Studies on thermal reactivity of β-(1,2-allenyl)butenolides and 2-allyl-3-allenylcyclohex-2-enones

Article abstract of DOI:10.1002/chem.200701171

A series of thermal pericyclic reactions of β-allenylfuranones have been studied. It was observed that β-allenylfuranones would undergo 1,5-hydrogen shift to afford a new type of trienes upon heating. Due to their high reactivity, these trienes would undergo subsequent pericyclic reactions based on the nature of the substituent group R: When R is an alkyl group, the intermediate 4a or 4b would undergo a further 1,7-hydrogen shift to afford a more stable conjugated triene 3; with R being phenyl or cyclopropyl group, the 1,7-hydrogen shift was inhibited and the 4-type conjugated triene would form a six-membered ring 5 via 6π-electrocyclization. Interestingly, introducing another C=C double bond into the triene intermediate (R = CH=CH₂), the 18-type intermediate would undergo 8π-electrocyclization reaction to form an eight-membered ring. Such a transformation was also observed with 2-allyl-3-allenylcyclohex-2-enones. The deuterium-labeling mechanistic studies show that the alkyl groups at the allenyl moiety of 1 participated in the isomerization process via 1,7-hydrogen shifts between 18 A, 20A, and 29 A.

Full text of DOI:10.1002/chem.200701171

FULL PAPER
DOI: 10.1002/chem.200701171
Studies on Thermal Reactivity of b-(1,2-Allenyl)butenolides and
2-Allyl-3-allenylcyclohex-2-enones
Zhenhua Gu and Shengming Ma*[a]
Abstract: A series of thermal pericyclic
reactions of b-allenylfuranones have
been studied. It was observed that b-al-
lenylfuranones would undergo 1,5-hy-
drogen shift to afford a new type of tri-
enes upon heating. Due to their high
reactivity, these trienes would undergo
subsequent pericyclic reactions based
on the nature of the substituent group
R: When R is an alkyl group, the inter-
mediate 4a or 4b would undergo a fur-
more stable conjugated triene 3; with
CH2), the 18-type intermediate would
undergo 8p-electrocyclization reaction
to form an eight-membered ring. Such
a transformation was also observed
with 2-allyl-3-allenylcyclohex-2-enones.
The deuterium-labeling mechanistic
studies show that the alkyl groups at
the allenyl moiety of 1 participated in
the isomerization process via 1,7-hy-
drogen shifts between 18A, 20A, and
29A.
Rbeing phenyl or cyclopropyl group,
the 1,7-hydrogen shift was inhibited
and the 4-type conjugated triene would
form a six-membered ring 5 via 6p-
electrocyclization. Interestingly, intro-
ducing another C=C double bond into
the triene intermediate (R
= CH=
Keywords: allenes
· cyclization ·
hydrogen shift · ketones · lactones
ther 1,7-hydrogen shift to afford
a
Introduction
available structures, has been of great theoretical and practi-
cal interest.[5] For example, the classical thermal 1,7-hydro-
gen shift is considered to be a pivotal event in the metabolic
production of vitamin D.[6] Hoeger et al. studied the stereo-
chemistry of 1,7-H of the vitamin D-type compounds
(Scheme 1).[6c] Okamura et al. and Jensen systematically
studied the pericyclic reactions of vinylallenes, respectively
(Scheme 2).[7] An interesting Alder–ene reaction between an
Furanones are an important structural unit in natural prod-
ucts and useful intermediates in organic synthesis. The fura-
none-containing natural products usually exhibit interesting
biological activities.[1,2] Thus, many methods for the synthesis
of furanone derivatives have been developed.[3] Recently an
efficient protocol has been developed in this group for the
synthesis of b-allenylfuranones.[4] The interesting 1,3,4-triene
within b-allenylfuranones has shown some synthetic poten-
tial, that is, the Diels–Alder reaction with electron-deficient
alkynes for the synthesis of poly- or fully-substituted ben-
zenes.[4] On the other hand, the sigmatropic hydrogen migra-
tion, which provides an efficient route to some not-readily-
Scheme 1.
[a] Dr. Z. Gu, Prof. Dr. S. Ma
State Key Laboratory of Organometallic Chemistry
Shanghai Institute of Organic Chemistry
Chinese Academy of Sciences, 354 Fenglin Lu
Shanghai 200032 (PRChina)
Fax : (+86)21-6416-7510
E-mail: masm@mail.sioc.ac.cn
Supporting information for this article is available on the WWW
1
under http://www.chemeurj.org/ or from the author: H/13C NMR
spectra of all new compounds and experimental details not listed in
the text.
Scheme 2.
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2453

allene and an alkene was reported by Bäckvall et al.[8a] since
allenes and alkenes preferentially form cyclobutanes via
[2+2] cycloaddition rather than Alder–ene products
(Scheme 3). Hashmi and Szeimies have also reported ene re-
Results and Discussion
Preparation of starting materials: The b-allenylfuranone de-
rivatives were synthesized via the palladium-catalyzed cross-
coupling reaction of 2,3-allenoic acids with propargyl carbo-
nates.[4] The results are listed in Scheme 5.
2-Allyl-3-allenylcyclohex-2-enone derivatives were pre-
pared via the Negishi coupling of 2-allyl-3-(pseudo)halocy-
clohex-2-enone derivatives with the allenylic zinc reagent
(Scheme 6).
Scheme 3.
actions for intramolecular allenes.[8b] During the study of the
cross-coupling reaction of 2,3-allenoic acids with methyl pro-
pionate, we have also observed an interesting p-bond migra-
tion, which may proceed through double 1,7-hydrogen shifts
via the intermediates A and B (Scheme 4).[9] In this paper,
we wish to report our observation on the thermal reactivities
of b-allenylfuranones and 2-allyl-3-allenylcyclohex-2-enone.
Scheme 6.
Sequential 1,5-H shift and 1,7-H shift reactions of a-alkyl-b-
allenylfuranones: The pericyclic reaction of 1a was explored
first. Interestingly, heating 1a in xylene under reflux afford-
ed two isomeric conjugated trienes (E,E)-3a and (E,Z)-3a
Scheme 4.
Scheme 7.
Scheme 5.
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Thermal Reactivity of Butenolides and Cyclohexenone Derivatives
FULL PAPER
together with some unidentified products (Scheme 7). The
structure of (E,Z)-3a was further confirmed by the X-ray
diffraction analysis (Figure 1).[10] These results greatly en-
Scheme 9.
Figure 1. ORTEP representation of (E,Z)-3a.
couraged us to further explore this reaction. We proposed
that 1,5-hydrogen shift of 1a would afford the intermediate
4. The two conformers of 4, that is, 4a and 4b, would give
(E,E)-3a and (E,Z)-3a via 1,7-hydrogen shift, respectively.[9]
To the best of our knowledge, the report on 1,7-hydrogen
shift of acyclic triene via 4a-type conformation is fairly
rare.[6,7] Due to the steric hindrance, conformer 4a should
be favorable. Actually, when the more sterically hindered
1b with an isobutyl group at a-position was used, (E)-3b
was formed as the only isomer. Furthermore, under the
same conditions, the reaction of 1c afforded (E)-3c in 66%
yield with 10% of the starting material remaining even with
a prolonged the reaction time of 6 h (Scheme 8).
Figure 2. ORTEP representations of trans-5d (top) and trans-5e
(bottom).
Scheme 8. [a] 10% of 1c was recovered.
trans-5d (Figure 2, top).[11] Interestingly, even the reaction of
1e did not form triene 3e although there is a hydrogen in
the intermediate 4e for possible 1,7-hydrogen shift
(Scheme 10). The formation of 5e and its relative stereo-
chemistry were further established by its X-ray diffraction
study (Figure 2, bottom).[12]
Sequential 1,5-H shift and 6p-electrocyclization reaction of
a-benzyl (or cyclopropylmethyl)-b-allenylfuranones: It was
reasoned that if a benzyl group was introduced at the a-po-
sition of the starting butenolide, for example, 1d, the subse-
quent 1,7-hydrogen shift of the 1,5-H shift product 4d would
be impossible, and may thus undergo a 6p-electrocyclization
reaction to afford a new six-membered ring. In fact, such a
transformation was observed at a higher temperatures:
when heating 1d at 2008C in xylene in a Schlenk tube with
a screw cap, bicyclic lactone 5d was formed in 70% yield
with a diastereoselectivity of 1.9:1 (Scheme 9). The stereo-
chemistry was established by the X-ray diffraction studies of
Cycloisomerization of a-allyl-b-allenylfuranones: The results
mentioned above encouraged us to develop a new reaction
based on these a-allyl-b-allenylfuranones. It was reasoned
that the intermediate 4 f may undergo 8p-electrocyclization
reaction to afford an eight-membered ring.[13,14] Fortunately,
it is interesting to observe that stirring the a-allyl substituted
b-allenyl-butenolide 1 f under a milder condition (1008C,
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2455

S. Ma and Z. Gu
11–14% yield (Scheme 12). The structure of 7 was further
established by the X-ray diffraction analysis of 7s
(Figure 3).[19]
Scheme 10.
6 h) in xylene afforded the eight-membered product 6 f in
89% isolated yield (Scheme 11).[14] The importance of eight-
membered cyclic compounds[15–18] has prompted us to con-
duct a comprehensive study on this isomerization reaction.
Scheme 12.
Scheme 11.
The general studies on the cycloisomerization reaction at
1008C in xylene were listed in Table 1. The substituents R1,
R2 at the 5-position of the furanones and R3, R4 at the
allene moiety proved to be general.[14]
It is interesting to observe when R3,R4 is -(CH2)4-, besides
the formation of the eight-membered products, we also iso-
lated the intramolecular tricyclic Diels–Alder products 7 in
Figure 3. ORTEP representation of 7s.
Cycloisomerization of 2-allyl-3-allenylcyclohex-2-enone de-
rivatives: For a more general understanding of the scope of
this cycloisomerization reaction, 2a, which has a 2-cyclohex-
enone core, was synthesized. To our surprise, heating 8za at
808C for 3 h in xylene, instead of forming the eight-mem-
bered product, we isolated two isomeric products 8aa and
8ab. The bromination of one of the isomers, that is, 8ab, af-
forded two products 10aba and 10abb for structural deter-
mination. Thus, the identities of 8aa and 8ab have been suc-
cessfully established by the X-ray diffraction studies of
10aba (Figure 4, top).[20] Compounds 8aa and 8ab are obvi-
ously the intermolecular Diels–Alder products of two mole-
cules of the possible tricyclic intermediate 9a (Scheme 13).
Based on these results, another pathway for this isomeri-
zation shown in Scheme 14 has been proposed: [2+2] cyclo-
addition of allene–ene of 1 would afford tricyclic intermedi-
ate 11. Subsequent 1,5-hydrogen shift of 11 would give 12,
which is likely to afford 5 via electrocyclic rearrangement.
In order to trap the intermediate 9a, some electron-deficient
alkenes were added to the reaction mixture: upon heating
of compound 2a in the presence of 13 at 558C in xylene,
products 14 were formed as the only diastereomer in moder-
Table 1. Cycloisomerization reaction of a-allyl-b-allenylfuranones 1.[a]
Entry
Substrate 1
Yield of 6 [%]
R1
R2
R3
R4
1[b]
2
3
4
5
6
7
8
9
Ph
Ph
Me
Me
H
H
Me
Me
Me
H
H
H
H
H
Me
Me (1g)
84 (6g)
80 (6h)
83 (6i)
-(CH2)5- (1h)
Et
Et (1i)
Me
Ph
Et
Me
Et
Et (1j)
Me (1k)
Et (1l)
Me (1m)
Et (1n)
Me (1o)
Et (1p)
74 (6j)
48 (6k)
97 (6l)
87 (6m)
95 (6n)
84 (6o)
84 (6p)
89 (6q)
Me
a-naphthyl
a-naphthyl
p-BrC6H4
p-BrC6H4
Et
Me
Et
10
11
Et
H
-(CH2)5- (1q)
[a] Under an argon atmosphere, a solution of 0.15–0.25 mmol of 1 in
4 mL xylene was stirred at 1008C for 6 h. [b] The reaction time was 7 h.
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Thermal Reactivity of Butenolides and Cyclohexenone Derivatives
FULL PAPER
an equilibrium between bicyclic conjugated trienes 15 and
tricyclic dienes 9 via the reversible 6p-pericyclic process.[22]
As expected, heating the bicyclic ketone 15b at 558C in the
presence of 13b also afforded 14bb in 53% yield, which
confirmed that 15b and 9b did interconvert upon heating
(Scheme 18).
Mechanistic study of cycloisomerization of (1,2,4Z,7)-tet-
raenes: However, there still remains an important issue for
this 1,5-H shift process: in principle, the 1,5-H shift of 1
would give two stereoisomers 18 and 20 via transition states
17 and 19, respectively (Scheme 19). Furthermore, com-
pound 20 would not give the eight-membered ring com-
pounds via 8p-electrocyclization due to steric reasons.
To further confirm this 1,5-H shift process, we applied
deuterium labeled a-allyl-b-allenylfuranones as mechanistic
probes. Compound [D5]-1g-(allyl) was synthesized according
to the chemistry shown in Scheme 20. Based on the proce-
dures established by Lebeau et al.,[23] we synthesized fully
deuterated allyl mesylate [D5]-24-(allyl). In the presence of
CuI, allylic mesylate [D5]-24-(allyl) coupled with 1-phenyl-
prop-2-yn-1-ol to afford 4,4,5,6,6-pentadeutero-1-phenyl-2-
hexyn-5-enol [D5]-25-(allyl),[24] which was converted to 2,3-
allenoic acid [D5]-26-(allyl) under the catalysis of [Pd-
AHCTREUNG
cross-coupling cyclization of [D5]-26-(allyl) with methyl 2-
methylbut-3-yn-2-yl carbonate.[4] Heating [D5]-1g-(allyl) at
1108C for 6 h in xylene gave [D5]-6g in 64% yield.[13] Based
1
on careful H NMRanalysis, it was observed that the proton
connected to the center carbon atom of the allene moiety in
[D5]-1g-(allyl) was 93% deuterated. In addition, to our sur-
prise, only 82% [D] was incorporated at the 4-position of
[D5]-6g (Scheme 21). This means that ~18% of deuterium
atom at the methenyl group of [D5]-1g-(allyl) was lost
during this cycloisomerization process. Further studies show
that ~3% of D were incorporated into the two methyl
groups (Figure 5a). These results prompted us to consider
that the two methyl groups in [D5]-1g-(allyl) may be in-
volved in the isomerization process.
Figure 4. ORTEP representations of 10aba (top) and 14aa (bottom).
ate to high yields. The structure was also determined by the
X-ray diffraction analysis of 14aa (Figure 4, bottom).[21] The
electron-deficient alkyne DMAD 13d also reacted with 2a
to afford products 14ad highly stereoselectively in 52%
yield (Scheme 15).
In order to suppress the intermolecular Diels–Alder reac-
tion, the more sterically demanding substrates 2b–d were
synthesized. To our delight, we obtained the expected eight-
membered compounds 15b–d in moderate yields by heating
these compounds at 908C for 2 h in xylene. Furthermore, we
even isolated tricyclic product 9c in 8% yield with R =
nBu, while the formation of product 9b (R = Me) could be
observed by 1H NMRspectroscopy (Scheme 16).
In order to clarify the mechanism further, butenolide
[D6]-1g-(CD3)2, where all the hydrogen atoms of the two
methyl groups of the allenyl moiety were deuterated, was
synthesized according to Scheme 22. The reaction of ethy-
nylmagnesium bromide with CD3COCD3 produced [D6]-27-
(CD3)2-H(D), which can be easily converted to propargyl
1
carbonate [D6]-28-(CD3)2-H(D). The H NMRspectra clear-
ly show that the terminal alkyne was partially deuterated.
The treatment of terminal alkyne [D6]-28-(CD3)2-H(D) with
nBuLi in THF at À788C followed by quenching with water
at this temperature produced [D6]-28-(CD3)2. Compound
[D6]-1g-(CD3)2 was then synthesized via the palladium-cata-
lyzed coupling reaction of 2-allyl-4-phenylbuta-2,3-dienoic
acid with [D6]-28-(CD3)2 in 54% yield with 95% of deuteri-
um content.[4]
Interestingly, reaction of (1,2,4Z,7)-tetraene 2e, which
was prepared in situ via the Claisen-type rearrangement re-
action of 16 with CH3C(OEt)3, afforded tricyclic compound
G
9e instead of the formation of eight-membered ring com-
pound (Scheme 17).
Trapping of the intermediate 9, however, is not enough to
confirm the route shown in Scheme 14 since there may exist
Under the same reaction conditions, [D6]-6g was formed
in 73% yield with 60% [D] incorporated at 4-position while
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S. Ma and Z. Gu
Taking all these experimental
data into account as well as the
stereochemistry
shown
in
Scheme 19, we proposed the
following reaction pathway
(Scheme 24). First, 1,5-H shift
of 1A would afford two stereo-
isomers, 18A and 20A. Howev-
er, tetraene 18A would give the
eight-membered ring compound
6A via 8p-electrocyclization
while 20A could not due to the
steric requirement of the 8p-
electrocyclization.[13] However,
1,7-H shift of 20A may afford
intermediate 29A, which could
give 18A or 20A via another
1,7-H shift. The equilibrium of
18A and 20A upon heating via
the intermediate 29A was clear-
ly supported the D-labeling re-
sults shown in Schemes 21 and
23.
Scheme 13.
Scheme 14.
Scheme 16.
Scheme 17.
Scheme 15.
the deuterium incorporation at methyl group dropped from
95 to 85% (Scheme 23), which clearly indicates that the
methyl groups were involved in the cycloisomerization pro-
cess (Figure 5b).
Scheme 18. [a] 28% of 15b was recovered.
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Thermal Reactivity of Butenolides and Cyclohexenone Derivatives
FULL PAPER
Scheme 22. Synthesis of [D6]-1g-(CD3)2: a) C2H5Br, Mg, THF, then acety-
lene; b) CD3COCD3, 34%; c) NaH, Et2O, then ClCO2Me, 71%; d)
nBuLi, Et2O, À788C; then H2O, À788C, 38%; e) 2-allyl-4-phenylbuta-
2,3-dienoic acid, Pd(OAc)2/TFP, K2CO3, DMSO, 54%.
A
Scheme 19.
Scheme 23. Isomerization of [D6]1g(CD3)2.
A
Conclusion
Scheme 20. Synthesis of [D5]-1g-(allyl): a) n-C6H13OH, cat. pTsOH, ben-
zene, 100%; b) D2O, K2CO3, TBAB, repeat 4”, 96% [D]; c) LiAlD4,
Et2O, then D2O; d) MsCl, Et3N, Et2O, 39% for three steps; e) 1-phenyl-
prop-2-yn-1-ol, CuI, K2CO3, DMF, 74%; f) nBuLi, LiBr, THF, À788C,
We have studied the thermal reaction of b-allenylfuranones.
It is interesting to observe that 1,5-hydrogen shift of b-alle-
nylfuranones 1 is general upon heating, which would afford
a new conjugated trienes, that is, 4 and 18. Due to their high
reactivity, these trienes would undergo subsequent pericyclic
reaction based on the nature of the Rgroup (Scheme 25):
When Ris an alkyl groups, the intermediate 4 would under-
go a further 1,7-hydrogen shift to afford a more stable
triene 3; when R = phenyl or cyclopropyl group, triene 4d
or 4e would form a six-membered ring via 6p-electrocyliza-
tion; Interesting 8p-electrocylization reaction of tetraene 18
forming eight-membered ring was observed when Ris a
vinyl group. Furthermore, not only the furanone derivatives,
then pTsCl; g) [Pd(PPh3)4], CO, THF, H2O, 43% for two steps; h)
N
methyl 2-methylbut-3-yn-2-yl carbonate, Pd
62%.
A
Scheme 21. Cycloisomerization of [D5]-1g-(allyl).
Figure 5. 1H NMRspectrum of a) [D ]-6g; b) [D6]-6g; c) 6g.
5
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S. Ma and Z. Gu
Synthesis of the starting materials b-allenylfuran-2(5H)-ones
3-Isobutyl-4-(3’-methylbuta-1’,2’-dienyl)-5-phenylfuran-2(5H)-one (1b):
Under an argon atmosphere, a mixture of 2-isobutyl-4-phenylbuta-2,3-di-
enoic acid (217 mg, 1.00 mmol), methyl 2-methylbut-3-yn-2-yl carbonate
(282 mg, 2.00 mmol), Pd(OAc)2 (11 mg, 0.05 mmol), tri-2-furylphosphine
G
(TFP) (23 mg, 0.10 mmol), and K2CO3 (138 mg, 1.00 mmol) in DMSO
(4 mL) was stirred at 308C for 3 h. After complete consumption of the
starting material as monitored by TLC, the mixture was directly purified
via flash chromatography on silica gel (petroleum ether/ethyl acetate
15:1) to afford 1b (106 mg, 38%). 1H NMR(300 MHz, CDCl 3): d
=
7.38–7.22 (m, 3H), 7.20–7.10 (m, 2H), 5.90 (heptet, J=3.0 Hz, 1H), 5.68
(s, 1H), 2.35–2.19 (m, 2H), 2.11–1.91 (m, 1H), 1.63 (d, J=3.0 Hz, 3H),
1.01 (d, J=3.0 Hz, 3H), 0.963 (d, J=6.3 Hz, 3H), 0.957 ppm (d, J=
6.3 Hz, 3H); 13C NMR(75.4 MHz, CDCl 3): d = 18.8, 19.4, 22.4, 22.5,
27.9, 32.5, 83.0, 83.8, 99.7, 125.8, 127.5, 128.5, 128.9, 136.1, 155.9, 174.1,
208.0 ppm; IR(neat): n˜ = 1951, 1752, 1643, 1456, 1300, 1083, 1003 cmÀ1
;
MS (EI): m/z (%): 282 (5.38) [M+], 57 (100); HRMS: m/z: calcd for
C19H22O2: 282.1620 [M+]; found: 282.1629.
Synthesis of 2-allylic 3-allenylic cyclohex-2-enone derivatives
2-Allyl-3-(3’-methylbuta-1’,2’-dienyl)cyclohex-2-enone (2a)—Typical Pro-
cedure for the preparation of 2-allylic 3-allenylic cyclohex-2-enone
a) Preparation of the allenyllic zinc reagent: To a flame dried Schlenk
tube were added zinc (flame dried, 0.448 g, 7.0 mmol) and fleshly distilled
(Na/benzophenone) THF (5 mL). To this suspension was added
BrCH2CH2Br (20 mL) followed by heating to gentle reflux. After cooling
down to RT, TMSCl (20 mL) was added to the reaction mixture with stir-
ring. After the formation of gray suspension, a solution of 1-bromo-3-
methylbuta-1,2-diene[26] in THF (3 mL) was added dropwise to the reac-
tion tube and allowed to stir at RT for 4 h to afford the zinc reagent
needed for next step.
Scheme 24. Plausible pathway.
b) Palladium-catalyzed coupling of 2-allyl-3-iodocyclohex-2-enone with
zinc reagent: The allenyl zinc reagent (0.625 molLÀ1 in THF, prepared
above) (1.60 mL, 1.00 mmol) was added to a mixture of [Pd
(18 mg, 0.026 mmol),
ACHTREUNG
2-allyl-3-iodocyclohex-2-enone[27]
0.5 mmol), and THF (4 mL) with stirring in a flame dried Schlenk tube.
Then the mixture was stirred at RT for 1.5 h. After complete consump-
tion of the starting material as monitored by TLC, THF was removed by
evaporation and the residue was purified via flash chromatography on
silica gel (petroleum ether/ethyl acetate 25:1) to afford 2a (64 mg, 64%).
1H NMR(300 MHz, CDCl ): d = 6.12 (heptet, J=3.0 Hz, 1H), 5.82–5.68
3
(m, 1H), 5.00–4.88 (m, 2H), 3.14 (d, J=6.0 Hz, 2H), 2.45–2.35 (m, 4H),
2.00–1.85 (m, 2H), 1.76 ppm (d, J=3.0 Hz, 6H); 13C NMR(75.4 MHz,
CDCl3): d = 19.8, 22.1, 27.6, 28.7, 37.9, 92.0, 98.7, 114.6, 132.0, 136.0,
151.7, 198.3, 207.5 ppm; IR(neat): n˜ = 1945, 1660, 1593, 1434, 1363,
1184 cmÀ1; MS(EI): m/z (%): 202 (6.32) [M+], 41 (100); HRMS: m/z:
calcd for C14H18O: 202.1358 [M+]; found: 202.1355.
Scheme 25.
Sequential 1,5-H shift and 1,7-H shift reactions of 3-alkyl-4-allenylfuran-
2(5H)-ones
3-(Prop-1’(E)-enyl)-4-(3’-ethylpent-1’(E)-enyl)-5-(naphth-1’-yl)furan-
2(5H)-one [(E,E)-3a] and 3-(prop-1’(E)-enyl)-4-(3-ethylpent-1’(Z)-enyl)-
5-(naphth-1’-yl)furan-2(5H)-one [(E,Z)-3a]: Under an argon atmosphere,
a solution of 1a (140 g, 0.40 mmol) in xylene (6 mL) was stirred under
reflux for 6 h. After complete consumption of the starting material as
monitored by TLC, the mixture was directly purified via flash chromatog-
raphy on silica gel to afford (E,Z)-3a (less polar, 10 mg, 7%), (E,E)-3a
(more polar, 41 mg, 29%), and unidentified products (70 mg). (E,Z)-3a:
Solid; m.p. 72–748C (Et2O/petroleum ether); 1H NMR(300 MHz,
CDCl3): d = 8.20 (d, J=8.4 Hz, 1H), 7.88 (t, J=9.0 Hz, 2H), 7.65–7.50
(m, 2H), 7.40 (t, J=7.8 Hz, 1H), 7.24 (d, J=7.2 Hz, 1H), 7.09 (dq, J=
6.9, 15.3 Hz, 1H), 6.80 (s, 1H), 6.32 (dd, J=1.2, 15.3 Hz, 1H), 6.29 (d, J=
12.0 Hz, 1H), 5.49 (t, J=12.0 Hz, 1H), 1.94 (d, J=6.9 Hz, 3H), 1.82–1.68
(m, 1H), 1.40–1.18 (m, 1H), 1.12–0.90 (m, 2H), 0.74 (t, J=7.5 Hz, 3H),
0.80–0.60 (m, 1H), 0.15 ppm (t, J=7.5 Hz, 3H); 13C NMR(75.4 MHz,
CDCl3): d = 10.8, 11.7, 19.5, 26.9, 27.1, 42.9, 79.0, 118.4, 119.3, 122.6,
124.4, 125.2, 125.7, 126.0, 127.0, 128.9, 130.0, 131.3, 131.7, 133.8, 134.2,
145.4, 153.2, 171.9 ppm; IR(neat): n˜ = 1752, 1637, 1456 cmÀ1; MS (ESI):
m/z: 369 [M+Na+], 347 [M++H]; HRMS: m/z: calcd for C24H26O2:
346.1933 [M+]; found: 346.1928. (E,E)-3a: 1H NMR(300 MHz, CDCl 3):
but also (1,2,4Z,7)-tetraenes bearing a 2-cyclohexenone core
have been studied for the formation of eight-membered
compounds. The deuterium-labeling experiments show that
the alkyl groups at the allenyl moiety of a-allyl-b-furanones
were involved in the isomerization process. The 1,7-hydro-
gen shifts may play an important role in the conversion
from (Z)-tetraene 20 to (E)-tetraene 18. Further studies in
this area are being conducted in this laboratory.
Experimental Section
The analytic data of 1a, 6 f–r, 6t, 14ab, 14bb, and 15b, as well as general
methods have been published in the Supporting Information of referen-
ces [4] and [15].
2460
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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2453 – 2464

Thermal Reactivity of Butenolides and Cyclohexenone Derivatives
FULL PAPER
d = 8.29 (d, J=8.7 Hz, 1H), 7.90 (t, J=9.0 Hz, 2H), 7.68–7.51 (m, 2H),
7.42 (t, J=7.8 Hz, 1H), 7.28 (dd, J=1.2, 7.2 Hz, 1H), 6.81 (s, 1H), 6.30
(d, J=16.2 Hz, 1H), 6.20–6.03 (m, 2H), 5.45 (dd, J=9.3, 16.2 Hz, 1H),
1.90–1.72 (m, 4H), 1.37–1.15 (m, 2H), 1.15–1.00 (m, 1H), 0.96–0.77 (m,
1H), 0.72 (t, J=7.2 Hz, 3H), 0.52 ppm (t, J=7.5 Hz, 3H); 13C NMR
(75.4 MHz, CDCl3): d = 11.5, 11.7, 16.1, 26.9, 27.2, 47.6, 78.8, 118.3,
121.7, 123.0, 124.2, 125.0, 126.1, 126.3, 126.9, 128.9, 130.1, 131.8, 131.9,
133.6, 133.8, 147.9, 155.8, 172.6 ppm; IR(neat): n˜ = 1754, 1639, 1512,
1457, 1036 cmÀ1; MS (ESI): m/z: 347 [M++H]; HRMS: m/z: calcd for
C24H26O2Na: 369.1825 [M++Na]; found: 369.1839.
1398, 1258, 1195 cmÀ1; MS (EI): m/z (%): 292 [M+À2
N
C(Me)2]]; found: 292.1464.
Compounds 10aba and 10abb: To a stirred solution of 8ab (41 mg,
0.10 mmol) in CH2Cl2 (3 mL) was added Br2 (1.0 mL, 0.188 molLÀ1 in
CH2Cl2) and stirred at RT for 15 min. After complete consumption of the
starting material as monitored by TLC, an aqueous solution of Na2S2O3
was added. The mixture was extracted with ether (50 mL), washed with
brine, and dried over anhydrous Na2SO4. After evaporation of the sol-
vent, the residue was purified via flash chromatography on silica gel (pe-
troleum ether/ethyl acetate 10:1) to afford 10aba (less polar, 28 mg,
57%) and 10abb (more polar, 19 mg, 39%). 10aba: Solid, m.p. 154–
Sequential 1,5-H shift and 6p-electrocyclization reaction of 3-benzyl (or
cyclopropylmethylene)-4-allenylfuran-2(5H)-ones
1558C (CH2Cl2/Et2O); 1H NMR(300 MHz, CDCl 3): d
6,6-Dimethyl-3,7-diphenyl-6,7-dihydroisobenzofuran-1(3H)-one
(5d):
2.7 Hz, 1H), 4.54 (t, J=4.5 Hz, 1H), 3.44 (d, J=3.3 Hz, 1H), 3.15–3.10
(m, 1H), 2.90–2.75 (m, 1H), 2.60–2.20 (m, 11H), 2.15 (s, 1H), 2.15–1.90
(m, 2H), 1.60–1.48 (m, 2H), 1.17 (s, 3H), 1.10–1.00 (m, 4H), 0.95 (t, J=
10.2 Hz, 1H), 0.79 ppm (s, 6H); 13C NMR(75.4 MHz, CDCl 3): d = 23.3,
23.8, 24.9, 25.6, 28.0, 29.1, 31.0, 31.4, 33.6, 35.2, 35.5, 36.4, 37.3, 37.5, 38.8,
39.0, 39.2, 41.8, 46.3, 47.3, 49.9, 55.3, 128.8, 134.3, 140.3, 160.6, 195.6,
203.4 ppm; IR(neat): n˜ = 1700, 1662, 1451, 1398, 1261, 1192 cmÀ1; MS-
Under an argon atmosphere, a mixture of 1d (53 mg, 0.17 mmol) in
xylene (4 mL) in a Schlenk tube with a screw cap was stirred at 2008C
for 5 h. The mixture was directly purified via flash chromatography on
silica gel to afford trans-5d (less polar, 24 mg, 45%) and cis-5d (more
polar, 13 mg, 25%). trans-5d: Solid, m.p. 157–1598C (ethyl acetate/petro-
leum ether); 1H NMR(300 MHz, CDCl 3): d = 7.48–7.37 (m, 3H), 7.36–
7.18 (m, 7H), 6.06 (d, J=9.3 Hz, 1H), 6.01 (d, J=9.3 Hz, 1H), 6.00 (s,
1H), 3.60 (s, 1H), 1.22 (s, 3H), 0.89 ppm (s, 3H); 13C NMR(75.4 MHz,
CDCl3): d = 25.4, 29.3, 38.0, 47.2, 82.2, 116.5, 125.7, 126.9, 127.4, 128.3,
129.0, 129.3, 134.5, 138.0, 149.0, 156.2, 172.4 ppm; IR(neat): n˜ = 1751,
1656, 1582, 1454, 1297, 1230, 1032 cmÀ1; MS(EI): m/z (%): 316 (40.08)
[M +], 105 (100); HRMS: m/z: calcd for C22H20O2: 316.1463 [M+]; found:
316.1476. cis-5d: 1H NMR(300 MHz, CDCl 3): d = 7.48–7.35 (m, 3H),
7.30–7.18 (m, 5H), 7.18–7.08 (m, 2H), 5.99 (d, J=9.6 Hz, 1H), 5.94 (d,
J=9.6 Hz, 1H), 5.89 (s, 1H), 3.55 (s, 1H), 1.25 (s, 3H), 0.84 ppm (s, 3H);
A
calcd (%) for C28H35BrO2: C 69.56, H 7.30; found: C 69.17, H 7.23.
10abb: 1H NMR(300 MHz, CDCl 3): d = 5.80 (d, J=2.4 Hz, 1H), 5.19
(dd, J=4.8, 12.3 Hz, 1H), 3.13 (t, J=2.7 Hz, 1H), 3.03 (d, J=3.0 Hz,
1H), 2.79–2.60 (m, 2H), 2.60–2.50 (m, 7H), 2.50–2.18 (m, 2H), 2.18–1.98
(m, 4H), 1.70–1.50 (m, 2H), 1.25–1.15 (m, 4H), 1.10–1.00 (m, 4H),
0.79 ppm (s, 6H); 13C NMR(75.4 MHz, CDCl 3): d = 23.2, 23.8, 24.8,
26.2, 28.2, 30.3, 30.8, 33.3, 33.7, 35.3, 36.0, 36.1, 37.2, 37.4, 38.76, 38.80,
39.1, 42.2, 45.0, 46.8, 55.0, 56.7, 129.8, 133.5, 140.7, 158.7, 195.1,
13C NMR(75.4 MHz, CDCl 3): d
125.4, 126.8, 127.4, 128.2, 128.4, 129.0, 129.3, 134.7, 138.5, 148.9, 156.2,
= 25.4, 29.5, 38.1, 46.7, 82.2, 116.2,
200.3 ppm; IR(neat): n˜ = 1720, 1660, 1451, 1396, 1257 cmÀ1; MS
(ESI):
G
m/z: 507 [(81Br)M+Na+], 505 [(79Br)M+Na+], 485 [(81Br)M++H], 483
[(79Br)M++H]; HRMS: m/z: calcd for C28H35O2BrNa:: 505.1713
[(79Br)M+Na+]; found: 505.1702.
172.6 ppm; IR(neat): n˜
= 1755, 1658, 1580, 1454, 1298, 1231, 1027,
1001 cmÀ1; MS (EI): m/z (%): 316 (13.92) [M +], 84 (100); HRMS: m/z:
calcd for C22H20O2: 316.1463 [M +]; found: 316.1464.
Cycloisomerization of 3-allyl-4-allenylfuran-2(5H)-ones
Preparation of 14aa via the Diels–Alder reaction of 2a with maleic anhy-
dride 13a: Under an argon atmosphere,
a solution of 2a (40 mg,
(3aZ,4Z,8Z)-6,6-Tetramethylene-3-phenyl-6,7-dihydrocycloocta[c]furan-
1(3H)-one (6r) and 7r: A solution of 1r (52 mg, 0.178 mmol) in xylene
(4 mL) was stirred at 1008C for 6 h. After complete consumption of the
starting material as monitored by TLC, the mixture was directly purified
via flash chromatography on silica gel to afford 7r (6 mg, 12%) and 6r[14]
(35 mg, 67%). 7r: 1H NMR(300 MHz, CDCl 3): d = 7.45–7.28 (m, 5H),
[6.16 (s), 5.60 (s), 6.12 (s), 5.98 (s), 2H], [2.75 (d, J=6.0 Hz), 2.71 (d, J=
6.0 Hz), 1H], 2.49–2.37 (m, 1H), 2.35–2.08 (m, 5H), 1.79–1.70 (m, 1H),
1.70–1.50 (m, 4H), [1.20 (dd, J=3.6, 6.9 Hz), 1.13 ppm (dd, J=3.6,
6.9 Hz), 1H]; IR(neat): n˜ = 1777, 1292, 1139, 1101 cmÀ1; MS (EI): m/z
(%): 292 (20.94) [M+], 84 (100); HRMS: m/z: calcd for C20H20O2:
292.1463 [M+]; found: 292.1465.
0.20 mmol) and 13a (98 mg, 1.00 mmol) in xylene (8 mL) was stirred at
558C for 24 h. After complete consumption of the starting material as
monitored by TLC, the reaction mixture was directly purified via flash
chromatography on silica gel (petroleum ether/ethyl acetate 5:1) to
afford 14aa (29 mg, 49%). Solid, m.p. 172–1748C (ethyl acetate/petrole-
um ether); 1H NMR(300 MHz, CDCl 3): d = 3.87 (dd, J=3.0, 4.2 Hz,
1H), 3.23 (t, J=3.0 Hz, 1H), 3.16–3.02 (m, 2H), 2.78–2.58 (m, 2H), 2.55–
2.37 (m, 3H), 2.18–1.98 (m, 3H), 1.66 (ddd, J=2.1, 8.7, 10.2 Hz, 1H),
1.16 (s, 3H), 1.09 (dd, J=6.6, 12.3 Hz, 1H), 0.85 ppm (s, 3H); 13C NMR
(75.4 MHz, CDCl3): d = 23.0, 23.8, 30.4, 30.9, 31.9, 32.4, 35.5, 36.3, 37.0,
39.8, 44.2, 44.6, 48.6, 135.6, 161.8, 171.2, 171.8, 194.2 ppm; IR(KBr): n˜ =
1835, 1779, 1666, 1625, 1401, 1231, 1076 cmÀ1; MS (ESI): m/z: 333
[M+MeOH+H+], 318 [M+NH4+], 301 [M++H]; elemental analysis
calcd (%) for C18H20O4: C 71.98, H 6.71; found: C 71.77, H 6.75.
Cycloisomerization of 2-allyl-3-allenylcyclohex-2-enone
Compounds 8aa and 8 ab: Under an argon atmosphere, a solution of 2a
(74 mg, 0.37 mmol) in xylene (4 mL) was stirred at 808C for 3 h. After
complete consumption of the starting material as monitored by TLC, the
reaction mixture was directly purified via flash chromatography on silica
gel (petroleum ether/ethyl acetate 20:1 and 10:1) to afford 8aa (26 mg,
35%) and 8ab (34 mg, 46%). 8aa: 1H NMR(300 MHz, CDCl 3): d =
5.55 (d, J=2.4 Hz, 1H), 3.10 (d, J=2.7 Hz, 1H), 3.00 (d, J=4.5 Hz, 1H),
2.85–2.56 (m, 4H), 2.56–2.08 (m, 8H), 2.08–1.95 (m, 2H), 1.79–1.60 (m,
3H), 1.59–1.40 (m, 2H), 1.18–0.98 (m, 8H), 0.78 (s, 3H), 0.71 ppm (s,
3H); 13C NMR(75.4 MHz, CDCl 3): d = 23.3, 23.9, 25.1, 27.4, 28.1, 31.8,
31.9, 32.0, 32.6, 33.2, 35.26, 35.29, 36.6, 37.0, 37.4, 37.6, 38.9, 39.6, 40.0,
45.1, 47.1, 60.6, 127.6, 136.4, 137.7, 161.8, 195.9, 210.3 ppm; IR(neat): n˜
= 1704, 1663, 1631, 1450, 1399, 1261, 1215 cmÀ1; MS (EI): m/z (%): 404
(7.29) [M+], 147 (100); HRMS: m/z: calcd for C24H28O2: 348.2089 [M+
Preparation of 14ac via the Diels–Alder reaction of 2a with N-phenyl-
maleimide 13c: Under an argon atmosphere, a solution of 2a (41 mg,
0.20 mmol) and 13c (69 mg, 0.40 mmol) in xylene (3 mL) was stirred at
558C for 36 h. After complete consumption of the starting material as
monitored by TLC, the reaction mixture was directly purified via flash
chromatography on silica gel (petroleum ether/ethyl acetate 4:1) to
afford 14ac (69 mg, 91%). Solid, m.p. 221–2238C (ethyl acetate/ether);
1H NMR(300 MHz, CDCl 3): d = 8.08–7.82 (m, 3H), 7.70–7.58 (m, 2H),
4.47 (d, J=2.1 Hz, 1H), 3.83 (s, 1H), 3.60–3.40 (m, 2H), 3.40–3.13 (m,
2H), 3.13–2.80 (m, 3H), 2.78–2.41 (m, 3H), 2.21 (t, J=10.5 Hz, 1H),
1.80–1.60 (m, 4H), 1.43 ppm (s, 3H); 13C NMR(75.4 MHz, CDCl 3): d =
23.1, 23.9, 30.4, 31.5, 32.4, 35.4, 36.4, 37.2, 40.0, 43.7, 44.0, 49.0, 125.8,
128.4, 129.0, 131.4, 135.3, 162.0, 176.2, 176.3, 194.3 ppm; IR(KBr): n˜ =
1778, 1711, 1662, 1618, 1598, 1499, 1390, 1187 cmÀ1; MS (ESI): m/z 398
[M+Na+], 393 [M+NH4+], 376 [M++H]; elemental analysis calcd (%)
for C24H25NO3: C 76.77, H 6.71, N 3.73; found: C 76.39, H 6.68, N 3.45.
1
ÀCH2=C(Me)2]; found: 348.2080. 8ab: H NMR(300 MHz, CDCl 3): d =
5.71 (d, J=2.4 Hz, 1H), 3.12–3.05 (m, 2H), 2.82–2.68 (m, 1H), 2.65–2.18
(m, 12H), 2.18–2.07 (m, 2H), 2.07–1.93 (m, 2H), 1.77–1.48 (m, 3H), 1.16
(s, 3H), 1.10–0.95 (m, 4H), 0.78 ppm (s, 6H); 13C NMR(75.4 MHz,
CDCl3): d = 23.1, 23.9, 24.8, 26.2, 26.6, 28.2, 30.5, 31.0, 33.0, 33.4, 34.8,
35.3, 35.9, 37.2, 37.5, 38.8, 39.1, 39.3, 42.1, 45.1, 46.3, 56.0, 128.1, 135.5,
140.2, 159.9, 195.3, 209.4 ppm; IR(neat): n˜ = 1702, 1657, 1635, 1448,
Preparation of 14ad via the Diels–Alder reaction of 2a with dimethyl
but-2-ynedioate 13d: Under an argon atmosphere, a solution of 2a
(41 mg, 0.20 mmol) and 13d (114 mg, 0.80 mmol) in xylene (8 mL) was
Chem. Eur. J. 2008, 14, 2453 – 2464
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2461

S. Ma and Z. Gu
stirred at 558C for 34 h. After complete consumption of the starting ma-
terial as monitored by TLC, the reaction mixture was directly purified
via flash chromatography on silica gel (petroleum ether/ethyl acetate 5:1)
to afford 14ad (36 mg, 52%). 1H NMR(300 MHz, CDCl 3): d = 4.53 (d,
J=4.5 Hz, 1H), 3.95 (d, J=3.3 Hz, 1H), 3.73 (s, 6H), 2.72–2.48 (m, 3H),
2.48–2.28 (m, 2H), 2.12–1.98 (m, 3H), 1.57 (dd, J=8.1, 12.0 Hz, 1H),
1.11 (s, 3H), 0.92–0.82 (m, 1H), 0.83 ppm (s, 3H); 13C NMR(75.4 MHz,
CDCl3): d = 23.4, 23.7, 29.7, 31.6, 32.0, 32.6, 34.6, 36.9, 39.3, 46.8, 51.0,
52.2, 52.3, 138.9, 140.2, 144.7, 164.5, 165.4, 166.3, 194.3 ppm; IR(neat): n˜
Mechanistic study of cycloisomerization of 1,2,4Z,7-tetraenes
Synthesis of hexyl 3-deuteropropiolate ([D]-23):[23] Under an argon at-
mosphere, to Schlenk tube was added hexyl propiolate (10.0 g,
a
65 mmol), D2O (5.0 mL), K2CO3 (0.25 g, 1.8 mmol), TBAB (0.75 g,
2.3 mmol). After stirring at room temperature for 24 h, the aqueous layer
was discarded. To the organic layer were added D2O (5.0 mL), K2CO3
(0.25 g, 1.8 mmol), and TBAB (75 mg, 0.23 mmol). Then the mixture was
stirred at RT for 24 h. After repeating this procedure for four times, the
organic layer was dried over Na2SO4. This crude hexyl 3-deuteropropio-
late ([D]-23) is pure enough for the next step. 1H NMR(300 MHz,
CDCl3): d = 4.19 (t, J=6.6 Hz, 2H), 2.87 (s, 0.01H), 1.75–1.60 (m, 2H),
1.42–1.20 (m, 6H), 0.89 ppm (t, J=7.2 Hz, 3H).
=
1718, 1667, 1615, 1434, 1263, 1236, 1071 cmÀ1; MS (ESI): m/z 362
[M+NH4+], 345 [M++H]; HRMS: m/z: calcd for C20H24O5Na: 367.1516
[M+Na+]; found: 367.1514.
1,1,2,3,3-Pentadeuteroallyl mesylate ([D5]-24-(allyl)):[23] Under an argon
(4aE,5Z,9Z)-7,7-Dimethyl-9-butyl-3,4,7,8-tetrahydrocycloocta[c]cyclohex-
an-1(2H)-one (15c) and (2a,8a)-8a-butyl-2,2-dimethyl-1,2,2a,5,6,8a-hexa-
hydrocyclobuta[b]naphthalen-7(4H)-one (9c): Under an argon atmos-
phere, a solution of 2c (62 mg, 0.24 mmol) in xylene (4 mL) was stirred
at 908C for 2 h. After complete consumption of the starting material as
monitored by TLC, the reaction mixture was directly purified via flash
chromatography on silica gel (petroleum ether/ethyl acetate 50:1) to
afford 9c (5 mg, 8%) and 15c (35 mg, 56%). 9c: 1H NMR(300 MHz,
CDCl3): d = 6.68 (s, 1H), 5.28 (d, J=6.0 Hz, 1H), 2.55 (d, J=6.0 Hz,
1H), 2.51–2.42 (m, 2H), 2.42–2.32 (m, 2H), 1.94 (d, J=11.7 Hz, 1H),
1.91–1.64 (m, 3H), 1.59–1.40 (m, 2H), 1.38–1.18 (m, 3H), 1.18–1.05 (m,
4H), 1.03 (s, 3H), 0.85 ppm (t, J=7.2 Hz, 3H); 13C NMR(75.4 MHz,
CDCl3): d = 14.0, 21.4, 23.2, 25.3, 26.3, 30.6, 32.4, 35.5, 39.95, 40.04, 44.0,
47.6, 51.2, 120.1, 131.3, 131.7, 143.1, 198.5 ppm; IR(neat): n˜ = 1693,
1639, 1579, 1460, 1257, 1230 cmÀ1; MS (ESI): m/z: 259 [M++H]; HRMS:
m/z: calcd for C18H27O: 259.2056 [M++H]; found: 259.2055. 15c:
1H NMR(300 MHz, CDCl 3): d = 6.23 (s, 1H), 5.63 (d, J=13.5 Hz, 1H),
5.53 (d, J=13.5 Hz, 1H), 2.42 (t, J=6.6 Hz, 4H), 2.22 (t, J=7.5 Hz, 2H),
2.15 (s, 2H), 2.08–1.95 (m, 2H), 1.53–1.40 (m, 2H), 1.40–1.21 (m, 2H),
1.08 (s, 6H), 0.90 ppm (t, J=7.2 Hz, 3H); 13C NMR(75.4 MHz, CDCl 3):
d = 14.0, 21.9, 22.5, 30.5, 31.4, 31.7, 37.7, 38.0, 38.8, 41.9, 122.6, 125.4,
131.9, 143.5, 146.9, 152.1, 199.0 ppm; IR(neat): n˜ = 1669, 1597, 1455,
atmosphere, to
a three-necked flask containing LiAlD4 (5.92 g,
141.0 mmol) and anhydrous Et2O (180 mL) was added a solution of [D]-
23 (prepared above) in Et2O (20 mL) over 1 h with the temperature
below À108C. The reaction was allowed to warm up to RT and stirred
for additional 6 h. After cooling to 08C, D2O (6.0 mL, 300 mmol) was
carefully added to the reaction mixture followed by stirring for 2 h. After
the addition of 10% NaOH (12 mL) and H2O (18 mL), the reaction mix-
ture was then filtered. The distillation of the filtrate afforded a mixture
of 1,1,2,3,3-pentadeuteroallyl alcohol and ether for the next step.
The distillate and Et3N (9.74 mL, 70 mmol) were added to a 250 mL
flask. Then MsCl (5.4 mL, 8.02 g, 70 mmol) was added to the mixture
with stirring at 08C over 20 min. The mixture was filtered and the filtrate
was evaporated. The residue was purified via flash chromatography on
silica gel to afford [D5]-24-(allyl) (3.61 g, 39% for three steps). 1H NMR
(300 MHz, CDCl3): d
= 5.93 (0.02H), 5.45–5.41 (m, 0.09H), 5.36 (s,
0.02H), 4.70 (s, 0.02H), 3.00 ppm (s, 3H).
4,4,5,6,6-Pentadeutero-1-phenyl-2-hexyn-5-enol
([D5]-25-(allyl)):[24]
Under an argon atmosphere, a mixture of 1-phenylprop-2-yn-1-ol (1.32 g,
10.0 mmol), [D5]-24 (1.55 g, 11.0 mmol), CuI (0.19 g, 1.0 mmol), K2CO3
(2.76 g, 20.0 mmol), and DMF (30 mL) was stirred at 308C for 12 h.
After complete consumption of the starting material as monitored by
TLC, the reaction mixture was filtered through a short column on silica
gel. The filtrate was diluted with water (100 mL) and extracted with Et2O
(50 mL”3). The combined organic layer was washed with brine and
dried over Na2SO4. The solvent was removed by evaporation and the res-
idue was purified via flash chromatography on silica gel to afford [D5]-
25-(allyl) (1.31 g, 74%). 1H NMR(300 MHz, CDCl 3): d = 7.61–7.52 (m,
2H), 7.46–7.28 (m, 3H), 5.82–5.80 (m, 0.01H), 5.49 (d, J=6.3 Hz, 1H),
5.32–5.30 (m, 0.04H), 5.13–5.10 (m, 0.02H), 2.22 ppm (d, J=6.3 Hz, 1H).
1270, 1215, 1140, 1110 cmÀ1; MS(ESI): m/z: 259 [M++H]; HRMS: m/z:
A
calcd for C18H27O: 259.2056 [M++H]; found: 259.2060.
(4aE,5Z,9Z)-7,7-Dimethyl-9-phenyl-3,4,7,8-tetrahydrocycloocta[c]cyclo-
hexan-1(2H)-one (15d): Under argon atmosphere,
a solution of 2d
(64 mg, 0.23 mmol) in xylene (4 mL) was stirred at 908C for 2 h. After
complete consumption of the starting material as monitored by TLC, the
reaction mixture was directly purified via flash chromatography on silica
gel (petroleum ether/ethyl acetate 25:1) to afford 15d (49 mg, 77%).
1H NMR(300 MHz, CDCl 3): d = 7.45–7.38 (m, 2H), 7.36–7.18 (m, 3H),
6.61 (s, 1H), 5.69 (d, J=13.8 Hz, 1H), 5.57 (d, J=13.8 Hz, 1H), 2.73 (s,
2H), 2.53–2.40 (m, 4H), 2.13–2.00 (m, 2H), 0.91 ppm (s, 6H); 13C NMR
(75.4 MHz, CDCl3): d = 21.9, 31.4, 31.8, 37.9, 38.0, 40.9, 125.3, 125.9,
126.3, 127.0, 128.1, 132.3, 143.9, 144.4, 145.7, 152.9, 198.9 ppm; IR(neat):
n˜ = 1666, 1639, 1592, 1451, 1360, 1270, 1187, 1132 cmÀ1; MS (ESI): m/z:
279 [M++H]; HRMS: m/z: calcd for C20H23O: 279.1743 [M++H]; found:
279.1751.
2-(1’,1’,2’,3’,3’-Pentadeuteroallyl)-4-phenylbuta-2,3-dienoic acid ([D5]-
26)[25] [D5]-25-(allyl) (1.06 g, 6.0 mmol) and THF (35 mL) was added to a
dried 100 mL three-necked flask containing LiBr [dried from 0.63 g,
(6.0 mmol) of LiBr?H2O with
a heating gun]. nBuLi (2.64 mL,
2.5 molLÀ1 in hexanes, 6.6 mmol) was added dropwise at À788C with stir-
ring. After the reaction mixture was stirred for 30 min at this tempera-
ture, pTsCl (1.26 g, 6.6 mmol) was added in one portion, then the mixture
warmed up to RT and stirred at this temperature for 1.5 h. Then the mix-
ture was transferred to autoclave followed by the addition of H2O
ACHTREUNG
(1.2 mL) and [Pd(PPh3)4] (138 mg, 0.12 mmol). The mixture in autoclave
G
was then stirred with a CO pressure of 300 psi at RT for 2 h. After care-
fully deflating the excess CO gas, the mixture was dried over Na2SO4.
The solvent was evaporated and the residue was filtrated through a short
column on silica gel. The crude product was purified via recrystallization
to afford [D5]-26-(allyl) (0.53 g, 43%). Solid, m.p. 64–688C (Et2O/petrole-
um ether); 1H NMR(300 MHz, CDCl 3): d = 7.42–7.17 (m, 5H), 6.63 (s,
1H), 5.88–5.83 (m, 0.01H), 1.15–5.10 (m, 0.04H), 3.13–3.05 ppm (m,
0.06H).
AHCTREUNG
AHCTREUNG
(162 mg, 1.00 mmol) was added to the mixture and stirred for additional
2 h. After being cooling down to RT, the reaction mixture was directly
purified via flash chromatography on silica gel (petroleum ether/ethyl
acetate 20:1) to afford 9e (31 mg, 41%) together with other unidentified
products. 1H NMR(300 MHz, CDCl 3): d = 6.70 (s, 1H), 4.12 (q, J=
7.2 Hz, 2H), 3.18 (d, J=15.0 Hz, 1H), 2.70 (d, J=15.0 Hz, 1H), 2.56 (s,
1H), 2.55–2.30 (m, 4H), 1.97 (d, J=11.7 Hz, 1H), 1.93–1.75 (m, 3H),
1.24 (t, J=7.2 Hz, 3H), 1.14 (s, 6H), 0.94 ppm (s, 3H); 13C NMR
(75.4 MHz, CDCl3): d = 14.2, 20.7, 24.4, 26.0, 29.3, 32.0, 33.2, 38.4, 38.9,
39.4, 51.5, 53.4, 60.6, 122.8, 128.4, 130.8, 143.0, 170.8, 198.6 ppm; IR
(neat): n˜ = 1733, 1692, 1634, 1581, 1459, 1251, 1179, 1034 cmÀ1; MS (EI):
m/z (%): 302 (4.02) [M+], 172 (100); HRMS: m/z: calcd for C19H26O3:
302.1882 [M+]; found: 302.1883.
3-(1’,1’,2’,3’,3’-Pentadeuteroallyl)-4-(3’-methylbuta-1’,2’-dienyl)-5-phenyl-
furan-2(5H)-one ([D5]-1g-(allyl)): The reaction of [D5]-26-(allyl)
(123 mg, 0.60 mmol), methyl 2-methylbut-3-yn-2-yl carbonate (170 mg,
1.20 mmol), Pd(OAc)2 (7 mg, 0.030 mmol), TFP (14 mg, 0.060 mmol),
A
and K2CO3 (83 mg, 0.60 mmol) in DMSO (2.5 mL) afforded [D5]-1g-
(allyl) (86 mg, 53%). 1H NMR(300 MHz, CDCl 3): d = 7.35–7.18 (m,
3H), 7.18–7.02 (m, 2H), 5.88 (heptet, J=3.0 Hz, 1H), 5.82 (s, 0.02H),
5.64 (s, 1H), 5.15–5.01 (m, 0.10H), 3.08 (s, 0.06H), 1.58 (d, J=3.0 Hz,
2462
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2453 – 2464

Thermal Reactivity of Butenolides and Cyclohexenone Derivatives
FULL PAPER
3H), 0.96 ppm (d, J=3.0 Hz, 3H); IR(neat): n˜ = 2212, 1950, 1752, 1643,
Acknowledgements
1456, 1301, 1152, 1102, 1103 cmÀ1; MS(ESI): m/z: 272 [M++H]; HRMS:
N
m/z: calcd for C18H13D5O2Na: 294.1513 [M+Na+]; found: 294.1531.
Financial supports from National Natural Science Foundation of China
(20121202, 20332060, and 20423001), State Basic and Research Develop-
ment Program (Grant No. 2006CB806105), and Shanghai Municipal
Committee of Science and Technology are greatly appreciated.
[D5]-6g: Under an argon atmosphere, mixture of [D5]-1g-(allyl)
a
(72 mg, 0.27 mmol) in xylene (4 mL) was stirred at 1108C for 6 h. After
complete consumption of the starting material as monitored by TLC, the
mixture was directly purified via flash chromatography on silica gel to
afford [D5]-6g (46 mg, 64%) as well as unidentified products (10 mg).
Solid, m.p. 114–1188C (ethyl acetate/petroleum ether); 1H NMR
(300 MHz, CDCl3): d = 7.42–7.33 (m, 3H), 7.33–7.20 (m, 2H), 6.41 (s,
0.18H), 6.37 (s, 0.02H), 5.92 (d, J=12.6 Hz, 0.07H), 5.77 (s, 1H), 5.52–
5.42 (m, 1H), 2.21 (d, J=10.2 Hz, 0.06H), 1.11 (s, 3H), 0.99 ppm (s, 3H);
IR(neat): n˜ = 2239, 2196, 2135, 2082, 1741, 1699, 1622, 1494, 1457, 1331,
[1] For some of the most recent examples, see: a) Y. Chia, F. Chang, Y.
Wu, Tetrahedron Lett. 1999, 40, 7513; b) S. Takahashi, K. Maeda, S.
Hirota, T. Nakata, Org. Lett. 1999, 1, 2025; c) B. S. Siddiqui, F.
Afshan, F. Ghiasuddin; S. Faizi, S. N.-H. Naqvi, R. M. Tariq, J.
Chem. Soc. Perkin Trans. 1 1999, 2367; d) D. A. G. Cortez, J. B. Fer-
nandes, P. C. Vieria, M. F. G. F. Silva, A. G. Ferreira, Q. B. Cass, J. R.
Pirani, Phytochemistry 1998, 49, 2493; e) H. Otsuka, K. Kotani, M.
Bando, M. Kido, Y. Takeda, Chem. Pharm. Bull. 1998, 46, 1180; f) S.
Guo, L. Wang, D. Chen, India J. Chem. Sect. B 1997, 36, 339; g) A.
Evidente, L. Sparapano, J. Nat. Prod. 1994, 57, 1720; h) S. Damtoft,
S. R. Jensen, Phytochemistry 1995, 40, 157; i) T. Seki, M. Satake, L.
Mackenzie, H. F. Kaspar, T. Yasumoto, Tetrahedron Lett. 1995, 36,
7093; j) M. Ahmed, A. A. Ahmed, Phytochemistry 1990, 29, 2715;
k) F. S. De Guzman, F. J. Schmitz, J. Nat. Prod. 1990, 53, 926; l) J. A.
Marshall, A. Piettre, M. A. Paige, F. Valeriote, J. Org. Chem. 2003,
68, 1780.
1141, 1018 cmÀ1; MS(ESI): m/z: 294 [M+K]+, 289 [M+Na+], 272 [M+
U
+H]; HRMS: m/z: calcd for C18H14D5O2: 272.1693 [M++H]; found:
272.1702.
[D6]-28-(CD3)2-H(D):
A
solution of [D6]-28-(CD3)2-H(D) (2.70 g,
30 mmol, prepared according to the literature[30] in Et2O (5 mL) was
added to a mixture of NaH (2.10 g, 60% in mineral oil, 51 mmol) and
Et2O (150 mL) in a 250 mL three-necked flask under stirring. After the
addition, the mixture was stirred for 3 h under reflux. After cooling down
to RT, a solution of ClCO2Me (3.48 mL, 45 mmol) in Et2O (5 mL) was
added over 30 min and stirred overnight. The reaction was quenched
with water and extracted with Et2O. The organic layer was washed with
brine and dried over Na2SO4. The solvent was removed by evaporation
[2] a) R. C. Larock, B. Riefling, C. A. Fellows, J. Org. Chem. 1978, 43,
131 and references therein; b) B. M. Trost, F. D. Toste, J. Am. Chem.
Soc. 2003, 125, 3090.
and the distillation of the residue afforded [D6]-28-(CD3)2-H(D) (2.55 g,
1
71%). B.p. 49–508C at 10 mmHg; H NMR(300 MHz, CDCl ): d = 3.74
[3] a) E. Negishi, M. Kotora, Tetrahedron 1997, 53, 6707; b) P. Deshong,
D. R. Sidler, G. A. Slough, Tetrahedron Lett. 1987, 28, 2233; c) C.
Schmit, S. Sahraoui-Taleb, E. Differding, C. G. D. Lombaert, L.
Ghosez, Tetrahedron Lett. 1984, 25, 5043; d) J. A. Marshall, M. A.
Wolf, J. Org. Chem. 1996, 61, 3238; e) W. Xiao, H. Alper, J. Org.
Chem. 1997, 62, 3422; f) A. Arcadi, E. Bernocchi, A. Burini, S.
Cacchi, F. Marinelli, B. Pietroni, Tetrahedron 1988, 44, 481; g) J. M.
Clough, G. Pattenden, P. G. Wight, Tetrahedron Lett. 1989, 30, 7469;
h) G. B. Gill, M. S. H. Idris, Tetrahedron Lett. 1985, 26, 4811; i) C.
Kejian, M. A. Sanner, R. M. Carlson, Synth. Commun. 1990, 20, 901;
j) E. Yoneda, T. Kaneko, S. Zhang, K. Onitsuka, S. Takahashi, Org.
Lett. 2000, 2, 441; k) M. Renurd, L. A. Ghosez, Tetrahedron 2001,
57, 2597; l) P. Langer, I. Friefold, Synlett 2001, 523; m) S. Ma, Acc.
Chem. Res. 2003, 36, 701, and references therein.
3
(s, 3H), 2.54 ppm (s, 0.16H).
Methyl 1,1-di(trideuteromethyl)prop-2-yn-1-yl carbonate ([D6]-28-
(CD3)2): Under an argon atmosphere, to a solution of [D6]-28-(CD3)2-
H(D) (1.51 g, 10.2 mmol) in Et2O (30 mL) was added nBuLi (9.56 mL,
1.6 molLÀ1 in hexane, 15.3 mmol) at À788C with stirring over 50 min.
After being stirred at À788C for 20 min, the reaction mixture was
quenched with H2O at this temperature. The mixture was allowed to
warm up to RT spontaneously. The organic layer was washed with brine
and dried over Na2SO4. The solvent was removed by evaporation and the
residue was purified via flash chromatography on silica gel (pentane/
Et2O 50:1) to afford [D6]-28-(CD3)2 (0.58 g, 38%), which was used direct-
1
ly for the next step without further characterization. H NMR(300 MHz,
CDCl3): d = 3.76 (s, 3H), 2.56 ppm (s, 1H).
[4] S. Ma, Z. Gu, Y. Deng, Chem. Commun. 2006, 94.
3-Allyl-4-[3’,3’-di(trideuteromethyl)propa-1’,2’-dienyl]-5-phenylfuran-
[5] a) R. B. Woodward, R. Hoffmann “ The Conservation of Orbital
Symmetry”, Verlag Chemie, Weinheim (Germany), and Academic
Press, New York, 1970; b) G. B. Q. Gill, Rev. Chem. Soc. 1968, 22,
338; c) T. L. Gilchrist, R. C. Storr “ Organic Reactions and Orbital
Symmetry”, Cambridge University Press, London, 1972; d) C. W.
Spangler, Chem. Rev. 1976, 76, 187.
[6] a) I. D. Gridnev, M. E. Gurskii, A. V. Ignatenko, Y. N. Bubnov, Y. V.
Il’ichev, Organometallics 1993, 12, 2487; b) W. H. Okamura, H. Y.
Elnagar, M. Ruther, S. Dobreff, J. Org. Chem. 1993, 58, 600;
c) C. A. Hoeger, W. H. Okamura, J. Am. Chem. Soc. 1985, 107, 268;
2(5H)-one ([D6]-1g-
enoic acid (150 mg, 0.75 mmol), [D6]-28-(CD3)2) (221 mg, 1.50 mmol), Pd-
(OAc)2 (5 mg, 0.020 mmol), TFP (9 mg, 0.040 mmol), and K2CO3
A
ACHTREUNG
(104 mg, 0.75 mmol) in DMSO (3 mL) afforded [D6]-1g-(CD3)2 (110 mg,
54%). 1H NMR(300 MHz, CDCl 3): d = 7.40–7.25 (m, 3H), 7.22–7.15
(m, 2H), 6.00–5.85 (m, 2H), 5.72 (s, 1H), 5.22–5.08 (m, 2H), 3.19 (d, J=
6.3 Hz, 2H), 1.68–1.61 (m, 0.16H), 1.05–1.00 ppm (m, 0.15H); 13C NMR
(75.4 MHz, CDCl3): d = 18.1 (heptet), 27.6, 83.0, 83.5, 99.4, 116.3, 123.7,
127.5, 128.5, 128.8, 133.4, 135.8, 156.2, 173.5, 208.2 ppm; IR(neat): n˜ =
2237, 2203, 2107, 1949, 1752, 1642, 1456, 1355, 1302, 1084, 1005 cmÀ1
;
ˇ
for MO calculations see: B. A. Hess, L. J. Schaad, J. Panoir, J. Am.
Chem. Soc. 1985, 107, 149.
[7] a) G. D. Zhu, W. H. Okamura, Chem. Rev. 1995, 95, 1877; b) F.
Jensen, J. Am. Chem. Soc. 1995, 117, 7487.
MS(EI): m/z (%): 273 [M++H]; HRMS: m/z: calcd for C18H12D6O2:
272.1683 [M+]; found: 272.1683.
[D6]-6g: A solution of [D6]-1g-(CD3)2 (90 mg, 0.33 mmol) in xylene
(4 mL) was stirred at 1108C for 6 h. After complete consumption of the
starting material as monitored by TLC, the mixture was directly purified
via flash chromatography on silica gel to afford product [D6]-6g (76 mg
(76 mg). The product was further purified by one recrystallization from
ethyl acetate and petroleum ether (66 mg, 73%). Solid, m.p. 116–1188C
(ethyl acetate/petroleum ether); 1H NMR(300 MHz, CDCl 3): d = 7.45–
7.35 (m, 3H), 7.35–7.22 (m, 2H), 6.46–6.32 (m, 1.22H), 5.93 (d, J=
13.2 Hz, 1H), 5.77 (s, 1H), 5.48 (d, J=13.2 Hz, 1H), 2.32–2.17 (m, 2H),
1.15–1.05 (m, 0.45H), 1.03–0.96 ppm (m, 0.45H); IR(neat): n˜ = 2215,
[8] a) K. Närhi, J. FranzØn, J.-E. Bäckvall, J. Org. Chem. 2006, 71, 2914;
b) A. S. K. Hashmi, G. Szeimies, Chem. Ber. 1994, 127, 1075.
[9] a) Z. Gu, S. Ma, Angew. Chem. 2006, 118, 6418; Angew. Chem. Int.
Ed. 2006, 45, 6002; b) H. Jiao, P. R. Schleyer, Angew. Chem. 1993,
105, 1833; Angew. Chem. Int. Ed. Engl. 1993, 32, 1763; c) M. E. Gur-
skii, I. D. Gridnev, Y. V. Il’ichev, A. V. Ignatenko, Y. N. Bubnov,
Angew. Chem. 1992, 104, 791; Angew. Chem. Int. Ed. Engl. 1992, 31,
781.
[10] Crystal data for (E,Z)-3a: C24H26O2, MW =346.45, monoclinic; space
group P2(1)/n, a=12.625(3), b=11.011(2), c=15.681(3) Š, a = 90,
1743, 1624, 1495, 1457, 1265, 1125, 1035, 1003 cmÀ1; MS
(ESI): m/z: 290
A
b=111.653(4), g=908, V=2026.0(7) Š3, T=293(2) K, Z=4, MoKa
,
[M+NH4+], 273 [M++H]; HRMS: m/z: calcd for C18H12D6O2: 272.1683
[M+]; found: 272.1679.
final R indices [I > 2s(I)], R1=0.0519, wR2=0.1045; R indices (all
data): R1=0.1635, wR2=0.1342; reflections collected/unique:
Chem. Eur. J. 2008, 14, 2453 – 2464
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2463

S. Ma and Z. Gu
10364/3780 (Rint =0.1251); number of observations [I>2s(I)] 1154,
parameters: 239. CCDC 647592 contains the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
[18] For the synthesis of cyclooctanoids via the [4+2+2] cyclization,
see: a) A. Greco, A. Carbonaro, G. Dall’Asta, J. Org. Chem. 1970,
35, 271; b) A. Carbonaro, F. Cambisi, G. Dall’Asta, J. Org. Chem.
1971, 36, 1443; c) M. Lautens, W. Tam, C. Sood, J. Org. Chem. 1993,
58, 4513; d) M. Lautens, W. Tam, J. C. Lautens, L. G. Edwards, C. M.
Crudden, A. C. Smith, J. Am. Chem. Soc. 1995, 117, 6863; e) P. A.
Evans, J. E. Robinson, E. W. Baum, A. N. Fazal, J. Am. Chem. Soc.
2002, 124, 8782; f) S. R. Gilbertson, B. DeBoef, J. Am. Chem. Soc.
2002, 124, 8784.
[11] Crystal data for trans-5d: C22H20O2, MW =316.38, monoclinic; space
group P2(1)/n, a=9.5944(10), b=12.7764(13), c=13.7255(14) Š, a
=90, b=96.046(2), g=908, V=1673.1(3) Š3, T=293(2) K, Z=4,
MoKa final R indices [I > 2s(I)], R1=0.0598, wR2=0.1530; R indi-
ces (all data): R1=0.0759, wR2=0.1652; reflections collected/
unique: 9684/3645 (Rint =0.1342); number of observations [I>2s(I)]
2656, parameters: 228; CCDC 647595 contains the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
[19] Crystal data for 7s: C16H20O2, MW =244.32, monoclinic; space group
P2(1)/n, a=10.3056(13), b=10.7788(13), c=12.7196(15) Š, a=90,
b=104.149(2), g=908, V=1370.1(3) Š3, T=293(2) K, Z=4, MoKa
,
final R indices [I > 2s(I)], R1=0.0620, wR2=0.1834; R indices (all
data): R1=0.0850, wR2=0.1979; reflections collected/unique: 7603/
2836 (Rint =0.1396); number of observations [I>2s(I)] 1778, param-
eters: 174; CCDC 647593 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[12] Crystal data for trans-5e: C19H20O2, MW =280.35, monoclinic; space
group P2(1), a=8.4041(9), b=7.7989(9), c=11.9701(13) Š, a=90,
b=103.336(2), g=908, V=763.40(15) Š3, T=293(2) K, Z=2, MoKa
,
final R indices [I > 2s(I)], R1=0.0424, wR2=0.1055; R indices (all
data): R1=0.0442, wR2=0.1070; reflections collected/unique: 4491/
1785 (Rint =0.0864); number of observations [I>2s(I)] 1670, param-
eters: 205; CCDC 647594 contains the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif
[20] Crystal data for 10aba: C28H35BrO2, MW=483.47, monoclinic;
space group P2(1)/n, a=9.6751(11), b=18.841(2), c=13.5790(15) Š,
a=90, b=106.572(2), g=908, V=2372.4(5) Š3, T=293(2) K, Z=4,
MoKa, final R indices [I > 2s(I)], R1=0.0404, wR2=0.0777; Rindi-
ces (all data): R1=0.0787, wR2=0.0840; reflections collected/
unique: 13970/5361 (Rint =0.0814); number of observations [I>
2s(I)] 2959, parameters: 292; CCDC 647590 contains the supple-
mentary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif
[21] Crystal data for 14aa: C18H20O4, MW =300.34, monoclinic; space
group P2(1)/c, a=12.2043(14), b=11.8230(14), c=10.7171(12) Š,
a=90, b=92.944(2), g=908, V=1544.3(3) Š3, T=293(2) K, Z=4,
MoKa, final R indices [I > 2s(I)], R1=0.0491, wR2=0.1266; R indi-
ces (all data): R1=0.0633, wR2=0.1348; reflections collected/
unique: 8749/3359 (Rint =0.0777); number of observations [I>2s(I)]
2642, parameters: 226. CCDC 647591 contains the supplementary
crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[13] For the formation of the cyclooctanoid compounds via the 8p-elec-
trocyclization of 1,3,5,7-tetraenes, see: a) D. J. Kerr, A. C. Willis,
B. L. Flynn, Org. Lett. 2004, 6, 457; b) S. Brꢁcker, J. E. Baldwin,
R. M. Adlington, T. D. W. Claridge, B. Odell, Tetrahedron 2004, 60,
2785; c) R. Huisgen, A. Dahmen, H. Huber, J. Am. Chem. Soc.
1967, 87, 7130; d) G. Pohnert, W. Boland, Tetrahedron 1994, 50,
10235.
[14] S. Ma, Z. Gu, J. Am. Chem. Soc. 2006, 128, 4942.
[15] For recent reviews on metal-mediated synthesis of cycloctanoids
see: a) N. A. Petasis, M. A. Patane, Tetrahedron 1992, 48, 5757; b) S.
Sieburth, T. Cunard, Tetrahedron 1996, 52, 6251; c) G. Mehta, V.
Singh, Chem. Rev. 1999, 99, 881, and references therein; d) L. Yet,
Chem. Rev. 2000, 100, 2963.
[16] The first transition metal-mediated synthesis of a cyclootaniod, see:
a) W. Brenner, P. Heimbach, H. Hey, E. W. Mueller, G. Wilke,
Justus Liebigs Ann. Chem. 1969, 727, 161; for the synthesis of cyclo-
octanoids via the [6+2] cyclization, see: b) P. A. Wender, A. G.
Correa, Y. Sato, R. Sun, J. Am. Chem. Soc. 2000, 122, 7815; for the
synthesis of cyclooctanoids via the [5+2+1] cyclization, see:
c) P. A. Wender, G. G. Gamber, R. D. Hubbard, L. Zhang, J. Am.
Chem. Soc. 2002, 124, 2876.
[22] A. C. Cope, A. C. Haven, F. L. Ramp, E. R. Trumbull, J. Am. Chem.
Soc. 1952, 74, 4867.
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Received: July 30, 2007
Published online: January 21, 2008
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