Regioselective tandem ring closing/cross metathesis of 1,5-hexadien-3-ol derivatives: Application to the total synthesis of rugulactone

Article abstract of DOI:10.1002/ejoc.201000187

A tandem ring-closing metathesis/cross-metathesis procedure was devised for the synthesis of various pyrones. The reaction occurred with high regioselectivity and E stereocon-trol of the lateral unsaturated chain. This process was applied to the synthesis of rugulactone, an inhibitor of the nuclear factor NF-?B according to a four-step sequence.

Full text of DOI:10.1002/ejoc.201000187

FULL PAPER
DOI: 10.1002/ejoc.201000187
Regioselective Tandem Ring Closing/Cross Metathesis of 1,5-Hexadien-3-ol
Derivatives: Application to the Total Synthesis of Rugulactone
Fanny Cros,[a,b] Béatrice Pelotier,[a,b] and Olivier Piva*[a,b]
Keywords: Metathesis / Oxygen heterocycles / Isomerization / Regioselectivity / Cyclization
A
tandem ring-closing metathesis/cross-metathesis pro-
trol of the lateral unsaturated chain. This process was applied
to the synthesis of rugulactone, an inhibitor of the nuclear
cedure was devised for the synthesis of various pyrones. The
reaction occurred with high regioselectivity and E stereocon- factor NF-κB according to a four-step sequence.
rugulactone and related pyrones appears as an interesting
Introduction
subject of research. Since the discovery of efficient cata-
A large number of 5,6-dihydropyrones isolated from
lysts,[7] ring-closing metathesis (RCM) is nowadays one the
Annonaceae species like goniothalamin (1) exhibit potent
best methods to prepare pyrones. To date, three syntheses of
antitumor activities (Figure 1).[1] They usually possess a
3 have been reported, respectively, by the groups of Yadav,
styryl chain attached to the 6-position and have attracted
Venkateswarlu, and Fadnavis.[8] For two of them, the py-
the efforts of chemists over the past two decades.[2,3]
rone subunit was built by a RCM reaction, whereas the lat-
Pyrones substituted by an allyl chain at this position have
eral chain was functionalized by a Wittig reaction and a
been more rarely isolated from nature. Among them, tubero-
cross-metathesis process, respectively.[8a,8b] It should be
lactone (2) identified as a trace in tuberose oil plays a major
noted that a one-pot hydrosilylation/RCM/protodesilylation
role in fragrance and flavor industries.[4,5]
sequence was earlier devised by Cossy et al. to prepare a
related structure.[9]
Results and Discussion
In connection with our interest in the synthesis of 6-alk-
enylpyrones, we described some years ago, a tandem RCM/
cross metathesis (CM) sequence from symmetric 3-O-(1,4-
pentadienyl) vinyl acetate 4 promoted by Grubbs’ ruthe-
nium catalyst 5 (Scheme 1).[10,11] This strategy, which
is complementary to ring rearrangement metatheses
(RRM),[12] was later applied to unsaturated ethers to deliver
functionalized dihydropyrans.[13]
Figure 1. Naturally occurring pyrones.
Recently, rugulactone (3) was extracted by Cardellina et
al. from the plant Cryptocaria rugulosa.[6] This compound,
produced in very small amounts (7 mg isolated from 725 g
of the dried leaves), is an efficient inhibitor of the nuclear
factor (NK-κB) activation pathway. This factor has a major
biological role. Bound to discrete DNA sequences, it can
initiate gene expressions that are implicated in major dis-
eases like cancer and diabetes. Therefore, the synthesis of
[a] Université de Lyon 1, ICBMS, UMR CNRS 5246, Bat. Raulin,
43, Bd du 11 novembre 1918, 69622 Villeurbanne Cedex, France
Fax: +33-4-72448136
E-mail: piva@univ-lyon1.fr
[b] Université de Lyon,
69622 Lyon cedex, France
Scheme 1. Tandem ring closing/cross metathesis of ester 4.
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F. Cros, B. Pelotier, O. Piva
FULL PAPER
To expand the scope of this tandem process, we also re-
ported the reaction of 3-O-(1,5-hexadienyl) α,β-unsaturated
ester 9, which delivered a mixture of butenolide 10 and hex-
enolide 11 in moderate yields (Scheme 2). While the work
described in the present publication was in progress, Quinn
and co-workers reported an efficient synthesis of a naturally
occurring pyrone on the basis of, first, RCM of a substi-
tuted 3-O-(1,5-hexadienyl) 3-butenoate and, second, after
addition of a chosen alkene, by cross metathesis on the lat-
eral chain.[14] In that case, Hoveyda–Grubbs catalyst 5b was
however required to prevent additional isomerization of the
newly created internal double bond. Disappointingly, the
tandem procedure was unsuccessful, leading mainly to a
product resulting from cross metatheses between the less-
substituted double bonds.
Scheme 3. Retrosynthetic analyses for 3 and related 6-allyl hexenol-
ides 12.
intractable oligomeric forms instead of the expected lactone
(Scheme 4). The same procedure was carried out with sim-
pler alkene 1-hexene (16a). Interestingly, the tandem reac-
tion took place and delivered lactone 12a, albeit in a very
disappointing yield. As recently pointed out by Quinn et
al., the presence of a hydroxy group close to the double
bond seems to be detrimental to the efficiency of the reac-
tion.[14] The reactivity of 13 in the absence of any alkene
partner was also investigated. In that case, new structure 20
was isolated, resulting from a cascade reaction involving
two double ring closures and a cross metathesis. Interest-
ingly, when 20 was placed under classic metathetical condi-
tions and in the presence of alcohol 14a, compounds 18 and
19 were solely obtained as new products of the reaction,
demonstrating the robustness of the dimeric structure to-
ward cross-metathesis reactions.
Scheme 2. RCM and alkenyl transfer from 3-O-(1,5-hexadienyl)
ester 9.
Having in mind all these results, we have investigated the
synthesis of 3 and parent compounds 12 and considered
their synthesis according to two disconnections summarized
in Scheme 3. The first one was based on tandem RCM/CM
starting from acrylate 13, readily prepared from commer-
cially available 1,6-heptadien-4-ol (pathway a). Although
the competitive formation of a cyclopentene derivative
could not be totally excluded by RCM of the two terminal
double bonds fixed on the alkoxy group,[15] it was expected
that in presence of an alkene partner, the tandem RCM/
CM procedure could take place Ϫ even starting from a de-
activated acrylate Ϫ leading directly to the core structure
of 3 or analogues 12. The second strategy (pathway b),
which is similar to the process recently reported by Quinn,
consisted in using less-deactivated ester 15, prepared from
vinylacetic acid and unsymmetrical 1,5-hexadien-3-ol. In
this approach, RCM of the two terminal alkenes fixed on
the alkoxy group leading to a cyclobutene derivative could
be excluded for steric reasons. Otherwise, the reaction be-
tween the unsaturation fixed on the acid chain could take
place more favorably with the vinyl group to form a 6-allyl-
pyrone structure compared to the reaction involving the al-
lyl rest leading to a 7-vinyl caprolactone.[14,16,17]
Scheme 4. Tandem RCM/CM starting from ester 13.
Treatment of 13 with alcohol 14a in the presence of
Grubbs type II catalyst 5 afforded dimer structure 18,
The first strategy gave disappointing results, and the re-
ketone 19[18] resulting from the isomerization of the ter- activity of unsymmetrical ester 15 was thus next considered.
minal double bond[19] and further reketonization, and also Placed in the presence of catalyst 5 (2.5 mol-%) and in the
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Total Synthesis of Rugulactone
absence of any alkene as reactant, 15 afforded a new di- Table 1. RCM/CM between ester 15 and elkenes 16a–e.
meric structure identified as 21 in high yield (Scheme 5).
[a] Isolated yield.
Scheme 5. RCM/dimerization of ester 15.
At this stage, it was anticipated that RCM proceeded first
before the dimerization; effectively, when the above reaction
was stopped after only 7 h of heating, 21 was isolated in
59% yield, although 6-allylpyrone 22 was obtained in only
19%. The selective formation of hexenolides confirmed the
hypothesis concerning the regioselectivity for the ring clo-
Scheme 7. Tandem RCM/CM process from ester 15 with alkene
sure of substrate 15. This ester was next placed in the pres-
ence of different alkenes 16a–e under dilute conditions and
in the presence of catalyst 5. To our delight, the RCM/CM
process occurred nicely in a majority of cases and delivered
lactones 17 in good yields (Scheme 6). Whatever, the nature
of the alkene, including phenol derivative eugenol 16e, the
tandem procedure delivered expected pyrones 17a–e in 60–
70% yield (Table 1). In each case, the E configuration of
the double bond on the lateral chain was attributed by mea-
surement of the coupling constant between the two olefinic
protons. The β,γ-unsaturated pyrones were efficiently recon-
jugated into hexenolides 3b–f by treatment at room tem-
perature with a catalytic amount of DBU (0.1 equiv.),
(Scheme 7).[20] Interestingly, pyrone 18g underwent two
C=C bond migrations in the same pot to afford compound
3gЈ in 49% yield.
16f.
metathesis conditions, leading promptly to dimerization[21]
or double-bond isomerization. Therefore, enone 14b was
chosen as partner for the RCM/CM process. Cross-coupling
of lactone 22 with 14b (3 equiv.) was investigated under mi-
crowave (MW) activation.[22] After a reaction time of only
30 min, a conversion of 71% was noticed and lactone 23,
the β,γ-unsaturated isomer of 3, was isolated in 56% yield
(Scheme 8).
Scheme 8. RCM/CM of ester 15 in the presence of enone 14b.
The tandem procedure was tested with 15 under conven-
Scheme 6. Synthesis of pyrones 12a–e by RCM/CM from ester 15.
While the overall process appeared efficient with a large tional heating and afforded 23 in a similar yield and lactone
number of alkenes, we next considered the synthesis of rug- 22 as a minor compound (25%). Unfortunately, attempts to
ulactone from ester 15. As demonstrated above with ester convert 23 into rugulactone by treatment with DBU[20] led
13, the reactivity of alkene 14a seemed problematic under to the decomposition of the material. This inefficiency was
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F. Cros, B. Pelotier, O. Piva
FULL PAPER
4-Hepta-1,6-dienyl Acrylate (13): To a solution of 1,6-heptadien-4-
ol (0.50 mL, 3.85 mmol) in dichloromethane (19 mL) was added
triethylamine (1.18 mL, 8.47 mmol) and DMAP (24 mg,
0.19 mmol). After cooling to 0 °C, acryloyl chloride (0.63 mL,
7.70 mmol) was added dropwise. The resulting mixture was stirred
at room temperature for 4 h. After hydrolysis with a saturated
aqueous solution of ammonium chloride, the aqueous layer was
extracted with dichloromethane. The organic layer was successively
washed with water and brine and dried with MgSO4. After fil-
tration, the solvent was removed by concentration, and the mixture
attributed to the competitive abstraction of the proton at
the γ-position of the keto group, followed by further elimi-
nation to a linear trienic structure. An alternative isomer-
ization of the internal double bond based on the in situ
formation of ruthenium hydride was tested.[23] Unfortu-
nately, this procedure directly combined with the formation
of compound 23 furnished a complex mixture of com-
pounds.
To prevent the side reaction observed during the basic
reconjugation, the keto group of 23 had to be selectively was purified by flash chromatography on silica (EtOAc/hexanes,
reduced. Corey–Bakshi–Shibata conditions[24] were chosen
5:95). Ester 13 (281 mg, 1.69 mmol) was obtained as a colorless oil.
Yield: 44%. 1H NMR: δ = 2.33–2.38 (m, 4 H, CH2=CH-CH2-),
5.02–5.11 (m, 5 H, CH2=CH-CH2- and -CH-O), 5.69–5.80 (m, 2
H, CH2=CH-CH2-), 5.80 (dd, J = 10.3, 1.1 Hz, 1 H, CH2=CH-
for two purposes. At first, the keto group could be smoothly
reduced in the presence of a lactone moiety,[25] and second,
this asymmetric process could furnish the corresponding
alcohols as an enriched mixture of diastereomers. Neverthe-
less, to avoid the reduction of the pyrones, a short reaction
time (only 2 min) was required. Resulting hydroxyactones
CO, Hcis), 6.09 (dd, J = 17.3, 10.3 Hz, 1 H, CH2=CH-CO), 6.38
(dd, J = 17.3, 1.1 Hz, 1 H, 1 H, CH2=CH-CO, Htrans) ppm. 13C
NMR: δ = 37.8 (CH2), 72.3 (C-O), 117.7 (2 CH2=CH), 128.6
(CH2=CH), 130.2 (CH2=CH), 133.2 (2 CH2=CH), 165.3 (CO2)
25 were thus obtained in a moderate 52% yield and unfor-
tunately as an inseparable mixture of diastereomers. To
complete the synthesis, the mixture was finally treated with
Dess–Martin periodinane[26] to deliver rugulactone (3) in
55% yield (Scheme 9).
ppm.
3-(1,5-Hexadienyl) But-3-enoate (15): To a solution of 1,5-hexa-
dien-3-ol (1.13 mL, 10.0 mmol) in dichloromethane (50 mL) cooled
to 0 °C was successively added DCC (2.27 g, 11.0 mmol), DMAP
(0.367 g, 3.0 mmol), and vinylacetic acid (0.94 mL, 11.0 mmol). Af-
ter 15 min, the solution was warmed to room temperature and
stirred overnight. The resulting suspension was concentrated under
vacuum. After addition of ethyl ether (20 mL), urea was filtered
off. The resulting mixture was purified by flash chromatography on
silica (hexanes/EtOAc, 95:5) to give 15 (1.535 g, 9.24 mmol). Yield:
92%. 1H NMR: δ = 2.39 (t, J = 6.6 Hz, 2 H), 3.10 (dt, J = 6.9,
1.4 Hz, 2 H), 5.06–5.22 (m, 5 H), 5.27–5.35 (m, 2 H), 5.66–5.99 (m,
3 H) ppm. 13C NMR: δ = 38.6 (CH2), 39.1 (CH2), 73.5 (CH-O),
116.6 (CH=CH2), 117.8 (CH=CH2), 118.1 (CH=CH2), 130.2
(CH=CH2), 132.9 (CH=CH2), 135.7 (CH=CH2), 170.1 (CO2) ppm.
IR: ν = 919, 989, 1100, 1171, 1251, 1318, 1426, 1643, 1739, 2930,
˜
2984, 3082 cm–1.
Tandem RCM/Cross Metathesis with Alkene 14a: A solution of
ester 13 (1 mmol) and alcohol 14a in dichloromethane (100 mL)
was deoxygenated by bubbling an argon stream through the solu-
tion for 10 min. Grubbs type II catalyst 5 (21 mg, 0.025 mmol) was
added in one portion, and the resulting homogeneous solution was
heated for 16 h. After concentration, diol 18 and ketone 19 were
isolated after flash chromatography on silica (EtOAc/hexanes,
20:80).
Scheme 9. Completion of the synthesis of rugulactone (3).
Conclusions
1,8-Diphenyl-oct-4-en-3,6-diol (18): Brown oil. Data for dia-
stereomer 1: 1H NMR: δ = 1.81–1.90 (m, 4 H), 2.67–2.75 (m, 4 H),
4.14 (m, 2 H), 5.71–5.73 (m, 2 H), 7.18–7.20 (m, 6 H), 7.27–7.28
(m, 4 H, 4 H) ppm. 13C NMR: δ = 31.8 (CH2), 38.8 (CH2), 71.6
(CH), 126.0 (CHar), 128.6 (CHar), 133.7 (CHar), 141.8 (C) ppm.
In conclusion, a regioselective tandem RCM/CM pro-
cedure was developed for rapid access to functionalized
pyrones. This sequence was successfully applied to the four-
step synthesis of (Ϯ)-rugulactone from readily available
starting materials in a 16% overall yield.
1
Data for diastereomer 2: H NMR: δ = 1.50–2.00 (m, 4 H), 2.62–
2.79 (m, 4 H), 4.14 (m, 2 H), 5.71–5.73 (m, 2 H), 7.18–7.20 (m, 6
H), 7.27–7.28 (m, 4 H, 4 H) ppm. 13C NMR: δ = 31.8 (CH2), 38.8
(CH2), 71.7 (CH), 126.0 (CHar), 128.6 (CHar), 133.9 (CHar), 141.8
Experimental Section
(C) ppm. IR: ν = 698, 747, 1030, 1056, 1100, 1453, 1495, 1602,
˜
2858, 2924, 3025, 3100–3500 cm–1. MS (CI): m/z (%) = 280 (18)
General: All manipulations with air-sensitive reagents were carried
out under a dry argon atmosphere by using standard Schlenk tech-
niques. Solvents were purified according to standard procedures:
THF and ether with sodium/benzophenone and dichloromethane
with CaH2. Column flash chromatography was performed by using
Kieselgel 60 (230–400 mesh). 1H and 13C NMR spectra were re-
corded at 300 and 75 MHz, respectively, in CDCl3; chemical shifts
(δ) are referenced to tetramethylsilane. FTIR spectra were mea-
sured with KBr plates.
[M]+, 279, 261.
Reactivity of Ester 13 in the Absence of Alkene
Cyclopent-3-enyl 4-(6-Oxo-3,6-dihydro-2H-pyran-2-yl)-but-2-enoate
(20): Ester 13 (183 mg, 1.10 mmol) was dissolved in dichlorometh-
ane (100 mL). Argon was bubbled through the solution for 10 min.
Grubbs type II catalyst 5 (23 mg, 0.03 mmol) was added to the
solution, and the homogeneous mixture was heated under reflux
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Total Synthesis of Rugulactone
overnight. After concentration, the crude mixture was purified by
flash chromatography on silica (EtOAc/hexanes, 50:50). Ester 20
(72 mg, 0.26 mmol) was isolated as a light brown oil. Yield: 53%.
NMR: δ = 0.88 (t, J = 7.1 Hz, 3 H, CH3), 1.25–1.35 (m, 4 H, CH2-
CH2), 2.00 (br. q, J = 7.3 Hz, 2 H, =CH-CH2), 2.44 (t, J = 6.8 Hz,
2 H, OCH-CH2), 3.02–3.03 (m, 2 H, CH2-CO2), 4.96–5.00 (m, 1
1H NMR: δ = 2.34–2.40 (m, 4 H, CH2-CH-CH2), 2.45–2.69 (m, 2 H, CH-O), 5.35–5.42 (m, 1 H, CH=), 5.53–5.63 (m, 1 H, CH=),
H, CH2-CH-), 2.72–2.80 (m, 2 H, CH2-CH-), 4.56 (br. quint., J =
7.0 Hz, 1 H, CH2-CH-CH2), 5.40–5.45 (m, 1 H, CH2-CH-CH2), (CH2), 30.0 (CH2-CO2), 31.3 (CH2), 32.3 (=CH-CH2-), 38.6 (-CH2-
5.85 (br. s, 2 H, -CH=CH-) ppm. 13C NMR: δ = 13.8 (CH3), 22.1
5.72 (br. s, 2 H, CH2-CH=CH-CH2), 5.93 (dt, J = 15.8, 1.4 Hz, 1
H, CH2-CH=CH), 6.04 (dt, J = 9.7, 1.7 Hz, 1 H, CH=CH-CO),
6.85–6.91 (m, 2 H, CH=CH) ppm. 13C NMR: δ = 28.9 (CH2), 37.3
CH-O), 79.3 (-CH-O), 121.6 (-CH=), 122.6 (-CH=), 125.9 (-CH=),
135.9 (-CH=), 169.0 (CO ) ppm. IR: ν = 739, 1265, 1376, 1735,
˜
2
2935, 3028 cm–1. HRMS: calcd. for C12H19O2 [M + H]+ 194.1307;
(CH2), 39.7 (2 CH2), 74.3 (O-CH), 76.1 (O-CH), 121.4 (CH=), found 194.1307.
125.3 (CH=), 128.3 (CH=), 141.8 (CH=), 144.7 (CH=), 163.8
6-Hex-2-enyl-3,6-dihydropyran-2-one (17b): Eluent: hexanes/
(CO ), 165.8 (CO ) ppm. IR: ν = 735, 815, 1045, 1188, 1248, 1316,
˜
EtOAc, 80:20. Colorless oil. Yield: 60% (97 mg, 0.21 mmol) 1H
NMR: δ = 0.87 (t, J = 7.3 Hz, 3 H, CH3), 1.37 (sext., J = 7.3 Hz,
2 H, CH2-CH3), 1.98 (br. q, J = 7.0 Hz, 2 H, =CH-CH2), 2.44 (t,
J = 6.7 Hz, 2 H, CH2-CH=), 3.02–3.03 (m, 2 H, CH2-CO2), 4.96–
5.00 (m, 1 H, CH-O), 5.33–5.43 (m, 1 H, CH2-CH=), 5.53–5.62
(m, 1 H, CH2-CH=), 5.84 (br. s, 2 H, -CH=CH-) ppm. 13C NMR:
δ = 13.3 (CH3), 22.3 (CH2-CH3), 30.0 (CH2-CO2), 34.7 (CH2-CH2),
38.6 (CH2-CH=), 79.3 (CH-O), 121.6 (CH=), 122.8 (CH=), 125.9
2
2
1387, 1426, 1657, 1716, 2852, 2923, 3061 cm–1. HRMS: calcd. for
C14H16O4 [M + H]+ 249.1127; found 249.1126.
Reactivity of Ester 15
Reactivity in the Absence of Alkene
Conditions A: A solution of ester 15 (183 mg, 1.10 mmol) dissolved
into dichloromethane (100 mL) was deoxygenated by bubbling with
a stream of argon for 10 min. Grubbs type II catalyst (23 mg,
0.03 mmol) was added at once, and the resulting solution was
heated overnight. After concentration, the crude mixture was puri-
fied by flash chromatography on silica (hexanes/EtOAc, 50:50) af-
fording dimer 21 (111 mg, 0.45 mmol). Yield: 81%.
(CH=), 135.7 (CH=), 169.0 (CO ) ppm. IR: ν = 738, 1268, 1377,
˜
2
1733, 2930, 3024 cm–1. HRMS: calcd. for C11H17O2 [M + H]+
181.1229; found 181.1229.
6-(Cinnamyl)-3,6-dihydropyran-2-one (17c): Eluent: hexanes/EtOAc,
80:20 then 50:50. Colorless oil. Yield: 62% (120 mg, 0.56 mmol).
1H NMR: δ = 2.64–2.70 (m, 2 H, CH2-CH=), 3.02–3.04 (m, 2 H,
CH2-CO2), 5.09–5.13 (m, 1 H, CH-O), 5.89 (br. s, 2 H, CH=CH),
6.18 (dt, J = 16.0, 7.1 Hz, 1 H, CH2-CH=), 6.51 (d, J = 16.0 Hz,
1 H, =CH-Ph), 7.22–7.32 (m, 5 H, CHar) ppm. 13C NMR: δ =
29.9 (CH2-CO2), 38.8 (CH2), 78.9 (CH-O), 122.0 (CH), 122.9 (CH),
125.6 (CH), 126.1 (2 CH), 127.4 (CH), 128.4 (2 CH), 134.2 (CH),
Conditions B: A solution of ester 15 (500 mg, 3.01 mmol) dissolved
into dichloromethane (300 mL) was deoxygenated by bubbling with
a stream of argon for 10 min. Grubbs type II catalyst (64 mg,
0.07 mmol) was added at once, and the resulting solution was
heated for only 7 h. After concentration, the crude mixture was
purified by flash chromatography on silica (hexanes/EtOAc, 80:20
then 50:50) affording dimer 21 (219 mg, 0.88 mmol) in 59% yield.
Lactone 22 (80 mg, 0.58 mmol) was isolated as a side product in
19% yield.
136.8 (C), 168.7 (CO ) ppm. IR: ν = 693, 746, 968, 1070, 1156,
˜
2
1225, 1380, 1738, 2922, 3027 cm–1. HRMS: calcd. for C14H14O2
[M]+· 214.0994; found 214.0992.
1
6-(5-Methylhex-2-enyl)-3,6-dihydropyran-2-one (17d): Eluent: hex-
anes/EtOAc, 80:20. Colorless oil. Yield: 61% (107 mg, 0.55 mmol).
1H NMR: δ = 0.86 (d, J = 6.6 Hz, 6 H, 2 CH3), 1.57–1.64 [m, 1
H, CH(CH3)2], 1.86–1.93 (m, 2 H, =CH-CH2), 2.46 (t, J = 6.3 Hz,
2 H, CH2-CH=), 3.02–3.03 (m, 2 H, CH2-CO2), 4.99–5.01 (m, 1 H,
CH-O), 5.32–5.41 (m, 1 H, =CH), 5.51–5.61 (m, 1 H, =CH), 5.84
(br. s, 2 H, 2 = CH) ppm. 13C NMR: δ = 22.2 (CH3), 22.3 (CH3),
28.3 (CH), 30.0 (CH2-CO2), 38.7 (CH2-CH=), 42.0 (CH=CH2),
79.4 (CH-O), 121.7 (CH), 123.8 (CH), 126.0 (CH), 134.6 (CH),
Dimeric Structure 21: Brown oil. H NMR: δ = 2.46–2.50 (m, 4 H,
CH2-CH-O), 3.04–3.05 (m, 4 H, CH2-CO2), 4.99–5.02 (m, 2 H,
CH-O), 5.58–5.60 (m, 2 H, -CH=), 5.79–5.86 (m, 4 H, -CH=CH-)
ppm. 13C NMR: δ = 29.9 (2 -CH2-CO2), 38.6 (2 -CH2-CH-O), 78.8
(2 -CH-O), 122.0 (2 =C-H), 125.5 (2 =C-H), 128.2 (2 =C-H), 168.8
(2 -CO -) ppm. IR: ν = 738, 1071, 1265, 1386, 1735, 2846, 2919,
˜
2
3058 cm–1. HRMS (CI): calcd. for C14H16O4 [M + H]+ 249.1127;
found 249.1128.
6-Allyl-3,6-dihydro-pyran-2-one (22): 1H NMR: δ = 2.51 (t, J =
5.8 Hz, 2 H, CH2-CH-O), 3.03–3.05 (m, 2 H, CH2-CO2), 5.02–5.05
(m, 1 H, CH-O), 5.15–5.21 (m, 2 H, CH2=CH-), 5.73–5.79 (m, 1
H, CH2=CH-), 5.81–5.89 (m, 2 H, -CH=CH-) ppm. 13C NMR: δ
= 29.9 (-CH2-CO2), 39.6 (-CH2-CH-O), 78.2 (-CH-O), 119.3
(-CH=CH2), 121.8 (-CH2-CH=), 125.6 (=CH-CHO-), 131.5 (CH2-
CH=), 168.7 (CO2), 121.8 (CH, C3), 125.6 (CH, C4), 131.5 (CH,
169.0 (CO ) ppm. IR: ν = 701, 972, 1069, 1160, 1223, 1383, 1465,
˜
2
1740, 2956, 3019 cm–1. HRMS: calcd. for C12H19O2 [M + H]+
195.1385; found 195.1385.
6-[4-(4-Hydroxy-3-methoxyphenyl)but-2-enyl]-3,6-dihydropyran-2-
one (17e): Eluent: hexanes/EtOAc, 80:20 then 50:50. Orange oil.
Yield: 70% (239 mg, 0.87 mmol). 1H NMR: δ = 2.46–2.51 (m, 2 H,
CH2-CH=), 2.99–3.01 (m, 2 H, CH2-CO2), 3.27 (d, J = 6.6 Hz, 2
H, CH2-Ar), 3.87 (s, 3 H, O-CH3), 4.99–5.02 (m, 1 H, CH-O), 5.47
(dt, J = 15.4, 6.9 Hz, 1 H, CH2-CH=), 5.48 (s, 1 H, OH), 5.73 (dt,
J = 15.4, 6.6 Hz, 1 H, CH=CH2), 5.80 (br. s, 2 H, 2 CH=), 6.65
(m, 2 Har), 6.83 (dd, J = 7.1, 1.1 Hz, 1 Har) ppm. 13C NMR: δ =
29.8 (CH2-CO2), 38.3 (CH2), 38.5 (CH2), 55.7 (CH3), 79.0 (CH-O),
111.0 (CH), 114.2 (CH), 120.8 (CH), 121.7 (CH), 124.0 (CH), 125.7
(CH), 131.7 (C) 134.3 (CH), 143.8 (C), 146.5 (C), 169.0 (CO2) ppm.
C7), 168.7 (C, C1) ppm. IR: ν = 700, 736, 1074, 1262, 1454, 1714,
˜
2854, 2925 cm–1. HRMS: calcd. for C8H11O2 [M + H]+ 139.0759;
found 139.0759.
General Procedure for Tandem RCM/CM Reactions between Ester
15 and Alkenes 16a–f: Ester 15 (1 mmol) and alkene 16 (3 mmol)
were dissolved in dichloromethane (100 mL). After bubbling with
an argon stream for 10 min, Grubbs type II catalyst (0.025 mmol)
was directly added, and the resulting solution was heated to reflux
until complete disappearance of ester 17 (TLC control). After con-
centration under vacuum, corresponding pyrone 18 was purified by
flash chromatography on silica.
IR: ν = 735, 972, 1034, 1122, 1151, 1233, 1268, 1382, 1430, 1514,
˜
1601, 1735, 2936, 3413 cm–1. HRMS: calcd. for C16H18O4 [M]+·
274.1205; found 274.1205.
Benzyl 5-(6-Oxo-5,6-dihydro-2H-pyran-2-yl)-pent-3-enoate (17f):
Eluent: hexanes/EtOAc, 80:20. Colorless oil. Yield: 54% (140 mg,
0.49 mmol). 1H NMR: δ = 2.49 (tt, J = 6.7, 1.1 Hz, 2 H, CH2-
6-Hept-2-enyl-3,6-dihydropyran-2-one (17a): Eluent: hexanes/
EtOAc, 80:20. Colorless oil. Yield: 61% (71 mg, 0.37 mmol). 1H
Eur. J. Org. Chem. 2010, 5063–5070
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5067

F. Cros, B. Pelotier, O. Piva
FULL PAPER
CH=), 3.01–3.02 (m, 2 H, CH2-CO2), 3.10 (dd, J = 6.7, 0.9 Hz, 2
H, CH2-CO2), 4.99–5.02 (m, 1 H, CH-O), 5.12 (s, 2 H, CH2-O),
1 H, CH=), 6.01 (dt, J = 9.8, 1.8 Hz, 1 H, CH-CO2), 6.87 (dt, J =
9.8, 4.5 Hz, 1 H, CH=) ppm. 13C NMR: δ = 22.2 (2 CH3), 28.2
5.52–5.62 (m, 1 H, CH=), 5.67–5.77 (m, 1 H, CH=), 5.81 (br. s, 2 (CH), 28.6 (CH2), 37.9 (CH2), 41.9 (CH2), 77.7 (CH-O), 121.2
H, CH=CH) 7.35 (s, 5 Har) ppm. 13C NMR: δ = 29.9 (CH2-CO2), (CH), 124.5 (CH), 133.8 (CH), 145.2 (CH), 164.4 (CO2) ppm. IR:
38.0 (CH2), 38.5 (CH2), 66.5 (O-CH2), 78.9 (O-CH), 122.0 (CH),
125.6 (CH), 126.7 (CH), 127.6 (CH), 128.3 (3 CH), 128.6 (2 CH),
ν = 736, 814, 972, 1040, 1151, 1247, 1386, 1465, 1727, 2956,
˜
3018 cm–1. HRMS: calcd. for C12H19O2 [M + H]+ 195.1385; found
195.1385.
135.8 (C), 168.8 (CO ), 171.3 (CO ) ppm. IR: ν = 699, 736, 1163,
˜
2
2
1731, 2943, 3054 cm–1. HRMS: calcd. for [M + H]+ 287.1283;
6-[4-(4-Hydroxy-3-methoxyphenyl)but-2-enyl]-5,6-dihydropyran-2-
one (12e): Eluent: hexanes/EtOAc, 50:50. Orange oil. Yield: 52%
(135 mg, 0.49 mmol). 1H NMR: δ = 2.31–2.35 (m, 2 H, CH2-
CHO), 2.44–2.53 (m, 2 H, CH2-CHO), 3.29 (d, J = 6.6 Hz, 2 H,
CH2-ar), 3.87 (s, 3 H, O-CH3), 4.42–4.51 (m, 1 H, CH-O), 5.47 (s,
1 H, OH), 5.54 (dt, J = 15.0, 6.9 Hz, 1 H, CH2-CH=), 5.69 (dt, J
= 15.0, 6.6 Hz, 1 H, CH2-CH=), 6.02 (dt, J = 9.6, 1.7 Hz, 1 H,
CH-CO2), 6.64–6.67 (m, 2 H, 1 CH= and 1 CHar), 6.82–6.90 (m,
2 H, 2 CHar) ppm. 13C NMR: δ = 28.6 (CH2), 37.6 (CH2), 38.5
(CH2), 55.7 (CH3), 77.5 (CH-O), 111.1 (CH), 114.2 (CH), 120.8
(CH), 121.0 (CH), 124.7 (CH), 132.0 (C), 133.7 (CH), 143.8 (C),
found 287.1281.
General Procedure for Reconjugation: Pyran-2-one 17 (1 mmol) was
first dissolved in THF (100 mL). After addition of DBU
(0.1 mmol), the resulting mixture was stirred overnight until com-
plete disappearance of the starting material (TLC control). The
mixture was hydrolyzed with a saturated aqueous solution of am-
monium chloride (15 mL). The solvent was removed by concentra-
tion, and the aqueous phase was extracted with dichloromethane.
The organic layer was successively washed with water (10 mL) and
brine (10 mL) and finally dried with MgSO4. After filtration, the
solution was concentrated under vacuum, and the crude mixture
was purified by flash chromatography on silica.
145.2 (CH), 146.5 (C), 164.4 (CO ) ppm. IR: ν = 733, 910, 1037,
˜
2
1122, 1149, 1266, 1387, 1514, 1612, 1715, 2939, 3537 cm–1. HRMS:
calcd. for C16H18O4 [M]+· 274.1205; found 274.1209.
6-Hept-2-enyl-5,6-dihydropyran-2-one (12a): Eluent: hexanes/
EtOAc, 95:5. Colorless oil. Yield: 70% (50 mg, 0.26 mmol). 1H
Benzyl 5-(6-Oxo-3,6-dihydro-2H-pyran-2-yl)pent-2-enoate (12fЈ):
NMR: δ = 0.88 (t, J = 7.1 Hz, 3 H, 3 H, CH3), 1.31–1.33 (m, 4 H, Eluent: hexanes/EtOAc, 80:20 then 50:50. Yield: 49% (68 mg,
1
CH2-CH2), 2.01 (br. q, J = 7.0 Hz, 2 H, =CH-CH2), 2.30–2.36 (m, 0.23 mmol). Orange oil. H NMR: δ = 1.74–1.84 (m, 1 H, O-CH-
2 H, CH2-CH=), 2.39–2.53 (m, 2 H, CH2), 4.43 (br. quint., J =
7.0 Hz, 1 H, CH-O), 5.39–5.46 (m, 1 H, CH=), 5.51–5.58 (m, 1 H,
CH=), 6.01 (dt, J = 9.8, 1.8 Hz, 1 H, CH-CO2), 6.87 (dt, J = 9.8,
CH2), 1.90–2.01 (m, 1 H, O-CH-CH2), 2.28–2.36 (m, 2 H, CH2-
CH=), 2.40–2.53 (m, 2 H, CH2-CH=), 4.38–4.47 (m, 1 H, CH-O),
5.17 (s, 2 H, O-CH2), 5.92 (dt, J = 15.6, 1.5 Hz, 1 H, CH=), 6.03
4.3 Hz, 1 H, =CH) ppm. 13C NMR: δ = 13.9 (CH3), 22.2 (CH2), (dt, J = 9.6, 1.8 Hz, 1 H, CH-CO2), 6.87 (dt, J = 9.6, 4.5 Hz, 1 H,
28.7 (CH2), 31.5 (CH2), 32.3 (CH2), 38.0 (CH2), 77.8 (CH-O), 121.6
(CH), 123.4 (CH), 135.2 (CH), 145.2 (CH), 164.5 (CO2) ppm. IR:
CH=), 6.99 (dt, J = 15.6, 6.9 Hz, 1 H, CH=), 7.36 (s, 5 H, Har)
ppm. 13C NMR: δ = 27.4 (CH2), 29.4 (CH2), 33.1 (CH2), 66.2 (O-
ν = 736, 816, 1042, 1251, 1387, 1721, 2918, 3011 cm–1. HRMS: CH2), 77.4 (CH-O), 121.4 (CH), 122.1 (CH), 128.2 (3 CH), 128.4
˜
calcd. for C12H19O2 [M + H]+ 194.1307; found 194.1307.
(2 CH), 136.0 (C), 144.9 (CH), 147.8 (CH), 164.1 (CO2), 166.1
(CO ) ppm. IR: ν = 735, 816, 1040, 1164, 1253, 1380, 1654, 1719,
˜
2
6-Hex-2-enyl-5,6-dihydropyran-2-one (12b): Eluent: hexanes/
EtOAc, 95:5. Colorless oil. Yield: 80% (64 mg, 0.36 mmol). 1H
NMR: δ = 0.88 (t, J = 7.2 Hz, 3 H, CH3), 1.38 (sext., J = 7.3 Hz,
2 H, CH2), 1.99 (br. q, J = 7.2 Hz, 2 H, CH2), 2.31–2.37 (m, 2 H,
CH2-CH=), 2.39–2.52 (m, 2 H, CH2-CH=), 4.39–4.48 (m, 1 H, CH-
O), 5.42 (dt, J = 15.3, 6.6 Hz, 1 H, CH=), 5.56 (dt, J = 15.3, 6.6 Hz,
1 H, CH=), 6.02 (dt, J = 9.8, 1.8 Hz, 1 H, CH-CO2), 6.87 (dt, J =
9.8, 4.2 Hz, 1 H, CH=) ppm. 13C NMR: δ = 13.6 (CH3), 22.4
(CH2), 28.7 (CH2), 34.7 (CH2), 37.9 (CH2), 77.7 (CH-O), 121.3
(CH), 123.6 (CH), 134.9 (CH), 145.2 (CH), 164.5 (CO2) ppm. IR:
2944, 3059 cm–1. HRMS: calcd. for [M + H]+ 287.1283; found
287.1282.
Synthesis of Rugulatone (3)
6-(4-Oxo-6-phenyl-hex-2-enyl)-3,6-dihydropyran-2-one (23): A solu-
tion of ester 15 (140 mg, 0.84 mmol) and 5-phenyl-pent-1-en-3-one
(14b; 674 mg, 4.21 mmol) in dichloromethane (168 mL) was deoxy-
genated by bubbling an argon stream for 10 min. Grubbs type II
catalyst 5 (36 mg, 0.04 mmol) was directly added, and the resulting
solution was heated for 6 h. After cooling, an additional amount
of 5 (18 mg, 0.02 mmol) was promptly added. The mixture was
heated to reflux overnight. After cooling, the solvent was removed
by concentration. Compound 23 (119 mg, 0.44 mmol) was isolated
pure as a pale yellow oil after flash chromatography on silica
(EtOAc/hexanes, 5:95 then 20:80). Yield: 57%. 1H NMR: δ = 2.61–
ν = 735, 815, 1040, 1248, 1387, 1723, 2930, 3028 cm–1. HRMS:
˜
calcd. for C11H16O2 [M]+· 180.1150; found 180.1151.
6-(Cinnamyl)-5,6-dihydropyran-2-one (12c): Eluent: hexanes/EtOAc,
80:20 then 50:50. Colorless oil. Yield: 67% (80 mg, 0.37 mmol). 1H
NMR: δ = 2.37–2.42 (m, 2 H, CH2-CH=), 2.63–2.73 (m, 2 H, CH2-
CH=), 4.52–4.61 (m, 1 H, CH-O), 6.03 (dt, J = 9.6 and 1.7 Hz, 1 2.68 (m, 2 H, O-CH-CH2), 2.83–2.95 (m, 4 H, CH2-CH2), 3.03–
H, CH-CO2), 6.24 (dt, J = 15.8 and 7.1 Hz, 1 H, CH2-CH=), 6.50 3.06 (m, 2 H, CH2-CO2), 5.08–5.12 (m, 1 H, CH-O), 5.78–5.83 (m,
(d, J = 15.8 Hz, 1 H, CH-Ph), 6.88 (dt, J = 9.6 and 3.7 Hz, 1 H, 1 H, CH=), 5.88–6.24 (m, 1 H, CH=), 6.22 (d, J = 15.8 Hz, 1 H,
CH-CH2), 7.22–7.30 (m, 5 H, Har) ppm. 13C NMR: δ = 28.7 (CH2), CH-CO), 6.76 (dt, J = 15.8, 7.3 Hz, 1 H, CH2-CH), 7.17–7.28 (m,
38.2 (CH2), 77.4 (CH-O), 121.3 (CH), 123.7 (CH), 126.2 (2 CH), 5 H, Har) ppm. 13C NMR: δ = 29.8 (CH2), 29.9 (CH2), 38.4 (CH2-
127.5 (CH), 128.5 (2 CH), 133.7 (CH), 136.9 (C), 145.1 (CH), 164.3
CH=), 42.1 (CH2-CO), 77.9 (CH-O), 122.9 (CH), 125.2 (CH),
126.2 (CH), 128.4 (2 CH), 128.5 (2 CH), 133.7 (CH), 139.5 (CH),
(CO ) ppm. IR: ν = 694, 736, 817, 855, 967, 1043, 1147, 1250,
˜
2
1387, 1494, 1598, 1719, 2911, 3027, 3057 cm–1. HRMS: calcd. for
C14H14O2 [M]+·: 214.0994; found 214.0993.
141.1 (C), 168.9 (CO ), 198.8 (CO) ppm. IR: ν = 700, 735, 976,
˜
2
1073, 1157, 1225, 1377, 1454, 1496, 1633, 1673, 1740, 2926,
3027 cm–1. HRMS: calcd. for C17H19O3 [M + H]+ 271.1334; found
271.1334.
6-(5-Methyl-hex-2-enyl)-5,6-dihydropyran-2-one (12d): Eluent: hex-
anes/EtOAc, 95:5 then 90:10. Colorless oil. Yield: 65% (66 mg,
0.34 mmol). 1H NMR: δ = 0.87 (d, J = 6.6 Hz, 6 H, 2 CH3), 1.58–
1.65 [m, 1 H, CH(CH3)2], 1.90 (t, J = 7.1 Hz, 2 H, CH2), 2.31–2.35
(m, 2 H, CH2), 2.38–2.53 (m, 2 H, CH2), 4.39–4.48 (m, 1 H, CH-
O), 5.41 (dt, J = 15.2, 6.9 Hz, 1 H, CH=), 5.54 (dt, J = 15.2, 7.1 Hz,
6-(4-Hydroxy-6-phenylhex-2-enyl)-3,6-dihydropyran-2-one (25):
A
1  solution of (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2c]-
[1,3,2]-oxazaborole (24) in toluene (0.02 mL, 0.02 mmol) was
poured, under an argon atmosphere, into a flask containing di-
5068
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5063–5070

Total Synthesis of Rugulactone
chloromethane (1 mL). After cooling to 0 °C, a 1:1 complex
borane–dimethylsulfide in dichloromethane (0.14 mL, 0.14 mmol)
was added dropwise. After 30 min at this temperature, lactone 23
(63 mg, 0.23 mmol) dissolved in dichloromethane (1 mL) was
rapidly added. After only 2 min, the reaction mixture was hy-
drolyzed with a saturated solution of ammonium chloride. The
aqueous layer was extracted with dichloromethane (2ϫ5 mL). The
organic layer was successively washed with water and brine. After
drying with MgSO4 and filtration, the solvent was removed by con-
centration. The residue was purified by flash chromatography on
silica (EtOAc/hexanes, 20:80) to deliver compound 25 (32 mg,
1265, 1422, 1724, 3055 cm–1. HRMS: calcd. for [C17H18O3 + H]+
271.1334; found 271.1333.
Acknowledgments
We thank the Université de Lyon and Centre national de la recher-
che scientifique (CNRS) for financial support. F.C. acknowledges
the “Ministère de la Recherche et de l’Enseignement Supérieur” for
a research fellowship. We are grateful to Mr. Jeremy Ruiz for some
complementary experiments.
1
0.12 mmol) as a pale yellow oil. Yield: 52%. H NMR: δ = 1.79–
1.90 (m, 2 H, CHOH-CH2), 2.50–2.51 (m, 2 H, CH2-CH=), 2.65–
2.75 (m, 2 H, CH2-Ph), 3.03–3.05 (m, 2 H, CH2-CO2), 4.09–4.18
(m, 1 H, CH-OH), 5.02–5.03 (m, 1 H, CH-O), 5.65–5.68 (m, 1 H,
CH=), 5.71–5.73 (m, 1 H, CH2-CH=), 5.81–5.89 (m, 2 H,
CH=CH), 7.18–7.34 (m, 5 H, Har) ppm. 13C NMR: δ = 29.9 (CH2),
31.6 (CH2-Ph), 31.7 (CH2), 38.6 (CH2-CH2-Ph), 71.6 (CH-OH),
78.9 (CH-O), 121.9 (CH), 124.1 (CH), 124.2 (CH), 125.6 (CH),
125.8 (2 CH), 128.3 (CH), 133.8 (CH), 137.9 (CH), 141.8 (C), 169.1
[1] A. de Fatima, L. V. Modolo, L. S. Conegero, R. A. Pilli, C. V.
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(CO ) ppm. IR: ν = 701, 738, 1072, 1265, 1454, 1735, 2927,
˜
2
[4] G. Sabitha, V. Bhaskar, J. S. Yadav, Tetrahedron Lett. 2006, 47,
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6-(4-Hydroxy-6-phenylhex-2-enyl)-5,6-dihydropyran-2-one
(26):
Lactone 25 (110 mg, 0.40 mmol) was dissolved in THF (2 mL). Af-
ter addition of DBU (5 µL, 0.04 mmol, 0.1 equiv.), the reaction
mixture was stirred at room temperature for 2 h. After addition of
a solution of ammonium chloride (2 mL), the aqueous layer was
extracted with dichloromethane (2ϫ3 mL). The organic layer was
washed with water (2 mL) then with brine (2 mL) and finally dried
with MgSO4. After filtration, the solvent was removed by concen-
tration. The crude mixture isolated as a colorless oil was directly
used in the next step. 1H NMR: δ = 2.31–2.35 (m, 2 H, CHOH-
CH2), 2.46–2.52 (m, 2 H, CH2-CH=), 2.67–2.74 (m, 2 H, CH2-Ph),
3.72–3.76 (m, 2 H, CH2-CH=), 4.09–4.13 (m, 1 H, CH-OH), 4.42–
4.49 (m, 1 H, CH-O), 5.66–5.71 (m, 2 H, 2 CH=), 6.00–6.04 (m, 1
H, CH-CO2), 6.84–6.88 (m, 1 H, CH=), 7.18–7.31 (m, 5 H, Har)
ppm. 13C NMR: δ = 28.7 (CH2), 31.7 (CH2-Ph), 37.4 (CH2), 38.7
(CH2-CH2-Ph), 71.6 (CH-OH), 77.2 (CH-O), 121.2 (CH-CO2),
124.8 (CH), 124.9 (CH), 125.8 (CH), 128.3 (2 CH), 133.8 (CH),
137.2 (CH), 141.9 (C), 145.2 (CH=), 164.4 (CO2) ppm.
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Rugulactone (3): To
a solution of compound 26 (110 mg,
0.40 mmol) in dichloromethane (2 mL) was added at 0 °C a solu-
tion of Dess–Martin periodinane in the same solvent (1.04 mL,
0.49 mmol). After stirring for 15 min the reaction was allowed to
reach room temperature and was stirred for an additional hour.
The mixture was hydrolyzed with a saturated aqueous solution of
ammonium chloride (2 mL) followed by a saturated aqueous solu-
tion of Na2S2O3. After extraction with dichloromethane, the or-
ganic layers were successively washed with water and brine. After
drying over MgSO4 and filtration, the solvent was removed by con-
centration. The crude product was purified by flash chromatog-
raphy on silica (EtOAc/hexanes, 50:50). Rugulactone (3; 60 mg,
0.22 mmol) was isolated as a colorless oil. Yield: 55% over 2 steps.
1H NMR: δ = 2.30–2.35 (m, 2 H, CH2-CO), 2.60–2.67 (m, 2 H,
CH2-Ph), 2.87–2.96 (m, 4 H, 2 CH2), 4.54 (br. quint., J = 6.9 Hz,
1 H, CH-O), 6.04 (dt, J = 9.8, 1.8 Hz, 1 H, CH-CO2), 6.19 (dt, J
= 15.8, 1.3 Hz, 1 H, CH-CO), 6.79 (dt, J = 15.8, 7.1 Hz, 1 H,
=CH), 6.87 (dt, J = 9.8, 4.3 Hz, 1 H, =CH), 7.16–7.35 (m, 5 H,
Har) ppm. 13C NMR: δ = 28.9 (CH2), 30.0 (CH2-Ph), 37.5 (CH2),
41.7 (CH2-CO), 76.1 (CH-O), 121.4 (CH-CO2), 126.1 (CH), 128.4
(2 CH), 128.5 (CH), 133.5 (CH), 140.1 (CH), 141.2 (CH), 144.8
(CH), 163.8 (CO ), 199.0 (CO) ppm. IR: ν = 703, 738, 896, 1046,
˜
2
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Published Online: July 20, 2010
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