Titanocene(III) chloride mediated stereoselective synthesis of trisubstituted tetrahydrofurans and a spirolactone by tandem radical reactions

Article abstract of DOI:10.1002/ejoc.201400097

The titanocene(III) chloride (Cp₂TiCl) mediated stereoselective synthesis of highly substituted tetrahydrofurans has been achieved by a reaction that proceeds through a tandem radical cyclization reaction between a Baylis-Hillman adduct and an activated bromo/iodo compound. The reaction of an epoxide with the Baylis-Hillman adduct furnished a spirolactone through a radical cyclization followed by an in situ lactonization. Cp₂TiCl was prepared in situ from commercially available Cp₂TiCl₂ and zinc dust in tetrahydrofuran.

Full text of DOI:10.1002/ejoc.201400097

FULL PAPER
DOI: 10.1002/ejoc.201400097
Titanocene(III) Chloride Mediated Stereoselective Synthesis of Trisubstituted
Tetrahydrofurans and a Spirolactone by Tandem Radical Reactions
[a]
[a]
[a]
Shirshendu Mukherjee, Rajdip Roy, and Subhas Chandra Roy*
Keywords: Synthetic methods / C–C coupling / Radicals / Cyclization / Titanium / Spiro compounds
The titanocene(III) chloride (Cp
2
TiCl) mediated stereoselec-
epoxide with the Baylis–Hillman adduct furnished a spiro-
lactone through a radical cyclization followed by an in situ
tive synthesis of highly substituted tetrahydrofurans has
been achieved by a reaction that proceeds through a tandem
radical cyclization reaction between a Baylis–Hillman adduct
and an activated bromo/iodo compound. The reaction of an
lactonization. Cp
2
TiCl was prepared in situ from commer-
TiCl and zinc dust in tetrahydrofuran.
cially available Cp
2
2
Introduction
much attention by organic chemists over the years. In ad-
dition, some tetrahydrofurans are precursors to α-methyl-
ene-γ-butyrolactones, an important structural unit that is
mainly present in sesquiterpenes and other cytotoxic and
Carbon–carbon bond formation and functional group
transformations are the most important reactions for
designing molecular frameworks in organic chemistry.
[
1]
Amongst the large number of carbon–carbon bond-forming
reactions, the Baylis–Hillman reaction[ is considered a use-
ful carbon–carbon bond-forming protocol, and attention
for it has increased because of its two important features –
atom economy and the generation of functional groups in
close proximity to provide valuable intermediates for syn-
thetic organic chemists. Radical-mediated reactions have
also become an important synthetic tool for the develop-
ment of efficient carbon–carbon bond-forming reactions
because of the mild reaction conditions, high levels of regio-
and stereoselectivity, and significant functional group toler-
[
7]
antitumor agents. Spirolactones also contain an impor-
tant fragment that is found in a wide range of natural prod-
2]
[
8]
ucts and related biologically active compounds. As a re-
[6]
sult, the syntheses of substituted tetrahydrofurans and
[
9]
spirolactones have for years received much attention, and,
still, it is a challenge to organic chemists to develop a viable
method. We report, herein, a mild and efficient method for
the syntheses of trisubstituted tetrahydrofurans and a spiro-
lactone in satisfactory yields. The reaction proceeds through
a tandem radical reaction by employing a Baylis–Hillman
[
10]
adduct
and either an activated bromo/iodo compounds
[
3]
ance. An intramolecular radical cyclization reaction is a
well-known and useful tool to construct carbocyclic and
[5a]
or epoxide along with Cp TiCl as a radical generator
.
2
[
4]
heterocyclic rings. When carbon–carbon bond formation
is achieved through an intermolecular tandem radical cycli-
zation, it obviously becomes an important synthetic ap-
proach to synthesize many useful intermediates for natural
product synthesis. The mild and efficient bis(cyclopentadi-
Results and Discussion
Tandem radical reactions between methyl 2-[aryl(prop-2-
ynyloxy)methyl]acrylates and activated bromo/iodo com-
III
pounds with Ti species as the radical initiator provided
enyl)titanium(III) chloride (Cp TiCl) mediated radical reac-
2
methyl
4-methylene-3-arylethyl-2-aryltetrahydrofuran-3-
tions have been in the spotlight in recent years to utilize
radical technology for the development of significant proto-
cols for the syntheses of natural products and related useful
carboxylates as the sole product. Not only esters but also
several 2-[aryl(prop-2-ynyloxy)methyl]acrylonitriles under-
went similar radical reactions under these conditions (see
Scheme 1).
[
5]
compounds.
Substituted tetrahydrofurans are widely found in various
types of bioactive natural products. Because of their wide-
spread occurrence in nature and broad range of biological
activities, trisubstituted tetrahydrofurans[6] have attracted
Initially, the reaction was performed with methyl 2-
[phenyl(prop-2-ynyloxy)methyl]acrylate (1a) and benzyl
bromide in tetrahydrofuran (THF, 26 mL per mmol) in the
presence of Cp TiCl in dry deoxygenated THF to afford 2a
2
in an unsatisfactory yield. When the reaction was per-
formed in a concentrated solution in THF (0.067 m), how-
ever, the yield of 2a increased considerably. Thus, a series
of activated ester and cyano compounds 1 were subjected to
the titanocene(III) chloride mediated reaction with various
bromo/iodo compounds to furnish 2, and the results are
[
a] Department of Organic Chemistry, Indian Association for the
Cultivation of Science,
Jadavpur, Kolkata 700032, India
E-mail: ocscr@iacs.res.in
http://www.iacs.res.in
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201400097.
2980
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 2980–2985

Titanocene(III) Chloride Mediated Synthesis of Tetrahydrofurans
Table 1. Titanocene(III) mediated synthesis of tetrahydrofurans.
Scheme 1. Titanocene(III) chloride mediated synthesis of tetra-
hydrofurans.
summarized in Table 1. It is noteworthy that no other iso-
mer was produced or any unreacted starting material was
recovered in all the transformations.
The reaction was initiated by an intermolecular addition
of the radical species that is generated from the activated
bromide or iodide to the activated double bond of the carb-
oxylate or carbonitrile (i.e., 1) followed by an intramo-
lecular radical cyclization that involves the triple bond of
the propargyl group to give 2. It was shown that electron-
donating groups on the benzene ring of the bromo com-
pound (see Table 1, Entry 8) provided the optimum yield to
give 2h. Both a substituted bromo compound (see Table 1,
Entries 2 and 7) and a chloro-substituted bromo compound
(see Table 1, Entries 3 and 6) were employed, but there were
no significant differences in the yields of these reactions.
Activated iodo compounds also underwent a similar reac-
tion with good yield of the product (see Table 1, Entries 9–
12). However, when a strong electron-withdrawing group
(
i.e., NO ) was present on the aromatic ring (see Table 1,
2
Entry 13), the reaction did not proceed, and only the start-
ing compound was isolated. We also observed no significant
difference between the yields of reactions that used 2-[aryl-
(prop-2-ynyloxy)methyl]acrylonitriles and those resulting
from the corresponding acrylate esters. The structural con-
nectivity and the relative stereochemistry of all the products
2a–2h were determined by spectral and analytical studies
and finally confirmed by a single-crystal X-ray diffraction
study of 3-(4-chlorophenylethyl)-4-methylene-2-p-tolyltetra-
hydrofuran-3-carbonitrile (2f, see Figure 1).
Figure 1. X-ray crystal structure of 2f.
Eur. J. Org. Chem. 2014, 2980–2985
[a] Isolated yield after column chromatography.
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2981

S. Mukherjee, R. Roy, S. Chandra Roy
FULL PAPER
In continuation of the synthesis of trisubstituted tetra- stereoselectivity in the radical cyclization steps is not clear
hydrofurans, we have also developed a method for the syn- at this stage.
thesis of a spirolactone, the reaction of which proceeds
On the basis of the stereochemistry of 2f, which was al-
through a tandem radical cyclization and in situ lacton- ready established by X-ray studies, the stereochemistry of
ization in one pot with Cp TiCl as the radical initiator (see other derivatives of tetrahydrofuran could be easily pre-
2
Scheme 2). Thus, the treatment of the ester 1b with cyclo- dicted. The stereochemistry of spirolactone 3 was deter-
hexene epoxide in the presence of Cp TiCl in THF at room mined by spectral and analytical studies and finally con-
2
temperature afforded only spirolactone 3 in moderate yield firmed by a single-crystal X-ray diffraction study (see Fig-
after column chromatography. There was no trace amount ure 2).
of any other isomer or the starting material. The moderate
yield of compound 3 is probably a result of the formation
of some polymeric material, which could not be isolated or Conclusions
characterized.
In summary, we have developed an efficient method for
the stereoselective synthesis of trisubstituted tetra-
hydrofurans and a spirolactone. These reactions proceed
through a tandem radical cyclization by using Cp TiCl as
2
the radical initiator to give the products in satisfactory
yields.
Scheme 2. Synthesis of spirolactone 3.
Experimental Section
The probable mechanism for the formation of spirolact-
one 3 is shown in Scheme 3. The reason for the high dia-
General Methods: Melting points were measured in open capillary
1
13
tubes. The H and C NMR spectroscopic data were recorded with
a Bruker DPX 300 spectrometer by using CDCl with tetramethyl-
3
silane as the internal standard. IR spectra were recorded with a
Shimadzu FT IR-8300. Column chromatography was performed
on silica gel (60–120 mesh), and preparative TLC was performed
with precoated silica 60 F254 plates (0.2 mm). High resolution
mass spectrometry was carried out with a Qtof Micro YA263 in-
strument. Diethyl ether and tetrahydrofuran were freshly distilled
from sodium. Methylene chloride was freshly distilled from calcium
hydride. Light petroleum with a boiling range of 60–80 °C was used
for chromatography.
Typical Procedure for the Synthesis of (2S,3R)-Methyl 4-Methylene-
3-phenethyl-2-phenyltetrahydrofuran-3-carboxylate (2a): A solution
of Cp TiCl (270 mg, 1.09 mmol) in dry deoxygenated THF (5 mL)
2
2
was stirred with activated Zn dust (161 mg, 2.47 mmol) for 1 h un-
der argon. [The activated zinc dust was prepared by washing com-
mercially available Zn dust (20 g) with of 4 n HCl (60 mL) and
then with water until the washings were neutral. The Zn was then
washed with dry acetone and dried in vacuo.] The resulting green
solution, without the zinc dust, was transferred through a cannula
into a dropping funnel. The solution was then was added dropwise
over a period of 8 h to a stirred solution of benzyl bromide (84 mg,
Scheme 3. Probable mechanism for the formation of spirolactone
3.
0.5 mmol) and methyl 2-[phenyl(prop-2-ynyloxy)methyl]acrylate
(
1a, 75 mg, 0.33 mmol) in dry deoxygenated THF (2.5 mL) under
argon. The reaction mixture was stirred for an additional 4 h and
then quenched with saturated aqueous sodium dihydrogen phos-
phate solution (2 mL). The solvent was removed under reduced
pressure, and the residue was extracted with diethyl ether (3ϫ
2
1
5 mL). The combined ether layers were washed with brine (2ϫ
0 mL) and dried with anhydrous Na SO . After removal of the
2
4
solvent, the crude residue was purified by chromatography on a
silica gel column (0.5% ethyl acetate in light petroleum, R = 0.24)
f
to furnish methyl 4-methylene-3-phenethyl-2-phenyltetrahydro-
furan-3-carboxylate (2a, 62 mg, 58%) as a colorless oil. IR (neat):
–
1 1
ν˜ = 1731, 1514, 1454, 1234 cm . H NMR (500 MHz, CDCl
1.69–1.82 (m, 2 H), 2.14–2.2 (m, 1 H), 2.38–2.44 (m, 1 H), 3.84
s, 3 H), 4.57 (d, J = 13.5 Hz, 1 H), 4.71 (d, J = 13.0 Hz, 1 H),
5.19 (t, J = 2.5 Hz, 2 H), 5.59 (s, 1 H), 6.85 (d, J = 7.5 Hz, 2 H),
3
): δ
=
(
Figure 2. X-ray structure of 3.
982
2
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Eur. J. Org. Chem. 2014, 2980–2985

Titanocene(III) Chloride Mediated Synthesis of Tetrahydrofurans
.09 (t, J = 7.0 Hz, 2 H), 7.16 (t, J = 7.5 Hz, 2 H), 7.29–7.4 (m, 4 139.0, 147.1 ppm. HRMS (ESI): calcd. for C21H20NOClNa [M +
7
13
+
H) ppm. C NMR (125 MHz, CDCl
3
): δ = 29.9, 31.1, 35.2, 52.5,
0.7, 71.0, 86.2, 107.2, 125.8, 126.7, 127.9, 128.2, 128.3, 128.4,
28.5, 129.3, 137.6, 142.4, 150.8, 173.6 ppm. HRMS (ESI): calcd.
Na] 360.1131; found 360.1131.
2S,3S)-3-(4-Methylphenethyl)-4-methylene-2-p-tolyltetrahydro-
furan-3-carbonitrile (2g): Crystalline solid (66 mg, 55% yield); m.p.
0–55 °C. IR (neat): ν˜ = 3010, 1731, 1718, 1650, 1515, 1406, 1261,
6
1
(
+
22 3
for C21H O Na [M + Na] 345.1467; found 345.1468.
5
–
1 1
Methyl (2S,3R)-3-(4-Methylphenethyl)-4-methylene-2-phenyltetra-
hydrofuran-3-carboxylate (2b): Colorless oil (78 mg, 66% yield). IR
3
1062, 1024 cm . H NMR (500 MHz, CDCl ): δ = 1.44–1.52 (m,
2 H), 2.27 (s, 3 H), 2.34 (s, 3 H), 2.38–2.46 (m, 1 H), 2.58–2.66 (m,
1 H), 4.59 (d, J = 14.0 Hz, 1 H), 4.71 (d, J = 14.0 Hz, 1 H), 5.18
(d, J = 4.4 Hz, 1 H), 5.35 (s, 1 H), 5.50 (t, J = 2.4 Hz, 1 H), 6.86
–
1 1
(neat): ν˜ = 3010, 1732, 1650, 1514, 1455, 1434, 1234, 1087 cm . H
NMR (500 MHz, CDCl ): δ = 1.67–1.79 (m, 2 H), 2.09–2.16 (m, 1
3
H), 2.26 (s, 3 H), 2.33–2.37 (m, 1 H), 3.84 (s, 3 H), 4.56 (d, J = (d, J = 7.2 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 2 H), 7.17 (d, J = 8.0 Hz,
1
3
13.5 Hz, 1 H), 4.69 (d, J = 13.0 Hz, 1 H), 5.16–5.19 (m, 2 H), 5.59
3
2 H), 7.34 (d, J = 8.0 Hz, 2 H) ppm. C NMR (125 MHz, CDCl ):
(
s, 1 H), 6.75 (d, J = 8.0 Hz, 2 H), 6.98 (d, J = 7.5 Hz, 2 H), 7.28–
δ = 21.0, 21.3, 22.8, 29.8, 30.4, 33.2, 50.8, 69.9, 75.2, 86.2, 111.3,
): δ = 21.1, 29.9, 118.8, 120.4, 126.2, 128.3, 128.9, 129.1, 129.2, 129.3, 129.9, 135.8,
13
7
3
1
.39 (m, 5 H) ppm. C NMR (125 MHz, CDCl
3
0.6, 35.3, 52.6, 60.7, 71.0, 76.7, 86.2, 107.3, 126.7, 127.9, 128.2,
137.5, 138.5, 147.8 ppm. HRMS (ESI): calcd. for C22
H23NONa [M
+ Na]+ 340.1677; found 340.1677.
28.3, 128.8, 128.9, 129.1, 135.3, 137.6, 139.3, 150.8, 173.6 ppm.
+
HRMS (ESI): calcd. for C22
59.1620.
H
24
O
3
Na [M + Na] 359.1623; found
(
2S,3S)-3-(3-Bromo-4,5-dimethoxyphenethyl)-4-methylene-2-p-tolyl-
3
tetrahydrofuran-3-carbonitrile (2h): Crystalline solid (114 mg, 68%
yield); m.p. 65–70 °C. IR (neat): ν˜ = 3010, 1731, 1644, 1515, 1406,
Methyl (2S,3R)-3-(4-Chlorophenethyl)-4-methylene-2-phenyltetra-
hydrofuran-3-carboxylate (2c): Colorless oil (70 mg, 58% yield). IR
–
1 1
1
261, 1023 cm . H NMR (500 MHz, CDCl
1 H), 1.64–1.70 (m, 1 H), 2.34 (s, 3 H), 2.42–2.49 (m, 1 H), 2.76–
.82 (m, 1 H), 3.77 (s, 3 H), 3.80 (s, 3 H), 4.59 (d, J = 13.5 Hz, 1
H), 4.76 (d, J = 13.5 Hz, 1 H), 5.19 (s, 1 H), 5.38 (s, 1 H), 5.53 (s,
H), 6.45 (s, 1 H), 6.91 (s, 1 H), 7.18 (d, J = 8.0 Hz, 2 H), 7.36 (d,
3
): δ = 1.33–1.39 (m,
–1 1
(
(
2
neat): ν˜ = 3010, 1732, 1655, 1514, 1455, 1234, 1087 cm . H NMR
500 MHz, CDCl ): δ = 1.63–1.78 (m, 2 H), 2.1–2.16 (m, 1 H),
.34–2.41 (m, 1 H), 3.84 (s, 3 H), 4.56 (d, J = 13.5 Hz, 1 H), 4.68
2
3
1
(d, J = 13.5 Hz, 1 H), 5.17 (t, J = 2.0 Hz, 1 H), 5.19 (s, 1 H), 5.58
1
3
J = 8.0 Hz, 2 H) ppm. C NMR (125 MHz, CDCl
3
): δ = 14.2,
(
s, 1 H), 6.76 (d, J = 8.5 Hz, 2 H), 7.13 (d, J = 7.0 Hz, 2 H), 7.29–
1
3
21.3, 22.8, 29.5, 29.8, 31.3, 32.1, 50.6, 56.2, 56.3, 70.1, 86.1, 110.2,
7
5
1
.38 (m, 5 H) ppm. C NMR (125 MHz, CDCl
2.6, 60.5, 71.0, 86.1, 107.2, 126.5, 128.0, 128.3, 128.4, 129.7, 137.4,
40 8, 150.7, 173.4 ppm. HRMS (ESI): calcd. for C21 22ClO [M
3
): δ = 30.4, 35.1,
1
1
13.3, 114.0, 115.8, 120.4, 126.3, 129.6, 131.8, 138.5, 146.8, 148.3,
48.6 ppm. HRMS (ESI): calcd. for C23H24BrNO Na [M + Na]
3
+
H
3
+
464.0837; found 464.0837.
Synthesis of Spirolactone 3: A solution of Cp
.55 mmol) in dry deoxygenated THF (6 mL) was stirred with acti-
+
H] 357.125; found 357.1172.
2
2
TiCl (137 mg,
Methyl (2S,3R)-4-Methylene-3-phenethyl-2-p-tolyltetrahydrofuran-
3
0
-carboxylate (2d): Colorless oil (72 mg, 60% yield). IR (neat): ν˜ =
–1
1
vated Zn dust (82 mg, 1.26 mmol) for 1 h under argon. [The acti-
vated zinc dust was prepared by washing commercially available Zn
dust (20 g) with of 4 n HCl (60 mL) an then with water until the
washings were neutral, The Zn dust was then washed with dry acet-
one and dried in vacuo.] The resulting green solution, without the
zinc dust, was transferred through a cannula into a dropping fun-
nel. The solution was then added dropwise over a period of 8 h to
a stirred solution of cyclohexene oxide (61 mg, 0.62 mmol) and the
ester methyl 2-[(prop-2-ynyloxy)(p-tolyl)methyl]acrylate (1b, 75 mg,
3
010, 1732, 1650, 1514, 1455, 1087 cm . H NMR (500 MHz,
): δ = 1.68–1.80 (m, 2 H), 2.18–2.24 (m, 1 H), 2.36 (s, 3 H),
.39–2.45 (m, 1 H), 3.83 (s, 3 H), 4.56 (d, J = 13.0 Hz, 1 H), 4.68
d, J = 13.0 Hz, 1 H), 5.18 (d, J = 10.5 Hz, 2 H), 5.54 (s, 1 H),
.88 (d, J = 7.0 Hz, 2 H), 7.08–7.18 (m, 5 H), 7.24 (m, 2 H) ppm.
CDCl
2
(
3
6
1
3
C NMR (125 MHz, CDCl
0.9, 86.2, 107.2, 125.7, 126.5, 128.3, 128.4, 129.0, 134.4, 137.5,
42.5, 150.7, 173.6 ppm. HRMS (ESI): calcd. for C22 Na [M
3
): δ = 21.3, 29.8, 31.1, 34.9, 52.5, 60.6,
7
1
+
24 3
H O
+
Na] 359.1623; found 359.1625.
0
.30 mmol) in dry deoxygenated THF (2.5 mL) under argon. The
2S,3S)-4-Methylene-3-phenethyl-2-p-tolyltetrahydrofuran-3-carbo- reaction mixture was stirred for an additional 4 h and then carefully
nitrile (2e): Crystalline solid (72 mg, 66% yield); m.p. 60–65 °C. IR
quenched with 20% aqueous H SO (2 mL). The solvent was re-
(
2
4
–
1 1
(neat): ν˜ = 3012, 1731, 1718, 1650, 1515, 1406, 1261, 1062 cm . H
moved under reduced pressure, and the residue was extracted with
NMR (500 MHz, CDCl ): δ = 1.47–1.53 (m, 1 H), 1.59–1.64 (m, 1
3
diethyl ether (3ϫ 25 mL). The combined ether layers were washed
H), 2.34 (s, 3 H), 2.43–2.49 (m, 1 H), 2.63–2.69 (m, 1 H), 4.59 (d, with brine (2ϫ 10 mL) and dried with anhydrous Na SO . After
2
4
J = 13.5 Hz, 1 H), 4.71 (d, J = 13.5 Hz, 1 H), 5.18 (s, 1 H), 5.36 removal of the solvent, the crude residue was purified by
(
7
s, 1 H), 5.52 (d, J = 2.5 Hz, 1 H), 6.99 (d, J = 7.5 Hz, 2 H), 7.14–
.23 (m, 5 H), 7.36 (d, J = 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl ): δ = 21.3, 29.8, 30.8, 33.1, 50.8, 69.9, 86.2, 110.0, 120.4,
26.2, 128.4, 128.6, 129.3, 131.7, 138.5, 140.6, 147.2 ppm. HRMS
chromatography on a silica gel column (0.3% ethyl acetate in light
petroleum, R = 0.25) to furnish spirolactone 3 (42 mg, 45% yield)
f
3
as a crystalline solid; m.p. 110–115 °C. IR (neat): ν˜ = 2927, 1720,
–
1 1
1
(
3
1514, 1456, 1330, 1226, 1062 cm . H NMR (400 MHz, CDCl ):
3
+
ESI): calcd. for C21
26.1523.
H
21NONa [M + Na] 326.1521; found
δ = 0.87–0.90 (m, 1 H), 1.09–1.17 (m, 1 H), 1.21–1.26 (m, 2 H),
1.43 (dd, J = 2.8, 13.4 Hz, 2 H), 1.62–1.66 (m, 2 H), 1.79 (d, J =
1
0.8 Hz, 2 H), 2.06 (dd, J = 12.4, 3.2 Hz, 1 H), 2.34 (s, 3 H), 3.57
(
2S,3S)-3-(4-Chlorophenethyl)-4-methylene-2-p-tolyltetrahydro-
(
(
(
(
dt, J = 21.8 Hz, J = 4.0 Hz, 1 H), 4.61 (d, J = 13.2 Hz, 1 H), 4.68
d, J = 13.2 Hz, 1 H), 5.07 (d, J = 6.8 Hz, 2 H), 5.69 (s, 1 H), 7.14
furan-3-carbonitrile (2f): Crystalline solid (101 mg, 56% yield); m.p.
9
1
2
0–95 °C. IR (neat): ν˜ = 3012, 1731, 1718, 1650, 1515, 1406, 1261,
1
3
d, J = 8.0 Hz, 2 H), 7.21 (d, J = 8.0 Hz, 2 H) ppm. C NMR
100 MHz, CDCl ): δ = 21.3, 24.2, 25.2, 30.5, 32.2, 32.4, 34.7, 58.7,
0.1, 84.6, 86.6, 106.6, 126.2, 129.1, 134.0, 137.6, 154.3, 172.0 ppm.
HRMS (ESI): calcd. for C20
Na [M + Na]+ 335.1623; found
35.1625.
–1 1
062, 1024 cm . H NMR (400 MHz, CDCl
3
): δ = 1.42–1.54 (m,
3
H), 2.36 (s, 3 H), 2.41–2.46 (m, 1 H), 2.59–2.67 (m, 1 H), 4.58
7
(d, J = 13.6 Hz, 1 H), 4.71 (d, J = 13.5 Hz, 1 H), 5.18 (s, 1 H),
24 3
H O
5
.36 (s, 1 H), 5.50 (dd, J = 3.6 Hz, J = 2.0 Hz, 1 H), 6.91 (d, J =
.4 Hz, 2 H), 7.16–7.20 (m, 4 H), 7.35 (d, J = 8.4 Hz, 2 H) ppm.
3
8
1
3
C NMR (100 MHz, CDCl
3
): δ = 21.3, 29.8, 30.2, 33.1, 50.6, 69.9,
Typical Procedure for the Synthesis of Methyl 2-[Phenyl(prop-2-
86.2, 110.1, 120.2, 126. 2, 128.7, 129.4, 129.8, 131.6, 132.1, 138.6,
ynyloxy)methyl]acrylate (1a): Methyl 2-[hydroxy(phenyl)methyl]-
Eur. J. Org. Chem. 2014, 2980–2985
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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2983

S. Mukherjee, R. Roy, S. Chandra Roy
FULL PAPER
acrylate (415 mg, 2.15 mmol) was treated with lithium bis(tri-
methylsilyl)amide (1.0 m in THF, 2 equiv.) and hexamethylphos-
phoramide (0.76 mL, 4.3 mmol) in dry THF (2 mL) at –40 °C for
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anhydrous Na
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80 mg, 77%) as a colorless oil. IR (neat): ν˜ = 3303, 2160, 1722,
406, 1255 cm . H NMR (500 MHz, CDCl ): δ = 2.44 (d, J =
3
.0 Hz, 1 H), 3.69 (s, 3 H), 4.03 (dd, J = 15.5 Hz, J = 2.0 Hz, 1 H),
.15 (dd, J = 16.0 Hz, J = 2.0 Hz, 1 H), 5.50 (s, 1 H), 6.00 (s, 1 H),
.37 (s, 1 H), 7.28–7.37 (m, 5 H) ppm. 13C NMR (125 MHz,
–1 1
CDCl
3
): δ = 51.9, 56.0, 74.8, 77.8, 79.6, 125.5, 128.0, 128.3, 128.5,
1
+
38.6, 140.7, 166.2 ppm. HRMS (ESI): calcd. for C14 Na [M
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14 3
H O
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255 cm . H NMR (500 MHz, CDCl
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H), 4.06 (dd, J = 15.7 Hz, J = 2.0 Hz, 1 H), 5.39 (s, 1 H), 5.92
s, 1 H), 6.27 (s, 1 H), 7.0 (d, J = 8.0 Hz, 2 H), 7.18 (d, J = 7.5 Hz,
3
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1
(
2
7
9750–9762; l) J. Wegner, S. V. Ley, A. Kirschning, A.-L. Han-
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9.6, 125.2, 127.9, 129.2, 135.6, 138.0, 140.8, 166.2 ppm. HRMS
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O
3
Na [M + Na] 267.0997; found 267.0996.
2-[(Prop-2-ynyloxy)(p-tolyl)methyl]acrylonitrile (1c): Colorless oil
(
411 mg, 68% yield). IR (neat): ν˜ = 3303, 2227, 2160, 1722, 1514,
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2
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6
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.5 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 7.26 (d, J = 7.5 Hz, 2
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234.0890.
Supporting Information (see footnote on the first page of this arti-
1
13
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Received: January 20, 2014
Published Online: March 27, 2014
Eur. J. Org. Chem. 2014, 2980–2985
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2985