Ruthenium catalyzed enyne cycloisomerizations and hydroxycyclizations with skeletal rearrangement

Article abstract of DOI:10.1016/j.jorganchem.2006.01.009

A neutral arene-tethered ruthenium complex was found to be a catalyst precursor for enyne cycloisomerizations and hydroxycyclizations. The observed products were the result of a skeletal rearrangement process, and include an unusual cyclization to form a six-membered ring. Labeling studies on the six-membered ring product are in accord with an electrophilic activation mechanism that proceeds via cationic cyclopropyl carbene intermediates.

Full text of DOI:10.1016/j.jorganchem.2006.01.009

Journal of Organometallic Chemistry 691 (2006) 1912–1918
www.elsevier.com/locate/jorganchem
Ruthenium catalyzed enyne cycloisomerizations
and hydroxycyclizations with skeletal rearrangement
*
J.W. Faller , Philip P. Fontaine
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, CT 06520-8107, United States
Received 15 December 2005; accepted 5 January 2006
Available online 3 March 2006
Abstract
A neutral arene-tethered ruthenium complex was found to be a catalyst precursor for enyne cycloisomerizations and hydroxycycli-
zations. The observed products were the result of a skeletal rearrangement process, and include an unusual cyclization to form a six-
membered ring. Labeling studies on the six-membered ring product are in accord with an electrophilic activation mechanism that
proceeds via cationic cyclopropyl carbene intermediates.
ꢀ 2006 Elsevier B.V. All rights reserved.
Keywords: Carbene; Cycloisomerization; Enyne
1. Introduction
2. Results and discussion
Transition-metal catalyzed cycloisomerizations of 1,6-
enynes have received much attention in recent years, and
there are now a wide range of catalysts that can mediate
these reactions [1–3]. Most involve the formation of a
metallacycle, a p-allyl complex, or a vinyl–metal complex,
and generally tend to produce five-membered rings of
various types (I–III) as shown in Fig. 1 [1].
When the cyclizations were performed in anhydrous
CH2Cl2, two classes of compounds were produced: five-
membered ring skeletally rearranged products (type III)
and six-membered rings (type IV). When undried THF
was used as the solvent, hydroxycyclized products were
observed (type V), presumably owing to the incorporation
of adventitious water in the solvent (see Table 1).
Products of type IV, although they have been observed
occasionally, are much less common [4–7]. In addition,
there are several catalysts which, in the presence of water
or alcohol, give rise to products of type V [8–10].
We have found that the planar chiral arene-tethered
ruthenium complex that has been recently synthesized
and resolved in our laboratory is a catalyst precursor for
the cycloisomerization of 1,6-enynes [11,12]. Addition of
two molar equivalents of AgSbF6 results in the active spe-
cies, which was observed to yield products of types III, IV,
and V depending on the substrate and reaction conditions
as shown in Fig. 2.
Terminal alkyl substitution on the olefin moiety favored
the cyclization to form the six-membered ring under anhy-
drous conditions (entries 1 and 2). Enyne substrates with
di- and trialkyl-substituted olefins both selectively formed
4a and 4b, respectively, although the trisubstituted enyne
was cyclized more selectively. The reaction of 2a in undried
THF resulted in the selective formation of the hydroxyl-
ated product 5a, and no traces of 3a or 4a were observed.
Instead, a small amount (4%) of the common Alder-ene
product (type I) was observed. The use of enantiopure cat-
alyst resulted in an enantioenriched product, although the
selectivity was low (23% ee) [13]. Generally the desired
products in these reactions are not chiral and enantiopure
catalysts would not be needed. In this case, however, the
observation of non-racemic products serves to demonstrate
that the chiral ruthenium complex is involved in the catal-
*
Corresponding author. Fax: +1 203 432 6144.
E-mail address: jack.faller@yale.edu (J.W. Faller).
0022-328X/$ - see front matter ꢀ 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2006.01.009

J.W. Faller, P.P. Fontaine / Journal of Organometallic Chemistry 691 (2006) 1912–1918
1913
Table 1
X
X
Catalytic results
R
R
Entry
Enyne
Conc. (M)
Solvent
Major product
Yield (%)
R
R
X
X
1
2
3
4
5
6
7
2a
2b
2a
2c
2c
2d
2e
0.02
0.02
0.03
0.02
0.04
0.02
0.03
CH2Cl2
CH2Cl2
THF
CH2Cl2
THF
4a
4b
5a
3c
5c
3d
3e
89
II
I
OR
R
75a
82
R
R
R
X
R
R
X
R
V
37
R
30
CH2Cl2
THF
12b
93
III
IV
Fig. 1. Cycloisomerization of 1,6-enynes.
The concentration values correspond to the substrate concentration. All
reactions were done at room temperature, stirring for 16 h. Yields are
isolated yields, except where otherwise indicated.
a
ysis rather than another acid produced by hydrolysis or
decomposition of the complex.
Enyne 2b had an E:Z ratio of 9:1. The major product could not be
isolated in pure form, due to the presence of several minor isomers. In this
case, the conversion was determined by 1H NMR with the addition of
mesitylene as a standard.
The reaction was sluggish when the olefin was terminally
substituted with an aryl group, though the five-membered
ring was produced with modest conversion. In undried
THF the hydroxylated product 5c was formed, albeit in
lower yield than with the alkyl-substituted enyne 2a, and
once again the enantioselectivity was low (9% ee) when
enantiopure catalyst was used. The reaction of enyne 2d,
which contains a monosubstituted olefin, only proceeded
to 12% of 3d. Enyne 2e, which is dialkyl-substituted though
not terminally substituted, was cyclized selectively to 3e.
No trace of the hydroxylated product was observed when
the reaction was performed in undried THF.
b
Yield determined by 1H NMR.
Table 2
Effect of concentration on product distribution
cat (10%)
X
+
X
X
THF
OH
2a
5a
6
Entry
Conc. (M)
Products (%)
The incorporation of water from the solvent into the cyc-
lic products was seen to be very sensitive to reactant concen-
trations. Specifically, changes in the concentrations of
catalyst and substrate resulted in varying product distribu-
tions. Table 2 shows the effect of changing concentrations
on the reaction. The optimal substrate concentration in
terms of conversion to 5a was 0.03 M; concentrations lower
than this resulted in lower yields of 5a and increased yields
of 6 although the net conversion to cyclized product was
lower. Catalyst decomposition is also favored by higher
water concentrations, as addition of 10 equiv. (with respect
to catalyst) of water resulted in no conversion to cyclized
product. These results illustrate the dramatic effect of con-
centration on the cyclization reactions. The concentration
5a
6
1
2
3
0.03
0.02
0.005
82
32
14
4
23
8
Percent conversion was determined by 1H NMR.
dependency is perhaps best viewed as a kinetic effect owing
to the relative concentration of water in comparison to the
substrate and catalyst concentrations. That is, the relative
rates of the various reactions (hydroxycyclization, Alder-
ene cyclization, and catalyst decomposition) are affected
to very different extents by the various concentration
X
R''
R'
cat (10%)
X
X
X
R
+
+
R'
OH
R'
R''
R
R'
R
R''
R''
2
3
4
5
X = C(CO2Me)2
cat =
NMe2
a: R = H, R' =R'' = Me
b: R = R'' = H, R' = Me, (E/Z = 9/1)
c: R = R'' =H, R' = Ph
Ru
+ 2 AgSbF6
Cl
d: R = R' = R'' = H
P
Cy2
e: R = Me, R' = R'' = H
Cl
1
Fig. 2. Cycloisomerization of enynes by 1/AgSbF6.

1914
J.W. Faller, P.P. Fontaine / Journal of Organometallic Chemistry 691 (2006) 1912–1918
changes of the reagents. The lower conversions at lower cat-
alyst concentrations, for example, could be a result of the
faster decomposition of the catalyst relative to the product
forming reactions.
D
D
cat (10%)
cat (10%)
X
X
X
The five-membered ring products 3c–e are the result of a
skeletal rearrangement of the substrate during the catalytic
cycle, which involves the breaking of the C–C bonds in the
olefin. PtCl2 [14–16], GaCl3 [17], [RuCl2(CO)3]2 [18], [Au-
(PPh3)]+ [4], and Grubbs’ catalyst Cl2RuL(PCy3)@CHPh
[6,19,20] are all effective at eliciting this type of cyclization.
In order to determine whether the six-membered ring prod-
ucts were the result of a similar rearrangement process, 2H
and 13C labeling experiments were performed as shown in
Figs. 3 and 4.
The labeling studies are consistent with a ring-closing
metathesis process that leads to the six-membered ring for-
mation [6,20]. Alternatively, the position of the labels is
suggestive of an electrophilic activation mechanism that
has been proposed which proceeds via non-stabilized cyclo-
propyl metal carbene intermediates [4,14,16,21–26]. This
mechanism, in contrast to enyne metathesis, can also give
rise to the observed hydroxycyclization.
X
13C
13C
Net Rearrangement:
4
2
2 1
cat (10%)
X
1
3
3
4
X
Fig. 4. Labeling experiments.
This latter process has been postulated for other electro-
philic transition metal centers, mainly PtCl2 and cationic
Au complexes, which activate the triple bond through g2-
coordination of the alkyne toward nucleophilic attack by
the pendant olefin. The six-membered rings 4a–b would
be a result of a 6-endo attack, followed by a rearrangement
sequence that has only been observed in one other instance
[4]. The preference for this pathway, as opposed to the
more commonly observed pathway involving 5-exo attack,
has been attributed to the relative activation energies of the
two transition states. Theoretical studies have focused on
such factors as the propargylic substituents [27] and the
effect of heteroatoms within the substrate [25] on control-
ling the regiochemistry of the nucleophilic attack. It has
also been noted that the electronegativity of the substitu-
ents on the substrate can have an influence on the outcome
of these reactions [15,22]. This present study suggests that
the steric environment of the metal catalyst can also play
an important role in determining the regioselectivity. For
example, in Echavarren’s report [4], substrates 2a and 2b
D
MeO2C
MeO2C
MeO2C
D2O
NaH
A:
B:
MeO2C
THF
-78 C
2H-2a
O
O
O
13C
O
13C
NaH,
THF
DIBAL
EtO
13C
P
OH
EtO
OEt
OEt
CH2Cl2
dimethyl propargyl
malonate
MeO2C
MeO2C
HBr
13C
Br
13C
Cs2CO3, acetone
13C-2a
Fig. 3. Preparation of isotopically labeled enynes. (A) 2H-labeled 2a. (B) 13C-labeled 2a.

J.W. Faller, P.P. Fontaine / Journal of Organometallic Chemistry 691 (2006) 1912–1918
1915
2+
+
2+
R
Ru
R'
Ru
Ru
6-endo
+
P
P
P
X
X
X
Cy2
Cy2
Cy2
X
X
R'
R'
R'
R
R
R
2+
+
2+
X
Ru
Ru
Ru
5-exo
+
P
P
P
Cy2
X
Cy2
Cy2
X
R'
R'
R'
R
R
R
R'
R
X
R
R'
HO
Fig. 5. Possible mechanism for skeletal rearrangement.
given substrate. Applications are currently being investi-
gated which will probe the scope of this catalyst system
for alkyne activation in different substrates, as well as in
areas that could better exploit the chirality of the catalyst,
such as desymmetrization reactions.
Ru
Ru
H
H
Ru
X
X
H
X
Ru
Ru
4. Experimental
H
H
X
X
4.1. General methods
All synthetic manipulations were done under nitrogen
atmosphere using standard Schlenk techniques. CH2Cl2
and THF were dried by distillation over the appropriate
drying agents prior to use, except when indicated other-
wise. AgSbF6 (Strem), crotyl alcohol, dimethyl propargyl-
malonate (Fluka), CsCO3, NaH, allylic halides, DIBAL,
and triethyl phosphonoacetate-1-13C (Aldrich) were all
used as received. NMR spectra were recorded on Bruker
400 and 500 MHz instruments, and chemical shifts are
reported in ppm relative to solvent peaks. Enantiomeric
excesses were determined with the use of europium
tris[3-heptafluoro-propylhydroxymethylene-(+)-camphor-
ate] as a chiral shift agent. The chiral shift experiments
were done in C6D6, and it was observed that a resonance
corresponding to the protons on one of the methoxy
groups would begin to split after a downfield shift of
ꢀ0.5 ppm.
Fig. 6. Initial step viewed as a metal–carbene and carbene attack on the
olefin.
were seen to react via the 5-exo pathway (see Fig. 5). Since
in our case the 6-endo pathway was observed for the iden-
tical substrates, it is reasonable to assume that the unique
steric environment of our catalyst plays a major role in
controlling the regioselectivity. This can be viewed as
favoring the initial formation of a more-substituted metal
carbene while the other carbon of the alkyne assumes car-
bene-like reactivity as shown in Fig. 6.
3. Conclusions
The following compounds have been previously
described: 2a [10], 2b [28], 2c [29], 2d [30], 2e [9], 3e [31],
5a [8] and 5c [8].
In conclusion, the arene-tethered ruthenium complex 1
has been shown to be a catalyst precursor for enyne cyclo-
isomerizations and hydroxycyclizations. The observed
products are the result of a skeletal rearrangement process,
and a rare cyclization to produce a six-membered ring has
been observed. Thus, this catalyst complements the existing
platinum and gold catalysts in that it may offer the poten-
tial of accessing different rearrangement pathways for a
4.2. Synthesis of 1,6-enynes
Enynes 2a–e were synthesized according to a previously
reported protocol [28].

1916
J.W. Faller, P.P. Fontaine / Journal of Organometallic Chemistry 691 (2006) 1912–1918
4.2.1. 2-(3-Methyl-but-2-enyl)-2-prop-2-ynyl-malonic acid
dimethyl ester (2a)
for 90 min. Quenching was done with D2O (3 mL) at 0 ꢁC.
The THF was removed under vacuum on a rotary-evapora-
tor, and the aqueous solution was extracted three times with
Et2O (3 · 5 mL). The combined organic extracts were dried
with MgSO4. Removal of solvent under vacuum resulted in
quantitative recovery of H-labeled 2a. H NMR (CDCl3,
400 MHz): 4.89 (t, 1H, J = 8.0 Hz), 3.73 (s, 6H), 2.78 (br s,
2H), 2.77 (br s, 2H), 1.69 (s, 3H), 1.65 (s, 3H). 13C NMR
(CDCl3, 100.6 MHz): 169.5, 136.0, 115.9, 77.8 (t, J =
7.4 Hz), 70.0 (t, J = 38.2 Hz), 56.1, 51.7, 29.8, 25.1, 21.4,
17.0.
Dimethyl propargylmalonate (0.40 mL, 2.6 mmol) and
Cs2CO3 (1.26 g, 3.9 mmol) were added to a flask containing
acetone (10 mL) under a stream of nitrogen. To this was
added 3,3-dimethylallyl bromide (0.60 mL, 5.3 mmol),
and the mixture was heated under reflux for 16 h. Filtra-
tion, and drying of the crude mix under vacuum, followed
by chromatography over silica gel eluting with 6:1 petro-
leum ether:diethyl ether yielded the desired product. Iso-
lated yield: 886 mg (93%).
2
1
4.2.2. 2-But-2-enyl-2-prop-2-ynyl-malonic acid dimethyl
ester (2b)
4.3.2. Synthesis of 13C labeled 2a
Each of the intermediate 13C labeled species (ethyl-
3,3-dimethylacrylate, 3-methyl-2-buten-1-ol, and 3,3-di-
methylallylbromide) have been previously synthesized and
characterized [32].
A flask was charged with crotyl alcohol (4.25 mL,
E/Z = 9.0:1) and hexachloroacetone (15 mL), and was
cooled to 0 ꢁC. Triphenylphosphine (13.6 mg) was added
slowly over 30 min, and then the mixture was allowed to
warm to room temperature. After 1 h, the crotyl chloride
was vacuum distilled into a cold trap (2.2 g, 28%). The
E/Z ratio of 9.0:1 was retained. A portion of the crotyl
chloride (0.65 mL) obtained in this manner was reacted
directly without further purification with dimethyl propar-
gylmalonate (0.50 mL, 3.3 mmol) and Cs2CO3 (1.64 g,
5.0 mmol) in analogous fashion to that described in the
synthesis of 2a. Isolated yield: 651 mg (88%).
A flask equipped with an addition funnel and under a
nitrogen atmosphere was charged with NaH (108 mg,
4.5 mmol) and THF (7 mL). Triethyl phosphonoacetate
(997 mg, 4.4 mmol) was added dropwise by addition funnel
in THF (3 mL). The resulting mixture was stirred at room
temperature for 45 min, before cooling to 0 ꢁC, at which
point acetone (0.5 mL) was added dropwise by addition
funnel in THF (3 mL). Subsequent to this addition, the
solution was allowed to warm to room temperature and
was stirred overnight. A saturated aqueous NH4Cl solution
(6 mL) was added to quench the reaction. The organic
layer was separated, and the aqueous layer was extracted
twice more with Et2O (2 · 5 mL). The combined organic
extracts were dried with MgSO4, and purified by column
chromatography over silica gel with 1:9 EtOAc/hexanes
as eluent. Isolated yield of ethyl-3,3-dimethylacrylate:
473 mg (83%).
4.2.3. 2-(3-Phenyl-allyl)-2-prop-2-ynyl-malonic acid
dimethyl ester (2c)
Prepared analogously to 2a with dimethyl propargylmal-
onate (0.30 mL, 2.0 mmol), cinnamyl bromide (0.60 mL,
4.0 mmol), and Cs2CO3 (0.97 g, 3.0 mmol). Isolated yield:
560 mg (99%).
4.2.4. 2-Allyl-2-prop-2-ynyl-malonic acid dimethyl ester
(2d)
Prepared analogously to 2a with dimethyl propargyl-
malonate (0.50 mL, 3.3 mmol), allyl bromide (0.60 mL,
6.9 mmol) and Cs2CO3 (1.64 g, 5.0 mmol). Isolated yield:
675 mg (97%).
A flask equipped with an addition funnel and under a
nitrogen atmosphere was charged with DIBAL (6 mL,
1 M in CH2Cl2) and was cooled to À78 ꢁC. Ethyl-3,3-dim-
ethylacrylate (327 mg 2.55 mmol) was added dropwise by
addition funnel in CH2Cl2 (8 mL). The mixture was
allowed to warm to room temperature, and was stirred
overnight, at which point it was quenched with EtOAc
(5 mL), and then water (5 mL). The solution was filtered
through Celite, and the organic layer was separated. The
aqueous portion was extracted twice more with Et2O
(2 · 5 mL), and the combined organic extracts were dried
with MgSO4. Isolated yield of 3-methyl-2-buten-1-ol:
200 mg (91%).
4.2.5. 2-(2-Methyl-allyl)-2-prop-2-ynyl-malonic acid
dimethyl ester (2e)
Prepared analogously to 2a with dimethyl propargyl-
malonate (0.50 mL, 3.3 mmol), 3-bromo-2-methyl-propene
(0.67 mL, 6.6 mmol) and Cs2CO3 (1.64 g, 5.0 mmol). Iso-
lated yield: 670 mg (91%).
A flask was charged with 3-methyl-2-buten-1-ol (200 mg,
2.32 mmol) and CH2Cl2 (7.5 mL), and was cooled to 0 ꢁC.
HBr (48%, 3 mL) was added, and the mixture was vigor-
ously stirred with the exclusion of light for 90 min. MgSO4
(800 mg), and 5 mL of additional CH2Cl2 were then added,
and the solution was warmed to room temperature. The
organic portion was separated, and the aqueous portion
was extracted twice more with CH2Cl2 (2 · 5 mL). The
combined organic extracts were dried with MgSO4. Isolated
yield of 3,3-dimethylallylbromide was 262 mg (76%).
4.3. Synthesis of isotopically labeled enynes
2
4.3.1. Synthesis of H labeled 2a
A flame-dried flask equipped with an addition funnel and
under a nitrogen atmosphere was charged with NaH (10 mg,
0.42 mmol) and THF (10 mL). The solution was cooled to
À78 ꢁC, and 2a (90 mg, 0.38 mmol) was added dropwise
via addition funnel. The mixture was stirred for 10 min at
À78 ꢁC, and then warmed to room temperature and stirred

J.W. Faller, P.P. Fontaine / Journal of Organometallic Chemistry 691 (2006) 1912–1918
2
1917
The 13C labeled 3,3-dimethylallylbromide was then sub-
4.5.4. H-labeled 4a
jected to analogous conditions as was described for the
preparation of 2a. H NMR (CDCl3, 400 MHz): 4.86 (m,
1H NMR (CDCl3, 400 MHz): 5.55 (br t, 1H), 3.64 (s,
6H), 2.77 (br s, 2H), 2.60 (m, 2H), 1.71 (s, 3H, Me), 1.70
(s, 3H, Me). 13C NMR (CDCl3, 100.6 MHz): 172.2,
130.0, 125.8 (t, J = 24 Hz), 124.1, 122.7, 54.5, 53.0, 32.5,
31.4, 20.9, 20.4.
1
1H), 3.70 (s, 6H), 2.75 (dd, 2H, JCH = 132.0 Hz,
J = 8.0 Hz), 2.73 (dd, 2H, J = 4.0 Hz, 3.0 Hz), 1.98 (t,
1H, J = 3.0 Hz), 1.66 (s, 3H), 1.62 (s, 3H). 13C NMR
(CDCl3, 100.6 MHz): 170.4, 136.8, 117.0 (d, J = 45 Hz),
79.2, 57.1 (d, J = 34 Hz), 52.6, 30.7, 26.0 (d, J = 5 Hz),
22.5, 17.8.
4.5.5. 13C-labeled 4a
1H NMR (CDCl3, 400 MHz): 6.47 (m, 1H), 5.65 (m,
1H), 3.73 (s, 6H), 2.86 (m, 2H), 2.69 (dm, 2H,
JCH = 131.6 Hz), 1.80 (s, 3H, Me), 1.79 (s, 3H, Me). 13C
NMR (CDCl3, 125.8 MHz): 171.8, 129.7, 125.7, 123.8,
122.5 (d, J = 40 Hz), 53.1 (d, J = 41 Hz), 52.6, 32.1, 31.1,
20.5, 20.0. A COSY spectrum showed coupling between
the CH2 resonance corresponding to the protons on the
13C atom and the olefin resonance at 5.65 ppm. Also, an
NOE difference spectrum showed contacts between these
same resonances (at 2.69 and 5.65 ppm).
4.4. General method for ruthenium catalyzed enyne
cycloisomerization
A
flame-dried flask was charged with 1 (6 mg,
0.010 mmol) under a stream of nitrogen. The appropriate
amount of solvent was then added by syringe, and to this
solution was added the 1,6-enyne (0.10 mmol), and then
AgSbF6 (7 mg, 0.020 mmol) under a stream of nitrogen.
The resulting mixture was allowed to stir with the exclusion
of light overnight for 16 h, at which point it was dried
under vacuum. The residue was passed through a small sil-
ica plug in Et2O in order to remove the inorganic species.
Purification of the organic portion was done by column
chromatography over silica gel eluting with 1:9
EtOAc:hexanes.
Appendix A. Supporting information
1
Selected 13C and H NMR of new compounds. Supple-
mentary data associated with this article can be found,
in the online version, at doi:10.1016/j.jorganchem.2006.
01.009.
4.5. Spectral characterization for new products
References
4.5.1. 5-Isopropylidene-cyclohex-3-ene-1,1-dicarboxylic acid
dimethyl ester (4a)
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1H NMR (CDCl3, 400 MHz): 6.45 (dt, 1H, J = 10.1 Hz,
J = 1.8 Hz), 5.64 (dt, 1H, J = 10.1 Hz, J = 4.0 Hz), 3.72 (s,
6H), 2.87 (br s, 2H), 2.67 (m, 2H), 1.80 (s, 3H, Me), 1.79 (s,
3H, Me). 13C NMR (CDCl3, 100.6 MHz): 172.2, 130.1,
126.0, 124.1, 122.9, 54.5, 53.0, 32.5, 31.4, 20.9, 20.4.
4.5.2. 5-Ethylidene-cyclohex-3-ene-1,1-dicarboxylic acid
dimethyl ester (4b)
1H NMR (CDCl3, 400 MHz): 6.43 (dt, 1H, J = 10.4 Hz,
J = 2 Hz), 5.77 (dt, 1H, J = 10.4 Hz, J = 4.8 Hz), 5.35 (q,
1H, J = 7.2 Hz), 3.71 (s, 6H, OMe), 2.80 (m, 2H), 2.70
(m, 2H), 1.70 (d, 3H, J = 7.2 Hz). 13C NMR (CDCl3,
125.8 MHz): 170.5, 128.8, 124.2, 122.7, 121.9, 53.0, 51.9,
36.2, 30.7, 11.8. The stereochemistry was determined by
an NOE difference experiment in which irradiation of the
exo olefinic proton resonance resulted in an NOE enhance-
ment to the methyl protons as well as a CH2 resonance at
2.80 ppm.
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4.5.3. 3-Styryl-cyclopent-3-ene-1,1-dicarboxylic acid
dimethyl ester (3c)
1H NMR (CDCl3, 400 MHz): 7.42 (d, 2H, J = 7.2 Hz),
7.33 (t, 2H, J = 7.2 Hz), 7.25 (d, 1H, J = 7.2 Hz), 6.92 (d,
1H, J = 16.0 Hz), 6.47 (d, 1H, J = 16.0 Hz), 5.72 (br s,
1H), 3.79 (s, 6H), 3.29 (br s, 2H), 3.19 (br s, 2H). 13C
NMR (CDCl3, 125.8 MHz): 172.9, 140.1, 137.6, 130.4,
129.0, 128.0, 127.8, 126.8, 124.7, 59.3, 53.4, 41.4, 40.1.
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