NMR (CDCl3, TMS) δ 29.47,
58.24, 90.11, 127.79, 129.18, 130.85, 133.57, 137.67, 203.95 ppm; IR (CHCl3) ν 1716, 1579, 1475,
1354, 1156, 740 cm-1; FAB MS m/z 318 (M+). Anal. Calcd for C11H11OIS: C, 41.52; H, 3.48. Found: C,
41.65; H, 3.59.
1
(3Z)-4-Iodo-5-phenylthiopent-3-en-2-one (5e): colorless oil; 25% yield; H NMR (CDCl3, TMS) δ
2.13 (s, 3 H), 3.94 (s, 2 H), 6.54 (s, 1 H), 7.2-7.4 (m, 5 H) ppm; 13C NMR (CDCl3, TMS) δ 30.71, 47.69,
110.00, 127.59, 129.65, 131.59, 133.71, 140.11, 195.81 ppm; IR (CHCl3) ν 1703, 1575, 1478, 1177 cm-1;
FAB MS m/z 318 (M+). HRMS calcd for C11H11OIS 317.9575, found 317.9583.
Preparation of (4Z)-4-iodo-5-phenoxypent-4-en-2-ol (6a) as the representative procedure for the
reduction of deconjugated and conjugated iodo enones: To a cooled (0-5°C) solution of 4a (0.30 g, 1
mmol) in 2 mL of methanol was added in one portion of sodium borohydride (0.05 g, 1.2 mmol), the
mixture was then stirred at room temperature and monitored by TLC. After the disappearance of the
iodo enone, the reaction mixture was added to 2 mL of water and was extracted with ethyl acetate. The
combining organic extracts were washed with brine and dried over magnesium sulfate. After filtration
and evaporation of the solvent, the crude product was purified by chromatography (silica gel, ethyl
acetate/ hexane = 1/6) to give 6a (0.28 g, 93%) as a colorless oil: 1H NMR (CDCl3, TMS) δ 1.25 (d, J =
6.3 Hz, 3 H), 2.2-2.4 (m, 2 H), 2.5-2.6 (m, 1 H), 4.05-4.15 (m, 1 H), 6.68 (s, 1 H), 6.95-7.35 (m, 5 H)
13
ppm; C NMR (CDCl3, TMS) δ 22.74, 54.86, 66.89, 68.55, 112.15, 124.50, 129.40, 143.60, 157.20; IR
(CHCl3) ν 1658, 1588, 1485, 1229, 1119, 1074, 748 cm-1; MS m/z 304 (M+), 303, 260, 259, 131, 104.
Anal. Calcd for C11H13O2I: C, 43.44; H, 4.31. Found: C, 43.56; H, 4.43.
(3Z)-4-Iodo-5-phenoxypent-3-en-2-ol (7a): colorless oil; 94% yield; 1H NMR (CDCl3, TMS) δ 1.25 (d,
J = 6.3 Hz, 3 H), 2.56 (s, 1 H), 4.45-4.55 (m, 1 H), 4.62 (s, 2 H), 6.09 (d, J = 7.8 Hz, 1 H), 6.8-7.0 (m, 3
H), 7.26 (t, J = 7 Hz, 2 H) ppm; 13C NMR (CDCl3, TMS) δ 21.73, 71.91, 75.28, 100.11, 115.04, 121.48,
129.43, 140.64, 157.58 ppm; IR (CHCl3) ν 3390, 1594, 1491, 1229, 1061, 748 cm-1; MS m/z 304 (M+),
260, 159, 133, 94. HRMS calcd for C11H13O2I 303.9960; found 303.9973.
(4Z)-5-(4-Fluorophenoxy)-4-iodopent-4-en-2-ol (6b): colorless oil; 83% yield; 1H NMR (CDCl3, TMS)
δ 1.27 (d, J = 7.2 Hz, 3 H), 1.97 (br s, 1 H), 2.53 (d, J = 6.2 Hz, 2 H), 4.0-4.2 (m, 1 H), 6.64 (s, 1 H),
13
6.98 (s, 2 H), 7.01 (d, J = 2.2 Hz, 2 H) ppm; C NMR (CDCl3, TMS) δ 22.13, 47.29, 66.10, 81.35,
116.22 (d, J = 57 Hz), 118.37 (d, J = 28 Hz), 145.00, 154.48 (d, J = 305 Hz), 161.34 ppm; IR ν 3377,
1645, 1498, 1203, 1126, 831 cm-1; MS m/z 322 (M+), 278, 112, 83. Anal. Calcd for C11H12O2FI: C,

41.02; H, 3.75. Found: C, 41.22; H, 3.91
(3Z)-5-(4-Fluorophenoxy)-4-iodopent-3-en-2-ol (7b): colorless oil; 87% yield; 1H NMR (CDCl3, TMS)
δ 1.29 (d, J = 6.6 Hz, 3 H), 1.86 (s, 1 H), 4.5-4.6 (m, 1 H), 4.62 (s, 2 H), 6.09 (d, J = 7.5 Hz, 1 H),
13
6.8-7.0 (m, 4 H) ppm; C NMR (CDCl3, TMS) δ 21.86, 72.05, 76.19, 100.21, 116.08 (d, J = 49 Hz),
116.22, 140.26, 153.82, 157.71 (d, J = 238 Hz) ppm; IR (CHCl3) ν 3364, 1505, 1202, 1019, 828 cm-1;
MS m/z 323 (M+ + 1), 290, 231, 179, 155, 136, 112. HRMS calcd for C11H12O2FI 321.9866; found
321.9876.
1
(3Z)-3-Iodo-4-phenoxy-1-(3,4,5-trimethoxyphenyl)but-3-en-1-ol (6c): colorless oil; 92% yield; H
NMR (CDCl3, TMS) δ 2.2 (br s, 1 H), 2.7-2.9 (m, 2 H), 3.81 (s, 3 H), 3.83 (s, 6 H), 4.9-4.95 (m, 1 H),
6.58 (s, 1 H), 6.62 (s, 2 H), 6.90 (d , J = 7.8 Hz, 2 H), 7.10 (t, J = 7 Hz, 1 H), 7.73 (t, J = 7 Hz, 2 H) ppm;
13C NMR (CDCl3, TMS) δ 47.77, 56.04, 60.73, 72.47, 80.75, 102.78, 116.61, 123.52, 129.47, 137.31,
138.59, 145.15, 153.17, 156.20 ppm; IR (CHCl3) ν 3456, 1593, 1491, 1231, 1125, 1005, 757 cm-1; MS
m/z 456 (M+), 439, 307, 197, 154, 136; HRMS calcd for C19H21O5I 456.0434, found 456.0445.
1
(2Z)-3-Iodo-4-phenoxy-1-(3,4,5-trimethoxyphenyl)but-2-en-1-ol (7c): colorless oil; 89% yield; H
NMR (CDCl3, TMS) δ 2.62 (br s, 1 H), 3.81 (s, 6 H), 3.83 (s, 3 H), 4.68 (s, 2 H), 5.42 (d, J = 8 Hz, 1 H),
13
6.28 (d, J = 8 Hz, 1 H), 6.64 (s, 2 H), 6.7-7.3 (m, 5 H) ppm; C NMR (CDCl3, TMS) δ 56.02, 60.70,
75.32, 77.43, 99.57, 102.22, 102.94, 114.92, 121.54, 129.45, 137.26, 138.07, 153.28, 157.57 ppm; IR
(CHCl3) ν 3454, 1588, 1491, 1460, 1414, 1324, 1228, 1126, 1004, 754 cm-1; MS m/z 457 (M+ + 1), 440,
308, 219, 198, 154; HRMS calcd for C19H21O5I 456.0434, found 456.0445.
(3Z)-4-(4-Fluorophenoxy)-3-iodo-1-(3,4,5-trimethoxyphenyl)but-3-en-1-ol (6d): colorless oil; 94%
yield; 1H NMR (CDCl3, TMS) δ 1.82 (br s, 1 H), 2.7-2.9 (m, 2H), 3.81 (s, 3 H), 3.84 (s, 6 H), 4.92 (t, J
13
= 5.5 Hz, 1 H), 6.51 (s, 1 H), 6.63 (s, 2 H), 6.85-7.0 (m, 4 H) ppm; C NMR (CDCl3, TMS) δ 47.83,
56.20, 60.85, 72.62, 80.89, 102.96, 115.99 (d, J = 47 Hz), 116.46, 118.12 (d, J = 12 Hz), 138.62, 145.54,
152.45, 153.39 (d, J = 361 Hz), 161.37 ppm; IR (CHCl3) ν 3461, 1592, 1202, 1126, 1007, 831 cm-1; MS
m/z 474 (M+). HRMS calcd for C19H20O5FI 474.0340; found 474.0352.
(2Z)-4-(4-Fluorophenoxy)-3-iodo-1-(3,4,5-trimethoxyphenyl)but-2-en-1-ol (7d): colorless oil; 78%
yield; 1H NMR (CDCl3, TMS) δ 2.32 (br s, 1 H), 3.83 (s, 9 H), 4.65 (s, 2 H), 5.43 (d, J = 7.9 Hz, 1 H),
6.26 (d, J = 7.9 Hz, 1 H), 6.65 (s, 2H), 6.8-6.95 (m, 4 H) ppm; 13C NMR (CDCl3, TMS) δ 56.09, 60.78,
76.16, 77.53, 102.33, 102.95, 115.90 (d, J = 23 Hz), 116.35 (d, J = 8 Hz), 137.22, 137.64, 138.34,
153.40, 153.71, 157.69 (d, J = 238 Hz) ppm; IR (CHCl3) ν 3461, 1589, 1498, 1460, 1421, 1325, 1229,
1203, 1126, 998, 831 cm-1. HRMS calcd for C19H20O5FI 474.0340; found 474.0348.
(4Z)-4-Iodo-5-phenylthiopent-4-en-2-ol (6e): colorless oil; 90% yield; 1H NMR (CDCl3, TMS) δ 1.24
(d, J = 6.2 Hz, 3 H), 1.75 (s, 1 H), 2.63 (d, J = 6.2 Hz, 2 H), 4.0-4.15 (m, 1 H), 6.80 (s, 1 H), 7.25-7.45
13
(m, 5 H) ppm; C NMR (CDCl3, TMS) δ 22.01, 54.03, 66.46, 99.02, 127.60, 129.28, 130.62, 133.89,
135.08 ppm; IR (CHCl3) ν 3356, 1578, 1474, 1241, 1063, 728 cm-1; MS m/z 320 (M+), 302, 276, 220,

148, 147, 109. HRMS calcd for C11H13OIS 319.9732; found 319.9741.
(3Z)-4-Iodo-5-phenylthiopent-3-en-2-ol (7e): colorless oil; 92% yield; 1H NMR (CDCl3, TMS) δ 1.01
(d, J = 6.4 Hz, 3 H), 1.69 (br s, 1 H), 3.83 (br s, 2 H), 4.3-4.4 (m, 1 H), 5.53 (d, J = 7.4 Hz, 1 H),
7.25-7.4 (m, 5 H) ppm; 13C NMR (CDCl3, TMS) δ 21.58, 49.75, 72.50, 102.44, 127.51, 128.88, 132.21,
134.00, 141.09 ppm; IR (CHCl3) ν 3364, 1581, 1472, 1434, 1401, 1248, 1062, 889, 741 cm-1; MS m/z
320 (M+), 276, 218, 149, 110. HRMS calcd for C11H13OIS 319.9732; found 319.9739.
Preparation of (Z)-5-methyl-3-phenoxymethylene-4,5-dihydrofuran-2-one (8a) as the
representative procedure for the palladium-catalyzed CO insertion and lactonization of iodo enols:
To a flask were charged under nitrogen with 6a (0.31 g, 1 mmol), triethylamine (0.14 mL, 1 mmol),
tetrakis(triphenylphosphine)palladium (0.12 g, 0.1 mmol), and 3 mL of toluene. A balloon was flushed
three times with carbon monoxide and connected via a needle to a condenser attached to the above
reaction flask. The system was flushed with a gentle steam of carbon monoxide for 1 min and then
placed in an oil bath at 50°C for 3-18 h. Upon completion of the reaction, the reaction mixture was
quenched with 10% ammonium hydroxide aqueous solution. Extraction (ethyl acetate), washing (brine),
drying (magnesium sulfate), concentration, and chromatography (silica gel, ethyl acetate/hexane = 1/8)
gave 8a (0.17 g, 84%) as a colorless oil: 1H NMR (CDCl3, TMS) δ 1.43 (d, J = 6.2 Hz, 3 H), 2.56 (ddd,
J = 15.1, 8.6, 2.1 Hz, 1 H), 3.06 (ddd, J = 15.1, 7.5, 1.7 Hz, 1 H), 4.6-4.7 (m, 1 H), 6.91 (s, 1 H), 7.11 (d,
13
J = 8.9 Hz, 2 H), 7.16 (t, J = 7.5 Hz, 1 H), 7.37 (t, J = 7.9 Hz, 2 H) ppm; C NMR (CDCl3, TMS) δ
21.72, 33.02, 74.02, 106.29, 117.53, 124.63, 129.76, 148.69, 157.08, 167.87 ppm; MS m/z 204 (M+),
160, 132, 131, 104, 103. Anal. Calcd for C12H12O3: C, 70.57; H, 5.92. Found: C, 70.77; H, 5.99.
1
5-Methyl-3-phenoxymethyl-5-hydrofuran-2-one (9a): colorless oil, 87% yield; H NMR (CDCl3,
TMS) δ 1.43 (d, J = 6.9 Hz, 3 H), 4.77 (t, J = 1.9 Hz , 2 H), 5.05-5.15 (m, 1 H), 6.86 (d, J = 8.1 Hz, 2 H),
6.97 (t, J = 7.2 Hz, 1 H), 7.30 (t, J = 8.1 Hz, 2 H), 7.39 (s, 1 H) ppm; 13C NMR (CDCl3, TMS) δ 18.83,
61.86, 78.46, 114.50, 121.48, 129.59, 129.94, 151.49, 157.82, 171.69 ppm; IR (CHCl3) ν 1755, 1683,
1599, 1496, 1234, 1201, 1083, 1022, 755 cm-1; MS m/z 204 (M+), 159, 111, 110, 94. HRMS calcd for
C12H12O3 204.0786; found 204.0798.
(Z)-3-[(4-Fluorophenoxy)methylene]-5-methyl-4,5-dihydrofuran-2-one (8b): colorless oil; 86% yield;
1H NMR (CDCl3, TMS) δ 1.44 (d, J = 6.2 Hz , 3 H) , 2.55 (ddd, J = 15.2 , 6.5, 2.1 Hz, 1 H), 3.06 (ddd, J
13
= 15.2, 7.5, 1.7 Hz , 1 H) , 4.6-4.75 (m , 1 H) , 6.82 (t, J = 1.7 Hz, 1 H) , 7.0-7.15 (m, 4 H) ppm; C
NMR (CDCl3, TMS) δ 21.79, 33.05, 74.08, 106.59, 116.40 (d, J = 24 Hz), 119.15 (d, J = 8 Hz), 148.83,
153.29, 159.57 (d, J = 242 Hz), 167.79 ppm; IR (CHCl3) ν 1751, 1674, 1501, 1202, 1080, 835 cm-1; MS
m/z 222 (M+), 150, 124, 112, 83. Anal. Calcd for C12H11O3F: C, 64.86; H, 4.99. Found: C, 64.98; H,
5.10.
1
3-[(4-Fluorophenoxy)methyl]-5-methyl-5-hydrofuran-2-one (9b): colorless oil; 95% yield; H NMR
(CDCl3 , TMS) δ 1.47 (d, J = 6.9 Hz, 3 H), 4.76 (t, J = 1.8 Hz, 2 H), 5.1-5.15 (m, 1 H), 6.85-6.9 (m, 2 H),

13
6.95-7.0 (m, 2 H), 7.40 (s, 1 H) ppm; C NMR (CDCl3, TMS) δ 18.84, 62.57, 78.47, 115.67 (d, J = 8
Hz), 116.01 (d, J = 23 Hz), 130.23, 151.64, 154.01, 157.65 (d, J = 238 Hz), 171.63 ppm; IR (CHCl3) ν
1748, 1504, 1209, 1087, 1017, 825 cm-1; MS m/z 222 (M+), 176, 166, 154, 136. HRFABMS calcd for
C12H12O3F 223.0770 (MH+), found 223.0760.
(Z)-3-Phenoxymethylene-5-(3,4,5-trimethoxyphenyl)-4,5-dihydrofuran-2-one (8c): colorless oil;
63% yield; 1H NMR (CDCl3, TMS) δ 2.92 (ddd, J = 15.3, 7.4, 2.1 Hz, 1 H), 3.35 (ddd, J = 15.3, 7.8, 1.4
Hz, 1 H), 3.85 (s 3 H), 3.87 (s, 6 H), 5.48 (t, J = 7.5 Hz, 1 H), 6.57 (s, 2 H), 6.96 (t, J = 1.8 Hz, 1 H),
13
7.1-7.4 (m, 5 H) ppm; C NMR (CDCl3, TMS) δ 34.38, 56.23, 60.82, 78.11, 102.28, 105.44, 117.60,
124.87, 129.87, 135.73, 137.96, 149.23, 153.57, 157.08, 167.58 ppm; IR (CHCl3) ν 1756, 1501, 1202,
1126 cm-1; MS m/z 356 (M+), 263, 189, 136; HRFABMS calcd for C20H21O6 357.1338 (MH+), found
357.1353.
1
3-Phenoxymethyl-5-(3,4,5-trimethoxyphenyl)-5-hydrofuran-2-one (9c): colorless oil; 78% yield; H
NMR (CDCl3, TMS) δ 3.81 (s, 6 H), 3.83 (s, 3 H), 4.62 (s, 2 H), 5.6-5.7 (m, 1 H), 6.60 (s, 2 H), 6.8-7.1
(m, 5 H), 7.68 (d, J = 6 Hz, 1 H); 13C NMR (CDCl3, TMS) δ 56.25, 61.63, 63.67, 79.96, 103,04, 115.36,
121.40, 130.04, 137.90, 143.43, 150.89, 155.78, 159.86, 168.90 ppm; IR (CHCl3) ν 1750, 1509, 1226,
831 cm-1; MS m/z 356 (M+), 341, 263, 136; HRFABMS calcd for C20H21O6 357.1338 (MH+), found
357.1351.
(Z)-3-[(4-Fluorophenoxy)methylene]-5-(3,4,5-trimethoxyphenyl)-4,5-dihydrofuran-2-one
(8d):
colorless oil; 68% yield; 1H NMR (CDCl3, TMS) δ 2.92 (ddd, J = 15.3, 7.2, 2.2 Hz, 1 H), 3.35 (ddd, J =
15.3, 7.9, 1.7 Hz, 1 H), 3.85 (s, 3 H), 3.88 (s, 6 H), 5.49 (t, J = 7.5 Hz, 1 H), 6.57 (s, 2 H), 6.88 (t, J =
13
1.9 Hz, 1 H), 7.0-7.15 (m, 4 H) ppm; C NMR (CDCl3, TMS) δ 34.36, 56.29, 60.85, 78.14, 102.36,
104.24, 105.73, 116.48 (d, J = 35 Hz), 119.16 (d, J = 13 Hz), 135.63, 149.29, 153.23, 153.64, 159.69 (d,
J = 363 Hz), 168.08 ppm; IR (CHCl3) ν 1755, 1673, 1593, 1502, 1463, 1202, 1127, 1025, 835 cm-1;
FAB MS m/z 374 (M+), 280, 279, 263. HRMS calcd for C20H19O6F 374.1166; found 374.1175.
3-[(4-Fluorophenoxy)methyl]-5-(3,4,5-trimethoxyphenyl)-5-hydrofuran-2-one (9d): colorless oil;
72% yield; 1H NMR (CDCl3, TMS) δ 3.81 (s, 6 H), 3.83 (s, 3 H), 4.68 (s, 2 H), 5.65-5.75 (m, 1 H), 6.60
(s, 2 H), 6.8-7.2 (m, 4 H), 7.58 (d, J = 6 Hz, 1 H); 13C NMR (CDCl3, TMS) δ 56.80, 61.34, 63.50, 80.34,
102.43, 117.68 (d, J = 39 Hz), 119.03 (d, J = 8 Hz), 129,67, 137.87, 143.43, 150.34, 153.78, 156.65,
157.89 (d, J = 270 Hz), 169.69 ppm; IR (CHCl3) ν 1745, 1666, 1590, 1509, 1468, 1225, 831 cm-1; MS
m/z 374 (M+), 359, 280; HRMS calcd for C20H19O6F 374.1166; found 374.1178.
(Z)-5-Methyl-3-phenylthiomethylene-4,5-dihydrofuran-2-one (8e): colorless oil; 93% yield; 1H NMR
(CDCl3, TMS) δ 1.42 (d, J = 6.3 Hz, 3 H), 2.58 (ddd, J = 16.2, 6.2, 2.2 Hz, 1 H), 3.11 (ddd, J = 16.2,
7.7, 1.8 Hz, 1 H), 4.65-4.75 (m , 1 H), 7.06 (t, J = 2.0 Hz, 1 H) , 7.35-7.5 (m, 5 H) ppm; 13 C NMR
(CDCl3, TMS) δ 22.01, 36.42, 74.65, 119,57, 128.22, 129.41, 131.04, 135.62, 140.68, 169.76 ppm; IR
(CHCl3) ν 1729, 1607, 1440, 1344, 1190, 1081, 1036, 831, 741 cm-1; MS m/z 220 (M+), 147, 109.

HRMS calcd for C12H12O2S 220.0558; found 220.0563.
1
5-Methyl-3-phenylthiomethyl-5-hydrofuran-2-one (9e): colorless oil; 95% yield; H NMR (CDCl3,
TMS) δ 1.33 (d, J = 6.8 Hz, 3 H), 3.73 (t, J = 1.5 Hz, 2 H), 4.9-5.0 (m, 1 H), 6.99 (dd, J = 2.7, 1.2 Hz, 1
13
H), 7.2-7.35 (m, 5 H) ppm; C NMR (CDCl3, TMS) δ 18.90, 28.36, 77.55, 126.99, 129.05, 130.23,
130.46, 134.61, 151.49, 172.27 ppm; IR (CHCl3) ν 1752, 1581, 1497, 1318, 1074, 1024, 743 cm-1; MS
m/z 220 (M+), 119, 85, 84. HRMS calcd for C12H12O2S 220.0558; found 220.0568.
ACKNOWLEDGMENTS
The authors thank the National Science Council and Academia Sinica of the Republic of China for their
financial support.
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