A two-step, three-component queuing cascade leading to dihydrobenzoxepine and dihydrobenzazepine derivatives

Article abstract of DOI:10.1002/ejoc.200700354

A palladium-catalyzed reaction of methylenespiropentane (11) with iodobenzene (12) under typical Heck conditions [Pd(OAc)₂, PPh ₃, Et₃N, DMF] produced a mixture of the unstable [3]dendralene 13 and allylidenecyclopropane 1

Full text of DOI:10.1002/ejoc.200700354

FULL PAPER
DOI: 10.1002/ejoc.200700354
A Two-Step, Three-Component Queuing Cascade Leading to
Dihydrobenzoxepine and Dihydrobenzazepine Derivatives[‡]
[a][‡‡‡]
Baris Yucel,[a][‡‡] Natasa Valentic,
´
Mathias Noltemeyer[b] and Armin de Meijere*[a]
ˇ
Dedicated to Professor Waldemar Adam on the occasion of his 60th birthday
Keywords: π-Allylpalladium species / Benzazepine / Benzoxepine / Bicyclopropylidene / Methylenespiropentane
A palladium-catalyzed reaction of methylenespiropentane
(11) with iodobenzene (12) under typical Heck conditions
[Pd(OAc)2, PPh3, Et3N, DMF] produced a mixture of the un-
stable [3]dendralene 13 and allylidenecyclopropane 14 in
38% yield. When an analogous reaction with iodobenzene
was carried out in the presence of morpholine (25) and of
tris(2-furyl)phosphane (TFP) instead of triphenylphosphane,
the dienes 26, 28 and 31 were generated by nucleophilic
trapping of π-allylpalladium intermediates 30 and 32. The
cross coupling of methylenespiropentane (11) with the func-
tionalized aryl iodides 33a–g in the presence of a palladium
precatalyst [Pd(OAc)2, TFP, Et3N, DMF] at 80 °C, 3 h, pro-
vided the seven-membered 3,4-dimethylene-substituted het-
erocycles 34a–g and 35b which, upon addition of dimethyl
fumarate (19), underwent Diels–Alder reactions to furnish bi-
cyclic and higher oligocyclic dihydrobenzoxepine and
-benzazepine derivatives 36a–g and 37b, yet in rather mod-
erate yields of 18–29% only. The overall process constitutes
a one-pot, two-step, three-component queuing cascade.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
Introduction
spiro[2.5]octene derivatives 3 in a single operation (Scheme
1).[3b] Under slightly modified conditions, i.e. in the pres-
ence of tris(2-furyl)phosphane (TFP) instead of tri-
The highly strained and thereby unusually reactive tetra-
substituted alkene bicyclopropylidene (1), which can easily
be prepared on a multigram scale,[1] has been turned into a
versatile C6 building block for various synthetic applica-
tions.[2] It is particularly remarkable that the double bond
in bicyclopropylidene (1) undergoes exceptionally fast car-
bopalladations in Heck-type reactions.[3] These coupling re-
actions with various aryl and alkenyl iodides can be carried
out in the presence of a dienophile such as methyl acrylate
and, in a sequence of carbopalladation across the double
bond in 1, cyclopropylmethyl- to homoallylpalladium re-
arrangement, β-dehydropalladation and [4+2] cycload-
dition of the thus formed allylidenecyclopropanes, yield the
[‡] Cyclopropyl Building Blocks in Organic Synthesis, 143. Part
142: H. Schill, A. de Meijere, Org. Lett., in press. Part 141: V. S.
Korotkov, O. V. Larionov, A. Hofmeister, J. Magull, A. de Mei-
jere, J. Org. Chem., in press.
[a] Institut für Organische und Biomolekulare Chemie, Georg-Au-
gust-Universität Göttingen,
Tammanstrasse. 2, 37077 Göttingen, Germany
Fax: +49-551-399475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b] Institut für Anorganische Chemie, Georg-August-Universität
Göttingen,
Tammannstrasse 4, 37077 Göttingen, Germany
[‡‡]New address: Istanbul Technical University, Science Faculty,
Department of Chemistry,
Scheme 1. Two recently developed one-pot reactions of bicyclopro-
pylidene (1) involving palladium-catalyzed Heck couplings, cy-
clopropylcarbinyl to homoallyl rearrangements, β-dehydropallada-
tions, rehydridopalladation and Diels–Alder reactions. (A)
Pd(OAc)2, PPh3, Et4NCl, K2CO3, Me3CN, 80 °C, 48 h. (B)
Pd(OAc)2, TFP, Et3N, DMF, 80 °C, 2 h.
34469 Maslak, Istanbul, Turkey
[‡‡‡]New address: Department of Organic Chemistry, Faculty of
Technology and Metallurgy, University of Belgrade,
Karnegijeva 4, P. O. Box 3503, 11120 Belgrade, Serbia
Eur. J. Org. Chem. 2007, 4081–4090
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B. Yucel, N. Valentic´, M. Noltemeyer, A. de Meijere
FULL PAPER
phenylphosphane, the initial products of type 6 undergo re-
hydridopalladation with reverse regioselectivity to yield the
π-allylpalladium complexes 8 which are trapped by nucleo-
philes, e.g. morpholine, in a regioselective manner. When
the coupling partner is a vinyl iodide, such coupling-substi-
tution products 7 are also reactive 1,3-dienes, and thus can
undergo [4+2] cycloadditions with, e.g., added tert-butyl
acrylate to furnish the 1-morpholinoethyl-substituted tert-
butyl spiro[2.5]octenecarboxylate 10. Methylenespiro-
pentane (11), the strain energy (74.6 kcal/mol) of which is
only 2.8 kcal/mol lower than that of bicyclopropylidene
(1),[5] would be expected to undergo similarly rapid carbo-
palladations and subsequent rearrangements as 1 does. Be-
cause methylenespiropentane (11) is easily available on a
multigram scale by thermal rearrangement of 1,[4] we set
out to explore palladium-catalyzed cross couplings of 11
with aryl iodides and possible subsequent transformations
of the products.
Scheme 2. Heck coupling of methylenespiropentane (11) with iodo-
benzene (12).
ever, with 11 this reaction always produced inseparable mix-
tures that contained the Diels–Alder product 20 stemming
from 14 as well as the two regioisomeric monocycloadducts
21, 22 and several diastereomers of the regioisomeric trans-
missive cycloadducts 23, 24 arising from the cross-conju-
gated triene 13. In addition, the yields were low, and thus
the different products could not be fully characterized.
Results and Discussion
An initially performed coupling of methylenespiropen-
tane (11) with iodobenzene (12) under usual Heck condi-
tions [Pd(OAc)2, PPh3, Et3N] in DMF at 90 °C after 15 h
gave a mixture of the cross-conjugated triene ([3]dendra-
lene) 13 and (2-phenylallylidene)cyclopropane (14) (ratio
5.3:1.0) as an unstable oil in 38% yield. All attempted tun-
ing of the reaction conditions did not lead to increased
yields and/or selectivities. The formation of the two prod-
ucts 13 and 14 can be rationalized as arising from the cleav-
age of the two different proximal bonds [(a) and (b)] in the
cyclopropane ring adjacent to the iodopalladiummethyl
group in the intermediate 16 arising upon carbopalladation
of the double bond in 11 by the initially formed phenylpal-
ladium iodide. The σ-homoallylpalladium species 15
formed along path (a) undergoes another cyclopropylcarbi-
nyl-to-homoallyl rearrangement, and subsequent β-dehy-
dropalladation in the thus formed homoallylpalladium in-
termediate 18 leads to the conjugated triene 13. On the
other hand, the σ-homoallylpalladium complex 17 stem-
ming from cleavage of the proximal bond (b) in 16 un-
dergoes an immediate β-hydride elimination to produce the
diene 14 (Scheme 2).
Scheme 3. A domino Heck–Diels–Alder reaction involving methyl-
enespiropentane (11), iodobenzene (12) and dimethyl fumarate
(19). E = CO2Me.
This reaction essentially represents another novel access
In order to particularly trap the product stemming from
to [3]dendralenes and allylidenecyclopropanes, yet in low the major intermediate 18 of the carbopalladation/re-
yields. Because this is at least partly due to the susceptibility arrangement sequence more efficiently, the reaction of 11
of both compounds[6,7] to undergo polymerization, cycload- with 12 was carried out in the presence of tris(2-furyl)phos-
ducts or other consecutive products might be obtained in phane (TFP). The latter is known from previous work[3b,3f]
better yields if the compounds 13 and 14 were trapped di- to stimulate the formation of π-allylpalladium complexes,
rectly upon formation, as previously demonstrated for the which would be captured by an added nucleophile such as
regioisomer of 14 formed in the Heck cross coupling of bi- morpholine (25) to furnish more stable dienes 26, 28 and
cyclopropylidene (1) with iodobenzene.[3c] Thus, methylene- 31 instead of the cross-conjugated triene 13 and allylidene-
spiropentane (11) and iodobenzene (12) in the presence of cylopropane 14. In order to prevent Michael addition of
dimethyl fumarate (19) were treated with a palladium pre- the nucleophile onto the dienophile, the latter should not be
catalyst system [Pd(OAc)2, PPh3, Et4NCl, K2CO3, Me3CN] present in the reaction mixture from the beginning. Indeed,
that previously had given the best results in such domino treatment of 11, 12 and morpholine (25) in DMF with the
processes with bicyclopropylidene (1) (Scheme 3).[3b] How- palladium precatalyst established for such transformations
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Dihydrobenzoxepine and Dihydrobenzazepine Derivatives
FULL PAPER
[Pd(OAc)2, TFP, Et3N][3b] at 80 °C for 3 h, then addition of sequent [4+2] cycloaddition with added dimethyl fumarate
dimethyl fumarate (19) and subsequent heating of the mix- (19) to furnish dihydrobenzoxepine and dihydrobenzazep-
ture at 80 °C for 48 h, led to the three separable products[3f] ine derivatives 36a–g. The structure of 36c was rigorously
26, (5% yield), 27 (39%) and 28 (8%) (Scheme 4).
proved by X-ray diffractometry (Figure 1),[8] those of the
others were assigned on the basis of their analogous NMR
spectroscopic data.
Scheme 5. One-pot, two-step, three-component queuing cascade in-
volving methylenespiropentane (11). o-iodobenzyl alcohols and
-amines 33a–g as well as dimethyl fumarate (19). (A) Pd(OAc)2,
TFP, Et3N, DMF, 80 °C, 3 h. E = CO2Me. For details see Table 1.
Scheme 4. One-pot palladium-catalyzed reaction of methylenespi-
ropentane (11) with iodobenzene (12) and morpholine (25) with
subsequent trapping of a formed 1,3-diene by dimethyl fumarate
(19). (A) Pd(OAc)2, TFP, Et3N, DMF, 80 °C, 3 h. NuH = morph-
oline. E = CO2Me.
Table 1. One-pot, two-step, three component queuing cascade in-
volving methylenespiropentane (11), o-iodobenzyl alcohols and
-amines 33a–g as well as dimethyl fumarate (19) (see Scheme 5).
Aryl iodide
R1
R2
R3
X
Product Yield (%)[a] dr[b]
Apparently, the σ-allylpalladium intermediate 29 formed
by preferred regioselective readdition of the hydridopallad-
ium species onto the terminal vinyl group in 13, which is in
an equilibrium with the π-allylpalladium intermediate 30, is
predominantly attacked by morpholine (25) at the more
highly substituted site to give the diene 31 as the major
product, and the latter undergoes a cycloaddition with di-
methyl fumarate (19) to yield the cyclohexene derivative 27.
The minor conjugated diene 28, stemming from the same
π-allylpalladium intermediate 30, due to its 1,2,3-trisubsti-
tution obviously is less reactive, and the non-conjugated
diene 26, arising along path (b) with subsequent ring open-
33a
33b
33c
33d
33e
33f
33g
H
H
H
H
H
H
H
H
H
H
O
36a
22
22 + 5
18
1:1
1.6:1[c]
1.6:1
1:1
NBn 36b + 37b
O
O
NBn
O
O
OMe OMe
–OCH2O–
–OCH2O–
–O(CH2)2O–
H
36c
36d
36e
36f
36g
21
20
23
29
1.5:1
1.1:1
1.1:1
–OCH2O–
[a] Isolated yields. [b] Diastereomeric ratios were determined by
integration of relevant 1H NMR signals in the spectra of the crude
products. [c] Diastereomeric ratio of the benzazepine derivative 36b.
Only in one case (Entry 2, Table 1) was an isomeric dihy-
ing of the cyclopropylpalladium iodide moiety in 17 to a π- drobenzazepine derivative 37b with the methyl substituent
allylpalladium intermediate 32 and its trapping by 25, can- on the cyclohexene ring isolated in 5% yield as a single
not react with the dienophile 19.
diastereomer in addition to 22% of two diastereomeric
More interesting and relevant types of products were ob- products 36b. The isomer 37b must originate from the iso-
tained, when o-iodobenzyl alcohols and -amines 33a–g were meric diene 35b which must have been formed by nucleo-
employed in this two-step, one-pot reaction (Scheme 5, philic attack of the benzylamino group at the non-substi-
Table 1). The intramolecular nucleophilic trapping of the π- tuted terminus of the π-allylpalladium intermediate of type
allylpalladium intermediate of type 30 in this case occurred 30 [path (b) in Scheme 4]. In none of the other examples
almost exclusively at the more highly substituted end of the was any of this type of reaction mode detected as the spec-
allyl moiety to yield 5,6-benzo-3,4-dimethylenetetra- tra of the crude products did not indicate even traces of
hydrooxepines and -azepines. 34a–g which underwent sub- products of type 37b.
Eur. J. Org. Chem. 2007, 4081–4090
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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B. Yucel, N. Valentic´, M. Noltemeyer, A. de Meijere
FULL PAPER
Cs2CO3 in the presence of Et4NCl or nBu4NCl), other pal-
ladium derivatives [Pd(dba)2, Pd2(dba)3·CHCl3], other tem-
peratures (60, 100, 120 °C) and different reaction times (be-
tween 0.5 h and 2 d for the first step) furnished any better
yields than 22% of 36a.
An attempted extension of this method to the formation
of doubly annelated six- and eight-membered heterocycles
was unsuccessful, too. Thus, o-iodoaniline (38) and 2-iodo-
phenethyl alcohol (40) did not yield the desired products 39
and 41, respectively, at all. However, with o-iodobenzoic
acid (42) as a coupling partner with an internal nucleophilic
group, the benzo-annelated ε-caprolactone 43 was pro-
duced, albeit in only 8% yield (Scheme 6).
Figure 1. Structure of compound 36c (major diastereomer) in the
crystal.[8] C21H26O7 (390.42); crystal size 0.30ϫ0.30ϫ0.30 mm; tri-
clinic; a = 727.68(7), b = 1188.90(12), c = 1290.95(12) pm; α =
109.904(7), β = 93.316(8), γ = 106.331(8)°; V = 0.99306(17) nm3; Z
–3
Conclusions
¯
= 2; space group P1; T = 133(2) K; ρ = 1.306 Mg/m ; µ =
0.098 mm–1; Fo = 416; θ range for data collection: 1.70–24.79°; re-
flections collected: 11159; Rint = 3356 [0.0370]; data/restraints/para-
maters: 3356/0/253; Goof on F2 = 1.115; final R indices [IϾ2σ(I)]:
Despite providing generally low yields (18–29%), this
new sequential reaction is interesting as it produces valuable
R1 = 0.0505, wR2 = 0.1480; R indices (all data): R1 = 0.0672, wR2 doubly fused seven-membered heterocycles (36a–g and 37b,
= 0.1562; largest difference peak/hole: 0.839/–0.314 eÅ–3.
43), resembling the skeletons of several natural and non-
natural biologically active compounds.[10] Moreover, diox-
ole also often plays an important role in physiologically
Yields were moderate to poor, the best one (29%) was
achieved with (5-iodobenzo[1,3]dioxol-4-yl)methanol (33g).
Inspired by successful literature protocols for palladium-
active molecules.[11] Thus, incorporation of the essential fea-
tures of benzoxepines and benzazepines in combination
with dioxole subunits in 33d–g might provide enhanced bio-
logical activities.
catalyzed annelations involving an intramolecular trapping
of π-allylpalladium intermediates,[9] numerous reaction con-
ditions were tried out with the combination of methylene-
spiropentane (11), o-iodobenzyl alcohol (33a) and dimethyl
fumarate (19) in order to improve the yields of these new
Experimental Section
General Remarks: NMR spectra were recorded with Bruker AM
250 (250 MHz for 1H and 62.9 MHz for 13C NMR) and Varian
UNITY-300 (300 MHz for 1H and 75.5 MHz for 13C NMR) instru-
ments. Chemical shifts δ are given in ppm relative to residual peaks
of deuterated solvents and coupling constants, J, are reported in
Hz. The following abbreviations are used to describe spin multi-
plicities in 1H NMR spectra: s = singlet; bs = broad singlet; d =
doublet; t = triplet; q = quartet; dd = doublet of doublets; ddd =
doublet of doublets of doublets; dt = doublet of triplets; dq =
doublet of quartets; m = multiplets. Multiplicities in 13C NMR
spectra were determined by DEPT (Distortionless Enhancement
by Polarization Transfer): + = primary or tertiary (positive DEPT
signal), – = secondary (negative DEPT Signal), Cquat = quaternary
carbon atoms or APT (Attached Proton Test) measurements.
HMQC (Heteronuclear Multiple Quantum Coherence) spectra
were also measured in certain cases. IR spectra were recorded with
a Bruker IFS 66 spectrometer and measured as KBr pellets or as
oils between KBr plates. Low resolution mass spectra (EI at 70 eV
or DCI with NH3) were obtained with a Finnigan MAT 95 spec-
trometer. High-resolution mass spectra (HRMS) were obtained
with a Finnigan MAT 95 spectrometer by preselected-ion peak
matching at R ≈ 10000 to be within Ϯ2 ppm of the exact masses.
Elemental analyses were carried out by the “Mikroanalytisches La-
boratorium des Instituts für Organische und Biomolekulare
Chemie der Universität Göttingen”. Chromatographic separations
were performed with Merck Silica 60 (200–400 or 70–230 mesh).
The dimensions of the columns are given as “diameterϫheight of
the silica gel column”. TLC was performed with Macherey–Nagel
TLC Alugram® Sil G/UV 254 plates, detection was under UV light
at 254 nm and development with MOPS reagent (10% molybdo-
phosphoric acid in ethanol). All reagents were used as purchased
sequential reactions. However, none of the tested conditions
in terms of other bases (NaOAc, KOAc, K2CO3, Ag2CO3,
Scheme 6. Attempted syntheses of six- and eight-membered hetero-
cycles 39, 41 and formation of the benzo-annelated ε-caprolactone
derivative 43 from 11, o-iodobenzoic acid and 19.
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Dihydrobenzoxepine and Dihydrobenzazepine Derivatives
FULL PAPER
from commercial suppliers without further purification unless
otherwise indicated. Acetonitrile was dried with P2O5, DMF and
CH2Cl2 were distilled from CaH2. Diethyl ether and THF were
freshly distilled from sodium benzophenone ketyl. Solvents for col-
umn chromotography, ethyl acetate and light petroleum were dis-
tilled in a rotary evaporator. The following compounds were pre-
pared according to known literature methods: methylenespiropen-
ture, the reaction mixture was taken up in diethyl ether (50 mL).
The solution was washed with water (5ϫ25 mL) and dried
(MgSO4). After removal of the solvent in a rotary evaporator, the
residue was subjected to chromatography on silica gel (2ϫ20 cm,
hexane/diethyl ether, 3:1). The obtained 71 mg of a milky colorless
1
oil did not give interpretable H and 13C NMR spectra.
Sequential Reaction Involving Methylenespiropentane (11) Iodo-
benzene (12), Morpholine (25) and Dimethyl Fumarate (19): Palla-
dium acetate (22.4 mg, 100 µmol, 5 mol-%) and tris(2-furyl)phos-
phane (46.4 mg, 200 µmol, 10 mol-%), were suspended in anhy-
drous DMF (1 mL) in a screw-cap Pyrex bottle. Argon was bubbled
through the mixture for 5 min, then morpholine (25, 174 mg,
2.00 mmol), triethylamine (202 mg, 2.00 mmol), iodobenzene (12,
408 mg, 2.00 mmol) and methylenespiropentane (11) (320 mg,
4.00 mmol) were added. After having stirred the mixture at 80 °C
for 3 h, the bottle was cooled to ambient temperature, dimethyl
fumarate (19, 576 mg, 4.00 mmol) was added, and the mixture was
stirred at 80 °C for 48 h in a preheated oil bath. After cooling to
room temperature, the reaction mixture was taken up in diethyl
ether (20 mL). The solution was washed with water (2ϫ20 mL).
The aqueous phase was extracted with diethyl ether (2ϫ20 mL).
The combined organic phases were dried (MgSO4). After removal
of the solvent in a rotary evaporator, the residue was subjected to
column chromatography on silica gel (100 g, 3ϫ30 cm, light petro-
leum/ethyl acetate, 1:1) to yield 26 (25 mg, 5%, colorless oil), 27
(240 mg, 31%, colorless oil) and 28 (39 mg, 8%, colorless oil).
tane
(11),[4]
2,3-dihydrobenzo[1,4]dioxine-6-carbaldehyde,[12]
benzo[1,3]dioxole-4-carbaldehyde,[12] (3,4-dimethoxyphenyl)meth-
anol,[13] piperonylic alcohol,[14] (2,3-dihydrobenzo[1,4]dioxin-6-yl)-
methanol,[14] (benzo[1,3]dioxol-4-yl)methanol,[15] 2-iodo-4,5-di-
methoxybenzyl alcohol (33c),[16] (6-iodobenzo[1,3]dioxol-5-yl)-
methanol (33d),[17] (5-iodobenzo[1,3]dioxol-4-yl)methanol (33g),[15]
5-chloromethyl-6-iodobenzo[1,3]dioxole,[18] 2-iodobenzyl methane-
sulfonate,[19] (benzyl)(2-iodobenzyl)amine (33b),[20] 2-(2-iodo-
phenyl)ethanol (40).[21]
Heck Reaction of Methylenespiropentane (11) with Iodobenzene
(12). 3-Methylene-4-phenyl-1,4-pentadiene (13) and 1-Cyclopropyli-
dene-2-phenylpropene (14): Palladium acetate (22.4 mg, 100 µmol,
10 mol-%) and triphenylphosphane (78.6 mg, 300 µmol, 30 mol-%),
were suspended in anhydrous DMF (5 mL) in a screw-cap Pyrex
bottle. Argon was bubbled through the mixture for 5 min, and then
triethylamine (202 mg, 2.00 mmol), iodobenzene (12, 1.00 mmol,
204 mg) and methylenespiropentane (11) (160 mg, 2.00 mmol) were
added. After having stirred the mixture at 90 °C for 15 h, the bottle
was cooled to ambient temperature. The reaction mixture was
taken up in hexane (20 mL), the solution washed with water
(15 mL), and the aqueous phase was extracted with hexane
(5ϫ20 mL). The combined organic phases were dried (MgSO4).
After removal of the solvent in a rotary evaporator, the residue was
subjected to chromatography on silica gel (2ϫ45 cm, hexane) to
yield a mixture of 13 and 14 (61 mg, 38%, colorless oil, ratio 5.3:1
4-(2-Methylene-4-phenylpent-4-enyl)morpholine (26): Rf
= 0.60
(light petroleum/ethyl acetate, 3:1). IR (film): ν = 3081, 3023, 2958,
˜
2912, 2853, 2805, 1739, 1701, 1650, 1626, 1574, 1495, 1453, 1346,
1329, 1290, 1268, 1243, 1118, 1071, 1035, 1012, 965, 867, 779, 733,
1
705 cm–1. H NMR (250 MHz, CDCl3): δ = 2.35 (t, J = 4.3 Hz, 4
H, CH2NCH2), 2.86 (s, 2 H), 3.30 (s, 2 H), 3.70 (t, J = 4.7 Hz, 4
H, CH2OCH2), 4.94 (d, J = 15 Hz, 2 H, vinyl-H), 5.14 (s, 1 H,
vinyl-H), 5.45 (d, J = 1.6 Hz, 1 H, vinyl-H), 7.24–7.34 (m, 3 H,
Ph), 7.44–7.48 (m, 2 H, Ph) ppm. 13C NMR (50.3 MHz, CDCl3,
DEPT): δ = 40.01 (–, CH2), 53.56 (–, CH2NCH2), 63.94 (–, CH2),
67.13 (–, CH2OCH2), 114.55 (–, vinyl-C), 114.81 (–, vinyl-C),
126.12 (+, 2ϫPh), 127.31 (+, Ph), 128.08 (+, 2ϫPh), 140.98
(Cquat), 143.70 (Cquat), 145.65 (Cquat) ppm. MS (70 eV, EI): m/z (%)
= 243 (74) [M+], 228 (15), 213 (10), 198 (13), 184 (8), 143 (23), 138
(46), 115 (20), 100 (100), 95 (18), 77 (12), 56 (14).
1
according to GC of the crude product). 13: Rf = 0.5 (hexane). H
NMR (250 MHz, C6D6): δ = 7.07–7.41 (m, 5 H, Ph), 6.35 (dd, J =
10.5, 17.3 Hz, 1 H), 5.42 (d, J = 1.5 Hz, 1 H), 5.21 (d, J = 1.5 Hz,
1 H), 5.14 (d, J = 17.5 Hz, 1 H), 5.14 (dd, J = 1.0, 1.5 Hz, 2 H),
4.95 (d, J = 10.8 Hz, 1 H) ppm. 13C NMR (62.9 MHz, CDCl3,
DEPT): δ = 148.22 (Cquat), 147.97 (Cquat), 137.27 (+), 128.20 (+),
127.56 (+), 126.71 (+), 118.36 (–), 117.48 (–), 114.86 (–) ppm. 14:
1H NMR (250 MHz, C6D6): δ = 7.07–7.41 (m, 5 H, Ph), 6.71 (dd,
J = 2.0, 2.3 Hz, 1 H), 5.33 (s, 1 H), 5.23 (s, 1 H), 0.69–0.97 (m, 4
H) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 147.47 (Cquat),
141.17 (Cquat), 136.98 (Cquat), 127.95 (+), 127.73 (+), 127.14 (+),
119.20 (+), 114.63 (–), 4.77 (–), 1.32 (–) ppm. MS (70 eV, EI): m/z
(%) = 157 (29) [M+ + 1], 156 (91) [M+], 155 (87), 154 (14), 153
(25), 152 (13), 144 (9), 143 (18), 142 (18), 141 (100), 130 (12), 129
(53), 128 (71), 127 (20), 115 (74), 105 (12), 103 (16), 102 (15), 91
(33), 89 (8), 86 (10), 84 (15), 82 (8), 78 (12), 77 (35), 76 (10). C12H12
(156.2): calcd. 156.0939 (correct HRMS). The purified mixture of
isomers 13 and 14 was used for 1H, 13C NMR, and EI-MS and
HRMS measurements.
Dimethyl 4-[1-(Morpholin-4-yl)ethyl]-5-phenylcyclohex-4-ene-1,2-di-
carboxylate (27): Rf = 0.61 (light petroleum/ethyl acetate, 1:1). IR
(film): ν = 3054, 3020, 2952, 2849, 2805, 2688, 1734, 1600, 1492,
˜
1437, 1379, 1346, 1331, 1297, 1259, 1221, 1162, 1117, 1070, 1004,
1
911, 864, 798, 771, 744, 704 cm–1. H NMR (300 MHz, CDCl3): δ
= 0.97 (d, J = 6.8 Hz, 3 H, CH3), 2.10–2.30 (m, 4 H, CH2NCH2),
2.34–2.40 (m, 1 H, 3-H or 6-H), 2.49–2.58 (m, 1 H, 3-H or 6-H),
2.67–2.91 (AB system: δA = 2.89, δB = 2.70, JAB = 13.0 Hz, 2 H,
3-H or 6-H), 2.96–3.12 (m, 3 H, 3ϫCH), 3.56–3.61 (m, 4 H,
CH2OCH2), 3.63 (s, 3 H, OCH3), 3.69 (s, 3 H, OCH3), 6.95–6.99
(m, 2 H, Ph), 7.17–7.29 (m, 3 H, Ph) ppm. 13C NMR (75.5 MHz,
CDCl3, DEPT): δ = 15.66 (+, CH3), 31.01 (+, CH), 35.80 (–, C-3
or C-6), 36.75 (+, CH), 46.08 (+, CH), 51.65 (+, OCH3), 51.79
(+, OCH3), 53.22 (–, CH2NCH2), 57.89 (–, C-3 or C-6), 60.82 (–,
CH2OCH2), 126.61 (+, Ph), 128.00 (+, 2ϫPh), 128.13 (+, 2ϫPh),
133.69 (Cquat), 133.41 (Cquat), 141.70 (Cquat), 174.06 (Cquat, C=O),
175.86 (Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 387 (100)
[M+], 356 (8), 328 (10), 268 (8), 241 (14), 181 (40), 100 (12).
C22H29NO5 (387.5): calcd. C 68.20, H 7.54; found C 67.97, H 7.69.
Sequential Heck/Diels–Alder Reaction Involving Methylenespiropen-
tane (11), Iodobenzene (12) and Dimethyl Fumarate (19): A screw-
cap Pyrex bottle was charged with anhydrous acetonitrile (1 mL),
K2CO3 (276 mg, 2.00 mmol) and Et4NCl (166 mg, 1.00 mmol). Ar-
gon was bubbled through the mixture for 5 min, Pd(OAc)2
(11.2 mg, 50 µmol, 5 mol-%), and triphenylphosphane (39.3 mg,
150 µmol, 15 mol-%) were added, and the mixture was stirred once
more for an additional 5 min with argon bubbling through, before
iodobenzene (12, 204 mg, 1.00 mmol), methylenespiropentane (11,
160 mg, 2.00 mmol) and dimethyl fumarate (19, 288 mg,
2.00 mmol) were added. The bottle was tightly closed, and the mix-
ture was stirred at 80 °C for 48 h. After cooling to room tempera-
4-[2-(1-Phenylvinyl)but-2-enyl]morpholine (28): Rf = 0.71 (light pe-
troleum/ethyl acetate, 1:1). IR (film): ν = 3056, 3023, 2954, 2850,
˜
Eur. J. Org. Chem. 2007, 4081–4090
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4085

B. Yucel, N. Valentic´, M. Noltemeyer, A. de Meijere
FULL PAPER
2804, 2759, 1737, 1496, 1458, 1437, 1411, 1381, 1349, 1329, 1298,
1206, 1223, 1197, 1162, 1117, 1066, 1004, 982, 915, 864, 801, 771,
742, 706 cm–1. 1H NMR (250 MHz, CDCl3): δ = 1.68 (d, J =
(Cquat, C=O), 175.11 (Cquat, C=O) ppm. MS (70 eV, EI): m/z (%)
= 330 (30) [M+], 315 (11) [M+ – CH3], 299 (17), 270 (22), 252 (70),
227 (38), 211 (18), 195 (22), 193 (66), 167 (100), 165 (34), 105 (34),
6.8 Hz, 3 H, CH3), 2.38 (t, J = 4.6 Hz, 4 H, CH2NCH2), 2.91 (s, 2 84 (85), 79 (38), 53 (24), 43 (38). C19H22O5 (330.4): calcd. C 69.07,
1
H), 3.65 (t, J = 4.7 Hz, 4 H, CH2OCH2), 5.05 (d, J = 1.6 Hz, 1 H,
vinyl-H), 5.58 (d, J = 1.6 Hz, 1 H, vinyl-H), 5.78 (q, J = 6.8 Hz, 1
H, vinyl-H), 7.17–7.39 (m, 5 H, Ph) ppm. 13C NMR (50.3 MHz,
H 6.71; found C 68.77, H 6.56. H and 13C NMR chemical shifts
are given in a single series for both diastereomers, because the
peaks in the H and 13C NMR spectra could not be fully assigned
1
CDCl3, DEPT): δ = 14.56 (+, CH3), 53.39 (–, CH2NCH2), 64.47 to individual diastereomers. IR, EI-MS measurements and elemen-
(–, CH2), 66.99 (–, CH2OCH2), 114.78 (–, vinyl-C), 125.83 (+, vi-
nyl-C), 126.41 (+, 2ϫPh), 127.36 (+, Ph), 128.20 (+, 2ϫPh),
137.59 (Cquat), 139.79 (Cquat), 146.76 (Cquat) ppm. MS (70 eV, EI):
m/z (%) = 243 (48) [M+], 228 (8), 198 (8), 143 (8), 128 (9), 115 (8),
100 (100), 56 (10).
tal analysis were carried out with the mixture of diastereomers.
Dimethyl 6-Benzyl-5-methyl-2,3,4,5,6,7-hexahydro-1H-dibenzo[c,e]-
azepine-2,3-dicarboxylate (36b) and Dimethyl 6-Benzyl-4-methyl-
2,3,4,5,6,7-hexahydro-1H-dibenzo[c,e]azepine-2,3-dicarboxylate
(37b): According to the GP, Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-
furyl)phosphane (46.4 mg, 200 µmol), Et3N (202 mg, 2.00 mmol),
(benzyl)(2-iodobenzyl)amine (33b, 646 mg, 2.00 mmol) and methyl-
enespiropentane (11, 320 mg, 4.00 mmol) were stirred in anhydrous
DMF (1 mL) at 80 °C for 3 h. After cooling the mixture to room
temperature, dimethyl fumarate (19, 576 mg, 4.00 mmol) was
added, and the mixture was stirred at 80 °C for 48 h. Workup and
column chromatography on silica gel (100 g, 3ϫ30 cm, light petro-
leum/ethyl acetate, 1:1) yielded 36b (186 mg, 22%, colorless oil) as
a mixture of two diastereomers (ratio 1.6:1 according to NMR)
and 37b (43 mg, 5% colorless oil).
General Procedure for the One-Pot, Two-Step Queuing Cascade In-
volving Methylenespiropentane (11), Functionalized Iodoarenes 33a–
g, 42 and Dimethyl Fumarate (19) (GP): Palladium acetate
(22.4 mg, 100 µmol, 5 mol-%) and tris(2-furyl)phosphane (46.4 mg,
200 µmol, 10 mol-%), were suspended in anhydrous DMF (1 mL)
in a screw-cap Pyrex bottle. Argon was bubbled through the mix-
ture for 5 min, then triethylamine (202 mg, 2.00 mmol), the respec-
tive iodoarene (33a–g or 42, 2.00 mmol) and methylenespiropen-
tane (11) (320 mg, 4.00 mmol) were added. After having stirred the
mixture at the stated temperature for the given time, the bottle was
cooled to ambient temperature, dimethyl fumarate (19, 576 mg,
4.00 mmol) was added, and then the mixture was stirred at the
given temperature in a preheated oil bath for an additional time as
stated. After cooling to room temperature, the reaction mixture
was taken up in diethyl ether (20 mL). The solution was washed
with water (2ϫ20 mL). The aqueous phase was extracted with di-
ethyl ether (2ϫ20 mL). The combined organic phases were dried
(MgSO4). After removal of the solvent in a rotary evaporator, the
residue was subjected to chromatography on silica gel.
Major Diastereomer 36b: Rf = 0.54 (light petroleum/ethyl acetate,
1:1). IR (film): ν = 3064, 3037, 2991, 2895, 2798, 1734, 1726, 1455,
˜
1437, 1373, 1325, 1300, 1242, 1202, 1175, 1154, 1130, 1088, 1067,
1029, 1007, 911, 877, 836, 807, 755, 734, 701 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 1.13 (d, J = 6.8 Hz, 3 H, CH3), 2.33–2.45
(m, 2 H, 1-H or 4-H), 2.73–2.80 (m, 1 H, 1-H or 4-H), 2.88–3.02
[m, 4 H, 1-H or 4-H, 2-H, 3-H, 5-H], 3.24–3.38 (AB system: δA
=
3.35, δB = 3.27, JAB = 12.2 Hz, 2 H, Bn), 3.58 (s, 2 H, 7-H), 3.71
(s, 3 H, OCH3), 3.75 (s, 3 H, OCH3), 7.14–7.41 (m, 9 H, Ar, Ph)
ppm. 13C NMR (50.3 MHz, CDCl3, DEPT): δ = 16.26 (+, CH3),
30.79 (–, C-1 or C-4), 31.63 (–, C-1 or C-4), 41.81 (+, C-2 or C-3),
41.89 (+, C-2 or C-3), 52.03 (+, OCH3), 52.06 (+, OCH3), 54.81
(–, Bn), 55.63 (–, C-7), 56.72 (+, C-5), 125.50 (+, Ar), 126.88 (+,
Ar), 127.10 (+, Ar), 127.37 (+, Ar), 128.36 (+, 2ϫPh), 128.98 (+,
2ϫPh), 129.73 (+, Ph), 133.26 (Cquat), 133.54 (Cquat), 135.54
(Cquat), 140.01 (Cquat), 141.04 (Cquat), 175.04 (Cquat, C=O), 175.40
(Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 419 (8) [M+], 404
(100) [M+ – CH3], 388 (5), 91 (40). C26H29NO4 (419.5): calcd. C
74.44, H 6.97; found C 74.21, H 6.72.
Dimethyl 5-Methyl-1,2,3,4,5,7-hexahydrodibenzo[c,e]oxepine-2,3-di-
carboxylate (36a): According to the GP, Pd(OAc)2 (22.4 mg,
100 µmol), tris(2-furyl)phosphane (46.4 mg, 200 µmol), Et3N
(202 mg, 2.00 mmol), 2-iodobenzyl alcohol (33a, 468 mg,
2.00 mmol) and methylenespiropentane (11, 320 mg, 4.00 mmol)
were stirred in anhydrous DMF (1 mL) at 80 °C for 3 h. After cool-
ing the mixture to room temperature, dimethyl fumarate (19,
576 mg, 4.00 mmol) was added, and the mixture stirred at 80 °C
for 48 h. After workup and column chromatography on silica gel
(100 g, 3ϫ30 cm, light petroleum/ethyl acetate, 3:1), 36a (145 mg,
22%, colorless solid) was obtained as a mixture of two dia-
stereomers (ratio 1:1 according to NMR). Rf = 0.32 (light petro-
Minor Diastereomer 36b: Rf = 0.49 (light petroleum/ethyl acetate,
1
1:1). H NMR (300 MHz, CDCl3): δ = 1.00 (d, J = 6.7 Hz, 3 H,
leum/ethyl acetate, 3:1). IR (film): ν = 2953, 2857, 1735, 1487, 1437,
˜
CH3), 2.45–2.75 (m, 2 H, 1-H + 4-H), 3.05–3.16 (m, 3 H, 2-H, 3-H,
5-H), 3.20–3.37 (AB system: δA = 3.35, δB = 3.22, JAB = 11.1 Hz, 2
H, Bn), 3.51–3.86 (AB system: δA = 3.83, δB = 3.54, JAB = 13.1 Hz,
2 H, 7-H), 3.72 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3), 7.17–7.41 (m,
9 H, Ar, Ph) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 17.92
(+, CH3), 30.57 (–, C-1 or C-4), 31.13 (–, C-1 or C-4), 41.28 (+, C-
2 or C-3), 41.32 (+, C-2 or C-3), 52.07 (+, 2ϫOCH3), 55.95 (–,
Bn), 57.10 (+, C-5), 57.45 (–, C-7), 125.05 (+, Ar), 126.89 (+, Ar),
127.03 (+, Ar), 127.39 (+, Ar), 128.30 (+, 2ϫPh), 128.87 (+,
2ϫPh), 129.42 (+, Ph), 131.45 (Cquat), 132.95 (Cquat), 136.00
(Cquat), 139.83 (Cquat), 142.01 (Cquat), 174.79 (Cquat, C=O), 174.86
(Cquat, C=O) ppm.
1
1381, 1333, 1246, 1198, 1176, 1083, 1036, 914, 843, 755 cm–1. H
NMR (300 MHz, CDCl3): δ = 1.16 (d, J = 6.9 Hz, 3 H, CH3), 1.17
(d, J = 6.1 Hz, 3 H, CH3), 2.19–2.49 (m, 2 H, 1-H or 4-H), 2.54–
2.65 (m, 3 H, 1-H or 4-H), 2.79–3.13 [m, 7 H, 2ϫ(2-H + 3-H), 1-
H or 4-H], 3.68 (s, 9 H, 3ϫOCH3), 3.71 (s, 3 H, OCH3), 3.76–3.89
(m, 2 H, 2ϫ5-H), 4.17 (d, J = 12.5 Hz, 1 H, 7-H), 4.21 (d, J =
12.5 Hz, 1 H, 7-H), 4.37 (d, J = 3.1 Hz, 1 H, 7-H), 4.41 (d, J =
3.1 Hz, 1 H, 7-H), 7.19–7.37 (m, 8 H, Ar) ppm. 13C NMR
(62.9 MHz, CDCl3, DEPT): δ = 16.22 (+, CH3), 16.63 (+, CH3),
26.99 (–, C-1 or C-4), 28.07 (–, C-1 or C-4), 30.39 (–, C-1 or C-4),
31.20 (–, C-1 or C-4), 40.92 (+, C-2 or C-3), 40.93 (+, C-2 or C-
3), 41.55 (+, C-2 or C-3), 41.78 (+, C-2 or C-3), 52.00 (+,
2ϫOCH3), 52.04 (+, 2ϫOCH3), 67.72 (–, C-7), 67.77 (–, C-7),
69.51 (+, C-5), 70.17 (+, C-5), 125.19 (+, Ar), 125.55 (+, Ar),
127.59 (+, Ar), 127.89 (+, Ar), 128.23 (+, Ar), 128.25 (+, Ar),
128.88 (+, Ar), 129.27 (+, Ar), 132.38 (Cquat), 132.84 (Cquat), 133.60
IR, 1H and 13C NMR and EI-MS measurements and elemental
analysis were carried out with the mixture of diastereomers.
37b: IR (film): ν = 3061, 3025, 2950, 2799, 1734, 1495, 1436, 1362,
˜
1265, 1198, 1174, 1121, 1063, 1027, 912, 848, 755, 736, 700, 668
(Cquat), 134.26 (Cquat), 136.04 (Cquat), 136.45 (Cquat), 140.80 (Cquat), cm–1. H NMR (300 MHz, CDCl3): δ = 1.30 (d, J = 7.1 Hz, 3 H,
1
141.94 (Cquat), 174.49 (Cquat, C=O), 174.53 (Cquat, C=O), 174.77 CH3), 2.33 (d, J = 11.0 Hz, 1 H, 5-H), 2.40–2.50 (m, 1 H, 1-H),
4086
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 4081–4090

Dihydrobenzoxepine and Dihydrobenzazepine Derivatives
FULL PAPER
2.59–2.67 (m, 2 H, 2-H or 3-H and 4-H), 2.80 (d, J = 11.1 Hz, 1
H, 5-H), 2.93 (dd, J = 4.8, 17.0 Hz, 1 H, 1-H), 3.03–3.12 (m, 1 H,
2-H or 3-H), 3.35–3.49 (m, 2 H, Bn or 7-H), 3.69 (s, 3 H, OCH3),
3.73 (s, 3 H, OCH3), 3.63–3.77 (m, 2 H, Bn or 7-H), 7.19–7.36 (m,
9 H, Ar, Ph) ppm. 13C NMR (50.3 MHz, CDCl3, DEPT): δ = 19.22
(+, CH3), 30.80 (–, C-1), 38.21 (+, C-2 or C-3), 42.54 (+, C-2 or
C-3), 50.40 (+, C-4), 51.90 (+, OCH3), 51.97 (+, OCH3), 52.90 (–,
C-5), 55.50 (–, Bn or C-7), 59.71 (–, Bn or C-7), 125.70 (+, Ar),
126.94 (+, 2ϫAr), 127.30 (+, Ar), 128.24 (+, 2ϫPh), 128.81 (+,
ture, dimethyl fumarate (19, 576 mg, 4.00 mmol) was added, and
the mixture stirred at 80 °C for 48 h. After workup and column
chromatography on silica gel (100 g, 3ϫ30 cm, light petroleum/
ethyl acetate, 3:1), 36d (155 mg, 21%, colorless solid) was obtained
as a mixture of two diastereomers (ratio 1.6:1 according to NMR).
R = 0.24 (light petroleum/ethyl acetate, 3:1). IR (KBr): ν = 2977,
˜
f
2953, 2907, 2857, 1724, 1504, 1484, 1436, 1381, 1324, 1267, 1242,
1195, 1155, 1077, 1039, 1014, 976, 934, 871, 820, 793, 739 cm–1. 1H
NMR (250 MHz, CDCl3): δ = 1.17 (d, J = 6.6 Hz, 3 H, CH3), 1.18
2ϫPh), 129.92 (+, Ph), 132.99 (Cquat), 134.94 (Cquat), 135.94 (d, J = 7.0 Hz, 3 H, CH3), 2.17–2.41 (m, 2 H, 1-H or 4-H), 2.52–
(Cquat), 139.31 (Cquat), 141.00 (Cquat), 174.53 (Cquat, C=O), 175.34 2.64 (m, 3 H, 1-H or 4-H), 2.74–2.89 (m, 2 H, 1-H or 4-H), 2.91–
(Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 419 (42) [M+], 388 3.05 [m, 3 H, 2ϫ(2-H or 3-H), 1-H or 4-H], 2.08–3.13 [m, 2 H,
(8), 327 (16), 318 (12), 268 (14), 220 (20), 192 (23), 182 (34), 165
(32), 150 (22), 105 (83), 91 (100), 84 (78), 59 (54), 45 (35). HRMS-
ESI for C26H29NO4 (419.53): calcd. for [M + H]+ 420.21693, found
420.21705.
2ϫ(2-H or 3-H)], 3.72 (s, 9 H, 3ϫOCH3), 3.74 (s, 3 H, OCH3),
3.77–3.90 (m, 2 H, 2ϫ5-H), 4.10 (t, J = 10.5 Hz, 2 H, 7-H), 4.27
(d, J = 3.0 Hz, 1 H, 7-H), 4.32 (d, J = 3.3 Hz, 1 H, 7-H), 5.96 (s,
2 H, 10-H), 5.97 (s, 2 H, 10-H), 6.76 (s, 1 H, Ar), 6.78 (s, 1 H, Ar),
6.80 (s, 1 H, Ar), 6.81 (s, 1 H, Ar) ppm. 13C NMR (62.9 MHz,
CDCl3, DEPT): δ = 16.47 (+, CH3), 17.34 (+, CH3), 26.73 (–, C-1
or C-4), 27.96 (–, C-1 or C-4), 30.33 (–, C-1 or C-4), 31.30 (–, C-1
or C-4), 40.84 [+, 2ϫC-2 or C-3], 41.51 (+, C-2 or C-3), 41.74 (+,
C-2 or C-3), 52.04 (+, 4ϫOCH3), 67.24 (–, C-7), 67.36 (–, C-7),
69.28 (+, C-5), 69.74 (+, C-5), 101.16 (–, C-10), 101.23 (–, C-10),
105.48 (+, Ar), 105.87 (+, Ar), 109.09 (+, Ar), 109.45 (+, Ar),
130.03 (Cquat), 130.57 (Cquat), 131.67 (Cquat), 132.23 (Cquat), 133.60
(Cquat), 134.17 (Cquat), 134.77 (Cquat), 136.02 (Cquat), 146.71 (Cquat),
146.97 (Cquat), 147.64 (Cquat), 147.73 (Cquat), 174.42 (Cquat, C=O),
174.50 (Cquat, C=O), 174.75 (Cquat, C=O), 175.10 (Cquat, C=O)
Dimethyl 9,10-Dimethoxy-5-methyl-1,2,3,4,5,7-hexahydrodibenzo-
[c,e]oxepine-2,3-dicarboxylate (36c): According to the GP, Pd-
(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)phosphane (46.4 mg,
200 µmol), Et3N (202 mg, 2.00 mmol), 2-iodo-4,5-dimethoxybenzyl
alcohol (33c, 588 mg, 2.00 mmol) and methylenespiropentane (11,
320 mg, 4.00 mmol) were stirred in anhydrous DMF (1 mL) at
80 °C for 3 h. After cooling the mixture to room temperature, di-
methyl fumarate (19, 576 mg, 4.00 mmol) was added, and the mix-
ture stirred at 80 °C for 48 h. After workup and column chromatog-
raphy on silica gel (100 g, 3ϫ30 cm, light petroleum/ethyl acetate,
3:1), 33c (142 mg, 18%, colorless solid) was obtained as a mixture
of two diastereomers (ratio 1.6:1 according to NMR). Rf = 0.51
ppm. MS (70 eV, EI): m/z (%) = 374 (64) [M+], 359 (34) [M+
–
CH3], 343 (16), 314 (21), 296 (34), 271 (100), 239 (20), 237 (28),
211 (35), 181 (64), 153 (27), 128 (12), 115 (11), 57 (26), 43 (73).
C20H22O7 (374.4): calcd. C 64.16, H 5.92; found C 64.39, H 5.80.
1H and 13C NMR chemical shifts are given in a single series for
both diastereomers, because the peaks in the 1H and 13C NMR
spectra could not be fully assigned to the individual diastereomers.
IR, EI-MS measurements and elemental analysis were carried out
with the mixture of diastereomers.
(light petroleum/ethyl acetate, 3:1). IR (KBr): ν = 2952, 2854, 1736,
˜
1605, 1573, 1515, 1437, 1375, 1248, 1199, 1174, 1131, 1081, 1023,
1
863, 803, 768 cm–1. H NMR (300 MHz, CDCl3): δ = 1.15 (d, J =
6.9 Hz, 3 H, CH3), 1.16 (d, J = 6.6 Hz, 3 H, CH3), 2.15–2.41 (m,
2 H, 1-H or 4-H), 2.52–2.61 (m, 3 H, 1-H or 4-H), 2.71–3.08 [m, 7
H, 2ϫ(2-H + 3-H), 1-H or 4-H], 3.67 (s, 3 H, OCH3), 3.68 (s, 6
H, 2ϫOCH3), 3.69 (s, 3 H, OCH3), 3.73–3.82 (m, 2 H, 2ϫ5-H),
3.84 (s, 6 H, 2ϫOCH3), 3.85 (s, 3 H, OCH3), 3.86 (s, 3 H, OCH3),
4.09–4.22 (m, 4 H, 2ϫ7-H), 6.73 (s, 1 H, Ar), 6.78 (s, 2 H, Ar),
6.80 (s, 1 H, Ar) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ =
16.52 (+, CH3), 17.46 (+, CH3), 26.91 (–, C-1 or C-4), 28.01 (–, C-
1 or C-4), 30.45 (–, C-1 or C-4), 31.31 (–, C-1 or C-4), 40.91 (+,
C-2 or C-3), 40.96 (+, C-2 or C-3), 41.55 (+, C-2 or C-3), 41.82 (+,
C-2 or C-3), 52.00 (+, 4ϫOCH3), 55.78 (+, 2ϫOCH3), 55.84 (+,
2ϫOCH3), 67.31 (–, C-7), 67.40 (–, C-7), 69.39 (+, C-5), 69.95 (+,
C-5), 108.07 (+, Ar), 108.48 (+, Ar), 111.65 (+, Ar), 111.99 (+, Ar),
(Benzyl)(6-iodobenzo[1,3]dioxol-5-ylmethyl)amine (33e): A solution
of 5-(chloromethyl)-6-iodobenzo[1,3]dioxole (0.785 g, 2.65 mmol),
benzylamine (1.16 mL, 10.6 mmol) and K2CO3 (1.82 g, 13.2 mmol)
in DME (15 mL) was heated under reflux. The progress of the reac-
tion was monitored by TLC, and the heating was terminated, when
the starting dioxole had disappeared (ca. 4 h). The reaction mixture
was filtered at ambient temperature and concentrated in a rotary
evaporator. The residue was subjected to column chromatography
128.84 (Cquat), 129.32 (Cquat), 131.56 (Cquat), 132.08 (Cquat), 133.19 on silica gel (100 g, 3ϫ30 cm, light petroleum/ethyl acetate, 3:1) to
(Cquat), 133.61 (Cquat), 134.21 (Cquat), 134.49 (Cquat), 148.07 (Cquat), yield 33e (812 mg, 84%, yellowish oil). IR (film): ν = 3315, 3084,
˜
148.30 (Cquat), 148.72 (2ϫCquat), 174.47 (Cquat, C=O), 174.59
(Cquat, C=O), 174.77 (Cquat, C=O), 175.11 (Cquat, C=O) ppm. MS
(70 eV, EI): m/z (%) = 390 (100) [M+], 375 (47) [M+ – CH3], 359
(22), 312 (16), 287 (55), 253 (9), 227 (12), 59 (10). C21H26O7 (390.4):
3061, 3025, 2893, 2829, 1500, 1476, 1453, 1406, 1385, 1363, 1230,
1113, 1039, 933, 864, 829, 738, 698 cm–1. 1H NMR (250 MHz,
CDCl3): δ = 1.78 (br. s, 1 H, NH), 3.75 (s, CH2), 3.80 (s, CH2),
5.96 (s, OCH2O), 6.95 (s, 1 H, Ar), 7.24–7.36 (m, 6 H, Ar, Ph) ppm.
13C NMR (62.9 MHz, CDCl3, DEPT): δ = 52.93 (–, CH2), 57.36
(–, CH2), 87.09 (Cquat), 101.51 (–, OCH2O), 109.86 (+, Ar), 118.52
(+, Ar), 126. 95 (+, Ph), 128. 14 (+, 2ϫPh), 128. 34 (+, 2ϫPh),
135.62 (Cquat), 139.99 (Cquat), 147.37 (Cquat), 148.33 (Cquat) ppm.
MS (70 eV, EI): m/z (%) = 367 (26) [M+], 276 (14), 261 (42), 240
(41), 135 (74), 106 (18), 91 (100), 76 (14). C15H14INO2 (367.19):
calcd. C 49.07, H 3.84; found C 48.95, H 3.83.
1
calcd. C 64.60, H 6.71; found C 64.35, H 6.41. H and 13C NMR
chemical shifts are given in a single series for both diastereomers,
because the peaks in the 1H and 13C NMR spectra could not be
fully assigned to the individual diastereomers. IR, EI-MS measure-
ments and elemental analysis were carried out with the mixture of
diastereomers.
Dimethyl 5-Methyl-2,3,5,7-tetrahydro-1H,4H-6,9,11-trioxabenzo-
[3,4]cyclohepta[1,2-f]indene-2,3-dicarboxylate (36d): According to
the GP, Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)phosphane
(46.4 mg, 200 µmol), Et3N (202 mg, 2.00 mmol), (6-iodobenzo[1,3]-
dioxol-5-yl)methanol (33d, 556 mg, 2.00 mmol) and methylenespi-
ropentane (11, 320 mg, 4.00 mmol) were stirred in anhydrous DMF
(1 mL) at 80 °C for 3 h. After cooling the mixture to room tempera-
Dimethyl 6-Benzyl-5-methyl-2,3,4,5,6,7-hexahydro-1H-9,11-dioxa-
6-azabenzo[3,4]cyclohepta[1,2-f]indene-2,3-dicarboxylate (36e): Ac-
cording to the GP, Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)-
phosphane (46.4 mg, 200 µmol), Et3N (202 mg, 2.00 mmol), (ben-
zyl)(6-iodobenzo[1,3]dioxol-5-ylmethyl)amine
(33e,
734 mg,
2.00 mmol) and methylenespiropentane (11, 320 mg, 4.00 mmol)
Eur. J. Org. Chem. 2007, 4081–4090
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4087

B. Yucel, N. Valentic´, M. Noltemeyer, A. de Meijere
FULL PAPER
were stirred in anhydrous DMF (1 mL) at 80 °C for 3 h. After cool-
ing the mixture to room temperature, dimethyl fumarate (19,
576 mg, 4.00 mmol) was added, and the mixture stirred at 80 °C
for 48 h. After workup and column chromatography on silica gel
(100 g, 3ϫ30 cm, light petroleum/ethyl acetate, 1:1) 36e (185 mg,
20%, colorless solid) was obtained as a mixture of two dia-
stereomers (ratio 1.5:1 according to NMR). Rf = 0.52 (light petro-
2.00 mmol) and methylenespiropentane (11, 320 mg, 4.00 mmol)
were stirred in anhydrous DMF (1 mL) at 80 °C for 3 h. After cool-
ing the mixture to room temperature, dimethyl fumarate (19,
576 mg, 4.00 mmol) was added, and the mixture stirred at 80 °C
for 48 h. After workup and column chromatography on silica gel
(100 g, 3ϫ30 cm, light petroleum/ethyl acetate, 3:1), 36f (178 mg,
23%, colorless solid) was obtained as a mixture of two dia-
leum/ethyl acetate, 1:1). IR (KBr): ν = 2948, 2891, 2789, 1732, stereomers (ratio 1.1:1 according to NMR). Rf = 0.55 (light petro-
˜
1502, 1483, 1457, 1437, 1369, 1325, 1261, 1239, 1177, 1129, 1035,
leum/ethyl acetate, 3:1). IR (KBr): ν = 2952, 2849, 1728, 1573,
˜
1
930, 884, 826, 749, 730, 703 cm–1. H NMR (300 MHz, CDCl3): δ
1500, 1437, 1370, 1309, 1248, 1197, 1177, 1156, 1067, 1041, 1002,
= 1.01 (d, J = 6.8 Hz, 3 H, CH3), 1.13 (d, J = 6.8 Hz, 3 H, CH3), 978, 948, 926, 901, 887, 847, 783, 749 cm–1. H NMR (300 MHz,
1
2.27–2.73 [m, 8 H, 2ϫ(1-H + 4-H)], 2.79–3.00 (m, 3 H, 2-H, 3-H,
CDCl3): δ = 1.20 (d, J = 6.6 Hz, 3 H, CH3), 1.21 (d, J = 6.6 Hz, 3
5-H), 3.06–3.23 [m, 7 H, (2-H + 3-H), (Bn or 7-H), 5-H], 2.48–3.62 H, CH3), 2.18–2.42 (m, 2 H, 1-H or 4-H), 2.54–2.56 (m, 2 H, 1-H
(m, 3 H, Bn or 7-H), 3.70 (s, 3 H, OCH3), 3.71 (s, 3 H, OCH3), or 4-H), 2.63–2.65 (m, 1 H, 1-H or 4-H), 2.74–2.87 (m, 2 H, 1-H
3.72 (s, 3 H, OCH3), 3.74 (s, 3 H, OCH3), 3.70–3.74 (m, 1 H, Bn
or 7-H)*, 5.91–5.94 (m, 4 H, 2ϫ10-H), 6.64 (s, 1 H, Ar), 6.65 (s,
1 H, Ar), 6.73 (s, 1 H, Ar), 6.78 (s, 1 H, Ar), 7.24–7.29 (m, 10 H,
Ph) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 16.12 (+,
CH3), 17.62 (+, CH3), 30.50 (–, C-1 or C-4), 30.61 (–, C-1 or C-4),
30.79 (–, C-1 or C-4), 31.82 (–, C-1 or C-4), 41.18 (+, C-2 or C-3),
or 4-H), 2.91–3.05 [m, 3 H, 2ϫ(2-H or 3-H), 1-H or 4-H], 3.08–
3.13 [m, 2 H, 2ϫ(2-H or 3-H)], 3.73 (s, 9 H, 3ϫOCH3), 3.75 (s, 3
H, OCH3), 3.83–3.98 (m, 2 H, 2ϫ5-H), 4.11–4.34 (m, 4 H, 2ϫ7-
H), 4.26 [s, 8 H, 2ϫ(10-H + 11-H)], 6.80 (s, 1 H, Ar), 6.82 (s, 1 H,
Ar), 6.84 (s, 2 H, Ar) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT):
δ = 16.59 (+, CH3), 17.58 (+, CH3), 26.93 (–, C-1 or C-4), 28.04
41.21 (+, C-2 or C-3), 41.80 (+, C-2 or C-3), 41.86 (+, C-2 or C- (–, C-1 or C-4), 30.38 (–, C-1 or C-4), 31.33 (–, C-1 or C-4), 40.82
3), 52.03 (+, 4ϫOCH3), 54.31 (–, Bn or C-7), 55.38 (–, Bn or C-
7), 55.46 (–, Bn or C-7), 56.88 (+, C-5), 57.23 (+, C-5), 57.23 (–,
Bn or C-7), 100.94 (–, C-10), 100.99 (–, C-10), 105.55 (+, Ar),
105.97 (+, Ar), 109.66 (+, Ar), 109.90 (+, Ar), 126.85 (+, 2ϫPh),
128.27 (+, 2ϫPh), 128.33 (+, 2ϫPh), 128.79 (+, 2ϫPh), 128.87
[+, 2ϫC-2 or C-3], 41.53 (+, C-2 or C-3), 41.76 (+, C-2 or C-3),
51.95 (+, OCH3), 51.99 (+, 3ϫOCH3), 64.28 [–, 2ϫ(C-10 + C-
11)], 67.07 (–, 2ϫC-7), 69.45 (+, C-5), 70.31 (+, C-5), 114.09 (+,
Ar), 114.46 (+, Ar), 117.45 (+, Ar), 117.77 (+, Ar), 129.86 (Cquat),
130.13 (Cquat), 131.51 (Cquat), 131.83 (Cquat), 133.04 (Cquat), 133.85
(+, 2ϫPh), 129.39 (Cquat), 129.79 (Cquat), 131.23 (Cquat), 132.06 (Cquat), 134.08 (Cquat), 135.23 (Cquat), 142.61 (Cquat), 142.88 (Cquat),
(Cquat), 132.58 (Cquat), 133.21 (Cquat), 134.65 (Cquat), 135.65 (Cquat), 143.29 (Cquat), 143.36 (Cquat), 174.46 (Cquat, C=O), 174.55 (Cquat
,
139.83 (Cquat), 139.95 (Cquat), 146.24 (Cquat), 146.34 (Cquat), 146.95 C=O), 174.80 (Cquat, C=O), 175.16 (Cquat, C=O) ppm. MS (70 eV,
(Cquat), 146.97 (Cquat), 174.68 (Cquat, C=O), 174.78 (Cquat, C=O), EI): m/z (%) = 388 (54) [M+], 373 (22) [M+ – CH3], 357 (14), 328
174.95 (Cquat, C=O), 175.35 (Cquat, C=O) ppm. MS (70 eV, EI):
(22), 310 (44), 285 (100), 251 (32), 225 (45), 59 (32), 49 (45), 43
m/z (%) = 448 (100) [M+], 432 (4) [M+ – CH3], 91 (72). C27H29NO6 (51). C21H24O7 (388.4): calcd. C 64.94, H 6.23; found C 64.64, H
(463.5): calcd. C 69.96, H 6.31; found C 70.22, H 6.11. 1H and 13
C
6.03. H and 13C NMR chemical shifts are given in a single series
for both diastereomers, because the peaks in the 1H and 13C NMR
spectra could not be fully assigned to the individual diastereomers.
IR, EI-MS measurements and elemental analysis were carried out
with the mixture of diastereomers.
1
NMR chemical shifts are given in a single series for both dia-
stereomers, because the peaks in the 1H and 13C NMR spectra
could not be fully assigned to the individual diastereomers. * This
multiplet overlaps with singlets of methoxy groups. IR, EI-MS
measurements and elemental analysis were carried out with the
mixture of diastereomers.
Dimethyl 6-Methyl-4,6,7,8,9,10-hexahydro-1,3,5-trioxabenzo[3,4]cy-
clohepta[1,2-e]indene-8,9-dicarboxylate (36g): According to the GP,
Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)phosphane (46.4 mg,
200 µmol), Et3N (202 mg, 2.00 mmol), (5-iodobenzo[1,3]dioxol-4-
yl)methanol (33g, 556 mg, 2.00 mmol) and methylenespiropentane
(11, 320 mg, 4.00 mmol) were stirred in anhydrous DMF (1 mL) at
80 °C for 3 h. After cooling the mixture to room temperature, di-
methyl fumarate (19, 576 mg, 4.00 mmol) was added, and the mix-
ture stirred at 80 °C for 48 h. After workup and column chromatog-
raphy on silica gel (100 g, 3ϫ30 cm, light petroleum/ethyl acetate,
1:1), 36g (219 mg, 29%, colorless solid) was obtained as a mixture
of two diastereomers (ratio 1.1:1 according to NMR). Rf = 0.56
(7-Iodo-2,3-dihydrobenzo[1,4]dioxin-6-yl)methanol (33f): To a solu-
tion of (2,3-dihydrobenzo[1,4]dioxin-6-yl)methanol (2.15 g,
12.93 mmol) in anhydrous CHCl3 (30 mL) at –5 °C were success-
ively added silver trifluoroacetate (3.14 g, 14.2 mmol) and iodine
(3.61 g, 14.2 mmol). After stirring for 5 min, the resulting hetero-
geneous mixture was filtered through a pad of Celite. The filtrate
was washed with satd. aq. Na2S2O3 (10 mL), dried with MgSO4,
filtered and concentrated in vacuo to give a pale yellow solid.
Recrystallization from CHCl3 afforded 33f (3.5 g, 92%, colorless
solid), m.p. 80–82 °C. IR (KBr): ν = 3283, 2977, 2922, 1734, 1576,
˜
1483, 1456, 1401, 1299, 1273, 1260, 1180, 1147, 1070, 1051, 1042,
(light petroleum/ethyl acetate, 1:1). IR (KBr): ν = 2972, 2953, 2686,
˜
1
986, 962, 917, 892, 874, 852, 705, 664 cm–1. H NMR (250 MHz,
1725, 1503, 1480, 1457, 1437, 1379, 1275, 1247, 1197, 1176, 1102,
1082, 1070, 1041, 1014, 977, 933, 887, 859, 797, 744 cm–1. 1H NMR
(300 MHz, CDCl3): δ = 1.17 (d, J = 6.1 Hz, 3 H, CH3), 1.18 (d, J
= 6.9 Hz, 3 H, CH3), 2.17–2.41 (m, 2 H, 9-H or 12-H), 2.46–2.58
(m, 3 H, 9-H or 12-H), 2.71–3.10 [m, 7 H, 2ϫ(10-H + 11-H), 9-H
or 12-H], 3.69 (s, 9 H, 3ϫOCH3), 3.71 (s, 3 H, OCH3), 3.86–3.97
(m, 2 H, 2ϫ8-H), 3.97 (d, J = 11.3 Hz, 1 H, 6-H), 4.04 (d, J =
11.1 Hz, 1 H, 6-H), 4.68 (t, J = 11.0 Hz, 2 H, 6-H), 5.95 (d, J =
4.5 Hz, 4 H, 2ϫ2-H), 6.75 (d, J = 1.9 Hz, 2 H, Ar), 6.78 (s, 2 H,
Ar) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 16.53 (+,
CH3), 17.43 (+, CH3), 26.65 (–, C-9 or C-12), 28.03 (–, C-9 or C-
12), 30.54 (–, C-9 or C-12), 31.61 (–, C-9 or C-12), 40.78 (+, C-10
or C-11), 40.84 (+, C-10 or C-11), 41.55 (+, C-10 or C-11), 41.86
CDCl3): δ = 1.90 (br. s, 1 H, OH), 4.24 [s, O(CH2)2O], 4.56 (s, 2
H, Bn), 6.97 (s, 1 H, Ar), 7.31 (s, 1 H, Ar) ppm. 13C NMR
(62.9 MHz, CDCl3, DEPT): δ = 64.13 [–, O(CH2)2O], 68.34 (–, Bn),
85.44 (Cquat), 117.17 (+, Ar), 127.00 (+, Ar), 135.56 (Cquat), 143.42
(Cquat), 143.71 (Cquat), 155.37 (Cquat) ppm. MS (70 eV, EI): m/z (%)
= 392 (100) [M+], 137 (40), 93 (9), 65 (14), 53 (18), 50 (15). C9H9IO3
(292.1): calcd. C 37.01, H 3.11; found C 36.81, H 2.85.
Dimethyl 5-Methyl-2,3,5,7,10,11-hexahydro-1H,4H-6,9,12-trioxa-
benzo[3,4]cyclohepta[1,2-b]naphthalene-2,3-dicarboxylate (36f): Ac-
cording to the GP, Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)-
phosphane (46.4 mg, 200 µmol), Et3N (202 mg, 2.00 mmol), (7-
iodo-2,3-dihydrobenzo[1,4]dioxin-6-yl)methanol (33f, 584 mg,
4088
www.eurjoc.org
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 4081–4090

Dihydrobenzoxepine and Dihydrobenzazepine Derivatives
FULL PAPER
(+, C-10 or C-11), 52.00 (+, 2ϫOCH3), 52.05 (+, 2ϫOCH3), 59.84
for 48 h. After workup and attempted column chromatography on
(–, 2ϫC-6), 69.83 (+, C-8), 70.41 (+, C-8), 101.11 (–, C-2), 101.20 silica gel (100 g, 3ϫ30 cm, light petroleum/ethyl acetate, 3:1), none
(–, C-2), 107.81 (+, Ar), 107.85 (+, Ar), 117.48 (Cquat), 117.73 of the fractions contained any identifiable product.
(Cquat), 118.61 (+, Ar), 119.07 (+, Ar), 131.18 (Cquat), 131.61
Attempted Synthesis of Dimethyl 5-Methyl-1,3,4,5,7,8-hexahydro-
(Cquat), 133.45 (Cquat), 134.04 (Cquat), 135.19 (Cquat), 136.51 (Cquat),
2H-6-oxadibenzo[a,c]cyclooctene-2,3-dicarboxylate (41): According
145.31 (Cquat), 145.64 (Cquat), 146.46 (Cquat), 146.75 (Cquat), 174.46
to the GP, Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)phosphane
(Cquat, C=O), 174.51 (Cquat, C=O), 174.81 (Cquat, C=O), 175.17
(46.4 mg, 200 µmol), Et3N (202 mg, 2.00 mmol), 2-(2-iodophenyl)
(Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 374 (74) [M+], 359
ethanol (40, 496 mg, 2.00 mmol) and methylenespiropentane (11,
(13) [M+ – CH3], 343 (17), 314 (26), 296 (83), 271 (100), 255 (30),
320 mg, 4.00 mmol) were stirred in anhydrous DMF (1 mL) at
237 (40), 211 (46), 207 (24), 181 (66), 153 (28), 128 (15), 43 (22).
80 °C for 3 h. After cooling the mixture to room temperature, di-
C20H22O7 (374.4): calcd. C 64.16, H 5.92; found C 64.12, H 5.74.
methyl fumarate (19, 576 mg, 4.00 mmol) was added, and the mix-
1H and 13C NMR chemical shifts are given in a single series for
ture stirred at 80 °C for 48 h. After workup and attempted column
both diastereomers, because the peaks in the 1H and 13C NMR
chromatography on silica gel (100 g, 3ϫ30 cm, light petroleum/
spectra could not be fully assigned to the individual diastereomers.
ethyl acetate, 3:1), none of the fractions contained any identifiable
IR, EI-MS measurements and elemental analysis were carried out
product.
with the mixture of diastereomers.
Dimethyl 5-Methyl-7-oxo-1,2,3,4,5,7-hexahydrodibenzo[c,e]oxepine-
2,3-dicarboxylate (43): According to the GP, Pd(OAc)2 (22.4 mg,
100 µmol), tris(2-furyl)phosphane (46.4 mg, 200 µmol), Et3N Acknowledgments
(202 mg, 2.00 mmol), 2-iodobenzoic acid (42, 468 mg, 2.00 mmol)
and methylenespiropentane (11, 320 mg, 4.00 mmol) were stirred in
anhydrous DMF (1 mL) at 80 °C for 3 h. After cooling the mixture
to room temperature, dimethyl fumarate (19, 576 mg, 4.00 mmol)
was added, and the mixture stirred at 80 °C for 48 h. After workup
and column chromatography on silica gel (100 g, 3ϫ30 cm, light
petroleum/ethyl acetate, 3:1), 43 (55 mg, 8%, yellowish oil) was ob-
tained as a mixture of two diastereomers (ratio 1.8:1 according to
This work was supported by the State of Niedersachsen as well as
Bayer AG, BASF AG and Degussa AG (chemicals). The authors
are grateful to Stefan Beußhausen for technical support in prepar-
ing this manuscript in its final form.
[1] A. de Meijere, S. I. Kozhushkov, T. Späth, Org. Synth. 2000,
78, 142–151.
[2] a) A. de Meijere, S. I. Kozhushkov, A. F. Khlebnikov, Top.
Curr. Chem. 2000, 207, 89–147; b) A. de Meijere, S. I. Kozhush-
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[3] a) S. Bräse, A. de Meijere, Angew. Chem. 1995, 107, 2741–2743;
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M. Noltemeyer, A. de Meijere, Angew. Chem. 2001, 113, 3509–
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S. Bräse, S. I. Kozhushkov, M. Noltemeyer, M. Es-Sayed, A.
de Meijere, Chem. Eur. J. 2002, 8, 2350–2369; d) A. de Meijere,
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Scheurich, L. Arve, J. Organomet. Chem. 2003, 687, 249–255;
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592; f) B. Yücel, L. Arve, A. de Meijere, Tetrahedron 2005, 61,
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[4] A. de Meijere, S. I. Kozhushkov, D. Faber, V. Bagutskii, R.
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[5] T. S. Kuznetsova, Habilitation Thesis, Moscow State Univer-
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de Meijere, Eur. J. Org. Chem. 2005, 4167–4178.
[7] Dendralenes are most frequently prepared by pyrolytic or other
elimination reactions, see: a) H. Hopf, Angew. Chem. 1984, 96,
947–958; Angew. Chem. Int. Ed. Engl. 1984, 23, 948–960; b) H.
Hopf, Classics in Hydrocarbon Chemistry, Wiley-VCH,
Weinheim, 2000, pp. 253–260.
[8] CCDC-644579 (36c) 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.
[9] a) R. C. Larock, J. Organomet. Chem. 1999, 576, 111–124; b)
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NMR). R = 0.30 (light petroleum/ethyl acetate, 3:1). IR (film): ν
˜
f
= 3064, 2978, 2951, 2847, 1734, 1601, 1437, 1382, 1327, 1285, 1259,
1198, 1175, 1125, 1093, 1058, 1025, 1010, 936, 917, 769, 714 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.42 (d, J = 7.4 Hz, 3 H, CH3),
1.45 (d, J = 7.1 Hz, 3 H, CH3), 2.26–2.39 (m, 2 H, 1-H or 4-H),
2.56–2.63 (m, 3 H, 1-H or 4-H), 2.80–3.14 [m, 7 H, 2ϫ(2-H + 3-
H), 1-H or 4-H], 3.67 (s, 3 H, OCH3), 3.68 (s, 3 H, OCH3), 3.70
(s, 3 H, OCH3), 3.71 (s, 3 H, OCH3), 4.71–4.79 (m, 2 H, 2ϫ5-H),
7.30–7.41 (m, 4 H, Ar), 7.48–7.55 (m, 2 H, Ar), 7.82–7.86 (m, 2 H,
Ar) ppm. 13C NMR (62.9 MHz, CDCl3, DEPT): δ = 15.82 (+,
CH3), 16.48 (+, CH3), 26.79 (–, C-1 or C-4), 27.47 (–, C-1 or C-4),
30.25 (–, C-1 or C-4), 31.11 (–, C-1 or C-4), 40.75 (+, C-2 or C-3),
40.86 (+, C-2 or C-3), 41.05 (+, C-2 or C-3), 41.28 (+, C-2 or C-
3), 52.15 (+, 4ϫOCH3), 72.80 (+, 2ϫC-5), 125.37 (+, Ar), 125.97
(+, Ar), 128.08 (+, Ar), 128.30 (+, Ar), 130.73 (+, Ar), 130.85
(Cquat), 131.03 (+, Ar), 131.82 (Cquat), 132.02 (+, Ar), 133.81
(Cquat), 134.08 (Cquat), 134.37 (Cquat), 134.49 (Cquat), 136.76 (Cquat),
137.95 (Cquat), 169.95 (Cquat, C=O), 170.07 (Cquat, C=O), 173.92
(Cquat, C=O), 174.06 (Cquat, C=O), 174.45 (Cquat, C=O), 174.60
(Cquat, C=O) ppm. MS (70 eV, EI): m/z (%) = 344 (10) [M+], 312
(29), 284 (30), 267 (37), 253 (86), 239 (28), 207 (41), 181 (100), 165
(49), 152 (26), 115 (13), 59 (16). HRMS-ESI for C19H20O6 (344.37):
calcd. for [M + H]+ 345.13326, found 345.13314; calcd. for [M +
NH4]+ 362.15981, found 362.15974. 1H and 13C NMR chemical
shifts are given in a single series for both diastereomers, because
1
the peaks in the H and 13C NMR spectra could not be fully as-
signed to the individual diastereomers. IR, EI-MS and ESI-HRMS
measurements were carried out with the mixture of diastereomers.
Attempted Synthesis of Dimethyl 6-Methyl-5,6,7,8,9,10-hexahy-
drophenanthridine-8,9-dicarboxylate (39): According to the GP,
Pd(OAc)2 (22.4 mg, 100 µmol), tris(2-furyl)phosphane (46.4 mg,
200 µmol), Et3N (202 mg, 2.00 mmol), 2-iodoaniline (38, 438 mg,
2.00 mmol) and methylenespiropentane (11, 320 mg, 4.00 mmol)
were stirred in anhydrous DMF (1 mL) at 80 °C for 3 h. After cool-
ing the mixture to room temperature, dimethyl fumarate (19,
576 mg, 4.00 mmol) was added, and the mixture stirred at 80 °C
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www.eurjoc.org
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Received: April 20, 2007
Published Online: July 3, 2007
4090
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 4081–4090