Alkylative cyclization of 1,6-enynes in water with an amphiphilic resin-supported palladium catalyst

Article abstract of DOI:10.1055/s-2006-951498

An alkylative cyclization of a 1,6-enyne with aryl halides was performed with an amphiphilic polystyrene-poly(ethylene glycol) (PS-PEG) resin supported phosphine-palladium complex in water under heterogeneous conditions to give benzylidenecyclohexenes in

Full text of DOI:10.1055/s-2006-951498

LETTER
3065
Alkylative Cyclization of 1,6-Enynes in Water with an Amphiphilic
Resin-Supported Palladium Catalyst
A
Y
lkylative Cycliz
a
a
tion of 1,6-
s
Enynes in
u
Water shi Nakai, Tsutomu Kimura, Yasuhiro Uozumi*
Institute for Molecular Science, The Graduate University for Advanced Studies, CREST, Higashiyama 5-1, Myodaiji, Okazaki 444-8787,
Japan
Fax +81(564)595574; E-mail: uo@ims.ac.jp
Received 11 April 2006
Dedicated to Professor Richard Heck in honor of his scientific achievements
Abstract: An alkylative cyclization of a 1,6-enyne with aryl halides
was performed with an amphiphilic polystyrene-poly(ethylene gly-
col) (PS-PEG) resin supported phosphine–palladium complex in
water under heterogeneous conditions to give benzylidenecyclo-
hexenes in good to high yields, which proceeds via formation of a
vinylpalladium intermediate and subsequent intramolecular Heck
reaction. The polymeric palladium catalyst can be readily recovered
and recycled.
PdX
R
H
β-hydride
elimination
R
6-endo-insertion
(R = Ar)
Key words: cyclization, 1,6-enyne, aqueous media, polymer sup-
port, palladium catalyst
alkyne
insertion
±HX
Pd0
ArX
PdX
X–Pd–H
X–Pd–Ar
Transition-metal-catalyzed carbocyclization of enynes of-
fers a powerful means to construct a variety of syntheti-
cally useful carbo- and heterocycles. Palladium-
R
1
5
-exo-insertion
catalyzed alkylative cyclization of 1,6-enynes with aryl
β-hydride
elimination
(R = H)
halides produces cyclohexenes bearing exocyclic olefins
PdX
2
H
[
Scheme 1, (1)]. We have recently developed amphi-
philic polystyrene-poly(ethylene glycol) (PS-PEG) resin
H
supported transition-metal catalysts which promote vari-
3
ous catalytic transformations smoothly in water under
4
,5
heterogeneous conditions to meet the requirements of
safe, green, and high-throughput chemical processes.6–8
Thus, for example, p-allylic substitution, the cross-cou-
pling reaction, and the Heck reaction have all been
Scheme 2
achieved in water with palladium complexes immobilized by coordination with a phosphine ligand anchored on an
amphiphilic PS-PEG resin.
alkylative cyclization
As part of our effort to develop wide utility of this hetero-
geneous aquacatalytic system, we decided to examine the
Ar
[
Pd]
(
1)
palladium-catalyzed alkylative cyclization of 1,6-enynes.
We wish to report here the preliminary results on the het-
erogeneous aquacatalytic alkylative cyclization of a 1,6-
enyne with aryl halides, which is catalyzed by 5 mol%
palladium of the PS-PEG resin supported palladium–
phosphine complex.
+
Ar–X
(
–HX)
cycloisomerization
[
Pd]
(
2)
3)
5
HX
We have previously reported that the Heck reaction as
6e
well as cycloisomerization of 1,6-enynes took place in
water with PS-PEG resin supported palladium–phosphine
complexes [Scheme 1, (2) and (3)]. The reaction pathway
of the Heck reaction must include the formation of Ar–
PdX and alkene insertion into the Ar–Pd bond. The cy-
cloisomerization should proceed via the alkyne insertion
to the H–PdX species generated in situ and the intramo-
lecular Heck reaction of the resulting alkenylpalladium
intermediate in a 5-exo fashion [Scheme 2 (bottom-half)].
These successful results with the Heck reaction as well as
with the cycloisomerization made us realize that alkyla-
Heck reaction
Ar
[
Pd]
(
+
Ar–X
(
–HX)
Scheme 1
SYNLETT 2006, No. 18, pp 3065–3068
Advanced online publication: 25.10.2006
DOI: 10.1055/s-2006-951498; Art ID: S06706ST
Georg Thieme Verlag Stuttgart · New York
0
3
.1
1
.2
0
0
6
©

3
066
Y. Nakai et al.
LETTER
tive cyclization of 1,6-enynes with aryl halides might also
be promoted by an amphiphilic PS-PEG resin supported
palladium catalyst in water via Ar–PdX formation, alkyne
insertion to form an alkenylpalladium intermediate, and
the intramolecular Heck reaction [Scheme 2 (top-half)].
Pd
4
E
E
(5 mol% Pd)
+ I
NaHCO3, H2O
3a
reflux, 90 min
E
82%
1
2a
We have examined several amphiphilic polymer-support-
ed palladium–phosphine complexes and bases for the
alkylative cyclization of diethyl allyl(propargyl)malonate
E
(
E = COOEt)
O
C
(
1) and iodobenzene (2a). It was found that the combina-
PS
O
O
N
H
PPh2 + Pd (dba) ·CHCl
tion of the PS-PEG resin supported bisphosphine–palladi-
n
2
3
3
9
um complex 4, sodium bicarbonate, and water is essential
φ = 90 µm, P-loading = 0.22 mmol/g
to construct an efficient catalyst system for the water-
based alkylative cyclization. Thus, when a suspension of
diethyl 1 and 2a in water was refluxed for 90 minutes in
the presence of 5 mol equivalents of sodium bicarbonate
and 5 mol% palladium of PS-PEG resin supported bis-
Ph
O
O
C
Ph2
P
O
O
O
O
N
H
n
n
Pd
4
PS
6
e
Pd
Ph
phosphine–palladium complex 4, which was prepared
from PS-PEG phosphine and tris(dibenzylideneace-
tone)dipalladium (P/Pd = 2:1), it afforded an 82% yield of
H
N
C
O
P
Ph2
4
3
-benzylidenecyclohexene 3a (Scheme 3). The selectivity
for the cyclization product is strongly affected by the base Scheme 3
and the solvent used. Thus, with triethylamine in water,
the reaction of 1 and 2a gave the Sonogashira product,
phenylalkyne 5a, in 84% yield exclusively (Scheme 4).10
Pd
4
Using a homogeneous Pd (dba) –PPh catalyst system in
2
3
3
(
5 mol% Pd)
E
E
toluene, the reaction with sodium bicarbonate resulted in
no product and the one with triethylamine gave the cy-
clized product 3a in 64% yield. The alkylative cyclization
and the Sonogashira coupling should proceed by way of a
neutral side-on alkyne complex (A) and an anionic endo-
on alkyne complex (B), respectively. An aqueous solution
of a strong organic base (Et N in H O at 18 °C: pK @ 3.0)
1 + 2a
Et3N, H2O, reflux, 90 min
5a
84%
Pd2(dba)3, PPh3
5 mol% Pd, Pd/P = 1:2)
(
no reaction
1 + 2a
NaHCO3, toluene, reflux, 90 min
3
2
b
should promote the formation of the intermediate B,
whereas, in general, the Sonogashira coupling hardly pro-
ceeds in the absence of a Cu(I) species.
Pd2(dba)3, PPh3
(5 mol% Pd, Pd/P = 1:2)
3a 64%, 5a 0%
1
+ 2a
Et3N, toluene, reflux, 90 min
R
Scheme 4
R
Ln(X) Pd Ar
A: neutral side-on
Figure 1
Lm Pd Ar
and electron-deficient aryl iodides 2e and 2f under similar
conditions to give 63% and 77% yields of 3e and 3f [un-
optimized results; Scheme 5, (4) and (5)]. The reaction of
B: anionic endo-on
1
with bromobenzene (2a¢) proceeded smoothly in reflux-
ing water to afford 80% isolated yield of 3a [Scheme 5,
–
Use of sodium bicarbonate as a weak base in water ( HCO3 (6)]. Recycling experiments were examined for the alky-
in H O at 20 °C: pK @ 7.6) is essential to promote the ini- lative cyclization of 1 with 2a [Scheme 5, (7)]. After the
2
b
tial alkyne insertion prior to forming the vinylpalladium first use of the polymeric palladium catalyst 4 to give 82%
intermediate via the p-alkyne–palladium complex A.
yield of cyclohexene 3a, the recovered catalyst beads
were taken on to two subsequent reuses and exhibited sta-
ble catalytic activity (2nd use: 80%, 3rd use: 81%).1
Scheme 5 shows that various aryl halides undergo alkyla-
tive cyclization in water to give the benzylidene cyclo-
1,12
hexenes bearing substituted aromatic groups. Thus, 1,6- In summary, we have developed an alkylative cyclization
enyne 1 reacted with o-, m-, and p-tolyl iodides (2b–d) to of a 1,6-enyne with aryl halides using a PS-PEG resin sup-
give the 2-, 3-, and 4-methyl products 3b, 3c, and 3d in ported palladium catalyst to give alkylidene cyclo-
6
5%, 84%, and 80% yields, respectively [unoptimized re- hexenes. Simple starting materials, a readily recyclable
sults; Scheme 5, (1), (2), and (3)], whereas an ortho-sub- catalyst, and aqueous conditions should make the present
stituent somewhat lowered the yield of the cyclized method highly useful from a synthetic as well as a green
product 3b presumably due to steric hindrance. The alky- chemical point of view.
lative cyclization also took place with both electron-rich
Synlett 2006, No. 18, 3065–3068 © Thieme Stuttgart · New York

LETTER
Alkylative Cyclization of 1,6-Enynes in Water
3) For reviews on aqueous-switching of organic
3067
(
Pd
4
transformations, see: (a) Li, C.-J.; Chan, T.-H. Organic
Reactions in Aqueous Media; Wiley-VCH: New York,
(1)
H3C
E
(5 mol% Pd)
H3C
1997. (b) Grieco, P. A. Organic Synthesis in Water; Kluwer
+
I
Academic Publishers: Dordrecht, 1997. (c) Herrmann, W.
A.; Kohlpaintner, C. W. Angew. Chem., Int. Ed. Engl. 1993,
32, 1524. (d) Lindström, U. M. Chem. Rev. 2002, 102, 2751.
NaHCO3, H2O
E
3
b
reflux, 90 min
1
2b
E
65%
E
(4) For reviews on heterogeneous-switching of organic
transformations, see: (a) Bailey, D. C.; Langer, S. H. Chem.
Rev. 1981, 81, 109. (b) Shuttleworth, S. J.; Allin, S. M.;
Sharma, P. K. Synthesis 1997, 1217. (c) Shuttleworth, S. J.;
Allin, S. M.; Wilson, R. D.; Nasturica, D. Synthesis 2000,
1035. (d) Dörwald, F. Z. Organic Synthesis on Solid Phase;
Wiley-VCH: Weinheim, 2000. (e) Leadbeater, N. E.;
Marco, M. Chem. Rev. 2002, 102, 3217. (f) McNamara, C.
A.; Dixon, M. J.; Bradley, M. Chem. Rev. 2002, 102, 3275.
H3C
CH3
(2)
+
I
3
c
2
c
E
84%
E
CH3
(
g) Chiral Catalyst Immobilization and Recycling; De Vos,
(
3)
+
D. E.; Vankelecom, I. F. J.; Jacobs, P. A., Eds.; Wiley-VCH:
Weinheim, 2000. (h) Fan, Q.-H.; Li, Y.-M.; Chan, A. S. C.
Chem. Rev. 2002, 102, 3385. (i) Ley, S. V.; Baxendale, I.
R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom,
D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J. J.
Chem. Soc., Perkin Trans. 1 2000, 3815. (j) Immobilized
Catalysts, In Topics in Current Chemistry, Vol. 242;
Kirschning, A., Ed.; Springer: Berlin/Heidelberg, 2004.
5) For a recent review of solid-phase reactions using palladium
catalysts, see: (a) Uozumi, Y.; Hayashi, T. Solid-Phase
Palladium Catalysis for High-Throughput Organic
Synthesis, In Handbook of Combinatorial Chemistry;
Nicolaou, K. C.; Hanko, R.; Hartwig, W., Eds.; Wiley-VCH:
Weinheim, 2002, Chap. 19. (b) Uozumi, Y. Top. Curr.
Chem. 2004, 242, 77.
6) For studies on organic transformations with polymer-
supported complex catalysts in water, see: (a) Uozumi, Y.;
Danjo, H.; Hayashi, T. Tetrahedron Lett. 1997, 38, 3557; p-
allylic substitution. (b) Danjo, H.; Tanaka, D.; Hayashi, T.;
Uozumi, Y. Tetrahedron 1999, 55, 14341; p-allylic
substitution. (c) Uozumi, Y.; Danjo, H.; Hayashi, T. J. Org.
Chem. 1999, 64, 3384; cross-coupling. (d) Uozumi, Y.;
Watanabe, T. J. Org. Chem. 1999, 64, 6921; carbonylation
reaction. (e) Shibatomi, K.; Nakahashi, T.; Uozumi, Y.
Synlett 2000, 1643. (f) Uozumi, Y.; Nakai, Y. Org. Lett.
I
CH3
3
d
2
d
E
80%
E
OCH3
(
4)
+
+
I
I
OCH3
(
(
3e
2e
E
E
63%
E
E
CF3
(5)
CF3
3f
2f
77%
(6)
+
Br
3a
2
a'
E
80%
E
2002, 4, 2997; Suzuki–Miyaura coupling. (g) Uozumi, Y.;
Kimura, T. Synlett 2002, 2045; Heck reaction. (h) Uozumi,
Y.; Nakazono, M. Adv. Synth. Catal. 2002, 344, 274.
(i) Uozumi, Y.; Kobayashi, Y. Heterocycles 2003, 59, 71;
Sonogashira reaction. (j) Uozumi, Y.; Kikuchi, M. Synlett
1
st use: 82% yield
2nd use: 80% yield
rd use: 81% yield
(
7)
1
+
2a
3a
3
Scheme 5
2005, 1775; Suzuki–Miyaura coupling.
(
7) For examples of chiral processes with polymer-supported
catalysts in water, see: (a) Uozumi, Y.; Danjo, H.; Hayashi,
T. Tetrahedron Lett. 1998, 39, 8303. (b) Hocke, H.;
Uozumi, Y. Synlett 2002, 2049. (c) Hocke, H.; Uozumi, Y.
Tetrahedron 2003, 59, 619. (d) Hocke, H.; Uozumi, Y.
Tetrahedron 2004, 60, 9297. (e) Nakai, Y.; Uozumi, Y.
Org. Lett. 2005, 7, 291. (f) Uozumi, Y.; Shibatomi, K. J.
Am. Chem. Soc. 2001, 123, 2919. (g) Shibatomi, K.;
Uozumi, Y. Tetrahedron: Asymmetry 2002, 13, 1769.
Acknowledgment
This work was supported by the CREST program, sponsored by the
JST. We also thank the JSPS (GRANT-in-AID for Scientific Rese-
arch, No.15205015) and the MEXT (Scientific Research on Priority
Areas, No. 420) for partial financial support of this work.
(
6
h) Uozumi, Y.; Tanaka, H.; Shibatomi, K. Org. Lett. 2004,
, 281. (i) Uozumi, Y.; Kimura, M. Tetrahedron:
Asymmetry 2006, 17, 161.
References and Notes
(1) For a recent review, see: Aubert, C.; Buisine, O.; Malacria,
M. Chem. Rev. 2002, 102, 813.
(8) For studies on organic transformations with polymer-
supported nano metal catalysts in water, see: (a) Uozumi,
Y.; Nakao, R. Angew. Chem. Int. Ed. 2003, 42, 194.
(b) Uozumi, Y.; Nakao, R. Angew. Chem. 2003, 115, 204.
(
2) (a) Trost, B. M.; Dumas, J. Tetrahedron Lett. 1993, 34, 19.
(
9
b) Trost, B. M.; Dumas, J. J. Am. Chem. Soc. 1992, 114,
836.
(
(
c) Nakao, R.; Rhee, H.; Uozumi, Y. Org. Lett. 2005, 7, 163.
d) Yamada, Y. M. A.; Uozumi, Y. Org. Lett. 2006, 8, 1375.
Synlett 2006, No. 18, 3065–3068 © Thieme Stuttgart · New York

3
068
Y. Nakai et al.
LETTER
(
9) TentaGel NH (F = 90 mm, loading value = 0.3 mmol/g)
CH=CHCH ), 6.20 (d, J = 9.5 Hz, 1 H, CH=CHCH ), 6.37
2
2
2
was used as a starting polymer support.
(s, 1 H, ArCH=C), 7.03 (d, J = 7.7 Hz, 1 H, ArH), 7.11 (s, 1
H, ArH), 7.13 (d, J = 7.7 Hz, 1 H, ArH), 7.23 (t, J = 7.7 Hz,
(
10) For reviews on cross-coupling catalysis, see: (a) Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F.; Stang,
P. J., Eds.; Wiley-VCH: Weinheim, 1998. (b) Cross-
Coupling Reactions: A Practical Guide, In Topics in
Current Chemistry, Vol. 219; Miyaura, N., Ed.; Springer:
Berlin/Heidelberg, 2002. (c) Special Issue – 30 Years of
Cross-Coupling Reaction, J. Organomet. Chem., Vol. 653;
Tamao, K.; Negishi, E.-i.; Hiyama, T., Eds.; Elsevier:
Amsterdam, 2002.
1
3
1 H, ArH). C NMR (125 MHz, CDCl ): d = 13.9
3
(CH CH ), 21.4 (CH ), 31.2 (CH ), 31.5 (CH ), 54.0
2
3
3
2
2
(CH CCH ), 61.4 (OCH ), 125.5 (Ar), 126.0 (CH=CHCH ),
2
2
2
2
127.4 (Ar), 128.0 (Ar), 129.0 (ArCH=C), 129.7 (Ar), 131.1
(CH=CHCH ), 132.8 (ArCH=C), 137.0 (Ar), 137.6 (Ar),
2
+
171.0 (C=O). MS: m/z = 328 [M ], 255, 225, 181, 165.
HRMS: m/z calcd for C H O : 344.1624; found: 344.1620.
2
0
24
5
Diethyl (Z)-5-[(4-Methylphenyl)methylene]-3-
(
11) General Procedure for Alkylative Cyclization of 1,6-
Enyne 1 with Aryl Halides.
cyclohexene-1,1-dicarboxylate (3d).
1
H NMR (500 MHz, CDCl ): d = 1.15 (t, J = 7.0 Hz, 6 H,
3
A mixture of 1 (95 mg, 0.4 mmol), the aryl halide 2 (0.4
mmol), 5 mol% palladium of 4 (90 mg, 20 mmol Pd), 170 mg
of NaHCO (2.0 mmol), and 4 mL of H O was refluxed for 90
CH CH ), 2.34 (s, 3 H, CH ), 2.74 (dd, J = 1.8, 4.5 Hz, 2 H,
2
3
3
CH=CHCH ), 3.15 (d, J = 1.8 Hz, 2 H, CH=CCH ), 4.08–
2
2
4.18 (m, 4 H, OCH ), 5.80 (td, J = 4.5, 9.8 Hz, 1 H,
3
2
2
min. After it was cooled, the mixture was filtered and the
collected resin beads were extracted by washing with
EtOAc. The washing was concentrated in vacuo to give the
alkylative cyclized product 3. An analytically pure product
was isolated by silica gel chromatography. Spectroscopic
data of new compounds are given below.
CH=CHCH ), 6.20 (d, J = 9.8 Hz, 1 H, CH=CHCH ), 6.37
2
2
(s, 1 H, ArCH=C), 7.14 (d, J = 7.9 Hz, 2 H, ArH), 7.21 (d,
1
3
J = 7.9 Hz, 2 H, ArH). C NMR (125 MHz, CDCl ): d =
3
13.9 (CH CH ), 21.2 (CH ), 31.2 (CH ), 31.5 (CH ), 53.9
2
3
3
2
2
(CH CCH ), 61.4 (OCH ), 125.3 (CH=CHCH ), 128.85,
2
2
2
2
128.87 (3 C, 2 Ar, ArCH=C), 131.1 (CH=CHCH ), 132.3
2
Diethyl (Z)-5-(Phenylmethylene)-3-cyclohexene-1,1-
(ArCH=C), 134.2 (Ar), 136.3 (Ar), 171.0 (C=O). MS: m/z =
328 [M ], 255, 225, 181, 165. HRMS: m/z calcd for
+
dicarboxylate (3a).
1
H NMR (500 MHz, CDCl ): d = 1.15 (t, J = 7.0 Hz, 6 H,
C H O : 328.1675; found: 328.1673.
3
20 24
4
CH ), 2.75 (dd, J = 1.8, 4.3 Hz, 2 H, CH=CHCH ), 3.16 (d,
Diethyl (Z)-5-[(4-Methoxyphenyl)methylene]-3-
3
2
J = 1.2 Hz, 2 H, CH=CCH ), 4.08–4.19 (m, 4 H, OCH ),
cyclohexene-1,1-dicarboxylate (3e).
2
2
1
5
9
7
.83 (td, J = 4.3, 9.5 Hz, 1 H, CH=CHCH ), 6.21 (td, J = 1.8,
H NMR (500 MHz, CDCl ): d = 1.16 (t, J = 7.3 Hz, 6 H,
2
3
.5 Hz, 1 H, CH=CHCH ), 6.41 (s, 1 H, ArCH=C), 7.20–
CH CH ), 2.74 (dd, J = 1.8, 4.3 Hz, 2 H, CH=CHCH ), 3.14
2
2
3
2
1
3
.23 (m, 1 H, ArH), 7.31–7.35 (m, 4 H, ArH). C NMR (125
(d, J = 1.8 Hz, 2 H, CH=CCH ), 3.82 (s, 3 H, OCH ), 4.08–
2
3
MHz, CDCl ): d = 13.9 (CH ), 31.2 (CH ), 31.5 (CH ), 54.0
4.19 (m, 4 H, OCH ), 5.78 (td, J = 4.3, 9.5 Hz, 1 H,
3
3
2
2
2
(
CH CCH ), 61.5 (OCH ), 125.8 (CH=CHCH ), 126.6 (Ar),
CH=CHCH ), 6.19 (td, J = 1.8, 9.5 Hz, 1 H, CH=CHCH ),
2
2
2
2
2
2
1
28.2 (Ar), 128.89 (ArCH=C), 128.93 (Ar), 131.0
6.34 (s, 1 H, ArCH=C), 6.88 (d, J = 8.6 Hz, 2 H, ArH), 7.26
1
3
(CH=CHCH ), 132.9 (ArCH=C), 137.0 (Ar), 171.0 (C=O).
(d, J = 8.6 Hz, 2 H, ArH). C NMR (125 MHz, CDCl ): d =
2
3
+
MS: m/z = 314 [M ], 241, 211, 167. HRMS: m/z calcd for
13.9 (CH CH ), 31.2 (CH ), 31.5 (CH ), 53.9 (CH CCH ),
2
3
2
2
2
2
C H O : 314.1518; found: 314.1507.
55.2 (OCH ), 61.4 (OCH ), 113.7 (Ar), 124.9 (CH=CHCH ),
19
22
4
3
2
2
Diethyl (Z)-5-[(2-Methylphenyl)methylene]-3-
128.5 (ArCH=C), 129.7 (Ar), 130.2 (Ar), 131.2
cyclohexene-1,1-dicarboxylate (3b).
(CH=CHCH ), 131.5 (ArCH=C), 158.3 (Ar), 171.0 (C=O).
MS: m/z = 344 [M ], 270, 241, 197. HRMS: m/z calcd for
2
1
+
H NMR (500 MHz, CDCl ): d = 1.16 (t, J = 7.1 Hz, 6 H,
3
CH CH ), 2.23 (s, 3 H, CH ), 2.74 (dd, J = 1.5, 4.2 Hz, 2 H,
C H O : 328.1675; found: 328.1689.
2
3
3
20 24
4
CH=CHCH ), 2.98 (d, J = 1.8 Hz, 2 H, CH=CCH ), 4.12 (q,
Diethyl (Z)-5-[(4-Trifluoromethylphenyl)methylene]-3-
2
2
J = 7.1 Hz, 4 H, OCH ), 5.83 (td, J = 4.2, 9.5 Hz, 1 H,
cyclohexene-1,1-dicarboxylate (3f).
2
1
CH=CHCH ), 6.26 (td, J = 1.8, 9.5 Hz, 1 H, CH=CHCH ),
H NMR (500 MHz, CDCl ): d = 1.16 (t, J = 7.0 Hz, 6 H,
2
2
3
6
.41 (s, 1 H, ArCH=C), 7.13–7.19 (m, 3 H, ArH), 7.25–7.27
CH ), 2.78 (dd, J = 1.5, 4.0 Hz, 2 H, CH=CHCH ), 3.12 (d,
3
2
1
3
(m, 1 H, ArH). C NMR (125 MHz, CDCl ): d = 13.9
J = 1.8 Hz, 2 H, CH=CCH ), 4.09–4.19 (m, 4 H, OCH ),
3
2
2
(CH CH ), 19.9 (CH ), 31.39 (CH ), 31.41 (CH ), 54.0
5.90 (td, J = 4.0, 9.3 Hz, 1 H, CH=CHCH ), 6.22 (td, J = 1.8,
2
3
3
2
2
2
(
1
CH CCH ), 61.4 (OCH ), 125.4 (CH=CHCH ), 125.6 (Ar),
26.9 (Ar), 127.9 (ArCH=C), 129.0 (Ar), 129.7 (Ar), 130.7
9.3 Hz, 1 H, CH=CHCH ), 6.41 (s, 1 H, ArCH=C), 7.42 (d,
2
2
2
2
2
1
3
J = 8.5 Hz, 2 H, ArH), 7.59 (d, J = 8.5 Hz, 2 H, ArH).
C
(
1
CH=CHCH ), 132.8 (ArCH=C), 136.0 (Ar), 136.5 (Ar),
71.0 (C=O). MS: m/z = 328 [M ], 255, 225, 181, 165.
NMR (125 MHz, CDCl ): d = 13.9 (CH ), 31.3 (CH ), 31.5
2
3
3
2
+
2
(CH ), 53.9 (CH CCH ), 61.6 (OCH ), 125.2 (2 C, q, J
=
2
2
2
2
C–F
HRMS: m/z calcd for C H F O : 382.1392; found:
3.8 Hz, 2 Ar), 127.26 (CH=CHCH or ArCH=C), 127.31
2
0
21
3
4
2
1
382.1374.
(CH=CHCH or ArCH=C), 128.5 (q, J = 32.4 Hz, CF3),
2 C–F
Diethyl (Z)-5-[(3-Methylphenyl)methylene]-3-
129.1 (Ar), 130.7 (CH=CHCH ), 135.0 (ArCH=C), 140.7
(Ar), 171.0 (C=O). MS: m/z = 382 [M ], 363, 309, 279, 235,
2
+
cyclohexene-1,1-dicarboxylate (3c).
1
H NMR (500 MHz, CDCl ): d = 1.16 (t, J = 6.7 Hz, 6 H,
165. HRMS: m/z calcd for C H O : 328.1675; found:
3
20 24
4
CH CH ), 2.35 (s, 3 H, CH ), 2.75 (dd, J = 1.8, 4.5 Hz, 2 H,
328.1688.
2
3
3
CH=CHCH ), 3.15 (d, J = 1.8 Hz, 2 H, CH=CCH ), 4.10–
(12) Davis, I. W.; Matty, L.; Hughes, D. L.; Reider, P. J. J. Am.
Chem. Soc. 2001, 123, 10139.
2
2
4
.18 (m, 4 H, OCH ), 5.81 (td, J = 4.5, 9.5 Hz, 1 H,
2
Synlett 2006, No. 18, 3065–3068 © Thieme Stuttgart · New York