4,5-Dihydro-3H-benzo[c]azepines from 1,7-electrocyclization reactions of 2-aza-4,5-benzoheptatrienyllithium compounds

Article abstract of DOI:10.1002/ejoc.200400206

Various differently substituted (2-alkenylbenzylidene)amines 4b-d gave, upon deprotonation with amide bases and addition of an electrophile, the respective 4,5-dihydro-3H-benzo[c]azepines 6a-k in moderate to good yields. The imines 4 are easily accessible

Full text of DOI:10.1002/ejoc.200400206

FULL PAPER
4
,5-Dihydro-3H-benzo[c]azepines from 1,7-Electrocyclization Reactions of
2
-Aza-4,5-benzoheptatrienyllithium Compounds
[a]
[a]
[a]
[a]
Klaus Gerdes, Pramod Sagar, Roland Fröhlich, Birgit Wibbeling, and
Ernst-Ulrich Würthwein*[
a]
Keywords: 1,7-Anionic electrocyclization reaction / Dihydrobenzo[c]azepines / 2-Azaheptatrienyl anions / Lithium
compounds / Quantum chemical calculations
Various differently substituted (2-alkenylbenzylidene)am- The corresponding allylimines 4e,f do not give nine-
ines 4b−d gave, upon deprotonation with amide bases and
addition of an electrophile, the respective 4,5-dihydro-3H-
benzo[c]azepines 6a−k in moderate to good yields. The im-
membered heterocycles 7, but rather the corresponding 3-
vinyl-4,5-dihydro-3H-benzo[c]azepines 6l,m. Molecular
structures of several compounds 6 in the solid state were de-
ines 4 are easily accessible from 2-bromobenzaldehyde (1) termined by X-ray crystallography, including the structure of
by Wittig olefination, formylation with DMF, and subsequent
condensation with benzylamine. The ring-closure reaction is
interpreted as an anionic 1,7-electrocyclization reaction in-
a 14-membered ring dimer 8. High-level quantum chemical
calculations on model anions concerning structures and rel-
ative energies of possible intermediates and transition states
volving benzo-annulated 2-azaheptatrienyllithium com- support the pericyclic mechanism suggested for the ring-
pounds. This reaction, and the subsequent addition of the
electrophiles, proceed with excellent diastereoselectivity, de-
termined by the (E) or (Z) configuration of the imines 4b−d.
closure reaction.
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2004)
Introduction
Seven-membered heterocycles constitute an important
class of compounds that has found many applications in
medicinal chemistry.[1,2] Of special interest within this class
of compounds are benzo-annulated systems, among them
dibenzoazepines (e.g. imipramine) and benzodiazepines
(
e.g. clonazepam, diazepam, chlordiazepoxide).[3] We have
previously reported a new synthetic pathway to partially
unsaturated seven-membered nitrogen heterocycles, based
on an electrocyclization reaction of azapolyenylmetal com-
pounds, where the nitrogen atoms are placed in even posi-
tions of the anionic chain (Scheme 1).[
4,5]
Only when this
condition is fulfilled can facile ring-closure reactions by
anionic electrocyclization take place; azapolyenylmetal
compounds with nitrogen atoms in odd positions are
thermodynamically stable and do not cyclize easily. These
experimental observations were rationalized by molecular
[6]
orbital arguments (topological charge stabilization ); since
nitrogen atoms are electronegative, they strongly prefer the
odd positions within an unsaturated hydrocarbon chain, as Scheme 1
this is where the bigger coefficients in the HOMO are
located. For the corresponding cations, the opposite rules
In this report, we extend our studies from simple 2- or 4-
apply (ring closure is favored when the nitrogen atoms are
in the odd positions).
azaheptatrienylmetal compounds to 2-aza-4,5-benzohepta-
trienyllithium systems, in order to investigate the scope of
the electrocyclic ring-closure reaction, and eventually gain
access to differently substituted benzo-annulated seven-
membered nitrogen heterocycles. Special emphasis in our
[
a]
Organisch-Chemisches Institut, Universität Münster,
Corrensstraße 40, 48149 Münster, Germany
Fax: (internat.) ϩ 49-251-83-39772
E-mail:wurthwe@uni-muenster.de
Eur. J. Org. Chem. 2004, 3465Ϫ3476
DOI: 10.1002/ejoc.200400206
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3465

K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
FULL PAPER
studies is directed towards the elucidation of the stereoelec-
tronic properties of the ring-closure reaction and the sub-
sequent electrophilic addition to the intermediate anionic
species. For a more detailed discussion of the reaction
mechanism, we include high level quantum chemical calcu-
lations in this study.
Anionic electrocyclization reactions to form seven-mem-
bered rings are rare.[
4,5,7,8]
However, many examples are
known that involve neutral [1,7]-dipoles; these species are
isoelectronic to the corresponding anions.[
9Ϫ12]
Scheme 3
Results and Discussion
For the preparation of the anionic reactive intermediates
by deprotonation, the corresponding 2-(alkenyl)benzaldim-
ine derivatives 4 were synthesized using a three-step pro-
cedure starting from 2-bromobenzaldehyde (1). In the first
step, the alkenyl moiety of the styrene derivatives 2 was es-
tablished by a Wittig reaction as reported by Hibino et
al.[ (Scheme 2). This gave an (E)/(Z) mixture of 2 [(Z)/
13]
(
E) ϭ 1:0.5Ϫ0.7]. Pure (E)-2b was obtained by isomeriz-
[14]
Figure 1. Molecular structure of compound 4g in the solid state
ation of the (E)/(Z) mixture using iodine. Formylation of
2
(
X-ray diffraction)
to yield the 2-(alkenyl)benzaldehydes 3 was accomplished
by metalation with n-butyllithium and subsequent addition
of dimethylformamide, also according to a procedure given
by Hibino et al. In the third step, condensation with ben-
[
13]
The deprotonation of the imines 4 to generate the inter-
zylamine in the presence of molecular sieves yielded the 2- mediate anions requires a carefully optimized protocol,
alkenyl)benzaldimines 4aϪd (Scheme 2).[ Condensation which starts with the preparation of a small excess (ca. 20%)
15]
(
with allylamine produced the imines 4eϪg (Scheme 3). The of lithium diisopropylamide (LDA) from n-butyllithium
solid-state structure of derivative 4g was determined by X- and diisopropylamine in THF at Ϫ40 °C, warming to room
[
16]
ray crystallography. It shows the (E) configuration of the temperature and subsequent cooling to Ϫ78 °C. At this
CϭC bond, and a conformation of the imine moiety rela- temperature, a solution of the imine 4bϪd in THF is added
tive to the benzene ring resulting from rotation around the dropwise to the base over 30 min. The reaction is completed
CϪCN bond away from the stilbene part of the molecule by warming the mixture to 0 °C and stirring at this tem-
(Figure 1).
perature for 30 min before addition of the respective elec-
trophile 5 and aqueous workup (Scheme 4). After column
chromatography on silica gel, using petroleum ether/ethyl
acetate (10:2 to 10:1) as eluent, the major component of the
reaction mixture could be isolated as the first fraction.
In this way, the 4,5-dihydro-3H-benzo[c]azepines 6 were
obtained in moderate to good isolated yields (Scheme 4), as
oily or slowly crystallizing materials. They were fully
characterized, and in some cases, X-ray analysis was ob-
tained. For the preparation of 6k, LiTMP (lithium 2,2,6,6-
tetramethylpiperidide) proved to be superior to LDA. The
reaction is interpreted as a 1,7-electrocyclic ring-closure re-
action, as indicated above. The driving force of the reaction
is the generation of the energetically favored bicyclic 1-aza-
pentadienyl anion, in which the nitrogen atom is in a posi-
tion with a large HOMO coefficient, from the disfavored 2-
azaheptatrienyl anion, in which the nitrogen atom is in a
[
4]
nodal position of the HOMO.
However, deprotonation of the styrene derivative 4a and
Scheme 2
466
subsequent electrophilic addition does not lead to cyclic
3
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 3465Ϫ3476

4,5-Dihydro-3H-benzo[c]azepines
FULL PAPER
Scheme 5
we use the Chemical Abstracts (R*,S*) system for the
[
17]
assignment of the relative configurations.
d and 6f show the same relative configuration at the
carbon atoms C3 and C4 of the seven-membered ring
(3R*,4S*,5S*) for 6d and (3R*,4S*) for 6f]. This is differ-
ent from the configuration of 6b and 6c, which both have a
3R*,4R*,5R*) configuration. On the basis of these crystal
Compounds
6
[
Scheme 4
(
1
13
products, presumably due to anionic polymerization. Simi- structures, the H and C NMR spectra of all compounds
larly, 4g decomposes on deprotonation to give polymers. 6 could be clearly differentiated with respect to the relative
In order to investigate the possible extension of this syn- configurations of the possible diastereomers. We found the
thetic method to nine-membered benzo-annulated hetero- X-ray diffraction study of one other example of a 4,5-di-
cycles, the allylimine derivatives 4e,f were synthesized and hydro-3H-benzo[c]azepine (dibromo derivative) in the lit-
[
18]
deprotonated (Scheme 5). However, after addition of the erature.
electrophiles, workup and characterization of the products, These crystal structures exemplify nicely how sensitively
all spectroscopic and analytical evidence was in full agree- the conformations of such 4,5-dihydro-3H-benzo[c]azepines
ment with the 4,5-dihydro-3H-benzo[c]azepine structures react to changes in substitution pattern and relative con-
6
l,m with vinyl groups in the 3-positions. There was no indi- figuration. Table 1 summarizes the dihedral angles around
cation of the formation of nine-membered ring derivatives the seven-membered rings (note that 6f has no substituent
with the structure shown (Scheme 5) or isomeric products at position 5).
7
resulting from electrophilic attack at any of the other posi-
tions.
Interestingly, in all cases, the successful reactions of the
(E)/(Z) mixtures of 4 led to crude mixtures of products,
After isolation by column chromatography and crystalli- from which pure diastereomers (with the exception of 6b
zation, we were able to obtain the molecular structures in and 6i) with relative (3R*,4S*) configuration could be sepa-
the solid state of the main fractions of four 4,5-dihydro-3H- rated by column chromatography (Scheme 6). From the
benzo[c]azepine derivatives 6b,c,d,f by X-ray diffraction (see yields obtained, one can trace back the formation of this
Figure 2 for the structures of 6b and 6d). This allowed an particular diastereomer to the major isomer of 4, which is
easy and unambiguous assignment of the relative configu- the (Z) form (Z)-4 (major isomer), as obtained from the
rations. Since we are dealing here with racemic compounds, Wittig reaction in the first step. In the case of 6b, small
Figure 2. Molecular structure of compounds (3R*,4R*,5R*)-6b (left) and (3R*,4S*,5S*)-6d (right) in the solid state (X-ray analysis; only
one enantiomer of each is shown)
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K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
FULL PAPER
Table 1. Dihedral angles [°] of the seven-membered ring of four 4,5-dihydro-3H-benzo[c]azepines 6, as determined by X-ray crystallogra-
phy
(3R*,4R*,5R*)-6b
(3R*,4R*,5R*)-6c[a]
(3R*,4S*,5S*)-6d
(3R*,4S*)-6f
C7ϪC1ϪN2ϪC3
C1ϪN2ϪC3ϪC4
N2ϪC3ϪC4ϪC5
C3ϪC4ϪC5ϪC6
C4ϪC5ϪC6ϪC7
C5ϪC6ϪC7ϪC1
C6ϪC7ϪC1ϪN2
Ϫ4.9(2)
76.82(17)
Ϫ53.19(17)
Ϫ28.75(18)
63.16(18)
Ϫ7.3(2)
4.5(8)
Ϫ77.1(6)
54.0(6)
28.5(6)
Ϫ62.3(6)
6.3(7)
Ϫ1.8(3)
31.3(2)
Ϫ71.35(16)
74.25(15)
Ϫ36.95(19)
3.3(2)
Ϫ4.76(19)
80.58(13)
Ϫ53.44(12)
Ϫ33.61(14)
67.27(15)
Ϫ4.80(17)
Ϫ45.05(19)
Ϫ41.7(2)
43.0(8)
1.2(3)
[
a]
One of two similar, independent molecules in the asymmetric unit cell.
In one experiment (deprotonation of 4b and quenching
with water to form 6a), a surprising dimeric compound 8
was isolated, in very low yield. Nevertheless, it was possible
to characterize this compound by X-ray analysis (Figure 3).
It crystallizes centrosymmetrically, forming an approximate
rectangle with (R*,S*) configuration, as observed in the
corresponding seven-membered ring 6a. Acid-catalyzed
equilibria between dimers and monomers of 4,5-dihydro-
benzo[c]azepines have been reported previously by Gold-
[
20]
man et al.
Scheme 6
amounts of the minor isomer (ca. 14%) (3R*,4R*,5R*)-6b,
originating from (E)-4b, could be isolated and charac-
terized. The fate of the minor isomers, originating from the
other olefins (E)-4, could not be clarified in most cases, due
to their less favorable chromatographic properties.
Figure 3. Molecular structure of the macrocycle 8 in the solid state
X-ray diffraction)
(
These observations are in agreement with an experiment
in which pure (E)-4b was subjected to the conditions of the
1
Using low-temperature H NMR techniques (600 MHz),
deprotonation reaction. In this case, diastereomer 6b, with we were able to investigate the ring-closure reaction of the
the relative (3R*,4R*,5R*) configuration, was obtained ex- imine derivative (E,Z)-4b directly. The deprotonation using
clusively in 68% yield.
LDA was performed at Ϫ78 °C in [D ]THF in an NMR
8
Hence, the formation of the new C3ϪC4 single bond dur- tube. At Ϫ20 °C, two sets of signals (among others) could
ing the cyclization reaction is a highly diastereoselective be identified; the more intense set was assigned to the pre-
process, which is in full agreement with a conrotatory dominant anion Li-4b, having a (Z) configuration at the
electrocyclization
WoodwardϪHoffmann rules for 8π systems.
mode,
as
predicted
by
the CϭC bond (Table 2). In comparison to the neutral starting
[19]
Further- material, a high-field shift of most of the signals was ob-
more, the addition of the electrophile to position 5 of the served, which was particularly pronounced at the odd posi-
intermediate anion obviously occurs with high diastereosel- tions of the conjugated anionic system. This was as ex-
ectivity, as the incoming electrophile is always found in the pected, given the electron distribution in the HOMO. This
trans position to the substituent at center C4. In summary, species may be considered as a benzo-annulated 2-aza-
of the four possible diastereomers of the (racemic) product, heptatrienyl anion.
only one is formed during the reaction sequence, as deter-
On warming of the sample to temperatures above Ϫ10
mined by the stereochemistry of the ethenyl moiety of the °C, new signals appeared. The new signals became more
starting material 4 and the subsequent stereoselective ad- intense at 25 °C, and the initially observed signals disap-
dition of the electrophile.
peared. The two new sets of signals may be unambiguously
3468
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Eur. J. Org. Chem. 2004, 3465Ϫ3476

4,5-Dihydro-3H-benzo[c]azepines
FULL PAPER
1
Table 2. Selected H NMR chemical shifts [ppm] for starting mate-
At first, we did a conformational search of the anionic
rial (Z)-4b, the corresponding lithium compound Li-4b at Ϫ20 °C, imine derivative, using the 1-(2-ethenylphenyl)-2-azaallyl
the resulting cyclic lithium compound Li-6b at 25 °C, and for the
anion (9) as a simplified model for the experimentally
product (3R*,4S*,5S*)-6b (after hydrolysis) (600 MHz); com-
studied lithium compounds. With the exception of 9e, which
pounds 4 are numbered as 2-azaheptatrienyl anions; compounds 6
is kept planar by an intramolecular hydrogen bond, all
structures are more or less twisted with respect to the vinyl
groups (9a,b,c) or to the vinyl- and 2-azaallyl moieties
as 4,5-dihydro-3H-benzo[c]azepines
H1
H3
H6
H7
(
9d,f,g). Structure 9a, with the W-shape of the 2-azaallyl
(
Z)-4b
4.79
6.62
8.58
7.58
6.65
6.28
5.92
5.38
moiety, was found to be lowest in energy. It corresponds
exactly to the structure of the imine precursor 4g, as deter-
mined by X-ray crystallography (see Figure 1); 9b and 9c
are only slightly more energy-rich. The formation of the
Li-4b
H3
H1
H5
H4
Li-6b
3.86
4.44
7.35
8.76
5.13
2.42/2.80
1.90 cyclic structure 10 from the open-chain structures is signifi-
(
3R*,4S*,5S*)-6b
2.80
cantly exothermic, indicating a gain of energy during the
ring-closure reaction of 8Ϫ10 kcal/mol with respect to the
best open-chain structure 9a. The methods employed (RHF,
MP2, SCS-MP2, G3MP2) produce quite similar data sets.
Since MP2 values are already quite good, the performance
of SCS-MP2 is not as superior as was observed earlier.[
Secondly, we looked for some relevant transition states,
in order to obtain an estimate for the kinetics of the ring-
closure reaction. Here, the methods disagree markedly over
the existence of a U form and a related barrier for ring
closure to form 10. RHF finds a minium for such a U form
attributed to the bicyclic anion Li-6b, of which the more
intense set was assigned to the (3R*,4S*) diastereomer. The
most significant change in chemical shift was observed for
23]
1
7
the protons H and H of the open-chain anion, since the
respective carbon atoms change their hybridization from
2
3
sp to sp , due to the formation of the new single bond.
Interestingly, the protons of the benzo ring of the depro-
tonated starting material (E,Z)-4b, as well as of the bicyclic
anion show alternately high and low relative shifts, indicat-
ing substantial involvement of these centers in the conju-
gation of the anion.
(Erel ഠ 14 kcal/mol), and predicts a substantial barrier (ca.
23 kcal/mol). MP2 optimization (as integrated in the
G3MP2 model chemistry) does not localize a U-shaped
Quantum Chemical Calculations
In order to obtain an estimate of the thermodynamics
and kinetics of the ring-closure reaction to form the seven-
membered ring, quantum chemical model calculations on
the RHF, MP2, SCS-MP2[ and G3MP2 level were per-
formed. Previous studies have shown that DFT calculations
of the B3LYP/6-31G* level underestimate both barriers and
21]
[22]
[
23]
[24]
products.
The program package GAUSSIAN98
was
used throughout for the calculations. All stationary points
were characterized by frequency calculations. All energies
are given in kcal/mol, including zero point corrections
Figure 4. Conformations and configurations of the anions 9aϪg
and 10
(ZPE, unscaled for RHF, MP2 and SCS-MP2).
Table 3. Relative energies of various structures of 9 and 10 and of some relevant transition states at different levels of theory [kcal/mol]
RHF//6-
MP2-Full/6-
31G*//MP2/6-
31G*ϩZPE
SCS-MP2-Full/6-
31G*//MP2/6-
31G*ϩZPE
MP2/GTMP2Large//
MP2/6-31G*ϩZPE
SCS-MP2/GTMP2Large//
MP2/6-31G*ϩZPE
G3MP2
3
3
1G*//RHF/6-
1G*ϩZPE
9
9
9
9
9
9
9
a
b
c
d
e
f
0.00
2.36
2.70
8.07
8.91
11.38
12.95
20.07
20.41
18.86
0.00
1.73
1.88
6.19
6.82
8.37
9.69
0.00
1.86
2.07
6.77
7.24
0.00
1.98
1.44
5.08
6.59
7.04
7.93
0.00
2.11
1.69
5.72
7.13
7.97
8.86
0.00
1.98
1.47
5.51
6.57
7.53
8.50
9.18
g
10.40
20.29
20.41
15.16
Ϫ13.92
TS-9h
TS-9i
TS-9j
20.48
22.34
14.60
Ϫ14.47
18.97
21.16
12.12
Ϫ11.89
18.70
19.22
12.97
Ϫ11.55
18.86
18.76
12.86
Ϫ11.07
10
Ϫ12.49
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K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
FULL PAPER
pending on the substitution pattern and relative configura-
tion. A 14-membered ring dimer 8 was isolated in low yield,
and characterized by X-ray crystallography. High-level
quantum chemical calculations on model anions 9 and 10,
which serve as models of of possible intermediates and tran-
sition states, are in good agreement with the pericyclic
mechanism suggested for the ring-closure reaction.
Experimental Section
Materials and Methods: IR: Nicolet FT-IR 5DXC, 1H NMR:
Bruker WM 300 (300.13 MHz), AMX 400 (400.13 MHz) and
Varian Unity plus (599.86 MHz), internal reference tetramethylsil-
1
3
ane. C NMR: Bruker WM (75.47 MHz), Varian Unity Plus
150.85 MHz), internal reference tetramethylsilane or solvent. GC:
Figure 5. Calculated structures of three relevant transition states
(
for internal rotation and ring closure [9a Ǟ TS-9h Ǟ 9b (top left),
Hewlett-Packard 6890 with HP5 quartz capillary (30 m). GC/MS:
Varian MAT CH7A with GC Varian 3400 plus data system SS 200;
Varian MAT 8230 with GC Varian 3400 plus data system SS300.
CHN: Perkin-Elmer Dia CHN 240. Column chromatography: Sil-
ica gel 60 (Merck), 0.063Ϫ0.200 mm. Melting points (uncorrected):
9
b Ǟ TS-9i Ǟ 9g (top right) and 9g Ǟ TS-9j Ǟ 10 (bottom) (MP2/
6
-31G*//MP2(6-31G*)]
structure at all, the small barrier towards cyclization TS-9j
(
12Ϫ13 kcal/mol) is connected to the internal rotation of Büchi B-540. All solvents were rigorously dried by standard meth-
9g, which is directly transformed into the cyclic form 10. ods. When necessary, the experiments were carried out with com-
Similarly, other internal rotations also proceed without plete exclusion of moisture (argon, septum-syringe technique) in
glassware that had been thoroughly dried by repeated heating un-
der argon and subsequent evacuation. The 2-(alkenyl)bromobenz-
higher barriers (e.g. TS-9h for the conversion of 9a into 9b,
and TS-9i for the conversion of 9b into 9g, both ca. 19 kcal/
enes 2a,[ 2b, 2d,
2
13]
[14]
2c were prepared by Wittig olefination of
-bromobenzaldehyde (1) in accordance and analogy to literature
procedures. Pure (E) isomer (E)-2b was obtained upon isomeriz-
[26]
[
25]
mol at G3MP2),
in agreement with the mild reaction
conditions used experimentally. All these data fit well with
a one-step pericyclic ring-closure reaction without involve-
ment of intermediates.
[14]
ation of (E,Z)-2b in the presence of iodine. The 2-alkenylbenzal-
dehydes 3a, 3b, 3d, 3c were prepared by formylation of the
[13]
[14]
[27]
Some additional calculations (on lower levels of theory)
compounds 2aϪd using n-butyllithium and dimethylformamide ac-
for the ring-closure reaction of the experimentally studied cording to a literature procedure.[ For the preparation of (E)-3b
systems (E)-4b and (Z)-4b as anions, as well as neutral sys- pure (E)-2b was used.
tems including lithium cations as counterions, came to simi-
13]
General Procedure for the Synthesis of 4aϪd: 1 equiv. of the 2-
lar conclusions as the model calculations described above.
(
alkenyl)benzaldehyde 3 was added to 1 equiv. of benzylamine in
˚
the presence of molecular sieves (4 A) in 15 mL of dry dichloro-
methane in analogy to a published procedure.[ After 16 h of stir-
ring at room temperature, the molecular sieves were removed by
filtration and carefully washed with 25 mL of dichloromethane.
The solvent was removed under reduced pressure and the product,
15]
Conclusion
In this report, we describe a novel, straightforward
method for the preparation of various differently substi- if necessary, was purified by kugelrohr distillation or crystallisation.
tuted 4,5-dihydro-3H-benzo[c]azepines 6aϪk by depro- Benzyl(2-vinylbenzylidene)amine (4a) was prepared form 3a as re-
tonation of the corresponding [2-(alkenyl)benzylidene]am- ported in ref.[
15]
ines 4bϪd with amide bases, and addition of electrophiles.
(
E,Z)-Benzyl(2-propenylbenzylidene)amine [(E,Z)-4b]: The imine
The reaction proceeds smoothly on warming the lithiated
imine 4 from Ϫ78 °C to room temperature. The imines 4
were prepared from 2-bromobenzaldehyde (1) by Wittig ole-
was prepared from 1.17 g (8.0 mmol) of (E/Z)-2-(1-propenyl)benz-
aldehyde (3b) and 0.85 g (8.0 mmol) of benzylamine in dichloro-
methane. After removal of the molecular sieves, the solvent was
fination, formylation using DMF, and subsequent conden- evaporated under reduced pressure to give 4b (1.83 g, 7.7 mmol,
sation with benzylamine. The ring-closure reaction is inter- 96%) as a colorless liquid. (Z)/(E) ratio ϭ 1:0.55. IR (film): ν˜ ϭ
Ϫ1
preted in terms of an anionic 1,7-electrocyclization reaction 3091 cm (m, CHarom.,olef.), 3070 (m, CHarom.,olef.), 3021 (s,
CHarom.,olef.), 2940 (m, CHaliph.), 2905 (m, CHaliph.), 2878 (m,
CHaliph.), 2864 (m, CHaliph.), 1632 (vs, CϭN), 1590 (m), 1487 (m),
involving benzo-annulated 2-azaheptatrienyllithium com-
pounds. This reaction and the subsequent addition of the
electrophile proceed with excellent diastereoselectivity, de-
termined by the (E) or (Z) configuration of the imines
1
473 (w), 1446 (s), 1370 (m), 1349 (w), 1281 (m), 1026 (m), 964
1
(
(
3
m), 757 (s), 696 (s). H NMR (300.13 MHz, CDCl ): δ ϭ 1.65
3
4
3
dd, J ϭ 6.92, J ϭ 1.91 Hz, 3 H, CH
3
, Z), 1.91 (dd, J ϭ 6.67,
4aϪd. The corresponding allylimines 4e,f do not give nine-
4
4
J ϭ 1.90 Hz, 3 H, CH
3
, E), 4.79 (d, J ϭ 1.43 Hz, 2 H, NϪCH ,
2
membered heterocycles 7, but rather the corresponding 3-
vinyl-4,5-dihydro-3H-benzo[c]azepines 6l,m. Structures of
4
3
2
Z), 4.83 (d, J ϭ 1.43 Hz, 2 H, NϪCH , E), 5.92 (dq, J ϭ 6.92,
3
3
3
3
J ϭ 11.21 Hz, 1 H, CHϭCHϪCH , Z), 6.06 (dq, J ϭ 6.68, J ϭ
3
several compounds 6 in the solid state, as determined by X- 15.49 Hz 1 H, CHϭCHϪCH , E), 6.65 (m, J ϭ 11.21 Hz, 1 H,
ray crystallography, show variable ring conformations de- CHϭCHϪCH
3
3
3
, Z), 6.88 (m, J ϭ 15.50 Hz, 1 H, CHϭCHϪCH
3
,
3470  2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.eurjoc.org
Eur. J. Org. Chem. 2004, 3465Ϫ3476

4,5-Dihydro-3H-benzo[c]azepines
FULL PAPER
E), 7.16Ϫ7.40 (m, 8 H, CHarom., E/Z), 7.93 (m, 1 H, CHarom., E), (E)-Benzyl(2-styrylbenzylidene)amine [(E)-4d]: The imine was pre-
4
8
8
.07 (m, 1 H, CHarom., Z), 8.58 (d, J ϭ 1.43 Hz, 1 H, NϭCH, Z),
pared from 1.04 g (5.0 mmol) of 3d and 0.53 g (5.0 mmol) of ben-
zylamine in dichloromethane. After removal of the molecular si-
4
13
.72 (t, J ϭ 1.43 Hz, 1 H, NϭCH, E) ppm. C NMR (75.47 MHz,
): δ ϭ 14.48 (CH , Z), 19.25 (CH , E), 65.77 (NϪCH
5.83 (NϪCH , E), 122.77 (CHϭCHϪCH , Z), 127.26, 127.49, (E)-4d (1.34 g, 4.5 mmol, 90%) as a yellow solid. M.p. 115 °C. IR
27.83, 128.13, 128.34, 128.87, 129.58, 130.08, 130.42, 130.73
, E/Z), 133.20, 134.23, 138.53, 139.00, 140.01 (s, CHarom.,olef.), 2940 (m), 2905 (m, CHaliph.), 2878 (m, CHaliph.),
ipso, E/Z), 161.02 (NϭCH, Z), 161.30 (NϭCH, E) ppm. MS (70 2864 (m, CHaliph.), 1632 (vs, CϭN), 1590 (m), 1487 (m), 1473 (w),
CDCl
6
1
3
3
3
2
, Z), eves, the solvent was evaporated under reduced pressure to give
2
3
Ϫ1
(film): ν˜ ϭ 3091 cm (m, CHarom.,olef.), 3070 (m, CHarom.,olef.), 3021
(
(
Carom., CHϭCHCH
3
C
ϩ
ϩ
ϩ
eV): m/z (%) ϭ 235 (2) [M ], 220 (80) [M Ϫ CH
3
], 144 (3) [M
], 65 (10). C17
235.3): calcd. C 86.77, H 7.28, N 5.95; found C 86.34, H 7.03, NϪCH
1446 (s), 1370 (m), 1349 (w), 1281 (m), 1026 (m), 964 (m), 757 (s),
ϩ
2
1
Ϫ PhCH
(
N 5.63.
2
], 129 (6), 115 (8), 91 (100) [PhCH
H
17
N
696 (s). H NMR (300.13 MHz, CDCl
3
): δ ϭ 4.77 (s, 2 H,
), 6.85 (d, J ϭ 16.22 Hz, 1 H, PhCH), 7.10Ϫ7.40 (m, 12
H, CHarom., PhCH) 7.50 (m, 1H , CHarom.), 7.65 (m, 1 H, CHarom.),
.80 (m, 1 H, CHarom.), 8.68 (s, 1 H, NϭCH) ppm. 13C NMR
75.47 MHz, CDCl ): δ ϭ 65.55 (NϪCH ), 125.97, 126.70, 126.80,
127.60, 127.83, 128.00, 128.48, 128.64, 128.73, 129.09, 130.28,
32.24, (Carom.), 133.48, 137.32, 137.82, 139.44, (Cipso), 160.64 (Nϭ
3
2
7
(
3
2
(
E)-Benzyl(2-propenylbenzylidene)amine [(E)-4b]: 0.73 g (5.0 mmol)
of (E)-3b and 0.53 g (5.0 mmol) of benzylamine were mixed to-
gether in dry dichloromethane (20 ml) and stirred in the presence
of molecular sieves (4 A) at room temperature for 16 h. The molec-
ular sieves were removed by filtration and washed with dichloro-
methane (20 ml). The solvent was removed in vacuo to afford (E)-
b (1.10 g, 4.7 mmol, 95%) as brownish oil. IR (film): ν˜ ϭ 3014
cm , 3000 (m, CHarom.,olef.), 2867, 2850 (m, CHaliph.), 1616 (vs,
[
14]
1
ϩ
ϩ
CH) ppm. MS (70 eV): m/z (%) ϭ 297 (10) [M ], 220 (75) [M
Ϫ
˚
ϩ
Ph], 208 (32), 178 (34) 165 (10), 128 (6), 91 (100) [PhCH
10). C22 19N (297.3): calcd. C 88.85, H 6.44, N 4.71; found C
8.69, H 6.07, N 4.66.
2
], 65
(
8
H
4
Ϫ1
(
E,Z)-Allyl(2-propenylbenzylidene)amine [(E,Z)-4e]: The imine was
CϭN), 1579 (m), 1475(m), 1428 (s), 1359 (s), 1326 (s), 1270 (s),
prepared from 1.17 g (8.0 mmol) of (E,Z)-3b and 0.46 g (8.0 mmol)
of allylamine in dichloromethane. After removal of the molecular
sieves, the solvent was evaporated under reduced pressure. The
1
1
014 (s), 950 (s), 742 (s), 725 (s), 688 (s). H NMR (300.13 MHz,
3
4
CDCl
3
): δ ϭ 1.87 (dd, J ϭ 6.68, J ϭ 1.67 Hz, 3 H, CH
3
), 4.80
), 6.02 (dq, J ϭ 6.68, J ϭ 15.73
), 6.84 (m, 3J ϭ 15.74 Hz, 1 H, CHϭ
), 7.21Ϫ7.38 (m, 8 H, CHarom.), 7.90 (m, 1 H, CHarom.),
.70 (s, 1 H, NϭCH) ppm. 13C NMR (75.47 MHz, CDCl
): δ ϭ
8.71 (CH ), 65.30 (NϪCH ), 126.78, 126.83 (CHϭCHCH ),
4
3
3
(d, J ϭ 1.19 Hz, 2 H, NϪCH
2
crude product was purified by kugelrohr distillation (80 °C/3 ϫ
Hz, 1 H, CHϭCHϪCH
CHϪCH
3
Ϫ3
10
mbar) to give (E,Z)-4e (1.42 g, 7.7 mmol, 96%) as a colorless
3
Ϫ1
liquid. (Z)/(E) ratio ϭ 1:0.5. IR (film): ν˜ ϭ 3070 cm (m,
CHarom.,olef.), 3050 (m, CHarom.,olef.), 2974 (m, CHaliph.), 2919 (m,
CHaliph.), 2878 (s, CHaliph.), 2816 (m, CHaliph.), 1652 (vs, CϭN),
8
1
1
1
2
3
3
2
3
27.06, 127.63, 127.78, 127.81, 128.35, 129.80, 130.20, 132.68,
38.46, 139.47, 160.46 (NϭCH) ppm. MS (70 eV): m/z (%) ϭ 235,
20 (67), 144 (4), 129 (5), 115 (10), 91 (100), 77 (3), 65 (13) ppm.
1
597 (m), 1473 (m), 1446 (s), 1356 (s), 1315 (w), 1288 (m), 1033
1
(
(
m), 1012 (m), 971 (m), 923 (s), 813 (w), 764 (s), 716 (m). H NMR
300.13 MHz, CDCl ): δ ϭ 1.63 (dd, J ϭ 6.92, J ϭ 1.91 Hz, 3
3
3
4
C
17
H
17N (235.32): calcd. C 86.77, H 7.28, N 5.95; found C 86.33,
3
4
3 3
H, CH , Z), 1.91 (dd, J ϭ 6.67, J ϭ 1.90 Hz, 3 H, CH , E), 4.25
H 7.62, N 6.02.
4
2
3
2
(m, J ϭ 1.67 Hz, 2 H, NϪCH , E/Z), 5.20 (m, J ϭ 1.91, J ϭ
3
3
1
2
0.26, J ϭ 17.24 Hz, 2 H, CHϭCH , E/Z), 5.92 (dq, J ϭ 7.15,
3
(
E,Z)-Benzyl(2-pent-1-enylbenzylidene)amine [(E,Z)-4c]: The imine
3 2
J ϭ 11.44 Hz, 2 H, CHϭCHϪCH , Z, CHϭCH ), 6.07 (m, 2 H,
3
was prepared from 1.74 g (10.0 mmol) of (E,Z)-3c and 1.07g (10.0
mmol) of benzylamine in dichloromethane. After removal of the
molecular sieves, the solvent was evaporated under reduced press-
3 2
CHϭCHϪCH , E, CHϭCH ), 6.65 (d, J ϭ 11.44 Hz, 1 H, CHϭ
CHϪCH , Z), 6.88 (m, J ϭ 15.50 Hz, 1 H, CHϭCHϪCH , E),
3
3
3
7.10Ϫ7.41 (m, 3 H, CHarom., E/Z), 7.90 (m, 1 H, CHarom., E), 8.02
ure to give 3c (2.12 g, 8.0 mmol, 80%) as a colorless liquid. (Z)/(E)
ratio ϭ 1:0.5. IR (film): ν˜ ϭ 3085 cm (w, CHarom.,olef.), 3062 (m, CH, E) ppm. C NMR (75.47 MHz, CDCl ): δ ϭ 13.95 (CH , Z),
(m, 1 H, CH
, Z), 8.48 (s, 1 H, NϭCH, Z), 8.63 (s, 1 H, Nϭ
arom.
13
Ϫ1
3
3
CHarom.,olef.), 3026 (m, CHarom.,olef.), 2958 (s, CHaliph.), 2929 (m, 14.25 (CH3, E), 63.80 (NϪCH , Z), 63.87 (NϪCH , E), 115.84
2
2
CHaliph.), 2871 (m, CHaliph.), 1637 (vs, CϭN), 1596 (m), 1494 (m), (CHϭCH ) 126.65, 126.80, 126.90, 126.96, 127.06, 127.40, 127.48,
2
1
452 (s), 1377 (m), 1342 (w), 1286 (m), 1226 (w), 1028 (m), 964 127.77, 128.92, 129.13, 129.64, 129.94, 129.26, (Carom.), 133.80,
1
3
2 ipso
(m), 798 (w), 754 (s), 696 (s). H NMR (300.13 MHz, CDCl ): δ ϭ (Cipso), 136.13 (CHϭCH ), 138.00, 138.48, (C ), 160.53 (NϭCH,
3
3
ϩ
0
.85 (t, J ϭ 8.83 Hz, 3 H, CH
, E), 1.38 (m, 2 H, CH , Z), 1.52 (m, 2 H, CH
J ϭ 7.39 Hz, 2 H, CH , Z), 2.22 (m, J ϭ 6.91 Hz, 2 H, CH
3
, Z), 0.97 (t, J ϭ 7.40 Hz, 3 H, Z), 160.88 (NϭCH, E) ppm. MS (EI): m/z (%) ϭ 185 (68) [M ],
CH
3
2
2
, E), 2.00 (m, 171 (12), 158 (20), 157 (18), 144 (43), 131 (100). C H N (185.3):
1
3
15
3
3
2
2
3
, E), calcd. C 84.28, H 8.16, N 7.56; found C 83.77, H 8.45, N 7.24.
2
, E), 5.83 (dt, J ϭ
.39, J ϭ 11.44 Hz, 1 H, CHϭCHϪCH , Z), 6.05 (dt, J ϭ 6.91, (E,Z)-Allyl(2-pent-1-enylbenzylidene)amine [(E,Z)-4f]: The imine
3
, E), 6.63 (d, J ϭ 11.45 Hz, was prepared from 1.74 g (10.0 mmol) of (E,Z)-3c and 0.57g (10.0
4
7
.80 (s, 2 H, NϪCH
2
, Z), 4.83 (s, 2 H, NϪCH
3
3
3
3
3
J ϭ 15.50 Hz, 1 H, CHϭCHϪCH
3
CHϭCHϪCH
1
3
, 1 H, Z), 6.86 (d, J ϭ 15.49 Hz, CHϭCHϪCH
H, E), 7.10Ϫ7.40 (m, 8 H, CHarom., E/Z), 7.92 (d, 1 H, CHarom.
3
,
,
mmol) of allylamine in dichloromethane. After removal of the mo-
lecular sieves, the solvent was evaporated under reduced pressure
E), 8.06 (d, 1 H, CHarom., Z), 8.61 (s, 1 H, NϭCH, Z), 8.72 (s, 1
H, NϭCH, E) ppm. 13C NMR (75.47 MHz, CDCl
CH , Z), 19.25 (CH3, E), 65.77 (NϪCH , Z), 65.83 (NϪCH
22.77 (CHϭCHϪCH ), 127.26, 127.49, 127.83, 128.13, 128.34, CHaliph.), 2817 (m, CHaliph.), 1641 (vs, CϭN), 1596 (m), 1477 (m),
28.87, 129.58, 130.08, 130.42, 130.73 (Carom.), 133.20, 134.23, 1444 (s), 1375 (m), 1315 (m), 1288 (m), 1107 (w), 1022 (m), 991
to give 4f (1.93 g, 9.0 mmol, 90%) as a colorless liquid. (Z)/(E)
Ϫ1
): δ ϭ 14.48 ratio ϭ 1:0.4. IR (film): ν˜ ϭ 3062 cm (m, CHarom.,olef.), 3014 (s,
3
(
3
2
2
, E), CHarom.,olef.), 2933 (s, CHaliph.), 2912 (m, CHaliph.), 2875 (m,
1
1
1
3
1
38.53, 139.00, 140.01 (Cipso), 161.02 (NϭCH, Z), 161.30 (NϭCH, (m), 964 (m), 918 (s), 810 (w), 761 (s), 713 (w). H NMR (300.13
ϩ
ϩ
3
E) ppm. GC-MS (70 eV): m/z (%) ϭ 263 (2) [M ], 248 (5) [M
CH
Ϫ PhCH
Ϫ
MHz, CDCl
3
): δ ϭ 0.85 (t, J ϭ 7.39 Hz, 3 H, CH
, E), 1.38 (m, J ϭ 7.39 Hz, 2 H, CH
2
1.52 (m, J ϭ 7.40 Hz, 2 H, CH , E), 2.02 (m, J ϭ 7.39, J ϭ 1.67
3
, Z), 0.97 (t,
, Z),
ϩ
ϩ
5
ϩ
ϩ
3
3
3
], 220 (35) [M Ϫ C
Ϫ C
2
H
], 172 (30) [M Ϫ PhCH
2
], 129 [M
J ϭ 7.40 Hz, 3 H, CH
3
2
ϩ
3
3
4
2
2
H
5
], 115 (8), 91 (100) [PhCH
2
], 65 (12). C19
H
21
N
3
4
(263.3). C 86.65, H 8.04, N 5.32; found C 86.33, H 8.20, N 5.00.
Hz, 2 H, CH
2
, Z), 2.22 (m, J ϭ 7.16, J ϭ 1.67 Hz, 2 H, CH
2
,
Eur. J. Org. Chem. 2004, 3465Ϫ3476
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 3471

K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
FULL PAPER
E), 4.25 (m, 2 H, NϪCH
2
3
2
, E/Z), 5.15 (m, J ϭ 1.67, J ϭ 10.25
aqueous work up and extraction with diethyl ether, the combined
Hz, 1 H, CHϭCHcis, E/Z), 5.25 (m, J ϭ 1.67, J ϭ 17.16 Hz, 1 organic layers were dried with magnesium sulfate. The solvent was
2
3
3
3
H, CHϭCHtrans, E/Z), 5.83 (dt, J ϭ 7.39, J ϭ 11.44 Hz, 1 H, evaporated under reduced pressure and the crude product was puri-
CHϭCHϪCH , Z), 6.05 (m, 1 H, CHϭCHϪCH , E, and 1 H, fied by column chromatography [silica gel; petroleum ether (PE)/
CHϭCH , E/Z), 6.63 (m, J ϭ 11.45 Hz, 1 H, CHϭCHϪCH , Z), ethyl acetate (EA), 5:1 to 10:1].
, E), 7.10Ϫ7.43 (m, 3
H, CHarom., E/Z), 7.90 (m, 1 H, CHarom., E), 8.03 (m, 1 H, CHarom.
Z), 8.50 (s, 1 H, NϭCH, Z), 8.63 (s, 1 H, NϭCH, E) ppm. 13C
NMR (75.47 MHz, CDCl ): δ ϭ 14.12 (CH , Z), 14.35 (CH3, E),
2.86 (CH ), 23.34 (CH ), 30.91 (CH , Z), 35.79 (CH , E), 64.17
NϪCH , Z), 64.26 (NϪCH , E), 116.25 (CHϭCH ), 126.82,
26.92, 127.02, 127.45, 127.88, 128.39, 130.02, 130.35, 130.63
2
2
3
2
3
3
6
.86 (m, J ϭ 15.49 Hz, 1 H, CHϭCHϪCH
3
(
3R*,4S*)-4-Methyl-3-phenyl-4,5-dihydro-3H-benzo[c]azepine
,
[(3R*,4S*)-6a]: The imine (E,Z)-4b (352 mg, 1.50 mmol) was de-
protonated with 1.07 equiv. of LDA (1.60 mmol) in 30 mL of THF.
After warming to 0 °C, the reaction mixture was poured into a
sodium bicarbonate solution (10%; 200 ml). After extraction with
diethyl ether and evaporation of the solvent under reduced pres-
sure, the crude product was purified by column chromatography
3
3
2
(
1
2
2
2
2
2
2
2
(
(
(
C
C
arom., E/Z), 133.29 (Cipso), 134.19 (Cipso), 135.42, 135.76, 136.50
arom., E/Z), 138.80, 138.97, (Cipso), 160.98 (NϭCH, Z), 161.27
(
silica gel; petroleum ether/ethyl acetate, 10:1). (3R*,4S*)-6a (147
ϩ
mg, 0.62 mmol, 42%) was isolated as a colorless powder. R ϭ 0.15
f
NϭCH, E) ppm. MS (70 eV): m/z (%) ϭ 213 (10) [M ], 198 (7)
Ϫ1
ϩ
ϩ
ϩ
ϩ
ϩ
(silica gel; PE/EA, 10:1). M.p. 85 °C. IR (KBr): ν˜ ϭ 3060 cm (m,
[M
Ϫ CH
3
], 183 (23) [M Ϫ C
2
H
5
], 170 (100) [M Ϫ C
H19N (213.3): calcd. C 84.46,
3 7
H ],
CHarom.), 3024 (m, CHarom.), 2956 (s, CHaliph.), 2927 (s, CHaliph.),
1
30 (35), 113 (28), 91 (8), 77 (10). C15
H 8.98, N 6.57; found C 84.03, H 9.12, N 6.47.
2
1
869 (m, CHaliph.), 2850 (m), 1693 (w), 1620 (s, CϭN), 1600 (m),
571 (m), 1492 (m), 1450 (s), 1375 (m), 1311 (w), 1218 (m), 1191
(
E)-Allyl(2-styrylbenzylidene)amine [(E)-4g]: The imine was pre-
(m), 1112 (w), 1074 (w), 1029 (w), 964 (m), 943 (m), 923 (m), 896
(m), 848 (w), 752 (s), 725 (s), 702 (s), 657 (w), 648 (m), 601 (s).
pared from 1.04 g (5.0 mmol) of (E)-3d and 0.28 g (5.0 mmol) of
allylamine in dichloromethane. After removal of the molecular si-
eves, the solvent was evaporated under reduced pressure to give PhCH CHCH ), 2.42 (dd, J ϭ 2.82, J ϭ 12.50 Hz, 1 H, PhCH ),
1
3
3
H NMR (600 MHz, CDCl ): δ ϭ 0.86 (d, J ϭ 6.52 H, 3 Hz,
3
2
2
3
2
3
3
(E)-4g (1.13 g, 4.5 mmol, 88%) as a yellow solid. M.p. 88 °C. IR
2 2 3
2.80 (m, J ϭ 6.63 Hz, 2 H, PhCH , CH CHϪCH ), 4.44 (d, J ϭ
Ϫ1
(
KBr): ν˜ ϭ 3091 cm (m, CHarom.,olef.), 3070 (m, CHarom.,olef.), 3.16 Hz, 1 H, PhCHϪN), 7.20Ϫ7.50 (m, 9 H, CHarom.), 8.76 (s, 1
1
3
3
021 (s, CHarom.,olef.), 2940 (m, CHaliph.), 2905 (m, CHaliph.), 2878 H, CHϭN) ppm. C NMR (75.47 MHz, CDCl ): δ ϭ 18.02
3
(m, CHaliph.), 2864 (m, CHaliph.), 1632 (vs, CϭN), 1590 (m), 1487
(CH3), 41.45 (CH2), 49.12 (CHϪCH3), 68.53 (PhCH),
(
9
m), 1473 (w), 1446 (s), 1370 (m), 1349 (w), 1281 (m), 1026 (m), 120.50Ϫ130.78 (Carom.), 136.52, 140.24, 142.77 (C ), 164.52
ipso
1
ϩ
ϩ
64 (m), 757 (s), 696 (s). H NMR (300.13 MHz, CDCl
3
3
): δ ϭ 4.30
(CHϭN) ppm. MS (70 eV): m/z (%) ϭ 235 (90) [M ], 206 (5) [M
4
2
ϩ
ϩ
(m, J ϭ 1.43 Hz, 2 H, NϪCH
2
), 5.19 (m, J ϭ 1.91, J ϭ 10.25
2 5 9 9 8 8
Ϫ C H ], 165 (5), 131 (100) [C H N ], 115 (22) [C H N ], 91 (28)
2
3
ϩ
Hz, 1 H, CHϭCHcis), 5.21 (m, J ϭ 1.91, J ϭ 17.17 Hz, 1 H, [C H ], 77 (8). C H N (235.3): calcd. C 86.77, H 7.28, N 5.95;
CHϭCHtrans), 6.10 (m, J ϭ 10.25, J ϭ 17.17 Hz, 1 H, CHϭCH
6
7
7
17 17
3
3
2
), found C 86.34, H 7.03, N 5.63.
3
.95 (d, J ϭ 16.21 Hz, 1 H, PhCH), 7.25Ϫ7.90 (m, 10 H, CHarom.,
13
As a byproduct in very little yield crystals of 6,13-dimethyl-
PhCH), 8.68 (s, 1 H, NϭCH) ppm. C NMR (75.47 MHz,
CDCl ): δ ϭ 63.95 (NϪCH ), 115.91 (CHϭCH ), 125.72, 126.69,
26.80, 127.57, 127.88, 128.31, 128.68, 130.30, 132.48, (Carom.
PhCH), 133.50 (Cipso), 136.00 (Carom.), 137.31, 137.88 (Cipso),
7
,14-diphenyl-3,4;10,11-dibenzo-1,8-diazacyclotetradeca-1,3,8,10-
3
2
2
tetraene (8) were isolated.
1
,
X-ray Crystal Structure Analysis of 8:[16] Formula C34
34 2
H N , M ϭ
ϩ
1
(
60.51 (CHϭN) ppm. MS (70 eV): m/z (%) ϭ 235 (2) [M ], 220
4
70.63, colorless crystal, 0.60 ϫ 0.40 ϫ 0.25 mm, a ϭ 12.465(1),
ϩ
ϩ
80) [M Ϫ CH
3
], 144 (3) [M Ϫ PhCH
], 65 (10). C18 17N (247.3): calcd. C 87.41, H 6.93, N
.66; found C 86.80, H 6.93, N 5.22.
2
], 129 (6), 115 (8), 91 (100)
˚
˚
3
b ϭ 9.641(1), c ϭ 21.937(1) A, V ϭ 2636.3(4) A , ρcalcd. ϭ 1.186 g
cm , µ ϭ 5.20 cm , empirical absorption correction with ψ-scan
data (0.746 Յ T Յ 0.881), Z ϭ 4, orthorhombic, space group Pbca
ϩ
[PhCH
2
H
Ϫ3
Ϫ1
5
X-ray Crystal Structure Analysis of (E)-4g:[16] Formula C18
M ϭ 247.33, colorless crystal, 0.25 ϫ 0.10 ϫ 0.05 mm, a ϭ collected (Ϫh, Ϫk, ϩl), [(sinθ)/λ] ϭ 0.62 A , 2679 independent
5
6
sorption correction (0.983 Յ T Յ 0.997), Z ϭ 2, monoclinic, space
group P2
7
independent (Rint ϭ 0.052) and 1901 observed reflections [I Ն 2
σ(I)], 172 refined parameters, R ϭ 0.063, wR ϭ 0.124, max. re-
sidual electron density 0.20 (Ϫ0.26) e·A , hydrogen atoms calcu-
lated and refined as riding atoms.
H
˚
17N, (No. 61), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 2679 reflections
˚
Ϫ1
˚
and 2224 observed reflections [I Ն 2 σ(I)], 165 refined parameters,
.586(1), b ϭ 8.654(1), c ϭ 14.630(1) A, β ϭ 99.47(1)°, V ϭ
˚
3 Ϫ3 Ϫ1
2
97.6(2) A , ρcalcd. ϭ 1.177 g·cm , µ ϭ 0.68 cm , empirical ab-
R ϭ 0.039, wR ϭ 0.117, max. residual electron density 0.17
˚
Ϫ3
(Ϫ0.15) e·A , hydrogen atoms calculated and refined as riding
˚
atoms.
1
(No. 4), λ ϭ 0.71073 A, T ϭ 198 K, ω and ϕ scans,
140 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.65 A , 3144
˚
Ϫ1
4,5-Dimethyl-3-phenyl-4,5-dihydro-3H-benzo[c]azepines [(3R*,4S*,
2
5S*)-6b) and [(3R*,4R*,5R*)-6b]: From (E,Z)-4b (252 mg, 1.1
mmol), LDA (1.18 mmol) and methyl iodide (340 mg, 2.4 mmol).
The crude product was purified by column chromatography (silica
gel; petroleum ether/ethyl acetate, 10:1). Two diastereomeric iso-
mers (3R*,4S*,5S*)-6b (120 mg, 48%) and (3R*,4R*,5R*)-6b (35
˚
Ϫ3
General Procedure for the Synthesis of 4,5-Dihydro-3H-benzo[c]-
azepines 6: For the deprotonation of the benzaldimines 4 the sep-
tum-syringe technique was applied. Lithium diisopropylamide
f
mg, 0.14 mmol, 13%) were isolated as colorless oils. R ϭ 0.23, 0.15
(silica gel; PE/EA, 10:1). Analytical data for (3R*,4S*,5S*)-6b: IR
Ϫ1
(
LDA) was freshly prepared under argon from 1.2 equiv. (1Ϫ2
(film): ν˜ ϭ 3062 cm (m, CHarom.), 3026 (m, CHarom.), 2968 (s,
mmol) of diisopropylamine and 1.1 equiv. of n-butyllithium (1.6  CHaliph.), 2929 (s, CHaliph.), 2879 (CHaliph.), 1770 (w), 1712 (m),
in n-hexane) at Ϫ40 °C in dry THF; 1 equiv. of the benzaldimines
was dissolved in 10 mL of THF and added dropwise over a period
of 30 min to the LDA solution at Ϫ78 °C. After 1 h of stirring at
Ϫ78 °C, the reaction mixture was warmed up to 0 °C and was kept
at this temperature for another 30 min. The reaction mixture was
then treated with a surplus of the respective electrophile. After
1654 (s, CϭN), 1622 (s), 1571 (m), 1533 (w), 1492 (m), 1450 (s),
1380 (m), 1272 (m), 1215 (m), 1188 (m), 1126 (w), 1101 (w), 1060
(w), 1029 (m), 975 (w), 945 (m), 898 (m), 757 (s), 725 (s), 702 (s),
4
1
3
667 (m). H NMR (600 MHz, CDCl
H, PhCH(CH )CHCH
PhCH(CH )CHCH
3
): δ ϭ 0.89 [d, J ϭ 6.68 Hz,
3
3
3
3
], 1.41 [d,
], 2.30 [m, J ϭ 2.15, J ϭ 6.68 Hz, 1 H,
J ϭ 6.68 Hz, 3 H,
3
3
3
3
3472
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3465Ϫ3476

4,5-Dihydro-3H-benzo[c]azepines
FULL PAPER
PhCH(CH
PhCH(CH
3
3
)CHCH
3
], 2.58 [m, 3J ϭ 6.67, 3J ϭ 2.14 Hz, 1 H, (PhCHϪN), 127.05, 127.21, 128.67, 128.67, 128.95, 130.12, 131.67,
)CHCH
3
] 4.48 (m, 3J ϭ 2.14 Hz, 1 H, PhCHϪN), 133.35, 144.15, 144.85, 163.55 (CHϭN) ppm. MS (70 eV): m/z
3
7
.10Ϫ7.55 (m, 9 H, CHarom.), 8.65 (d, J ϭ 2.15 Hz, 1 H, CHϭN) (%) ϭ 263 (100), 234 (7), 220 (16), 193 (3), 159 (44), 117 (50), 91
13
ppm.
C
NMR (75.47 MHz, CDCl
)CHCH 17.64 [PhCH(CH
)CH], 54.92 [PhCH(CH )CH], 68.37 (PhCHϪN),
3
):
δ
ϭ
13.48
(44), 77 (8), 57 (2). C19H21N (263.38): calcd. C 86.65, H 8.04, N
[
[
PhCH(CH
PhCH(CH
3
3
]
3
)CHCH
3
],
41.82 5.32; found C 86.46, H 7.92, N 5.15.
3
3
X-ray Crystal Structure Analysis of (3R*,4R*,5R*)-6c:[16] Formula
1
1
26.56, 126.62, 127.30, 127.83, 128.47, 128.71, 130.36, (Carom.),
35.06, 143.21, 144.11 (Cipso), 162.88 (CHϭN) ppm. MS (70 eV):
C
19
H
21N, M ϭ 263.37, colorless crystal, 0.40 ϫ 0.20 ϫ 0.10 mm,
˚
ϩ
ϩ
a ϭ 11.676(2), b ϭ 11.250(1), c ϭ 23.090(2) A, β ϭ 99.36(1)°, V ϭ
2992.6(6) A , ρcalcd. ϭ 1.169 g·cm , µ ϭ 5.07 cm , no absorption
m/z (%) ϭ 249 (50) [M ], 213 (18), 145 (50) [C11
H
13 ], 127 (100),
], 77 (8), 57 (44). C18
249.3): calcd. C 86.70, H 7.68, N 5.62; found C 85.94, H 7.66, N
.50. For analytical data of (3R*,4R*,5R*)-6b see below.
˚
3
Ϫ3
Ϫ1
ϩ
ϩ
7
1
(
5
15 (10) [C
8
H
8
N ], 91 (28) [C
7
H
19
H N
correction (0.823 Յ T Յ 0.951), Z ϭ 8, monoclinic, space group
˚
P2
1
/c (No. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω/2θ scans, 5357 reflec-
˚
Ϫ1
tions collected (ϩh, ϩk, Ϯl), [(sinθ)/λ] ϭ 0.59 A , 5086 indepen-
(
3R*,4R*,5R*)-4,5-Dimethyl-3-phenyl-4,5-dihydro-3H-benzo[c]- dent (Rint ϭ 0.038) and 2208 observed reflections [I Ն 2 σ(I)], 366
2
azepine [(3R*,4R*,5R*)-6b]: From (E)-4b (235 mg, 1.00 mmol),
LDA (1.10 mmol), and methyl iodide (300 mg, 2.00 mmol). The
crude product was purified by flash chromatography (pentane/ethyl
acetate, 10:1) to give (3R*,4R*,5R*)-6b (169 mg, 0.68 mmol, 68%) ecules, max. residual electron density 0.25 (Ϫ0.25) e· A˚ , hydrogen
as colorless solid, m.p. 113 °C, R
refined parameters, R ϭ 0.077, wR ϭ 0.168, crystals are weakly
diffracting, leading to limited quality of data set and analysis,
asymmetric unit contains two nearly identical independent mol-
Ϫ3
f
ϭ 0.31 (pentane/EA, 10:1). IR
atoms calculated and refined as riding atoms.
(
2
KBr): ν˜ ϭ 3050 (w), 3030 (m, CHarom.,olef.), 2929 (w), 2906 (w),
873 (m, CHaliph.), 1596 (s, CϭN), 1469 (m), 1428 (s), 1346 (s),
184 (s), 1051 (s), 987 (m), 941 (s), 919 (s), 883 (s), 754 (s), 690 (s).
(
3R*,4S*,5S*)-5-Allyl-4-methyl-3-phenyl-4,5-dihydro-3H-benzo-
[c]azepine [(3R*,4S*,5S*)-6d]: From (E,Z)-4b (235 mg, 1.00 mmol),
1
1
3
LDA (1.10 mmol) and allyl bromide (242 mg, 2.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1) (3R*,4S*,5S*)-6d (155 mg, 0.56
mmol, 56%) was isolated as yellow solid, m.p. 88 °C. R ϭ 0.20
(silica gel; PE/EA, 10:1). IR (KBr): ν˜ ϭ 3060 cm (s, CHarom.,olef.),
H NMR (400.13 MHz, CDCl
3
): δϭ 0.81 [d, J ϭ 7.12 Hz, 3 H,
3
PhCH(CH
PhCH(CH
3
)CHCH
3
], 1.31 [d,
J
ϭ
3
7.37 Hz,
3
H,
3
3
3
)CHCH
3
], 2.50 [m, J ϭ 1.52, J ϭ 7.12, J ϭ 11.19
3
3
Hz, 1 H, PhCH(CH
H, PhCH(CH )CHCH
PhCHϪNϭCH), 7.21Ϫ7.35 (m, 9 H, CHarom.), 8.60 (d, J ϭ 2.29
3
)CHCH
3
], 2.74 [m, J ϭ 7.4, J ϭ 1.53 Hz, 1
f
Ϫ1
4
3
3
3
], 3.80 (m, J ϭ 2.29, J ϭ 11.19 Hz, 1 H,
4
3024 (m, CHarom.), 2972 (s, CHaliph.), 2927 (s, CHaliph.), 2877 (s,
Hz, 1 H) ppm. 1 C NMR (100.62 MHz, CDCl
3
CHaliph.), 1645 (s, CϭN), 1622 (s), 1571 (m), 1492 (m), 1450 (s),
3
): δ ϭ 20.69
)CHCH ], 47.08
)CH], 71.71 (PhCHϪN),
1415 (w), 1379 (m), 1342 (m), 1313 (m), 1267 (m), 1211 (m), 1178
[
[
PhCH(CH
PhCH(CH
3
)CHCH
)CH], 54.58 [PhCH(CH
26.54, 126.73, 128.17, 128.19, 128.71, 130.05, 130.08, 132.73
arom.), 144.27 (Cipso), 145.33 (Cipso), 163.05 (CHϭN) ppm. MS
3
],
24.84
[PhCH(CH
3
3
(
(
(
m), 1124 (w), 1076 (w), 1053 (w), 995 (m), 970 (m), 950 (m), 914
s), 850 (w), 810 (w), 757 (s), 730 (s), 702 (s), 665 (m). H NMR
3
3
1
1
3
600 MHz, CDCl
3
): δ ϭ 0.75 (d, J ϭ 6.96 Hz, 3 H, CH
3
), 2.42
(C
3
[m, J ϭ 7.04 Hz, 1 H, PhCH(CH
2
CHϭCH
2
)CH], 2.58 (m, 2 H,
(
70 eV): m/z (%) ϭ 249 (53), 213 (27), 145 (49), 127 (100), 91 (29).
3
3
CH
PhCH(CH
5
1
2
ϪCHϭCH
CHϭCH
.10 (m, 2 H, CHϭCH
H, CHarom.), 7.31Ϫ7.46 (m, 8 H, CHarom.), 8.69 (s, 1 H, CHϭ
2
), 2.75 [dt, J ϭ 6.41, J ϭ 7.86 Hz, 1 H,
18
C H19N (249.35): calcd. C 86.70, H 7.68, N 5.62; found C 85.76,
H 7.73, N 5.92.
3
2
2
)CH], 4.76 (d, J ϭ 6.41 Hz, 1 H, PhCHϪN),
), 5.82 (m, 1 H, CHϭCH ), 7.20Ϫ7.24 (m,
2
2
X-ray Crystal Structure Analysis of (3R*,4R*,5R*)-6b:[16] Formula
C
a ϭ 10.623(1), b ϭ 12.487(1), c ϭ 11.036(1) A, β ϭ 107.85(1)°, V ϭ
1
correction (0.973 Յ T Յ 0.986), Z ϭ 4, monoclinic, space group
P2
reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.66 A , 3306 inde-
pendent (Rint ϭ 0.044) and 2236 observed reflections [I Ն 2 σ(I)],
18
H
19N, M ϭ 249.34, colorless crystal, 0.40 ϫ 0.25 ϫ 0.20 mm,
N) ppm. C NMR (75.47 MHz, CDCl
CH ϪCHϭCH ), 46.97 (CHϪCH ), 48.70 [PhCH(CH
CH )], 65.31 (PhCHϪN), 116.83 (CHϭCH ),126.22, 126.45,
27.37, 128.03, 128.70, 130.04, 131.15, (Carom.), 133.84 (CHϭCH ),
42.43 (Cipso), 143.45 (Cipso), 162.00 (CHϭN) ppm. MS (70 eV):
13
): δ ϭ 13.02 (CH
), 38.03
3
3
˚
(
2
2
3
2
CHϭ
˚
3
Ϫ3
Ϫ1
393.4(2) A , ρcalcd. ϭ 1.189 g·cm , µ ϭ 0.68 cm , no absorption
2
2
1
1
2
˚
1
/c (No. 14), λ ϭ 0.71073 A, T ϭ 198 K, ω and ϕ scans, 5550
˚
Ϫ1
ϩ
ϩ
ϩ
m/z (%) ϭ 275 (15) [M ], 274 (35) [M Ϫ H], 260 (40) [M
Ϫ
ϩ
CH
3
], 232 (15), 218 (20) [M Ϫ CH
85), 129 (100) [M Ϫ C
3
Ϫ H Ϫ C
Ϫ Ph], 115 (50) [C
7 7
[C H ], 77 (9). C20H21N (275.4): calcd. C 87.23, H 7.69, N 5.09;
3 5
H ], 172(18), 143
H N ], 91 (30)
8 8
2
1
74 refined parameters, R ϭ 0.057, wR ϭ 0.114, max. residual
ϩ
ϩ
(
5
H
9
˚
Ϫ3
electron density 0.22 (Ϫ0.17) e·A , hydrogen atoms calculated and
refined as riding atoms.
ϩ
found C 86.58, H 7.01, N 4.85.
(
3R*,4R*,5R*)-5-Ethyl-4-methyl-3-phenyl-4,5-dihydro-3H-benzo-
X-ray Crystal Structure Analysis of (3R*,4S*,5S*)-6d:[16] Formula
[c]azepine [(3R*,4R*,5R*)-6c]: From (E)-4b (235 mg, 1.00 mmol),
C
20
H
21N, M ϭ 275.38, colorless crystal, 0.30 ϫ 0.15 ϫ 0.15 mm,
LDA (1.10 mmol), and ethyl bromide (220 mg, 2.00 mmol). The
crude product was purified by flash chromatography (pentane/ethyl
acetate, 10:1) to give (3R*,4R*,5R*)-6c (173 mg, 0.66 mmol, 66%)
˚
a ϭ 6.705(1), b ϭ 7.419(1), c ϭ 16.359(1) A, α ϭ 79.39(1), β ϭ
˚
3
Ϫ3
79.84(1), γ ϭ 77.84(1)°, V ϭ 773.9(2) A , ρcalcd. ϭ 1.182 g·cm ,
Ϫ1
µ ϭ 5.13 cm , no absorption correction (0.861 Յ T Յ 0.927), Z ϭ
as colorless solid, m.p. 100 °C, R
f
ϭ 0.24 (pentane/EA, 10:1). IR
KBr): ν˜ ϭ 3070 cm , 3050 (m, CHarom.), 2881 (m), 2854 (m,
CHaliph.), 1608 (s, CϭN), 1467 (s), 1436 (s), 1349(s), 1182(s), 1058
¯
˚
2, triclinic, space group P1 (No. 2), λ ϭ 1.54178 A, T ϭ 223 K, ω
Ϫ1
(
and ϕ scans, 5434 reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ
˚
Ϫ1
0
.59 A , 2615 independent (Rint ϭ 0.028) and 2115 observed re-
1
(w), 1018 (w), 933 (w), 873 (w), 746 (s), 692 (s). H NMR (300.13
2
flections [I Ն 2 σ(I)], 192 refined parameters, R ϭ 0.039, wR ϭ
.100, max. residual electron density 0.17 (Ϫ0.15) e·A , hydrogen
3
MHz, CDCl
3
): δ ϭ 0.56 (t, J ϭ 14.79 Hz, 3 H, CH
J ϭ 7.15 Hz, 3 H, CH ), 1.64 (m, 2 H, CH CH ), 2.33 (m, 1 H,
CH CH CH), 2.49 [m, 1 H, PhCH(CH )CHCH CH ], 3.75 (m,
J ϭ 1.9 Hz, 1 H, PhCHϪN), 7.10Ϫ7.30 (m, 9 H, CHarom.), 8.50 (3R*,4R*,5R*)-5-Allyl-4-methyl-3-phenyl-4,5-dihydro-3H-benzo-
2
CH
3
), 0.72 (d,
˚
Ϫ3
0
3
3
2
3
atoms calculated and refined as riding atoms.
3
2
3
2
3
4
d, J ϭ 1.9 Hz, 1 H, CHϭN) ppm. 13C NMR (75.47 MHz,
CDCl ): δ ϭ 13.25 (CH ), 21.51 (CH ), 31.74 (CH CH ), 53.86
PhCH(CH )CHCH CH ], 55.56 [PhCH(CH )CHCH CH
4
[c]azepine [(3R*,4R*,5R*)-6d]: From (E)-4b (235 mg, 1.00 mmol),
LDA (1.10 mmol), and allyl bromide (240 mg, 2.00 mmol). The
(
3
3
3
2
3
[
3
2
3
3
2
3
], 71.99 crude product was purified by flash chromatography (pentane/ethyl
Eur. J. Org. Chem. 2004, 3465Ϫ3476
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3473

K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
7.20 (m, 1 H, CHarom.), 7.26Ϫ7.38 (m, 6 H, CHarom.), 7.46 (m, 2
FULL PAPER
acetate, 100:8) to yield (3R*,4R*,5R*)-6d (198 mg, 0.72 mmol,
7
(
2%) as colorless viscous oil; R
film): ν˜ ϭ 3080 (w), 3000 (m, CHarom.), 2915 (w), 2892 (m, CDCl
CHaliph.), 1687 (s), 1625 (s, CϭN), 1535 (w), 1471 (w), 1438 (w), (PhCH
346 (w), 1278 (w), 1070 (w), 1006 (w), 975 (s), 906 (w), 750 (s), 127.51, 128.03, 128.18, 129.06, 129.79, 134.79 (Carom.), 140.37,
f
ϭ 0.20 (pentane/EA, 10:1). IR H, CHarom.), 8.66 (s, 1 H, CHϭN) ppm. 13C NMR (75.47 MHz,
3
): δ ϭ 14.01 (CH
3
2 3 2
), 20.04 (CH CH ), 31.87 (CHCH ), 37.71
2
CH), 53.35 (PhCH
2
CH), 67.00 (PhCHϪN), 126.20, 126.46,
1
6
1
3
96 (s). H NMR (300.13 MHz, CDCl
), 2.30 [m, 1 H, PhCH(CH
ϪCHϭCH ), 2.65 [m, 1 H, PhCH(CH
.72 (d, J ϭ 11.2 Hz, 1 H, PhCHϪN), 4.79 (m, 2 H, CHϭCH
.40 (m, 1 H, CHϭCH ), 7.10Ϫ7.26 (m, 9 H, CHarom.), 8.52 (s, 1
): δ ϭ 20.79
), 52.21 (CHϪCH ), 52.73
], 71.60 (PhCHϪN), 116.22 (CHϭCH ),
26.78, 127.37, 128, 128.23, 128.54, 129.88, 130.88, 133.09 (Carom.),
36.66 (CHϭCH ), 143.19, 144.24, 163.26 (CHϭN) ppm. MS (70
3
): δ ϭ 0.71 (d, J ϭ 6.92
CHϭCH )CH], 2.50 (m, (52) [M ], 220 (100) [M Ϫ C
CHϭCH
142.48 (Cipso), 162.77 (CHϭN) ppm. MS (70 eV): m/z (%) ϭ 263
ϩ
ϩ
Hz, 3 H, CH
3
2
2
3 7
H ], 206 (10), 159 (28), 129 (58)
ϩ
ϩ
2
3
5
H, CH
2
3
2
2
2
)CH],
),
[C
9
H
9
N ], 117 (69), 106 (10), 91 (52) [C
7 7
H ], 77 (10), 65 (5).
2
C H21N (263.3): calcd. C 86.65, H 8.04, N 5.32; found C 86.19, H
19
2
7.93, N 4.98.
1
3
H, CHϭN) ppm. C NMR (75.47 MHz, CDCl
CH ), 42.27 (CH ϪCHϭCH
PhCH(CH CHϭCH
3
X-ray Crystal Structure Analysis of (3R*,4S*)-6f:[16] Formula
(
[
1
1
3
2
2
3
C
19
H
21N, M ϭ 263.37, colorless crystal, 0.50 ϫ 0.40 ϫ 0.20 mm,
2
2
2
˚
a ϭ 7.599(1), b ϭ 19.064(1), c ϭ 10.413(1) A, β ϭ 94.73(1)°, V ϭ
˚
3
Ϫ3
Ϫ1
1503.4(3) A , ρcalcd. ϭ 1.164 g·cm , µ ϭ 5.04 cm , no absorption
2
correction (0.787 Յ T Յ 0.906), Z ϭ 4, monoclinic, space group
eV): m/z (%) ϭ 275 (36), 260 (39), 232 (14), 218 (15), 193 (7), 146
17), 129 (100), 115 (50), 91 (61), 77 (13), 55 (8). C20 21N (275.39):
calcd. C 87.23, H 7.69, N 5.09; found C 86.83, H 7.83, N 5.14.
˚
P2
1
/n (No. 14), λ ϭ 1.54178 A, T ϭ 223 K, ω and ϕ scans, 4351
(
H
˚
Ϫ1
reflections collected (Ϯh, Ϯk, Ϯl), [(sinθ)/λ] ϭ 0.59 A , 2537 inde-
pendent (Rint ϭ 0.022) and 2253 observed reflections [I Ն 2 σ(I)],
2
1
83 refined parameters, R ϭ 0.036, wR ϭ 0.089, max. residual
(
3R*,4S*,5S*)-5-Benzyl-4-methyl-3-phenyl-4,5-dihydro-3H-benzo-
˚
Ϫ3
electron density 0.15 (Ϫ0.13) e·A , hydrogen atoms calculated and
[c]azepine [(3R*,4S*,5S*)-6e]: From (E,Z)-4b (235 mg, 1.00 mmol),
refined as riding atoms.
LDA (1.10 mmol) and benzyl bromide (340 mg, 2.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1). (3R*,4S*,5S*)-6e (155 mg,
(
3R*,4S*,5S*)-5-Methyl-3-phenyl-4-propyl-4,5-dihydro-3H-benzo-
[c]azepine [(3R*,4S*,5S*)-6g]: From (E,Z)-4c (263 mg, 1.00 mmol),
0
.56 mmol, 56%) was isolated as yellow oil, which contains small
amounts of a diastereomeric compound of unkown configuration.
ϭ 0.12 (silica gel; PE/EA, 10:1). IR (film): ν˜ ϭ 3105 cmϪ1 (sh,
CHarom.), 3085 (m, CHarom.), 3032 (s, CHarom.), 2973 (s, CHaliph.),
LDA (1.10 mmol) and methyl iodide (284 mg, 2.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1). (3R*,4S*,5S*)-6g (136 mg,
R
f
f
0.49 mmol, 49%) was isolated as a colorless solid. R ϭ 0.22 (silica
2
1
933 (s, CHaliph.), 1663 (s, CϭN), 1630 (s), 1492 (m), 1453 (m),
gel; PE/EA, 10:1). M.p. 92Ϫ94 °C. IR (KBr): ν˜ ϭ 3060 (m,
CHarom.), 3024 (m, CHarom.), 2958 (s, CHaliph.), 2929 (s, CHaliph.),
380 (m), 1308 (w), 1262 (w), 1189 (m), 1025 (m), 952 (m), 906
1
(
m), 762 (m), 709 (s). H NMR (600 MHz, CDCl
3
): δ ϭ 0.59 (d,
), 2.33 [m, 1 H, PhCH(PhCH )CHCH ],
.02 [m, 3 H, PhCH(PhCH )CH], 4.89 (m, 1 H, PhCHϪN),
.10Ϫ7.40 (m, 14 H, CHarom.), 8.62 (s, 1 H, CHϭN) ppm.
): 13.07 (CH ), 41.25
)CH], 44.71 [PhCH(PhCH )CHϪCH ], 50.84
)CH], 65.20 (PhCHϪN), 126.16, 126.54, 126.87,
2
1
869 (s, CHaliph.), 1645 (m), 1622 (s, CϭN), 1571 (m), 1492 (m),
450 (s), 1377 (m), 1340 (m), 1303 (m), 1290 (m), 1213 (w), 1176
3
J ϭ 6.92 Hz, 3 H, CH
3
2
3
3
7
2
(
(
0
CH
CH
w), 1101 (w), 1070 (w), 1029 (m), 983 (w), 952 (w), 916 (m), 898
1
3
C
1
m), 759 (s), 736 (m), 702 (s). H NMR (600 MHz, CDCl
3
): δ ϭ
), 0.78 (m, 1 H,
), 1.02 (m, 1 H,
) 1.34 [d, J ϭ 6.93 Hz, 3 H, PhCH(CH )CH], 1.36
6.93 Hz, H,
NMR (75.47 MHz, CDCl
3
δ
ϭ
3
3
.55 (t, J ϭ 7.29 Hz, 3 H, CH
2
CH
CH
2
CH
CH
3
[
[
PhCH(PhCH
PhCH(PhCH
2
2
3
2
CH
CH
1
2
CH
CH
H, CH
3
), 0.93 (m, 1 H, CH
2
2
3
2
3
2
2
3
3
1
1
3
1
C
7
27.35, 128.00, 128.11, 128.24, 128.55, 129.53, 129.96, 131.04,
3
(m,
2
CH
2
CH
3
), 2.10 [m,
J
ϭ
1
32.31 (Carom., Cipso), 161.40 (CHϭN) ppm. MS (70 eV): m/z (%) ϭ
3
3
PhCH(CH
PhCH(CH
3
)CH], 2.85 [m, J ϭ 14.22, J ϭ 7.11 Hz, 1 H,
)CH], 4.65 (m, 1 H, PhCHϪN), 7.17 (m, 1 H, CHarom.),
ϩ
ϩ
7 7
25 (100) [M ], 234 (22) [M Ϫ C H ], 205 (10), 193 (8), 165(5),
3
ϩ
ϩ
ϩ
29 (25) [M Ϫ C
23N (325.4): calcd. C 88.57, H 7.12, N 4.30; found C 87.56, H
.42, N 4.07.
5 9 8 8 7 7
H ,ϪPh], 115 (13) [C H N ], 91 (68) [C H ].
7
.22Ϫ7.35 (m, 6 H, Carom.), 7.42 (m, 2 H, Carom.), 8.54 (s, 1 H,
24
H
13
CHϭN) ppm. C NMR (75.47 MHz, CDCl
CH CH CH ), 20.64 (CH ), 20.84 [PhCH(CH )CH], 29.56 (CH
0.25 [PhCH(CH )CH], 55.76 [PhCH(CH )CH], 65.49
PhCHϪN), 126.14, 126.24, 127.34, 128.03, 128.08, 130.13, 130.80,
33.80 (Carom.), 143.96 (Cipso), 144.42, 161.65 (CHϭN) ppm. MS
3
): δ ϭ 14.18
(
4
(
1
2
2
3
2
3
2
),
3
3
(
3R*,4S*)-3-Phenyl-4-propyl-4,5-dihydro-3H-benzo[c]azepine
[(3R*,4S*)-6f]: (E,Z)-4c (263mg, 1.00 mmol) was deprotonated
with 1.10 equiv. of LDA (1.10 mmol) in 30 mL of dry THF. After
warming to 0 °C, the reaction mixture was poured into sodium
bicarbonate solution (10%; 200 ml). After extraction with diethyl
ether and evaporation of the solvent under reduced pressure, the
crude product was purified by column chromatography (silica gel;
ϩ
(
70 eV): m/z (%) ϭ 277 (43) [M ], 219 (35), 205 (5), 171 (10), 132
ϩ
(
100), 117 (5), 106 (18) 91 (28) [C
7 7
H ]. C20H23N (277.3): calcd. C
86.59. H 8.36, N 5.05; found C 86.19, H 7.93, N 4.98.
(3R*,4S*,5S*)-5-Ethyl-3-phenyl-4-propyl-4,5-dihydro-3H-benzo-
petroleum ether/ethyl acetate, 10:1). (3R*,4S*)-6f (200 mg, 0.51 [c]azepine [(3R*,4S*,5S*)-6h]: From (E,Z)-4c (263 mg, 1.00 mmol),
mmol, 51%) was isolated as a colorless powder. R
gel; PE/EA, 10:1). M.p. 90 °C. IR (KBr): ν˜ ϭ 3051 cm (m,
CHarom.), 3026 (m, CHarom.), 2956 (s, CHaliph.), 2925 (s, CHaliph.),
f
ϭ 0.27 (silica
LDA (1.10 mmol) and ethyl bromide (284 mg, 2.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1). (3R*,4S*,5S*)-6h (110 mg,
Ϫ1
2856 (m, CHaliph.), 1704 (m), 1689 (m), 1625 (m), 1608 (s, CϭN), 0.38 mmol, 38%) was isolated as a colorless oil. R
f
ϭ 0.15 (silica
1
577 (m), 1512 (s), 1496 (m), 1456 (m), 1379 (m), 1330 (w), 1307 gel; PE/EA, 10:1). IR (film): ν˜ ϭ 3062 (m, CHarom.), 3026 (m,
(
9
m), 1263 (w), 1209 (m), 1170 (m), 1109 (m), 1043 (m), 1020 (m),
CHarom.), 2964 (s, CHaliph.), 2931 (s, CHaliph.), 2873 (s, CHaliph.),
): 1710 (m), 1650 (s, CϭN), 1602(m), 1575 (m), 1492 (m), 1450 (s),
), 1379 (m), 1342 (m), 1294 (m), 1253 (m), 1180 (w), 1116 (w), 1074
1
73 (w), 846 (w), 811 (m), 750 (s). H NMR (600 MHz, CDCl
3
3
δ ϭ 0.77 (t, J ϭ 7.16 Hz, 3 H, CH
3
), 1.05 (m, 1 H, CHCH
2
2
1
1
6
6
.21Ϫ1.40 (m, 3 H, CH
2
CH
2
CH
3
, CH
2 2 3
CH CH ), 2.38 (dd, J ϭ (w), 1029 (m), 986 (w), 958 (w), 916 (m), 892 (w), 829 (w), 757 (s),
3
3
3
1
3
3.95, J ϭ 10.89 Hz, 1 H, PhCH
2
CH), 2.69 (m, J ϭ 10.89, J ϭ 727 (m), 702 (s). H NMR (600 MHz, CDCl
3
): δ ϭ 0.57 (t, J ϭ
CH CH ), 1.03 (t,
CH CH ) 1.16
3
2
3
.30, J ϭ 5.63 Hz, 1 H, PhCH
2
CH), 2.84 (dd, J ϭ 13.95, J ϭ 7.12 Hz, 3 H, CH
2
CH
2
CH
3
), 0.82 (m, 2 H, CH
), 1.04 (m, 1 H, CH
2
2
3
3
3
.49 Hz, 1 H, PhCH CH), 4.50 (d, J ϭ 3.73 Hz, 1 H, PhCHϪN),
2
J ϭ 7.40 Hz, 3 H, CH
2
CH
3
2
2
3
3474
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3465Ϫ3476

4,5-Dihydro-3H-benzo[c]azepines
FULL PAPER
(
m, 1 H, CH CH CH ), 1.78 (m, 2 H, CH CH ), 2.25 [m, 1 H, [PhCH(PhCH )CH], 48.74 [PhCH(PhCH )CH], 64.55 (PhCHϪN),
2
2
3
2 3 2 2
], 2.83 [dt, J ϭ 14.52, 3J ϭ 8.06 Hz, 1 H, 126.05, 126.38, 126.68, 127.39, 127.93, 128.47, 129.04, 130.30,
3
PhCH(CH
PhCH(CH
2
2
CH
CH
3
)CH
2
3
3
)CH], 5.05 (m, J ϭ 3.28 Hz, 1 H, PhCHϪN), 7.24 131.00 (Carom.), 132.82 (Cipso), 134.77 (Carom.), 139.09, 142.72,
(
m, 1 H, CHarom.), 7.28Ϫ7.46 (m, 7 H, CHarom.), 7.51 (m, 1 H, 144.10 Cipso), 160.69 (CHϭN) ppm. MS (70 eV): m/z (%) ϭ 353
CHarom.), 8.54 (d, 3J ϭ 3.28 Hz, 1 H, CHϭN) ppm. C NMR (45) [M ], 310 (10) [M Ϫ C
13
ϩ
ϩ
H ], 262 (13), 220 (100) [C16H14N ],
ϩ
3 7
ϩ
ϩ
(
2
[
75.47 MHz, CDCl
0.34 (CH ),
PhCH(CH CH
3
): δ ϭ 12.19 (CH
28.11 (CH ),
)CH], 48.99 [PhCH(CH
2
CH
29.47
2
CH
3
), 13.95 (CH
(CH ),
)ϪCH(CH
2
CH
46.71
CH
3
), 193 (6), 129 (15), 115 (13) [C
8 8 7 7
H N ], 91 (72) [C H ].
2
2
2
(3R*,4R*)-3,4-Diphenyl-4,5-dihydro-3H-benzo[c]azepine [(3R*,4R*)-
2
3
2
CH
3
2
2
-
6k]: (E)-4d (297 mg, 1.00 mmol) was deprotonated with lithium
3
CH )], 64.97 (PhCHϪN), 126.11, 126.43, 127.44, 128.02, 128.08,
1
1
2
,2,6,6-tetramethylpiperidide (TMP; 1.00 mmol) in 40 mL of dry
28.29, 130.22, 130.54, (Carom.), 132.86 (Cipso), 134.08 (Carom.),
THF at Ϫ78 °C. To the reaction mixture were added some drops
of water at Ϫ78 °C. After aqueous workup and evaporation of
solvents, the crude product was purified by column chromatogra-
phy (silica gel; petroleum ether/ethyl acetate, 10:1). Small amounts
of remaining tetramethylpiperidine could not be separated from the
43.50, 144.10 (Cipso), 160.94 (CHϭN). MS (70 eV): m/z (%) ϭ 291
ϩ
(43) [M ], 219 (35), 205 (5), 171 (10), 132 (100), 117 (5), 106 (18)
ϩ
9
1 (28) [C
7 7
H ]. C21H25N (291.4): calcd. C 86.55, H 8.65, N 4.81;
found C 85.98, H 8.81, N 4.70.
f
product (3R*,4R*)-6k (GC purity ca. 81%, 155 mg, 29%). R ϭ
(
3R*,4S*,5S*)-5-Allyl-3-phenyl-4-propyl-4,5-dihydro-3H-benzo-
1
0
2
1
3
.17 (silica gel; PE/EA, 10:1). H NMR (300.13 MHz, CDCl ): δ ϭ
[c]azepine [(3R*,4S*,5S*)-6i]: From (E,Z)-4c (394 mg, 1.50 mmol),
2
3
1
2
.77 ppm (dd, J ϭ 14.07, J ϭ 1.43 Hz, 1 H, H ), 3.22 (dd, J ϭ
LDA (1.50 mmol) and allyl bromide (363 mg, 3.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1). (3R*,4S*,5S*)-6i (330 mg, 1.08
mmol, 72%) was isolated as a colorless solid, containing a second
diastereoemer of unknown configuration. R ϭ 0.12 (silica gel; PE/
f
EA, 10:1). M.p. 97 °C. IR (KBr): ν˜ ϭ 3062 (m, CHarom.), 3026 (m,
3
2
3
3
4.07, J ϭ 8.34 Hz, 1 H, H ), 3.71 (ddd, J ϭ 1.43, J ϭ 8.34,
3
3
3
4
J ϭ 11.68 Hz, 1 H, H ), 4.33 (dd, J ϭ 11.68, J ϭ 2.14 Hz, 1 H,
4
H ), 6.75 (m, 2 H, CHarom.), 7.00 (m, 9 H, CHarom.), 7.18 (m, 1 H,
CHarom.), 7.33 (m, 2 H, CHarom.), 8.62 (d, J ϭ 2.14 Hz, 1 H, CHϭ
4
N) ppm.
CHarom.), 2964 (s, CHaliph.), 2931 (s, CHaliph.), 2873 (s, CHaliph.),
(
3R*,4S*,5S*)-5-Ethyl-4-methyl-3-vinyl-4,5-dihydro-3H-benzo-
1710 (m), 1650 (s, CϭN), 1602(m), 1575 (m), 1492 (m), 1450 (s),
[c]azepine [(3R*,4S*,5S*)-6l]: From (E,Z)-4e (278 mg, 1.60 mmol),
1379 (m), 1342 (m), 1294 (m), 1253 (m), 1180 (w), 1116 (w), 1074
LDA (1.70 mmol) and ethyl bromide (327 mg, 3.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 5:1) and (3R*,4S*,5S*)-6l (151 mg,
(
w), 1029 (m), 986 (w), 958 (w), 916 (m), 892 (w), 829 (w), 757 (s),
1
3
7
7
2
27 (m), 702 (s). H NMR (600 MHz, CDCl
.30 Hz, 3 H, CH CH CH ), 0.85 (m, 2 H, CH
H, CH CH CH ), 2.28 [m, 1 H, CH(CH CH
CHϭCH
CHϭCH
), 5.88 (m, 1 H, CHϭCH
3
): δ ϭ 0.57 (t, J ϭ
CH CH ), 1.12 (m,
CH )], 2.52 [m, 2
)], 3.08 [m, J ϭ 13.25, J ϭ 7.40 Hz, 1
)CH], 5.07 (m, 1 H, PhCHϪN), 5.15 (m,
) 7.24 (m, 2 H, CHarom.),
2
2
3
2
2
3
0
f
.71 mmol, 44%) was isolated as a yellow oil. R ϭ 0.23 (silica gel;
2
2
3
2
2
3
Ϫ1
PE/EA, 5:1). IR (film): ν˜ ϭ 3060 cm (s, CHarom.,olef.), 3024 (m,
CHarom.), 2972 (s, CHaliph.), 2927 (s, CHaliph.), 2877 (s, CHaliph.),
1
1
3
3
H, PhCH(CH
H, PhCH(CH
2
7
7
2
2
2
2
645 (s, CϭN), 1622 (s), 1571 (m), 1492 (m), 1450 (s), 1415 (w),
379 (m), 1342 (m), 1313 (m), 1267 (m), 1211 (m), 1178 (m), 1124
H, CHϭCH
2
2
3
.30Ϫ7.40 (m, 5 H, CHarom.), 7.44 (d, J ϭ 7.20 Hz, 1 H, Carom.),
(
(
w), 1076 (w), 1053 (w), 995 (m), 970 (m), 950 (m), 914 (s), 850
w), 810 (w), 757 (s), 730 (s), 702 (s), 665 (m). H NMR (300.13
.50 (m, 1 H, CHarom.), 8.59 (s, 1 H, CHϭN) ppm. 13C NMR
1
(
(
4
75.47 MHz, CDCl
CH ), 41.19 (CH
6.87 [PhCH(CH CHϭCH
3
): δ ϭ 13.94 (CH
CHϭCH ), 46.40 [PhCH(CH
)CH], 64.41 (PhCHϪN), 117.19 (CHϭ
2
CH
2
CH
3
), 20.32 (CH
2
), 27.99
MHz, CDCl
3 2 3
): δ ϭ 0.92 (m, 6 H, CH CH3, CH ), 1.74 (m, 2 H,
2
2
2
2
CHϭCH
2
)CH],
2
1
3
CH CH ), 2.23 (m, 1 H, H ), 2.43 (m, 1 H, H ), 4.04 (m, J ϭ
3
3
2
3
2
2
4
3
2
3
3
.17, J ϭ 2.61 Hz, 1 H, H ), 5.18 (m, J ϭ 1.59, J ϭ 10.44, J ϭ
CH
2
), 126.11Ϫ144.20 (Carom., Cipso), 136.12 (CHϭCH
2
ϩ
), 160.82
3
3
.17 Hz, 1 H, CHϭCHcis), 5.30 (m, J ϭ 17.16, J ϭ 3.36 Hz, 1
(
CHϭN) ppm. GC-MS (70 eV): m/z (%) ϭ 303 (10) [M ], 274 (45)
3
3
H, CHϭCHtrans), 6.12 (m, J ϭ 10.45, J ϭ 17.16 Hz, 1 H, CHϭ
ϩ
ϩ
ϩ
[M
Ϫ C
2
H
5
], 260 (60) [M Ϫ C
3
ϩ
H
7
], 220 (75) [C16
H14N ], 158
4
CH
2
), 7.28Ϫ7.40 (m, 4 H, CHarom.), 8.69 (d, J ϭ 2.61 Hz, 1 H,
): δ ϭ 12.38
), 45.74 (CH), 50.73
), 126.19, 128.30, 130.04,
31.22, (Carom.), 133.15 (Cipso), 139.99 (CHϭCH ), 142.77 (Cipso),
ϩ
(
56), 143 (90), 129 (100) [C
25N (303.4): calcd. C 87.08, H 8.30, N 4.62; found C 86.10, H
.32, N 4.31.
9 7 7 7
H N ], 115 (80), 91 (83) [C H ].
CHϭN) ppm. 13C NMR (75.47 MHz, CDCl
3
22
C H
8
(CH
2 3 3 2 3
CH ), (13.80 (CH ), 26.00 (CH CH
CH), 64.26 (CH), 114.92 (CHϭCH
(
1
1
2
2
(
3R*,4S*,5S*)-5-Benzyl-3-phenyl-4-propyl-4,5-dihydro-3H-benzo-
ϩ
61.85 (CHϭN) ppm. MS (70 eV): m/z (%) ϭ 213 (10) [M ], 212
], 184 (95) [M Ϫ 2CH ],
3
8 8
68 (33), 159 (25), 143 (68), 129 (60), 115 (50) [C H N ], 91 (13)
[c]azepine [(3R*,4S*,5S*)-6j]: From (E,Z)-4c (406 mg, 1.60 mmol),
ϩ
ϩ
ϩ
(
22) [M Ϫ H], 198 (100) [M Ϫ CH
3
LDA (1.60 mmol) and benzyl bromide (513 mg, 3.00 mmol). The
crude product was purified by column chromatography (silica gel;
petroleum ether/ethyl acetate, 10:1). (3R*,4S*,5S*)-6j (155 mg, 0.44
ϩ
1
ϩ
[C
7
H
7
]. C15
H19N (213.2): calcd. C 84.46, H 8.98, N 6.57; found
C 84.43, H 9.25, N 6.66.
mmol, 27%) was isolated as a yellow oil. R
f
ϭ 0.17 (silica gel; PE/
Ϫ1
EA, 10:1). IR (film): ν˜ ϭ 3085 cm
(m, CHarom.), 3062 (s, (3R*,4S*,5S*)-5-Methyl-4-propyl-3-vinyl-4,5-dihydro-3H-benzo-
CHarom.), 3028 (m, CHarom.) 2958 (s, CHaliph.), 2929 (s, CHaliph.), [c]azepine [(3R*,4S*,5S*)-6m]: From (E,Z)-4f (213 mg, 1.00 mmol),
2
1
871(s), 1739 (w), 1649 (s, CϭN), 1602 (m), 1575 (m), 1494 (s),
456 (m), 1379 (m), 1340 (m), 1292 (m), 1259 (w), 1178 (m), 1114
LDA (1.10 mmol) and methyl iodide (284 mg, 2.00 mmol). The
crude product was purified by column chromatography (silica gel;
(
(
w), 1076 (w), 1029 (w), 983 (w), 956 (w), 916 (m), 892 (w), 844 petroleum ether/ethyl acetate, 10:1) and (3R*,4S*,5S*)-6m (30 mg,
w), 759 (m), 721 (m), 700 (s), 657 (m). 1H NMR (600 MHz,
0.13 mmol, 13%) was isolated as a yellow oil. R ϭ 0.28 (silica gel;
): δ ϭ 0.59 (m, 3 H, CH CH CH
), 0.80 (m, 2 H, PE/EA, 10:1). IR (film): ν˜ ؍ 3057 cm (m, CHarom.,olef.), 2974 (s,
CH CH ), 1.05 (m, 2 H, CH CH CH ), 2.15 [m, 1 H, CHaliph.), 2933 (s, CHaliph.), 2843 (m, CHaliph.), 1728(m), 1639 (s,
PhCH(PhCH )CH], 3.02 [m, 2 H, PhCH(PhCH )CH], 3.35 (m, 1 CϭN), 1487 (m), 1473 (s), 1377 (s), 1342 (m), 1313 (m), 1170 (m),
H, PhCH(PhCH )CH), 4.89 (m, 1 H, PhCHϪN), 7.10Ϫ7.40 (m,
4 H, CHarom.), 8.62 (s, 1 H, CHϭN) ppm. 13C NMR (75.47
f
Ϫ1
CDCl
CH
3
2
2
3
2
2
3
2
2
3
2
2
1
2
1129 (w), 1109 (s), 1033 (m), 930 (m), 914 (s), 757 (s). H NMR
3
1
(300.13 MHz, CDCl
3
): δ ϭ 0.83 (t, J ϭ 7.27 Hz, 3 H,
), 1.18 (m, 1 H, CH CH CH ), 1.25Ϫ1.36 (m, 5 H,
, CH ), 1.56 (m, 1 H, CH CH CH ), 2.01 (m, 1 H),
MHz, CDCl
3
): δ ϭ 13.78 (CH
), 43.56
3
), 20.19 (CH
[PhCH(PhCH
2
CH
)CH],
2
CH
3
), 27.88 CH
45.14 CH
2
CH
2
CH
3
2
2
3
(CH
2
CH
2
CH
3
2
2
CH
2
CH
3
3
2
2
3
Eur. J. Org. Chem. 2004, 3465Ϫ3476
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3475

K. Gerdes, P. Sagar, R. Fröhlich, B. Wibbeling, E.-U. Würthwein
FULL PAPER
2
3
3
2.85 (m, 1 H), 4.04 (m, 1 H), 5.18 (m, J ϭ 1.59, J ϭ 10.44, J ϭ
V. , 1994) and COLLECT (Nonius B. V., 1998), data reduction:
MolEN (K. Fair, EnrafϪNonius B. V., 1990) and Denzo-SMN
(Z. Otwinowski, W. Minor, Methods Enzymol. 1997, 276,
307Ϫ326), absorption correction for CCD data: SORTAV (R.
H. Blessing, Acta Crystallogr., Sect. A 1995, 51, 33Ϫ37; R. H.
Blessing, J. Appl. Crystallogr. 1997, 30, 421Ϫ426), structure
solution: SHELXS-97 (G. M. Sheldrick, Acta Crystallogr.,
Sect. A 1990, 46, 467Ϫ473), structure refinement: SHELXL-
97 (G. M. Sheldrick, University of Göttingen, 1997), graphics:
SCHAKAL (E. Keller, University Freiburg, 1997). CCDC-
230966 [(3R*,4S*)-6f], -230967 (8), -230968 [(3R*,4S*,5S*)-
6d], -230970 [(3R*,4R*,5R*)-6b], -230971 [(3R*,4R*,5R*)-6c],
and -230972 [(E)-4g] contain the supplementary crystallo-
graphic data for this paper. These data can be obtained free of
charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; Fax: (internat.) ϩ 44-1223-336033;
E-mail: deposit@ccdc.cam.ac.uk].
3
3
3.17 Hz, 1 H, CHϭCHcis), 5.30 (m, J ϭ 17.16, J ϭ 3.36 Hz, 1
3
3
H, CHϭCHtrans), 6.12 (m, J ϭ 10.45, J ϭ 17.16 Hz, 1 H, CHϭ
4
CH
2
) 7.28Ϫ7.40 (m, 4 H, CHarom.), 8.69 (d, J ϭ 2.61 Hz, 1 H,
): δ ϭ 14.42
CH CH ), 30.42
), 40.19 (CH), 53.94 (CH), 64.21 (CH), 114.59 (CHϭ
CHϭN) ppm. 13C NMR (75.47 MHz, CDCl
3
(CH
2
2
CH
CH
2
CH
3
), 20.37 (CH
3
), 21.32 (CH
2
2
3
(CH
2
CH
3
CH
CHϭCH
m/z (%) ϭ 227 (60) [M ], 212 (22) [M Ϫ CH
2
), 126.09, 127.91, 130.05, 130.65, (Carom.), 133.87 (Cipso), 140.60
(
2
), 144.45 (Cipso), 161.36 (CHϭN) ppm. MS (70 eV):
ϩ
ϩ
ϩ
3
], 198 (25) [M
Ϫ
ϩ
ϩ
C
2
H
5
], 184 (100) [M Ϫ C
3
H
7
], 170 (95) [M Ϫ C Ϫ CH ], 159
3
H
7
2
ϩ
(30), 143 (72), 127 (53), 117 (32), 91 (13) [C H ].
7 7
Acknowledgments
Support by the Graduiertenkolleg ‘‘Hochreaktive Mehrfachbin-
dungssysteme’’ (DFG), the Sonderforschungsbereich 424 (DFG),
the International Graduate School of Chemistry NRW and by the
Fonds der Chemischen Industrie (Frankfurt) is gratefully acknowl-
edged. We thank Prof. Dr. D. Hoppe for helpful discussions and
Mr. Ralph Reiermann for valuable technical assistance.
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1
Data sets were collected with Enraf Nonius CAD4 and Nonius
KappaCCD diffractometers, which, in the case of Mo radi-
ation, were equipped with a rotating anode generator Nonius
FR591. Programs used: data collection: EXPRESS (Nonius B.
Received March 26, 2004
3476
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 3465Ϫ3476