Intramolecular heck couplings and cycloisomerizations of bromodienes and enynes with 1′,1′-disubstituted methylenecyclopropane terminators: Efficient syntheses of [3]dendralenes

Article abstract of DOI:10.1002/ejoc.200500330

2-Bromoalka-1,n-dienes such as 9, 30 and 14 (n = 7) with tetrasubstituted methylenecyclopropane end groups, under palladium catalysis, underwent cyclization with cyclopropane-ring opening to give 2-ethenyl-3-methylene-1- cycloalkenes 41 (n = 6), 42 (n = 7

Full text of DOI:10.1002/ejoc.200500330

FULL PAPER
Intramolecular Heck Couplings and Cycloisomerizations of Bromodienes and
Enynes with 1Ј,1Ј-Disubstituted Methylenecyclopropane Terminators: Efficient
Syntheses of [3]Dendralenes[‡]
Stefan Bräse,[a][‡‡] Hanno Wertal (nee Nüske),[a] Daniel Frank,[a] Denis Vidovic´,[b] and
Armin de Meijere*[a]
Keywords: Heck reaction / Methylenecyclopropanes / Palladium catalysis / Domino reactions / Diels–Alder reaction
2-Bromoalka-1,n-dienes such as 9, 30 and 14 (n = 7) with
tetrasubstituted methylenecyclopropane end groups, under
palladium catalysis, underwent cyclization with cyclopro-
to yield the correspondingly phenyl-substituted cyclic
[3]dendralene 41-Ph (21%). The palladium-catalyzed cyclo-
isomerization of the alk-1-ene-7,12-diyne 33-H gave the bi-
pane-ring opening to give 2-ethenyl-3-methylene-1-cycloal- cyclic cross-conjugated tetraene 50-H (43%). Key features of
kenes 41 (n = 6), 42 (n = 7), and 43, which are substituted
monocyclic [3]dendralenes, in 65, 63 and 70% yield, respec-
tively. The same cross-conjugated trienes were isolated in
good to excellent yields (77–92%) from the corresponding
1,6- (10-H, 15) and 1,7-enynes (28-H) by a more atom-econ-
omic, palladium-catalyzed cycloisomerization. The vinylpal-
ladium halide intermediate generated by initial carbopallad-
ation of the 1,6-enyne 10-H with in situ generated phenylpal-
ladium iodide also underwent the same cyclization cascade
the mechanism of the palladium-catalyzed cycloisomeriza-
tion were proved using the specially designed model system
20-H. Like other cyclic [3]dendralenes, the ethenyl(methyl-
ene)cycloheptene 42 underwent a domino-Diels–Alder reac-
tion with N-phenyltriazoline-3,5-dione to give a single dia-
stereomer of the pentacyclic heterocycle 69 (77% yield).
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2005)
In the course of our studies on various intramolecular
Heck reaction cascades,[5] we examined all-intramolecular
domino-Heck–Heck 6π-electrocyclizations leading to tricy-
clic skeletons[6] and intra-intermolecular domino Heck–Di-
els–Alder processes,[7] which easily led to bicyclo[4.3.0]non-
ene derivatives. In this latter context, we noticed that the
intramolecular Heck reaction even proceeds with 2-bromo-
1,n-dienes containing highly strained methylenecyclopro-
pane end groups or (bromomethylene)cyclopropane start-
ers[8] to yield spirocyclopropanebicyclo[4.3.0]nonene skel-
etons without opening of the three-membered ring.[6c] Al-
though tetrasubstituted alkenes are frequently quoted –
with a few exceptions[9] – to be unreactive in the Heck reac-
Introduction
So-called atom-economic processes[1] have received an
ever increasing attention of the organic community for the
last two decades.[2] The unsurpassable efficiency and envi-
ronmental friendliness have made organic chemists search
for new cascade reactions in which an ultimate number of
bonds is formed chemo-, regio- and stereoselectively in a
single operation. In short, the strive for the “ideal synthe-
sis”[3] has only begun. In this context, palladium-catalyzed
domino reactions coupled with a variety of other transfor-
mations do play a major role.[4]
[‡] Cyclopropyl Building Blocks for Organic Synthesis, 117. Part tion, we were intrigued by the question, how methylenecy-
116: F. Brackmann, H. Schill, A. de Meijere, Chem. Eur. J., in
clopropane end groups with a tetrasubstituted double bond
press. Part 115: C. Liu, M. Tamm, M. W. Nötzel, K. Rauch, A.
in a 2-bromoalka-1,n-diene or an enyne would behave un-
der Heck reaction or cycloisomerization conditions.[6d]
Herein, we give the full account of this investigation, and
we present scope and limitations of this cascade reaction
leading to monocyclic [3]dendralenes.[10]
de Meijere, J. K. Schilling, A. Lakdawala, J. P. Snyder, S. L.
Bane, N. Shanker, R. Rudravajhala, D. G. I. Kingston, Eur. J.
Org. Chem., in press.
[a] Institut für Organische und Biomolekulare Chemie der Georg-
August-Universität Göttingen,
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: +49-551-399475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b] Institut für Anorganische Chemie der Georg-August-Uni-
versität Göttingen,
Tammannstrasse 4, 37077 Göttingen, Germany
[‡‡]Current address: Institut für Organische Chemie, Universität
Karlsruhe (TH),
Results and Discussion
When 2-bromo-1,6-dienes of type 1[11] (R = H) with
methylenecyclopropane end groups are treated with a suit-
able palladium catalyst cocktail in the presence of a dieno-
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Eur. J. Org. Chem. 2005, 4167–4178
DOI: 10.1002/ejoc.200500330
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4167

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
FULL PAPER
phile like methyl acrylate, they react in the usual way to
give vicinal exo-dimethylenecycloalkanes, which immedi-
ately undergo a Diels–Alder reaction to yield products of
type 3.[11b] A different situation arises when R = Me in the
bromodiene 1, as the intermediate cyclopropylpalladium
bromide 4 would probably be reluctant to undergo β-hy-
dride elimination (to give a cyclopropene) and might prefer
to couple with the added methyl acrylate. To prove this hy-
pothesis, several bromodienes of type 1 (R = Me) were pre-
pared, and subjected to the conditions of palladium-cata-
lyzed cross-coupling reactions. In close analogy, several en-
ynes of type 6 with a (1Ј-methylmethylene)cyclopropane
end group were prepared and subjected to cycloisomeriza-
tion conditions, since their cyclization intermediates were
expected to encounter the very same situation as the inter-
mediates 2 (Scheme 1).
Scheme 2. A: 0.01–5 mol-% Pd(dba)2, dppb, THF, 66 °C, 1–24 h. E
= CO2Me.
yield (Scheme 3). Under the same conditions, the alkylation
of 13 with propargyl bromide yielded the enyne 15 (69%).
Scheme 1. The concept.
Scheme 3. B: Br(CH2)3PPh3Br, KOtBu, PhH, 70 °C, 4 h. E =
CO2Et.
Preparation of Cyclization Precursors
Another 1,7-enyne 20-H, with a four-atom tether be-
The required methylenecyclopropane derivatives of types tween the methylenecyclopropane end group and the triple
1 and 6 with their tetrasubstituted double bonds were pre- bond, but with a 1,1-disubstituted cyclopropane moiety as
pared either by a palladium-catalyzed allylic substitution on a mechanistic probe adjacent to the double bond, was pre-
1-(2Ј-propenyl)cyclopropyl chloride (8-Cl) – the corre- pared from ethyl 1-acetylcyclopropanecarboxylate (17)
sponding tosylate 8-OTs[11] – or, less elegantly, by Wittig which is accessible in good yield by cycloalkylation of ethyl
olefination of a cyclopropanone hemiacetal.
acetoacetate (16) with 1,2-dibromoethane, analogous to a
Thus, the cyclopropane derivative 8-Cl is easily obtained literature procedure (Scheme 4).[15] The olefination of 17
in multigram quantities from (1Ј-chlorocyclopropyl) methyl under the same conditions as applied to 12 gave the methyl-
ketone (7-Cl) by a Wittig olefination in 88% yield enecyclopropane derivative 18. Reduction of 18 with lith-
(Scheme 2).[12] The palladium-catalyzed substitution with ium aluminum hydride and alkylation of the resulting
the enolate of the appropriately substituted (2Ј-bromoprop- alcohol 19 with propargyl bromide or better 3-(tert-butyldi-
2Ј-enyl)malonate gave the 2-bromo-1,6-diene 9 (59%), while methylsilyl)propargyl bromide, gave the ethers 20-H and 20-
the reaction with dimethyl propargylmalonate enolate fur- SitBuMe2, respectively. The latter was converted into the
nished the enyne 10-H in 73% yield. The substitution of the terminal alkyne 20-H by protiodesilylation with nBu4NF in
chloride 8-Cl with dimethyl malonate enolate gave the THF.
known diester 11 on an even larger scale (10 mmol) with
only 0.01 mol-% palladium catalyst in up to 42% yield (not the methylenecyclopropane and bromoethenyl or ethynyl
optimized). moiety, the synthesis started from ethyl acetoacetate (16)
For cyclization precursors with shorter tethers between
The monoesters 14 and 15 with the same skeleton as 9 (Scheme 5). Alkylation of the enolate of 16 with 2,3-dibro-
and 10-H were synthesized by two-step sequences starting mopropene, hydrolysis of the ester and decarboxylation fur-
with Wittig olefination of methyl levulinate (12) with (3- nished 5-bromohex-5-en-2-one (21) in 63% yield
bromopropyl)phosphonium bromide in benzene in the pres- (Scheme 5). Wittig olefination of 21 with (3-bromopropyl)
ence of 2.2 equiv. of potassium tert-butoxide (conditions B) phosphonium bromide in THF in the presence of sodium
[13]
to give the methylenecyclopropane derivative 13 in up hydride (conditions C)[16] proceeded to give 22 in 55% yield.
to 79% yield.[14] Subsequent alkylation of the enolate of 13
Hex-5-yn-2-one (23-H) was obtained by alkylation of 16
with 2,3-dibromopropene gave the bromodiene 14 in 87% with propargyl bromide in 52% yield. Wittig olefination of
4168
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178

Efficient Syntheses of [3]Dendralenes
FULL PAPER
Scheme 4. B: Br(CH2)3PPh3Br, KOtBu, PhH or PhMe, 70 °C, 4 h.
E = CO2Et.
Scheme 6. B: Br(CH2)3PPh3Br, KOtBu, PhH, 70 °C, 4 h. D:
(nBu)4NF, THF, 25 °C, 3 h. E: NaI, Me3SiCl, MeCN, 69%. F:
TsCl, Py, 65%. G: I2, PPh3, MeCN/Et2O, 81 %. H: NaI, Me2CO,
25 °C, 92 %. I: NaI, Me2CO, 25 °C, 90%. E = CO2Et (CO2Me for
38-H).
Scheme 5. C: Br(CH2)3PPh3Br, NaH, THF or PhH, 66–70 °C. E =
CO2Et.
23-H under the usual conditions (see above), gave only mix-
tures of different products. Therefore, the terminal alkyne
Alkylation of the malonate derivative 29 with 5-iodo-1-
moiety in 23-H was protected by first converting 23-H into trimethylsilyl-1-pentyne (35-I) gave the enyne 32-SiMe3 in
the acetal 25-H (84% yield), silylating the acetal at the ter- 87% yield, while with the tosylate 35-OTs or the chloride
minus (56%) and then cleaving the acetal[17] to give 23- 35-Cl, even in the presence of tetrabutylammonium iodide,
SiMe3 (76%). The silylated hexynone 23-SiMe3 underwent no conversion was observed. The iodide 35-I[21,22] was ob-
reasonably clean olefination, and the workup gave the desi- tained by treatment of the 5-silyloxy-1-pentyne 35-OSiMe3
lylated enyne 24-H in 42% yield.
with in situ generated trimethylsilyl iodide (TMSI)[23] to
Two additional cyclization precursors were synthesized give the alcohol 35-OH, and its subsequent treatment with
starting from methyl vinyl ketone (26) (Scheme 6). Michael triphenylphosphane/iodine. Alternatively, the alcohol 35-
addition of diethyl malonate gave diethyl (3Ј-oxobutyl)ma- OH was first converted into the tosylate 35-OTs, which, by
lonate (27),[18] which was in turn converted into the methyl- subsequent Finkelstein reaction, led to 35-I. Finkelstein re-
enecyclopropane derivative 29 under the same conditions as action of the corresponding chloride 35-Cl also furnished
applied to 12 (see above). The obtained malonate derivative the iodide 35-I in multigram quantities. Protiodesilylation
29 was alkylated with 2,3-dibromopropene to yield the bro- of 32-SiMe3 gave the unprotected enyne 32-H in 97% yield
modiene 30 (79%) and with propargyl bromide to give the (Scheme 6).
enyne 28-H (65%). An attempt to alkylate 29 with 1-bromo-
The 10-oxatridec-1-ene-7,12-diyne 33-H was also pre-
4-trimethylsilylbut-3-yne,[19] did not give the expected pro- pared by alkylation of 29, in this case with 4-oxaocta-1,6-
duct 31-SiMe3, but 4-trimethylsilylbut-1-en-3-yne (34), re- diynyl iodide (37-I). The latter was obtained starting from
sulting from dehydrobromination of the homopropargyl but-2-yne-1,4-diol (36), the alkylation of which with pro-
bromide.[20]
pargyl bromide gave the diynol 37-OH (39% yield) along
Eur. J. Org. Chem. 2005, 4167–4178
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4169

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
FULL PAPER
with the dipropargyl ether 37-OProp (25%). Treatment of
the alcohol 37-OH with PPh3/I2 led to the corresponding
iodide 37-I (Scheme 6). Analogously, the 9-oxadodec-1-ene-
6,11-diyne 38-H was obtained by alkylation of dimethyl (2Ј-
cyclopropylidenepropyl)malonate (11) with the extended
propargyl iodide 37-I.
For comparison with the methylenecyclopropane deriva-
tives, the analogous methylenecyclobutane 40 was prepared
from diethyl (3Ј-oxobutyl)malonate (27) by olefination with
the ylide generated from (4-bromobutyl)phosphonium bro-
mide[24] with potassium tert-butoxide in benzene and subse-
quent alkylation with propargyl bromide (Scheme 7).
Scheme 8. K: Pd(OAc)2, PPh3, Ag2CO3, MeCN, methyl acrylate,
80 °C, 48 h. L: Pd(OAc)2, PPh3, NEt3, DMF, 80 °C, 60 h or 100 °C,
24 h. E = CO2Me or CO2Et.
palladium acetate. By monitoring the purely thermal re-
1
arrangement of 22 in C6D6 by H NMR spectroscopy, the
half-reaction time was estimated to be approx. 24 h at
80 °C. This corresponds to a remarkably low activation en-
ergy for a Cope rearrangement. Even the single other re-
ported example[26] of a Cope rearrangement of a 1,5-diene
with a methylenecyclopropane end group most probably
has a higher activation energy.
Scheme 7. J: Br(CH2)4PPh3Br, KOtBu, PhH, 70 °C, 4 h. E =
CO2Et.
Palladium-Catalyzed Cyclizations
Since its development by Trost et al.,[27,28] the cycloisom-
erization of 1-ene-6-ynes has found wide application, be-
cause it yields the same products as the intramolecular
Heck reaction of 2-halo-1,6-dienes, but with optimal atom
economy. Thus, the enynes 10-H and 28-H in benzene were
treated with a catalytic amount of the Pd2(dba)3·CHCl3
complex in the presence of acetic acid according to an es-
tablished protocol. After 12 h at 25 °C, no starting materials
could be detected, and after column chromatography, the
cross-conjugated trienes 41 and 42 were isolated in 79 and
92% yield, respectively (Scheme 9). In the case of 10-H, the
product 41 was spectroscopically pure after filtration
The hypothesis put forward above (see Scheme 1) was
first tested with the 2-bromo-1,6-diene 9. Towards that end,
9 was treated with methyl acrylate under the conditions as
previously optimized for the domino-Heck–Diels–Alder re-
action [Pd(OAc)2, PPh3, Ag2CO3, MeCN].[6] However, no
cyclization/cross-coupling product of type 5 was isolated,
but rather a product which had no acrylate moiety incorpo-
rated. Under typical Heck conditions [Pd(OAc)2, PPh3,
NEt3], the new product could be isolated in 65% yield and
identified as the cross-conjugated triene 41 (Scheme 8).
Comparison with samples obtained from the first reaction
of 9 showed that the dendralene 41 was also formed, but
had slowly decomposed under those reaction conditions.
The homologous 2-bromo-1,7-diene 30 gave the homolo-
gous methylene(vinyl)cycloheptane derivative 42 in 63%
yield.
The 2-bromo-1,6-diene monoester 14 under the same re-
action conditions gave, besides the triene 43 (70%) also the
8-methylenespiro[2.5]oct-4-ene-6-carboxylate 44 in 9%
yield, but none of the double bond isomer 45. The 2-
bromo-1,5-diene 22 on the other hand led to a bromine-
containing product, with the same composition as the start-
ing material (according to MS).
The NMR spectra revealed that the product was actually
the bromodiene 46, resulting from a Cope rearrangement[25]
of 22. The comparison with the NMR spectra of the start-
ing material showed that this rearrangement is even detect-
able under the conditions for the preparation of 22. This
Scheme 9. M: Pd2(dba)3·CHCl3, P(oTol)3, HOAc, PhH, 25 °C,
rearrangement also proceeds smoothly in the absence of 12 h. E = CO2Me, EЈ = CO2Et.
4170 © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178

Efficient Syntheses of [3]Dendralenes
FULL PAPER
through Celite and removal of the solvent. The enyne 15
could be converted, like the bromodiene 14, to the triene 43
in 77% and the spiro[2.5]octene 44 in 13% yield.
While the reaction of the bromodienes 9 and 30 pro-
ceeded smoothly with almost the same yields even in the
presence of methyl acrylate, the reactions of the enynes 10-
H and 28-H were drastically slower or even completely in-
hibited by added acrylate. Apparently, the palladium ion is
coordinated by the acrylate and thus not catalytically active.
The 1-en-9-yne 32-H and the 1-en-5-yne 24-H as well as
the methylenecyclobutane derivative 40-H under the same
conditions, did not give any identified products.
Instead of a hydridopalladium species, an arylpalladium
halide can also initiate the cyclization of an enyne. There-
fore, the enyne 10-H was heated with iodobenzene under
Heck conditions [Pd(OAc)2, PPh3, NEt3]. After 12 h at
80 °C, two isomeric products could be isolated in 21 and
49% yield, respectively. The first one was identified as the
cross-conjugated triene 41-Ph with a (Z)-configured phenyl-
substituted exo-methylene moiety (according to an NOESY
spectrum). The other one was the terminally aryl-substi-
tuted enyne 10-Ph (Scheme 10). The arylation of alkynes
with haloarenes is well established,[29] but normally pro-
ceeds well only in the presence of copper salts. Purely palla-
dium-catalyzed couplings have rarely been reported.[30]
Scheme 11. K: Pd(OAc)2, PPh3, NEt3, DMF, 100 °C, 12 h. L:
Pd2(dba)3·CHCl3, P(oTol)3, HOAc, PhH, 25 °C, 72 h. E = CO2Me
or CO2Et.
Discussion and Outlook
All of the cross-conjugated trienes and tetraenes dis-
cussed above are obviously formed with ring opening of the
three-membered ring in the methylenecyclopropane unit of
the bromodiene or enyne precursor. Going by the products
only, this may occur by three mechanistic options. The most
straightforward, yet intriguing mode would be a direct car-
bopalladation across the single bond of the three-membered
ring in the intermediate 50 in an n-exo-trig(dig) mode to
yield the homoallylpalladium species 55 which, by β-hy-
dride elimination, would give the final product of type 58
(Scheme 12). It is more likely though, that the latter inter-
mediate is formed by a cyclopropylcarbynyl-to-homoallyl
rearrangement in 54, as is well documented to rapidly occur
with all kinds of cyclopropylcarbynylmetal derivatives.[32]
There is experimental evidence, in fact, that 54 is an inter-
mediate en route to 55, as in one case a methylenespiro[2.5]
oct-4-ene derivative of type 57, apparently formed by β-de-
hydropalladation from an intermediate of type 54, was iso-
lated as a by-product. The intermediate 54 could arise from
Scheme 10. K: Pd(OAc)2, PPh3, NEt3, DMF, 80–100 °C, 12–20 h.
E = CO2Me.
The enyne 24-H under the same conditions gave only the
terminally arylated enyne 24-Ph (13%) along with poly-
meric material.
Metal-catalyzed oligocyclizations of oligo-unsaturated,
open-chain compounds have been used for an elegant and
efficient assembly of oligocyclic systems.[31] Therefore, the
enediyne 33-H (Scheme 11) was treated with a palladium
catalyst under standard conditions [Pd2(dba)3·CHCl3,
HOAc, P(oTol)3, PhH, 25 °C]. After 12 h, the cross-conju-
gated tetraene 48-H was isolated in 43% yield. According
to a NOESY-NMR spectrum, the double bond between the
two rings in 48-H is (Z)-configured.
In the presence of iodobenzene and a palladium catalyst
[Pd(OAc)2, PPh3, NEt3] in DMF at 100 °C the enediyne 33-
H and its lower analogue 38-H did not yield any phenyl-
substituted cross-conjugated tetraene of type 48-H, but only
the terminally phenylated enediynes 33-Ph (44%) and 38-
Ph (30%), respectively.
Scheme 12. Mechanistic rationalization of the [3]dendralene forma-
tion.
Eur. J. Org. Chem. 2005, 4167–4178
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4171

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
FULL PAPER
an n-endo-trig cyclization of 50, but, according to literature 2-substituted 1,3-butadienes. In analogous Heck reactions
precedence and a stereochemical proof on a model system of butadienes, the initial carbopalladation occurs with the
for the formation of formal n-endo-trig products,[33] the opposite regioselectivity to form a π-allylpalladium inter-
most probable route to 54 is by (n–1)-exo-trig cyclization of mediate.[5] Methylenecyclopropanes can thus be considered
50 to give the cyclopropylpalladium intermediate 52, which as suitable precursors to substituted buta-1,3-dienes com-
would not want to undergo β-dehydropalladation, but plementing the recently found access by palladium-cata-
rather a 3-exo-trig cyclization, and the resulting highly lyzed ring opening of 2-halomethylenecyclopropanes.[36]
strained [(spiropentyl)methyl]palladium species 53 would
rapidly open one ring to yield 54 as a homoallylpalladium this new palladium-catalyzed cascade reaction, are so-called
species.
[3]dendralenes.[37] As such, they should be able to undergo
Cross-conjugated trienes such as the ones accessible by
Additional evidence could be expected from the cycliza- a sequential Diels–Alder reaction, a so-called transmissive
tion of a model precursor such as 20-H which, by either cycloaddition.[38] To test this possibility, the triene 42 was
of the two latter discussed reaction modes, would have to treated with the very reactive dienophile N-phenyltriazo-
unequivocally yield a (cyclopropylcarbynyl)palladium spe- line-3,5-dione (PTAD),[39] in situ prepared by oxidation of
cies. Under the established reaction conditions, the enyne the urazole 68 with lead tetraacetate in dichloromethane
20-H did indeed give two products, the ratio of which at –10 °C. The conversion of 42 was complete within
strongly depended on the dilution of the starting material. 10 min, and chromatography gave the pentacyclic com-
The more polar one was identified as the trienyne 59, a pound 69 as a single diastereomer in 81% yield.
dimer of 20-H. Apparently, a coupling of the hydridopal-
On the other hand, the reaction of 42 with tetracyano-
ladation product from 20-H with the acetylene terminus of ethylene (TCNE) at room temperature within 15 h only led
a second molecule 20-H took place. This type of reaction to the bicyclo[5.4.0]undecene derivative 70 (Scheme 14),
has previously been observed.[34] An unambiguous charac- which did not react any further to the tricycle 71, not even
terization of the other product from 20-H as the non-cross- at 80 °C. The structure of 70 was rigorously proved by an
conjugated triene 67 was possible only on the basis of 2D- X-ray crystal structure analysis (Figure 1).[40] Other dieno-
NMR spectra since, according to the 1H and 13C NMR
spectra, the two different constitutions 66 and 67 would
have been possible. Hence, the formation of the product 67
must proceed via the intermediate 63 (Scheme 13). Whether
this is formed directly by a 7-endo-trig-carbopalladation or
the sequence of 6-exo-trig-, 3-exo-trig-carbopalladation and
cyclopropylcarbynyl-to-homoallyl rearrangement, i.e. via
60 and 61, remains an open question. In the formation of
six- and seven-membered rings n-exo- as well as n-endo-ring
closure modes are known to occur.[35]
Scheme 14. E = CO2Et.
Scheme 13. B: Br(CH2)3PPh3Br, KOtBu, PhH, 80 °C, 4 h.
Figure 1. Structure of diethyl 8,8,9,9-tetracyano-7-methyl-2-meth-
ylenebicyclo[5.4.0]undec-11-ene-4,4-dicarboxylate (70) in the crys-
The ring opening in conjunction with the Heck coupling
of such methylenecyclopropanes as discussed above leads to tal.[40]
4172
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178

Efficient Syntheses of [3]Dendralenes
FULL PAPER
the residue after removal of the solvent was subjected to
chromatography on silica gel. Alternatively, the reaction mixture
can be directly chromatographed or recrystallized after filtration.
philes [dimethyl maleate, (E)-1,2-bis(phenylsulfonyl)ethene]
did not at all react with 42, neither at elevated temperature
nor under high pressure.[41]
General Procedure for Intramolecular Heck Reactions of Bromodi-
enes with Methylenecyclopropane End Groups (GP 3): A 50-mL Py-
rex bottle was charged under argon with anhydrous acetonitrile
(10 mL), palladium() acetate (11.2 mg, 49.9 µmol) and tri-
phenylphosphane (39.3 mg 150 µmol), argon was bubbled through
the mixture for 5 min, then 1.00 mmol of the respective bromodiene
and silver() carbonate (552 mg, 2.00 mmol) were added. The bottle
was closed with a screw cap, and the mixture was stirred at the
given temperature for the given time, then cooled to ambient temp.,
extracted with pentane (5×50 mL), the combined organic phases
were washed with 15 mL of water and dried (MgSO4). After re-
moval of the solvent in a rotary evaporator, the residue was sub-
jected to chromatography on silica gel eluting with petroleum ether/
ether (10:1 Ǟ 5:1).
Experimental Section
General Remarks: 1H and 13C NMR spectra were recorded with
Bruker AW 250, WM 500 or Varian Mercury 300, Inova 600 instru-
ments at 250, 300, 500 or 600 MHz and 62.9, 75.6, 125.0 or
150.8 MHz, respectively. Chemical shifts in CDCl3 or [D6]benzene
are reported in δ (ppm) relative to tetramethylsilane (TMS), chloro-
form or benzene as internal reference unless otherwise stated. IR
spectra were registered with a Perkin–Elmer 1720 FT-IR or a
Bruker IFS 66. Low-resolution EI and DCI MS (EI at 70 eV, DCI
with NH3): Finnigan MAT 95 spectrometer. High-resolution MS:
Finnigan MAT 95. HRMS: Preselected ion peak matching at R Ϸ
10000 to be within 2 ppm of the exact masses. ESI MS: Finnigan
LCQ. ESI HRMS: APEX IV 7T FTICR, Bruker Daltonic. Ele-
mental analyses were performed by the Mikroanalytisches Labora-
torium des Instituts für Organische und Biomolekulare Chemie der
Universität Göttingen, Germany. Melting points are uncorrected.
Solvents for extraction and chromatography were technical grade
and distilled before use. Flash chromatography was performed
using Merck silica gel 60 (200–400 mesh). Analytical gas
chromatography (GC) was performed using a Siemens Sichromat
4 equipped with a 25-m capillary column coated with CP-Sil-55-
5B. All reactions were carried out under dry nitrogen or argon
in oven- and/or flame-dried glassware. Unless otherwise specified,
solutions of NH4Cl and NaHCO3 are saturated aqueous solutions.
Tetrahydrofuran was distilled from potassium benzophenone ketyl,
Alternative General Procedure for Intramolecular Heck Reactions of
Bromodienes with Methylenecyclopropane End Groups (GP 4): A
50-mL Pyrex bottle was charged under argon with anhydrous DMF
(10 mL), palladium() acetate (11.2 mg, 49.9 µmol) and tri-
phenylphosphane (39.3 mg, 150 µmol), argon was bubbled through
the mixture for 5 min, then 1.00 mmol of the respective bromodiene
and triethylamine (202 mg, 2.00 mmol) were added. The bottle was
closed with a screw cap, and the mixture was stirred at the given
temperature for the given time, then the mixture was cooled to
room temp., extracted with pentane (5×50 mL), the combined or-
ganic phases were washed with 15 mL of water and dried (MgSO4).
After removal of the solvent in a rotary evaporator, the residue was
subjected to chromatography on silica gel eluting with petroleum
ether/ether (10:1 Ǟ 5:1).
and DMF and MeCN were distilled from CaH2. (3-Bromopropyl)
[42]
triphenylphosphonium bromide[24b] and 35-OSiMe3
were pre-
Dimethyl 4-Ethenyl-5-methyl-3-methylenecyclohex-4-ene-1,1-dicar-
boxylate (41-H). a) By Enyne Cycloisomerization: To a solution of
dimethyl (2Ј-cyclopropylidenepropyl)(prop-2-ynyl)malonate (10-H)
(250 mg, 1.00 mmol) in benzene (10 mL) were added tris(dibenzyli-
pared according to published procedures.
General Procedure for Palladium-Catalyzed Substitutions on Allyl
Sulfonates and Halides (GP 1): A solution of bis(dibenzylideneace-
tone)palladium(0) [Pd(dba)2] (5.8 mg, 10 µmol, 2.0 mol-%) and
11 µmol of a bidentate phosphane in 1 mL of THF was stirred at
ambient temp. for 5 min, and subsequently the mixture was treated
with 0.5 mmol of the allyl sulfonate or allyl halide. After ca. 5–
10 min, the reaction mixture turned green, and then a solution of
0.5–1.5 mmol of the sodium malonate in 5 mL of anhydrous THF,
prepared by addition of 0.5–1.5 mmol of the dialkyl malonate in
1.5 mL of anhydrous THF to 0.5–1.5 mmol of sodium hydride in
3.5 mL of anhydrous THF, was added dropwise. The reaction mix-
ture was stirred until the allyl component had been consumed com-
pletely (TLC control). The mixture was added to 10 mL of diethyl
ether and 20 mL of a 10% NH4Cl solution, the phases were sepa-
rated, the aqueous phase was extracted with diethyl ether
(3×5 mL), the combined organic phases were washed with 5 mL
of brine and dried. After removal of the solvent, the residue was
purified by flash chromatography.
deneacetone)dipalladium–chloroform
complex
(51.8 mg,
50.0 µmol, 5.0 mol-%), tris(o-tolyl)phosphane (15.2 mg, 49.9 µmol,
5 mol-%) and acetic acid (3 µL, 3 mg, 0.05 mmol, 5 mol-%), and
the mixture was stirred under argon at ambient temp. for 15 h.
Chromatography on silica gel (column 1×20 cm, petroleum ether/
ether, 10:1) gave 198 mg (79%) of 41-H as a colorless, unstable oil,
R = 0.26. IR (film): ν = 3060 cm–1, 1740 (C=O), 1670 (C=C),
˜
f
1655, 1625, 1570, 1090, 830, 755, 740, 710, 650. 1H NMR
(250 MHz, CDCl3): δ = 1.83 (s, 3 H, CH3), 2.66 (s, 2 H, CH2), 2.84
(s, 2 H, CH2), 3.69 (s, 6 H, OCH3), 4.86 (s, 1 H, C=CH2), 4.97 (s,
1 H, C=CH2), 5.07 (dd, 2J = 2.1, 3J = 15.8 Hz, 1 H, CH=CH2),
5.31 (dd, 2J = 2.1, 3J = 11.2 Hz, 1 H, CH=CH2), 6.24 (dd, 3J =
15.8, 3J = 11.2 Hz, 1 H, CH=CH2) ppm. 13C NMR (62.9 MHz,
CDCl3, DEPT): δ = 20.8 (+, CH3), 37.6 (–, CH2), 37.4 (–, CH2),
53.6 (+, OCH3), 59.6 [Cquat, C(CO2)2], 112.0 (–, CH2), 119.2 (–,
CH2), 131.2 (Cquat, C=C), 131.5 (Cquat, C=C), 133.5 (+, CH=C),
139.4 (Cquat, C=C), 171.2 (Cquat, CO) ppm. MS (70 eV, EI): m/z
(%) = 250 (12) [M+], 204 (100) [M+ – C2H6O]. C14H18O4 (250.3):
calcd. C 67.18, H 7.25; found C 67.52, H 7.01. b) By Intramolecular
Heck Reaction of 9 in the Presence of NEt3: According to GP 4,
bromodiene 9 (113 mg, 0.342 mmol) in acetonitrile (10 mL) in the
presence of triethylamine (69.0 mg, 0.682 mmol) was treated with
Pd(OAc)2 (3.8 mg, 17 µmol) and triphenylphosphane (11.1 mg,
42 µmol) at 100 °C for 24 h. Workup and purification gave 55.5 mg
(65%) of 41-H with spectroscopic data as above.
General Procedure for the Alkylation of Dialkyl Malonates and Sub-
stituted Dialkyl Malonates (GP 2): A solution of the corresponding
malonate in THF (0.1 , if not otherwise stated) was treated with
1.1–2.0 equiv. of sodium hydride, the mixture was stirred for
10 min, and subsequently 1.0–2.0 equiv. of the respective alkyl ha-
lide was added. After complete conversion (TLC or GC, 1–24 h),
the mixture was filtered, and the residue washed with water. The
combined organic layers were added to water, the aqueous layer
extracted with diethyl ether (3×50 mL) and the combined extracts
were washed twice with 20 mL each of water and brine. After hav-
ing been dried (MgSO4), the mixture was fractionally distilled or
Diethyl 4-Ethenyl-5-methyl-3-methylenecyclohept-4-ene-1,1-dicar-
boxylate (42). a) By Enyne Cycloisomerization: To a solution of
Eur. J. Org. Chem. 2005, 4167–4178
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4173

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
FULL PAPER
diethyl (3Ј-cyclopropylidenebutyl)(2ЈЈ-propynyl)malonate (28-H,
1.87 g, 6.40 mmol) in 90 mL of benzene were added tris(dibenzylid-
eneacetone)dipalladium–chloroform complex (190 mg, 186.3 µmol,
2.9 mol-%), tris(o-tolyl)phosphane (111 mg, 364.4 µmol, 6 mol-%)
and acetic acid (22 µL, 0.05 mmol, 6 mol-%), and the mixture was
stirred under argon at ambient temp. for 15 h. Chromatography on
(44). a) By Enyne Cycloisomerization: To a solution of ethyl 2-(2Ј-
cyclopropylidenepropyl)pentynoate (15, 207 mg, 1.00 mmol) in
40 mL of benzene were added tris(dibenzylideneacetone)dipalla-
dium–chloroform complex (21.6 mg, 20.9 µmol, 2 mol-%), tris(o-
tolyl)phosphane (12.7 mg, 41.7 µmol, 4 mol-%) and acetic acid
(2 mL, 2 mg, 0.03 mmol, 3 mol-%), and the mixture was stirred un-
silica gel (2×20 cm, pentane/ether, 10:1) gave 1.25 g (67%) of 42 der argon at ambient temp. for 36 h. After removal of the solvents
as a colorless oil, R = 0.32. IR (film): ν = 2981 cm–1, 2937, 1731
under reduced pressure, chromatography on silica gel (column
˜
f
(C=O), 1642 (C=C), 1446, 1367, 1239, 1178, 1063, 906, 859, 704. 2×20 cm, petroleum ether/ether, 10:1) gave three fractions: Frac-
1H NMR (250 MHz, CDCl3): δ = 1.24 (t, 3J = 7.6 Hz, 6 H, tion I: 5.3 mg (3%) of 15, Rf = 0.28. Fraction II: 160 mg (77%) of
1
OCH2CH3), 1.81 (s, 3 H, CH3), 2.08–2.13 (m, 2 H, 7-H), 2.26–2.30 43 as a colorless oil, Rf = 0.26. H NMR (250 MHz, CDCl3): δ =
(m, 2 H, 6-H), 2.84 (s, 2 H, 2-H), 4.16 (q, 3J = 7.6 Hz, 4 H, 1.54 (t, 3J = 7.2 Hz, 3 H, OCH2CH3), 1.83 (s, 3 H, CH3), 2.50–2.60
2
3
OCH2CH3), 4.89 (d, J = 1.9 Hz, 1 H, 1Ј-H), 5.08 (dd, 2J = 1.8, J
(m, 1 H), 2.60–2.70 (m, 2 H, CH2), 2.80–2.90 (m, 2 H, CH2), 3.54
2
3
= 10.8 Hz, 1 H, 2ЈЈ-HE), 5.14 (dd, J = 1.8, J = 17.2 Hz, 1 H, 2ЈЈ-
(q, 3J = 7.2 Hz, 2 H, OCH2CH3), 4.86 (s, 1 H, C=CH2), 4.97 (s,
HZ), 5.18 (d, 2J = 1.9 Hz, 1 H, 1Ј-H), 6.50 (dd, 3J = 17.2, 3J = 1 H, C=CH2), 5.07 (dd, J = 2.1, J = 15.8 Hz, 1 H, 2ЈЈ-HZ), 5.31
2
3
10.8 Hz, 1 H, 1ЈЈ-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): (dd, J = 2.1, J = 11.2 Hz, 1 H, 2ЈЈ-HE), 6.24 (dd, J = 15.8, J =
2
3
3
3
δ = 14.0 (+, OCH2CH3), 21.0 (+, CH3), 30.2 (–, CH2), 32.4 (–, 11.2 Hz, 1 H, 1ЈЈ-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT):
CH2), 39.5 (–, CH2), 58.2 (Cquat, C-1), 61.2 (–, OCH2CH3), 115.3
(–, C=CH2), 118.0 (–, C=CH2), 134.6 (+, C-1ЈЈ), 135.7 (Cquat, C- CH2), 59.6 (Cquat, C-5), 65.5 (–, OCH2CH3), 112.0 (–, CH2), 119.2
3*), 136.7 (Cquat, C-4*), 141.8 (Cquat, C-5*), 171.4 (Cquat, CO) ppm. (–, CH2), 131.2 (Cquat, C-1*), 131.5 (Cquat, C-2*), 133.5 (+, CH=C),
MS (70 eV, EI): m/z (%) = 292 (12) [M+], 246 (54) [M+ – C2H6O], 139.4 (Cquat, C-3*), 171.2 (Cquat, CO) ppm. Fraction III: 27.5 mg
δ = 15.4 (+, OCH2CH3), 20.8 (+, CH3), 37.6 (–, CH2), 37.4 (–,
218 (35) [M+ – C2H5OH – CO], 201 (15), 189 (20), 173 (18), 145
(100) [M+ – C2H5OH – CO – C2H5CO2]. C17H24O4 (292.37): calcd.
C 69.84, H 8.27; found C 69.79, H 8.03. b) By Enyne Cycloisomer-
ization in the Presence of tert-Butyl Acrylate: A solution of diethyl
(3Ј-cyclopropylidenebutyl)(2ЈЈ-propynyl)malonate (28-H, 145 mg
0.496 mmol) in 5 mL of benzene was stirred with tris(dibenzylid-
eneacetone)dipalladium–chloroform complex (12.7 mg, 12.3 µmol,
2.5 mol-%), tris(o-tolyl)phosphane (3.8 mg, 12 µmol), tert-butyl ac-
rylate (630 mg, 4.92 mmol) and acetic acid (2 µL, 2 mg, 0.03 mmol,
7 mol-%) under argon at ambient temp. for 15 h. After removal of
the solvents under reduced pressure, chromatography on silica gel
(column 2×20 cm, pentane/ether, 10:1) gave 200 mg (69%) of 42;
Rf = 0.32. As a second fraction, 9.3 mg (6%) of tetraethyl 2,14-
bis(cyclopropylidene)-9-methylenepentadeca-7-yne-5,5,11,11-tetra-
(13%) of 44 as a yellow oil, contaminated with dibenzylideneace-
tone, R = 0.24. IR (film): ν = 2990 cm–1, 1735 (C=O), 1670 (C=C),
˜
f
1090, 890, 830, 750. 1H NMR (250 MHz, CDCl3): δ = 0.85–0.90
4
(mc, 2 H, cPr-H), 1.03–1.08 (mc, 2 H, cPr-H), 1.51 (d, J = 1.1 Hz,
3 H, CH3), 1.62 (t, 3J = 7.2 Hz, 3 H, OCH2CH3), 2.93 (s, 2 H,
CH2), 3.79 (q, 3J = 7.2 Hz, 2 H, OCH2CH3), 4.62 (s, 1 H, C=CH2),
4.71 (s, 1 H, C=CH2), 5.68 (s, 1 H, C=CH) ppm. 13C NMR
(62.9 MHz, CDCl3, DEPT): δ = 12.4 (–, cPr-C), 13.3 (–, cPr-C),
15.11 (+, OCH2CH3), 20.9 (+, CH3), 36.2 (–, CH2), 42.5 (+, CH),
59.6 (Cquat, C-3), 66.8 (–, OCH2CH3), 112.7 (–, CH2), 129.4 (Cquat
,
C-4*), 132.7 (Cquat, C-8*), 133.5 (+, CH=C), 171.8 (Cquat, CO)
ppm. MS (70 eV, EI): m/z (%) = 206 (100) [M+]. b) By Enyne Cyclo-
isomerization in the Presence of Methyl Acrylate: To a solution of
of ethyl 2-(2Ј-cyclopropylidenepropyl)pentynoate (15, 164 mg,
795 µmol) in 40 mL of benzene were added tris(dibenzylideneace-
carboxylate was obtained as a colorless oil; R = 0.08. IR (film): ν
˜
f
= 3023 cm–1, 2878, 2856, 1734 (C=O), 1684 (C=C), 1448, 1368, tone)dipalladium–chloroform complex (17.0 mg, 16.4 µmol, 2 mol-
1
1277, 1127, 1032, 832, 668, 527. H NMR (250 MHz, CDCl3): δ = %), tris(o-tolyl)phosphane (10.0 mg, 32.9 µmol, 4 mol-%), acetic
0.8–1.0 (m, 8 H, cPr-H), 1.15–1.25 (m, 12 H, OCH2CH3), 1.4–1.5
acid (2 mL, 2 mg, 0.03 mmol, 4 mol-%), methyl acrylate (172 mg,
[m, 4 H, 4(12)-H], 1.75 [s, 6 H, 1(15)-H], 1.90–2.15 [m, 8 H, 2.00 mmol), and the mixture was stirred under argon at ambient
3(6,10,13)-H], 4.1–4.2 (m, 8 H, OCH2CH3), 5.5–5.6 (m, 2 H, temp. for 36 h. After removal of the solvents under reduced pres-
CH2=C) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 1.3 (–,
sure, chromatography on silica gel (column 2×20 cm, petroleum
cPr-C), 2.7 (–, cPr-C), 13.9 (+, OCH2CH3), 22.5 [+, C-1(15)], 29.6 ether/ether, 10:1) gave three fractions: Fraction I: 25 mg (15%) of
(–, CH2), 30.2 (–, CH2), 56.5 [Cquat, C-5(11)], 60.9 (–, OCH2CH3), 15, Rf = 0.28. Fraction II: 58 mg (35%) of 43 as a colorless oil, Rf
95.1 (Cquat, C-7*), 108.8 (Cquat, C-8*), 115.8 (Cquat, cPr-C), 117.3 = 0.26. Fraction III: 14 mg (9%) of 44, contaminated with dibenz-
(–, CH2), 123.0 [Cquat, C-2(14)], 125.5 (Cquat, C-9*), 170.0 (Cquat
,
ylideneacetone as a yellow oil, Rf = 0.24. c) By Intramolecular Heck
Reaction in the Presence of NEt3: According to GP 4, ethyl 4-
bromo-2-(2Ј-cyclopropylidenepropyl)pent-4-enoate (14, 287 mg,
1.00 mmol), of Pd(OAc)2 (3.8 mg, 17 µmol), PPh3 (11.1 mg,
42.3 µmol) and NEt3 (69.0 mg, 682 µmol) were heated at 100 °C for
24 h. After aqueous workup, chromatography on silica gel (column
CO) ppm. MS (70 eV, EI): m/z (%) = 513 (26), 436 (33), 422 (100),
392 (80), 378 (45), 91 (76). c) By Intramolecular Heck Reaction in
the Presence of Ag2CO3: According to GP 3, a mixture of diethyl
(2Ј-bromoprop-2Ј-enyl)(3ЈЈ-cyclopropylidenebutyl)malonate
(30,
373 mg, 1.00 mmol), Pd(OAc)2 (11.6 mg 51.7 µmol), PPh3
(26.3 mg, 100 µmol), Ag2CO3 (572 mg, 2.07 mmol), and tert-butyl 2×20 cm, petroleum ether/ether, 10:1) gave two fractions: Frac-
acrylate (455 mg, 3.55 mmol) was heated at 80 °C for 48 h. Accord-
ing to TLC and H NMR an intermediate product 42 was present
tion I: 145 mg (70%) of 43 as a colorless oil, Rf = 0.26. Fraction II:
18.5 mg (9%) of 44 as a colorless oil, Rf = 0.24.
1
(ca. 10%), but this decomposed after prolonged reaction time. d)
By Intramolecular Heck Reaction in the Presence of NEt3: Accord-
ing to GP 4, a mixture of the bromodiene 30 (127 mg, 0.340 mmol),
Pd(OAc)2 (3.8 mg, 17 µmol), PPh3 (11.1 mg, 42.3 µmol), NEt3
(69.0 mg, 0.682 mmol) and tert-butyl acrylate (135 mg, 1.05 mmol)
was heated at 100 °C for 24 h. Workup yielded 40 mg (40%) of 42.
The same reaction at 80 °C after 60 h gave 42 in 63% yield.
1-(2Ј-Bromoprop-2Ј-enyl)-1-(1ЈЈ-methylethenyl)cyclopropane (46): In
an NMR tube, a solution of 2-bromo-5-cyclopropylidenehexene
(22, 20 mg, 99 mmol) in 0.5 mL of [D6]benzene was heated at
80 °C. After certain time intervals, 1H NMR spectra were recorded,
indicating a conversion of 22 to 46 with a half-life of 24 2 h (15 h:
35% conversion, 40 h: 65% conversion). 1H NMR (250 MHz,
CDCl3): δ = 0.50–0.55 [m, 2 H, 2(3)-H], 0.75–0.80 [m, 2 H, 2(3)-
H], 1.75 (s, 3 H, CH3), 2.45 (s, 2 H, 1Ј-H), 4.85 (br. s, 2 H, C=CH2),
Ethyl
4-Ethenyl-3-methyl-5-methylenecyclohex-3-enecarboxylate
(43) and Ethyl 4-Methyl-8-methylenespiro[2.5]octane-6-carboxylate 5.25 (s, 1 H, C=CH2), 5.30 (s, 1 H, C=CH2) ppm. 13C NMR
4174 © 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178

Efficient Syntheses of [3]Dendralenes
FULL PAPER
H, cPr-H), 1.89 (t, J = 1.5 Hz, 3 H, 1-H), 2.46–2.67 (mc, 4 H, 3-
4
(62.9 MHz, CDCl3, DEPT): δ = 12.9 [–, C-2(3)], 20.8 (+, CH3),
24.5 (Cquat, C-1), 39.7 (–, C-1Ј), 110.4 (–, C=CH2), 113.1 (–, H, 4-H), 7.25–7.42 (mc, 5 H, C6H5) ppm. 13C NMR (62.9 MHz,
C=CH2), 145.5 (Cquat, C=CH2), 147.8 (Cquat, C=CH2) ppm. MS CDCl3, DEPT): δ = 1.4 (–, cPr-C), 3.1 (–, cPr-C), 18.1 (–, C-4),
(70 eV, EI): m/z (%) = 202/200 (0.1/0.1) [M+], 174/172 (12/12) [M+ –
20.7 (+, C-1), 35.9 (–, C-3), 80.5 (Cquat, C-5), 90.5 (Cquat, C-6),
C2H4], 121 (43) [M+ – Br], 93 (53) [M+ – Br – C2H4], 79 (100) 116.5 (Cquat, cPr-C), 122.7 (Cquat, C-1Ј), 124.1 (Cquat, C-2), 127.4
[M+ – Br – C3H6].
(+, C-4Ј), 128.1 (+, C-3Ј), 131.5 (+, C-2Ј) ppm. MS (70 eV, EI):
m/z (%) = 195 (46) [M+ – H], 181 (73) [M+ – CH3], 115 (100)
[C9H7+].
Dimethyl
(Z)-4-Ethenyl-3-methyl-5-(phenylmethylene)cyclohex-3-
ene-1,1-dicarboxylate (41-Ph) and Dimethyl (2Ј-Cyclopropyli-
denepropyl)(3ЈЈ-phenylprop-2ЈЈ-ynyl)malonate (10-Ph): Argon was Diethyl
(Z)-4-Ethenyl-5-methyl-3-(4Ј-methylenedihydrofuran-3Ј-
bubbled through a solution of of dimethyl (2Ј-cyclopropylidenepro-
pyl)(prop-2ЈЈ-ynyl)malonate (10-H, 85.3 mg, 341 µmol), Pd-
(OAc)2 (4.0 mg, 18 µmol, 5 mol-%) and PPh3 (14.0 mg, 53.4 µmol)
in 3 mL of DMF for 10 min, to the mixture were then added NEt3
(50.0 mg, 494 µmol) and iodobenzene (102 mg, 500 µmol), and it
was stirred at 100 °C for 12 h. After being cooled to ambient temp.,
the mixture was extracted with pentane (3×10 mL), the combined
organic phases were washed three times with 10 mL each of water
and brine, dried (MgSO4), and the solvent was removed in a rotary
evaporator. The residue was subjected to chromatography on silica
gel (column 1×20 cm, pentane/ether, 15:1). Fraction I: Iodo-
benzene, not completely evaporated, Rf = 0.90. Fraction II: 54.5 mg
ylidene)cyclohept-4-enedicarboxylate (48-H): A mixture of tris(di-
benzylideneacetone)dipalladium–chloroform complex (6.8 mg
(6.6 µmol), tris(o-tolyl)phosphane (4.0 mg, 13 µmol), of acetic acid
(2 µL, 2 mg, 30 µmol), tert-butyl acrylate (200 mg, 1.56 mmol) and
diethyl
(3ЈЈЈ-cyclopropylidenebutyl)[4Ј-(prop-2ЈЈ-ynyloxy)but-2Ј-
ynyl]malonate (33-H, 90.0 mg, 250 µmol) in 50 mL of benzene was
stirred under argon for 72 h. The solvent was removed under re-
duced pressure and the residue subjected to chromatography on
silica gel (column 2×20 cm, light petroleum/ether, 20:1) to yield
39 mg (43%) of 48-H as a yellowish oil, Rf = 0.25. 1H NMR
(250 MHz, CDCl3): δ = 1.20 (t, 3J = 7.1 Hz, 3 H, OCH2CH3), 1.25
(t, 3J = 7.1 Hz, 3 H, OCH2CH3), 1.85 (s, 3 H, CH3C=C), 1.93–
2.14 (m, 4 H, 6-H, 7-H), 2.80 (s, 2 H, 2-H), 4.02–4.27 (m, 4 H,
(49%) of 10-Ph as a colorless oil, R = 0.31. IR (film): ν = 3070
˜
f
cm–1, 2210, 1740 (C=O), 1670 (C=C), 1080, 900, 830, 780, 745, OCH2CH3), 4.37 (br. s, 2 H, CH2O), 4.47 (d, 2J = 12.6 Hz, 1 H,
705, 680. 1H NMR (250 MHz, CDCl3): δ = 1.04–1.07 (mc, 4 H, CH2O), 4.63 (d, J = 12.6 Hz, 1 H, CH2O), 4.90 (dd, J = 1.8, J
2
2
3
2
cPr-H), 1.76 (s, 3 H, 3Ј-H), 3.00 (s, 2 H, 1Ј-H*), 3.07 (s, 2 H, 1ЈЈ- = 10.4 Hz, 1 H, CH=CH2), 4.93 (s, 1 H, CH2), 5.02 (dd, J = 1.8,
H*), 3.75 (s, 6 H, CH3O), 7.26–7.28 (m, 3 H, Ar-H), 7.34–7.38 (s,
2 H, Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 2.7 17.1, 3J = 10.4 Hz, 1 H, CH=CH2) ppm. 13C NMR (62.9 MHz,
(–, cPr-C), 3.8 (–, cPr-C), 21.4 (+, C-3Ј), 23.7 (–, C-1ЈЈ), 39.0 (–, C- CDCl3, DEPT): δ = 13.9 (+, OCH2CH3), 19.1 (+, CH3C=C), 29.5
1Ј), 52.7 (+, CH3O), 57.2 (Cquat, C-1), 83.5 (Cquat, C-2ЈЈ*), 85.1 (–, C-7*), 32.0 (–, C-2*), 36.8 (–, C-6*), 56.8 (Cquat, C-1), 61.4 (–,
3J = 17.1 Hz, 1 H, CH=CH2), 5.10 (s, 1 H, CH2), 6.45 (dd, 3J =
(Cquat, C-3ЈЈ*), 118.8 (Cquat, cPr-C*), 122.4 (Cquat, C-2Ј*), 123.4
(Cquat, Ar-C*), 127.9 (+, Ar-C), 128.2 (+, Ar-C), 131.6 (+, Ar-C),
171.0 (Cquat, CO) ppm. MS (70 eV, EI): m/z (%) = 326 (8) [M+],
OCH2CH3), 72.0 (–, CH2O), 73.8 (–, CH2O), 107.9 (–, CH2=CH),
113.1 (–, CH2=C), 128.3 (Cquat, C=C), 129.6 (+, CH=CH2), 134.0
(Cquat, C=C), 135.8 (Cquat, C=C), 136.7 (Cquat, C=C), 142.9 (Cquat
,
294 (70) [M+ – CH4O], 207 (100) [M+ – CH3CO2H – CH3CO2], 77 C=C), 171.1 (Cquat, CO), 171.8 (Cquat, CO) ppm. MS (70 eV, EI):
(89) [C6H5+]. C20H22O4 (326.4): calcd. C 73.60, H 6.79; found C
m/z (%) = 360 (100) [M+], 332 (21) [M+ – CO], 314 (32) [M+
–
73.45, H 6.45. Fraction III: 23.4 mg (21%) of 41-Ph as a colorless
C2H5OH], 287 (26) [M+ – C2H5CO2], 257 (23), 241 (20), 229 (14),
213 (44), 183 (39), 173 (28), 127 (21), 91 (14). C21H28O5 (360.5):
360.1936 (correct HRMS).
oil; R = 0.28. IR (Film): ν = 3090 cm–1, 1740 (C=O), 1680 (C=C),
˜
f
1655, 1620 (C=C), 1585, 1080, 990, 920, 900, 830, 750, 740, 705,
1
650. H NMR (250 MHz, CDCl3): δ = 1.88 (s, 3 H, CH3), 2.72 (s,
Diethyl (3ЈЈЈ-Cyclopropylidenebutyl)[4Ј-(3ЈЈ-phenylprop-2ЈЈ-ynyloxy)
but-2Ј-ynyl]malonate (33-Ph): According to GP 4, a mixture of di-
ethyl (3ЈЈ-cyclopropylidenebutyl)[4Ј-(prop-2ЈЈ-ynyloxy)but-2Ј-ynyl]
malonate (33-H, 177 mg, 491 µmol), Pd(OAc)2 (6.2 mg, 28 µmol,
6 mol-%), PPh3 (21.9 mg, 83.5 µmol), NEt3 (101 mg, 1.00 mmol)
and iodobenzene (102 mg, 500 µmmol) was heated in 3 mL of
DMF at 100 °C for 12 h. After cooling to ambient temp., the mix-
ture was extracted with pentane (3×10 mL), the combined organic
phases were washed three times with 10 mL each of water and
brine, dried (MgSO4), and the solvent was removed in a rotary
evaporator. The residue was subjected to chromatography on silica
gel (column 1×20 cm, pentane/ether, 15:1). Fraction I: Iodo-
benzene, not completely evaporated, Rf = 0.90. Fraction II: 94.5 mg
2 H, 2-H), 3.09 (d, 4J = 1.1 Hz, 2 H, 6-H), 3.62 (s, 6 H, CH3O),
5.15 (dd, 2J = 2.2, 3J = 17.8 Hz, 1 H, CH=CH2), 5.42 (dd, 2J =
2.2, 3J = 11.2 Hz, 1 H, CH=CH2) 6.30 (dd, 2J = 17.8, 3J = 11.2 Hz,
1 H, CH=CH2), 6.55 (s, 1 H, CHPh=C), 7.17–7.35 (s, 2 H, Ar-H),
7.40–7.62 (m, 3 H, Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3,
DEPT): δ = 21.35 (+, CH3), 31.57 (–, C-2*), 37.49 (–, C-6*), 52.43
(+, OCH3), 53.99 (Cquat, C-1), 119.75 (–, CH2=CH), 126.14 (+,
C=CH), 127.17 (+, C=CH), 127.97 (+, C=CH), 128.82 (+, C=CH),
131.51 (Cquat), 132.35 (Cquat), 133.33 (Cquat), 134.00 (+, C=CH),
137.92 (Cquat), 171.20 (Cquat, CO) ppm. MS (70 eV, EI): m/z (%) =
326 (45) [M+], 294 (20) [M+ – CH4O], 207 (100) [M+ – CH3CO2H –
CH3CO2], 77 (55) [C6H5+]. C20H22O4 (326.4): calcd. C 73.60, H
6.79; found C 73.25, H 6.23.
1
(44%) of 33-Ph as a colorless oil, Rf = 0.31. H NMR (250 MHz,
3
2-Cyclopropylidene-6-phenylhex-5-yne (24-Ph): In a screw-cap Pyrex
bottle were placed 2-cyclopropylidenehex-5-yne (24-H, 460 mg,
3.83 mmol), iodobenzene (1.13 g, 5.54 mmol), triethylamine
(602 mg, 5.95 mmol), triphenylphosphane (157 mg, 599 µmol),
Pd(OAc)2 (47.0 mg, 209 µmol) in 15 mL of DMF, and the mixture
was heated under argon at 100 °C for 20 h. After being cooled to
ambient temperature, the mixture was extracted with pentane
(5×20 mL). The combined organic phases were extracted with
50 mL of water and dried (MgSO4). The solvent was removed in a
rotary evaporator at 20 °C and 300 Torr. Chromatography on silica
gel (column 3×20 cm, pentane) yielded 100 mg (13%) of 24-Ph as
CDCl3): δ = 0.88–1.15 (m, 4 H, cPr-H), 1.20 (t, J = 7.1 Hz, 6 H,
4
OCH2CH3), 1.76 (t, J = 1.5 Hz, 3 H, 4ЈЈЈ-H), 1.99–2.10 (m, 2 H,
1ЈЈЈ-H), 2.16–2.23 (m, 2 H, 2ЈЈЈ-H), 2.84 (t, 4J = 2.1 Hz, 2 H, 1Ј-
H), 4.10–4.18 (m, 8 H, OCH2CH3, 1ЈЈ-H, 4Ј-H), 7.10–7.29 (m, 5 H,
Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 1.38 (–, C-
cPr), 2.63 (–, C-cPr), 13.89 (+, OCH2CH3), 20.34 (–, C-1ЈЈЈ), 22.78
(+, C-4ЈЈЈ), 29.85 (–, C-2ЈЈЈ), 30.89 (–, C-1Ј), 55.82 (Cquat, C-1),
55.99 (–, CH2O), 56.51 (–, CH2O), 61.32 (–, OCH2CH3), 74.61
(Cquat, CϵC), 77.77 (Cquat, C-3ЈЈ), 78.83 (Cquat, CϵC), 82.03
(Cquat, CϵC), 116.13 (Cquat, C-cPr), 122.77 (–, C-3ЈЈЈ), 128.02 (+,
C–Ar), 128.43 (+, C–Ar), 131.09 (+, C–Ar), 149.88 (Cquat), 170.88
(Cquat, CO), 170.07 (Cquat, CO) ppm.
1
a colorless oil. H NMR (250 MHz, CDCl3): δ = 0.97–1.16 (mc, 4
Eur. J. Org. Chem. 2005, 4167–4178
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4175

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
Dimethyl (2ЈЈЈ-Cyclopropylidenepropyl)[4Ј-(3ЈЈ-phenylprop-2ЈЈ-yny- zene was stirred under argon for 36 h. Chromatography on silica
FULL PAPER
loxy)but-2Ј-ynyl]malonate (38-Ph): According to GP 4, a mixture
of dimethyl (2ЈЈЈ-cyclopropylidenepropyl)[4Ј-(prop-2ЈЈ-ynyloxy)-
but-2Ј-ynyl]malonate (38-H, 177 mg, 556 µmol), Pd(OAc)2 (6.2 mg,
28 µmol, 5 mol-%), PPh3 (21.9 mg, 83.5 µmol), NEt3 (101 mg,
1.00 mmol) and iodobenzene (102 mg, 500 µmol) was heated in
3 mL of DMF at 100 °C for 12 h. After cooling to ambient temp.,
the mixture was extracted with pentane (3×10 mL), the combined
organic phases were washed three times with 10 mL each of water
and brine, dried (MgSO4), and the solvent was removed in a rotary
evaporator. The residue was subjected to chromatography on silica
gel (column 1×20 cm, pentane/ether, 15:1). Fraction I: Iodo-
benzene Rf = 0.90. Fraction II: 60 mg (30%) of 38-Ph as a colorless
oil, Rf = 0.31. 1H NMR (250 MHz, CDCl3): δ = 1.00–1.16 (m, 4 H,
cPr-H), 1.73 (s, 3 H, 3ЈЈЈ-H), 2.78 (s, 2 H, 1Ј-H), 3.04 (s, 2 H, 1ЈЈЈ-
H), 3.70 (s, 6 H, OCH3), 4.32 (s, 2 H, 1ЈЈ-H), 4.45 (s, 2 H, 4Ј-H),
7.12–7.32 (m, 5 H, Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3,
DEPT): δ = 2.7 (–, cPr-C), 3.8 (–, cPr-C), 21.4 (+, C-3ЈЈЈ), 23.2
(–, C-1Ј), 39.0 (–, C-1ЈЈЈ), 52.7 (+, OCH3), 56.8 (–, CH2O), 56.9
(–, CH2O), 62.0 (Cquat, C-1), 77.5 (Cquat, CϵC), 78.3 (Cquat, CϵC),
78.9 (Cquat, CϵC), 82.7 (Cquat, CϵC), 118.7 (Cquat, cPr-C), 122.4
(Cquat, C-2ЈЈЈ), 128.3 (+, Ar-C), 128.5 (+, Ar-C), 131.8 (+, Ar-C),
149.2 (Cquat, Ar-C), 170.9 (Cquat, CO) ppm.
gel (column 2×20 cm, pentane Ǟ pentane/ether, 20:1) gave 120 mg
(59%) of 67 as a colorless oil.
Diethyl 13-Methyl-3,5,15,17-tetraoxo-4,16-diphenyl-2,4,6,14,16,18-
hexaazapentacyclo[11.6.1.02,6.08,20.014,18]eicosa-8(20)-ene-10,10-di-
carboxylate (69): To a solution of diethyl 4-ethenyl-5-methyl-3-
methylenecyclohept-4-ene-1,1-dicarboxylate
(42,
1.25 g,
4.28 mmol) and phenylurazole (1.73 g, 11.92 mmol) in 75 mL of
dichloromethane was added at –10 °C lead() acetate (4.57 g,
11.92 mmol, 95% + 5% AcOH) within 10 min. After an additional
30 min, the mixture was diluted with 500 mL of diethyl ether, fil-
tered, and the filtrate washed three times with 100 mL each of
water and brine, then dried (MgSO4), and filtered while hot. After
removal of the solvent, the residue was recrystallized from hexane/
dichloromethane to give 2.18 g (81%) of 69 as light yellow crystals,
m.p. 157–163 °C. IR (KBr): ν = 3455 cm–1, 2979, 1715, 1410, 1254,
˜
1
1202, 1134, 768, 689, 646. H NMR (250 MHz, CDCl3): δ = 1.21
(t, 3J = 7.1 Hz, 3 H, CH3), 1.22 (t, 3J = 7.1 Hz, 3 H, CH3), 2.05
(dt, J = 14.1, J = 2.8 Hz, 1 H, CH), 2.30 (dt, J = 15.2, J = 3.1 Hz,
1 H, CH), 2.57 (dd, J = 16.3, J = 2.0 Hz, 1 H, CH), 2.64 (dq, J =
12.7, J = 2.5 Hz, 1 H, CH), 3.12 (dt, J = 16.0, J = 1.2 Hz, 1 H,
CH), 3.39 (dd, J = 11.3, J = 9.2 Hz, 1 H, CH), 3.49 (ddd, J = 14.3,
J = 5.0, J = 3.2 Hz, 1 H, CH), 4.0–4.24 (m, 6 H, CH2, CH), 4.64
(dq, J = 9.1, J = 5.6 Hz, 1 H, CH), 4.93–4.95 (m, 1 H, CH), 7.15–
7.25 (m, 10 H, Ar-H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT):
δ = 14.0 (+, OCH2CH3), 14.1 (+, CCH3), 28.7 (–, CH2), 30.4 (–,
CH2), 35.1 (–, CH2), 44.0 (–, CH2), 49.7 (+, CH), 55.5 (–, CH2),
61.9 (–, CH2), 62.2 (–, CH2), 69.7 (Cquat, C-10), 125.4 (+, Ar-Cr),
125.8 (+, Ar-C), 126.4 (Cquat, Ar-C), 128.4 (+, Ar-C), 129.7 (+, Ar-
C), 129.3 (+, Ar-C), 130.9 (Cquat, Ar-C*), 131.0 (Cquat, C=C*),
133.6 (Cquat, C=C), 151.2 (Cquat, NCO), 151.7 (Cquat, NCO), 153.0
(Cquat, NCO), 169.4 (Cquat, CO2), 171.0 (Cquat, CO2) ppm. MS
(70 eV, EI): m/z (%) = 642 (8) [M+], 466 (23), 452 (41), 129 (72),
115 (100), 91 (55). C33H34N6O8 (642.2): calcd. C 61.67, H 5.33, N
13.08; found C 61.75, H 5.52, N 12.92.
8-Ethenyl-9-methyl-4-methylene-6-oxaspiro[2.6]non-8-ene (67) and
1,5-Bis(3Ј-cyclopropylidene-2Ј,2Ј-ethanobutoxy)-4-methylenepent-2-
yne (59). a) A mixture of tris(dibenzylideneacetone)dipalladium–
chloroform complex (29.8 mg, 28.8 µmol), tris(o-tolyl)phosphane
(17.5 mg, 57.5 µmol), acetic acid (2 µL, 2 mg, 0.03 mmol) and [1Ј-
(1ЈЈ-cyclopropylideneethyl)cyclopropylmethyl] (prop-2ЈЈ-ynyl) ether
(20-H, 203 mg, 1.15 mmol) in 7 mL of benzene was stirred under
argon for 12 h. Chromatography on silica gel (column 2×20 cm,
pentane Ǟ pentane/ether, 20:1) gave two fractions. Fraction I:
35.0 mg (17%) of 67 as a colorless oil, Rf = 0.30 (pentane/ether,
40:1). IR (film): ν = 3060 cm–1, 1665 (C=C), 1650, 1090, 990, 885,
˜
755, 740, 710. 1H NMR (250 MHz, CDCl3): δ = 0.85–1.02 (m, 4 H,
4
cPr-H), 1.72 (s, 3 H, CH3), 4.26 (s, 2 H, 7-H), 4.53 (dd, J = 1.0,
4J = 1.0 Hz, 2 H, 5-H), 4.90 (t, 4J = 1.0 Hz, 2 H, CH2C=CϽ),
Diethyl
8,8,9,9-Tetracyano-7-methyl-2-methylenebicyclo[5.4.0]un-
3
3
5.01 (d, J = 11.3 Hz, 1 H, CH=CH2), 5.15 (d, J = 17.5 Hz, 1 H, dec-11-ene-4,4-dicarboxylate (70): To a solution of the ester 42
CH=CH2), 6.63 (dd, 3J = 17.5, 3J = 11.3 Hz, 1 H, CH=CH2) ppm.
(800 mg, 2.87 mmol) in 50 mL of benzene was added tetracyano-
13C NMR (125.7 MHz, CDCl3, DEPT): δ = 14.2 (–, CH2), 16.1 (+, ethylene (290 mg, 2.29 mmol), and the mixture stirred for 15 h at
CH3), 29.5 (Cquat, cPr-C), 66.4 (–, OCH2), 74.6 (–, OCH2), 111.9 ambient temperature. The solvent was removed under reduced pres-
(–, C=CH2), 112.4 (–, C=CH2), 132.8 (Cquat, C=C), 134.6 (+, sure, and the residue recrystallized from benzene to give 533 mg
CH=C), 139.6 (Cquat, C=C), 149.1 (Cquat, C=C) ppm. MS (70 eV,
(55%) of 70 as colorless crystals, m.p. 134 °C. IR (KBr): ν = 2979
˜
EI): m/z (%) = 176 (100) [M+], 148 (65) [M+ – C2H4]. C12H16O cm–1, 2914, 1772, 1715, 1599, 1504, 1410, 1290, 1254, 1202, 1134,
1
(176.3): calcd. C 81.77, H 9.15; found C 81.56, H 9.20. Fraction II:
768, 689, 646. H NMR (600 MHz, CDCl3): δ = 1.22 ppm (t, J =
7.1 Hz, 3 H, OCH2CH3), 1.25 (t, J = 7.1 Hz, 3 H, OCH2CH3), 1.65
(s, 3 H, CH3), 1.90–1.96 (ddd, J = 1.6, 8.5, 16.3 Hz, 1 H, 6*-H),
2.22–2.28 (ddd, J = 1.6, 10.6, 17.6 Hz, 1 H, 6*-H), 2.34–2.42 (m,
1 H, 5*-H), 2.73 (d, J = 15.0 Hz, 1 H, 3-H), 3.00 (d, J = 15.0 Hz,
110 mg (54%) of 59 as a colorless oil, Rf = 0.35 (pentane/ether,
20:1). IR (film): ν = 3117 cm–1, 3038, 2944, 2856, 2115 (CϵC),
˜
1675 (C=C), 1456, 1372, 1281, 1202, 1011, 980, 736, 526. 1H NMR
(250 MHz, CDCl3): δ = 0.53–0.59 (m, 4 H, cPr-H), 0.73–0.87 (m,
8 H, cPr-H), 1.09–1.17 (m, 4 H, cPr-H), 2.13 (br. s, 6 H, CH3), 3.45 1 H, 3-H), 3.17 (ddc, J = 18.8, 3.5 Hz, 1 H, 10-H), 3.21 (ddc, J =
(s, 2 H, CH2O), 3.51 (s, 2 H, CH2O), 3.94 (s, 2 H, C=CCH2O), 4.24 18.8, 4.5 Hz, 1 H, 10-H), 4.12–4.23 (m, 4 H, OCH2CH3), 5.09 (d,
(s, 2 H, CϵCCH2O), 5.43 (s, 1 H, CH2=C), 5.45 (s, 1 H, CH2=C) J = 1.3 Hz, 1 H, =CH2), 5.13 (d, J = 1.3 Hz, 1 H, =CH2), 5.63 Hz
ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 0.2 (–, 4 × cPr- (ddc, J = 4.5, 3.4 Hz, 1 H, 11-H) ppm. 13C NMR (150.82 MHz,
C), 3.9, 4.1 (–, cPr–C), 10.3, 10.4 (–, cPr–C), 19.0, 19.1 (+, C-4Ј), CDCl3, additional DEPT): δ = 13.90 ppm (+, OCH2CH3), 13.95
24.9, 25.2 (Cquat, C-2Ј), 57.8 (–, CH2O), 72.1 (–, CH2O), 75.0 (–, (+, OCH2CH3), 22.9 (+, CH3), 27.4 (–, C-5), 32.6 (–, C-10), 34.0
CH2O), 75.7 (–, CH2O), 84.4 (Cquat, C-2*), 86.1 (Cquat, C-3*), (–, C-3), 36.4 (Cquat, C-7), 38.6 (–, C-6), 44.6 (Cquat, C-8*), 49.3
116.8, 117.0 (Cquat, C-3Ј*), 121.5 (–, CH2=C), 124.1, 124.3 (Cquat (Cquat, C-9*), 56.3 (Cquat, C-4), 61.82 (–, OCH2CH3), 61.84 (–,
OCH2CH3), 110.2 (Cquat,CN), 110.4 (Cquat, CN), 111.86 (Cquat
,
cPr-C), 128.2 (Cquat, C-4) ppm. MS (70 eV, EI): m/z (%): = 320
(9), 305 (32), 79 (100). b) A mixture of tris(dibenzylideneacetone)
dipalladium–chloroform complex (29.8 mg, 28.8 µmol), tris(o-tolyl)
phosphane (17.5 mg, 57.5 µmol), acetic acid (2 µL, 2 mg,
0.03 mmol) and [1Ј-(1ЈЈ-(cyclopropylideneethyl)cyclopropylmethyl]
(prop-2ЈЈ-ynyl) ether (20-H, 203 mg, 1.15 mmol) in 100 mL of ben-
,
CN), 111.93 (Cquat, CN), 116.0 (+, C-11), 120.7 (–, =CH2), 142.8
(Cquat, C-2*), 144.1 (Cquat, C-1*) 170.5 (–, COO), 170.7 (–, COO)
ppm. MS (70 eV, EI): m/z (%) = 420 (27) [M+], 375 (6) [M+
–
C2H5O], 347 (27) [M+ – CO2C2H5], 346 (33) [M+ – C2H5OH – CO],
317 (33), 301 (46), 300 (100) [M+ – 2 C2H5OH – CO], 273 (11), 246
4176
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178

Efficient Syntheses of [3]Dendralenes
FULL PAPER
haran, P. Stevenson, T. Worakun, J. Chem. Soc. Chem. Com-
mun. 1986, 1697–1699; d) R. Grigg, V. Loganathan, V. San-
thakumar, V. Sridharan, A. Teasdale, Tetrahedron Lett. 1991,
32, 687–690; e) M. M. Abelman, T. Oh, L. E. Overman, J. Org.
Chem. 1987, 52, 4130–4133; f) J. W. Dankwardt, L. A. Flippin,
J. Org. Chem. 1995, 60, 2312–2313; g) A. de Meijere, H. Nüske,
M. Es-Sayed, T. Labahn, M. Schroen, S. Bräse, Angew. Chem.
1999, 111, 3881–3884; Angew. Chem. Int. Ed. 1999, 38, 3669–
3672; h) H. Nüske, S. Bräse, S. I. Kozhushkov, M. Noltemeyer,
M. Es-Sayed, A. de Meijere, Chem. Eur. J. 2002, 8, 2350–2369.
Preliminary communication see: S. Bräse, A. de Meijere, An-
gew. Chem. 1995, 107, 2741–2743; Angew. Chem. Int. Ed. Engl.
1995, 34, 2545–2547.
a) A. Stolle, J. Salaün, A. de Meijere, Synlett 1991, 327–330; b)
A. Stolle, J. Ollivier, P. P. Piras, J. Salaün, A. de Meijere, J. Am.
Chem. Soc. 1992, 114, 4051–4067; c) J. Ollivier, P. P. Piras, A.
Stolle, P. Aufranc, A. de Meijere, J. Salaün, Tetrahedron Lett.
1992, 33, 3307–3310; d) A. Stolle, J. Salaün, A. de Meijere, Tet-
rahedron Lett. 1990, 31, 4593–4596; e) G. McGaffin, S. Michal-
ski, A. Stolle, S. Bräse, J. Salaün, A. de Meijere, Synlett 1992,
558–560.
(7). C23H24N4O4 (372.5): calcd. C 65.70, H 5.75, N 13.33; found C
66.04, H 5.83, N 13.18.
Supporting Information (see footnote on first page of this article):
Detailed experimental procedures for cyclization precursors de-
scribed in this article (19 pages).
Acknowledgments
[10]
[11]
This work was supported by the State of Niedersachsen and the
Fonds the Chemischen Industrie as well as BASF, Bayer, Degussa,
Hüls AG and Chemetall GmbH (chemicals). S. B. is indebted to
the Fonds der Chemischen Industrie for a graduate fellowship. The
authors are particularly grateful to Dr. Burkhard Knieriem,
Göttingen for his careful proofreading of the final manuscript and
Stefan Beußhausen for his technical support.
[1] B. M. Trost, Science 1991, 254, 1471–1477.
[2] a) G. H. Posner, Chem. Rev. 1986, 86, 831–844; b) L. F. Tietze,
J. Heterocycl. Chem. 1990, 27, 47–69; c) K. Sonogashira, in:
Comprehensive Organic Synthesis (Eds.: B. M. Trost, I. Flem-
ing), Pergamon Press, Oxford, 1991, vol. 5, pp. 521–549; d)
T.-L. Ho, Tandem Organic Reactions, Wiley-Interscience, New
York, 1992; e) E. Negishi, Pure Appl. Chem. 1992, 64, 323–334;
f) L. F. Tietze, U. Beifuß, Angew. Chem. 1993, 105, 137–170;
Angew. Chem. Int. Ed. Engl. 1993, 32, 131–163; g) L. F. Tietze,
Chem. Rev. 1996, 96, 115–136; h) P. J. Parsons, C. S. Penkett,
A. J. Shell, Chem. Rev. 1996, 96, 195–206; i) A. Heumann, M.
Réglier, Tetrahedron 1996, 52, 9289–9346.
[3] P. A. Wender, S. T. Handy, D. L. Wright, Chem. Ind. (London)
1997, 765.
[4] For comprehensive reviews see: E. Negishi, A. de Meijere
(Eds.) Handbook of Organopalladium Chemistry for Organic
Synthesis, Wiley, New York, 2002.
[5] For reviews see: a) B. M. Trost, T. R. Verhoeven, in: Compre-
hensive Organometallic Chemistry (Ed.: G. Wilkinson), Perga-
mon, Oxford, 1991, vol. 8, pp. 854–883; b) A. de Meijere, F. E.
Meyer, Angew. Chem. 1994, 106, 2473–2506; Angew. Chem. Int.
Ed. Engl. 1994, 33, 2379–2411; c) W. Cabri, I. Candiani, Acc.
Chem. Res. 1995, 28, 2–7; d) T. Tsuji, Palladium Reagents and
Catalysts. Innovations in Organic Synthesis, Wiley, Chichester,
1995; e) E. Negishi, C. Copéret, S. Ma, S.-Y. Liou, F. Liu,
Chem. Rev. 1996, 96, 365–394; f) A. de Meijere, S. Bräse, in:
Transition Metal Catalysed Reactions (Eds.: S.-i. Murahashi,
S. G. Davies), Blackwell Science, Oxford, 1999, pp. 99–131; g)
A. de Meijere, S. Bräse, J. Organomet. Chem. 1999, 576, 88–
110; h) S. Bräse, A. de Meijere, in: Metal-Catalyzed Cross-
Coupling Reactions (Eds.: A. de Meijere, F. Diederich), Wiley-
VCH, Weinheim, 2004, pp. 217–315; i) A. de Meijere, P.
von Zezschwitz, S. Bräse, Acc. Chem. Res. 2005, 38, 413–422.
[6] a) F. E. Meyer, P. J. Parsons, A. de Meijere, J. Org. Chem. 1991,
56, 6487–6488; b) F. E. Meyer, A. de Meijere, Synlett 1991,
777–778; c) F. E. Meyer, J. Brandenburg, P. J. Parsons, A.
de Meijere, J. Chem. Soc. Chem. Commun. 1992, 390–392; d)
F. E. Meyer, H. Henniges, A. de Meijere, Tetrahedron Lett.
1992, 33, 8039–8042; e) S. Schweizer, Z.-Z. Song, F. E. Meyer,
P. J. Parsons, A. de Meijere, Angew. Chem. 1999, 111, 1550–
1552; Angew. Chem. Int. Ed. 1999, 38, 1452–1454.
[7] a) F. E. Meyer, K. H. Ang, A. G. Steinig, A. de Meijere, Synlett
1994, 191–193; b) L. Bhat, A. G. Steinig, R. Appelbe, A.
de Meijere, Eur. J. Org. Chem. 2001, 1673–1680.
[8] K. H. Ang, S. Bräse, A. G. Steinig, F. E. Meyer, A. Llebaria,
K. Voigt, A. de Meijere, Tetrahedron 1996, 52, 11503–11528.
[9] For Heck reactions with tetrasubstituted alkenes see: a) G.
Dyker, J. Körning, P. G. Jones, P. Bubenitschek, Angew. Chem.
1993, 105, 1805–1807; Angew. Chem. Int. Ed. Engl. 1993, 32,
1733–1735; b) G. Dyker, J. Körning, P. Bubenitschek, P. G.
Jones, Liebigs Ann./Recueil 1997, 203–209; c) R. Grigg, V. Srid-
[12]
[13]
[14]
a) L. Fitjer, Synthesis 1977, 189–199; b) D. Baucke, Disser-
tation, University of Göttingen, 1994.
K. Utimoto, M. Tamura, K. Sisido, Tetrahedron 1973, 29,
1169–1171.
This was an improvement in comparison to a literature pro-
cedure, in which sodium hydride was used as the base in dime-
thoxyethane (DME); a) A. M. Bernard, P. Piras, J. Chem. Soc.
Chem. Commun. 1994, 257; b) J. A. Stafford, J. E. McMurry,
Tetrahedron Lett. 1988, 29, 2531–2534.
N. S. Zefirov, T. S. Kuznetsova, S. I. Koshushkov, L. S. Surm-
ina, Z. A. Rashchupkina, Zh. Org. Khim. 1983, 19, 541–548; J.
Org. Chem. USSR (Engl. Transl.) 1983, 19, 474–480.
H. Nemoto, H. Ishibashi, M. Nagamochi, K. Fukumoto, J.
Org. Chem. 1992, 57, 1707–1712.
F. Huet, A. Lechevallier, M. Pellet, J. M. Conia, Synthesis 1978,
63–65.
G. Fournet, G. Balme, J. Gore, Tetrahedron Lett. 1987, 28,
4533–4536.
C. Silveira, University of Göttingen, personal communication,
1995.
H. Becker, Dissertation, University of Göttingen, 1996.
a) D. Wendisch, in: Methoden in der Organischen Chemie
(Houben-Weyl) (Ed.: E. Müller), 1971, vol. 4/3, p. 615–632;
Examples: b) J. Al-Dulayyimi, M. S. Baird, Tetrahedron Lett.
1989, 30, 253–256; c) M. S. Baird, H. H. Hussain, W. Nether-
cott, J. Chem. Soc. Perkin Trans. 1 1986, 1845–1853.
H.-C. Militzer, S. Schömenauer, C. Otte, C. Puls, J. Hain, S.
Bräse, A. de Meijere, Synthesis 1993, 998–1012.
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
G. A. Olah, S. C. Narang, B. G. B. Gupta, R. Malhotra, J. Org.
Chem. 1979, 44, 1247–1251.
a) A. Mondon, Justus Liebigs Ann. Chem. 1957, 603, 115–129;
b) L. Fitjer, U. Quabeck, Synthesis 1987, 299–300.
a) H. Levy, A. C. Cope, J. Am. Chem. Soc. 1944, 66, 1684–
1688. Reviews: b) R. P. Lutz, Chem. Rev. 1984, 84, 205–247; c)
L. E. Overman, Angew. Chem. 1984, 96, 565–573; Angew.
Chem. Int. Ed. Engl. 1984, 23, 579–587; d) S. J. Rhoads, N. R.
Raulins, Org. React. 1972, 22, 1–252.
D. Kaufmann, A. de Meijere, Chem. Ber. 1984, 117, 1128–1138.
For an example see: B. M. Trost, M. Lautens, J. Am. Chem.
Soc. 1985, 107, 1781–1783.
a) B. M. Trost, D. M. T. Chan, J. Am. Chem. Soc. 1983, 105,
2315–2325; b) B. M. Trost, M. Lautens, M.-H. Hung, C. S.
Carmichael, J. Am. Chem. Soc. 1984, 106, 7641–7643.
For a recent review see: J. A. Marsden, M. M. Haley, in: Metal-
Catalyzed Cross-Coupling Reactions (Eds.: A. de Meijere, F. Di-
ederich), Wiley-VCH, Weinheim, 2004, pp. 319–394.
a) L. Cassar, J. Organomet. Chem. 1975, 93, 253–258; b) H. A.
Dieck, F. R. Heck, J. Organomet. Chem. 1975, 93, 259–263.
[26]
[27]
[28]
[29]
[30]
Eur. J. Org. Chem. 2005, 4167–4178
www.eurjoc.org
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4177

S. Bräse, H. Wertal (nee Nüske), D. Frank, D. Vidovic´, A. de Meijere
FULL PAPER
[31] Review: a) B. M. Trost, Acc. Chem. Res. 1990, 23, 34–42. For
examples see: b) M. Toyota, T. Wada, M. Matsuura, K. Fuku-
moto, Synlett 1995, 761–762.
960; b) H. Hopf, Angew. Chem. 2001, 113, 727–729; Angew.
Chem. Int. Ed. 2001, 40, 705–707.
[38] a) O. Tsuge, E. Wada, S. Kanemasa, Chem. Lett. 1983, 1525–
1528; b) O. Tsuge, E. Wada, S. Kanemasa, Chem. Lett. 1983,
239–242; c) K. Takahashi, S. Tarutani, J. Chem. Soc. Chem.
Commun. 1994, 519–520; d) M. Mühlebach, M. Neuen-
schwander, Helv. Chim. Acta 1994, 77, 1363–1376; e) J. I. G.
Cadogan, S. Cradock, S. Gillam, I. Gosney, J. Chem. Soc.
Chem. Commun. 1991, 114–115.
[39] Review: a) I. K. Korobitsyna, A. V. Khalikova, L. L. Rodina,
N. P. Shusherina, Chem. Rev. USSR 1983, 117–136; b) Exam-
ple: M. P. Johnson, C. J. Moody, J. Chem. Soc. Perkin Trans. 1
1985, 71–74.
[40] CCDC-274845 (70) 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.
[41] Reviews: a) K. Matsumoto, A. Sera, T. Uchida, Synthesis 1985,
1–26; b) N. S. Isaacs, Tetrahedron 1991, 47, 8463–8497; c) W. J.
le Noble, Chemie Unserer Zeit 1983, 17, 152–162.
[42] M. Duetsch, Dissertation, University of Göttingen, 1993.
Received: May 09, 2005
[32] a) P. A. Pinke, R. G. Miller, J. Am. Chem. Soc. 1974, 96, 4221–
4229; b) P. A. Pinke, R. D. Stauffer, R. G. Miller, J. Am. Chem.
Soc. 1974, 96, 4229–4234; c) P. Binger, A. Brinkmann, P. Wede-
mann, Chem. Ber. 1983, 116, 2920–2930; d) J. W. Herndon,
S. U. Tumer, Tetrahedron Lett. 1989, 30, 295–296; e) P. Binger,
Angew. Chem. 1972, 84, 352–353; Angew. Chem. Int. Ed. Engl.
1972, 11, 309–310; f) P. A. Wender, H. Takahashi, B. Witulski,
J. Am. Chem. Soc. 1995, 117, 4720–4721; g) cf. also: M. A.
Huffman, L. S. Liebeskind, J. Am. Chem. Soc. 1993, 115, 4895–
4896; h) S. U. Tumer, J. W. Herndon, L. A. McMullen, J. Am.
Chem. Soc. 1992, 114, 8394–8404.
[33] Z. Owczarczyk, F. Lamaty, E. J. Vawter, E. Negishi, J. Am.
Chem. Soc. 1992, 114, 10091–10092.
[34] a) B. M. Trost, C. Chan, G. Ruhter, J. Am. Chem. Soc. 1987,
109, 3486–3487; b) B. M. Trost, S. Matsubara, J. J. Caringi, J.
Am. Chem. Soc. 1989, 111, 8745–8746; c) R. W. Wagner, T. E.
Johnson, F. Li, J. S. Lindsey, J. Org. Chem. 1995, 60, 5266–
5273.
[35] J. E. Baldwin, J. Chem. Soc. Chem. Commun. 1976, 734–736.
[36] M. Brandl, S. I. Koshushkov, S. Bräse, A. de Meijere, Eur. J.
Org. Chem. 1998, 453–457.
[37] For reviews on dendralenes see: a) H. Hopf, Angew. Chem.
1984, 96, 947–958; Angew. Chem. Int. Ed. Engl. 1984, 23, 948–
Published Online: August 16, 2005
Note: Minor changes have been made to this manuscript
since its publication in Eur. J. Org. Chem. Early View.
4178
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 4167–4178