Highly regioselective heck coupling reactions of aryl halides and dihydropyran in the presence of an NHC-pyridine ligand

Article abstract of DOI:10.1055/s-0028-1087528

The Heck coupling reactions of aryl halides and 3,4-dihydro-2H-pyran facilitated the regioselective synthesis of arylated cyclic enol ethers. Good yields were obtained using 5 mol% of an NHC-ligand-Pd-catalyst complex in the presence of K₂CO₃ in DMF at 100°C. The use of this catalytic system broadens the substrate scope and improves the selectivity for this cross-coupling process. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1087528

LETTER
482
Highly Regioselective Heck Coupling Reactions of Aryl Halides and Dihydro-
pyran in the Presence of an NHC-Pyridine Ligand
Heck
Cou
a
pling React
m
ions of
A
ryl
H
alide
i
s
and
D
e
ihydropyran Jarusiewicz, Kyung Soo Yoo, Kyung Woon Jung*
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, CA 90089-0166,
USA
Fax +1(213)8214096; E-mail: kwjung@usc.edu
Received 2 August 2008
The preparation of the NHC-ligand precursor 4 is shown
Abstract: The Heck coupling reactions of aryl halides and 3,4-di-
in Scheme 1. The N-alkylation of benzimidazole 1 and 2-
bromomethyl pyridine 2 in the presence of KOH in THF
gave the corresponding pyridinyl benzimidazole com-
hydro-2H-pyran facilitated the regioselective synthesis of arylated
cyclic enol ethers. Good yields were obtained using 5 mol% of an
NHC-ligand–Pd-catalyst complex in the presence of K2CO3 in
DMF at 100 °C. The use of this catalytic system broadens the sub- pound 3 as a brown solid in 81% yield. N-Methylation of
strate scope and improves the selectivity for this cross-coupling pro-
cess.
3 with iodomethane while refluxing in THF for 12 hours
then gave 4 in 80% yield. Although synthesis of ligand 4
Key words: Heck reaction, N-heterocyclic carbine, pyridine
ligand, palladium, cyclic enol ether
was previously reported, the synthetic route used was not
as efficient as that employed by our group.7
KOH
Br
+
N-Heterocyclic carbenes (NHC) have become one of the
most popular ligand classes for transition metals.1 The sta-
bility of nitrogen-containing ligands and the use of car-
benes bearing appended N-heterocycles, such as pyridine,
have attracted particular attention and have shown prom-
ising potential in catalytic applications such as in Heck
coupling reactions.2 A ligand comprised of a benzimida-
zolium carbene tethered to pyridine by a short alkyl group
was expected to create a robust catalyst, which could
withstand high-temperature reaction conditions. Also,
since NHC are good s-donors, this could enhance the rate
of oxidative addition.3 Additionally, the steric bulk of this
type of ligand could assist with reductive elimination and
therefore be useful for Heck-type reactions.
NH
N
THF, reflux
81%
N
N
N
N
3
1
2
MeI
N
THF, reflux
80%
N
N
I
Me
4
Scheme 1 Synthesis of ligand precursor
To form the NHC–palladium complex 5, as shown in
Scheme 2, NHC precursor 4 was treated with silver(I) ox-
ide in predried dichloromethane at room temperature to
afford the silver–NHC complex. This was then followed
by metal exchange with Pd(OAc)2 in acetonitrile to give
the palladium(II)–NHC-ligand complex 5 as a pale orange
solid in 38% yield over two steps. The structure was con-
firmed by the complete disappearance of the imidazole
proton (d = 9.14 ppm) of 4, as well as the 1H NMR reso-
nance of the pyridine ortho-proton, which was observed
to have a downfield shift (d = 8.48 ppm to 8.98 ppm) upon
coordination to palladium. In addition, broadening of the
methylene at d = 5.96 ppm was observed in the coordinat-
ed complex 5. Attempts to form 5 by direct palladation
using potassium tert-butoxide led to the formation of a
mixture of compounds, which were not separable.
The Heck reaction, a powerful carbon–carbon bond-form-
ing reaction, is the palladium-catalyzed cross-coupling of
an aryl halide with an olefin and has been widely used by
chemists.4 The Heck reaction employing cyclic enol
ethers could serve as a route to synthetically important
glycosides, and the cyclic enol ether motif is one found in
different toxins, such as ciguatoxin, and other natural
products that display bioactivity.5 However, to our knowl-
edge, the scope of this particular reaction has been rela-
tively under-explored. Although there are examples of
reactions employing 2,3-dihydrofuran, previous studies
using 3,4-dihydro-2H-pyran (DHP) gave only modest
yields and mixtures of regioisomers and only one enantio-
selective reaction was reported.6 Therefore, we believed
that the development of a more versatile catalyst system to
expand the substrate scope of the Heck reaction using
DHP would be worthwhile, and our progress towards this
goal is presented herein.
1) Ag2O, CH2Cl2
N
4
2) Pd(OAc)2
MeCN
N
N
Pd
Me
OAc
AcO
38% for two steps
5
Scheme 2 Synthesis of palladium complex 5
SYNLETT 2009, No. 3, pp 0482–0486
x
x.
x
x.
2
0
0
9
Advanced online publication: 21.01.2009
DOI: 10.1055/s-0028-1087528; Art ID: S06908ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Heck Coupling Reactions of Aryl Halides and Dihydropyran
483
Table 1 Effect of Catalyst and Base on the Cross-Coupling Reactions of 4-Iodoanisole and DHPa
MeO
MeO
MeO
O
Pd–L (5 mol%)
O
O
+
+
base, DMF
100 °C, 48 h
I
6
7
9
8
Entry
Pd/ligand
Base
Yield (%)b (8:9)
50 (88:12)
36 (78:22)
60 (66:3)
1
2
3
4
5
6
7
Pd(OAc)2/none
K2CO3
K2CO3
K2CO3
K2CO3
Na2CO3
Cs2CO3
Et3N
Pd(OAc)2/phenc
Pd(OAc)2/dmphenc
5
5
5
5
80 (100:0)
43 (100:0)
10 (100:0)
41 (100:0)
a All reactions were carried out with 4-iodoanisole (0.5 mmol), DHP (6 mmol), base (0.75 mmol), and Pd–L (5 mol%) in solvent (1 mL) under
argon atmosphere.
b Isolated yield.
c phen: 1,10-phenanthroline, dmphen: 2,9-dimethylphenanthroline.
After obtaining palladium complex 5, we then turned our 50 °C or room temperature (entries 5 and 6). Only at high
attention to the cross-coupling of 4-iodoanisole with DHP temperature (100 °C) did the coupling reaction proceed
to see if yields and regioselectivity could be improved in well to afford compound 8. As a result, we determined
comparison with earlier work.6 As shown in Table 1, we that the optimal reaction conditions were in polar aprotic
initially investigated the effect of using Pd(OAc)2 with solvent, such as DMF, in the presence of K2CO3 at 100 °C.
commercially available amine ligands, but a mixture of
To diversify the scope of the reaction, it was then attempt-
ed to use less active aryl halides in the cross-coupling
reaction. However, as shown in Table 3, a reduction in
yields was observed when aryl bromides (entries 2 and 4)
regioisomers 8 and 9 was obtained with poor to modest
yields (entries 1–3).8 However, when 5 was used, com-
pound 8 was obtained as the exclusive product, and the
use of K2CO3 as a base led to high yield (entry 4). Consis-
and aryl chlorides (entry 5) were used. This result is con-
tent with previous results, which demonstrated that an ox-
sistent with the fact that oxidative addition of aryl
ygen near an olefin electronically assists with favorable
coordination of the Pd(II) center and inverts the polariza-
Table 2 Effect of Solvent and Temperature on the Cross-Coupling
tion of the double bond with respect to the traditional
Reactions of 4-Iodoanisole and DHP in the Presence of Pd–Ligand
Heck reaction, arylation was observed only at the a-car-
bon.6a,b In the past, double-bond isomerization of the Heck
product had been attributed to high-temperature reaction
conditions, but Jeffery and David determined that use of
an appropriate catalytic system could direct selectivity of
the reaction.6d We have also found that the use of our
NHC-ligand–Pd-catalyst complex allowed for isolation of
the arylated vinylic ether as the sole product, and therefore
demonstrated that these are selective reaction conditions.
This selectivity may be due to the unsymmetrical nature
of palladium complex 5.
After ascertaining that 510 and K2CO3 were the best com-
bination of catalytic complex and base for reaction selec-
tivity, we then investigated the role of solvent and
temperature as shown in Table 2. In the cases of toluene,
benzene, and THF, the reactions were incomplete and the
yields were low (entries 2–4). However, in polar aprotic
solvent such as DMF, the desired product 8 was obtained
in 80% yield (entry 1). The isomeric side product 9 was
not detected at all in any of those cases. Independent of
bases, the cross-coupling reaction was not efficient at
Complex 5a
MeO
MeO
O
5 (5 mol%)
O
+
K2CO3, solvent
temp, 48 h
I
6
7
8
Entry
Solvent
DMF
Temp (°C)
100
Yield (%)b
1
2
3
4
5
6
80
34
51
16
41
10
toluene
benzene
THF
100
100
100
DMF
50
DMF
23
a All reactions were carried out with 4-iodoanisole (0.5 mmol), DHP
(6 mmol), K2CO3 (0.75 mmol), and 5 (5 mol%) in solvent (1 mL) un-
der argon atmosphere.
b Isolated yield.
Synlett 2009, No. 3, 482–486 © Thieme Stuttgart · New York

484
J. Jarusiewicz et al.
LETTER
Table 3 Effect of Aryl Halide on the Cross-Coupling Reactions
with DHP in the Presence of Pd–Ligand Complex 5a
Table 4 Effect of Aryl Halide on the Cross-Coupling Reactions
with DHP in the Presence of Pd–Ligand Complex 5a
R
O
R
O
R
5 (5 mol%)
5 (5 mol%)
O
+
O
R
+
K2CO3, DMF
100 °C, 48 h
K2CO3, DMF
100 °C, 48 h
a ortho
b meta
c para
I
X
8 (R = OMe)
10 (R = H)
7
7
Entry
R
X
I
Yield (%)b
Entry
1
R
Products
Yield (%)b
1
2
3
4
5
OMe
OMe
H
80
21
51
35
<5
Me
11a (71)
11b (75)
11c (62)
Me
O
Br
I
2
3
4
5
OMe
CF3
12a (62)
12b (58)
H
Br
Cl
MeO
F3C
O
H
a All reactions were carried out with aryl halide (0.5 mmol), DHP (6
mmol), K2CO3 (0.75 mmol), and 5 (5 mol%) in solvent (1 mL) under
argon atmosphere.
13 (15)
O
b Isolated yield.
CN
14b (15)
14c (trace)
bromides and aryl chlorides to Pd(0) is more difficult due
to the greater bond strengths of the Ph–X bond in aryl
bromides and aryl chlorides compared to that of aryl io-
dides.9
NC
O
COMe
15a (trace)
15c (16)
With the optimized conditions in hand, the functionality
of the halide as coupling partner was varied to investigate
the range of substrates.11 As shown in Table 4, cross-
coupling proceeded well with electron-donating and neu-
tral substrates (entries 1 and 2); reactions of ortho-, meta-,
and para-methyl or methoxy phenyl iodide with DHP
took place to provide the desired products 11a to 11c (62–
75%) and 12a to 12b (58–62%), respectively. However,
the reactions with trifluoromethyl, cyano, and acetyl phe-
nyl iodides (entries 3–5), substituted with an electron-
withdrawing group, showed little reactivity and removal
of unreacted starting material proved laborious and
caused low yields (<16%). Therefore, aryl iodides includ-
ing an electron-donating or neutral substituent proved to
be the best for the coupling reaction with DHP.
O
O
Me
a All reactions were carried out with aryliodine (0.5 mmol), DHP (6
mmol), K2CO3 (0.75 mmol), and 5 (5 mol%) in solvent (1 mL) under
argon atmosphere.
b Isolated yield.
Me
Me
I
O
5 (5 mol%)
O
O
+
+
K2CO3, DMF
150 °C, 48 h
Me
Me
7
16 (55%)
Also, the sterically hindered substrates reacted smoothly,
but for the most hindered aryl halide an increase in tem-
perature was necessary to drive the reaction to comple-
tion. As shown in Scheme 3, the coupling reaction of 2,6-
dimethyl iodobenzene with DHP at 150 °C for 48 hours
proceeded to give the corresponding cross-coupling com-
pound 16 in 55% yield. In addition, this methodology is
applicable for the use of nitrogen-containing heterocycles
as well, as demonstrated by the successful coupling of 3-
iodopyridine with DHP to afford the desired product 17 in
61% yield (Scheme 3). The application of this reaction is
important because heterocyclic compounds are building
blocks for natural products and biologically active target
molecules.
O
5 (5 mol%)
N
N
K2CO3, DMF
100 °C, 48 h
I
7
17 (61%)
Scheme 3 Coupling reaction with hindered and heterocyclic halides
In summary, we have synthesized an NHC-pyridinyl
ligand–palladium complex 5 that was successfully em-
ployed in regioselective Heck reactions with DHP. Syn-
thesis of the catalyst is efficient and it may be useful in
additional palladium-catalyzed reactions.
Acknowledgment
We acknowledge generous financial support from the National
Institute of General Medical Sciences of the National Institutes of
Health (RO1 GM 71495).
Synlett 2009, No. 3, 482–486 © Thieme Stuttgart · New York

LETTER
Heck Coupling Reactions of Aryl Halides and Dihydropyran
485
(10) General Procedure for the Synthesis of Palladium(II)
Complex 5
References and Notes
(1) (a) Bourissou, D.; Guerret, O.; Gabbai, F.; Bertrand, G.
Chem. Rev. 2000, 100, 39. (b) Herrmann, W. A. Angew.
Chem. Int. Ed. 2002, 41, 1290. (c) Perry, M. C.; Burgess, K.
Tetrahedron: Asymmetry 2003, 14, 951. (d) Cesar, V.;
Bellemin-Laponnaz, S.; Gade, L. H. Chem. Soc. Rev. 2004,
33, 619. (e) Sigman, M. S.; Jensen, A. D. Acc. Chem. Res.
2006, 39, 221. (f) Douthwaite, R. E. Coord. Chem. Rev.
2007, 251, 702. (g) Kantchev, E. A. B.; O’Brien, C. J.;
Organ, M. G. Angew. Chem. Int. Ed. 2007, 46, 2768.
(h) Gade, L. H.; Bellemin-Laponnaz, S. In Top. Organomet.
Chem., Vol. 21; Glorius, F., Ed.; Springer: Berlin, 2007,
117–157. (i) Arduengo, A. J. III; Harlow, R. L.; Kline, M.
J. Am. Chem. Soc. 1991, 113, 361. (j) Enders, D.; Breuer,
K.; Raabe, G.; Runsink, J.; Teles, J. H.; Melder, J. P.; Ebel,
K.; Brode, S. Angew. Chem., Int. Ed. Engl. 1995, 34, 1021.
(k) Herrmann, W. A.; Elison, M.; Fischer, J.; Kocher, C.;
Artus, G. R. J. Chem. Eur. J. 1996, 2, 772.
To a solution of 4 (0.6 mmol) in anhyd CH2Cl2 (20 mL) was
added Ag2O (0.3 mmol), and the reaction mixture was stirred
at r.t. for 4 h. The reaction mixture was then gravity filtered
and dried under nitrogen to obtain a silver complex as a
white solid. The silver complex (0.4 mmol) was then
suspended in a solution of MeCN (20 mL) in a foil-covered
round-bottom flask. To the reaction mixture was then added
Pd(OAc)2 (0.4 mmol), and the reaction mixture was stirred
at r.t. for 24 h. The reaction mixture was then gravity filtered,
and the filtrate was concentrated in vacuo to obtain 5 (100
mg, 38% over two steps) as an orange solid. 1H NMR (250
MHz, CDCl3): d = 8.98–9.02 (m, 1 H), 7.82–7.90 (m, 1 H),
7.59 (d, J = 10.0 Hz, 1 H), 7.49–7.55 (m, 1 H), 7.32–7.45 (m,
4 H), 5.96 (br s, 2 H), 4.06 (s, 3 H), 2.02 (s, 6 H). 13C NMR
(62.5 MHz, CDCl3): d = 178.1, 153.5, 153.4, 139.8, 134.5,
132.7, 125.0, 124.9, 124.4, 124.1, 110.9, 110.4, 51.40,
33.40, 22.60.
(2) (a) Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000,
100, 3009. (b) Peris, E.; Crabtree, R. H. Coord. Chem. Rev.
2004, 248, 2239. (c) Grasa, G. A.; Singh, R.; Stevens, E. D.;
Nolan, S. P. J. Organomet. Chem. 2003, 687, 269.
(d) Najera, C.; Gil-Molto, J.; Karlstrom, S.; Falvell, L. R.
Org. Lett. 2003, 5, 1451. (e) Chen, W.; Xi, C.; Wu, Y.
J. Organomet. Chem. 2007, 692, 4381. (f) Khramov, D. M.;
Rosen, E. L.; Joyce, A. V.; Vu, P. D.; Lynch, V. M.;
Bielawski, C. W. Tetrahedron 2008, 64, 6853. (g) Taige,
M. A.; Zeller, A.; Ahrens, S.; Goutal, S.; Herdtweck, E.;
Strassner, T. J. Organomet. Chem. 2007, 692, 1519.
(h) Chen, T.; Gao, J.; Shi, M. Tetrahedron 2006, 62, 6289.
(i) Xu, Q.; Duan, W.; Lei, Z.; Zhu, Z.; Shi, M. Tetrahedron
2005, 61, 11225.
(3) Crabtree, R. H. J. Organomet. Chem. 2006, 691, 3146.
(4) (a) Mizoroki, T.; Mori, K.; Ozaki, A. Bull. Chem. Soc. Jpn.
1971, 44, 581. (b) Heck, R. F.; Nolley, J. P. Jr. J. Org. Chem.
1972, 37, 2320. (c) de Meijere, A.; Meyer, F. E. Angew.
Chem., Int. Ed. Engl. 1994, 33, 2379. (d) Crisp, G. T. Chem.
Soc. Rev. 1998, 27, 427. (e) Beletskaya, I. P.; Cheprakov,
A. V. Chem. Rev. 2000, 100, 3009. (f) Jeffery, T. In
Advances in Metal-Organic Chemistry, Vol. 5; Liebeskind,
L. S., Ed.; JAI: London, 1996, 153–260. (g) Nicolaou, K.
C.; Sorensen, E. J. Classics in Total Synthesis; VCH: New
York, 1996, Chap. 31. (h) Link, J. T.; Overman, L. E. In
Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.;
Stang, P. J., Eds.; Wiley-VCH: New York, 1998, Chap. 6.
(5) (a) Shimizu, Y. Chem. Rev. 1993, 93, 1685. (b) Yasumoto,
T. Chem. Rec. 2001, 1, 228. (c) Conway, J. C.; Urch, C. J.;
Quayle, P.; Xu, J. Synlett 2006, 776.
(11) General Procedure for the Preparation of Substituted
Dihydropyrans
An oven-dried resealable Schlenk flask was evacuated and
filled with argon, then were added 4-iodoanisole (117 mg,
0.5 mmol), 3,4-dihydro-2H-pyran (0.55 mL, 6 mmol),
K2CO3 (104 mg, 0.75 mmol), DMF (1 mL), palladium
complex 5 (22 mg, 0.05 mmol). The reaction mixture was
stirred at 100 °C. After 48 h the solution was then allowed to
cool to r.t. EtOAc (20 mL) was added to the reaction
mixture, and then the reaction mixture was washed with H2O
(3 × 10 mL). The organic layer was dried over Na2SO4. After
filtration, solvent was evaporated and purified by column
chromatography (hexanes–EtOAc, 19:1), to afford 2-(4-
methoxy-phenyl)-3,4-dihydro-2H-pyran (76 mg, 80%) as a
light orange oil.
Compound 11a: yellow oil (62 mg, 71%). 1H NMR (250
MHz, CDCl3): d = 7.43 (m, 1 H), 7.17–7.26 (m, 3 H), 6.56
(d, J = 7.5 Hz, 1 H), 5.00 (dd, J = 10.0 Hz, 1 H), 4.80 (m,
1 H), 2.35 (s, 3 H), 2.20–2.32 (m, 2 H), 1.84–2.12 (m, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 144.7, 140.0, 134.6,
130.4, 127.5, 126.3, 125.6, 100.6, 74.37, 29.29, 20.93,
18.95. GC-MS: m/z calcd for C12H14O: 174.1; found: 173.9.
Anal. Calcd for C12H14O: C, 82.72; H, 8.10. Found: C, 82.56;
H, 8.12.
Compound 11b: yellow oil (65 mg, 75%). 1H NMR (250
MHz, CDCl3): d: = 7.45–7.48 (m, 1 H), 7.38–7.42 (m, 1 H),
7.31–7.35 (m, 1 H), 7.17–7.27 (m, 1 H), 6.61 (d, J = 7.5 Hz,
1 H), 4.87–4.89 (m, 1 H), 4.83–4.87 (m, 1 H), 2.44 (s, 3 H),
2.26–2.36 (m, 2 H), 1.96–2.16 (m, 2 H). 13C NMR (62.5
MHz, CDCl3): d = 144.1, 137.9, 128.5, 127.9, 126.5, 124.2,
122.9, 100.5, 77.06, 30.22, 21.35, 20.29. GC-MS m/z calcd
for C12H14O: 174.1; found: 174.0. Anal. Calcd for C12H14O:
C, 82.72; H, 8.10. Found: C, 82.69; H, 8.11
(6) (a) Arai, I.; Doyle Daves, G. J. Org. Chem. 1978, 44, 21.
(b) Andersson, C.; Hallberg, A.; Doyle Daves, G. J. Org.
Chem. 1987, 52, 3529. (c) Larock, R. C.; Gong, W. H.;
Baker, B. E. Tetrahedron Lett. 1989, 30, 2603.
Compound 11c: yellow oil (54 mg, 62%). 1H NMR (250
MHz, CDCl3): d = 7.48 (d, J = 10.0 Hz, 2 H), 7.22 (d,
J = 10.0 Hz, 2 H), 6.53 (d, J = 7.5 Hz, 1 H), 4.82 (m, 1 H),
4.77 (m, 1 H), 2.35 (s, 3 H), 2.13–2.25 (m, 2 H), 1.90–2.08
(m, 2 H). 13C NMR (62.5 MHz, CDCl3): d = 140.1, 137.0,
129.0, 128.9, 126.8, 125.9, 92.47, 77.50, 32.67, 22.49,
21.10. GC-MS: m/z calcd: 174.1; found: 174.0.
(d) Loiseleur, O.; Hayashi, M.; Schmees, N.; Pfaltz, A.
Synthesis 1997, 1338. (e) Jeffery, T.; David, M.
Tetrahedron Lett. 1998, 39, 5751. (f) Dupont, J.; Gruber,
A. S.; Fonseca, G. S.; Monteiro, A. L.; Ebeling, G.
Organometallics 2001, 20, 171.
(7) Barczak, N. T.; Grote, R. E.; Jarvo, E. R. Organometallics
2007, 26, 4863.
(8) When using a combination of Pd(OAc)2 and 1,10-phenan-
throline or 2,9-dimethylphenanthroline, the catalyst and
ligand were premixed in DMF at r.t. for 30 min before the
addition of substrates.
Compound 12a: yellow oil (59 mg, 62%). 1H NMR (250
MHz, CDCl3): d = 7.43 (d, J = 10.0 Hz, 1 H), 7.22–7.35 (m,
1 H), 6.98 (t, J = 7.5 Hz, 1 H), 6.88 (d, J = 7.5 Hz, 1 H), 6.66
(d, J = 7.5 Hz, 1 H), 5.21 (d, J = 7.5 Hz, 1 H), 4.74–4.80 (m,
1 H), 3.84 (s, 3 H), 1.94–2.30 (m, 2 H), 1.72–1.88 (m, 2 H).
13C NMR (62.5 MHz, CDCl3): d = 158.1, 144.5, 128.1,
128.0, 126.4, 122.5, 111.0, 100.6, 72.47, 56.26, 29.58,
20.50. GC-MS: m/z calcd for C12H14O2: 190.1; found: 190.0.
(9) Littke, A. F.; Fu, G. C. Angew. Chem. Int. Ed. 2002, 41,
4176.
Synlett 2009, No. 3, 482–486 © Thieme Stuttgart · New York

486
J. Jarusiewicz et al.
LETTER
Anal. Calcd for C12H14O2: C, 75.76; H, 7.42. Found: C,
75.71; H, 7.48.
75.11, 26.03, 20.80, 20.51. GC-MS: m/z calcd for C13H16O:
188.1; found: 188.0. Anal. Calcd for C13H16O: C, 82.94; H,
8.57. Found: C, 82.89; H, 8.59.
Compound 13: yellow oil (17 mg, 15%). 1H NMR (250
MHz, CDCl3): d = 7.62 (d, J = 10.0 Hz, 2 H), 7.47 (d,
J = 10.0 Hz, 2 H), 6.54 (d, J = 7.5 Hz, 1 H), 4.90 (d, J = 7.5
Hz, 1 H), 4.75–4.84 (m, 1 H), 1.65–2.15 (m, 2 H), 1.55–1.64
(m, 2 H). GC-MS: m/z calcd: 230.1; found: 229.7.
Compound 16: orange oil (52 mg, 55%). 1H NMR (250
MHz, CDCl3): d = 6.98–7.11 (m, 3 H), 6.51 (d, J = 7.5 Hz, 1
H), 5.20 (d, J = 10.0 Hz, 1 H), 4.76–4.82 (m, 1 H), 2.39 (s, 6
H), 2.02–2.30 (m, 2 H), 1.80–1.94 (m, 2 H). 13C NMR (62.5
MHz, CDCl3): d = 143.9, 137.1, 136.0, 129.2, 127.2, 100.2,
Compound 17: a yellow oil (49 mg, 61%). 1H NMR (250
MHz, CDCl3): d = 8.61 (s, 1 H), 8.53–8.57 (m, 1 H), 7.67–
7.73 (m, 1 H), 7.27–7.33 (m, 1 H), 6.53 (d, J = 7.5 Hz, 1 H),
4.88 (d, J = 10.0 Hz, 1 H), 4.78–4.84 (m, 1 H), 2.18–2.30 (m,
2 H), 1.88–2.14 (m, 2 H). 13C NMR (62.5 MHz, CDCl3): d =
149.1, 147.8, 143.9, 133.6, 123.4, 101.0, 74.82, 30.14,
20.02. GC-MS: m/z calcd for C10H11NO: 161.1; found:
161.0. Anal. Calcd for C10H11NO: C, 74.51; H, 6.88; N, 8.69.
Found: C, 74.39; H, 6.91; N, 8.61.
Synlett 2009, No. 3, 482–486 © Thieme Stuttgart · New York

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