A convenient synthesis of the (E)-monoacetates of 2-alkylidenepropane-1,3- diols

Article abstract of DOI:10.1055/s-2008-1067211

Various kinds of 3-substituted (E)-2-(hydroxymethyl)prop-2-enyl acetates were conveniently obtained in excellent yields by the regiospecific acetylation of 2-alkylidenepropane-1,3-diols with 10 equivalents of vinyl acetate in the presence of 50% w/w porcine pancreatic lipase (PPL) type II; the starting materials or (Z)-monoacetate or diacetate byproducts were generally not present. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067211

PAPER
2695
A Convenient Synthesis of the (E)-Monoacetates of 2-Alkylidenepropane-
1,3-diols
A
Convenient
S
s
ynthesis
o
u
f
the
(
E
)-Mo
y
noacetates
o
o
f
2-Alkylide
s
nepropane
h
-1,3-diols i Miura, Kenjiro Okazaki, Kyoko Ogawa, Erika Otomo, Satoe Umetsu, Mauko Takahashi,
Yuya Kawashima, Yuki Jyo, Naka Koyata, Yasuoki Murakami, Nobuyuki Imai*
Faculty of Pharmacy, Chiba Institute of Science, 15-8 Shiomi-cho, Choshi, Chiba 288-0025, Japan
Fax +81(479)304610; E-mail: nimai@cis.ac.jp
Received 16 April 2008; revised 9 May 2008
The authors dedicate this article to Professor E. J. Corey at Harvard University on the occasion of his 80th birthday.
Table 1 Preparation of 2-Alkylidenepropane-1,3-diols 2 from
Diethyl 2-Alkylidenemalonates 1a
Abstract: Various kinds of 3-substituted (E)-2-(hydroxymeth-
yl)prop-2-enyl acetates were conveniently obtained in excellent
yields by the regiospecific acetylation of 2-alkylidenepropane-1,3-
diols with 10 equivalents of vinyl acetate in the presence of 50%
w/w porcine pancreatic lipase (PPL) type II; the starting materials
or (Z)-monoacetate or diacetate byproducts were generally not
present.
CO2Et
DIBAL-H (4.5 equiv)
toluene, –30 °C
R
OH
OH
R
CO2Et
1
2
Entry
1
R
Time (h) Product 2
Yield (%)
62
Key words: (E)-monoacetates, acetylation, diols, regioselectivity,
lipase
Ph
2
3
3
3
3
2
3
3
3
3
3
3
2
2a
2b
2c
2d
2e
2f
2
4-MeOC6H4
4-F3CC6H4
4-ClC6H4
4-Tol
48
3
34
The development of highly selective acetylation reactions
is an attractive research field because the acetyl group, as
one of the most popular protecting groups, plays an im-
portant role in organic synthesis.1 Enzymatic acetylation
using lipase and vinyl acetate is an excellent methodolo-
gy, and many papers have reported the enantioselective
acetylation of racemic alcohols in the presence of lipase.2
In the case of the unique highly regioselective acetylation
of 2-benzylidenepropane-1,3-diols using several kinds of
lipases reported by Takabe and co-workers,3 diacetates
and (Z)-monoacetates were obtained as byproducts in all
cases, and 1 equivalent of vinyl acetate had to be used to
avoid the production of the diacetates. We recently devel-
oped and reported in a preliminary communication the
preparation of 3-substituted (E)-2-(hydroxymethyl)prop-
2-enyl acetates by the regiospecific acetylation of 2-alky-
lidenepropane-1,3-diols with vinyl acetate using 50%
w/w porcine pancreatic lipase (PPL) type II,4 and the
preparation of 3-substituted (Z)-2-(hydroxymethyl)prop-
2-enyl acetates by the highly regioselective hydrolysis of
2-alkylidene-1,3-propylene diacetates using 100% w/w
PPL type II.5 Herein, we report the details of a regiospe-
cific acetylation of 2-alkylidenepropane-1,3-diols with vi-
nyl acetate using 50% w/w PPL type II.
4
53
5
57
6
3-Tol
55
7
2-Tol
2g
2h
2i
57
8
Mes
58
9
PhCH2CH2
2-naphthyl
2-furyl
2-thienyl
3-thienyl
20
10
11
12
13
2j
47
2k
2l
44
51
2m
47
a All reactions were carried out with diethyl 2-alkylidenemalonate 1
(1 equiv) and DIBAL-H (4.5 equiv) in toluene at –30 °C.
In a preliminary investigation, the reaction of 2-ben-
zylidenepropane-1,3-diol (2a)3a with vinyl acetate in the
presence of 50% w/w PPL in 1,4-dioxane afforded the
corresponding E-isomer 3a as the sole product in 95%
yield, as indicated in Table 2, entry 1. The overacetylated
1
2-Alkylidenepropane-1,3-diols 2 were easily prepared in
20–62% yield from diethyl 2-alkylidenemalonates 1,
which can be obtained from the Knoevenagel condensa-
tion of the corresponding aldehydes with diethyl mal-
onate,6 by reduction using diisobutylaluminum hydride
(DIBAL-H) (Table 1).7
product and the Z-isomer were not detected in the H
NMR spectroscopic analysis of the crude product. We ex-
amined the regioselective acetylation of 2-ben-
zylidenepropane-1,3-diols substituted on the benzene ring
by electron-donating or electron-withdrawing groups.
The results from the acetylation of various substituted 2-
benzylidenepropane-1,3-diols 2b–h and that of 2-alky-
lidene derivative 2i with vinyl acetate in the presence of
50% w/w PPL in 1,4-dioxane are collated in Table 2. We
selected methoxy and methyl substituents as representa-
tive electron-donating groups (entries 2 and 5–8, respec-
SYNTHESIS 2008, No. 17, pp 2695–2700
x
x.
x
x
.
2
0
0
8
Advanced online publication: 06.08.2008
DOI: 10.1055/s-2008-1067211; Art ID: F08808SS
© Georg Thieme Verlag Stuttgart · New York

2696
T. Miura et al.
PAPER
Table 2 E-Acetylation of 2-Alkylidenepropane-1,3-diols 2 in the
OH
Presence of Porcine Pancreatic Lipasea
OAc
4
vinyl acetate (10 equiv)
PPL
R
OAc
OH
R
OH
1,4-dioxane
OAc
OH
3
2
OAc
5
Entry
1
R
Time (h) Product 3
Yield (%)
95
Figure 1 Byproducts of the acetylation of 2-alkylidenepropane-1,3-
diol 2i
Ph
23
23
47
48
31
20
26
72
28
24
24
24
24
3a
3b
3c
3d
3e
3f
2
4-MeOC6H4
4-F3CC6H4
4-ClC6H4
4-Tol
94
OAc
3
90
H
MeO
OH
H
H
4
94
3b
NOESY
5
97
Figure 2 Determination of the structure of monoacetate 3b
6
3-Tol
92
7
2-Tol
3g
3h
3i
95
tively), trifluoromethyl and chloro substituents as
electron-withdrawing groups (entries 3 and 4, respective-
ly), and 2-(3-phenylpropylidene)propane-1,3-diol (2i) for
the reaction of an aliphatic species (entry 9). Fortunately,
all para-monosubstituted 2-benzylidenepropane-1,3-di-
ols 2b–e reacted under the above conditions to afford the
corresponding (E)-monoacetylated products 3b–e in ex-
cellent yields with complete regioselectivity. High regio-
selectivity was also observed in the reactions of the more-
hindered substrates 2f and 2g containing methyl groups at
the meta- and ortho-positions of the benzene ring (entries
8
Mes
30b
80c
38d
65e
82
9
PhCH2CH2
2-naphthyl
2-furyl
10
11
12
13
3j
3k
3l
2-thienyl
3-thienyl
3m
97
a All reactions were carried out with 2-alkylidenepropane-1,3-diol 2
(1 equiv), vinyl acetate (10 equiv), and 50% w/w PPL in 1,4-dioxane
(3 mL) at r.t.
6
and 7, respectively). 2-(2,4,6-Trimethylbenzyl-
idene)propane-1,3-diol (2h) was a poor substrate for
acetylation using PPL, probably because of the steric hin-
drance of the ortho-substituents on the benzene ring, and
its corresponding (E)-monoacetate 3h was obtained in
only 30% yield (entry 8). The reaction of 2-(3-phenylpro-
pylidene)propane-1,3-diol (2i) (entry 9) afforded the (E)-
monoacetate with lower regioselectivity than that ob-
served for the reactions of substituted 2-benzylidenepro-
pane-1,3-diols 2a–h. Although the corresponding E-
isomer 3i was obtained in 80% yield, Z-isomer 4 and di-
acetate 5 were produced as byproducts in 5 and 6% yield,
respectively (Figure 1). In addition to the above reactions,
polycyclic and heterocyclic aromatic diols 2j–m were
converted into the corresponding E-monoacetates 3j–m
with high regioselectivity (entries 10 and 11–13, respec-
tively); however, the reaction of polycyclic diol 2j con-
taining a 2-naphthyl group gave a lower yield because of
steric hindrance similar to that mentioned above for entry
8.
b Starting material 2h was recovered in 61% yield.
c Starting material 2i was recovered in 4% yield, and Z-isomer 4 and
diacetate 5 were obtained in 5 and 6% yield, respectively.
d Starting material 2j was recovered in 37% yield.
e Starting material 2k was recovered in 14% yield.
In summary, PPL works efficiently as a catalyst in the re-
giospecific acetylation of 2-alkylidenepropane-1,3-diols.
Although a large excess of vinyl acetate (10 equiv) was
used in the reaction, the corresponding (E)-monoacetates
were generally obtained as the sole products in high yields
without overacetylation. 3-Substituted (E)-2-(hydroxy-
methyl)prop-2-enyl acetates are potentially useful inter-
mediates in organic synthesis and may be used as building
blocks in the syntheses of natural products. Using our pro-
cedure, it is possible to prepare various kinds of (E)-
monoacetates.
The 1H NMR spectra were measured with a Bruker Ultrashield 400
Plus (400 MHz) spectrometer, with TMS as an internal standard.
13C NMR spectroscopy was performed on a Bruker Ultrashield 400
Plus (100 MHz) spectrometer, with TMS as an internal standard.
High-resolution mass spectra (HRMS) were recorded using a Wa-
ters LCT Premier (ESI-TOF-MS) spectrometer. For TLC, Merck
precoated TLC plates (silica gel 60 F254, Art 5715) were used. Por-
cine pancreatic lipase type II was commercially available from Sig-
ma.
The structure of monoacetate 3b was determined as the
E-isomer by nuclear Overhauser effect spectroscopy
(NOESY) (Figure 2). A NOESY relationship was ob-
served between the aromatic and the methylene protons
adjacent to the hydroxy group. All the other monoacetates
3a and 3c–m were also determined to be the E-isomers by
NOESY analysis.
Synthesis 2008, No. 17, 2695–2700 © Thieme Stuttgart · New York

PAPER
A Convenient Synthesis of the (E)-Monoacetates of 2-Alkylidenepropane-1,3-diols
2697
Diethyl 2-[4-(Trifluoromethyl)benzylidene]malonate (1c);
Typical Procedure
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H11F3O2: 255.0603;
found: 255.0646.
A clear, colorless solution of 4-(trifluoromethyl)benzaldehyde
(4.00 mL, 30.0 mmol, 1.00 equiv), diethyl malonate (4.76 mL, 31.5
mmol, 1.05 equiv), and benzoic acid (403 mg, 3.30 mmol, 0.11
equiv) in benzene (15 mL) was stirred at 120 °C for 17 h using a
Dean–Stark trap. The mixture was then diluted with EtOAc (200
mL), washed with sat. aq NaHCO3 (100 mL) and sat. aq NaCl (100
mL), and dried (anhyd MgSO4). The crude product was chromato-
graphed (silica gel, EtOAc–hexane, 1:10) to afford 1c. Yield: 8.99
g (95%); colorless plate crystals; mp 49–50 °C.
1H NMR (400 MHz, CDCl3): d = 1.28 (t, J = 7.1 Hz, 3 H, CH2CH3),
1.35 (t, J = 7.1 Hz, 3 H, CH2CH3), 4.33 (q, J = 7.1 Hz, 2 H,
CH2CH3), 4.34 (q, J = 7.1 Hz, 2 H, CH2CH3), 7.57 (d, J = 8.4 Hz, 2
H, ArH), 7.64 (d, J = 8.4 Hz, 2 H, ArH), 7.75 (s, 1 H, =CH).
2-(4-Chlorobenzylidene)propane-1,3-diol (2d)
Colorless cotton crystals; mp 103–105 °C.
1H NMR (400 MHz, CDCl3): d = 2.24 (br s, 2 H, 2 OH), 4.40 (s, 2
H, CH2), 4.42 (s, 2 H, CH2), 6.60 (s, 1 H, =CH), 7.21 (d, J = 8.5 Hz,
2 H, ArH), 7.32 (d, J = 8.5 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 60.6, 67.6, 128.5, 128.6, 130.2,
133.3, 134.6, 139.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H11ClO2: 221.0340;
found: 221.0321.
2-(4-Methylbenzylidene)propane-1,3-diol (2e)
Colorless plate crystals; mp 107–108 °C.
1H NMR (400 MHz, CDCl3): d = 2.08 (t, J = 4.8 Hz, 1 H, OH), 2.11
(t, J = 4.8 Hz, 1 H, OH), 2.36 (s, 3 H, CH3), 4.41 (d, J = 4.8 Hz, 2
H, CH2), 4.48 (d, J = 4.8 Hz, 2 H, CH2), 6.63 (s, 1 H, =CH), 7.17 (s,
4 H, ArH).
13C NMR (100 MHz, CD3OD): d = 21.2, 59.2, 65.5, 129.2, 129.9,
135.2, 137.9, 141.0.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H14O2: 201.0886;
13C NMR (100 MHz, CDCl3): d = 13.9, 14.1, 61.97, 61.99, 123.7 (q,
3
1JC–F = 272 Hz), 125.7 (q, JC–F = 3.7 Hz), 128.8, 129.5, 131.9 (q,
2JC–F = 32.8 Hz), 136.5, 140.2, 163.7, 166.0.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H15F3O4: 339.0815;
found: 339.0808.
Diethyl 2-(2,4,6-Trimethylbenzylidene)malonate (1h)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 0.95 (t, J = 7.1 Hz, 3 H, CH2CH3),
1.35 (t, J = 7.1 Hz, 3 H, CH2CH3), 2.17 (s, 6 H, 2 CH3), 2.26 (s, 3
H, CH3), 4.02 (q, J = 7.1 Hz, 2 H, CH2CH3), 4.32 (q, J = 7.1 Hz, 2
H, CH2CH3), 6.82 (s, 2 H, ArH), 7.87 (s, 1 H, =CH).
found: 201.0888.
2-(3-Methylbenzylidene)propane-1,3-diol (2f)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.30 (s, 3 H, CH3), 3.50 (br s, 1 H,
OH), 3.63 (br s, 1 H, OH), 4.31 (s, 2 H, CH2), 4.37 (s, 2 H, CH2),
6.55 (s, 1 H, =CH), 7.01–7.05 (m, 3 H, ArH), 7.18 (t, J = 8.0 Hz, 1
H, ArH-5).
13C NMR (100 MHz, CDCl3): d = 21.4, 60.1, 66.9, 125.9, 128.0,
128.2, 129.5, 129.7, 136.1, 137.8, 139.1.
13C NMR (100 MHz, CDCl3): d = 13.6, 14.2, 20.1, 21.0, 61.0, 61.6,
127.9, 130.5, 131.1, 135.1, 137.7, 145.5, 163.7, 165.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C17H22O4: 291.1591;
found: 291.1617.
2-(4-Methoxybenzylidene)propane-1,3-diol (2b); Typical
Procedure3a
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H14O2: 201.0886;
To a colorless solution of diethyl 2-(4-methoxybenzylidene)mal-
onate (1b)6 (5.44 g, 22.0 mmol, 1.00 equiv) in dry toluene (10 mL)
was added dropwise at –30 °C a solution of 0.99 M DIBAL-H in tol-
uene (100 mL, 99.0 mmol, 4.50 equiv) under an argon atmosphere.
The mixture was stirred at –30 °C for 3 h, and then quenched at the
same temperature with MeOH (10 mL). To the mixture was added
a solution of potassium sodium tartrate (126 g) in H2O (350 mL).
After stirring at r.t. for 1 h, the mixture was extracted with EtOAc
(3 × 200 mL), and the EtOAc layers were combined, washed with
brine, dried (anhyd MgSO4), and evaporated. The crude product
was chromatographed (silica gel, EtOAc–hexane, 2:1) to afford 2b.
Yield: 2.04 g (48%); colorless powder; mp 69–70 °C.
1H NMR (400 MHz, CDCl3): d = 2.14 (t, J = 5.7 Hz, 1 H, OH), 2.21
(t, J = 5.4 Hz, 1 H, OH), 3.82 (s, 3 H, OCH3), 4.39 (d, J = 5.4 Hz, 2
H, CH2), 4.47 (d, J = 5.7Hz, 2 H, CH2), 6.60 (s, 1 H, =CH), 6.89 (d,
J = 8.8 Hz, 2 H, ArH-3), 7.22 (d, J = 8.8 Hz, 2 H, ArH-2).
13C NMR (100 MHz, CDCl3): d = 55.3, 60.9, 68.0, 113.8, 128.7,
129.8, 130.2, 137.6, 158.9.
found: 201.0888.
2-(2-Methylbenzylidene)propane-1,3-diol (2g)
Colorless powder; mp 61–62 °C.
1H NMR (400 MHz, CDCl3): d = 2.23 (s, 3 H, CH3), 3.05 (br s, 1 H,
OH), 3.15 (br s, 1 H, OH), 4.29 (s, 2 H, CH2), 4.39 (s, 2 H, CH2),
6.62 (s, 1 H, =CH), 7.12–7.20 (m, 4 H, ArH).
13C NMR (100 MHz, CDCl3): d = 19.9, 60.5, 66.9, 125.6, 127.6,
128.6, 129.1, 129.9, 135.3, 136.4, 139.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H14O2: 201.0886;
found: 201.0888.
2-(2,4,6-Trimethylbenzylidene)propane-1,3-diol (2h)
Colorless powder; mp 88–89 °C.
1H NMR (400 MHz, CDCl3): d = 2.11 (s, 6 H, 2 CH3), 2.25 (s, 3 H,
CH3), 2.93 (br s, 1 H, OH), 3.27 (br s, 1 H, OH), 4.01 (s, 2 H, CH2),
4.38 (s, 2 H, CH2), 6.37 (s, 1 H, =CH), 6.83 (s, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.3, 20.9, 60.8, 66.1, 127.3,
128.0, 132.2, 135.9, 136.5, 139.8.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C11H14O3: 217.0835;
found: 217.0820.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H18O2: 229.1199;
found: 229.1197.
2-[4-(Trifluoromethyl)benzylidene]propane-1,3-diol (2c)
Colorless powder; mp 97–99 °C.
1H NMR (400 MHz, CDCl3): d = 3.35 (br s, 2 H, 2 OH), 4.36 (s, 2
H, CH2), 4.38 (s, 2 H, CH2), 6.64 (s, 1 H, =CH), 7.34 (d, J = 8.4 Hz,
2 H, ArH), 7.56 (d, J = 8.4 Hz, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 60.4, 67.3, 124.1 (q, 1JC–F = 272
Hz), 125.3 (q, 3JC–F = 3.8 Hz), 128.2, 129.1, 129.3 (q, 2JC–F = 32.5
Hz), 139.7, 141.2.
2-(3-Phenylpropylidene)propane-1,3-diol (2i)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.39 (q, J = 7.6 Hz, 2 H,
CH2CH=), 2.59 (br s, 1 H, OH), 2.67 (t, J = 7.6 Hz, 2 H, PhCH2),
3.01 (br s, 1 H, OH), 4.11 (s, 4 H, 2 CH2), 5.56 (t, J = 7.6 Hz, 1 H,
=CH), 7.15–7.20 (m, 3 H, ArH), 7.24–7.29 (m, 2 H, ArH).
Synthesis 2008, No. 17, 2695–2700 © Thieme Stuttgart · New York

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T. Miura et al.
PAPER
13C NMR (100 MHz, CDCl3): d = 29.3, 35.6, 59.4, 66.9, 126.0,
128.4, 128.5, 129.5, 137.9, 141.4.
CH2OAc), 6.67 (s, 1 H, =CH), 6.89 (d, J = 8.7 Hz, 2 H, ArH-3), 7.26
(d, J = 8.7 Hz, 2 H, ArH-2).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C12H16O2: 215.1043;
found: 215.1061.
13C NMR (100 MHz, CDCl3): d = 21.1, 55.3, 59.4, 67.8, 113.8,
128.2, 130.3, 132.8, 133.8, 159.2, 171.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H16O4: 259.0941;
found: 259.0958.
2-(2-Naphthylmethylene)propane-1,3-diol (2j)
Colorless powder; mp 107–108 °C.
1H NMR (400 MHz, CDCl3): d = 2.21 (br s, 2 H, 2 OH), 4.47 (s, 2
H, CH2), 4.55 (s, 2 H, CH2), 6.81 (s, 1 H, =CH), 7.40 (dd, J = 1.6,
8.4 Hz, 1 H, ArH), 7.45–7.51 (m, 2 H, ArH), 7.72 (s, 1 H, ArH),
7.80–7.84 (m, 3 H, ArH).
13C NMR (100 MHz, CDCl3): d = 60.9, 67.7, 126.1, 126.3, 126.9,
127.6, 127.8, 127.9, 128.1, 129.8, 132.5, 133.2, 133.6, 139.6.
(E)-2-(Hydroxymethyl)-3-phenylprop-2-enyl Acetate (3a)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.12 (s, 3 H, COCH3), 2.53 (br s,
1 H, OH), 4.31 (s, 2 H, CH2OH), 4.82 (s, 2 H, CH2OAc), 6.71 (s, 1
H, =CH), 7.25–7.36 (m, 5 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.1, 59.3, 67.2, 127.6, 128.3,
128.9, 132.5, 135.5, 135.7, 171.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H14O2: 237.0886;
found: 237.0865.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C12H14O3: 229.0835;
found: 229.0831.
2-(2-Furylmethylene)propane-1,3-diol (2k)
Pale yellow oil.
(E)-2-(Hydroxymethyl)-3-[4-(trifluoromethyl)phenyl]prop-2-
enyl Acetate (3c)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.15 (s, 3 H, COCH3), 2.49 (br s,
1 H, OH), 4.28 (s, 2 H, CH2OH), 4.84 (s, 2 H, CH2OAc), 6.73 (s, 1
H, =CH), 7.41 (d, J = 8.2 Hz, 2 H, ArH-2), 7.60 (d, J = 8.2 Hz, 2 H,
ArH-3).
1H NMR (400 MHz, CDCl3): d = 2.04 (br s, 1 H, OH), 2.22 (br s, 1
H, OH), 4.37 (s, 2 H, CH2), 4.65 (s, 2 H, CH2), 6.32 (d, J = 3.3 Hz,
1 H, ArH-3), 6.35 (s, 1 H, =CH), 6.42 (dd, J = 1.8, 3.3 Hz, 1 H, ArH-
4), 7.42 (d, J = 1.8 Hz, 1 H, ArH-5).
13C NMR (100 MHz, CDCl3): d = 60.8, 66.6, 110.8, 111.5, 116.1,
137.8, 142.5, 151.7.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C8H10O3: 177.0522;
found: 177.0517.
13C NMR (100 MHz, CDCl3): d = 21.0, 58.9, 66.8, 124.1 (q, 1JC–F
=
272 Hz), 125.3 (q, 3JC–F = 3.8 Hz), 129.2, 129.6 (q, 2JC–F = 32.5 Hz),
130.7, 137.6, 139.4, 171.4.
2-(2-Thienylmethylene)propane-1,3-diol (2l)
Colorless powder; mp 51–52 °C.
1H NMR (400 MHz, CDCl3): d = 2.17 (t, J = 5.2 Hz, 1 H, OH), 2.24
(t, J = 4.8 Hz, 1 H, OH), 4.40 (d, J = 5.2 Hz, 2 H, CH2), 4.65 (d, J =
4.8Hz, 2 H, CH2), 6.69 (s, 1 H, =CH), 7.01–7.04 (m, 2 H, ArH),
7.30–7.32 (m, 1 H, ArH).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H13F3O3: 297.0709;
found: 297.0739.
(E)-3-(4-Chlorophenyl)-2-(hydroxymethyl)prop-2-enyl Ace-
tate (3d)
Colorless oil.
13C NMR (100 MHz, CDCl3): d = 61.2, 67.4, 121.5, 126.3, 127.3,
1H NMR (400 MHz, CDCl3): d = 2.14 (s, 3 H, COCH3), 2.23 (br s,
1 H, OH), 4.28 (s, 2 H, CH2OH), 4.81 (s, 2 H, CH2OAc), 6.67 (s, 1
H, =CH), 7.24 (d, J = 8.4 Hz, 2 H, ArH-2), 7.33 (d, J = 8.4 Hz, 2 H,
ArH-3).
13C NMR (100 MHz, CDCl3): d = 21.0, 59.1, 67.1, 128.5, 130.3,
131.3, 133.6, 134.1, 136.1, 171.3.
128.3, 137.9, 138.6.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C8H10O2S: 193.0294;
found: 193.0312.
2-(3-Thienylmethylene)propane-1,3-diol (2m)
Colorless powder; mp 82–83 °C.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C12H13ClO3: 263.0445;
found: 263.0488.
1H NMR (400 MHz, CDCl3): d = 1.98 (t, J = 5.8 Hz, 1 H, OH), 2.07
(t, J = 5.4 Hz, 1 H, OH), 4.39 (d, J = 5.8 Hz, 2 H, CH2), 4.52 (d, J =
5.4 Hz, 2 H, CH2), 6.58 (s, 1 H, =CH), 7.09 (dd, J = 1.2, 5.0 Hz, 1
H, ArH), 7.23–7.25 (m, 1 H, ArH), 7.31 (dd, J = 3.0, 5.0 Hz, 1 H,
ArH).
13C NMR (100 MHz, CDCl3): d = 61.1, 67.7, 123.8, 124.0, 125.6,
128.5, 137.1, 138.6.
(E)-2-(Hydroxymethyl)-3-(4-tolyl)prop-2-enyl Acetate (3e)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.13 (s, 3 H, COCH3), 2.21 (t, J =
5.2 Hz, 1 H, OH), 2.35 (s, 3 H, CH3), 4.33 (d, J = 5.2 Hz, 2 H,
CH2OH), 4.81 (s, 2 H, CH2OAc), 6.70 (s, 1 H, =CH), 7.16 (d, J =
8.2 Hz, 2 H, ArH), 7.19 (d, J = 8.2 Hz, 2 H, ArH).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C8H10O2S: 193.0294;
found: 193.0273.
13C NMR (100 MHz, CDCl3): d = 21.1, 21.2, 59.2, 67.4, 128.9,
129.0, 132.6, 132.8, 134.8, 137.5, 171.4.
(E)-2-(Hydroxymethyl)-3-(4-methoxyphenyl)prop-2-enyl Ace-
tate (3b); Typical Procedure
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H16O3: 243.0992;
found: 243.1003.
A pale-yellow suspension of 2-(4-methoxybenzylidene)propane-
1,3-diol (2b) (194 mg, 1.00 mmol, 1.00 equiv), vinyl acetate (0.92
mL, 10.0 mmol, 10.0 equiv), and 50% w/w PPL (97 mg) in 1,4-di-
oxane (3 mL) was stirred at r.t. for 23 h. Then, the resulting suspen-
sion was diluted with EtOAc (10 mL) and dried (anhyd MgSO4).
The mixture was filtered, and the filtrate was evaporated. The crude
product was chromatographed (silica gel, EtOAc–hexane, 2:3) to
afford 3b.3a Yield: 222 mg (94%); colorless oil.
(E)-2-(Hydroxymethyl)-3-(3-tolyl)prop-2-enyl Acetate (3f)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.12 (s, 3 H, COCH3), 2.35 (s, 3
H, CH3), 2.40 (br s, 1 H, OH), 4.32 (s, 2 H, CH2OH), 4.81 (s, 2 H,
CH2OAc), 6.69 (s, 1 H, =CH), 7.08–7.10 (m, 3 H, ArH), 7.23 (t, J =
7.8 Hz, 1 H, ArH-5).
13C NMR (100 MHz, CDCl3): d = 21.1, 21.4, 59.2, 67.3, 126.0,
128.2, 128.4, 129.6, 132.7, 135.3, 135.7, 137.9, 171.4.
1H NMR (400 MHz, CDCl3): d = 2.13 (s, 3 H, COCH3), 2.23 (br s,
1 H, OH), 3.82 (s, 3 H, OCH3), 4.33 (s, 2 H, CH2OH), 4.80 (s, 2 H,
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A Convenient Synthesis of the (E)-Monoacetates of 2-Alkylidenepropane-1,3-diols
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HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H16O3: 243.0992;
found: 243.1003.
1H NMR (400 MHz, CDCl3): d = 2.11 (t, J = 6.0 Hz, 1 H, OH), 2.13
(s, 3 H, COCH3), 4.52 (d, J = 6.0 Hz, 2 H, CH2OH), 4.81 (s, 2 H,
CH2OAc), 6.77 (s, 1 H, =CH), 7.04 (dd, J = 3.6, 5.1 Hz, 1 H, ArH-
4), 7.08 (d, J = 3.6 Hz, 1 H, ArH-3), 7.34 (dd, J = 1.1, 5.1 Hz, 1 H,
ArH-5).
(E)-2-(Hydroxymethyl)-3-(2-tolyl)prop-2-enyl Acetate (3g)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.13 (s, 3 H, COCH3), 2.24 (s, 3
H, CH3), 2.40 (br s, 1 H, OH), 4.20 (s, 2 H, CH2OH), 4.85 (s, 2 H,
CH2OAc), 6.71 (s, 1 H, =CH), 7.15–7.22 (m, 4 H, ArH).
13C NMR (100 MHz, CDCl3): d = 19.9, 21.1, 59.1, 66.7, 125.6,
127.8, 129.1, 129.9, 131.2, 134.9, 135.6, 136.4, 171.4.
13C NMR (100 MHz, CDCl3): d = 21.1, 59.9, 67.3, 125.0, 126.9,
127.3, 129.1, 133.9, 138.1, 171.3.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H12O3S: 235.0399;
found: 235.0360.
(E)-2-(Hydroxymethyl)-3-(3-thienyl)prop-2-enyl Acetate (3m)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.09 (s, 3 H, COCH3), 3.11 (br s,
1 H, OH), 4.34 (s, 2 H, CH2OH), 4.76 (s, 2 H, CH2OAc), 6.60 (s, 1
H, =CH), 7.08–7.10 (m, 1 H, ArH-4), 7.26–7.28 (m, 2 H, ArH-2,
ArH-5).
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C13H16O3: 243.0992;
found: 243.1003.
(E)-2-(Hydroxymethyl)-3-mesitylprop-2-enyl Acetate (3h)
Colorless powder; mp 36–37 °C.
1H NMR (400 MHz, CDCl3): d = 2.12 (s, 6 H, 2 CH3), 2.13 (s, 3 H,
COCH3), 2.27 (s, 3 H, CH3), 3.92 (s, 2 H, CH2OH), 4.86 (s, 2 H,
CH2OAc), 6.48 (s, 1 H, =CH), 6.85 (s, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 21.0, 59.3, 67.3, 124.5, 125.5,
126.4, 128.5, 134.6, 136.7, 171.4.
13C NMR (100 MHz, CDCl3): d = 20.2, 20.96, 21.00, 59.4, 65.9,
128.0, 129.8, 131.8, 135.8, 136.5, 136.7, 171.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H12O3S: 235.0399;
found: 235.0399.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H20O3: 271.1305;
found: 271.1321.
(Z)-2-(Hydroxymethyl)-5-phenylpent-2-enyl Acetate (4)
Colorless oil.
(E)-2-(Hydroxymethyl)-5-phenylpent-2-enyl Acetate (3i)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.04 (s, 3 H, COCH3), 2.19 (br s,
1 H, OH), 2.46 (q, J = 7.4 Hz, 2 H, CH2CH=), 2.69 (t, J = 7.4 Hz, 2
H, CH2Ph), 4.07 (s, 2 H, CH2OH), 4.61 (s, 2 H, CH2OAc), 5.74 (t,
J = 7.4 Hz, 1 H, =CH), 7.15–7.20 (m, 3 H, ArH), 7.25–7.30 (m, 2
H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.9, 29.5, 35.6, 60.1, 65.6, 126.0,
128.38, 128.44, 132.2, 134.3, 141.3, 171.3.
1H NMR (400 MHz, CDCl3): d = 1.67 (br s, 1 H, OH), 2.06 (s, 3 H,
COCH3), 2.44 (q, J = 7.5 Hz, 2 H, CH2CH=), 2.69 (t, J = 7.5 Hz, 2
H, CH2Ph), 4.00 (s, 2 H, CH2OH), 4.59 (s, 2 H, CH2OAc), 5.67 (t,
J = 7.5 Hz, 1 H, =CH), 7.15–7.21 (m, 3 H, ArH), 7.26–7.30 (m, 2
H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.9, 29.3, 35.4, 58.1, 66.8, 126.0,
128.3, 128.5, 132.4, 134.4, 141.1, 171.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H18O3: 257.1148;
found: 257.1107.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C14H18O3: 257.1148;
found: 257.1150.
2-[(Acetyloxy)-methyl]-5-phenylpent-2-en-1-yl Acetate (5)
Colorless oil.
(E)-2-(Hydroxymethyl)-3-(2-naphthyl)prop-2-enyl Acetate (3j)
Colorless powder; mp 92–93 °C.
1H NMR (400 MHz, CDCl3): d = 2.16 (s, 3 H, COCH3), 2.18 (br s,
1 H, OH), 4.41 (s, 2 H, CH2OH), 4.88 (s, 2 H, CH2OAc), 6.89 (s, 1
H, =CH), 7.42 (dd, J = 1.7, 8.5 Hz, 1 H, ArH), 7.46–7.51 (m, 2 H,
ArH), 7.76 (s, 1 H, ArH-1), 7.81–7.85 (m, 3 H, ArH).
1H NMR (400 MHz, CDCl3): d = 2.03 (s, 3 H, COCH3), 2.06 (s, 3
H, COCH3), 2.45–2.50 (m, 2 H, CH2CH=), 2.70 (t, J = 7.3 Hz, 2 H,
CH2Ph), 4.55 (s, 4 H, 2 × CH2OAc), 5.81 (t, J = 7.5 Hz, 1 H, =CH),
7.16–7.21 (m, 3 H, ArH), 7.26–7.30 (m, 2 H, ArH).
13C NMR (100 MHz, CDCl3): d = 20.9, 21.0, 29.6, 35.4, 59.7, 66.5,
126.1, 128.4, 128.5, 129.8, 153.2, 141.0, 170.7, 170.8.
13C NMR (100 MHz, CDCl3): d = 21.1, 59.4, 67.4, 126.28, 126.34,
126.9, 127.6, 127.95, 128.05, 128.13, 132.6, 132.8, 133.17, 133.19,
135.8, 171.4.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H20O4Na: 299.1254;
found: 299.1215.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H16O3: 279.0992;
found: 279.1013.
Acknowledgment
This work was supported in part by the Ajinomoto Award in Syn-
thetic Organic Chemistry, Japan, and by a Grant-in-Aid for Scienti-
fic Research (C) (No. 18590014) from the Japan Society for the
Promotion of Science. This work was performed through the Scien-
tific Research Project by CIS (Chiba Institute of Science).
(E)-3-(2-Furyl)-2-(hydroxymethyl)prop-2-enyl Acetate (3k)
Colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.12 (s, 3 H, COCH3), 2.30 (br s,
1 H, OH), 4.55 (s, 2 H, CH2OH), 4.78 (s, 2 H, CH2OAc), 6.38 (d,
J = 3.4 Hz, 1 H, ArH-3), 6.40 (s, 1 H, =CH), 6.43 (dd, J = 1.8, 3.4
Hz, 1 H, ArH-4), 7.44 (d, J = 1.8 Hz, 1 H, ArH-5).
13C NMR (100 MHz, CDCl3): d = 21.0, 60.0, 67.1, 111.6, 111.8,
119.2, 133.5, 142.9, 151.3, 171.2.
HRMS (ESI-TOF): m/z [M + Na]+ calcd for C10H12O4: 219.0628;
found: 219.0602.
References
(1) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis, 3rd ed.; John Wiley and Sons: New York, 1999.
(2) (a) Faber, K. Biotransformations in Organic Chemistry;
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Enzymes in Synthetic Organic Chemistry; Pergamon:
Oxford, 1994.
(E)-2-(Hydroxymethyl)-3-(2-thienyl)prop-2-enyl Acetate (3l)
Colorless oil.
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T. Miura et al.
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Synthesis 2008, No. 17, 2695–2700 © Thieme Stuttgart · New York