First partially intramolecular palladium-catalyzed [2+2+2] cycloaddition of benzyne: Application to the synthesis of benzo[b]fluorenones

Article abstract of DOI:10.1002/ejoc.200390178

The palladium(O)-catalyzed reaction of benzyne with suitably functionalized benzodiynes to afford benzo[blfluorenones is described. The outcome of the reaction is affected by the steric and electronic properties of the diynes and proved to be regioselective when an unsymmetrically substituted aryne is used. This work represents the first example of a partially intramolecular [2+2+2] cycloaddition involving arynes. Wiley-VCH Verlag GmbH & Co, KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390178

FULL PAPER
First Partially Intramolecular Palladium-Catalyzed [2؉2؉2] Cycloaddition of
Benzyne: Application to the Synthesis of Benzo[b]fluorenones
[a]
[a]
[a]
[a]
´
´
˜
Diego Pena, Dolores Perez,* Enrique Guitian,* and Luis Castedo
Keywords: Alkynes / Arynes / Benzo[b]fluorenones / Cyclotrimerization / Palladium
The palladium(0)-catalyzed reaction of benzyne with suit-
tuted aryne is used. This work represents the first example
ably functionalized benzodiynes to afford benzo[b]fluor- of a partially intramolecular [2+2+2] cycloaddition involving
enones is described. The outcome of the reaction is affected
by the steric and electronic properties of the diynes and
proved to be regioselective when an unsymmetrically substi-
arynes.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
Results and Discussion
The requisite for a partially intramolecular cyclotrimeri-
zation is that two of the three cycloaddition partners are
linked in the same molecule. When considering the cocyclo-
addition between arynes and alkynes, the simplest scenario
for a partially intramolecular transformation would involve
the reaction of a molecule containing two alkyne moieties
(a diyne) with an external aryne. A literature precedent de-
scribing the stoichiometric reaction of a nickelϪbenzyne
complex with 1,7-octadiyne[8] led us initially to investigate
a catalytic version of this reaction. Our previous work on
intermolecular Pd0-catalyzed cocycloadditions of arynes
with alkynes had shown that, because of the extremely high
reactivity of arynes,[9] efficient cycloaddition involving two
alkyne moieties and one molecule of aryne was possible
only when a highly activated alkyne was used and Pd2(dba)3
acted as a catalyst. In these cases we postulated the initial
formation of a palladacyclopentadiene, by oxidative coup-
ling of two alkynes, as an intermediate in the catalytic
cycle.[2,10] With this information in mind we prepared diyne
1,[11] which contains two electron-withdrawing ethoxycar-
bonyl groups as substituents on the alkynes, and assessed
its reaction with benzyne (3), generated from 2-(trimethyl-
silyl)phenyl triflate (2),[12] in the presence of 5 mol %
Pd2(dba)3 (Scheme 1). The major product isolated from this
reaction was compound 4, which resulted from the inter-
molecular cocycloaddition between two molecules of
benzyne and one of the alkyne moieties of the diyne. The
expected tetrahydroanthracene 5, which should be formed
by a partially intramolecular reaction between 1 and 3, was
not detected, probably because of electronic and/or con-
formational factors precluding the generation of the re-
quired palladacyclic intermediate.
Intramolecular — or partially intramolecular — versions
of cycloaddition reactions are extremely useful tools in the
synthesis of polycyclic molecules, since they provide
methods for the construction of several rings in a single
step, with a concomitant increase in molecular complexity.
In particular, with regard to the transition metal mediated
[2ϩ2ϩ2] cycloaddition reactions of alkynes,[1] partially in-
tramolecular variants have allowed the (otherwise difficult)
control of the chemoselectivity and the regiochemistry of
such transformations, as well as the participation of alkenes
or nitriles as reaction partners.
Recently, we reported the intermolecular palladium-cata-
lyzed cocyclotrimerization of arynes with alkynes[2Ϫ4] and,
following our first reports, other groups have described
metal-catalyzed cocycloadditions of arynes.[5,6] Despite the
excellent control of the chemoselectivity achieved in those
reactions, the fact that they are ‘‘purely’’ intermolecular cle-
arly limits their scope for synthetic applications. As a con-
tinuation of our research project we envisioned the develop-
ment of partially intramolecular versions of the palladium-
catalyzed [2ϩ2ϩ2] cycloadditions involving arynes, which
have the potential to allow the construction of complex po-
lycyclic systems. In this paper we describe our initial efforts
in this field and, in particular, the application of the palla-
dium-catalyzed cocyclotrimerization of benzyne with diynes
in the synthesis of benzo[b]fluorenones, which constitute
the polycyclic skeleton of the antitumor antibiotics kinamy-
cins.[7]
[a]
´
´
Departamento de Quımica Organica, Universidad de Santiago
de Compostela and Unidad Asociada al CSIC,
15706 Santiago de Compostela, Spain
E-mail: qodolopm@usc.es
Next we decided to investigate a different model diyne
with a higher degree of conformational restrictions and
containing at least one highly electrophilic alkyne. In this
qoenrgui@usc.es
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 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0407Ϫ1238 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 1238Ϫ1243

Palladium-Catalyzed [2ϩ2ϩ2] Cycloaddition of Benzyne
FULL PAPER
Scheme 1
sense, we envisioned as potential candidates benzodiynes 6,
which upon [2ϩ2ϩ2] cycloaddition with benzyne should af-
ford benzo[b]fluorenones 7 (Scheme 2). We reasoned that in
this case, after initial coordination of one of the alkyne un-
its (electron-deficient) in 6 to the metal atom, entropic fac-
tors should favor the formation of a palladacycle of type 8,
which should subsequently react with benzyne to afford the
desired cycloaddition product 7.
Scheme 3
corporates a highly reactive diene system, finally evolved to
a mixture of dimers of 6a. As expected, ketone 6b (R1 ϭ
tBu), which lacks propargylic hydrogen atoms and therefore
cannot decompose through the previously proposed path-
way, was found to be considerably more stable.
Scheme 2
Scheme 4
Several diynes 6 with different steric and electronic prop-
erties were prepared according to the reaction sequence
shown in Scheme 3. Sonogashira coupling[13] of alkynes
10aϪc with 2-bromobenzaldehyde (9) afforded the corres-
ponding 2-alkynylbenzaldehydes 11aϪc, which upon reac-
tion with the lithium acetylide 12a, derived from ethyl pro-
piolate, gave alcohols 13aϪc in good to excellent yields. Ox-
idation of 13aϪc with MnO2 led to the quantitative isola-
tion of the corresponding ketones 6aϪc. Although we had
reasoned that the presence of at least one highly electron-
deficient alkyne in 6 should be a prerequisite for a success-
ful reaction, we also prepared 6d, with an alkyl group as
R1, in order to check this premise.[14] Compound 6d was
prepared in a similar way to 6aϪc and the reactions proved
equally efficient (Scheme 3).
It is worth noting also that diyne 6c (R1 ϭ Ph) is slowly
transformed into a mixture of products in which the major
compound (over 60%) was benzo[b]fluorenone 16, which is
probably formed by a formal intramolecular [4ϩ2] cycload-
dition via the cyclic allene 15 (Scheme 5).[15]
Scheme 5
With diynes 6 in hand, we proceeded to study their reac-
tion with benzyne, generated from 2-(trimethylsilyl)phenyl
Compounds 6aϪc, with R2 ϭ CO2Et, proved too labile triflate (2),[12] in the presence of a Pd0 complex (Scheme 6).
when stored at room temperature and it was necessary to The catalyst of choice was Pd2(dba)3, which according to
prepare these materials just prior to use from the corres- our previous work on the intermolecular version of this re-
ponding stable alcohols 13. Interestingly, we observed that action should favor the chemoselective cocycloaddition of
6a was transformed, upon standing at room temperature two molecules of alkyne with one molecule of aryne.[2,3] Sat-
for 7 h, into a more-polar yellow product whose structure isfyingly, the reaction catalyzed by Pd2(dba)3 between crude
was assigned on the basis of its 1H NMR spectrum as vinyl- 6a, prepared immediately before use from alcohol 13a as
allene 14. The formation of this compound can be ex- described above, and benzyne afforded the desired benzo-
plained in terms of an intramolecular ene reaction on fluorenone 7a in a moderate 38% yield,[16] together with
benzodiynone 6a (Scheme 4). This compound, which in- minor amounts of triphenylene (9%) and other products de-
Eur. J. Org. Chem. 2003, 1238Ϫ1243
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D. Pen˜a, D. Perez, E. Guitian, L. Castedo
FULL PAPER
rived from the decomposition of 6a through the ene reac-
tion outlined in Scheme 4.
Scheme 6
Scheme 7
The reaction of the more stable ketone 6b (R1 ϭ tBu)
under similar reaction conditions gave the benzofluorenone cycloaddition of benzyne to a suitably functionalized diyne.
7b in a lower yield (24%), with the major product of the The outcome of the reaction is affected by the steric and
reaction being the substituted phenanthrene 17 (38%), electronic properties of the diyne and, when an unsymmet-
which results from the [2ϩ2ϩ2] cycloaddition of two mole- rically substituted aryne was used, the reaction proved to
cules of benzyne with the more electrophilic alkyne unit in be regioselective. Although the moderate yields obtained
6b.[17] We attribute this result to the presence of the bulky limit the general applicability of the reaction for preparative
tert-butyl group, which probably disfavors the coordination purposes, the major interest of this work arises from the
of the second alkyne moiety to the metal atom and makes fact that it represents the first example of a partially intra-
the formation of a metallacyclic intermediate of type 8 molecular [2ϩ2ϩ2] cyclotrimerization involving arynes.
more difficult. The best result obtained in our study in- Work is in progress aimed at the rational design of novel
volved the reaction of ketone 6c, which is less labile than cycloaddition partners and the application of this methodo-
6a and contains a smaller R1 group (R1 ϭ Ph) than 6b. logy to the synthesis of other bioactive polycyclic com-
Reaction of 6c with benzyne in the presence of 5 mol % pounds.
Pd2(dba)3 afforded the corresponding benzofluorenone 7c
in 54% yield. As expected, the reaction of compound 6d
(R1 ϭ R2 ϭ Pr) failed, affording only a 9% yield of the
desired cocycloaddition product 7d and confirming our pre-
dictions regarding the electronic requirements of the diynes
(see above).
Experimental Section
General: All reactions were performed under argon. Solvents were
dried by distillation from a drying agent: Et2O and THF from Na/
benzophenone; CH3CN from CaH2. TMSCl and NEt3 were dis-
tilled from CaH2 prior to use. Reported melting points are uncor-
rected. 1H and 13C NMR spectra were recorded at 250.13 and
62.83 MHz, respectively. LR and HR mass spectra were recorded
using EI (70 eV) or FAB techniques. TLC was performed on Merck
silica gel 60 F254; chromatograms were visualized with UV light
(254 and 360 nm), phosphomolybdic acid, and/or p-anisaldehyde.
Column chromatography was performed on Merck silica gel 60
(ASTM 230Ϫ400 mesh). 2-(Trimethylsilyl)phenyl trifluoro-
methanesulfonate (2) and 3-methoxy-2-(trimethylsilyl)phenyl
trifluoromethanesulfonate (18) were prepared according to a re-
cently published procedure developed in our laboratories.[12]
Pd2(dba)3·CHCl3 and PdCl2(PPh3)2 were purchased from Strem;
other commercial reagents were purchased from Aldrich Chemical
Co. and were all used without further purification.
Finally, we carried out the reaction of ketone 6a with 3-
methoxybenzyne (19), generated from triflate 18, in order
to gain an insight into the regioselectivity of the process
when an unsymmetrically substituted aryne acts as a reac-
tion partner. Reaction of 6a with 18 under the reaction con-
ditions previously described afforded benzofluorenone 20
as the only cocycloaddition product in 43% yield. The 2-(1-Pentynyl)benzaldehyde
(11a):
PdCl2(PPh3)2
(0.215 g,
0.31 mmol) and CuI (0.097 g, 0.51 mmol) were added to a solution
of 2-bromobenzaldehyde (9, 1.877 g, 10.15 mmol), 1-pentyne (10a,
1.35 mL, 13.77 mmol), and NEt3 (2.8 mL, 20.40 mmol) in THF
(20 mL). The mixture was heated under reflux for 3 h under argon.
The solvent was evaporated under reduced pressure and the residue
was purified by flash chromatography (SiO2; Et2O/hexane, 2:98) to
yield 11a[18] (1.421 g, 81%) as a yellow oil. 1H NMR (CDCl3, 25
°C): δ ϭ 1.07 (t, J ϭ 7.3 Hz, 3 H, CH2CH2CH3), 1.68 (m, 2 H,
CH2CH2CH3), 2.47 (t, J ϭ 7.0 Hz, 2 H, CH2CH2CH3), 7.38 (m, 1
H, ArH), 7.51Ϫ7.53 (m, 2 H, ArH), 7.89 (d, J ϭ 7.7 Hz, 1 H,
structure of the product was established on the basis of
NOE and COSY experiments: irradiation of the OCH3
group (δ ϭ 3.94 ppm) afforded a positive difference NOE
to 8-H (δ ϭ 6.88 ppm, 5.1%) and to the terminal CH3 unit
of the ethoxyl group (δ ϭ 1.48 ppm, 0.8%), which had been
1
assigned previously with the help of a homonuclear H-1H
COSY spectrum. The other possible regioisomer 21 was not
detected in the reaction mixture (Scheme 7).
In summary, we report a novel approach to the
benzo[b]fluorenone nucleus by palladium-catalyzed co- ArH), 10.55 (d, J ϭ 0.8 Hz, 1 H, CHO) ppm. 13C NMR DEPT
1240
Eur. J. Org. Chem. 2003, 1238Ϫ1243

Palladium-Catalyzed [2ϩ2ϩ2] Cycloaddition of Benzyne
(CDCl3, 25 °C): δ ϭ 13.2 (CH3), 21.1 (CH2), 21.6 (CH2), 76.1 (C), 5.82 (d, J ϭ 6.9 Hz, 1 H, CHOH), 7.27Ϫ7.34 (m, 2 H, ArH), 7.42
FULL PAPER
97.6 (C), 126.4 (CH), 127.5 (CH), 132.9 (CH), 133.3 (CH), 135.5
(C), 191.5 (CO) ppm.
(dd, J ϭ 7.2, 2.3 Hz, 1 H, ArH), 7.51 (dd, J ϭ 6.7, 2.3 Hz, 1 H,
ArH) ppm.13C NMR DEPT (CDCl3, 25 °C): δ ϭ 13.8 (ethyl CH3),
28.1 (tBu C), 30.6 (tBu CH3), 62.0 (CH2), 62.8 (CHOH), 76.1 (al-
kyne C), 76.9 (alkyne C), 86.1 (alkyne C), 105.1 (alkyne C), 121.8
(C), 126.3 (CH), 128.0 (CH), 128.3 (CH), 132.2 (CH), 140.0 (C),
153.3 (ester CO) ppm. MS, m/z (%) ϭ 284 (3), 269 (7), 256 (10),
223 (58), 195 (100). HRMS for C18H20O3, calcd: 284.1413; found
284.1414.
2-(3,3-Dimethyl-1-butynyl)benzaldehyde
(11b):
PdCl2(PPh3)2
(0.268 g, 0.38 mmol) and CuI (0.121 g, 0.63 mmol) were added to
a solution of 2-bromobenzaldehyde (9, 2.35 g, 12.70 mmol), 3,3-
dimethyl-1-butyne (10b, 1.9 mL, 15.24 mmol), and NEt3 (3.5 mL,
25.40 mmol) in THF (24 mL). The mixture was heated under reflux
for 3 h under argon. The solvent was evaporated under reduced
pressure and the residue was purified by flash chromatography
(SiO2; Et2O/hexane, 1:99) to yield 11b[18] (2.103 g, 89%) as a yellow
Ethyl 4-Hydroxy-4-[2-(2-phenyl-1-ethynyl)phenyl]-2-butynoate (13c):
According to the experimental procedure described above for the
1
synthesis of 13a,
a solution of ethyl propiolate (0.307 mL,
oil. H NMR (CDCl3, 25 °C): δ ϭ 1.35 (s, 9 H, tBu), 7.36 (m, 1
3.04 mmol) in THF (15 mL) was treated with nBuLi (1.316 mL,
2.38  in hexanes, 3.13 mmol) and a solution of 11c (0.597 g,
2.90 mmol) in THF (5 mL). The residue obtained after workup was
purified by flash chromatography (SiO2; Et2O/hexane, 5:95) to yield
13c (0.568 g, 64%) as a colorless oil. 1H NMR (CDCl3, 25 °C): δ ϭ
1.29 (t, J ϭ 7.2 Hz, 3 H, OCH2CH3), 2.82 (d, J ϭ 6.5 Hz, 1 H,
CHOH), 4.23 (q, J ϭ 7.1 Hz, 2 H, OCH2CH3), 6.01 (d, J ϭ 6.4 Hz,
1 H, CHOH), 7.36Ϫ7.42 (m, 5 H, ArH), 7.56Ϫ7.60 (m, 3 H, ArH),
7.65 (d, J ϭ 7.7 Hz, 1 H, ArH) ppm. 13C NMR DEPT (CDCl3, 25
°C): δ ϭ 13.9 (CH3), 62.2 (CH2), 62.8 (CHOH), 77.4 (alkyne C),
85.8 (alkyne C), 86.0 (alkyne C), 95.4 (alkyne C), 121.4 (C), 122.5
(C), 126.8 (CH), 128.3 (CH), 128.7 (CH), 128.9 (CH), 131.6 (CH),
132.5 (CH), 140.0 (C), 153.3 (ester CO) ppm. MS: m/z (%) ϭ 304
(1), 289 (7), 276 (13), 231 (70), 202 (100).
H, ArH), 7.46Ϫ7.54 (m, 2 H, ArH), 7.88 (d, J ϭ 7.8 Hz, 1 H,
ArH), 10.53 (s, 1 H, CHO) ppm.
2-(2-Phenyl-1-ethynyl)benzaldehyde (11c): PdCl2(PPh3)2 (0.084 g,
0.12 mmol) and CuI (0.038 g, 0.20 mmol) were added to a solution
of 2-bromobenzaldehyde (9, 0.740 g, 4.00 mmol), phenylacetylene
(10c, 0.527 mL, 4.80 mmol), and NEt3 (1.1 mL, 8.00 mmol) in
THF (8 mL). The mixture was heated under reflux for 3 h under
argon. The solvent was evaporated under reduced pressure and the
residue was purified by flash chromatography (SiO2; Et2O/hexane,
2:98) to yield 11c[18] (0.763 g, 93%) as a yellow oil. 1H NMR
(CDCl3, 25 °C): δ ϭ 7.41Ϫ7.36 (m, 4 H, ArH), 7.47Ϫ7.66 (m, 4
H, ArH), 7.85 (dd, J ϭ 7.7, 0.9 Hz, 1 H, ArH), 10.65 (s, 1 H, CHO)
ppm. 13C NMR DEPT (CDCl3, 25 °C): δ ϭ 84.7 (alkyne C), 96.2
(alkyne C), 122.1 (C), 126.6 (C), 127.0 (CH), 128.3 (CH), 128.4
(CH), 128.9 (CH), 131.5 (CH), 133.0 (CH), 133.6 (CH), 135.5 (C),
191.4 (CHO) ppm. MS: m/z (%) ϭ 206 (100), 176 (47), 152 (28).
1-[2-(1-Pentynyl)phenyl]-2-hexyn-1-ol (13d): nBuLi (1.01 mL, 2.38 
in hexanes, 2.40 mmol) was added dropwise to a solution of 1-
pentyne (10a, 0.218 mL, 2.22 mmol) in THF (15 mL) at Ϫ78 °C.
The resulting solution was stirred for 10 min at Ϫ78 °C and then
a solution of 11d (0.332 g, 1.93 mmol) in THF (5 mL) was added.
The resulting mixture was warmed to room temp. and stirred for
12 h. 10% aq. NH4Cl (15 mL) was added, the organic layer was
separated and the aqueous layer was extracted with Et2O (2 ϫ
15 mL). The combined organic layers were dried (Na2SO4), filtered,
and concentrated under reduced pressure. The residue was purified
by flash chromatography (SiO2; Et2O/hexane, 8:92) to yield 13d
(0.415 g, 90%) as a colorless oil. 1H NMR (CDCl3, 25 °C): δ ϭ
0.99 (t, J ϭ 7.3 Hz, 3 H, CH2CH2CH3), 1.07 (t, J ϭ 7.3 Hz, 3 H,
CH2CH2CH3), 1.49Ϫ1.70 (m, 4 H, CH2CH2CH3), 2.25 (dt, J ϭ
7.1, 2.0 Hz, 2 H, CH2CH2CH3), 2.44 (t, J ϭ 7.0 Hz, 2 H,
CH2CH2CH3), 2.67 (d, J ϭ 4.8 Hz, 1 H, CHOH), 5.84 (br. s, 1 H,
CHOH), 7.21Ϫ7.35 (m, 2 H, ArH), 7.41 (dd, J ϭ 7.2, 1.6 Hz, 1 H,
ArH), 7.67 (d, J ϭ 7.5 Hz, 1 H, ArH) ppm.13C NMR DEPT
(CDCl3, 25 °C): δ ϭ 13.5 (CH3), 13.6 (CH3), 20.8 (CH2), 21.5
(CH2), 22.0 (CH2), 22.1 (CH2), 63.4 (CHOH), 78.1 (alkyne C), 79.3
(alkyne C), 87.2 (alkyne C), 95.9 (alkyne C), 122.0 (C), 126.5 (CH),
127.9 (CH), 128.0 (CH), 132.4 (CH), 142.6 (C) ppm. MS: m/z
(%) ϭ 240 (4), 225 (4), 211 (48), 197 (100). HRMS for C17H20O,
calcd: 240.1514; found 240.1521.
Ethyl 4-Hydroxy-4-[2-(1-pentynyl)phenyl]-2-butynoate (13a): nBuLi
(1.73 mL, 2.04  in hexanes, 3.53 mmol) was added dropwise to a
solution of ethyl propiolate (0.34 mL, 3.36 mmol) in THF (20 mL)
at Ϫ78 °C. Immediately, a solution of 11a (0.551 g, 3.20 mmol) in
THF (5 mL) was added and the resulting mixture was warmed to
room temp. and stirred for 12 h. 10% aq. NH4Cl (15 mL) was ad-
ded, the organic layer was separated, and the aqueous layer was
extracted with Et2O (2 ϫ 15 mL). The combined organic layers
were dried (Na2SO4), filtered, and concentrated under reduced
pressure. The residue was purified by flash chromatography (SiO2;
1
Et2O/hexane, 2:8) to yield 13a (0.733 g, 85%) as a colorless oil. H
NMR (CDCl3, 25 °C): δ ϭ 1.07 (t, J ϭ 7.3 Hz, 3 H, CH3), 1.31 (t,
J ϭ 7.1 Hz, 3 H, CH3), 1.67 (m, 2 H, CH2CH2CH3), 2.46 (t, J ϭ
7.0 Hz, 2 H, CH2CH2CH3), 2.84 (d, J ϭ 6.6 Hz, 1 H, CHOH), 4.24
(q, J ϭ 7.1 Hz, 2 H, OCH2CH3), 5.91 (d, J ϭ 6.6 Hz, 1 H, CHOH),
7.28Ϫ7.37 (m, 2 H, ArH), 7.44 (dd, J ϭ 7.1, 2.0 Hz, 1 H, ArH),
7.57 (d, J ϭ 8.0 Hz, 1 H, ArH) ppm.13C NMR DEPT (CDCl3, 25
°C): δ ϭ 13.3 (CH3), 13.6 (CH3), 21.2 (CH2), 21.7 (CH2), 61.9
(OCH2), 62.2 (CHOH), 77.4 (alkyne C), 76.7 (alkyne C), 86.2 (al-
kyne C), 96.5 (alkyne C), 121.9 (C), 126.2 (CH), 127.9 (CH), 128.2
(CH), 132.1 (CH), 139.8 (C), 153.3 (ester CO) ppm. MS: m/z (%) ϭ
270 (1), 255 (9), 241 (13), 208 (100). HRMS for C16H15O3, calcd:
255.1021; found 255.1034.
General Procedure for the Synthesis of Benzo[b]fluoren-11-ones 7:
MnO2 (300Ϫ400 mol %) was added in portions to a solution of
Ethyl 4-[2-(3,3-Dimethyl-1-butynyl)phenyl]-4-hydroxy-2-butynoate alcohol 13 (approx. 0.50 mmol) in Et2O (10 mL). The resulting sus-
(13b): According to the experimental procedure described above pension was stirred at room temp. for 5Ϫ60 min, filtered through
for the synthesis of 13a, a solution of ethyl propiolate (0.591 mL, Celite, and concentrated under reduced pressure to yield the corres-
3.36 mmol) in THF (30 mL) was treated with nBuLi (3.00 mL, 2.04
in hexanes, 6.14 mmol) and solution of 11b (1.037 g,
ponding ketone 6. The resulting product was dissolved in CH3CN
(approx. 5 mL) and to this solution was added 2-(trimethylsilyl)-

a
5.58 mmol) in THF (10 mL). The residue obtained after workup phenyl trifluoromethanesulfonate (3, 50 mol %), Pd2(dba)3·(5
was purified by flash chromatography (SiO2; Et2O/hexane, 1:9) to mol %), and CsF (100 mol %). The mixture was stirred under argon
yield 13b (1.50 g, 94%) as a colorless oil. 1H NMR (CDCl3, 25 °C): at room temp. for 12 h. The solvent was evaporated under reduced
δ ϭ 1.30 (t, J ϭ 7.1 Hz, 3 H, OCH2CH3), 1.36 (s, 9 H, tBu), 3.01 pressure and the residue was purified by flash chromatography to
(d, J ϭ 7.1 Hz, 1 H, CHOH), 4.23 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3), yield the corresponding benzofluorenone 7.
Eur. J. Org. Chem. 2003, 1238Ϫ1243
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D. Pen˜a, D. Perez, E. Guitian, L. Castedo
FULL PAPER
Ethyl 11-Oxo-5-propyl-11H-benzo[b]fluorene-10-carboxylate (7a):
61.7 (CH2), 77.7 (alkyne C), 105.4 (alkyne C), 122.7 (CH), 122.8
According to the general procedure described above, alcohol 13a (CH), 124.5 (C), 126.7 (CH), 127.16 (CH), 127.21 (CH), 127.3
(162 mg, 0.60 mmol) was treated with MnO2 (1.57 g, 18.00 mmol)
for 5 min to afford 4-[2-(1-pentynyl)phenyl]-4-oxo-2-butynoate (6a)
as a yellow oil. The resulting product was treated with 2-(trimethyl-
(CH), 127.5 (CH), 127.6 (C), 127.9 (CH), 128.1 (C), 128.2 (CH),
128.4 (C), 130.8 (C), 131.0 (CH), 131.1 (C), 132.1 (CH), 134.8
(CH), 137.9 (C), 138.9 (C), 167.5 (ester CO), 196.9 (CO) ppm. IR
silyl)phenyl trifluoromethanesulfonate (2, 0.073 mL, 0.30 mmol), (film): ν˜ ϭ 1725, 1662 cmϪ1. UV (CHCl3): λmax ϭ 256 nm. MS:
Pd2(dba)3·CHCl3 (16 mg, 0.015 mmol), [18]crown-6[19] (40 mg, m/z (%) ϭ 434 (36), 419 (100), 302 (57). HRMS for C30H26O3:
0.15 mmol), and CsF (114 mg, 0.75 mmol) in CH3CN (6 mL).
Workup and purification by flash chromatography (SiO2; Et2O/
hexane, 3:97 then 1:9) afforded triphenylene (2 mg, 9%) and 7a
calcd. 434.1882; found 434.1869.
Ethyl 5-Phenyl-11-oxo-11H-benzo[b]fluorene-10-carboxylate (7c):
According to the general procedure described above, alcohol 13c
(135 mg, 0.44 mmol) was treated with MnO2 (773 mg, 8.88 mmol)
for 30 min to afford 4-[2-(2-phenyl-1-ethynyl)phenyl]-4-oxo-2-
butynoate (6c) as a yellow oil. The resulting product was treated with
2-(trimethylsilyl)phenyl trifluoromethanesulfonate (2, 0.054 mL,
0.22 mmol), Pd2(dba)3·CHCl3 (11.5 mg, 0.011 mmol), and CsF
(68 mg, 0.44 mmol). Workup and purification by flash chromatog-
raphy (SiO2; Et2O/hexane, 4:96) afforded 7c (45 mg, 54%) as a
1
(39 mg, 38%) as a yellow solid. Data for 6a: H NMR (CDCl3, 25
°C): δ ϭ 1.07 (d, J ϭ 7.3 Hz, 3 H, CH3), 1.35 (t, J ϭ 7.1 Hz, 3 H,
CH3), 1.74Ϫ1.59 (m, 2 H, CH2CH2CH3), 2.46 (t, J ϭ 7.0 Hz, 2 H,
CH2CH2CH3), 4.32 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3), 7.39 (m, 1
H, ArH), 7.47Ϫ7.53 (m, 2 H, ArH), 8.01 (d, J ϭ 7.6 Hz, 1 H, ArH)
ppm. Data for 7a: M.p. 135 °C. 1H NMR (CDCl3, 25 °C): δ ϭ
1.20 (t, J ϭ 7.3 Hz, 3 H, CH3); 1.49 (t, J ϭ 7.1 Hz, 3 H, CH3),
1.85Ϫ1.75 (m,
2 H, CH2CH2CH3), 3.35Ϫ3.28 (m, 2 H,
1
yellow solid. Data for 6c: H NMR (CDCl3, 25 °C): δ ϭ 1.29 (t,
CH2CH2CH3), 4.65 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3), 7.35 (t, J ϭ
7.6 Hz, 1 H, ArH), 7.65Ϫ7.49 (m, 3 H, ArH), 7.86Ϫ7.76 (m, 3 H,
ArH), 8.11 (d, J ϭ 8.3 Hz, 1 H, ArH) ppm. 13C NMR DEPT
(CDCl3, 25 °C): δ ϭ 14.1 (CH3), 14.5 (CH3), 22.8 (CH2), 30.3
(CH2), 62.2 (benzylic CH2), 124.2 (CH), 124.5 (CH), 124.8 (CH),
127.4 (CH), 127.6 (CH), 128.7 (CH), 129.2 (CH), 129.4 (C), 129.8
(C), 134.1 (C), 135.3 (CH), 136.1 (2C), 136.2 (2C), 145.1 (C), 167.9
(ester CO), 191.6 (CO) ppm. UV (CHCl3): λmax ϭ 292 nm. MS:
m/z (%) ϭ 344 (87), 315 (100), 299 (30). HRMS for C23H20O3:
calcd. 344.1413; found 344.1415.
J ϭ 7.1 Hz, 3 H, OCH2CH3), 4.26 (q, J ϭ 7.1 Hz, 2 H, OCH2CH3),
7.35Ϫ7.38 (m, 3 H, ArH), 7.47 (dt, J ϭ 7.5, 1.3 Hz, 1 H, ArH),
7.56Ϫ7.69 (m, 4 H, ArH), 8.11 (d, J ϭ 7.7 Hz, 1 H, ArH) ppm.
13C NMR DEPT (CDCl3, 25 °C): δ ϭ 13.9 (CH3), 62.9 (CH2), 80.6
(alkyne C), 80.9 (alkyne C), 87.5 (alkyne C), 96.3 (alkyne C), 122.8
(C), 123.5 (C), 128.1 (CH), 128.3 (CH), 128.9 (CH), 131.9 (CH),
133.5 (CH), 134.5 (CH), 136.3 (C), 152.3 (ester CO), 175.3 (CO)
ppm. MS, m/z ϭ (%) ϭ 302 (47), 257 (48), 230 (100), 200 (85).
1
Data for 7c: M.p. 177 °C. H NMR (CDCl3, 25 °C): δ ϭ 1.53 (t,
J ϭ 7.2 Hz, 3 H, OCH2CH3), 4.69 (q, J ϭ 7.2 Hz, 2 H, OCH2CH3),
6.29 (dd, J ϭ 6.4, 1.7 Hz, 1 H, H-4), 7.16Ϫ7.23 (m, 2 H, ArH),
7.36Ϫ7.39 (m, 2 H, ArH), 7.45Ϫ7.54 (m, 3 H, ArH), 7.60Ϫ7.63
(m, 3 H, ArH), 7.71 (m, 1 H, ArH), 7.90 (dd, J ϭ 7.6, 1.4 Hz, 1
H, ArH), ppm. 13C NMR DEPT (CDCl3, 25 °C): δ ϭ 14.2 (CH3),
62.3 (CH2), 123.9 (CH), 124.3 (CH), 127.1 (CH), 127.4 (CH), 127.6
(CH), 128.46 (C), 128.53 (CH), 128.9 (CH), 129.2 (CH), 129.4
(CH), 129.5 (CH), 129.6 (C), 130.4 (C), 134.6 (C), 134.9 (CH),
135.7 (C), 136.0 (C), 136.7 (C), 137.0 (C), 144.7 (C), 167.6 (ester
CO), 191.4 (CO) ppm. UV (CHCl3): λmax ϭ 292 nm. MS: m/z
(%) ϭ 378 (66), 333 (42), 306 (54), 276 (100). HRMS for C26H18O3:
calcd. 378.1256; found 378.1260.
Ethyl 5-(3,3-Dimethyl-1-butynyl)-11-oxo-11H-benzo[b]fluorene-10-
carboxylate (7b): According to the general procedure described
above, alcohol 13b (145 mg, 0.51 mmol) was treated with MnO2
(1.78 g, 20.44 mmol) for 15 min to afford 4-[2-(3,3-dimethyl-1-bu-
tynyl)phenyl]-4-oxo-2-butynoate (6b) as a yellow oil. The resulting
product was treated with 2-(trimethylsilyl)phenyl trifluoromethane-
sulfonate (2, 0.062 mL, 0.26 mmol), Pd2(dba)3·CHCl3 (13 mg,
0.012 mmol), and CsF (97 mg, 0.64 mmol). Workup and purifica-
tion by flash chromatography (SiO2; Et2O/hexane, 4:96) afforded
7b (22 mg, 24%) and ethyl 10-[2-(3,3-dimethyl-1-butynyl)benzoyl]-
phenanthrene-9-carboxylate (17, 21 mg, 38%) as yellow solids.
Data for 6b: 1H NMR (CDCl3, 25 °C): δ ϭ 1.34 (s, 9 H, tBu), 1.35
(t, J ϭ 7.2 Hz, 3 H, OCH2CH3), 4.32 (q, J ϭ 7.2 Hz, 2 H,
OCH2CH3), 7.38 (m, 1 H, ArH), 7.50Ϫ7.52 (m, 2 H, ArH), 8.99
5,10-Dipropyl-11H-benzo[b]fluorene-11-one (7d): According to the
general procedure described above, alcohol 13d (117 mg,
(d, J ϭ 7.7 Hz, 1 H, ArH) ppm. MS: m/z (%) ϭ 282 (17), 267 (100), 0.49 mmol) was treated with MnO2 (1.7 g, 19.50 mmol) for 60 min
165 (89). Data for 7b: M.p. 122 °C. 1H NMR (CDCl3, 25 °C): δ ϭ
to afford 1-[2-(1-pentynyl)phenyl]-2-hexyn-1-one (6d) as a yellow
1.50 (t, J ϭ 7.1 Hz, 3 H, OCH2CH3), 1.77 (s, 9 H, tBu), 4.64 (q, oil. The resulting product was treated with 2-(trimethylsilyl)phenyl
J ϭ 7.1 Hz, 2 H, OCH2CH3), 7.32 (d, J ϭ 7.4 Hz, 1 H, ArH), trifluoromethanesulfonate (2, 0.059 mL, 0.24 mmol),
7.44Ϫ7.57 (m, 3 H, ArH), 7.73Ϫ7.78 (m, 2 H, ArH), 7.83 (d, J ϭ Pd2(dba)3·CHCl3 (13 mg, 0.012 mmol), and CsF (93 mg,
7.9 Hz, 1 H, ArH), 8.29 (dd, J ϭ 7.5, 1.8 Hz, 1 H, ArH) ppm. 13C
0.61 mmol). Work up and purification by flash chromatography
NMR DEPT (CDCl3, 25 °C): δ ϭ 14.1 (ethyl CH3), 32.7 (tert-butyl (SiO2; Et2O/hexane, 2:98) afforded 7d (7 mg, 9%) as a yellow solid.
1
CH3), 37.7 (tert-butyl C), 62.2 (CH2), 124.2 (CH), 126.5 (CH), Data for 6d: H NMR (CDCl3, 25 °C): δ ϭ 1.05 (t, J ϭ 7.3 Hz, 3
126.6 (CH), 126.7 (CH), 127.8 (CH), 128.3 (CH), 128.4 (C), 128.8
(CH), 130.0 (C), 130.3 (C), 133.8 (CH), 135.6 (C), 136.9 (C), 137.5
H, CH3), 1.07 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.66 (m, 4 H, 2 ϫ
CH2CH2CH3), 2.43 (t, J ϭ 7.0 Hz, 2 H, CH2CH2CH3), 2.45 (t, J ϭ
(C), 147.1 (C), 148.0 (C), 168.0 (ester CO), 191.4 (CO) ppm. IR 7.0 Hz, 2 H, CH2CH2CH3), 7.31Ϫ7.52 (m, 3 H, ArH), 8.05 (d, J ϭ
(film): ν˜ ϭ 1731, 1711 cmϪ1. UV (CHCl3): λmax ϭ 300, 257 nm. 7.6 Hz, 1 H, ArH) ppm. 13C NMR DEPT (CDCl3, 25 °C): δ ϭ
MS: m/z (%) ϭ 358 (100), 343 (51), 315 (56). HRMS for C24H22O3,
calcd: 358.1569; found 358.1572. Data for 17: M.p. 92 °C. 1H NMR
13.4 (2 ϫ CH3), 21.0 (CH2), 21.2 (CH2), 21.7 (CH2), 21.9 (CH2),
79.2 (alkyne C), 80.7 (alkyne C), 96.2 (alkyne C), 96.5 (alkyne C),
(CDCl3, 25 °C): δ ϭ 0.88 (s, 9 H, tBu), 1.16 (t, J ϭ 7.1 Hz, 3 H, 123.4 (C), 126.9 (CH), 131.5 (CH), 131.9 (CH), 134.4 (CH), 138.1
OCH2CH3), 4.14 (q, J ϭ 7.1 Hz, 2 H, OCH2CH3), 7.31 (d, J ϭ (C), 177.7 (CO) ppm. MS: m/z (%) ϭ238 (2), 223 (18), 210 (100).
1
7.7 Hz, 1 H, ArH), 7.42Ϫ7.56 (m, 3 H, ArH), 7.64Ϫ7.79 (m, 4 H, Data for 7d: M.p. 118 °C. H NMR (CDCl3, 25 °C): δ ϭ 1.12 (t,
ArH), 7.85 (d, J ϭ 8.2 Hz, 1 H, ArH), 8.27 (d, J ϭ 7.9 Hz, 1 H, J ϭ 7.3 Hz, 3 H, CH3), 1.23 (t, J ϭ 7.2 Hz, 3 H, CH3), 1.68Ϫ1.87
ArH), 8.74 (d, J ϭ 8.4 Hz, 1 H, ArH, H-4 or H-5), 8.75 (d, J ϭ (m, 4 H, 2 ϫ CH2CH2CH3), 3.26Ϫ3.33 (m, 2 H, CH2CH2CH3),
7.8 Hz, 1 H, ArH, H-4 or H-5) ppm. 13C NMR DEPT (CDCl3), 3.58Ϫ3.64 (m, 2 H, CH2CH2CH3), 7.34 (t, J ϭ 7.3 Hz, 1 H, ArH),
δ ϭ 13.6 (ethyl CH3), 27.8 (tert-butyl C), 30.2 (tert-butyl CH3),
7.64Ϫ7.49 (m, 3 H, ArH), 7.78 (d, J ϭ 6.8 Hz, 1 H, ArH), 7.79 (d,
1242
Eur. J. Org. Chem. 2003, 1238Ϫ1243

Palladium-Catalyzed [2ϩ2ϩ2] Cycloaddition of Benzyne
FULL PAPER
[3] [3a]
´
´
D. Pen˜a, D. Perez, E. Guitian, L. Castedo, Synlett 2000,
J ϭ 7.9 Hz, 1 H, ArH), 8.11 (d, J ϭ 8.2 Hz, 1 H, ArH), 8.19 (d,
J ϭ 7.7 Hz, 1 H, ArH) ppm. 13C NMR DEPT (CDCl3, 25 °C):
δ ϭ 14.60 (CH3), 14.61 (CH3), 22.9 (CH2), 24.3 (CH2), 28.0 (CH2),
30.4 (CH2), 124.0 (CH), 124.1 (CH), 125.0 (CH), 126.4 (CH), 126.7
(CH), 128.2 (CH), 128.5 (C), 128.6 (CH), 133.1 (C), 133.4 (C),
134.7 (CH), 135.2 (C), 136.1 (C), 137.1 (C), 142.1 (C), 144.5 (C),
[3b]
´ ´
D. Pen˜a, D. Perez, E. Guitian, L. Castedo, J.
1061Ϫ1063.
Org. Chem. 2000, 65, 6944Ϫ6950.
[4]
For related work by our group on Pd-catalyzed cyclotrimeriz-
ation of arynes, see: [4a] D. Pen˜a, S. Escudero, D. Perez, E. Gui-
´
´
tian, L. Castedo, Angew. Chem. Int. Ed. 1998, 37, 2659Ϫ2661.
[4b]
´
´
D. Pen˜a, D. Perez, E. Guitian, L. Castedo, Org. Lett. 1999,
194.5 (CO) ppm. IR (film): ν˜ ϭ 1699 cmϪ1. UV (CHCl3): λmax
291 nm. MS: m/z (%) ϭ 314 (59), 285 (51), 271 (100). HRMS for
C23H22O: calcd. 314.1671; found 314.1668.
ϭ
[4c]
´ ´
D. Pen˜a, A. Cobas, D. Perez, E. Guitian, L.
1, 1555Ϫ1557.
Castedo, Org. Lett. 2000, 2, 1629Ϫ1632.
[5]
[6]
[5a]
For reactions with alkynes, see:
K. V. Radhakrishnan, E.
Yoshikawa, Y. Yamamoto, Tetrahedron Lett. 1999, 40,
[5b]
Ethyl
9-Methoxy-11-oxo-5-propyl-11H-benzo[b]fluorene-10-carb-
7533Ϫ7535.
Int. Ed. 2000, 39, 173Ϫ175.
E. Yoshikawa, Y. Yamamoto, Angew. Chem.
oxylate (20): According to the general procedure described above,
alcohol 13a (162 mg, 0.60 mmol) was treated with MnO2 (1.57 g,
18.00 mmol) for 5 min to afford 6a as a yellow oil. The resulting
product was treated with 3-methoxy-2-(trimethylsilyl)phenyl tri-
fluoromethanesulfonate (18, 98 mg, 0.30 mmol), Pd2(dba)3·CHCl3
(16 mg, 0.015 mmol), [18]crown-6[19] (40 mg, 0.15 mmol), and CsF
(114 mg, 0.75 mmol). Workup and purification by flash chromatog-
raphy (SiO2; Et2O/hexane, 1:9 then 1:3) afforded 20 (48 mg, 43%).
1H NMR (CDCl3, 25 °C): δ ϭ 1.18 (t, J ϭ 7.3 Hz, 3 H,
CH2CH2CH3), 1.48 (t, J ϭ 7.2 Hz, 3 H, OCH2CH3), 1.73Ϫ1.82
(m, 2 H, CH2CH2CH3), 3.24Ϫ3.31 (m, 2 H, CH2CH2CH3), 3.94 (s,
3 H, OCH3), 4.52Ϫ4.52 (m, 2 H, OCH2CH3), 6.88 (d, J ϭ 7.7 Hz, 1
For carbonylation reactions, see: N. Chatani, A. Kamitani, M.
Oshta, Y. Fukumoto, S. Murai, J. Am. Chem. Soc. 2001, 123,
12686Ϫ12687.
[7] [7a]
[7b]
S. J. Gould, Chem. Rev. 1997, 97, 2499Ϫ2509.
S. J.
Gould, C. R. Melville, M. C. Cone, J. Chen, J. R. Carney, J.
Org. Chem. 1997, 62, 320Ϫ324, and references cited therein.
M. A. Bennett, E. Wenger, Organometallics 1996, 15,
[8]
[9]
5536Ϫ5541.
General reviews on aryne chemistry:
[9a]
R. W. Hoffmann, De-
hydrobenzene and Cycloalkynes, Academic Press, New York,
H. Hart, in: The Chemistry of Functional Groups,
Suppl. C2: The Chemistry of Triple-Bonded Functional Groups
[9b]
1967.
(Ed.: S. Patai), Wiley, Chichester, 1994, pp. 1017Ϫ1134.
´
H, H-8), 7.34 (t, J ϭ 7.6 Hz, 1 H, H-2 o H-3), 7.49Ϫ7.60 (m, 2 H,
[10] [10a]
K. Moseley, P. M. Maitlis, J. Chem. Soc., Chem. Commun.
H-7 and H-1 to H-4), 7.69 (d, J ϭ 8.3 Hz, 1 H, H-6), 7.75Ϫ7.79
(m, 2 H, ArH) ppm. 13C NMR DEPT (CDCl3, 25 °C): δ ϭ 14.2
(CH3), 14.5 (CH3), 22.7 (propyl CH2), 30.7 (propyl CH2), 56.2
(OCH3), 61.5 (ethyl CH2), 107.1 (CH), 117.4 (CH), 121.4 (C), 124.1
(CH), 124.4 (CH), 127.4 (C), 128.4 (C), 128.7 (CH), 129.7 (CH),
134.9 (C), 135.1 (CH), 135.6 (C), 136.2 (C), 137.9 (C), 144.6 (C),
157.8 (C), 168.9 (ester CO), 191.6 (CO) ppm. IR (film): ν˜ ϭ 1717
cmϪ1. UV (CHCl3): λmax ϭ 292 nm. MS: m/z (%) ϭ 374 (100), 345
(40), 329 (73).
[10b]
1971, 1604Ϫ1606.
K. Moseley, P. M. Maitlis, J. Chem.
Soc., Dalton Trans. 1974, 169Ϫ175.
P. Bhatarah, E. H. Smith, J. Chem. Soc., Perkin Trans. 1
1992, 2163Ϫ2168.
[11]
[12]
[13]
´
´
D. Pen˜a, A. Cobas, D. Perez, E. Guitian, Synthesis 2002,
1454Ϫ1458.
K. Sonogashira, in: Metal-catalyzed Cross-coupling Reactions
(Eds.: F. Diederich, P. J. Stang), Wiley-VCH, Weinheim, 1998,
pp. 203Ϫ229, and references cited therein.
[14]
We attempted also to prepare derivatives with an ester group
as R2, but we found them to be too unstable.
[15] [15a]
´
´
D. Rodrıguez, A. Navarro, L. Castedo, D. Domınguez, C.
Acknowledgments
[15b]
´
´
D. Rodrıguez, A. Nav-
Saa, Org. Lett. 2000, 2, 1497Ϫ1500.
´
´
´
arro-Vazquez, L. Castedo, D. Domınguez, C. Saa, Tetrahedron
Lett. 2002, 43, 2712Ϫ2720.
Financial support from the DGES (BQU2000-0464) and PGIDT
(01PXI20902PN) is gratefully acknowledged. We also thank the
Spanish Ministry of Education and Culture for the award of a fel-
lowship to D. P.
[16]
[17]
A two-fold excess of diyne was used in a typical experiment.
Yields are based on the use of the benzyne precursor as the
limiting reagent.
In accordance with our previous results on intermolecular
aryneϪalkyne cycloadditions (see refs.[3,4]), the use of
Pd(PPh3)4 as the catalyst clearly favored this mode of reaction,
allowing the isolation of 14 in 69% yield and 7b in only 5%
yield.
P. G. Dopico, M. G. Finn, Tetrahedron 1999, 55, 29Ϫ62.
Because of the lability of 6a, crown ether was added to acceler-
ate the rate of benzyne generation in these experiments.
Received September 2, 2002
[1] [1a]
K. P. C. Vollhardt, Angew. Chem. Int. Ed. Engl. 1984, 23,
539Ϫ556. [1b] N. E Schore, Chem. Rev. 1988, 88, 1081Ϫ1119. [1c]
D. B. Grotjahn, in: Comprehensive Organometallic Chemistry II
(Eds.: E. W. Abel, F. G. A. Stone, G. Wilkinson; Vol. Ed.: L.
H. Hegedus), Pergamon, Oxford, 1995, vol. 12, pp. 741Ϫ770.
[1d]M. Lautens, W. Klute, W. Tam, Chem. Rev. 1996, 96, 49Ϫ92.
[18]
[19]
[1e]
H.-W. Frühauf, Chem. Rev. 1997, 97, 523Ϫ596.
[2]
´
´
D. Pen˜a, D. Perez, E. Guitian, L. Castedo, J. Am. Chem. Soc.
1999, 121, 5827Ϫ5828.
[O02491]
Eur. J. Org. Chem. 2003, 1238Ϫ1243
1243