Synthesis of 2-cyano-1,4-cycloheptadiene derivatives via divinylcyclopropane rearrangement and alkylation of novel cycloheptadienyl anion species

Article abstract of DOI:10.1016/j.tetlet.2012.11.070

An efficient synthetic method for 2-cyano-1,4-cycloheptadiene derivatives was developed on the basis of divinylcyclopropane rearrangement. The substrates were prepared from 2-vinylcyclopropanecarbonitrile and an α,β- epoxysilane through a Peterson olefination. The resulting 2-cyano-1,4- cycloheptadiene underwent deprotonation at the doubly allylic methylene group to afford a novel cycloheptadienyl anion, a useful intermediate for synthesizing polycyclic compounds.

Full text of DOI:10.1016/j.tetlet.2012.11.070

Tetrahedron Letters 54 (2013) 522–525
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Synthesis of 2-cyano-1,4-cycloheptadiene derivatives via
divinylcyclopropane rearrangement and alkylation of novel cycloheptadienyl
anion species
Takumasa Yamada a, Fumihiko Yoshimura b, Keiji Tanino b,
⇑
a Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0810, Japan
b Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
An efficient synthetic method for 2-cyano-1,4-cycloheptadiene derivatives was developed on the basis of
divinylcyclopropane rearrangement. The substrates were prepared from 2-vinylcyclopropanecarbonitrile
Received 26 October 2012
Revised 16 November 2012
Accepted 19 November 2012
Available online 29 November 2012
and an
a,b-epoxysilane through a Peterson olefination. The resulting 2-cyano-1,4-cycloheptadiene
underwent deprotonation at the doubly allylic methylene group to afford a novel cycloheptadienyl anion,
a useful intermediate for synthesizing polycyclic compounds.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Cyclopropyl anion
Nitrile
Peterson olefination
Divinylcyclopropane rearrangement
Cycloheptadiene
Seven-membered carbocycles are found in a wide range of nat-
ural products, and various kinds of synthetic methods have been
explored. Intramolecular ring closure of an acyclic substrate is
widely applicable to cycloheptane synthesis,1 though efficiency
in forming a seven-membered ring is generally lower than those
for the five- or six-membered rings. Cycloaddition approach2
involving [4+3]3 and [5+2]4,5 type reactions also provides a power-
ful method for constructing seven-membered carbocycles.
ylation upon refluxing with NaHCO3 and LiCl in DMSO.10 This
three-step sequence can provide vinylcyclopropane 2 in decagram
quantities.11 It is noteworthy that preparation of the corresponding
ester 20 from diethyl malonate was unsuccessful, because the
decarboxylation step afforded a mixture of several compounds.12
Introduction of another vinyl group onto the cyclopropane ring
was achieved by using
a,b-epoxysilane 3 as a vinyl cation equiva-
lent (Scheme 3).
On the other hand, divinylcyclopropane rearrangement has
been used for this purpose,6 while the utility of the reaction de-
pends on the availability of the starting materials (Scheme 1).
To a THF solution of the a-cyano carbanion generated from ni-
trile 2 and n-butyllithium was added epoxide 3 that was prepared
from 1-octyne through regioselective silylcupration followed by
mCPBA oxidation. The reaction proceeded through regioselective
substitution of the epoxide followed by Peterson elimination of
the b-silyl alkoxide intermediate,13 giving rise to the desired prod-
uct 4 in good yield. While 4 was found to have the trans relation-
ship of the vinyl groups,14 refluxing in toluene induced smooth
rearrangement15 to afford cycloheptadiene 5.16
Cycloheptadiene 8 possessing a quaternary carbon atom was
also synthesized in a similar manner starting from a,b-epoxysilane
6 (Scheme 4). Interestingly, the use of six-membered nitrile 9 in-
stead of nitrile 2 in the reaction with 6 resulted in almost quanti-
tative recovery of the epoxide.
One method involves the reaction of an
a-vinylcarbenoid spe-
cies and a 1,3-diene that often affords a cycloheptadiene through
spontaneous rearrangement of the resulting divinylcyclopropane.7
Another method for preparing divinylcyclopropane is based on the
reaction of a 2-vinylcyclopropyl anion,8 although there are limited
examples of this type of transformation. Herein, we report a con-
cise synthesis of 2-cyano-1,4-cycloheptadiene derivatives from 2-
vinylcyclopropanecarbonitrile (2) that was easily prepared as
shown in Scheme 2.
In the presence of 2 equiv of DBU,9 ethyl cyanoacetate reacted
with trans-1,4-dibromo-2-butene to afford cyclopropane deriva-
tive 1 in 84% yield. Saponification of ester 1 with lithium hydroxide
gave the corresponding carboxylic acid that underwent decarbox-
The different behavior observed with the
a-cyano carbanions
generated from nitrile 2 and nitrile 9 would come from the highly
strained nature of the cyclopropane ring. Thus, the ketenimine res-
onance form usually contributes to the stabilization of an
carbanion. In the case of nitrile 2, however, the exocyclic double
a-cyano
⇑
Corresponding author.
E-mail address: ktanino@sci.hokudai.ac.jp (K. Tanino).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.11.070

T. Yamada et al. / Tetrahedron Letters 54 (2013) 522–525
523
CN
SiMe3 1) 2, n-BuLi
THF
Me3SiCH2Cl
O
s-BuLi
O
–78°C to rt
TMEDA
THF
2) toluene
reflux
64% (2 steps)
–78 to –50°C
11
10
83% (ref.17)
NC
CN
HO
2, n-BuLi
Martin sulfurane
xylene
THF, –78°C
rt to 150°C
12
13
65%
81%
Scheme 1. Synthesis of cycloheptane derivatives via divinylcyclopropane
rearrangement.
Scheme 5. Construction of spiro[6.5]undecane and bicyclo[4.5]undecane skeletons
from cyclohexanone.
Another useful preparative method for
a,b-epoxysilanes is the
reaction of an aldehyde or a ketone with chloro(trimethylsilyl)-
methyllithium,17 and spirocyclic compound 11 was synthesized
from cyclohexanone through the reaction of
a,b-epoxysilane 10
with nitrile 2 (Scheme 5). On the other hand, the direct use of
cyclohexanone as a coupling partner of nitrile 2 afforded tert-
alcohol 12 that was transformed into bicyclo[5.4]undecane
derivative 13 by heating with Martin sulfurane18 (bis[
a,a-bis(tri-
fluoromethyl)benzenemethanolato]diphenylsulfur). Martin sulfu-
rane was found to be the dehydrating agent of choice, and the
reactions of alcohol 12 promoted by Burgess reagent19 or a cata-
lytic amount of p-toluenesulfonic acid gave the desired compound
13 only in low yield.
Scheme 2. Preparation of cyclopropane derivative 2.
With the desired seven-membered nitriles in hand, we planned
to introduce an additional substituent onto the carbocycle. Thus,
treatment of
ionic species through abstraction of the
dergo an alkylation reaction at the -position (Scheme 6).
a
,b-unsaturated nitrile 5 with a base would afford an-
c
-proton that would un-
a
While treatment of nitrile 5 with LDA in THF led to the forma-
tion of a complex mixture even at ꢀ78 °C, addition of LDA to a mix-
ture of 5 and benzyl bromide afforded a mono-alkylation product
14 in 81% yield.20 It was found, however, that the product was
not the expected nitrile 15 but its isomer possessing a benzyl
group at the b0-position of the cyano group. The unexpected regio-
chemical outcome indicates the preferential formation of cyclo-
heptadienyl anion21 B rather than A in Scheme 6, despite the fact
that the negative charge of B cannot be delocalized into the cyano
group.
Scheme 3. Synthesis of cycloheptadiene 5 via divinylcyclopropane rearrangement
of nitrile 4.
Scheme 4. Remarkable reactivity of nitrile 2 toward a,b-epoxysilane.
bond of ketenimine imposes increased strain on the three-
membered ring, leading to enhanced reactivity toward
electrophiles.
Scheme 6. Alkylation of nitrile 5 mediated by LDA.

524
T. Yamada et al. / Tetrahedron Letters 54 (2013) 522–525
and applications in total synthesis of polycyclic natural compounds
are under investigation.
Acknowledgments
This work was partially supported by the Global COE Program
(Project No. B01: Catalysis as the Basis for Innovation in Materials
Science) and Grant-in-Aid for Scientific Research on Innovative
Areas (Project No. 2105: Organic Synthesis Based on Reaction Inte-
gration) from the Ministry of Education, Culture, Sports, Science
and Technology, Japan.
Scheme 7. Alkylation of cycloheptadiene derivatives possessing different
substituents.
With a view to clarify the role of a cyano group in the genera-
tion of the novel cycloheptadienyl anion, the alkylation reactions
of nitrile 8, ester 16, and silyl ether 17 were examined under sim-
ilar conditions (Scheme 7).22
Treatment of a mixture of nitrile 8 and benzyl bromide with
LDA at ꢀ78 °C led to the formation of the desired product 18 in
excellent yield. While alkylation product 19 was also obtained in
77% yield from the corresponding ester 16, the reaction of silyl
ether 17 resulted in the recovery of the substrate. These results
suggest that an electron-withdrawing group facilitates deprotona-
tion of the doubly allylic methylene group of the cycloheptadiene
derivative, even though the corresponding anion species is not in
conjugation with the cyano or ester group.
The novel alkylation reaction at the doubly allylic position led
us to develop a new method for constructing polycyclic carbon
frameworks via intramolecular cyclization reactions (Scheme 8).
The cyclization precursor 21 was prepared in nearly quantita-
tive yield by treating a mixture of nitrile 8 and 2-bromobenzyl
bromide with LDA at ꢀ78 °C. Under the influence of Pd(PPh3)4
and n-Bu3N, aryl bromide 21 underwent an intramolecular Heck
reaction23 to afford tricyclic compound 22 as a 5:1 mixture of dia-
stereomers. The cis relationship of the hydroazulene moiety in the
major diastereomer was determined by an NOE experiment. On the
other hand, treatment of 21 with n-butyllithium followed by aque-
ous hydrochloric acid gave tricyclic ketone 23 in moderate yield.
The reaction proceeds through halogen-metal exchange to form
an aryllithium that in turn attacks the cyano group.
References and notes
1. For selected reviews, see: (a) Yet, L. Tetrahedron 1999, 55, 9349–9403; (b) Yet, L.
Chem. Rev. 2000, 100, 2963–3007; (c) Nakashima, K.; Fujisaki, N.; Inoue, K.;
Minami, A.; Nagaya, C.; Sono, M.; Tori, M. Bull. Chem. Soc. Jpn. 2006, 79, 1955–
1962.
2. For a review on cycloaddition strategies: Battiste, M. A.; Pelphrey, P. M.;
Wright, D. L. Chem. Eur. J. 2006, 12, 3438–3447.
3. For reviews on [4+3] cycloaddition strategy, see: Rigby, J. H.; Pigge, F. C. In
Organic Reactions; Paquette, L. A., Ed.; John Wiley & Sons, Inc: New York, 1997;
Vol. 51, pp 351–476; (b) Harmata, M. Chem. Commun. 2010, 46, 8886–8903; (c)
Harmata, M. Chem. Commun. 2010, 46, 8904–8922.
4. For a recent review on [5+2] cycloaddition strategy Pellissier, H. Adv. Synth.
Catal. 2011, 353, 189–218.
5. The authors reported another type of [5+2] cycloaddition strategy: (a) Tanino,
K.; Shimizu, T.; Miyama, M.; Kuwajima, I. J. Am. Chem. Soc. 2000, 124, 6116–
6117; (b) Tanino, K.; Kondo, F.; Shimizu, T.; Miyashita, M. Org. Lett. 2002, 4,
2217–2219; (c) Mitachi, K.; Yamamoto, T.; Kondo, F.; Shimizu, T.; Miyashita,
M.; Tanino, K. Chem. Lett. 2010, 39, 630–632.
6. For a review, see: Hudlicky, T.; Fan, R.; Reed, J. W.; Gadamasetti, K. In Organic
Reactions; Paquette, L. A., Ed.; John Wiley & Sons, Inc: New York, 1992; Vol. 41,
pp 1–133.
7. For reviews, see: (a) Davies, H. M. L. Tetrahedron 1993, 49, 5203–5223; (b)
Davies, H. M. L.; Antoulinakis, E. G. In Organic Reactions; Overman, L. E., Ed.;
John Wiley & Sons, Inc: New York, 2001; Vol. 57, pp 1–326.
8. (a) Wender, P. A.; Filosa, M. P. J. Org. Chem. 1976, 41, 3490–3491; (b) Wender, P.
A.; Eissenstat, M. A.; Filosa, M. P. J. Am. Chem. Soc. 1979, 101, 2196–2198; (c)
Piels, E.; Reissig, H. U. Angew. Chem., Int. Ed. 1979, 18, 791–792; (d) Piels, E.;
Morton, H. E.; Nagakura, I.; Thies, R. W. Can. J. Chem. 1983, 61, 1226–1238; (e)
Piels, E.; Burmeister, M. S.; Reissig, H. U. Can. J. Chem. 1986, 64, 180–187.
9. Ono, N.; Yoshimura, T.; Saito, T.; Tamura, R.; Tanikage, R.; Kaji, A. Bull. Chem.
Soc. Jpn. 1979, 52, 1716–1719.
10. Babler, J. H.; Spina, K. P. Tetrahedron Lett. 1985, 26, 1923–1926.
11. To a mixture of trans-1,4-dibromo-2-butene (42.8 g, 200 mmol) and ethyl
cyanoacetate (24.8 mL, 200 mmol) in benzene (1 L) was added DBU (59.8 mL,
400 mmol) at 0 °C. After being stirred at rt for 1 h, the mixture was filtered
through a pad of celite which was rinsed with ether. Concentration of the
filtrate followed by silica gel column chromatography (hexane/EtOAc, 10:1)
gave 1 (27.6 g, 84%, a 1:1 inseparable mixture of diastereomers) as a colorless
oil; IR (neat) 3094, 2987, 2245, 1733, 1307, 1231, 1182, 994, 928, 853,
In summary, we have developed an efficient method for the
synthesis of 2-cyano-1,4-cycloheptadiene derivatives. Under the
influence of n-BuLi, 2-vinylcyclopropanecarbonitrile (2) reacted
with an a,b-epoxysilane to afford divinylcyclopropane via a Peter-
741 cmꢀ1 1H NMR (500 MHz, CDCl3) for an isomer 1a: d 5.70–5.59 (m, 1H),
;
son olefination. The product was subjected to thermal rearrange-
ment by refluxing in toluene, and the desired seven-membered
diene was obtained in good yield. Unexpectedly, treatment of the
2-cyano-1,4-cycloheptadiene derivative with LDA resulted in the
formation of a carbanion via deprotonation at the doubly allylic
methylene group. The utility of the novel cycloheptadienyl anion
was demonstrated through the synthesis of tricyclic compounds,
5.43 (d, J = 16.0 Hz, 1H), 5.37 (d, J = 10.3 Hz, 1H), 4.29–4.23 (m, 2H), 2.55 (q,
J = 8.6 Hz, 1H), 1.97 (dd, J = 9.2, 5.2 Hz, 1H), 1.65 (dd, J = 7.4, 5.2 Hz, 1H), 1.34 (t,
J = 6.9 Hz, 3H); 1H NMR (500 MHz, CDCl3) for another isomer 1b: d 5.70–5.59
(m, 1H), 5.44 (d, J = 17.8 Hz, 1H), 5.27 (d, J = 10.3 Hz, 1H), 4.29–4.23 (m, 2H),
2.60 (q, J = 9.0 Hz, 1H), 1.93 (dd, J = 8.6, 5.2 Hz, 1H), 1.89 (dd, J = 9.2, 5.2 Hz, 1H),
1.32 (t, J = 6.9 Hz, 3H); 13C NMR (125 MHz, CDCl3) for an isomer 1a: d 167.11,
132.10, 120.80, 116.70, 62.97, 33.72, 23.84, 21.06, 14.03; 13C NMR (125 MHz,
CDCl3) for another isomer 1b: d 165.15, 130.46, 121.33, 118.67, 62.80, 35.69,
22.47, 20.26, 14.10. A mixture of THF (170 mL) solution of 1 (27.6 g, 167 mmol)
and a 2 M aqueous LiOH solution (167 mL, 334 mmol) was stirred at rt for
40 min. A 6 M aqueous HCl solution (70 mL) was added, and the mixture was
extracted with ether. The organic layer was washed with H2O and brine, dried
over anhydrous MgSO4, and concentrated under reduced pressure. The crude
carboxylic acid was added to a suspension of NaHCO3 (21.1 g, 251 mmol) and
anhydrous LiCl (28.4 g, 669 mmol) in DMSO (334 mL), and then the mixture
was heated at 190 °C for 3 h. After cooling, the mixture was diluted with ether,
washed with water and brine, and dried over anhydrous MgSO4. Concentration
followed by distillation under reduced pressure (58–60 °C/56 mmHg) gave
nitrile 2 (11.4 g, 73%, a 1:1.5 inseparable mixture of diastereomers) as a
colorless oil: IR (neat) 3089, 3048, 2238, 1640, 1446, 1056, 988, 916, 852, 791,
760 cmꢀ1 1H NMR (500 MHz, CDCl3) for major isomer 2a: d: 5.59 (ddd, J = 16.6,
.
9.3, 7.9 Hz, 1H), 5.33 (d, J = 16.6 Hz, 1H), 5.24 (d, J = 10.3 Hz, 1H), 1.95 (q, J = 7.5,
Hz, 1H), 1.66 (td, J = 8.3, 5.7 Hz, 1H), 1.36–1.31 (m, 1H), 1.13–1.10 (m, 1H); 1H
NMR (500 MHz, CDCl3) for minor isomer 2b: d 5.38–5.33 (m, 1H), 5.23 (d,
J = 17.2 Hz, 1H), 5.09 (d, J = 10.3 Hz, 1H), 2.12–2.06 (m, 1H), 1.39 (dt, J = 9.9,
4.6 Hz, 1H), 1.36–1.31 (m, 1H), 1.10–1.08 (m, 1H); 13C NMR (125 MHz, CDCl3)
for major isomer 2a: d 134.32, 119.75, 118.19, 21.56, 13.71, 4.60; 13C NMR
(125 MHz, CDCl3) for minor isomer 2b: d 135.68, 120.90, 116.83, 24.01, 14.11,
4.56.
Scheme 8. Synthesis of tricyclic compounds from alkylation product 21.

T. Yamada et al. / Tetrahedron Letters 54 (2013) 522–525
525
12.
A
c
-lactone and a dicarboxylic acid were obtained, each in about 20% yield,
J = 6.8 Hz, 3H); 13C NMR (125 MHz, CDCl3): d 153.80, 130.55, 125.18, 120.36,
113.19, 37.88, 34.87, 31.08, 29.48, 29.18, 22.59, 13.92.
while the reaction mechanism for lactone formation is not clear.
17. Burford, C.; Cooke, F.; Roy, G.; Magnus, P. Tetrahedron 1983, 39, 867–876.
18. Martin, J. C.; Arhart, R. J. J. Am. Chem. Soc. 1971, 93, 4327–4329.
19. Atkins, G. M.; Burgess, E. M. J. Am. Chem. Soc. 1968, 90, 4744–4745.
20. Typical procedure: To a mixture of cycloheptadiene 8 (49.1 mg, 0.33 mmol)
and benzyl bromide (39.6
1.0 M THF solution of LDA (330
lL, 0.33 mmol) in THF (1.6 mL) was slowly added a
13. (a) Hudrlik, P. F.; Peterson, D.; Rona, R. J. J. Org. Chem. 1975, 40, 2263–2264; (b)
Zhang, Y.; Miller, J. A.; Negishi, E. J. Org. Chem. 1989, 54, 2043–2044; (c)
Alexakis, A.; Jachiet, D. Tetrahedron 1989, 45, 381–389.
14. The stereochemitsty of cyclopropanes 4 and 7 was established by observation
of NOEs between Ha and Hb as shown bellow. Treatment of alcohol 12 with
Martin sulfurane at room temperature afforded the corresponding diene, the
configuration of which was determined in a similar manner.
lL, 0.33 mmol) at ꢀ78 °C. After being stirred
for 30 min, a saturated aqueous NH4Cl solution was added, and the mixture
was extracted with ether. Drying over MgSO4, concentration under reduced
pressure followed by silica gel column chromatography (hexane/ethyl acetate,
20:1) afforded diene 18 as a colorless oil (75.6 mg, 95%): IR (neat): 3029, 2960,
2926, 2866, 2214, 1456, 700, 680 cmꢀ1 1H NMR (500 MHz, CDCl3) d 7.31–7.26
;
(m, 2H), 7.25–7.18 (m, 3H), 6.32 (s, 1H), 5.73 (dt, J = 10.9, 7.4 Hz, 1H), 5.60 (ddd,
J = 10.9, 6.3, 1.1 Hz, 1H), 3.36 (ddd, J = 7.4, 5.7, 4.6 Hz, 1H), 3.13 (dd, J = 13.2,
4.6 Hz, 1H), 2.93 (dd, J = 13.2, 10.3 Hz, 1H), 2.01 (dd, J = 14.3, 7.4 Hz, 1H), 1.89
(dd, J = 14.3, 5.7 Hz, 1H), 1.06 (s, 3H), 0.98 (s, 3H); 13C NMR (125 MHz, CDCl3): d
157.53, 138.29, 132.12, 129.44, 129.35, 128.22, 126.52, 120.71, 114.43, 42.07,
39.82, 38.11, 36.88, 29.92, 28.44.
15. Since rearrangement of trans-divinylcyclopropanes generally requires a high
reaction temperature, the cyano group of 4 may have a facilitating effect of the
rearrangement reaction. For a similar effect of an ester group, see: Piers, E.;
Jung, G. L.; Ruediger, E. H. Can. J. Chem. 1987, 65, 670–682.
21. Yasuda, H.; Ohnuma, Y.; Yamauchi, M.; Tani, H.; Nakamura, A. Bull. Chem. Soc.
Jpn. 1979, 52, 2036–2045.
22. Reduction of nitrile 8 with DIBAL afforded an aldehyde that was subjected to a
Pinnick oxidation followed by esterification to give 16. Triisopropylsilyl ether
17 was prepared via a Luche reduction of the aldehyde and protection of the
resulting alcohol.
16. Typical procedure: To
a mixture of a 2.64 M hexane solution of n-BuLi
(0.57 mL, 1.5 mmol) in THF (2.5 mL) was added a THF (1.5 mL) solution of
nitrile 2 (140 mg, 1.5 mmol) at ꢀ78 °C. After being stirred for 30 min, a THF
(1 mL) solution of epoxysilane 3 (234 mg, 1.0 mmol) was added. After being
stirred for 30 min at ꢀ78 °C and then for 2 h at rt, the reaction was quenched
with a saturated NH4Cl aqueous solution. The mixture was separated, and the
aqueous layer was extracted with ether. Drying over MgSO4, concentration,
followed by silica gel column chromatography (hexane/benzene, 3:1) afforded
diene 4 as a colorless oil (138 mg, 79%); IR (neat): 2958, 2928, 2857, 2236,
1288, 1124, 1072, 9844 965, 109 cmꢀ1 1H NMR (500 MHz, CDCl3) d 5.89 (dt,
;
J = 14.9, 6.8 Hz, 1H), 5.65 (ddd, J = 16.6, 9.5, 7.2 Hz, 1H), 5.30 (d, J = 16.6 Hz, 1H),
5.24 (d, J = 9.5 Hz, 1H), 4.92 (d, J = 14.9 Hz, 1H), 2.04 (q, J = 6.8 Hz, 2H), 1.89 (q,
J = 7.2 Hz, 1H), 1.49 (dd, J = 7.2, 5.4 Hz, 1H), 1.39-1.25 (m, 5H), 0.89 (t,
J = 7.2 Hz, 3H); 13C NMR (125 MHz, CDCl3): d 134.09, 132.63, 125.67, 119.77,
118.14, 31.77, 31.19, 31.35, 22.15, 21.87, 20.07, 13.87. A toluene (3.9 mL)
solution of diene 4 (137 mg, 0.79 mmol) was heated at 130 °C for 2 h. After
cooling, the mixture was directly purified by silica gel column chromatography
(hexane/ether, 1:0 to 20:1) to afford cycloheptadiene 5 as a colorless oil
(124 mg, 90%); IR (neat): 3033, 2961, 2867, 2215, 670 cmꢀ1
;
1H NMR
23. For review, see: (b) Link, J. T. In Organic Reactions; Overman, L. E., Ed.; John
Wiley & Sons, Inc: New York, 2002; Vol. 60, pp 157–534; (b) Lautens, M.;
Alberico, D.; Bressy, C.; Fang, Y.-Q.; Mariampillai, B.; Wilhelm, T. Pure Appl.
Chem. 2006, 78, 351–361.
(500 MHz, CDCl3) d 6.52 (dd, J = 5.2, 1.7 Hz, 1H), 5.76–5.70 (m, 1H), 5.64–
5.58 (m, 1H), 3.20 (dd, J = 18.6, 2.0 Hz, 1H), 2.86 (dd, J = 18.6, 6.3 Hz, 1H), 2.66–
2.59 (m, 1H), 2.26–2.20 (m, 1H), 2.14–2.09 (m, 1H), 1.45–1.24 (m, 6H), 0.90 (t,