New cycloaddition/fragmentation strategies for preparing 5-7-5 and 5-7-6 fused tricyclic ring systems

Article abstract of DOI:10.1016/j.tet.2013.05.129

Tethering additional functionality to cyclobutadienyl iron tricarbonyl complexes provides new opportunities for the rapid construction of medium-ring-containing polycyclic compounds. Specifically, an intramolecular cycloaddition between cyclobutadiene and a tethered olefin, followed by an intramolecular cyclopropanation of the resulting cyclobutene-containing adduct generates highly strained pentacyclic intermediates. These compounds can then be relaxed thermally to generate 5-7-5 and 5-7-6 fused tricyclic ring systems that are shared with numerous natural products.

Full text of DOI:10.1016/j.tet.2013.05.129

Tetrahedron 69 (2013) 7831e7839
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New cycloaddition/fragmentation strategies for preparing 5-7-5 and
5-7-6 fused tricyclic ring systems
*
Jing He, Marc L. Snapper
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, MA 02467, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 29 April 2013
Received in revised form 25 May 2013
Accepted 28 May 2013
Available online 4 June 2013
Tethering additional functionality to cyclobutadienyl iron tricarbonyl complexes provides new oppor-
tunities for the rapid construction of medium-ring-containing polycyclic compounds. Specifically, an
intramolecular cycloaddition between cyclobutadiene and a tethered olefin, followed by an intra-
molecular cyclopropanation of the resulting cyclobutene-containing adduct generates highly strained
pentacyclic intermediates. These compounds can then be relaxed thermally to generate 5-7-5 and 5-7-6
fused tricyclic ring systems that are shared with numerous natural products.
Keywords:
Ó 2013 Elsevier Ltd. All rights reserved.
Cyclobutadiene
Cycloaddition
Intramolecular
Cyclopropanation
Fragmentation
1. Introduction
served as a key step to annulate the six-membered ring on a bicyclic
hydroazulene precursor 1/2 in the study toward the synthesis of
Medium-ring-containing, polycyclic natural products, such as
phorbol, grayanotoxin, rarisetenolide, and xerantholide provide
ample motivation for improved strategies toward 5-7-5 or 5-7-6
tricyclic ring systems. The construction of these tricyclic ring sys-
tems has been accomplished by various approaches.1 Of the myriad
ring forming strategies that are possible, only a handful has been
used in total synthesis.
guanacastepene C.3 The second strategy highlighted is an intra-
molecular ring closure between the two outer rings to generate the
central seven-membered ring. A variety of general methods for
synthesis of seven-membered ring are applied in this category. For
example, the Overman group reported a convergent and enantio-
selective total synthesis of (þ)-guanacastepene
N featuring
a regioselective 7-endo Heck cyclization as the key step to afford the
tricyclic skeleton (3/4).4 In a related disconnection, the West
group used an oxonium ylide [1,2]-shift in their approach to the
tigliane-daphnane skeleton (5/6).5 Both high yield and selectivity
were achieved in this transformation.
OH
OH
HOH2C
Me
R3O
OH
Me
H
Me
Me
Me
OH
OH
HO
O
OH
HO
H
H
A third strategy is based on an intramolecular cycloaddition be-
tween two groups attached to a preexisting ring to generate two
additional rings. In the total synthesis of C8-epi-guanacastepene O,
the Yang team applied the intramolecular DielseAlder reaction be-
tween an alkyne and diene to form the desired tricyclic systems with
cis-annulated methyl groups in 60% yield.6 Wender’s successful
syntheses of phorbol and related natural products also featured this
general strategy.1b,7 The fourth approach represents a particularly
rapid means of generating complex ring systems from acyclic pre-
cursors. Transition-metal catalyzed cyclization plays a significant
role in this category. The Ojima’s group, for example, developed
a rhodium catalyzed, silane-mediated [2þ2þ2þ1] cycloaddition of
enediynes in moderate to excellent yields to provide tricycle 10.8
We have been interested in developing new methods of con-
structing medium-ring-containing compounds. In particular,
R
1R2
Me
Me
phorbol
grayanotoxin
O
O
Me
H
O
H
O
O
H
Me
xerantholide
Me
rarisetenolide
Some of the recent approaches are summarized in Scheme 1.
The first example relies on annulation of a third ring onto a fused
bicyclic ring precursor.2 For example, a Knoevenagel condensation
* Corresponding author. Tel.: þ1 617 552 8096; fax: þ1 617 552 1442; e-mail
address: marc.snapper@BC.edu (M.L. Snapper).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.129

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J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
prepare 5-7 ring systems. Interestingly, the stereochemistry at the
C2 position becomes inverted during the thermal rearrangement
step of this sequence. This synthetic strategy has been used in the
total syntheses of (þ)- and (ꢀ)-pleocarpenene and pleocarpenone.10
Given the prevalence of tricyclic ring systems among terpenoid
natural products, we thought that an efficient approach toward
these targets could be achieved by incorporating an intramolecular
cyclopropanation11 of the cyclobutene intermediate 12 in this re-
action sequence. While generating the strained precursor to the
central seven-membered ring, the intramolecular cyclopropanation
would also establish an additional ring of the polycyclic target.
Furthermore, as illustrated in Scheme 3, depending on the attach-
ment point of the tethered carbenoid precursor (Y in 15 and 18),
two unique tricyclic ring systems 17 and 20 should be accessible
through this approach (Eqs. 1 and 2). Described herein are our
preliminary studies exploring the feasibility of this strategy for
generating these medium-ring-containing tricyclic systems.
Scheme 1. Construction of 5-7-5(6) ring systems.
Scheme 3. Generation of tricyclic ring systems using an intramolecular
cyclopropanation.
intramolecular cycloadditions of iron tricarbonyl cyclobutadienyl
complexes have been shown to generate highly functionalized,
strained cyclobutene adducts that can be used to access medium
ring skeletons through subsequent fragmentations.9 For example, as
shown in Scheme 2, we have used this cycloaddition, followed by an
intermolecular cyclopropanation and thermal fragmentation to
2. Results and discussion
The first challenge to be addressed in advancing this strategy
was the introduction of the additional functionality on the
cyclobutadienyl iron tricarbonyl complex. A solution is summa-
rized in Scheme 4. DIBAL-H reduction of the iron methyl ester
complex 21, followed by formation of the MOM-ether 22 allowed
for the directed ortho lithiation, which generates a mixture of
1,2- and 1,3-disubstituted iron complexes 23 and 24 in a 5:1
ratio. At this stage, the separation of these regioisomers through
silica gel column chromatography was not readily feasible.
Therefore, the two regioisomers, 23 and 24 were carried through
the subsequent transformations together. Under acidic condi-
tions, the MOM group was replaced by an allyl group. Treatment
of the resulting ether with styrene in the presence of Hovey-
daeGrubbs second catalyst (HG2) provided efficiently com-
pounds 25 and 26, which were then oxidized with CAN to form
cyclobutenes 27 and 28. These two regioisomeric cycloadducts
were separable and each subjected independently to the fol-
lowing studies.
Scheme 2. 5-7 Ring systems through
a cyclobutadiene cycloaddition/cyclo-
propanation/thermal fragmentation sequence.

J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
7833
Scheme 4. Syntheses of functionalized cyclobutene compounds.
The reaction sequences to convert cyclobutenes 27 and 28 into
the polycyclic thermolysis precursors are shown in Scheme 5. A B-
alkyl SuzukieMiyaura cross-coupling12 on 27 was used to provide
intermediate 29, using a borane species prepared from acrolein
ethylene acetal. p-Toluenesulfonic acid-mediated acetal depro-
tection and Pinnick oxidation then delivered carboxylic acid 30. The
diazo motif in 31 was introduced through the intermediacy of an acid
chloride. An effective cyclopropanation was achieved by a Rh2(OAc)4
catalyzed diazo-decomposition of compound 31 to afford the highly
strained cyclopropane 32 as a white solid in a stereospecific manner.
Support for the stereochemical assignment was obtained through
NMR and X-ray crystallographic studies (Fig.1). Sodium borohydride
was used to reduce compound 32 to alcohol 33 as the sole di-
astereomer. Ina similarfashion, cyclopropane38 was generated from
cyclobutene adduct 28 (Scheme 6).
Fig. 1. Crystal structure of cyclopropane 32.
Scheme 6. Synthesis of polycyclic substrate 38.
Scheme 5. Synthesis of polycyclic substrate 33.
Scheme 7. Thermal rearrangement of cycloadduct 33.
With a reliable route to the alternative ring systems in hand, we
examined their thermal ring openings. When compound 33 was
subjected to 240 ꢁC for 5 h in benzene, two diastereomers (39 and
40), epimeric at C2 were generated in a 5:1 ratio and a combined
yield of 92% (Scheme 7).
A mechanism that accounts for the formation of these two di-
astereomeric products is suggested in Scheme 8. The strained
thermal precursor 33 is thought to rearrange through two com-
peting pathways (a and b) to deliver the corresponding di-
occur to adopt boat conformation 43. Reestablishing the C1eC2
bond through a Cope rearrangement at the expense of the C6eC7
cyclopropane bond then accounts for the stereo-inversion at C2 in
product 39. Moreover, homolytic bond cleavage of C7eC12 in 33 is
likely in this highly strained system (bond/path b). The resulting
diradical 44 could isomerize from the ‘anti’ to ‘syn’ conformation
45. Fragmentation of the C6eC13 bond would then lead to product
40 where the C2 stereocenter is retained.
astereomeric products 39 and 40. In pathway a,
a
divinyl
As summarized in Table 1, the nature of the C1 substituent
appears to influence the relative rates of these two thermal rear-
rangement pathways. Entries 1 and 2 indicated that replacing
the phenyl group with a methyl ester changes the ratio of the
cyclopropane intermediate 42 can be generated through either
a concerted or a stepwise diradical pathway. To facilitate the sub-
sequent Cope rearrangement, a bond rotation along C6eC7 can

7834
J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
Table 1
Thermal fragmentations
HO
H
12
Ph
1
13H
7
H
6
2
H
H
Ph
H
Ph
H
HO
O
Ph
H
H
2
H
13
(1)
Ph
12
H
Ph
H
H
H
HO
H
6
1
HO
HO
HO
HO
HO
O
O
H
H
7
H
H
O
O
(77%)
(15%)
H
O
H
CO2Me
H
CO2Me
H
H
CO2Me
(2)
HO
H
H
H
Ph
H
H
2
1
H
HO
OH
H
O
O
H
O
O
(21%)
(50%)
12
13
Ph
H
O
Ph
H
Ph
H
H
Ph
Ph
6
(3)
HO
7
OH
7
OH
H
H
6
HO
Me
HO
H
H
O
Me
Me
OH
H
H
(76%) Me
(9%)
HO
H
Me Me
H
H
Ph
H
Ph
H
Ph
H
OH
O
(4)
HO
Ph
H
H
H
1
Ph
HO
HO
2 H
O
H
O
O
H
2
(47%)
(40%)
N/A
HO
H
Ph
H
(5)
HO
O
Ph
H
Ph
H
Ph
H
H
H
O
H
H
HO
2
2
H
H
O
(49%)
HO
HO
O
O
(6)
HO
H
CO2Me
CO2Me
H
H
N/A
Scheme 8. Mechanism of thermal rearrangements.
O
HO
O
(70%)
Ph
(7)
H
Ph
Ph
H
HO
H
OH
Me
OH
diastereomeric products slightly from 4:1 to 2.4:1. The molecular
framework also has an impact on the stereochemical outcome;
both stereo-inverted and stereo-retained products were obtained
for substrates 33, 46, 49, 52, and 58 (entries 1e4 & 7), while
substrates 38 and 56 afforded exclusively stereo-inverted tricyclic
ring systems (entries 5 & 6).13 Substrates bearing all-carbon skel-
etons (entries 3 & 7) rearranged as smoothly as the oxygen con-
taining systems. Efforts were also made to extend this tricyclic ring
forming strategy to 5-7-6 ring architecture (entry 4). The six-
membered ring unit was incorporated in the cyclobutadiene
cycloaddition step by lengthening the tether between the olefin
and the iron tricarbonyl cyclobutadiene ring by one methylene
group.
The stereochemical identities of these fragmentation products
were determined through NMR studies. Specifically, the relative
stereochemistry of C1 and C2 in the rearranged products 59 and 60
was determined by examining the NOESY interactions relative to
the carbinol proton He. Fig. 2 summarizes the results of these ex-
periments. These findings indicated the inversion at C2 and re-
tention at C1 of diastereomer 59, while the retention of
stereochemistry at both C1 and C2 of diastereomer 60.
H
H
Me
Me
OH
H
H
HO
HO
Me
(33%)
(63%)
Me Me
H
H
OH
He
1
1
Hd
Hd
OH
He
2
2
Me
Me
H
H
HO
HO
Me
Me
59
60
strong correlation
weak correlation
Fig. 2. Stereochemistry determination by 2-D NOESY experiment.
4. Experimental section
4.1. General
3. Conclusion
Proton nuclear magnetic resonance spectra (H NMR) chemical
shifts are reported in parts per million downfield from tetrame-
thylsilane with the solvent resonance as the reference (CDCl3:
We have successfully developed a novel method to synthesis
5-7-5(6) tricyclic ring systems through an intramolecular cyclo-
propanation/thermal fragmentation strategy. The stereochemical
course of the fragmentation appears to be substrate dependent.
Nevertheless, a library of various tricyclic ring systems can be
generated fairly rapidly in good to moderate yields from a simple
precursor.
d
7.26 ppm; C6D6: d 7.16 ppm). Data are reported as follows:
chemical shift, integration, multiplicity (s¼singlet, d¼doublet,
t¼triplet, q¼quartet, br¼broad, m¼multiplet), and coupling con-
stants (Hz). Carbon nuclear magnetic resonance spectra (C NMR)
were recorded with complete proton decoupling. Chemical shifts

J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
7835
are reported in ppm downfield from tetramethylsilane with the
solvent resonance as the reference (CDCl3: 77.23 ppm; C6D6:
as a yellow oil. Compound 23:16 H NMR (500 MHz, CDCl3):
d
4.68
d
(2H, d, J¼2.5 Hz), 4.58 (1H, s), 4.41 (1H, s), 3.90 (1H, d, J¼12.5 Hz),
d
128.39 ppm). Infrared (IR) spectra are reported in wave numbers
3.82 (1H, d, J¼13.0 Hz), 3.41 (3H, s). C NMR (125 MHz, CDCl3):
(cmꢀ1). Bands are characterized as broad (br), strong (s), medium
(m), or weak (w). High resolution mass spectral analyses (HRMS)
were performed at Boston College. Melting points (mp) are re-
ported uncorrected.
d 213.1, 96.3, 96.2, 83.2, 67.3, 63.2, 62.1, 55.7. IR (KBr thin film,
CH2Cl2 solution): 3060 (w), 3027 (w), 2934 (w), 2048 (s), 1972 (s),
1150 (w), 1099 (w), 1041 (w), 613 (w), 583 (m) cmꢀ1. DART-HRMS
(m/z): calcd for [MꢀMOM]þ: 330.8555; Found: 330.8565.
Starting materials and reagents were purchased from commer-
cial suppliers and used without further purification except the
following: Dry CH2Cl2, DMF, hexane, toluene, diethyl ether, THF,
and benzene were used from a solvent purification system.14
Hexanes and Et2O used in chromatography were distilled before
use. Molecular sieves were dried in a 250 ꢁC oven overnight before
use. (Cyclobutadienyl)iron tricarbonyl was prepared as reported in
the literature and displayed satisfactory spectral data. All oxygen-
or moisture-sensitive reactions were carried out under N2
atmosphere in oven-dried (140 ꢁC, >4 h) or flame-dried glassware.
Air- or moisture-sensitive liquids were transferred by syringe or
cannula and were introduced into the reaction flasks through
rubber septa or through a stopcock under N2 positive pressure.
Degassing refers to a flow of dry N2(g) bubbling through reaction
solvent for 15 min. Unless otherwise stated, reactions were stirred
with a Teflon covered stir bar. Concentration refers to the removal
of solvent using a rotary evaporator followed by use of a vacuum
pump at approximately 1 Torr. Silica gel column chromatography
4.1.3. Ethers (25 & 26). In a round bottom flask (25 mL) with
condenser, stir bar and septum was placed a mixture of alcohols 23
& 24 (295.7 mg, 0.755 mmol), Amberlyst-15 (88.7 mg), and allyl
alcohol (4.0 mL, 0.20 M). The reaction mixture was heated to 90 ꢁC
until judged complete (4 h) by TLC analysis (Rf: 0.50 in 1:2 Et2O/
hexanes). After cooling to room temperature, the reaction mixture
was concentrated and purified by silica gel column chromatogra-
phy (10:1 hexanes/Et2O) to afford the allylic ethers of the iodocy-
clobutadienyl complexes (25a and 26a) (267.7 mg, 0.664 mmol, 88%
yield) as dark yellow oil. Compound 25a: H NMR (500 MHz, CDCl3):
d
5.91 (1H, m), 5.33 (1H, dd, J¼17.0, 2.0 Hz), 5.21 (1H, dd, J¼11.0,
2.0 Hz), 4.57 (1H, s), 4.40 (1H, s), 4.06 (2H, m), 3.77 (2H, s). C NMR
(125 MHz, CDCl3): 213.5, 134.5, 117.8, 83.7, 72.0, 67.2, 64.7, 63.2,
d
27.0. IR (KBr thin film, CH2Cl2 solution): 2955 (w), 2856 (w), 2359
(w), 2341 (w), 2050 (s), 1977 (s), 1116 (w), 1075 (w), 930 (w), 613
(m), 584 (m), 508 (w) cmꢀ1
. DART-HRMS (m/z): calcd for
[MꢀMOM]þ: 330.8555; Found: 330.8563. Compounds 25a & 26a: H
refers to flash chromatography15 and was performed using 60 A
NMR (500 MHz, CDCl3): d 5.89 (m), 5.21e5.35 (m), 4.57 (compound
ꢀ
(230e400 mesh ASTM) silica gel. Thin layer chromatography was
25a, 1H, s), 4.45 (compound 26a, 2H, s), 4.40 (compound 25a, 1H, s),
4.06 (compound 25a, 2H, m), 4.01 (compound 26a, 2H, td, J¼6.0,
1.5 Hz), 3.80 (compound 26a, 2H, s), 3.77 (compound 25a, 2H, s).
In a round bottom flask (25 mL) with condenser, stir bar and
septum were placed allylic ethers of the iodocyclobutadienyl com-
plexes (25a & 26a) (291.9 mg, 0.725 mmol), freshly purified styrene
ꢀ
performed on glass back 60 A (250
m
m thickness) silica gel plates.
4.1.1. Iron tricarbonyl cyclobutadiene-1-methyl-MOM-ether (22). In
a round bottom flask (50 mL) with a stir bar and septum were
placed iron tricarbonyl cyclobutadiene-1-methanol (2.26 g,
10.2 mmol) and (i-Pr)2NEt (10.2 mL, 1.0 M). The flask was cooled to
0 ꢁC and MOMCl (1.0 mL, 13.2 mmol) was added dropwise under N2
atmosphere. The reaction was allowed to warm to room tempera-
ture and stirred overnight. TLC analysis (Rf: 0.85 in 2:1 hexanes/
Et2O) indicated full conversion before saturated aqueous NH4Cl
solution (30 mL) was added to quench the reaction. The mixture
was transferred into a separatory funnel (125 mL) and the aqueous
layer was extracted with CH2Cl2 (3ꢂ30 mL). The combined organic
layer was washed with brine (20 mL) and dried over MgSO4. Con-
centration afforded a dark yellow oil that was purified immediately
by silica gel column chromatography (10:1 hexanes/Et2O) to collect
compound 22 (2.58 g, 9.69 mmol, 95% yield) as a yellow oil. H NMR
(322 mL, passed through a neutral Al2O3 plug to remove inhibitor),
HoveydaeGrubbs second-generation catalyst (22.8 mg, 5 mol %),
and CH2Cl2 (4.0 mL, 0.20 M). The reaction mixture was heated to
reflux for overnight. After allowing to cool, 30 wt % silica gel was
added to the flask and stirred vigorously at room temperature for
30 min. Filtration and concentration provided a dark orange oil,
which was then purified by silica gel column chromatography
(100:1 hexanes/Et2O with a gradient to 10:1 hexanes/Et2O) to afford
orange oil compounds 25 and 26 (291.3 mg, 0.631 mmol, 87% yield)
as a mixture of cis and trans isomers. Compound 25: H NMR
(500 MHz, CDCl3):
d
7.40 (2H, d, J¼7.5 Hz), 7.32 (2H, m), 7.25 (1H, m),
6.66 (1H, d, J¼20.0 Hz), 6.31 (1H, m), 4.59 (1H, s), 4.41 (1H, s), 4.23
(2H, m), 3.83 (2H, s). IR (KBr thin film, CH2Cl2 solution): 2953 (w),
2854 (w), 2049 (s),1977 (s),1116 (w),1073 (w), 967 (w), 737 (w), 613
(400 MHz, CDCl3):
s), 3.34 (3H, s). C NMR (100 MHz, CDCl3):
d
4.26 (2H, s), 4.12 (2H, s), 4.06 (1H, s), 3.85 (2H,
214.3, 95.9, 80.5, 64.7,
d
63.0, 62.7, 55.4. IR (KBr thin film): 2952 (w), 2886 (w), 2046 (s),
1966 (s), 1152 (w), 1101 (w), 1037 (m), 613 (m), 588 (s). DART-HRMS
(m/z): calcd for [MꢀMOM]þ: 204.9588; Found: 204.9589.
(m), 585 (m), 507 (w) cmꢀ1
. DART-HRMS (m/z): calcd for
[MꢀMOM]þ: 330.8555; Found: 330.8559. Compounds 25 & 26: H
NMR (500 MHz, CDCl3):
d
7.40 (d, J¼7.0 Hz), 7.32 (t, J¼7.5 Hz), 7.26
(m), 6.66 (m), 6.31 (m), 4.59 (compound 25, 1H, s), 4.47 (compound
26, 2H, s), 4.41 (compound 25, 1H, s), 4.23 (compound 25, 2H, m),
4.18 (compound 26, 2H, d, J¼6.0 Hz), 3.85 (s).
4.1.2. 1,2- and 1,3-Iodocyclobutadienyl iron tricarbonyl complexes
(23 & 24). To a solution of mom-ether 22 (2.58 g, 9.68 mmol) in
THF (48.0 mL, 0.20 M) under N2 atmosphere at ꢀ78 ꢁC was added
freshly titrated s-BuLi (9.68 mmol, 1.26 M in cyclohexane) drop-
wise. The resulting dark solution was allowed to stir at this tem-
perature for another 15 min before adding 1,2-diiodoethane (3.01 g,
10.7 mmol). Then the mixture was allowed to warm to room
temperature and allowed to stir for 1 h before saturated aqueous
NH4Cl solution (50 mL) was added to quench the reaction. The
mixture was then poured into a separatory funnel (250 mL). The
aqueous layer was extracted with Et2O (3ꢂ50 mL). The combined
organic layer was washed with brine (50 mL) and dried over
MgSO4. The resulting solution was concentrated and purified im-
mediately by silica gel column chromatography (100:1 hexanes/
Et2O with a gradient to 20:1 hexanes/Et2O) to afford a mixture of
compounds 23 and 24 (1.80 g, 4.64 mmol, 48% yield, 5:1 ortho/para)
4.1.4. Cyclobutadiene cycloaddition adducts (27 & 28). To a solution
of compounds 25 & 26 (291.3 mg, 0.631 mmol) in acetone
(316.0 mL, 0.0020 M) was added cerium ammonium nitrate (CAN)
(1.039 g, 1.90 mmol). The reaction was allowed to stir at room
temperature for 15 min while a vigorous evolution of gas was ob-
served. Then saturated aqueous NaHCO3 solution (5 mL) was added
to quench the reaction. Stirring was continued for 20 min to allow
precipitation of the cerium salts, which was removed by sub-
sequent vacuum filtration. The filtrate was dried over MgSO4. Fil-
tration and concentration provide an oil that was then purified by
silica gel column chromatography (20:1 hexanes/Et2O with a gra-
dient to 10:1 hexanes/Et2O) to afford cycloadduct 27 (90.8 mg,
0.278 mmol, 53% yield) as pale sticky yellow oil and cycloadduct 28

7836
J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
as a white solid (15.3 mg, 0.047 mmol, 45% yield). Cycloadduct 27: H
NMR (500 MHz, CDCl3):
(15 mL) and dried over MgSO4. The resulting solution was con-
centrated and purified immediately by silica gel column chroma-
tography (85:15 hexanes/EtOAc with a gradient to 35:65 hexanes/
EtOAc) to afford compound 30 (234.1 mg, 0.866 mmol, 63% yield
d
7.31 (2H, t, J¼7.5 Hz), 7.21 (1H, t,
J¼7.5 Hz), 7.10 (2H, d, J¼7.5 Hz), 4.11 (1H, dd, J¼9.5,1.5 Hz), 3.93 (1H,
d, J¼10.0 Hz), 3.89 (1H, dd, J¼10.0, 7.0 Hz), 3.73 (1H, d, J¼8.0 Hz),
3.46 (1H, d, J¼10.5 Hz), 3.40 (1H, dd, J¼7.5, 5.5 Hz), 2.75 (1H, m). C
over two steps) as colorless oil. H NMR (500 MHz, CDCl3):
d 7.27
NMR (125 MHz, CDCl3):
d
145.7, 141.9, 128.6, 127.4, 126.6, 93.1, 73.5,
(2H, t, J¼7.5 Hz), 7.17 (1H, t, J¼7.5 Hz), 7.09 (2H, d, J¼7.5 Hz), 5.76
(1H, t, J¼1.5 Hz), 4.09 (1H, d, J¼9.5 Hz), 3.91 (1H, d, J¼10.0 Hz), 3.84
(1H, dd, J¼9.5, 6.5 Hz), 3.69 (1H, d, J¼10.0 Hz), 3.44 (1H, dd, J¼8.5,
6.0 Hz), 3.28 (1H, d, J¼8.0 Hz), 2.79 (1H, t, J¼5.5 Hz), 2.58 (2H, t,
69.1, 65.1, 53.0, 47.0, 43.5. IR (KBr thin film, CH2Cl2 solution): 3026
(w), 2956 (s), 2840 (m), 2359 (w), 1529 (m), 1267 (w), 1091 (w),
1057 (m), 888 (s), 817 (m), 774 (w), 710 (w) cmꢀ1. DART-HRMS
(m/z): calcd for [MþH]þ: 325.0089; Found: 325.0100. Cycloadduct
J¼7.5 Hz), 2.47 (2H, m). C NMR (125 MHz, CDCl3):
d 178.7, 149.1,
28: (mp: 45e47 ꢁC). H NMR (500 MHz, CDCl3):
d
7.32 (3H, m), 7.24
142.9, 129.4, 128.3, 127.4, 126.0, 73.8, 69.1, 58.3, 46.7, 46.3, 44.8, 31.3,
23.7. IR (KBr thin film, CH2Cl2 solution): 3060 (s), 3027 (s), 3002 (s),
1732 (m), 1709 (m), 1447 (w), 1203 (br), 1063 (w), 887 (w), 712 (w),
590 (br) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 271.1334;
Found: 271.1344.
(2H, d, J¼7.0 Hz), 6.90 (1H, d, J¼1.5 Hz), 4.09 (1H, dd, J¼10.0, 1.5 Hz),
3.91 (1H, d, J¼10.0 Hz), 3.85 (1H, dd, J¼10.0, 6.5 Hz), 3.64 (2H, dd,
J¼10.0, 8.0 Hz), 3.56 (1H, dd, J¼7.5, 5.5 Hz), 2.99 (1H, m). C NMR
(125 MHz, CDCl3): d 146.2, 138.9, 128.3, 128.2, 126.7, 92.6, 73.6, 69.6,
62.7, 56.7, 44.8, 43.2. IR (KBr thin film, CH2Cl2 solution): 3067 (m),
3039 (s), 3018 (m), 2959 (w), 2897 (s), 2835 (w), 1530 (w), 1160 (w),
1060 (w), 853 (w), 710 (m), 594 (br) cmꢀ1. DART-HRMS (m/z): calcd
for [MþH]þ: 325.0089; Found: 325.0087.
4.1.7. Diazoketone (31). To a solution of compound 30 (234.1 mg,
0.866 mmol) in dry benzene (4.4 mL, 0.20 M) were added DMF
(0.67 mL, 1 mol %) and oxalyl chloride (223.1 m
L, 2.30 mmol) at 0 ꢁC
under N2 atmosphere. The reaction was allowed to slowly warm to
room temperature and stirring until no gas-evolution anymore
(2 h). The solvent and unreacted oxalyl chloride were removed
under vacuum. Then THF (4.4 mL, 0.20 M) and CH3CN (4.4 mL,
4.1.5. Cyclobutene (29). To a solution of 9-BBN (1.00 g, 8.24 mmol)
in THF (16.0 mL) at 0 ꢁC was added acrolein ethylene under N2
atmosphere. The reaction was allowed to stir at room temperature
for 4 h before DMF (0.83 mL, 1.6 M), H2O (2.2 mL, 0.60 M), Cs2CO3
(1.17 g, 3.59 mmol), Ph3As (80.0 mg, 0.266 mmol), compound 27
(430.7 mg, 1.33 mmol), and PdCl2(dppf) (68.1 mg, 7 mol %) were
sequentially added. The reaction was heated to 80 ꢁC for 15 h. After
cooling, the mixture was poured into a separatory funnel with 5%
LiCl aqueous solution (20 mL). The aqueous layer was extracted
with Et2O (3ꢂ20 mL). The combined organic layer was washed with
brine (20 mL) and dried over MgSO4. The resulting solution was
concentrated and immediately purified by silica gel column chro-
matography (10:1 hexanes/Et2O with a gradient to 1:1 hexanes/
Et2O) to afford cyclobutene 29 (361.3 mg, 1.21 mmol, 91% yield) as
0.20 M) were added at
0
ꢁC under N2 atmosphere. TMS-
diazomethane (0.866 mL, 2.0 M in cyclohexane) was added
slowly with an air-tight syringe. A bright yellow color developed
during the addition. The reaction was allowed to stir at room
temperature until judged complete (2 h) by TLC analysis (Rf¼0.3,
1:1 hexanes/EtOAc). The reaction mixture was concentrated and
purified by silica gel column chromatography (5% Et3N in hexanes
washed silica gel, 90:10 hexanes/EtOAc with a gradient to 75:25
hexanes/EtOAc) to afford compound 31 (137.6 mg, 0.468 mmol, 54%
yield over two steps) as a bright yellow oil. H NMR (500 MHz,
CDCl3):
d
7.27 (2H, t, J¼7.5 Hz), 7.17 (1H, t, J¼7.5 Hz), 7.09 (2H, dd,
colorless oil. 1H NMR (500 MHz, CDCl3):
d
7.26 (2H, t, J¼7.5 Hz), 7.16
J¼10.0, 8.0 Hz), 5.71 (1H, s), 5.22 (1H, br), 4.09 (1H, d, J¼9.5 Hz),
3.89 (1H, d, J¼10.0 Hz), 3.84 (1H, dd, J¼9.5, 6.5 Hz), 3.68 (1H, d,
J¼10.0 Hz), 3.43 (1H, dd, J¼8.0, 5.5 Hz), 3.27 (1H, d, J¼8.0 Hz), 2.78
(1H, t, J¼7.5 Hz), 7.10 (2H, d, J¼7.0 Hz), 5.72 (1H, d, J¼1.5 Hz), 4.89
(1H, t, J¼5.0 Hz), 4.09 (1H, d, J¼9.5 Hz), 3.96 (2H, m), 3.89 (1H, d,
J¼10.0 Hz), 3.85 (3H, m), 3.68 (1H, d, J¼10.0 Hz), 3.42 (1H, dd, J¼8.0,
6.0 Hz), 3.26 (1H, d, J¼8.0 Hz), 2.77 (1H, t, J¼6.0 Hz), 2.25 (2H, m),
(1H, t, J¼5.5 Hz), 2.46 (4H, m). C NMR (125 MHz, CDCl3):
d 193.8,
149.6, 143.1, 129.1, 128.3, 127.4, 126.0, 73.9, 69.2, 58.5, 46.7, 46.2,
44.8, 23.7. IR (KBr thin film, CH2Cl2 solution): 3060 (s), 3028 (s),
2931 (s), 2850 (w), 2360 (w), 2341 (w), 2103 (m), 1645 (w), 1371
(w), 746 (w), 697 (w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ:
295.1447; Found: 295.1448.
1.86 (2H, m). C NMR (125 MHz, CDCl3):
d 150.3, 143.2, 128.7, 128.3,
127.4, 126.0, 104.1, 73.9, 69.3, 65.2, 58.5, 46.8, 46.2, 44.9, 31.0, 23.2.
IR (KBr thin film, CH2Cl2 solution): 3080 (m), 3060 (s), 2957 (m),
2942 (s), 1600 (w), 1402 (w), 1383 (w), 1138 (m), 1029 (br), 895 (w),
758 (s), 701 (s), 537 (m), 448 (w) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 299.1647; Found: 299.1637.
4.1.8. Cyclopropane (32). To a solution of compound 31 (10 mg,
0.034 mmol) in CH2Cl2 (1.7 mL, 0.020 M) was added rhodium ac-
4.1.6. Carboxylic acid (30). To
a
solution of compound 29
etate (0.3 mg, 0.7 mmol, 2 mol %). The reaction was allowed to stir at
(456.0 mg, 1.53 mmol) in acetone (7.0 mL, 0.20 M) and water
(4.0 mL, 0.40 M) was added p-toluenesulfonic acid monohydrate
(319.8 mg, 1.68 mmol). The reaction was heated to reflux until
judged complete (4 h) by TLC analysis (Rf: 0.35, 1:1 hexanes/Et2O).
Then, saturated aqueous NaHCO3 solution (10 mL) was added to
quench the reaction. The aqueous layer was extracted with Et2O
(3ꢂ15 mL). The combined organic layer was washed with brine
(20 mL) and dried over MgSO4. The resulting solution was con-
centrated to provide the aldehyde intermediate without further
purification.
room temperature until judged complete (1 h) by TLC analysis
(Rf¼0.4, 1:1 hexanes/EtOAc). Then the reaction mixture was con-
centrated and purified by silica gel column chromatography (90:10
hexanes/EtOAc with a gradient to 50:50 hexanes/EtOAc) to afford
compound 32 (84% yield) as a white solid (mp: 117e125 ꢁC). H NMR
(500 MHz, CDCl3):
d
7.19e7.40 (5H, m), 4.05 (1H, d, J¼9.5 Hz), 3.86
(1H, dd, J¼9.5, 6.5 Hz), 3.73 (1H, d, J¼10.0 Hz), 3.71 (1H, t, J¼6.0 Hz),
3.47 (1H, d, J¼10.0 Hz), 3.24 (1H, t, J¼6.0 Hz), 2.69 (1H, d, J¼2.0 Hz),
2.27e2.32 (1H, m), 2.10 (1H, m), 2.01e2.04 (1H, m), 1.92 (1H, s), 1.74
(1H, s). C NMR (125 MHz, CDCl3):
d 212.3, 140.9, 128.6, 127.1, 126.4,
The aldehyde intermediate was dissolved in tert-butanol
(6.1 mL, 0.25 M) and H2O (3.0 mL, 0.50 M) in a round bottom flask
(25 mL) with a stir bar at 0 ꢁC. 2-Methyl-2-butene (several millili-
ters pipetted) was added followed by KH2PO4 (832.0 mg,
6.11 mmol) and NaClO4 (552.6 mg, 6.11 mmol). The reaction was
allowed to stir at room temperature overnight until judged com-
plete by TLC analysis (Rf: 0.55, 1:8 hexanes/Et2O). The mixture was
transferred to a separatory funnel and extracted with ethyl acetate
(3ꢂ15 mL). The combined organic layer was washed with brine
74.0, 69.1, 52.8, 44.7, 43.5, 43.4, 40.0, 37.9, 35.0, 24.0, 20.8. IR (KBr
thin film, CH2Cl2 solution): 3059 (m), 2955 (m), 2844 (br), 2360
(m), 2341 (m), 1730 (s), 1281 (w), 1172 (m), 1053 (w), 902 (w) cmꢀ1
.
DART-HRMS (m/z): calcd for [MþH]þ: 267.1385; Found: 267.1390.
4.1.9. Thermolysis precursor (33). To a solution of compound 32
(11.0 mg, 0.0413 mmol) in MeOH (0.60 mL, 0.065 M) at 0 ꢁC was
added NaBH4 (3.2 mg, 0.0826 mmol) slowly. The reaction was
allowed to stir at this temperature until judged complete (5 min) by

J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
7837
TLC analysis (Rf: 0.1, 1:1 hexanes/EtOAc). The reaction crude was
diluted by CH2Cl2 and carefully quenched with saturated aqueous
NH4Cl solution at 0 ꢁC. The aqueous layer was extracted with
CH2Cl2 (3ꢂ5 mL). The combined organic layer was washed with
brine (5 mL) and dried over MgSO4. The resulting solution was
concentrated and purified immediately by silica gel column chro-
matography (75:25 hexanes/EtOAc with a gradient to 50:50 hex-
anes/EtOAc) to afford compound 33 (10.6 mg, 0.0392 mmol) as
2.34 (1H, d, J¼3.0 Hz), 1.91 (2H, m), 1.73 (1H, td, J¼13.5, 9.0 Hz), 1.63
(1H, s), 1.22 (1H, dd, J¼13.0, 7.5 Hz). C NMR (125 MHz, CDCl3):
d
212.4, 141.8, 128.6, 126.7, 126.4, 74.0, 70.0, 52.5, 45.1, 44.2, 43.6,
38.9, 38.8, 35.3, 30.0, 23.1. IR (KBr thin film, CH2Cl2 solution): 3060
(m), 3028 (s), 3007 (s), 2851 (m), 2359 (w), 1728 (m), 1451 (w), 1384
(w), 1178 (w), 746 (w), 577 (w) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 267.1385; Found: 267.1379.
a colorless oil. H NMR (400 MHz, CDCl3):
d
7.34 (2H, dt, J¼1.6,
4.1.14. Compound (38). The procedure was followed as described
for compound 33 to afford compound 38 as colorless oil in 99%
7.6 Hz), 7.19e7.23 (3H, m), 4.55 (1H, m), 4.00 (1H, d, J¼9.6 Hz), 3.80
(1H, dd, J¼9.6, 5.6 Hz), 3.72 (1H, d, J¼10.0 Hz), 3.62 (1H, t, J¼6.8 Hz),
3.39 (1H, d, J¼9.6 Hz), 3.14 (1H, t, J¼6.4 Hz), 2.52 (1H, d, J¼7.6 Hz),
1.99 (1H, dd, J¼7.2, 12.4 Hz), 1.91 (1H, td, J¼12.4, 7.6 Hz), 1.74 (1H,
m), 1.69 (1H, s), 1.45 (1H, d, J¼4.8 Hz), 1.01 (1H, m). C NMR
yield. H NMR (500 MHz, CDCl3):
d
7.32 (2H, t, J¼7.5 Hz), 7.25 (2H,
d, J¼7.5 Hz), 7.21 (1H, t, J¼7.0 Hz), 4.44 (1H, q, J¼7.0 Hz), 3.94 (1H,
d, J¼9.5 Hz), 3.84 (1H, dd, J¼9.5, 6.5 Hz), 3.76 (1H, d, J¼10.0 Hz),
3.71 (1H, t, J¼7.0 Hz), 3.28 (1H, d, J¼9.5 Hz), 3.13 (1H, t, J¼6.5 Hz),
2.85 (1H, dd, J¼8.0, 3.0 Hz), 2.07 (1H, d, J¼2.5 Hz), 1.70 (1H, m),
1.33 (1H, d, J¼5.5 Hz), 1.29 (1H, m), 0.89 (2H, m). C NMR
(125 MHz, CDCl3):
d 141.7, 128.4, 127.3, 126.1, 74.2, 74.1, 69.4, 52.9,
43.9, 43.8, 43.3, 34.8, 32.5, 30.5, 22.3, 16.2. IR (KBr thin film, CH2Cl2
solution): 3385 (w), 3037 (m), 3026 (m), 2924 (s), 2905 (m), 2360
(s), 2341 (s), 1491 (w), 1054 (w), 779 (s), 743 (s), 682 (m), 540
(m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 269.1542; Found:
269.1530.
(125 MHz, CDCl3): d 142.6, 128.3, 126.9, 126.0, 74.1, 73.0, 70.6, 51.2,
45.4, 44.9, 44.4, 33.6, 33.2, 31.1, 24.3, 22.4. IR (KBr thin film,
CH2Cl2 solution): 3363 (w), 3057 (m), 3028 (s), 2952 (m), 2850
(w), 1492 (w), 1453 (w), 1384 (w), 1067 (w), 755 (s), 696 (s), 540
(s) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 269.1542; Found:
269.1535.
4.1.10. Compound (34). The procedure was followed as described
for compound 29 to afford compound 34 as a colorless oil in 83%
yield. H NMR (500 MHz, CDCl3):
d
7.25 (2H, t, J¼7.5 Hz), 7.17 (3H,
4.1.15. Thermolysis products (39 & 40). In a pressure vessel with
a stir bar was added a solution of compound 33 (32.2 mg,
0.120 mmol) and BHT (39.6 mg, 0.179 mmol) in dry benzene
(12.0 mL, 0.010 M). The reaction mixture was degassed for 5 min
before sealing the pressure vessel. Then, the flask was emerged
into a wax bath, heating from room temperature to 240 ꢁC. The
reaction was heated at this temperature for 5 h. After allowing to
cool, the reaction mixture was concentrated and purified imme-
diately by silica gel column chromatography (Rf: 0.5 in 1:4 hex-
m), 6.05 (1H, s), 4.67 (1H, t, J¼4.5 Hz), 4.05 (1H, d, J¼9.0 Hz), 3.84
(4H, m), 3.77 (2H, m), 3.64 (1H, d, J¼10.0 Hz), 3.41 (1H, dd, J¼8.0,
5.0 Hz), 3.30 (1H, d, J¼8.0 Hz), 2.86 (1H, t, J¼5.5 Hz), 1.61 (4H, m).
C NMR (125 MHz, CDCl3):
d 151.8, 142.4, 128.2, 127.9, 127.3, 126.2,
104.2, 74.0, 70.5, 65.0, 65.0, 54.5, 50.6, 45.6, 43.1, 31.1, 25.2. IR (KBr
thin film, CH2Cl2 solution): 2939 (s), 2849 (s), 1409 (w), 1136 (s),
1067 (s), 1036 (s), 943 (w), 897 (m), 712 (s), 866 (br), 551
(w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 299.1647; Found:
299.1636.
anes/Et2O, 100:10 hexanes/EtOAc with
a gradient to 80:20
hexanes/EtOAc) to afford compounds 39 (20.7 mg, 0.0769 mmol,
77% yield) and 40 (4.1 mg, 0.0153 mmol, 15% yield) as colorless oils.
4.1.11. Compound (35). The procedure was followed as described
for compound 30 to afford compound 35 as colorless oil in 59%
Compound 39: H NMR (500 MHz, C6D6):
d
7.30 (2H, dd, J¼8.0,
yield over two steps. H NMR (500 MHz, CDCl3):
d
7.27 (2H, t,
1.5 Hz), 7.19 (2H, m), 7.09 (1H, m), 5.77 (1H, m), 5.33 (1H, dd,
J¼10.0, 2.0 Hz), 4.03 (1H, d, J¼10.5 Hz), 3.93 (1H, t, J¼3.0 Hz), 3.89
(1H, t, J¼8.5 Hz), 3.74 (1H, m), 3.65 (1H, m), 3.28 (1H, br), 3.19 (1H,
m), 3.17 (1H, br), 2.41 (1H, m), 1.86 (1H, dd, J¼16.5, 9.0 Hz), 1.71
(1H, dd, J¼13.0, 8.0 Hz), 1.30 (1H, m). 13C NMR (125 MHz, C6D6):
J¼7.0 Hz), 7.18 (3H, m), 6.09 (1H, d, J¼1.5 Hz), 4.07 (1H, d, J¼9.5 Hz),
3.86 (2H, td, J¼9.5, 3.0 Hz), 3.64 (1H, d, J¼9.5 Hz), 3.43 (1H, dd,
J¼7.5, 5.5 Hz), 3.32 (1H, d, J¼8.5 Hz), 2.88 (1H, t, J¼5.5 Hz), 2.24 (2H,
m), 1.90 (1H, m), 1.75 (1H, m). C NMR (125 MHz, CDCl3):
d 178.6,
150.4, 142.2, 128.6, 128.3, 127.3, 126.4, 73.9, 70.4, 54.6, 50.8, 45.4,
43.0, 31.2, 25.6. IR (KBr thin film, CH2Cl2 solution): 3425 (w), 3183
(w), 2946 (m), 1732 (m), 1710 (m), 1504 (w), 1463 (m), 1167 (w), 762
(s), 697 (w), 580 (w), 546 (w) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 271.1334; Found: 271.1345.
d 141.0, 135.1, 134.7, 132.7, 131.0, 128.7, 127.4, 126.3, 77.1, 72.2, 71.6,
51.9, 48.0, 46.5, 33.2, 29.3. IR (KBr thin film, CH2Cl2 solution): 3059
(w), 3029 (m), 2934 (s), 2909 (m), 2359 (w), 2342 (w), 1449 (w),
757 (s), 701 (m), 541 (w) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 269.1542; Found: 269.1530. Compound 40: H NMR
(500 MHz, CDCl3):
d
7.31 (2H, t, J¼8.0 Hz), 7.23 (3H, m), 5.99 (2H, d,
4.1.12. Compound (36). The procedure was followed as described
for compound 31 to afford compound 36 as bright yellow oil in 72%
yield over two steps. H NMR (500 MHz, CDCl3): d 7.27 (2H, m), 7.18
J¼1.0 Hz), 4.34e4.40 (2H, m), 4.33 (1H, d, J¼13.0 Hz), 3.64 (1H, d,
J¼11.0 Hz), 3.49 (1H, br), 3.46 (1H, t, J¼7.0 Hz), 3.14 (1H, dd, J¼11.0,
8.0 Hz), 3.08 (1H, br), 2.36 (2H, br), 1.90 (2H, m). C NMR (125 MHz,
(3H, m), 6.06 (1H, d, J¼1.5 Hz), 4.98 (1H, s), 4.06 (1H, d, J¼9.5 Hz),
3.85 (2H, dd, J¼9.5, 5.5 Hz), 3.64 (1H, d, J¼10.0 Hz), 3.43 (1H, dd,
J¼8.0, 5.0 Hz), 3.30 (1H, d, J¼8.0 Hz), 2.87 (1H, t, J¼5.5 Hz), 2.16 (2H,
CDCl3): d 143.8, 138.2, 134.3, 129.8, 128.8, 128.0, 127.3, 126.7, 75.8,
73.4, 71.7, 48.3, 46.4, 45.7, 32.9, 27.9. IR (KBr thin film, CH2Cl2 so-
lution): 3398 (br), 3035 (w), 3019 (w), 2959 (s), 2920 (s), 2853 (s),
2362 (w), 1724 (w), 1384 (m), 1280 (w), 1066 (m), 762 (s), 572
(m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 269.1542; Found:
269.1551.
br), 1.90 (1H, m), 1.75 (1H, m). C NMR (125 MHz, CDCl3):
d 194.0,
150.4, 142.2, 128.5, 128.5, 128.1, 127.2, 126.2, 73.8, 70.2, 54.4, 50.6,
45.2, 42.8, 37.9, 25.8. IR (KBr thin film, CH2Cl2 solution): 3084 (w),
2956 (m), 2846 (m), 2359 (m), 2341 (m), 2103 (s), 1643 (s), 1373 (s),
1350 (s), 1150 (m), 712 (w), 552 (w) cmꢀ1. DART-HRMS (m/z): calcd
for [MþH]þ: 295.1447; Found: 295.1443.
4.1.16. Compound (46). The procedure was followed as described
for compound 33 to afford compound 46 as colorless oil in 81%
yield. H NMR (500 MHz, CDCl3):
d
4.56 (1H, dd, J¼13.5, 8.5 Hz), 3.89
4.1.13. Compound (37). The procedure was followed as described
for compound 32 to afford compound 37 as a white solid in quant.
(1H, d, J¼9.5 Hz), 3.71 (3H, s), 3.69 (1H, dd, J¼10.0, 6.5 Hz), 3.61 (1H,
d, J¼10.0 Hz), 3.30 (1H, d, J¼10.0 Hz), 3.17 (1H, t, J¼6.5 Hz), 3.12 (1H,
dd, J¼7.5, 6.0 Hz), 2.37 (1H, d, J¼8.0 Hz), 1.99 (1H, dd, J¼12.5,
7.5 Hz), 1.92 (1H, dt, J¼13.0, 7.5 Hz), 1.81 (2H, s), 1.68 (1H, m), 1.39
yield. H NMR (500 MHz, CDCl3):
d
7.34 (2H, t, J¼7.5 Hz), 7.28 (2H, d,
J¼7.5 Hz), 7.23 (1H, t, J¼7.5 Hz), 3.97 (1H, d, J¼9.5 Hz), 3.87 (1H, dd,
J¼9.5, 6.5 Hz), 3.79 (1H, t, J¼7.0 Hz), 3.73 (1H, d, J¼10.5 Hz), 3.30
(1H, d, J¼10.0 Hz), 3.22 (1H, t, J¼6.5 Hz), 2.97 (1H, dd, J¼8.0, 3.0 Hz),
(1H, d, J¼5.0 Hz), 1.09 (1H, m). 13C NMR (125 MHz, CDCl3):
d 173.5,
73.9, 73.6, 69.2, 53.8, 51.8, 42.8, 41.4, 40.7, 34.6, 32.3, 30.4, 22.2, 17.0.

7838
J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
IR (KBr thin film, CH2Cl2 solution): 3081 (w), 3060 (w), 3028 (m),
2926 (s), 1732 (w), 1600 (w), 1493 (w), 1449 (w), 1059 (w), 1028 (m),
755 (m), 698 (m), 539 (m) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 251.1283; Found: 251.1288.
1.81e1.91 (2H, m), 1.60e1.68 (1H, m), 1.60 (1H, s), 1.41 (1H, d,
142.0, 128.4,
J¼5.5 Hz), 0.93 (1H, m). C NMR (125 MHz, CDCl3):
d
127.4, 126.0, 74.0, 67.6, 64.1, 46.2, 43.5, 41.6, 38.9, 34.0, 31.0, 30.9,
30.4, 20.9, 16.7. IR (KBr thin film, CH2Cl2 solution): 3352 (w), 3030
(w), 2922 (s), 2359 (w), 1092 (m), 760 (s), 750 (s), 704 (s), 546
(w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 283.1698; Found:
283.1700.
4.1.17. Compounds (47 & 48). The procedure was followed as de-
scribed for compounds 39 & 40 to afford a mixture of compound 47
(50% yield) and compound 48 (21% yield) as colorless oil. Com-
pound 47: H NMR (500 MHz, C6D6):
d
5.62 (2H, m), 4.32 (1H, dd,
4.1.21. Compounds (53 & 54). The procedure was followed as de-
scribed for compounds 39 & 40 to afford a mixture of compound
53 (47% yield) and 54 (40% yield) as colorless oil. [Note: di-
astereomers 53 & 54 were not readily separable by column
chromatography until their disubstituted olefin in the cyclo-
heptadiene ring was reduced by hydrogenation.] To a solution of
the mixture (17.7 mg, 0.0628 mmol) in ethanol (1.3 mL, 0.050 M)
was added Pd/C (6.3 mg). Then the flask was purged with hy-
drogen gas (3ꢂ). The reaction was allowed to stir at room tem-
perature under H2 atmosphere for 1 h before filtered through
a silica plug and washed with EtOAc. After concentration, the
reaction crude was then purified by silica gel column chroma-
tography (10:1 hexanes/EtOAc with a gradient to 2:1 hexanes/
EtOAc) to afford compound 53a and 54a as clear colorless oil in
J¼13.0, 1.0 Hz), 4.13 (1H, t, J¼3.5 Hz), 4.02 (1H, dd, J¼12.5, 1.5 Hz),
3.83 (1H, dd, J¼9.0, 5.0 Hz), 3.75 (1H, t, J¼9.5 Hz), 3.26 (3H, s), 3.04
(1H, br), 2.93 (1H, td, J¼5.0, 2.0 Hz), 2.84 (1H, quintet, 1.5 Hz), 2.30
(1H, m), 1.91 (1H, dd, J¼13.0, 8.5 Hz), 1.85 (1H, ddd, J¼16.5, 9.5,
1.5 Hz), 1.39 (2H, m). C NMR (100 MHz, C6D6):
d 173.2, 133.1, 132.2,
131.6, 76.7, 73.6, 71.9, 53.8, 52.3, 47.7, 44.8, 33.8, 28.8. IR (KBr thin
film, CH2Cl2 solution): 3397 (br), 3070 (w), 3042 (s), 2950 (m),
2922 (m), 2870 (m), 2840 (w), 2359 (s), 2342 (s), 1721 (s), 1435 (m),
1266 (m), 1198 (s), 1171 (s), 1066 (m), 1016 (w), 748 (w), 701 (s),
531 (w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 251.1283;
Found: 251.1275. Compound 48: H NMR (400 MHz, C6D6): 6.11 (1H,
qd, J¼10.8, 2.8 Hz), 5.91 (1H, ddd, J¼10.8, 3.2, 2.4 Hz), 4.24 (1H, t,
J¼7.6 Hz), 4.21 (1H, dm, J¼15.2 Hz), 4.13 (1H, dm, J¼12.8 Hz), 3.81
(1H, t, J¼3.6 Hz), 3.47 (1H, dd, J¼11.2, 8.0 Hz), 3.39 (1H, ddq, J¼1.2,
2.8, 5.6 Hz), 3.26 (3H, s), 3.01 (1H, br), 2.81 (1H, br), 1.96 (1H, m),
1.76 (1H, dd, J¼9.6, 17.6 Hz), 1.46 (1H, dd, J¼8.4, 13.2 Hz), 1.27 (2H,
quant. yield. Compound 53a H NMR (500 MHz, C6D6):
d 7.09e7.22
(5H, m), 4.42 (1H, d, J¼12.0 Hz), 3.84 (1H, t, J¼3.5 Hz), 3.78 (1H,
m), 3.71 (1H, d, J¼11.5 Hz), 3.33 (1H, td, J¼12.5, 3.5 Hz), 3.15 (1H,
td, J¼11.0, 3.0 Hz), 2.60 (1H, m), 2.45 (2H, d, J¼11.0 Hz), 2.01e2.12
(2H, m), 1.80 (1H, m), 1.58e1.69 (3H, m), 1.53e1.57 (1H, m),
m). C NMR (100 MHz, C6D6): d 173.8, 133.7, 130.8, 130.7, 130.6, 75.6,
73.0, 71.5, 51.7, 48.2, 46.0, 42.8, 33.4, 28.3. IR (KBr thin film, CH2Cl2
solution): 3369 (br), 3060 (s), 3027 (s), 2910 (s), 2850 (m), 2360
(m), 2341 (m), 1737 (m), 1492 (w), 1449 (m), 1331 (w), 1260 (w),
1196 (w), 1160 (m), 1079 (w), 1041 (w), 753 (m), 697 (m), 544
(w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 251.1283; Found:
251.1284.
1.27e1.39 (3H, m). C NMR (125 MHz, CDCl3):
d 146.3, 139.9, 132.3,
129.3, 129.0, 127.0, 77.0, 72.0, 68.9, 48.9, 45.9, 45.2, 34.4, 30.8, 30.3,
29.2, 26.6. IR (KBr thin film, CH2Cl2 solution): 3428 (br), 3060 (m),
3028 (m), 2949 (s), 2899 (s), 2843 (s), 1725 (w), 1460 (m), 1378
(m), 1250 (m), 1093 (m), 775 (w), 566 (w) cmꢀ1. DART-HRMS (m/
z): calcd for [MþH]þ: 285.1855; Found: 285.1848. Compounds 53a
4.1.18. Compound (49). The procedure was followed as described
for compound 33 to afford compound 49 as colorless oil in quant.
and 54a: H NMR (500 MHz, C6D6): d 7.19 (m), 7.10 (m), 7.00 (d,
J¼7.5 Hz), 4.59 (54a, 1H, J¼7.5 Hz), 4.41 (53a, 1H, d, J¼12.0 Hz),
3.84 (53a, 1H, t, J¼3.5 Hz), 3.83 (54a, 1H, s), 3.78 (m), 3,71 (53a,
1H, d, J¼11.5 Hz), 3.66 (54a, 1H, d, J¼13.0 Hz), 3.33 (53a, 1H, td,
J¼12.5, 3.5 Hz), 3.24 (54a, 1H, m), 3.15 (53a, 1H, td, J¼11.0, 3.0 Hz),
2.91 (54a, 1H, t, J¼11.5 Hz), 2.60 (m), 2.44 (m), 2.32 (54a, 1H, dd,
J¼16.0, 8.0 Hz), 2.07 (m), 1.92 (54a, m), 1.81 (m), 1.42e1.69 (m),
1.23e1.39 (m), 1.12 (54a, m), 0.85e1.00 (54a, m).
yield. H NMR (500 MHz, CDCl3):
d
7.32 (2H, t, J¼8.0 Hz), 7.21 (3H,
m), 4.52 (1H, m), 4.05 (1H, t, J¼6.5 Hz), 3.96 (1H, d, J¼7.5 Hz), 3.13
(1H, dd, J¼8.0, 6.0 Hz), 2.50 (1H, d, J¼7.5 Hz), 1.87 (2H, dd, J¼10.5,
7.5 Hz), 1.65 (1H, s), 1.56 (3H, m), 1.54 (1H, d, J¼14.0 Hz), 1.42 (1H, d,
J¼14.0 Hz), 1.38 (1H, d, J¼5.5 Hz), 1.10 (3H, s), 0.99 (3H, s), 0.85 (1H,
d, J¼6.5 Hz). C NMR (125 MHz, CDCl3):
d 142.9, 128.3, 127.6, 125.7,
80.6, 74.3, 50.2, 47.9, 45.1, 44.7, 41.8, 38.8, 35.4, 32.0, 30.7, 28.8,
22.0, 21.7, 17.4. IR (KBr thin film, CH2Cl2 solution): 3424 (br), 3356
(s), 2955 (s), 2875 (m), 1449 (w), 1048 (s), 762 (m), 690 (w), 558
(m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 311.2011; Found:
311.2004.
4.1.22. Compound (55). The procedure was followed as described
for compounds 39 & 40 to afford compound 55 as colorless oil in
49% yield. H NMR (500 MHz, CDCl3): d 7.20e7.29 (5H, m), 5.91 (1H,
s), 5.68 (1H, d, J¼2.5 Hz), 4.40 (1H, s), 4.07 (1H, d, J¼12.5 Hz), 4.01
(1H, t, J¼8.0 Hz), 3.65e3.68 (2H, m), 3.58 (1H, s), 3.54 (1H, s), 3.49
(1H, d, J¼3.0 Hz), 3.63 (1H, m), 2.51 (1H, m), 1.83 (2H, m). C NMR
4.1.19. Compound (50). The procedure was followed as described
for compounds 39 & 40 to afford compound 50 as colorless oil in
(125 MHz, CDCl3):
d 144.9, 141.0, 140.5, 130.2, 128.2, 127.0, 125.5,
76% yield. H NMR (500 MHz, C6D6):
d
7.30 (2H, m), 7.21 (2H, m), 7.11
118.2, 76.5, 72.0, 71.9, 49.0, 45.7, 45.4, 32.6, 31.4. IR (KBr thin film,
CH2Cl2 solution): 3430 (br), 3059 (s), 3037 (s), 2957 (m), 2852 (m),
2358 (w), 2338 (w), 1600 (w), 1490 (w), 1450 (m), 1383 (m), 1062
(m), 751 (s), 699 (w), 540 (m) cmꢀ1. DART-HRMS (m/z): calcd for
[MþH]þ: 269.1542; Found: 269.1547.
(1H, m), 6.02 (1H, qd, J¼10.5, 2.5 Hz), 5.95 (1H, td, J¼10.5, 3.0 Hz),
4.08 (1H, dd, J¼11.0, 5.0 Hz), 3.97 (1H, t, J¼3.5 Hz), 3.26 (1H, br),
3.09 (1H, m), 2.96 (1H, s), 2.36 (1H, m), 2.25 (1H, d, J¼16.5 Hz), 2.11
(1H, dd, J¼17.5, 9.0 Hz), 1.98 (1H, d, J¼16.5 Hz), 1.62 (1H, dd, J¼13.5,
8.5 Hz), 0.89 (3H, s), 0.73 (3H, s). C NMR (125 MHz, C6D6):
d 146.1,
138.8, 135.8, 133.0129.3, 128.7, 128.6, 128.2, 126.9, 82.5, 76.3, 51.0,
48.7, 45.7, 45.6, 39.5, 33.5, 29.6, 28.5, 24.0. IR (KBr thin film, CH2Cl2
solution): 3425 (br), 3060 (s), 3028 (s), 2935 (s), 1452 (w), 1077 (w),
760 (w), 701 (w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ:
311.2011; Found: 311.2012.
4.1.23. Compound (56). The procedure was followed as described
for compound 33 to afford compound 56 as colorless oil in 89%
yield. H NMR (500 MHz, CDCl3):
d 4.52 (1H, br), 3.84 (1H, d,
J¼9.5 Hz), 3.71 (1H, m), 3.70 (3H, s), 3.66 (1H, d, J¼10.0 Hz), 3.19
(1H, d, J¼10.5 Hz), 3.12 (1H, quintet, J¼5.0 Hz), 2.70 (1H, dd, J¼7.5,
2.5 Hz), 2.12 (1H, d, J¼2.5 Hz), 1.93 (2H, m), 1.77 (1H, dd, J¼12.0,
7.0 Hz), 1.69 (1H, td, J¼11.5, 7.0 Hz), 1.45 (1H, d, J¼3.0 Hz), 1.34 (1H,
4.1.20. Compound (52). The procedure was followed as described
for compound 33 to afford compound 52 as colorless oil in 91%
d, J¼5.5 Hz), 1.11 (1H, m). C NMR (125 MHz, CDCl3):
d 174.2, 73.5,
yield. H NMR (500 MHz, CDCl3):
d
7.33 (2H, m), 7.20 (3H, m), 4.50
73.0, 70.3, 52.3, 51.8, 43.2, 42.9, 42.6, 33.4, 32.6, 31.0, 23.1, 21.9. IR
(KBr thin film, CH2Cl2 solution): 3441 (w), 3060 (s), 3040 (s), 2921
(s), 2359 (w), 1732 (m), 1449 (w), 1265 (w), 1174 (w), 1070 (w), 758
(1H, m), 3.90 (1H, m), 3.64e3.71 (3H, m), 3.47 (1H, m), 2.96 (1H, m),
2.67 (1H, d, J¼10.0 Hz), 2.27 (1H, m), 1.96 (1H, dd, J¼10.0, 7.5 Hz),

J. He, M.L. Snapper / Tetrahedron 69 (2013) 7831e7839
7839
(w), 595 (w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 251.1283;
CH2Cl2 solution): 3502 (w), 3425 (w), 3348 (w), 3059 (m), 3026 (s),
2936 (s), 2853 (w), 2406 (w), 1449 (w), 1384 (w), 1068 (w), 761 (s),
696 (s), 544 (m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ:
311.2011; Found: 311.2017.
Found: 251.1283.
4.1.24. Thermolysis product (57). The procedure was followed as
described for compounds 39 & 40 to afford compound 57 as col-
orless oil in 70% yield. H NMR (500 MHz, C6D6): d 5.63 (1H, s), 5.45
Acknowledgements
(1H, dd, J¼6.0, 2.0 Hz), 4.50 (1H, d, J¼12.0 Hz), 4.19 (1H, d,
J¼12.0 Hz), 3.99 (1H, t, J¼3.5 Hz), 3.81 (2H, d, J¼7.0 Hz), 3.30 (3H,
s), 2.97e3.01 (3H, m), 2.41 (1H, m), 2.17 (1H, dd, J¼15.5, 10.5 Hz),
1.63e1.68 (1H, m), 1.36e1.44 (1H, m). C NMR (125 MHz, CDCl3):
J.H. acknowledges a Boston College Graduate Fellowship for fi-
nancial support. We also wish to congratulate Paul Wender on re-
ceiving the 2012 Tetrahedron Prize for his many creative
contributions to organic chemistry.
d
172.9, 145.6, 144.4, 119.7, 118.4, 75.9, 73.0, 72.8, 51.9, 50.0, 46.4,
43.9, 32.8, 32.2. IR (KBr thin film, CH2Cl2 solution): 3422 (br), 3059
(s), 3026 (m), 2902 (w), 2359 (s), 2341 (s), 1735 (m), 1491 (w),
1450 (m), 1196 (m), 1168 (m), 1062 (w), 757 (s), 698 (s), 540
(m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 251.1283; Found:
251.1287.
Supplementary data
Additional experimental procedures, compound data, and 1H
NMR and 13C NMR spectra are available. Supplementary data re-
lated to this article can be found at http://dx.doi.org/10.1016/
j.tet.2013.05.129.
4.1.25. Compound (58). The procedure was followed as described
for compound 33 to afford compound 58 as colorless oil in 86%
yield. H NMR (500 MHz, CDCl3):
d
7.26 (3H, m), 7.15 (2H, t, J¼7.0 Hz),
References and notes
4.38 (1H, q, J¼7.0 Hz), 4.11 (1H, t, J¼7.0 Hz), 3.99 (1H, d, J¼8.5 Hz),
3.12 (1H, t, J¼6.5 Hz), 2.80 (1H, dd, J¼7.5, 2.5 Hz), 1.90 (1H, d,
1. Select examples: (a) Wender, P. A.; Lee, H. Y.; Wilhelm, R. S.; Williams, P. D. J.
Am. Chem. Soc. 1989, 111, 8954; (b) Wender, P. A.; McDonald, F. E. J. Am. Chem.
Soc. 1990, 112, 4956; (c) Shigeno, K.; Sasai, H.; Shibasaki, M. Tetrahedron Lett.
1992, 33, 4937; (d) Tokuno, R.; Tomiyama, H.; Sodeoka, M.; Shibasaki, M. Tet-
rahedron Lett. 1996, 37, 2449.
2. For a review of 5-7 ring formation strategies, see: Deak, H. L. Cyclopropanation/
Isomerization Strategies toward the Synthesis of Bicyclo[5.3.0]decane (5-7 Ring
Systems) and Application in Total Synthesis Ph.D. dissertation; Department of
Chemistry, Boston College: Chestnut Hill, 2004.
J¼2.5 Hz). C NMR (125 MHz, CDCl3):
d 143.7, 128.1, 127.2, 125.6, 80.5,
73.1, 49.1, 48.9, 46.9, 45.1, 42.9, 36.0, 34.0, 33.1, 31.2, 29.1, 26.9, 24.5,
21.8. IR (KBr thin film, CH2Cl2 solution): 3439 (m), 3356 (br), 3024
(s), 2952 (m), 2893 (w), 1601 (w), 1452 (m), 1055 (m), 760 (s), 697
(s), 557 (w), 538 (w) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ:
311.2011; Found: 311.1997.
3. Mehtn, G.; Pallavi, K.; Umarye, J. D. Chem. Commun. 2005, 4456.
4. Iimura, S.; Overman, L. E.; Paulini, R.; Zakarian, A. J. Am. Chem. Soc. 2006, 128,
13095.
5. Steward, C.; McDonald, R.; West, F. G. Org. Lett. 2011, 13, 720.
6. Li, C.; Wang, C.; Liang, B.; Zhang, X.; Deng, L.; Liang, S.; Chen, J.; Wu, Y.; Yang, Z.
J. Org. Chem. 2006, 71, 6892.
4.1.26. Compounds (59 & 60). The procedure was followed as de-
scribed for compounds 39 & 40 to afford a mixture of compounds
59 (63% yield) and 60 (33% yield) as colorless oils. Compound 59: H
NMR (500 MHz, C6D6):
d
7.46 (2H, d, J¼8.5 Hz), 7.16 (2H, m), 7.07
(1H, m), 5.70 (1H, br), 5.65 (1H, br), 3.96 (1H, t, J¼4.0 Hz), 3.71 (1H,
t, J¼2.0 Hz), 3.36 (1H, d, J¼8.5 Hz), 3.10 (1H, br), 2.99 (1H, br), 2.51
(1H, m), 2.28 (1H, m), 1.84 (1H, d, J¼14.0 Hz), 1.55 (2H, m), 1.41 (1H,
7. For example, see: Wender, P. A.; Jesudason, C. D.; Nakahira, H.; Tamura, N.;
Tebbe, A. L.; Ueno, Y. J. Am. Chem. Soc. 1997, 119, 12976.
8. Bennacer, B.; Fujiwara, M.; Lee, S.; Ojima, I. J. Am. Chem. Soc. 2005, 127, 17756.
9. (a) Limanto, J.; Snapper, M. L. J. Am. Chem. Soc. 2000, 122, 8071; (b) Bader, S. J.;
Snapper, M. L. J. Am. Chem. Soc. 2000, 127, 1201; (c) Randall, M. L.; Lo, P. C. K.;
Bonitatebus, P. J., Jr.; Snapper, M. L. J. Am. Chem. Soc. 1999, 121, 4534; (d) Lo, P. C.
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Intramolecular [2þ2] Photocycloadditions: using New Cycloaddition/Fragmenta-
tion Strategies toward Medium Ring-containing Natural Products Ph.D. disserta-
tion; Department of Chemistry, Boston College: MA, 2008.
m), 0.85 (3H, s), 0.72 (3H, s). C NMR (125 MHz, C6D6): d 144.2, 143.3,
140.7, 131.1, 128.7, 128.6, 128.2, 127.2, 125.9, 121.8, 82.3, 76.7, 52.1,
49.5, 47.7, 45.8, 40.8, 32.8, 32.0, 26.3, 20.2. IR (KBr thin film, CH2Cl2
solution): 3421 (w), 3334 (w), 2957 (m), 2926 (m), 2899 (w), 2359
(s), 2341 (s), 1698 (w), 1541 (w), 1464 (w), 778 (s), 767 (s), 739 (m),
529 (m) cmꢀ1. DART-HRMS (m/z): calcd for [MþH]þ: 311.2011;
10. Williams, M. J.; Deak, H. L.; Snapper, M. L. J. Am. Chem. Soc. 2007, 129, 486.
11. Padwa, A.; Krumpe, K. E. Tetrahedron 1992, 48, 5385.
Found: 311.2011. Compound 60: H NMR (500 MHz, C6D6):
d 7.21
12. Chemler, S. R.; Trauner, D.; Danishefsky, S. J. Angew. Chem., Int. Ed. 2001, 40, 4544.
13. Experimental details regarding the preparation of substrates not described in
the text can be found in the Supplementary data section He, J. Intramolecular
Cycloaddition of Cyclobutadiene: applications toward Functionalized 5-7-5 Tri-
cyclic Ring Systems and Guaiane Natural Products Ph.D. dissertation; Department
of Chemistry, Boston College: USA, 2013.
(3H, m), 7.10 (2H, m), 5.81 (1H, dd, J¼4.5, 2.0 Hz), 5.35 (1H, t,
J¼1.5 Hz), 4.04 (1H, t, J¼3.5 Hz), 3.89 (1H, dt, J¼7.5, 2.5 Hz), 3.14 (2H,
m), 2.99 (1H, s), 2.72 (1H, m), 2.63 (1H, d, J¼15.0 Hz), 2.23 (1H, dd,
J¼16.0,12.5 Hz), 2.13 (1H, d, J¼16.0 Hz),1.78 (1H, dd, J¼13.0, 8.0 Hz),
1.37 (1H, m), 0.87 (3H, s), 0.71 (3H, s). C NMR (125 MHz, C6D6):
14. Panborn, A. B.; Giardello, M. A.; Grubbs, R. H.; Rosen, R. K.; Timmers, F. J. Or-
ganometallics 1996, 12, 1518.
15. Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923.
16. Only compound 23 could be isolated in a pure state.
d
148.1, 145.9, 142.7, 129.7, 129.0, 128.6, 128.1, 126.6, 118.2, 82.4, 76.8,
52.2, 50.4, 46.7, 45.0, 39.2, 32.1, 30.6, 27.7, 23.2. IR (KBr thin film,