Insertion of allenes into the Pd-C bond of ortho-palladated primary arylamines of biological relevance: Phenethylamine, phentermine, (l)-Phenylalanine methyl ester, and (l)-tryptophan methyl ester. Synthesis of tetrahydro-3-benzazepines and their salts

Article abstract of DOI:10.1021/om300928j

The previously reported ortho-metalated complexes [Pd(C,N-ArCH ₂CRR'NH₂-2)(μ-X)]₂ derived from phenethylamine (Ar = C₆H₄, R = R' = H, X = Cl, Br), phentermine (Ar = C₆H₄, R = R' = Me, X = Cl), (l)-phenylalanine methyl ester (Ar = C₆H₄, R = H, R' = CO₂Me, X = Cl, Br)), and (l)-tryptophan methyl ester (Ar = C ₈H₅N, R = H, R' = CO₂Me, X = Cl) react with various allenes to give (1) the corresponding η³-allyl complexes derived from the insertion of one molecule of the allene into the Pd-C bond, the formation of which has been studied by DFT using a model complex, or (2) Pd(0) and the tetrahydro-3-benzazepinium salts, resulting from the decomposition of the above mentioned η³-allyl complexes, containing an exocyclic double bond, which, subsequently, react with a base to afford the corresponding benzazepines. The regiochemistry of these decomposition reactions has been studied and compared with that described for similar processes involving five-membered palladacycles. The crystal structures of the salts of some benzazepines and one isoquinoline, derived from a five-membered palladacycle, have been determined by X-ray diffraction studies.

Full text of DOI:10.1021/om300928j

Article
pubs.acs.org/Organometallics
Insertion of Allenes into the Pd−C Bond of Ortho-Palladated Primary
Arylamines of Biological Relevance: Phenethylamine, Phentermine,
(L)‑Phenylalanine Methyl Ester, and (L)‑Tryptophan Methyl Ester.
Synthesis of Tetrahydro-3-benzazepines and Their Salts
Jose-Antonio García-Lopez,† Isabel Saura-Llamas,*,† John E. McGrady,*,‡ Delia Bautista,§
́
́
and Jose Vicente*,†
́
†Grupo de Química Organometal
Murcia, Spain
́
ica, Departamento de Química Inorgan
́
ica, Facultad de Química, Universidad de Murcia, E−30071
‡Department of Chemistry, Inorganic Chemistry Laboratory, University of Oxford, OX1 3QR, U.K.
§SAI, Universidad de Murcia, E−30071 Murcia, Spain
S
* Supporting Information
ABSTRACT: The previously reported ortho-metalated com-
plexes [Pd(C,N-ArCH2CRR'NH2-2)(μ-X)]2 derived from phe-
nethylamine (Ar = C6H4, R = R' = H, X = Cl, Br), phentermine
(Ar = C6H4, R = R' = Me, X = Cl), (L)-phenylalanine methyl
ester (Ar = C6H4, R = H, R' = CO2Me, X = Cl, Br)), and (L)-
tryptophan methyl ester (Ar = C8H5N, R = H, R' = CO2Me, X =
Cl) react with various allenes to give (1) the corresponding η3-
allyl complexes derived from the insertion of one molecule of the
allene into the Pd−C bond, the formation of which has been
studied by DFT using a model complex, or (2) Pd(0) and the tetrahydro-3-benzazepinium salts, resulting from the
decomposition of the above mentioned η3-allyl complexes, containing an exocyclic double bond, which, subsequently, react with
a base to afford the corresponding benzazepines. The regiochemistry of these decomposition reactions has been studied and
compared with that described for similar processes involving five-membered palladacycles. The crystal structures of the salts of
some benzazepines and one isoquinoline, derived from a five-membered palladacycle, have been determined by X-ray diffraction
studies.
reactivity of six-membered cyclopalladated amines toward
allenes. There is a study of a seven-membered palladacycle
derived from (2-ethynylphenyl)-N,N-dimethylmethanamine.11
Therefore, we also report here the first insertion reactions of
allenes into the Pd−C bond of ortho-palladated primary
amines.
INTRODUCTION
■
Allenes insert into the Pd−Caryl bonds to give η3-allyl
complexes in which a new bond forms between the previously
metalated carbon and the central carbon of the allene
moiety.1−3 These insertion reactions have been widely
investigated because they are the key step in the palladium-
catalyzed coupling reactions of 1,2-dienes and aryl halides to
afford carbo- and heterocycles.1,4−6 We report here a study of
the reactivity toward allenes of six-membered palladacycles
derived from amines of biological relevance, such as as
phenethylamine, phentermine, (L)-phenylalanine methyl ester,
and (L)-tryptophan methyl ester, the functionalization of which
was also an objective of the work. There are just a few examples
of insertion reactions of allenes into the Pd−Caryl bond of stable
κ2(C,N)-palladacycles.3,7 These include mainly five-membered
cyclometalated complexes derived from α-tetralone ketimine,8
benzo[h]quinoline, 2-phenylpyridine,9,10 N,N-dimethylbenzyl-
amine, N,N-dimethylnaphthylamine, and N,N-dimethylpropar-
gylamines,11 although there are two examples containing six-
membered derivatives of 2-benzylpyridine and N-phenyl-N-(2-
pyridyl)-amine.9,10 As the latter amine is bonded to Pd through
the pyridine group, our study represents the first devoted to the
η3-Allyl complexes and, in appropriate conditions, the
corresponding tetrahydro-3-benzazepines, resulting from C−
N coupling processes, have been isolated. These heterocycles
are present in natural alkaloids12−14 with great potential as
drugs. Thus, some tetrahydro-3-benzazepines have been used as
antileukemic agents12,15 and some others show high affinity and
selectivity for dopamine (D1, D3, or D5),16−18 serotonine,19 or
N-methyl-(D)-aspartate (NMDA)20,21 receptors. Because of this
last activity, 3-benzazepines can be used as antihypertensive16,22
and antipsychotic18,23 agents and in the treatment of
Alzheimer’s disease,24 obesity,19,25 or tobacco addiction
syndrome.26
Received: October 2, 2012
© XXXX American Chemical Society
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The most commonly employed syntheses of tetrahydro-3-
benzazepines involve intramolecular cyclization of highly N-
functionalized phenethylamines via radical mechanisms,27
condensation reactions,21 electrophilic aromatic substitu-
tions,16,23,25,28 or Heck-type coupling processes.25,29,30
In this paper, we describe (1) the insertion reactions of
symmetrical and nonsymmetrical allenes into the Pd−C bond
of palladacycles derived from phenethylamine, phentermine,
(L)-phenylalanine methyl ester, and (L)-tryptophan methyl
ester, which lead to the synthesis of the corresponding η3-allyl
complexes of Pd(II), (2) the decomposition reactions of these
η3-allyl complexes to give tetrahydro-3-benzazepine derivatives,
and (3) the steric and electronic factors that affect the
regiochemistry of the decomposition reactions.
Experimental Section), complex 2g was isolated (Scheme 1).
This method was also applied to synthesize 2c from 1b (via 1c
and B).
All complexes 2, except 2a and 2e, were insoluble in CH2Cl2,
CHCl3, and acetone, and insoluble or unstable in DMSO,
1
which precluded their characterization by H and 13C NMR.
Nevertheless, their elemental analyses were in agreement with
the formulas shown in Scheme 1.
1
The H and 13C NMR spectra of complexes 2a and 2e in
CDCl3 at room temperature showed a unique set of signals. In
the case of 2e, the signals could be partially asigned with the
help of APT and HMQC techniques. We propose in solution
the structure shown in Chart 1 for these complexes because the
Chart 1. Proposed Structure for Complex 2e
RESULTS AND DISCUSSION
■
Synthesis and Structure of η3-Allyl Complexes. The
reaction of the previously reported palladacycles derived from
phenethylamine (1a, 1b),31,32 phentermine (1d),33 (L)-phenyl-
alanine methyl ester (1e),32,34 or (L)-tryptophan methyl ester
(1g)33 with two equiv of 1,1-dimethylallene (A) or 1-methyl-1-
(trimethylsilyl)allene (B) at room temperature led to the
formation of the corresponding complexes 2 (Scheme 1).
The reaction of 1e with allene B afforded a solid, whose
elemental analysis and reactivity did not correspond with the
expected η3-allyl complex. However, using the corresponding
triflato complex 1f, prepared in situ from 1i and TlTfO (see the
chemical shifts of the amine protons (2.64−3.20 ppm) are in
the range of all complexes we have prepared containing C,N-
chelating ligands derived from the studied amines (2.50−3.10
ppm) and is far away from that of the free amines (ca. 1.20
ppm), ruling out a dinuclear structure in which the amine was
not coordinated. In addition, all the crystal structures of
cyclopalladated primary amines show the NH2 coordination in
the solid state.32,34−36 Finally, similar structures have been
proposed for isolated η3-allyl complexes derived from cyclo-
palladated tertiary benzylamines, (dimethylamino)methyl
ferrocenes, dimethylanilines, or alkylpyridines on the basis of
NMR37 and X-ray diffraction studies.38 Furthermore, a NOESY
2D experiment of the complex 2e showed cross-peaks between
the resonance corresponding to the H6 aromatic proton and
both substituents (Me and SiMe3) of the allene. These data
suggest a trans position of the NH2 group with respect to the
Me/Me3Si groups, which was supported by a DFT study (see
the Supporting Information) that showed this geometry being
slightly more stable than the cis isomer. This must also be the
geometry of the rest of the complexes derived from the allene
B, given the structure of their decomposition products (see
below). For the same reason and on steric grounds, we assume
Scheme 1. Synthesis of Complexes Derived from the
Reaction of Palladacycles 1 with 1,1-Dimethylallene or 1-
Methyl-1-(trimethylsilyl)allene
1
an anti arrangement of the aryl and Me3Si groups. The H
NMR spectrum of complex 2a was not easy to interpret,
because the CH2CH2NH2 and allyl CH2 protons appear as
broad and overlapped signals in the 2.53−3.97 region.
To elucidate the nature of the process that broadens the
signals corresponding to the phentermine and the allylic
fragments in complex 2e, its 1H NMR was recorded at variable
temperature (CD2Cl2, from −40 to 25 °C; CDCl3, from 25 to
60 °C). Unfortunately, broad signals, whose chemical shifts
slightly changed, were observed at all temperatures. However,
from −40 to 60 °C, both protons of the CH2 group of the
allylic moiety appeared as two separated singlets, which
indicated that an anti/syn isomerization did not take place.
Probably, a low activation energy of the trans-to-cis isomer-
ization through an η3-η1-η3 mechanism (Scheme 2), as well as
the inherent fluxionality of the nonrigid palladacycle, was
responsible for the broadening of the CH2 signals. In fact, the
B
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CMe2 one. Each possibility generated two isomers, as the
remaining noncoordinated double bond could be located on
each side of the metal coordination plane (Figure 1).
Coordination of the allene trans to the aryl group was not
considered, as only cis coordination is relevant for the insertion
process (that is, if coordination of the allene took place trans to
the aryl group, the complex should isomerize to the cis form
before the insertion reaction).
Scheme 2. Proposed Mechanism for Cis/Trans
Isomerization for η3-Allyl Complexes 2 through η1-Allyl
Intermediates (I or II)
The two isomers where the allene was coordinated through
the CCH2 bond (Y and Y') were more stable (2.8−8.1 kcal/
mol) than those where the allene was coordinated through the
CCMe2 bond (Z and Z'), probably due to sterical effects.39
Nevertheless, the four coordination isomers could easily
interconvert through energetically accessible transition states.
For example, the conversion process Z → Y' had a barrier of
13.9 kcal/mol (see the Supporting Information, TSi).
When the insertion step was studied from complex Y, two
possible pathways were found, which afforded two slightly
different η3-allyl complexes, trans-2j and trans-2k. These η3-allyl
complexes had slightly different energies due to small
conformation changes in the aliphatic chain (the NH2 group
of both η3-allyl complexes was located trans to the CH2 group
of the allyl moiety: N−Pd−CH2 = 157°, N−Pd−CMe2 =
107°). There was a single-stage pathway, through the transition
state TSz (Figure 2), which afforded directly the η3-allyl
complex trans-2k. The energy barrier to reach this transition
state was high (36.8 kcal/mol). In this process, the phenyl ring
migrated to the central carbon of the coordinated allene,
forming a new bond and, simultaneously, the palladium atom
approached the noncoordinated double bond. The other
pathway consisted of a three-stage pathway, in which, first, Y
was transformed into the isomer Y' through the rotation of the
η2-alkene−palladium bond (transition state TSy, activation
energy = 13.7 kcal/mol; Figure 2). Y' then reached the
transition state TSx (activation energy = 12.9 kcal/mol) to give
an intermediate alkylvinyl complex X (similar to intermediate I
or II proposed in Scheme 2), where the central carbon of the
allene moiety was bound to the aromatic carbon, and the
phenyl ring was η2-coordinated to the palladium atom. Finally,
the vinyl complex X led easily to the formation of the η3-allyl
complex trans-2j through the transition state TSw (activation
energy = 0.4 kcal/mol).
isomerization of cis-2e to trans-2e has a calculated activation
energy of 12.2 kcal/mol (see the Supporting Information)
DFT Study of the Insertion Reaction of Allenes into
the Pd−C Bond of Palladacycles. To elucidate if there were
kinetics reasons that favored the formation of one of the
isomers (η3-anti/cis-2 or η3-anti/trans-2), we studied in detail
the insertion reaction of 1,1-dimethylallene (A) into the Pd−
Caryl bond of six-membered palladacycles through DFT
calculations, using the complex [Pd(C,N-C6H4CH2CH2NH2-
2)(μ-Cl)]2 (1a) as a model. In agreement with the accepted
mechanism for insertion reactions, this process was likely to
happen in two steps: (1) coordination of the allene to the metal
center and (2) subsequent insertion of the coordinated allene
into the Pd−C bond to afford an η3-allyl complex.
According to these calculations, we propose that the
insertion process of the coordinated ligand takes place through
the pathway where an intermediate alkylvinyl complex X is
involved. This mechanism is similar to that proposed by Lin et
The allene could coordinate to the palladium atom in an η2-
mode through (1) the CCH2 double bond or (2) the C
Figure 1. Relative energies (kcal/mol) of η2-allene complexes compared to Y and view of their optimized structures. Most hydrogen atoms are
omitted for clarity.
C
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Figure 2. Calculated energy profile for the insertion of 1,1-dimethylallene into the Pd−C bond of palladacycle 1a.
Figure 3. Comparison of energy profiles for both types of η3-allyl complexes. Only species Z, Z', X', and cis-2j are depicted in the figure.
al. for the insertion reactions of allenes in palladium aryl
complexes [PdI(Ph)(PPh3)]2 and [PdI(Ph)(dppe)].40
of Y and the similar energies of both transition states. The
intermediate X' was 5.7 kcal/mol less stable than X, probably
due to the higher steric hindrance of the CMe2 group compared
with that of the CH2 group, which rendered the coordination of
the aromatic ring to the palladium atom (distance Pd−CAr in X
and X': 2.357 and 2.403 Å, respectively) more difficult. In the
obtained η3-allyl complex cis-2j, the NH2 group was located
trans to the CMe2 group (N−Pd−CMe2 = 158°, N−Pd−CH2
When the calculations for the insertion reaction were carried
out using isomer Z as precursor, a similar pathway involving
three stages was found (Figure 3). In this case, the energy
barrier to reach TSy' was 8.6 kcal/mol, slightly lower than that
found in the case of complex Y to get to TSy (13.7 kcal/mol),
because of the higher energy of complex Z compared with that
D
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= 103°). Complex cis-2j was 4 kcal/mol more stable than η3-
allyl complex trans-2j. This difference could be explained by the
greater steric hindrance between the CMe2 group and the
aliphatic chain of the amine in complex trans-2j compared with
that of complex cis-2j.
Scheme 4. Synthesis of Tetrahydro-3-benzazepinium Salts.
Method A
According to these data, we concluded that coordination of
the allene to Pd(II) through the least-substituted double bond
(intermediates Y and Y') led to trans-2j, and coordination of
the allene through the most-substituted double bond (Z and
Z') led to cis-2j. Unfortunately, the calculations described here
did not permit us to distinguish which η3-allyl complex was
preferentially formed (cis or trans). Neither the stability of both
complexes nor the activation energies involved in the reaction
pathways that render them were significantly different. That is,
there were neither thermodynamic nor kinetic reasons that
substantially favored the formation of one isomer, in agreement
with the proposed equilibrium in solution shown in Scheme 2.
Synthesis of Tetrahydro-3-benzazepinium Salts.
Pfeffer et al. have reported the stoichiometric synthesis of N-
heterocycles from allenes and palladacycles containing
functionalized pyridines, tertiary anilines, or N,N-dimethyl
amines.10,11 For instance, the reaction of [Pd(C,N-
C6H4CH2NMe2-2)(μ-Cl)]2 (1h; Scheme 3) with 1,1-dimethyl-
Scheme 3. Synthesis of Isoquinolinium Salt from 1,1-
Dimethylallene and Ortho-Metalated N,N-
Dimethylbenzylamine
Method A. When a suspension of an η3-allyl complex in
CHCl3 was stirred under a CO atmosphere at room
temperature, decomposition to metallic palladium and
formation of a benzazepinium salt 3 or 4 took place (Scheme
4). When 2d was used, a 5:1 mixture of the regioisomeric
benzazepinium chlorides 3b and 4b was obtained, which could
not be separated. However, when this mixture was treated with
Na2CO3 and then with HOTf, the pure triflate 3e could be
isolated (Scheme 4).
Method B. This method was designed to obtain some
benzazepinium salts at room temperature from complexes 1
without isolation of the η3-allyl complex or the need to use CO.
Two routes were successfully attempted. Path B1 involved in
situ formation of the corresponding triflato complex (Scheme
5) from 1d or 1i, which reacted with allenes H2CC
C(R3)R4 (R3 = Me, R4 = Me3Si (B), R3 = R4 = Ph (C), R3 = H,
R4 = CO2Et (D)), to give 4g, 4h, or 4i, respectively. In this way,
4g was obtained from 1d in 60% yield, exceeding the global
34% yield of the two-step method used to obtain 4c. The
second route, Path B2, involved the reaction of complexes 1
with an allene containing electron-withdrawing substituents,
such as D, which afforded a benzazepinium salt, probably
through an unstable η3-allyl complex intermediate. Thus, the
allene in the presence of PPh3 affords the isoquinolinium salt
Q.11 It was proposed that this reaction occurred through (1)
formation of an η3-allyl complex, in which the NMe2 group was
not coordinated to the metal, and (2) nucleophilic attack of the
free amino group to the less-hindered external carbons of the
allylic moiety.
We tried a similar method to decompose the η3-allyl
complexes derived from our six-membered palladacycles.
However, when complex 2d was reacted with PPh3 (molar
ratio Pd/PPh3 = 1:1) in CH2Cl2 at room temperature for 1 h,
depalladation took place, but no pure organic compound could
1
be isolated from the reaction mixture. The H and 31P NMR
spectra of this mixture indicated the presence of the expected
benzazepinium salt 3b (Scheme 4) along with OPPh3 and
traces of [Pd(PPh3)]4. Alternatively, we tested two other
methods to synthesize the N-heterocyclic derivatives.
E
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Scheme 5. Synthesis of Tetrahydro-3-benzazepinium Salts.
Method B
Scheme 7. Proposed Mechanism for the Desilylation of 4e to
Give Compound 4l
palladacycle 1b or 1d reacted with D to give metallic palladium
and the salt 4j or 4k, respectively.
Reactivity of Tetrahydro-3-benzazepinium Salts. Some
3-benzazepinium salts were reacted with Na2CO3 to afford the
corresponding benzazepines 5 or 6 (Scheme 6).
carbocation, which would be stabilizated by the β effect of the
silicon atom and by resonance with the aromatic system, (2)
rotation around the C−C σ-bond to minimize the steric
hindrance, and (3) nucleophilic attack of chloride at the silicon
atom, and the restoration of the double bond character
(Scheme 7). Similar desilylation reactions are well-docu-
mented.41
Scheme 6. Synthesis of Tetrahydro-3-benzazepines
None of the 3-benzazepinium salts or 3-benzazepines
reported in this work have been described previously, although
similar compounds containing exocyclic double bonds are
known. They were mainly prepared by (1) insertion reactions
of allenes into the Pd−C bond of N-palladacycles containing
tertiary amines, N,N-disubstituted anilines, or pyridines;8,9 (2)
palladium-catalyzed coupling reactions of allenes and 2-
haloaryl-alkylamines or imines;5,6,10,11 (3) intramolecular
Heck-coupling reactions;25,29,42 and (4) palladium-catalyzed
intramolecular coupling of aryl halides and alkynes.14,24,43 Our
derivatives are the first obtained from primary amines.
Structure of Tetrahydro-benzazepines and Tetrahy-
dro-benzazepinium salts. All the tetrahydro-3-benzazepines
and tetrahydro-3-benzazepinium salts have been characterized
by IR and NMR spectroscopies and by elemental analysis (solid
compounds) or exact mass (liquid products). Additionally, the
crystal structures of compounds 3a, 3e, 4a, 4c·CH2Cl2, and 4h
have been determined by X-ray diffraction studies (see the
Supporting Information).
When 4e was dissolved in a saturated solution of HCl in
CH2Cl2 (Scheme 7), quantitative formation of 4l, a MeCH
CCH2 (E) derivative, was obtained. The process involves the
replacement of the SiMe3 group by a hydrogen atom and the
isomerization of the exocyclic double bond to give the E
isomer, which minimizes the steric hindrance between the
bulkiest substituent of the exocyclic double bond (Me) and the
indol group. A possible mechanism for this reaction would
involve (1) protonation of the double bond and generation of a
1
In the H NMR spectra, the CH2 protons appear as two
singlets between 4.99 and 5.72 ppm. The most shielded proton
(4.99−5.38 ppm) is the one nearest to the aromatic ring (Ha),
which shows a NOE interaction with H9 (see Chart 2 for the
numbering scheme). As observed in the crystal structures of 3a
and 3b, the CH2 and the aryl groups are not coplanar, which
allows the Ha proton to be shielded by the aryl ring. Contrarily,
in compound 3d, Ha is deshielded with respect to Hb (5.58 vs
F
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2e in CH2Cl2 or CHCl3 was stable for days, whereas the
complex decomposed in DMSO or when its CHCl3 solution
was stirred in the presence of CO.
Chart 2. Numbering Schemes for Representative
Tetrahydro-3-benzazepine Derivatives (Compounds 3 and
4)
Larock et al.5 proposed that the palladium-catalyzed
formation of medium-ring nitrogen heterocycles from allenes
and aryl iodides bearing amine fuctionalities occurred through
oxidative addition of the aryl iodide to Pd(0) and insertion of
the allene into the Pd−C bond to give η3-allyl complexes,
followed by intramolecular nucleophilic substitution. In this last
step, the amine functionality is assumed to attack one of the
two extremes of the coordinated allylic moiety. A similar
mechanism was proposed by Pfeffer et al. for the stoichiometric
synthesis of N-heterocycles from allenes and palladacycles
containing functionalized pyridines, tertiary anilines, or N,N-
dimethyl amines (see above; Scheme 3).10,11 However, in our
case, decoordination of the NH2 group is very unlikely, taking
into account the great strength of the Pd−N bond. We consider
more probable that the formation of the 3-benzazepinium salts
from the η3-allyl complexes occurs in two steps: (1) conversion
of η3-allyl-2 to η1-allyl-2, induced by coordination of the added
ligand L (CO, DMSO) and (2) a reductive elimination reaction
to give 3 or 4 through a C−N coupling (Scheme 8).
Scheme 8. Proposed Mechanism for the Decomposition of
the η3-Allyl Derivatives 2 in the Presence of CO
5.51 ppm, respectively). In this case, both protons can be easily
distinguished by an NOE effect with the indol NH group (Ha)
or with one of the two methyl groups of the inserted allene
(Hb).
Although two isomers were possible for the 3-benzazepines
and 3-benzazepinium salts resulting from the insertion of 1-
methyl-1-(trimethylsilyl)allene and ethyl buta-2,3-dienoate,
only products with Z stereochemistry were isolated. This has
been established in solution (4g, 4e, 4l, 6a) or in the solid state
by X-ray diffraction studies (4a and 4c). On the basis of these
data and because this is the expected geometry from the anti
isomers of the η3-allyl complexes 2 (Scheme 2), we assume the
same geometry for the rest.
The crystal structures of benzazepinium salts show that the
azepane ring adopts a chair (3e, 4a, 4c), a boat (4h), or both
(3a) conformations. The bond lengths and angles are in the
expected intervals, and they are comparable to those found for
other 3-benzazepines containing an exocyclic double bond (see
details in the Supporting Information).43,44 In all cases, the
organic cations are associated with the anions forming dimers
(4h), zigzag (4a, 4c·CH2Cl2), or double chains (3a, 3e)
through classical N−H···O, N−H···Cl, and N−H···Br or
nonclassical C−H···Cl and C−H···O hydrogen bond inter-
actions. Additionally, the chains of 4c·CH2Cl2 are associated
through nonclassical hydrogen interaction, C−H···Cl, with the
crystallization solvent to give layers (see the Supporting
Information).
Regioselectivity of the Decomposition Reactions of
the η3-allyl Complexes Containing Primary Arylalkyl-
amines. The chloro- or bromo-η3-allyl complexes derived from
the insertion of A or B decomposed only when they were
reacted with a ligand, such as CO or PPh3, or dissolved in a
coordinating solvent, such as DMSO. For instance, a solution of
To support this proposal, reactions of compounds 2d and 2e
and 4-picoline (pic) were investigated. We could not isolate any
complex from these reactions at room temperature because (1)
complex 2d did not react with pic (1:2, CH2Cl2); and (2) when
pic was added to a pale yellow solution of complex 2e in
CH2Cl2, a bright yellow solution initially formed, but attempts
to precipitate a solid from the reaction mixture led to the
recovery of 2e. The 1H NMR spectrum of the 2e + pic (1:2.5)
solution in CDCl3 showed a unique set of signals, some of
which were rather broad, different from those observed in the
starting materials. The existence of a unique set of signals for
the pic, despite using a slight excess of the ligand, proves the
existence of an equilibrium between free picoline and the
coordination complex. At 55 °C, the 1H NMR spectrum of this
G
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sample showed sharper signals and the protons of the CH2
group and the Me of the CMe2 fragment were diastereotopic.
This is compatible with our proposal that assumes that the NH2
group remains coordinated to Pd(II). Unfortunately, the signals
of the NH2 group were not observed at this temperature. A
NOESY 2D experiment for the sample 2e + 2.5pic showed a
cross-peak between the resonance corresponding to the H6
aromatic proton and the Me substituent of the allene, but not
with the SiMe3 group, as happened with the starting η3-allyl
complex 2e, which is compatible with the proposed η3-allyl to
η1-allyl change. Longer NMR experiments could not be
performed because the sample started to decompose after
several minutes, to give the 3-benzazepinium salt 4c. The molar
conductivity of the mixture of 2e + 2.5pic in 1,2-dichloroethane
(1.3 × 10−3 mol L−1) at room temperature was practically zero,
which proved that pic had not replaced the chloro ligand.
Although all of these data do not conclusively prove that the 2e
+ 2.5pic reaction affords an η1-allyl complex, they suggest such
a possibility. Correspondingly, similar compounds could be
intermediates in the formation of benzazepinium salts from the
η3-allyl complexes (Scheme 8). The role of the ligand L in this
proposal, when CO or PPh3 was not used (Method B, Scheme
5), could be played by the solvent (THF) or the allene (D).
From the results obtained (Schemes 4 and 5), it can be
concluded that the C−NH2 coupling takes place with the
carbon bonded to the most electron-releasing or less
voluminous substituents of the allyl ligand, leaving the most
electron-withdrawing or the largest groups bonded to the
exocyclic carbon. Thus, in the reaction with the allene A (R3 =
R4 = Me), the carbon involved in the C−NH2 coupling is the
Me2C carbon, affording 3-benzazepinium salts 3, containing the
exocyclic CH2 group. Correspondingly, with the allene B (R3
= Me, R4 = SiMe3), for steric reasons, and with the other
allenes, because of the electron-withdrawing nature of R3 and/
or R4 (C, R3 = R4 = Ph; D, R3 = H, R4  CO2Et), the carbon
implicated in the coupling process is the CH2, giving salts 4,
with the exocyclic CR3R4 group. A reasonable explanation
for these electronic effects is that the reduction of the metal is
favored in the η1-allyl isomer in which the carbon bonded to Pd
is the most electron-rich. Consequently, the cyclization occurs
after the resulting carbocation attacks the amine nitrogen. The
influence of steric hindrance associated with the amine moiety
is reflected in the reaction involving the palladacycle 1d. The
α,α-disubstitution in the aliphatic chain may slightly favor the
formation of the η1-allyl complex with the CH2 group bonded
to the metal, which explains the generation of a small amount
of the benzazepinium salt 4b.
Scheme 9. Synthesis of the Isoquinolinium Salt from 1,1-
Dimethylallene and Five-Membered Palladacycle 1j
conformation. The exocyclic CCH2 double bond is not
coplanar with the aromatic ring, with a torsion angle C(9)−
C(4)−C(4A)−C(5) of 21.9°, notably lower than that observed
for 3-benzazepinium rings. The organic cations are associated
through hydrogen bonds with the bromide anions, giving single
chains (see the Supporting Information).
CONCLUSION
■
Ortho-metalated primary arylalkylamines react with 1,1-
dimethylallene and 1-methyl-1-(trimethylsilyl)allene to give
the corresponding η3-allyl complexes of Pd(II). These η3-allyl
complexes decompose in the presence of auxiliary ligands (CO,
PR3, DMSO, THF) to give metallic palladium and tetrahydro-
3-benzazepinium salts with an exocyclic double bond. The
decomposition reactions of some η3-allyl complexes occur
spontaneously when cationic palladacycles and polar solvents
are used, or when the allene contains electron-withdrawing
groups. The C−NH2 coupling takes place with the carbon
bonded to the most electron-releasing or less voluminous
substituents of the allyl ligand, leaving the most electron-
withdrawing or the largest groups bonded to the exocyclic
carbon. The strength of the Pd−NH2 bond, in the palladacycles
under study may induce the formation of an η1-allyl complex,
by contrast to the nucleophilic substitution reported for η3-allyl
complexes arising from palladacycles containing tertiary amines.
This change in the mechanism might be responsible for the
different regiochemistry observed in the decomposition process
of the complexes arising from 1,1-dimethylallene.
EXPERIMENTAL SECTION
■
General Procedures. Infrared spectra were recorded on a Perkin-
Elmer 16F-PC-FT spectrometer. Mass spectra and exact masses were
recorded on an AUTOSPEC 5000 VG mass spectrometer. C, H, N,
and S analyses; conductance measurements; and melting point
determinations were carried out as described elsewhere.36 NMR
spectra were recorded in Bruker Avance 300 or 400 spectrometers,
using CDCl3 solutions unless otherwise stated. Chemical shifts are
We have also carried out the reaction of 1,1-dimethylallene
with the five-membered palladacycle derived from a primary
arylalkylamine [Pd(C,N-C6H3CH2NH2-2,OMe-5)(μ-Br)]2 (1j;
Scheme 9). Under the usual experimental conditions (molar
ratio allene/palladium =1:1, CH2Cl2 and nitrogen atmosphere),
salt 7a was obtained. As the reaction follows the same
regiochemistry as that of complexes 2 obtained from the same
allene, a similar mechanism can be suggested. Consequently,
the different regiochemistry with respect to that reported by
Pfeffer et al.11 in the synthesis of the isoquinolinium salt Q
(Scheme 3) is not caused by the different number of members
of the cycle, but by the nature of the amine, primary or tertiary,
respectively.
referenced to TMS (1H and 13C). Signals in the H and 13C{1H}
1
NMR spectra were assigned with the help of APT, HMQC, and
HMBC techniques.
1,1-Diphenylallene (C)45 and the ortho-metalated complexes
[Pd2(C,N-C6H4CH2CH2NH2-2)2(μ-X)2] (X  Cl, 1a; Br, 1b),32
[Pd2(C,N-C6H4CH2CMe2NH2-2)2(μ-Cl)2] (1d),33 (S,S)-[Pd2{C,N-
C6H4CH2CH(CO2Me)NH2-2}2(μ-X)2] (X  Cl, 1i; Br, 1e),32
(S,S)-[Pd2{C,N-C8H5N(CH2CH(CO2Me)NH2-2}2(μ-Cl)2] (1g),33
and [Pd2(C,N-C6H3CH2NH2-2,OMe-5)2(μ-Br)2] (1j)31 were pre-
pared as previously reported. 1,1-Dimethylallene (A; Fluka), 1-
methyl-1-(trimethylsilyl)allene (B; Aldrich), ethyl 1,2-butadienoate
(D; Aldrich), HTfO (HSO3CF3) (Fluka), Na2CO3 (Aldrich), and
The crystal structure of the isoquinolinium salt 7a has been
determined by X-ray diffraction studies (see the Supporting
Information). The six-membered azacycle shows an envelope
H
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Pd(OAc)2 (Johnson Matthey) were used as received. TlTfO was
prepared by reaction of Tl2CO3 and HO3SCF3 (1:2) in water, and
recrystallized from acetone/Et2O. Chart 2 gives the numbering
schemes for the organic compounds. Synthesis and data of 3b, 3c,
4b, 4d, 4f, 4i, 4j, and 4k are included within the epigraphs of 3e, 5a,
3e, 6a, 3e, 6b, 6c, and 6d, respectively.
Synthesis of 2a. 1-Methyl-1-(trimethylsilyl)allene (170 μL, 1.022
mmol) was added to a suspension of palladacycle 1a (250 mg, 0.477
mmol) in dry CH2Cl2 (15 mL) under a N2 atmosphere, and the
mixture was stirred for 3 h. The resulting solution was filtered through
a plug of Celite, the filtrate was concentrated to ca. 2 mL, and Et2O
(20 mL) was added. The suspension was filtered, and the solid was
washed with Et2O (2 × 5 mL) and air-dried to give complex 2a as a
colorless solid. Yield: 270 mg, 0.695 mmol, 73%. dec pt: 194 °C. Anal.
Calcd for C15H24ClNPdSi (388.320): C, 46.39; H, 6.23; N, 3.61.
Found: C, 46.24; H, 6.16; N, 3.54. IR (cm−1): ν(NH) 3446 br, 3313
w, 3218 m. 1H NMR (400.91 MHz): δ 0.31 (br s, 9H, SiMe3), 1.23 (br
s, 3H, Me), 2.53 (br s, 1H), 2.64 (br s, 1H), 2.97 (br s, 2H), 3.16 (br s,
1H), 3.48 (m, 1H), 3.65 (m, 1H), 3.97 (m, 1H), 6.95 (d, 1H, Ar, 3JHH
= 6.8 Hz), 7.15 (m, 3H, Ar).
Synthesis of 2b. 1,1-Dimethylallene (70 μL, 0.706 mmol) was
added to a suspension of palladacycle 1b (200 mg, 0.326 mmol) in dry
CH2Cl2 (15 mL) under a N2 atmosphere, and the mixture was stirred
for 4 h. The resulting suspension was filtered, and the solid was
washed with CH2Cl2 (2 × 3 mL) and air-dried to give a first crop of
complex 2b (171 mg) as a yellow solid. A solid precipitated in the
mother liquors. The suspension was filtered, and the solid was washed
with Et2O (5 mL) and air-dried to give a second crop of complex 2b
(30 mg) as a yellow solid. Yield: 201 mg, 0.536 mmol, 82%. dec pt:
168 °C. Anal. Calcd for C13H18BrNPd (374.603): C, 41.68; H, 4.84;
N, 3.74. Found: C, 41.32; H, 4.81; N, 3.68. IR (cm−1): ν(NH) 3219
m. Complex 2b was insoluble in CH2Cl2, CHCl3, acetone, and DMSO,
which prevented us from measuring its NMR spectra.
Synthesis of 2c. TlTfO (231 mg, 0.653 mmol) was added to a
suspension of palladacycle 1b (200 mg, 0.326 mmol) in CH2Cl2 (40
mL). The resulting suspension was stirred for 12 h and filtered
through a plug of Celite to remove the TlBr formed. The solvent was
removed, the residue was dissolved in CH2Cl2 (15 mL) under a N2
atmosphere, 1-methyl-1-(trimethylsilyl)allene (120 μL, 0.721 mmol)
was added, and the mixture was stirred for 5 h. The resulting
suspension was filtered, and the solid was washed with CH2Cl2 (2 × 5
mL) and air-dried to give a first crop of complex 2c (260 mg, 0.517
mmol) as an off-white solid. The filtrate was concentrated to ca. 4 mL,
and Et2O (20 mL) was added. The resulting suspension was filtered,
and the solid was washed with Et2O (2 × 5 mL) and air-dried to give a
second crop of complex 2c as a pale yellow solid (55 mg, 0.109
mmol). Yield: 315 mg, 0.627 mmol, 96%. mp: 201 °C dec. Anal. Calcd
for C16H24F3NO3PdSSi (501.932): C, 38.29; H, 4.82; N, 2.79; S, 6.39.
Found: C, 38.67; H, 4.97; N, 3.02; S, 3.53.46 IR (cm−1): ν(NH) 3255
w; ν(SO) 1279 s, 1030 s; ν(CF3) 1160 m. Complex 2c was insoluble
in CH2Cl2, CHCl3, and acetone and unstable in DMSO, which
prevented us from measuring its NMR spectra.
complex 2e as a colorless solid. Yield: 194 mg, 0.466 mmol, 91%. dec
pt: 187 °C. Anal. Calcd for C17H28ClNSiPd (416.374): C, 49.04; H,
6.78; N, 3.36. Found: C, 49.12; H, 6.86; N, 3.66. IR (cm−1): ν(NH)
3288 w, 3224 w. 1H NMR (400.91 MHz): δ 0.37 (s, 9H, SiMe3), 1.07
(br s, 3H, Me), 1.27 (br s, 3H, Me, CMe2), 1.31 (br s, 3H, Me, CMe2),
2.64−3.20 (m, 4H, CH2 + NH2), 3.31 (br s, 1H, CH2C), 3.70 (br s,
1H, CH2C), 7.27 (br s, 3H, C6H4), 7.80 (br s, 1H, C6H4). 13C
NMR (100.81 MHz): δ 1.7 (s, SiMe3), 21.1 (s, Me), 29.8 (br s, CMe2),
45.4 (br s, CH2), 54.4 (s, CMe2), 58.6 (br s, CH2C), 87.5 (br s,
C(Me)SiMe3C), 127.9 (s, CH), 130.7 (s, CH), 131.8 (s, CH), 133.7
(s, C), 137.1 (s, C), 139.4 (s, C).
Synthesis of 2f. 1,1-Dimethylallene (65 μL, 0.655 mmol) was
added to a solution of palladacycle 1e (200 mg, 0.274 mmol) in dry
CH2Cl2 (15 mL) under a N2 atmosphere. The mixture was stirred for
12 h and filtered through a plug of Celite. The filtrate was
concentrated to ca. 1 mL, and Et2O (25 mL) was added. The
resulting suspension was filtered, and the solid was washed with Et2O
(2 × 5 mL) and air-dried to give complex 2f as a yellow solid. Yield:
189 mg, 0.437 mmol, 79%. mp: 172 °C dec. Anal. Calcd for
C15H20BrNO2Pd (432.639): C, 41.64; H, 4.66; N, 3.24. Found: C,
41.73; H, 4.85; N, 3.54. IR (cm−1): ν(NH) 3390 br, 3200 br; ν(CO)
1737 s. Complex 2f was insoluble in CH2Cl2, CHCl3, acetone, and
DMSO, which prevented us from measuring its NMR spectra.
Synthesis of 2g. TlTfO (222 mg, 0.628 mmol) was added to a
solution of palladacycle 1i (200 mg, 0.312 mmol) in acetone (10 mL).
The resulting suspension was stirred for 30 min and filtered through a
plug of Celite to remove the TlCl formed. The solvent was removed,
the residue was dissolved in dry CH2Cl2 (10 mL) under a N2
atmosphere, and 1-methyl-1-(trimethylsilyl)allene (115 μL, 0.691
mmol) was added. The resulting yellow solution was stirred for 12 h
and filtered through a plug of Celite. The filtrate was concentrated to
ca. 1 mL, and Et2O (15 mL) was added. The suspension was filtered,
and the solid was washed with Et2O (2 × 5 mL) and air-dried to afford
complex 2g as a yellow solid. Yield: 222 mg, 0.396 mmol, 64%. mp:
170 °C dec. Anal. Calcd for C18H26F3NO5PdSSi (559.968): C, 38.61;
H, 4.68; N, 2.50; S, 5.73. Found: C, 38.68; H, 4.67; N, 2.74; S, 3.62.46
IR (cm−1): ν(NH) 3239 w; ν(CO) 1741 s; ν(SO) 1283 s, 1029 s;
ν(CF3) 1163 s. Complex 2g was insoluble in CH2Cl2, CHCl3 and
acetone, and unstable in DMSO, which prevented us from measuring
its NMR spectra.
Synthesis of 2h·1/2H2O. 1,1-Dimethylallene (100 μL, 1.010
mmol) was added to a suspension of palladacycle 1g (300 mg, 0.374
mmol) in dry CH2Cl2 (10 mL) under a N2 atmosphere, and the
mixture was stirred for 12 h. The resulting suspension was filtered, and
the solid was washed with CH2Cl2 (2 × 5 mL) and air-dried to give
complex 2h·1/2H2O as a dark orange solid. Yield: 247 mg, 0.566
mmol, 76%. dec pt: 190 °C. Anal. Calcd for C17H21ClN2O2Pd·1/2H2O
(436.227): C, 46.81; H, 5.08; N, 6.42. Found: C, 46.34; H, 5.19; N,
6.22. IR (cm−1): ν(NH) 3220 br; ν(CO) 1732 s. Complex 2h·1/2H2O
was insoluble in CH2Cl2, CHCl3, acetone, and DMSO, which
prevented us from measuring its NMR spectra.
Synthesis of 2i. 1-Methyl-1-(trimethylsilyl)allene (64 μL, 0.384
mmol) was added to a suspension of palladacycle 1g (150 mg, 0.187
mmol) in dry CH2Cl2 (10 mL) under a N2 atmosphere, and the
mixture was stirred for 6 h. The resulting suspension was filtered, and
the solid was washed with CH2Cl2 (2 × 5 mL) and air-dried to give
complex 2i contaminated with traces of metallic palladium, as a gray
solid. Yield: 110 mg, 0.226 mmol, 60%. dec pt: 198 °C. Anal. Calcd for
C19H27ClN2O2PdSi (485.388): C, 47.01; H, 5.61; N, 5.77. Found: C,
45.70; H, 5.52; N, 5.59. IR (cm−1): ν(NH) 3228 br; ν(CO) 1741 s.
Complex 2i was insoluble in CH2Cl2, CHCl3, and acetone, and
unstable in DMSO, which prevented us from purifying it and
measuring its NMR spectra.
Synthesis of 2d·1/2H2O. 1,1-Dimethylallene (80 μL, 0.806
mmol) was added to a solution of palladacycle 1d (220 mg, 0.379
mmol) in dry CH2Cl2 (15 mL) under a N2 atmosphere, and the
mixture was stirred for 12 h. The resulting suspension was filtered, and
the solid was washed with CH2Cl2 (5 mL) and Et2O (2 × 5 mL) and
air-dried to give complex 2d·1/2H2O as a colorless solid. Yield: 264
mg, 0.719 mmol, 95%. dec pt: 169 °C. Anal. Calcd for
C15H22ClNPd·1/2H2O (367.208): C, 49.06; H, 6.31; N, 3.81.
Found: C, 49.19; H, 6.40; N, 3.79. IR (cm−1): ν(H2O) 3452 br w;
ν(NH) 3303 m, 3212 m, 3138 m. Complex 2d·1/2H2O was insoluble
in CH2Cl2, CHCl3, acetone, and DMSO, which prevented us from
measuring its NMR spectra.
Synthesis of 2e. 1-Methyl-1-(trimethylsilyl)allene (86 μL, 0.516
mmol) was added to a solution of palladacycle 1d (150 mg, 0.258
mmol) in dry CH2Cl2 (15 mL) under a N2 atmosphere, and the
resulting solution was stirred for 5 h. The solvent was evaporated to ca.
2 mL, and Et2O (20 mL) was added. The suspension was filtered, and
the solid was washed with Et2O (2 × 5 mL) and air-dried to give
Synthesis of 1-Methylen-2,2-dimethyl-2,3,4,5-tetrahydro-
benzo[d]azepinium Bromide (3a). A suspension of the η3-allyl
complex 2b (150 mg, 0.400 mmol) in CHCl3 (15 mL) was stirred
under a CO atmosphere for 5 h. Decomposition to metallic palladium
was observed. The suspension was filtered through a plug of Celite, the
filtrate was concentrated to ca. 2 mL, and n-pentane (20 mL) was
added. The suspension was filtered, and the solid was washed with n-
I
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pentane (2 × 5 mL) and air-dried to afford compound 3a as a colorless
solid. Yield: 59 mg, 0.22 mmol, 55%. mp: 170 °C. ΛM (Ω−1 cm2
mol−1) = 20 (5.2 × 10−4 M). Anal. Calcd for C13H18BrN (268.203): C,
(20 mL) was added. The suspension was filtered, and the solid was
washed with Et2O (2 × 5 mL) and air-dried to afford the salt 3e (55
mg) as a colorless solid. The mother liquors were concentrated to ca. 1
mL, and n-pentane (20 mL) was added. The suspension was filtered,
and the colorless solid was washed with n-pentane (2 × 5 mL) and air-
dried to give a mixture of regioisomers 3e and 4f (35 mg, 0.096
mmol). 3e: Yield: 55 mg, 0.150 mmol, 28%. mp: 215 °C. ΛM (Ω−1 cm2
mol−1) = 140 (4.9 × 10−4 M). Anal. Calcd for C16H22F3NO3S
(365.414): C, 52.59; H, 6.07; N, 3.83; S, 8.77. Found: C, 52.43; H,
6.21; N, 3.93; S, 8.49. IR (cm−1): ν(NH) 3104 s; ν(SO) 1288 s, 1030
1
58.22; H, 6.76; N, 5.22. Found: C, 57.86; H, 7.03; N, 5.31. H NMR
(400.91 MHz): δ 1.67 (br s, 6H, CMe2), 3.14 (br s, 2H, CH2Ar), 3.39
(br s, 2H, CH2N), 5.36 (s, 1H, CH2C), 5.72 (s, 1H, CH2C),
7.09−7.17 (m, 2H, H6 + H9), 7.22−7.32 (m, 2H, H7 + H8), 9.32 (br
s, 2H, NH2). 13C{1H} NMR (100.81 MHz): δ 25.1 (br s, CMe2), 31.8
(s, CH2Ar), 41.5 (s, CH2N), 59.1 (s, CMe2), 119.8 (s, CH2C), 127.8
(s, CH, C7), 128.65 (s, CH, C6 or C8), 128.68 (s, CH, C6 or C8),
129.6 (s, CH, C9), 134.9 (s, C5a), 140.3 (s, C9a), 149.3 (s, CH2C).
Single crystals suitable for an X-ray diffraction study were obtained by
slow diffusion of n-pentane into a solution of 3a in CH2Cl2.
1
s; ν(CF3) 1156 s. H NMR (300.1 MHz): δ 1.49 (s, 6H, CMe2CH2),
1.64 (s, 6H, CMe2C), 2.94 (br s, 2H, CH2Ar), 5.28 (s, 1H, CH2
C), 5.59 (s, 1H, CH2C), 7.10−7.13 (m, 1H, H6), 7.16−7.20 (m,
1H, H9), 7.29−7.35 (m, 2H, H7 + H8). The NH2 group appeared as a
broad singlet, partially obscured by the signal corresponding to H7 +
Synthesis of (S)-1-Methylen-2,2-dimethyl-4-(methoxycar-
bonyl)-2,3,4,5-tetrahydro-indolo[2,1-d]azepinium Chloride
Monohydrate (3d·H2O). A suspension of the η3-allyl complex
2h·1/2H2O (205 mg, 0.470 mmol) in CHCl3 (15 mL) was stirred
under a CO atmosphere for 12 h. Decomposition to metallic
palladium was observed. The suspension was filtered through a plug
of Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (20 mL)
was added. The resulting suspension was filtered, and the solid was
washed with Et2O (2 × 5 mL) and air-dried to afford compound
3d·H2O as a pale yellow solid. Yield: 144 mg, 0.425 mmol, 90%. mp:
172−174 °C. ΛM (Ω−1 cm2 mol−1) = 12 (4.9 × 10−4 M). Anal. Calcd
for C17H21ClN2O2·H2O (338.835): C, 60.26; H, 6.84; N, 8.27. Found:
C, 59.85; H, 6.86; N, 8.07. IR (cm−1): ν(NH) 3388 br, 3186 br;
H8. 13C{1H} NMR (75.45 MHz): δ 27.4 (br s, CMe2CH2
+
CMe2C), 43.8 (s, CH2Ar), 61.3 (s, CMe2CH2), 62.8 (s, CMe2C),
1
118.3 (s, CH2C), 119.9 (q, CF3, JCF = 318.8 Hz), 128.3 (s, CH,
C8), 128.9 (s, CH, C7), 129.6 (s, CH, C9), 129.7 (s, CH, C6), 132.9
(s, C5a), 139.7 (s, C9a), 149.4 (s, CH2C). Single crystals suitable
for an X-ray diffraction study were obtained by slow diffusion of n-
hexane into a solution of 3e in acetone. 4f: The data corresponding to
4f were extracted from the spectrum of the mixture. 1H NMR (400.91
MHz): δ 1.17 (br s, 3H, Me, CMe2CH2), 1.27 (br s, 3H, Me,
CMe2CH2), 1.70 (s, 3H, Me, Me2C), 2.05 (s, 3H, Me, Me2C),
2.47 (br d, 1H, CH2, 2JHH = 12.8 Hz), 3.36 (br m, 2H, 1H of CH2Ar +
1H of CH2C), 4.18 (br d, 1H, CH2, 2JHH = 11.2 Hz), 8.98 (br s, 2H,
NH2). The signals corresponding to aromatic protons were overlapped
with the ones from the isomer 3e.
1
ν(CO) 1749 s. H NMR (400.91 MHz): δ 1.72 (s, 3H, Me, CMe2),
1.87 (s, 3H, Me, CMe2), 1.92 (br s, partially obscured by the signal
2
corresponding to the Me group, H2O), 3.46 (dd, 1H, CH2, JHH
=
16.8, 3JHH = 3.2 Hz), 3.66 (dd, 1H, CH2, 2JHH = 16.4, 3JHH = 10.8 Hz),
3.77 (s, 3H, MeO), 4.39 (dd, 1H, CHCO2Me, 3JHH = 10.4, 3JHH = 3.2
Hz), 5.51 (s, 1H, CH2C), 5.58 (s, 1H, CH2C), 7.09 (td, 1H, H7,
Synthesis of (Z)-1-(1-(trimethylsilyl)ethyliden)-2,3,4,5-tetra-
hydro-benzo[d]azepinium Triflate (4a). A suspension of the η3-
allyl complex 2c (200 mg, 0.398 mmol) in THF (10 mL) was stirred
under a CO atmosphere for 48 h. Decomposition to metallic
palladium was observed. The suspension was filtered through a plug
of Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (10 mL)
was added. The resulting suspension was filtered through a plug of
Celite, the solvent was removed from the filtrate, n-pentane (15 mL)
was added, and the mixture was vigorously stirred in an ice bath. The
suspension was filtered, and the solid was washed with n-pentane (2 ×
5 mL) and air-dried to give crude 4a as a pale yellow solid. Yield: 54
mg, 0.137 mmol, 37%. Crude 4a (25 mg, 0.063 mmol) was dissolved
in CH2Cl2 (1 mL), and n-pentane (20 mL) was added. The suspension
was filtered, and the solid was washed with n-pentane (2 × 5 mL) and
air-dried to give analytically pure 4a (16 mg, 0.040 mmol,
recrystallization yield: 64%). mp: 181 °C. ΛM (Ω−1 cm2 mol−1) =
140 (5.2 × 10−4 M). Anal. Calcd for C16H24F3NO3SSi (395.512): C,
48.59; H, 6.12; N, 3.54; S, 8.11. Found: C, 48.72; H, 6.31; N, 3.58; S,
3JHH = 8.0, JHH = 0.8 Hz), 7.18 (td, 1H, H8, JHH = 8.0, JHH = 0.8
4
3
4
Hz), 7.37 (d, 1H, H9, 3JHH = 8.0 Hz), 7.46 (d, 1H, H6, 3JHH = 8.0 Hz),
8.73 (s, 1H, NH indole). The resonance corresponding to the NH2
group was not observed. 13C{1H} NMR (100.81 MHz): δ 25.2 (s, Me,
CMe2), 25.3 (s, CH2Ar), 28.0 (s, Me, CMe2), 53.6 (s, MeO), 56.6 (s,
CHCO2Me), 64.3 (s, CMe2), 108.1 (s, C5a), 111.3 (s, CH, C9), 117.6
(s, CH2C), 118.4 (s, CH, C6), 120.1 (s, CH, C7), 123.3 (s, CH,
C8), 127.7 (s, C5b), 132.0 (s, C10a), 135.9 (s, C9a), 141.4 (s, CH2
C), 169.0 (s, CO).
Synthesis of 1-Methylen-2,2,4,4-tetramethyl-2,3,4,5-tetra-
hydro-benzo[d]azepinium Triflate (3e). A suspension of the η3-
allyl complex 2d·1/2H2O (200 mg, 0.545 mmol) in CHCl3 (15 mL)
was stirred under a CO atmosphere for 5 h. Decomposition to metallic
palladium was observed. The suspension was filtered through a plug of
Celite, the filtrate was concentrated to ca. 1 mL, and n-pentane (20
mL) was added. The suspension was filtered, and the colorless solid
was washed with n-pentane (2 × 5 mL) and air-dried (75 mg). The 1H
NMR of this solid proved it to be a 5:1 mixture of the regioisomers 3b
and 4b, which could not be separated neither by fractional
1
7.61. IR (cm−1): ν(SO) 1299 s, 1028 s; ν(CF3) 1235 s. H NMR
(400.91 MHz): δ 0.31 (s, 9H, SiMe3), 1.70 (s, 3H, Me), 2.87 (br s, 1H,
CH2), 3.02 (br s, 1H, CH2), 3.18 (br s, 1H, CH2), 3.47 (br s, 1H,
CH2), 3.65 (br s, 1H, CH2C), 4.27 (br s, 1H, CH2C), 6.18 (br s,
2H, NH2), 7.03−7.06 (m, 1H, H9), 7.18−7.21 (m, 1H, H6), 7.23−
7.26 (m, 2H, H7 + H8). 13C{1H} NMR (100.81 MHz): δ 0.11 (s,
SiMe3), 20.9 (s, MeCC), 32.7 (s, CH2Ar), 46.2 (s, CH2N), 50.6 (s,
1
crystallization nor by chromatography. The H NMR data of both
isomers were extracted from the spectrum of the mixture. 3b: 1H
NMR (400.91 MHz): δ 1.62 (br s, 6H, CMe2CH2), 1.79 (br s, 6H,
Me2C), 2.86 (br s, 2H, CH2Ar), 5.20 (s, 1H, CH2C), 5.51 (s, 1H,
CH2C), 7.06−7.33 (m, 4H, Ar), 8.95 (br s, 2H, NH2). 4b: 1H NMR
(400.91 MHz): δ 1.15 (br s, 3H, Me, CMe2CH2), 1.71 (s, 3H, Me,
Me2C), 1.74 (br s, 3H, Me, CMe2CH2), 2.08 (s, 3H, Me, Me2C),
2.45 (br d, 1H, CH2, 2JHH = 14.8 Hz), 3.34 (br d, 1H, CH2, 2JHH = 14.8
Hz), 3.39 (br d, 1H, CH2, 2JHH = 13.2 Hz), 4.16 (br d, 1H, CH2, 2JHH
= 13.2 Hz), 7.06−7.33 (m, 4H, Ar), 9.60 (br s, 2H, NH2). The signals
corresponding to the aromatic protons of both isomers were
overlapped.
1
CH2C), 120.0 (q, CF3, JCF = 318.8 Hz), 127.1 (s, CH, C8), 128.0
(s, CH, C7), 129.5 (s, CH, C6), 139.5 (s, CH, C9), 135.6 (s, C5a),
140.2 (s, MeCC), 141.2 (s, C9a), 144.9 (s, MeCC). Single
crystals suitable for an X-ray diffraction study were obtained by slow
evaporation of a solution of 4a in acetone.
Synthesis of (Z)-1-(1-(Trimethylsilyl)ethyliden)-4,4-dimethyl-
2,3,4,5-tetrahydro-benzo[d]azepinium Chloride (4c). A solution
of the η3-allyl complex 2e (130 mg, 0.313 mmol) in CHCl3 (15 mL)
was stirred under a CO atmosphere for 12 h. Decomposition to
metallic palladium was observed. The suspension was filtered through
a plug of Celite, the filtrate was concentrated to ca. 1 mL, and n-
pentane (30 mL) was added. The resulting suspension was filtered,
and the solid was washed with n-pentane (2 × 5 mL) and air-dried to
give compound 4c as a colorless solid. Yield: 30 mg, 0.097 mmol, 37%.
mp: 172 °C. ΛM (Ω−1 cm2 mol−1) = 4 (5.5 × 10−4 M). Anal. Calcd for
C17H28ClNSi (309.949): C, 65.88; H, 9.11; N, 4.52. Found: C, 65.41;
This solid was dissolved in CHCl3, Na2CO3 (300 mg, 2.83 mmol)
was added, and the mixture was stirred for 2 h. The suspension was
filtered, the filtrate was concentrated to ca. 1 mL, n-pentane (30 mL)
was added, and the resulting suspension was filtered. The solvent was
removed from the filtrate, the residue was dissolved in CH2Cl2 (10
mL), and HTfO (100 μL, 1.146 mmol) was added. The solution was
stirred for 15 min, the solvent was concentrated to ca. 2 mL, and Et2O
J
dx.doi.org/10.1021/om300928j | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1
H, 9.14; N, 4.10. H NMR (300.1 MHz): δ 0.23 (s, 9H, SiMe3), 1.21
SiMe3), 20.3 (s, MeCC), 43.9 (s, CH2Ar), 45.6 (s, CH2C), 57.7
(s, CMe2), 127.8 (s, CH, C8), 128.3 (s, CH, C7), 129.7 (s, CH, C6),
130.5 (s, CH, C9), 132.5 (s, C5a), 138.2 (s, C9a), 139.0 (s, MeCC),
140.7 (s, MeCC). The 13C NMR resonances corresponding to
CMe2 and CF3 were not observed.
(br s, 3H, Me, CMe2), 1.55 (br s, partially obscured by the signal
corresponding to MeCC, 3H, Me, CMe2), 1.57 (s, 3H, MeCC),
2.35 (br d, 1H, CH2Ar, 2JHH = 13.5 Hz), 3.02 (br d, 1H, CH2Ar, 2JHH
= 13.5 Hz), 3.66 (br d, 1H, CH2C, 2JHH = 12.6 Hz), 3.92 (br d, 1H,
2
CH2C, JHH = 13.5 Hz), 7.06−7.16 (m, 2H, H6 + H9), 7.16−7.27
Synthesis of 1-(Diphenylmethylen)-4,4-dimethyl-2,3,4,5-tet-
rahydro-benzo[d]azepinium Triflate (4h). TlTfO (171 mg, 0.483
mmol) was added to a solution of palladacycle 1d (140 mg, 0.241
mmol) in acetone (15 mL). The suspension was stirred for 30 min and
filtered through a plug of Celite to remove the TlCl formed. The
solvent was removed from the filtrate, the residue was suspended in
dry THF (15 mL) under a N2 atmosphere, 1,1-diphenylallene (120
mg, 0.624 mmol) was added, and the mixture was stirred for 12 h.
Decomposition to metallic palladium was observed. The suspension
was filtered through a plug of Celite, the filtrate was concentrated to
ca. 1 mL, and Et2O (20 mL) was added. The resulting suspension was
filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried
to give crude compound 4h as an orange solid. Yield: 144 mg, 0.294
mmol, 61%. Crude 4h was dissolved in CH2Cl2 (15 mL), and the
resulting solution was filtered trough a plug of Celite. The filtrate was
concentrated to ca. 2 mL, and Et2O (20 mL) was added. The
suspension was filtered, and the solid was washed with Et2O (2 × 5
mL) and air-dried to give analytically pure 4h as a yellow solid (66 mg,
0.135 mmol, recrystallization yield: 28%). mp: 256 °C. Anal. Calcd for
C26H26F3NO3S (489.526): C, 63.79; H, 5.35; N, 2.86; S, 6.55. Found:
C, 63.15; H, 5.56; N, 2.88; S, 6.05. IR (cm−1): ν(NH) 3370 w; ν(SO)
1288 s, 1028 s; ν(CF3) 1249 s. 1H NMR (400.91 MHz): δ 1.34 (s, 6H,
CMe2), 3.02 (br s, 2H, CH2Ar), 3.96 (s, 2H, CH2C), 6.75−6.78 (m,
2H, o-H, Ph), 6.87 (dd, 1H, H9, 3JHH = 7.6, 4JHH = 0.8 Hz), 6.99−7.05
(m, 4H, H8 + p-H of Ph + m-H of Ph), 7.13 (dd, 1H, H6, 3JHH = 7.2,
(m, 2H, H7 + H8), 8.80 (br s, 1H, NH2), 9.70 (br s, 1H, NH2).
13C{1H} NMR (75.45 MHz): δ −0.03 (s, SiMe3), 20.3 (s, MeCC),
24.2 (s, Me, CMe2), 25.6 (s, Me, CMe2), 44.1 (s, CH2Ar), 44.2 (s,
CH2C), 56.6 (s, CMe2), 127.4 (s, CH, C8), 128.0 (s, CH, C7),
129.4 (s, CH, C6), 130.5 (s, CH, C9), 132.8 (s, C5a), 138.3 (s, C9a),
138.7 (s, MeCC), 140.0 (s, MeCC). Single crystals suitable for an
X-ray diffraction study were obtained by slow diffusion of n-pentane
into a solution of 4c in CH2Cl2.
Synthesis of (Z)-(S)-1-(1-(Trimethylsilyl)ethyliden)-4-(me-
thoxycarbonyl)-2,3,4,5-tetrahydro-indolo[2,1-d]azepinium
Chloride (4e). A suspension of the η3-allyl complex 2i (155 mg, 0.319
mmol) in CHCl3 (15 mL) was stirred under a CO atmosphere for 7 h.
Decomposition to metallic palladium was observed. The suspension
was filtered through a plug of Celite, the filtrate was concentrated to
ca. 1 mL, and Et2O (30 mL) was added. The resulting suspension was
filtered, and the solid was washed with Et2O (2 × 5 mL) and air-dried
to give a first crop of compound 4e (67 mg) as a pale yellow solid. The
mother liquors were concentrated to ca. 2 mL, and n-pentane (30 mL)
was added. The suspension was filtered, and the solid was washed with
n-pentane (2 × 5 mL) and air-dried to give a second crop of
compound 4e (26 mg). Yield: 93 mg, 0.245 mmol, 77%. mp: 185 °C
dec. The insolubility of complex 4e in acetone prevented us from
measuring its conductivity. Anal. Calcd for C19H27ClN2O2Si
(378.968): C, 60.22; H, 7.18; N, 7.39. Found: C, 59.84; H, 7.45; N,
7.43. IR (cm−1): ν(NH) 3234 m; ν(CO) 1755 s. H NMR (300.1
1
3
4
4JHH = 0.8 Hz), 7.18 (td, 1H, H7, JHH = 7.2, JHH = 1.2 Hz), 7.24−
7.27 (m, 2H, o-H, Ph), 7.32−7.35 (m, 1H, p-H, Ph), 7.38−7.42 (m,
2H, m-H, Ph). The resonance corresponding to the NH2 group was
obscured by the aromatic protons. 13C{1H} NMR (100.81 MHz): δ
MHz): δ 0.40 (s, 9H, SiMe3), 2.05 (s, 3H, MeCC), 3.60 (m,
partially obscured by the signal corresponding to the OMe group, 2H,
2
CH2Ar), 3.65 (s, 3H, MeO), 4.24 (d, 1H, CH2C, JHH = 12.0 Hz),
2
1
4.38 (d, 1H, CH2C, JHH = 12.0 Hz), 4.60 (br s, 1H, CHCO2Me),
43.8 (s, CH2C), 44.4 (s, CH2Ar), 57.4 (s, CMe2), 119.8 (q, CF3, JCF
7.11 (t, 1H, H7, 3JHH = 7.5 Hz), 7.18 (t, 1H, H8, 3JHH = 7.2 Hz), 7.33
= 318.9 Hz), 127.2 (s, p-CH, Ph), 127.6 (s, m-CH, Ph), 128.1 (s, p-
CH, Ph), 128.3 (s, CH, C8), 128.4 (s, CH, C7), 128.5 (s, Ph2CC),
128.9 (s, m-CH, Ph), 129.3 (s, o-CH, Ph), 129.6 (s, CH, C6), 129.8 (s,
o-CH, Ph), 131.7 (s, CH, C9), 133.5 (s, C5a), 138.1 (s, C9a), 139.9 (s,
i-C, Ph), 140.8 (s, i-C, Ph). The 13C{1H} NMR resonances
corresponding to CMe2 and Ph2CC were not observed. Single
crystals suitable for an X-ray diffraction study were obtained by slow
diffusion of Et2O into a solution of 4h in CH3Cl.
(d, 1H, H9, 3JHH = 7.8 Hz), 7.47 (d, 1H, H6, JHH = 7.8 Hz), 8.16 (s,
3
1H, NH indole), 9.81 (br s, 1H, NH2), 10.82 (br s, 1H, NH2).
13C{1H} NMR (75.45 MHz): δ 0.5 (s, SiMe3), 21.5 (s, MeCC), 24.0
(s, CH2Ar), 48.6 (s, CH2C), 53.1 (s, MeO), 57.1 (s, CHCO2Me),
108.9 (s, C5a), 111.0 (s, CH, C9), 118.2 (s, CH, C6), 120.0 (s, CH,
C7), 122.8 (s, CH, C8), 127.3 (s, C5b), 130.9 (s, MeCC), 135.0 (s,
C10a), 137.3 (s, C9a), 147.9 (s, MeCC), 168.6 (s, CO).
Synthesis of (Z)-1-(1-(Trimethylsilyl)ethyliden)-4,4-dimethyl-
2,3,4,5-tetrahydro-benzo[d]azepinium Triflate (4g). TlTfO (122
mg, 0.345 mmol) was added to a solution of palladacycle 1d (100 mg,
0.172 mmol) in acetone (15 mL). The suspension was stirred for 30
min and filtered through a plug of Celite to remove the TlCl formed.
The solvent was removed from the filtrate, the residue was dissolved in
dry THF (15 mL) under a N2 atmosphere, 1-trimethylsilyl-1,2-
butadiene (58 μL, 0.348 mmol) was added, and the mixture was stirred
for 12 h. Decomposition to metallic palladium was observed. The
suspension was filtered through a plug of Celite, the solvent was
removed from the filtrate, and Et2O (2 mL) and n-pentane (20 mL)
were added. The resulting suspension was filtered, and the solid was
washed with n-pentane (2 × 5 mL) and air-dried to give crude 4g as a
colorless solid. Yield: 88 mg, 0.208 mmol, 60%. Crude 4g (75 mg,
0.177 mmol) was dissolved in CH2Cl2 (1 mL), and n-pentane (15 mL)
was added. The suspension was filtered, and the solid was washed with
n-pentane (2 × 5 mL) and air-dried to give analytically pure 4g (68
mg, 0.160 mmol, recrystallization yield: 90%). mp: 184 °C. ΛM (Ω−1
cm2 mol−1) = 143 (4.8 × 10−4 M). Anal. Calcd for C18H28F3NO3SSi
(423.565): C, 51.04; H, 6.66; N, 3.31; S, 7.57. Found: C, 51.01; H,
Synthesis of (Z)-(S)-1-(Ethyliden)-4-(methoxycarbonyl)-
2,3,4,5-tetrahydro-indolo[2,1-d]azepinium Chloride Monohy-
drate (4l·H2O). The salt 4e (30 mg, 0.079 mmol) was dissolved in a
HCl-saturated solution of CHCl3 (15 mL). The mixture was stirred for
12 h, upon which time a solid precipitated. The suspension was
filtered, and the solid was washed with a 1:5 mixture of CHCl3 and
Et2O (6 mL), then with Et2O (5 mL), and air-dried to afford
compound 4l·H2O as a pale yellow solid. Yield: 20 mg, 0.062 mmol,
78%. mp: 224 °C dec. The insolubility of complex 4l·H2O in acetone
prevented us from measuring its conductivity. Anal. Calcd for
C16H19ClN2O2·H2O (324.808): C, 59.17; H, 6.52; N, 8.62. Found:
C, 58.75; H, 6.44; N, 8.77. IR (cm−1): ν(NH) 3248 br; ν(CO) 1745 s.
1H NMR (300.1 MHz, DMSO-d6): δ 1.91 (d, 3H, Me, 3JHH = 6.9 Hz),
3.35, 3.50 (AB part of an ABM system, 2H, CH2Ar, 2JAB = 16.6, 3JBM
=
9.1, 3JAM = 2.9 Hz), 3.70 (s, 3H, MeO), 4.14 (br s, 2H, CH2C), 4.48
(br s, 1H, CHCO2Me), 5.44 (br s, H2O), 6.35 (q, 1H, CHC, 3JHH
=
3
3
6.9 Hz), 6.99 (t, 1H, H7, JHH = 7.2 Hz), 7.09 (t, 1H, H8, JHH = 7.2
Hz), 7.30 (d, 1H, H9, 3JHH = 7.8 Hz), 7.47 (d, 1H, H6, 3JHH = 7.5 Hz),
9.47 (br s, 1H, NH2), 10.38 (br s, 1H, NH2), 11.27 (s, 1H, NH,
indole). 13C{1H} NMR (DMSO-d6, 100.81 MHz): δ 13.6 (s, Me),
22.8 (s, CH2Ar), 42.1 (s, CH2C), 53.1 (s, MeO), 58.7 (s,
CHCO2Me), 107.1 (s, C5a), 110.9 (s, CH, C9), 117.8 (s, CH, C6),
118.0 (s, CH, C7), 122.1 (s, CH, C8), 124.2 (s, CHC), 127.3 (s,
CHC), 127.6 (s, C5b), 135.1 (s, C10a), 135.7 (s, C9a), 169.0 (s,
CO).
6.99; N, 3.22; S, 7.40. IR (cm−1): ν(SO) 1263 s, 1030 s. H NMR
1
(300.1 MHz): δ 0.21 (s, 9H, SiMe3), 1.21 (br s, 3H, Me, CMe2), 1.43
(br s, 3H, Me, CMe2), 1.58 (s, 3H, MeCC), 2.42 (br s, 1H, CH2Ar),
3.00 (br s, 1H, CH2Ar), 3.80 (br s, 1H, CH2C), 4.00 (br s, 1H,
CH2C), 7.01−7.06 (m, 2H, H6 + H9), 7.16−7.24 (m, 2H, H7 +
H8), 7.60 (br s, 1H, NH2). The resonance corresponding to the NH2
group was not observed. 13C{1H} NMR (75.45 MHz): δ −0.21 (s,
Synthesis of (S)-1-Methylen-3,3-dimethyl-4-(methoxycar-
bonyl)-2,3,4,5-tetrahydro-benzo[d]azepine (5a). A suspension
K
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Organometallics
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of the η3-allyl complex 2f (150 mg, 0.346 mmol) in CHCl3 (15 mL)
was stirred under a CO atmosphere for 12 h. Decomposition to
metallic palladium was observed. The suspension was filtered through
a plug of Celite, the solvent was removed from the filtrate, and the oily
min and filtered through a plug of Celite to remove the TlCl formed.
The solvent was removed from the filtrate, the residue was suspended
in dry CH2Cl2 (15 mL) under a N2 atmosphere, ethyl 2,3-butadienoate
(80 μL, 0.654 mmol) was added, and the mixture was stirred for 24 h.
Decomposition to metallic palladium was observed. The suspension
was filtered through a plug of Celite, the solvent was removed from the
filtrate, and the oily residue was vacuum-dried to give compound 4i.
1H NMR (400.91 MHz): δ 1.32 (t, 3H, MeCH2, 3JHH = 7.2 Hz), 3.39
1
residue was vacuum-dried to give compound 3c. H NMR (300.10
MHz): δ 1.64 (br s, 3H, Me, CMe2), 1.92 (br s, 3H, Me, CMe2), 3.26,
2
3
3.36 (AB part of an ABX system, 2H, CH2Ar, JAB = 14.1, JAX = 6.3,
3JBX = 2.7 Hz), 3.83 (br s, 3H, MeO), 4.33 (br m, 1H, CHCO2Me),
5.33 (s, 1H, CH2C), 5.67 (s, 1H, CH2C), 7.12−7.21 (m, 2H, Ar),
7.27−7.33 (m, 2H, Ar). The signal corresponding to the resonance of
the NH2 group is not observed.
3
(m, 2H, CH2Ar), 3.86 (s, 3H, MeO), 4.23 (q, 2H, CH2O, JHH = 7.2
4
Hz), 4.54 (br t, 1H, CHCO2Me, JHH = 6.0 Hz), 4.79 (br s, 2H,
CH2C), 6.17 (s, 1H, CHC), 7.15−7.38 (m, 4H, Ar). The
resonance corresponding to the resonance of NH2 group is not
observed.
The oily residue was dissolved in CHCl3 (15 mL), Na2CO3 (100
mg, 0.943 mmol) was added, and the mixture was stirred for 3 h. The
suspension was filtered, the solvent was removed from the filtrate, and
n-pentane (30 mL) was added. The suspension was filtered through a
plug of Celite, the solvent was removed from the filtrate, and the
residue was vacuum-dried to afford compound 5a as a pale yellow oil.
Yield: 51 mg, 0.21 mmol, 60%. Anal. Calcd for C13H18BrN (268.203):
C, 58.22; H, 6.76; N, 5.22. Found: C, 57.86; H, 7.03; N, 5.31. IR
(cm−1): ν(NH) 3287 m, 3227 m; ν(CO) 1739 vs EI-HRMS: exact
mass calcd. for C15H19NO2 245.1416; found 245.1419; Δ = 0.0003. 1H
NMR (400.91 MHz): δ 1.30 (s, 3H, Me, CMe2), 1.39 (br s, 3H, Me,
The oily residue was dissolved in CH2Cl2 (15 mL), Na2CO3 (200
mg, 1.88 mmol) was added, and the mixture was stirred for 3 h. The
suspension was filtered through a plug of Celite, the filtrate was
concentrated ca. 1 mL, and n-pentane (20 mL) was added. A small
amount of solid precipitated, which was separated by filtration. The
solvent was removed from the filtrate, and the residue was vacuum-
dried to give the benzazepine 6b as a pale yellow oil. Yield: 47 mg,
0.163 mmol, 26%. IR (cm−1): ν(NH) 3368 m; ν(CO) 1712 br. EI-
HRMS: exact mass calcd for C16H19NO4 289.1314; found 289.1304; Δ
1
3
CMe2), 1.85 (br s, 1H, NH), 2.93 (dd, 1H, CH2Ar, 2JHH = 14.2, 3JHH
=
= 0.001. H NMR (300.1 MHz): δ 1.24 (t, 3H, MeCH2, JHH = 7.2
2
3
Hz), 1.96 (br s, 1H, NH), 3.01 (m, 2H, CH2Ar), 3.67 (s, 3H, MeO),
4.4 Hz), 3.21 (dd, 1H, CH2Ar, JHH = 14.2, JAM = 6.4 Hz), 3.72 (s,
3H, MeO), 3.97 (dd, 1H, CHCO2Me, 3JHH = 6.4, 3JHH = 4.8 Hz), 4.99
(s, 1H, CH2C), 5.24 (s, 1H, CH2C), 7.01−7.03 (m, 1H, H6),
7.14−7.26 (m, 1H, H9), 7.23 (m, 2H, H7 + H8). 13C{1H} NMR
(100.81 MHz): δ 25.6 (s, Me, CMe2), 32.3 (s, Me, CMe2), 52.0 (s,
MeO), 54.1 (s, CMe2), 54.2 (s, CHCO2Me), 112.6 (s, CH2C),
127.0 (s, CH, C8), 127.8 (s, CH, C7), 128.29 (s, CH, C6), 128.3 (s,
CH, C9), 134.1 (s, C5a), 142.1 (s, C9a), 160.2 (s, CH2C), 173.7 (s,
CO). The 13C NMR resonance corresponding to CH2Ar was not
observed.
3
3.74 (m, 1H, CHCO2Me), 4.13 (q, 2H, CH2O, JHH = 7.2 Hz), 4.15
(dd, partially obscured by the signal corresponding to the CH2O
2
4
group, 1H, CH2C, JHH = 20.1, JHH = 2.4 Hz), 4.28 (dd, 1H,
CH2C, 2JHH = 20.1, 4JHH = 2.4 Hz), 5.84 (t, 1H, CHC, 4JHH = 2.4
Hz), 7.03−7.06 (m, 1H, H6), 7.19−7.28 (m, 3H, H7 + H8 + H9).
13C{1H} NMR (50.30 MHz): δ 14.3 (s, MeCH2), 35.3 (s, CH2Ar),
46.6 (s, CH2C), 52.1 (s, MeO), 58.1 (s, CHCO2Me), 60.0 (s,
CH2O), 117.3 (s, CHC), 127.7 (s, CH), 127.8 (s, CH), 128.6 (s,
CH, C6), 129.4 (s, CH), 135.1 (s, C5a), 140.1 (s, C9a), 164.8 (s,
CHC), 166.1 (s, CO2Et), 173.3 (s, CO2Me).
Synthesis of (Z)-(S)-1-(1-(Trimethylsilyl)ethyliden)-4-(carbo-
methoxy)-2,3,4,5-tetrahydro-benzo[d]azepine (6a). A solution
of the η3-allyl complex 2g (190 mg, 0.339 mmol) in acetone (15 mL)
was stirred under a CO atmosphere for 12 h. Decomposition to
metallic palladium was observed. The suspension was filtered through
a plug of Celite, the solvent was removed from the filtrate, and the
residue was vacuum-dried to give compound 4d as a waxy solid (101
Synthesis of (Z)-1-((Ethoxycarbonyl)methylen)-2,3,4,5-tetra-
hydro-benzo[d]azepine (6c). Ethyl 1,2-butadienoate (80 μL, 0.654
mmol) was added to a suspension of palladacycle 1b (192 mg, 0.313
mmol) in dry CH2Cl2 (10 mL) under a N2 atmosphere, and the
resulting yellow solution was stirred for 7 h. Decomposition to metallic
palladium was observed. The suspension was filtered through a plug of
Celite, the filtrate was concentrated to ca. 1 mL, and Et2O (20 mL)
was added. The suspension was filtered, and the solid was washed with
Et2O (2 × 5 mL) and air-dried to give crude compound 4j as a gray
1
mg). H NMR (200.13 MHz): δ 0.24 (s, 9H, SiMe3), 1.62 (s, 3H,
2
MeCC), 3.17, 3.35 (AB part of an ABX system, 2H, CH2Ar, JAB
=
14.6, 3JAX = 6.3 Hz), 3.66 (br s, 3H, MeO), 4.10 (br s, 2H, CHCO2Me
or CH2C), 4.51 (br s, 1H, CHCO2Me or CH2C), 6.96 (m, 1H,
Ar), 7.13−7.24 (m, 3H, Ar), 8.20 (br s, 2H, NH2).
1
solid (characterized by H NMR). To this solid were added CHCl3
(15 mL) and Na2CO3 (200 mg, 1.88 mmol), and the mixture was
stirred for 12 h. The suspension was filtered, the solvent was removed
from the filtrate, and n-pentane (30 mL) was added. The suspension
was filtered through a plug of Celite, the solvent was removed from the
filtrate, and the residue was vacuum-dried to afford compound 6c as a
colorless liquid (69 mg, 0.298 mmol, 48%). Characterization of 4j: It
was not possible to obtain a correct elemental analysis of 4j because it
The waxy solid was dissolved in acetone (15 mL), Na2CO3 (100
mg, 0.94 mmol) was added, and the mixture was stirred for 6 h. The
suspension was filtered through a plug of Celite, the solvent was
removed from the filtrate, and n-pentane (30 mL) was added. The
mixture was filtered through a plug of Celite, the solvent was removed
from the filtrate, and the residue was vacuum-dried to give compound
6a as a colorless liquid. Yield: 62 mg, 0.204 mmol, 60%. Anal. Calcd
for C18H28F3NO3SSi (423.565): C, 51.04; H, 6.66; N, 3.31; S, 7.57.
Found: C, 51.01; H, 6.99; N, 3.22; S, 7.40. IR (cm−1): ν(CO) 1742 m.
EI-HRMS: exact mass calcd for C17H25NO2Si 303.1655; found
303.1646; Δ = 0.0009. 1H NMR (400.91 MHz): δ 0.26 (s, 9H,
SiMe3), 1.62 (s, 3H, MeCC), 1.88 (s, 1H, NH), 3.02 (br s, 2H,
CH2Ar), 3.48 (br s, 1H, CHCO2Me or CH2C), 3.65 (br s, 1H,
CHCO2Me or CH2C), 3.74 (s, 3H, MeO), 3.85 (br s, 1H,
1
was contaminated with traces of colloidal palladium. H NMR (300.1
3
MHz): δ 1.32 (t, 3H, MeCH2, JHH = 7.2 Hz), 3.17 (“t”, 2H, CH2Ar,
3
3JHH = 5.4 Hz), 3.53 (“t”, 2H, CH2N, JHH = 5.4 Hz), 4.22 (q, 2H,
CH2O, 3JHH = 7.2 Hz), 4.57 (s, 2H, CH2C), 6.14 (s, 1H, CHC),
7.22 (d, 1H, H6, 3JHH = 6.6 Hz), 7.27−7.39 (m, 3H, H7 + H8 + H9),
8.61 (br s, 2H, NH2). 13C{1H} NMR (75.45 MHz): δ 14.1 (s,
MeCH2), 30.0 (s, CH2Ar), 44.8 (s, CH2N), 45.0 (s, CH2C), 60.8 (s,
CH2O), 122.8 (s, CHC), 128.0 (s, CH), 128.3 (s, CH), 129.5 (s,
CH, C6), 130.2 (s, CH), 134.7 (s, C5a), 138.1 (s, C9a), 149.8 (s,
CH=C), 165.1 (s, CO). Characterization of 6c: IR (cm−1): ν(NH)
3418 br; ν(CO) 1721 s. EI-HRMS: exact mass calcd for C14H17NO2
3
4
CHCO2Me or CH2C), 7.03 (dd, 1H, H9, JHH = 8.0, JHH = 2.8
Hz), 7.15−7.25 (m, 3H, H6 + H7 + H8). 13C{1H} NMR (75.45
MHz): δ 0.3 (s, SiMe3), 20.2 (s, MeCC), 29.6 (s, CH2Ar), 49.8 (s,
CH2C=), 52.0 (s, MeO), 126.4 (s, CH, C7 or C8), 126.9 (s, CH, C7
or C8), 128.9 (s, CH, C6), 129.0 (s, CH, C9), 151.5 (s, MeC=C),
173.6 (s, CO). The 13C NMR resonances corresponding to
CHCO2Me, C5a, C9a, and MeCC were not observed.
1
231.1259; found 231.1254; Δ = 0.0005. H NMR (400.91 MHz): δ
1.31 (t, 3H, MeCH2, 3JHH = 6.8 Hz), 1.67 (br s, 1H, NH), 2.81 (t, 2H,
3
3
CH2Ar, JHH = 6.4 Hz), 3.03 (t, 2H, CH2N, JHH = 6.4 Hz), 4.16 (d,
4
3
2H, CH2C, JHH = 2.0 Hz), 4.20 (q, 2H, CH2O, JHH = 6.8 Hz),
4
3
5.89 (t, 1H, CHC, JHH = 2.4 Hz), 7.13 (dd, 1H, H6, JHH = 7.2,
4JHH = 0.4 Hz), 7.24−7.33 (m, 3H, H7 + H8 + H9). 13C{1H} NMR
(100.81 MHz): δ 14.2 (s, MeCH2), 34.1 (s, CH2Ar), 46.3 (s, CH2N),
48.5 (s, CH2C), 59.9 (s, CH2O), 117.1 (s, CHC), 127.0 (s, CH,
Synthesis of (Z)-(S)-1-((Ethoxycarbonyl)methylen)-4-(carbo-
methoxy)-2,3,4,5-tetrahydro-benzo[d]azepine (6b). TlTfO (221
mg, 0.625 mmol) was added to a solution of palladacycle 1i (200 mg,
0.312 mmol) in acetone (15 mL). The suspension was stirred for 30
L
dx.doi.org/10.1021/om300928j | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
C8), 127.5 (s, CH, C7), 128.3 (s, CH, C6), 129.3 (s, CH, C9), 137.5
(s, C5a), 140.5 (s, C9a), 166.1 (s, CO), 166.3 (s, CHC).
transferred to a Bruker SMART diffractometer. Data were recorded at
100(2) K, using graphite-monochromated Mo Kα radiation (λ =
0.71073 Å) and ω-scan mode. Multiscan absorption corrections were
applied for complexes 3a, 3e, 4a, 4h, and 7a. Structure solution and
refinements: Crystal Structures were solved by the direct method and
all non-hydrogen atoms were refined anisotropically on F2 using the
program SHELXL-97.47 Hydrogen atoms were refined as follows:
Compounds 3a and 4c·CH2Cl2: NH2, free with SADI; methyl, rigid
group; all others, riding. Compounds 3e, 4a, and 4h: NH2, free;
methyl, rigid group; all others, riding. Compound 7a: NH2, free with
DFIX; methyl, rigid group; all others, riding. Special features:
Compound 3a: absolute structure (Flack) parameter48 −0.013(5).
Compound 4a: the triflate anion is disordered over two positions with
a ca. 85:15 occupancy distribution. Compound 7a: Flack parameter
0.014(10).
Computational Details. Density funtional calculations were
carried out using the Gaussian 03 package.49 The hybrid density
functional BP8650 was applied, employing the SDD basis set51 to
describe the Cl and Pd atoms and 6-31G* for N, C, and H.52 After
geometry optimizations, analytical frequency calculations were carried
out to determine the nature of the stationary points found and confirm
that they were minima or transition states.
Synthesis of (Z)-1-((Ethoxycarbonyl)methylen)-4,4-dimeth-
yl-2,3,4,5-tetrahydro-benzo[d]azepine (6d). Ethyl 1,2-butadie-
noate (90 μL, 0.736 mmol) was added to a solution of palladacycle
1d (200 mg, 0.345 mmol) in dry CH2Cl2 (15 mL) under a N2
atmosphere, and the resulting yellow solution was stirred for 12 h.
Decomposition to metallic palladium was observed. The suspension
was filtered through a plug of Celite, the filtrate was concentrated to
ca. 1 mL, and Et2O (20 mL) was added. The suspension was filtered,
the filtrate was concentrated to ca. 1 mL, and n-pentane (30 mL) was
added. The resulting suspension was filtered, and the solid was washed
with n-pentane (2 × 5 mL) and air-dried to give the salt 4k as a pale
yellow solid (109.0 mg, 0.368 mmol, 53%). The solvent from the
mother liquors was removed, and the residue was vacuum-dried to
afford the 3-benzazepine 6d as a colorless liquid (73.0 mg, 0.281
mmol, 41%). Characterization of 4k: It was not possible to obtain a
1
correct elemental analysis of 4k due to its hygroscopic character. H
3
NMR (400.91 MHz): δ 1.31 (t, 3H, MeCH2, JHH = 6.8 Hz), 1.50 (s,
6H, CMe2), 2.72 (s, 2H, CH2Ar), 4.21 (q, 2H, CH2O, 3JHH = 6.8 Hz),
4.51 (br s, 2H, CH2C), 6.00 (t, 1H, CHC, 4JHH = 2.4 Hz), 7.08−
7.10 (m, 1H, H6), 7.37−7.39 (m, 2H, H8 + H7 or H9), 7.44−7.64 (m,
1H, H7 or H9), 9.62 (br s, 2H, NH2). 13C{1H} NMR (100.81 MHz):
δ 14.2 (s, MeCH2), 24.5 (s, CMe2), 42.3 (s, CH2C), 43.2 (s,
CH2Ar), 58.2 (s, CMe2), 60.4 (s, CH2O), 120.6 (s, CHC), 128.8 (s,
CH, C8), 129.7 (s, CH, C6), 129.8 (s, CH, C7 or C9), 130.9 (s, CH,
C7 or C9), 132.4 (s, C5a), 137.3 (s, C9a), 152.4 (s, CHC), 165.3 (s,
CO). Characterization of 6d: IR (cm−1): ν(NH) 3402 w; ν(CO) 1712
vs EI-HRMS: exact mass calcd for C16H21NO2 259.1572; found
259.1568; Δ = 0.0004. 1H NMR (400.91 MHz): δ 1.12 (s, 6H, CMe2),
1.31 (t, 3H, MeCH2, 3JHH = 6.4 Hz), 2.62 (s, 2H, CH2Ar), 4.20 (q, 2H,
CH2O, 3JHH = 6.8 Hz), 4.24 (d, 2H, CH2C, 4JHH = 2.4 Hz), 5.90 (t,
1H, CHC, 4JHH = 2.4 Hz), 7.07 (dd, 1H, H6, 3JHH = 7.6, 4JHH = 1.6
Hz), 7.25−7.32 (m, 2H, H7 + H8), 7.35 (dd, 1H, H9, 3JHH = 7.2, 4JHH
= 1.6 Hz). The resonance corresponding to NH was not observed.
13C{1H} NMR (100.81 MHz): δ 14.3 (s, MeCH2), 27.3 (s, CMe2),
ASSOCIATED CONTENT
* Supporting Information
■
S
Complete set of Cartesian coordinates for all computed
structures; energy profiles for the isomerizations of Z into Y'
and cis-2e into trans-2e; details (including symmetry operators)
of hydrogen bondings, and CIF files for compounds 3a, 3e, 4a,
4c·CH2Cl2, 4h, and 7a. This material is available free of charge
via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: jvs1@um.es (J.V.), ims@um.es (I.S.-L.), john.
mcgrady@chem.ox.ac.uk (J.E.M.).
■
44.8 (s, CH2C), 45.0 (s, CH2Ar), 52.1 (s, CMe2), 59.9 (s, CH2O),
116.8 (s, CHC), 127.1 (s, CH, C8), 127.9 (s, CH, C9), 129.2 (s,
CH, C7), 129.4 (s, CH, C6), 136.9 (s, C5a), 139.3 (s, C9a), 166.2 (s,
CO), 166.6 (s, CHC).
Notes
The authors declare no competing financial interest.
Synthesis of 3,3-Dimethyl-4-methylen-6-methoxy-1,2,3,4-
tetrahydroisoquinolinium bromide (7a). 1,1-Dimethylallene (76
μL, 0.766 mmol) was added to a suspension of palladacycle
[Pd2{κ2(C,N)-C6H3CH2NH2-2,OMe-5}2(μ-Br)2] (1j; 240 mg, 0.372
mmol) in dry CH2Cl2 (15 mL) under a N2 atmosphere, and the
mixture was stirred for 12 h. Decomposition to metallic palladium was
observed. The suspension was filtered through a plug of Celite, the
filtrate was concentrated to ca. 2 mL, and Et2O (20 mL) was added.
The resulting suspension was filtered, and the solid was washed with
Et2O (2 × 5 mL) and air-dried to give crude compound 7a as a pale
yellow solid. Yield: 152 mg, 0.634 mmol, 85%. An analytically pure
sample of 7a was obtained by recrystallization from CH2Cl2/Et2O
(108 mg, 0.451 mmol, recrystallization yield: 71%). mp: 186 °C. ΛM
(Ω−1 cm2 mol−1): 14 (4.9 × 10−4 M). Anal. Calcd for C13H18BrNO
(284.202): C, 54.94; H, 6.38; N, 4.93. Found: C, 54.39; H, 6.39; N,
ACKNOWLEDGMENTS
We thank Ministerio de Educacion
(CTQ2007-60808/BQU), and Fundacion
■
́
y Ciencia (Spain), FEDER
Seneca (04539/
́
́
GERM/06) for financial support. J.-A.G.-L. is grateful to the
Fundacion Seneca for a research grant.
́
́
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