CO2 on a tightrope: Stabilization, room-temperature decarboxylation, and sodium-induced carboxylate migration

Article abstract of DOI:10.1002/chem.201202298

A sterically shielded 3-substituted zwitterionic N,N- dimethylisotryptammonium carboxylate has been synthesized by consecutive chemoselective double alkylation of indole. The carboxylate undergoes a quantitative and unusually facile decarboxylation in dim

Full text of DOI:10.1002/chem.201202298

FULL PAPER
DOI: 10.1002/chem.201202298
CO2 on a Tightrope: Stabilization, Room-Temperature Decarboxylation, and
Sodium-Induced Carboxylate Migration
Achim Hꢀußermann, Frank Rominger, and Bernd F. Straub*[a]
Abstract: A sterically shielded 3-substi-
tuted zwitterionic N,N-dimethylisotryp-
tammonium carboxylate has been syn-
thesized by consecutive chemoselective
double alkylation of indole. The car-
boxylate undergoes a quantitative and
unusually facile decarboxylation in di-
methyl sulfoxide (DMSO) or dimethyl
formamide (DMF) at room tempera-
ture. The breaking of a nearly equidis-
tant hydrogen bond by solvent mole-
age. The decarboxylation rate decreas-
es with increasing CO2 partial pressure,
proving the competitiveness of proto-
nation and re-carboxylation of the
high thermal stability. Addition of an
excess of methyllithium to the sodium
salt triggers a reaction sequence com-
prising
a deprotonation, carboxylate
carb
N
transfer, and nucleophilic trapping of
the rearranged carboxylate by another
equivalent of methyllithium. Hydrolytic
work-up of the geminal diolate leads to
an acetyl product. The role of the
sodium counterion and the mechanism
of the rearrangement have been unrav-
eled by deuteration experiments.
ing spiro compounds containing sily-
lene and stannylene moieties show
Keywords: carbon dioxide · decar-
boxylation · rearrangement · spiro
compounds · zwitterions
À
cules initiates heterolytic C C cleav-
Introduction
Scientific and industrial interest in reactions of CO2 with in-
expensive organic substrates to produce useful bulk chemi-
cals has greatly increased recently.[1] In such reactions, car-
boxylates are a mandatory intermediate or the final product.
Controlling the stability of carboxylates is crucial for carbon
dioxide fixation with a low thermodynamic driving force,
which is tantamount to energy efficiency. In natural CO2 fix-
ation, the alternatives of hydrogen bonding versus magnesi-
um coordination to the carboxylate in the ribulose-1,5-bi-
sphosphate carboxylase oxygenase (RuBisCo) active site are
a matter of recent discussions.[2] Besides CO2 fixation, car-
boxylic acids and the corresponding carboxylates are ubiqui-
tous both in organic chemistry as well as in biochemistry.[3]
Various classes of pharmacologically or industrially impor-
tant compounds, such as stilbenes,[4] hydroxystyrenes,[5] or in-
doles,[6] as well as chiral auxiliaries for asymmetric synthe-
sis,[7] are prepared from their parent acids by decarboxyla-
tion (Scheme 1). Ketonization by decarboxylation,[8] decar-
boxylative palladation reactions in Heck-type olefination,[9]
the synthesis of biaryls by catalytic decarboxylative cou-
pling,[10] and the Kolbe reaction,[11] a decarboxylative elec-
Scheme 1. General scheme of anionic aliphatic decarboxylation and of
CO2 fixation.
trochemical dimerization, are valuable tools for the synthe-
sis of various substances starting from carboxylic acids.
Besides ambient enzymatic decarboxylative systems in
nature, the decarboxylation reaction in organic synthesis has
remained one of the more difficult transformations. There
are numerous procedures in the literature for the elimina-
tion of CO2 from organic substrates. The simplest transfor-
mations merely require heating, for example the preparation
of tryptamine from tryptophan.[12] Generally, however, de-
carboxylation reactions require the use of a base[6d,13] or
prior activation by a metal catalyst.[14] Microwave heating
provides a useful tool for acceleration of reactions and
broadening the scope of usable substrates.[5a,6a,13,15] Conver-
sion into Barton esters followed by treatment with tributyl-
tin hydride,[16] photochemical decarboxylation,[17] or ketone
catalysis[18] are further decarboxylation methods.
The decarboxylation reactions mentioned above either in-
volve a catalyst or some kind of activation by ultraviolet ra-
diation, microwave radiation, or thermal energy. There are
only a few carboxylic acids that undergo decarboxylation at
room temperature. A well-known reaction is the decarboxy-
lation of 3-keto acids (Scheme 2, top), first reported by
Pollak et al. in 1907.[19] Numerous studies concerning the de-
carboxylation of 3-keto acid derivatives and the acceleration
thereof by amine catalysts have been carried out.[20] Some
acetic acid derivatives bearing strong electron-withdrawing
[a] A. Hꢀußermann, Dr. F. Rominger, Prof. Dr. B. F. Straub
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
Fax : (+49)6221-54-4205
E-mail: straub@oci.uni-heidelberg.de
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201202298.
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ess between the carbanion and carbon dioxide. The fact that
other Brønsted acids show no effect led Kluger to propose
that pyridinium pre-associates with the substrate by p-stack-
ing effects between the positively charged pyridinium and
the phenyl ring of benzoyl formate (Scheme 3).
In this particular arrangement, the proton is in special
proximity to enter an effective proton-transfer process. It
promotes the departure of carbon dioxide by preventing in-
ternal return of this molecule. The acceleration of the decar-
boxylation of MTh by pyridinium ions results from pre-asso-
ciation forming a weak complex and effective protonation
of the nascent carbanion formed upon decarboxylation.
Building on the concept of pre-association catalysis, Kluger
et al. revealed another important factor that can control the
rate of a reaction.[3c] The fact that many ThDP-dependent
decarboxylases contain a nucleophile at their active site that
could facilitate the expulsion of carbon dioxide highlights
the importance of reversibility in decarboxylation proces-
ses.[3b,29,31]
Apart from enzymatic decarboxylation, there are only a
limited number of decarboxylation reactions that proceed at
room temperature. While working on tridentate ligands for
transition metal catalysis, we observed that a 3-substituted
N,N-dimethylisotryptamine (isoDMT)-based amino acid
shows unprecedented mobility of its CO2 fragment. We in-
vestigated the decarboxylation of compound 1 to understand
the origin of this facile process, and to identify factors that
stabilize or destabilize carboxylates.
Scheme 2. Decarboxylation of 3-keto acid derivatives (top row); decom-
position of monoalkyl carbonates (bottom row).
À
substituents undergo C C bond cleavage at ambient temper-
ature. 2,4,6-Trinitrobenzoic acid in ethanol[21] and nitroacetic
acid in aqueous solution[22] easily eliminate carbon dioxide.
Tribromoacetic acid is unstable at ambient temperature[23]
and triiodoacetic acid decomposes rapidly in solution.[24] The
decarboxylation of monoalkyl carbonates is rapid in aque-
ous alkali and depends on the basicity of the residual alkox-
ide.[25] Sauers and co-workers showed that the rate of decar-
boxylation of a series of monoalkyl carbonates has a linear
dependence on the pKa value of the residual alkoxides.[26]
This correlation can provide an estimation of the pKa values
of weakly acidic alcohols (Scheme 2, bottom).
Enzyme-catalyzed decarboxylations in biochemistry are a
fundamental field of research. Hilvert and co-workers inves-
tigated the decarboxylation of 5-nitro-3-carboxybenzisoxa-
zoles,[27] which is particularly sensitive to solvation in organic
solvents and towards antibody catalysis. Decomposition in-
creases rapidly on changing from a protic to an aprotic sol-
vent. 4-Pyridylacetic acid is also an excellent model sub-
strate for enzyme-catalyzed decarboxylations. A common
feature of these reactions is charge neutralization of the
zwitterionic intermediate.[28] Furthermore, the enzymatic
decarboxylation of benzoylformic acid to benzaldehyde,
catalyzed by the thiamine diphosphate (ThDP)-depen-
dent enzyme benzoyl formate decarboxylase (BFD), was
thoroughly investigated by Kluger and co-workers
(Scheme 3).[3a,b,29] They used mandelylthiamine (MTh), a
Results and Discussion
Amino acid 1 was prepared on a multigram scale by a three-
step procedure starting from commercially available indole
and dibenzosuberone. First, we optimized the N-alkylation
of indole to afford 1-[2-(N,N-dimethylamino)ethyl]indole
(N,N-dimethylisotryptamine, isoDMT), a reaction that has
been described previously by several groups (Scheme 4, left
column).[32]
The second fragment of amino acid 1, 5-hydroxydibenzo-
AHCTUNGTREG[NNUN a,d]cycloheptene-5-carboxylic acid, was synthesized by re-
ductive carboxylation of commercially available dibenzosu-
berone (Scheme 4, middle column).[33] The insoluble crude
Scheme 3. Pre-association in pyridinium-catalyzed decarboxylation of
mandelylthiamine.[3c,30d]
conjugate of thiamine and benzoyl formate, as a model of
the intermediate in BFD in their studies. They found that
the decarboxylation of MTh is subject to catalysis by pyri-
dine-based buffers.[30] An explanation of their findings is
given by the assumption that if a catalyst can block the re-
verse reaction, the net decarboxylation rate will be en-
hanced. Pyridinium accelerates the elimination of carbon di-
oxide from MTh by efficiently transferring a proton to the
nascent carbanion, thereby facilitating the separation proc-
Scheme 4. Synthesis of 5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-
10,11-dihydro-5H-dibenzoACHTNUTRGNE[NUG a,d]cycloheptene-5-carboxylic acid (1).
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Zwitterionic N,N-Dimethylisotryptammonium Carboxylate
FULL PAPER
product, presumably a polyester, was recrystallized from
boiling 1,4-dioxane. Soluble, colorless crystals composed of
5-hydroxydibenzoACHTUNGTRENNUNG[a,d]cycloheptene-5-carboxylic acid and
1,4-dioxane in a 2:1 ratio were obtained. Single-crystal X-
ray analysis revealed the presence of dimers bridged by two
hydrogen bonds between the hydroxy and carbonyl moieties.
These dimers form a chain structure with 1,4-dioxane
through hydrogen bonding (Figure 1).
Figure 2. ORTEP plot of 1; ellipsoids are drawn at the 50% probability
level, some hydrogen atoms have been omitted for clarity. Selected
À
À
À
lengths [ꢂ]: N32 H32 1.302, H32 O12A 1.272, N32 O12A 2.555; angles
[8]: O12A-H32-N32 166.0.
Figure 1. ORTEP plot of the chain structure of 5-hydroxydibenzo-
ACHTUNGTRENNUNG[a,d]cycloheptene-5-carboxylic acid based on intermolecular hydrogen
spectively (Scheme 5). Heating solid compound 1 to 2008C
for 30 s also results in the formation of the decarboxylated
product 2.
bonding. Dimers are connected through hydrogen bonding with 1,4-diox-
ane molecules. Ellipsoids are drawn at the 50% probability level; some
hydrogen atoms have been omitted for clarity.
To complete the synthesis of amino acid 1, isoDMT and
the suberone-derived hydroxy acid 2 were combined in an
electrophilic aromatic substitution reaction with an interme-
diary carbocation carboxylate zwitterion acting as an elec-
trophilic reagent (Scheme 4). The use of acetic acid as sol-
vent was necessary for two reasons. Firstly, a Brønsted acid
is mandatory for the elimination of water, thereby generat-
ing the benzhydryl cation that is the actual reactive alkylat-
ing reagent. Secondly, acetic acid as solvent inhibits decar-
boxylation of product 1. In the solid state, two amino acid
molecules 1 are connected by nearly linear hydrogen bonds
between the carboxylic acids and the amino units (Figure 2).
The electron density distribution shows that the acidic
proton is located almost in the middle between the carboxy-
late oxygen atom and the amino nitrogen atom. In other A-
H···B systems, the A-H distance is typically about 100–
110 pm, whereas the H···B distance is about 160–200 pm.
The dimer has similar O-H (127 pm) and N-H (130 pm) dis-
tances. The observed N-O distance of 255 pm is much short-
er than the typical N-O distance of 275–285 ppm.[34]
Scheme 5. Synthesis of 5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-
10,11-dihydro-5H-dibenzoACTHNUGRTNEUNG[a,d]cycloheptene (2).
An important factor influencing the rate of decarboxyla-
tion is the thermodynamic stability of the carbanion being
formed. In his work on the decomposition of monoalkyl car-
bonates, Sauers quantified the influence of the basicity of
the residual ion on the decarboxylation rate.[26] He found
that electron-donating substituents stabilize the monoalkyl
carbonates relative to the free alkoxides. These findings ex-
trapolate logically to carbanions, implying that electron-
withdrawing substituents should stabilize the nascent car-
banion and favor decarboxylation. In the present case, there
are two phenyl rings and an indole residue attached, making
the carbanion a strong base. The pKa value should be com-
parable to that of triphenylmethane (33) or diphenylme-
thane (35).[35] Sharma et al. investigated the decarboxylation
of a variety of N-heteroaryl carboxylic acids and aromatic
acid derivatives incorporating the two fragments of structure
1.[15c] Precisely the two characteristic fragments that consti-
Decarboxylation: In general, decarboxylations are thermo-
dynamically favorable but kinetically unfavorable. The high
intrinsic barrier for decarboxylation originates from the high
distortion energy in the transition state. The angle change at
the carboxylate carbon amounts to roughly 608 due to sp2-sp
rehybridization.[20a] Amino acid 1, whilst being stable in the
solid state, quantitatively eliminates carbon dioxide in
DMSO or DMF solution with half-lives of 5 h and 7 h, re-
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B. F. Straub et al.
tute compound 1 showed the best results in their respective
classes due to good stabilization of the arising intermediates
(Scheme 6). Moreover, carboxylate solvation is hindered by
steric crowding increasing the energy of the carboxylate.
These findings support the assumption that decarboxylation
of 1 is accelerated by mesomeric, inductive, and steric ef-
fects of the substituents.
(Scheme 7). DMSO separates ion pairs better than DMF
due to its ability to replace the hydrogen bonds in the
dimer. In DMSO, compound 1 predominantly exists as the
monomeric zwitterion that can directly release carbon diox-
À
Scheme 7. Pre-equilibrium forming the free carboxylate prior to C C
cleavage.
Scheme 6. Compound 1 as a combination of two substrates investigated
ide according to a first-order rate law. In DMF, ion pair sep-
aration is not as good as in DMSO, and the reactive species
first has to evolve in a pre-equilibrium. Assuming that the
substrate undergoes reversible dissociation prior to the
carbon-carbon bond-breaking step, leading to product for-
mation and release of carbon dioxide, the graph of decar-
boxylation in DMF (Figure 3, dotted curve) is plausible. An
autocatalytic effect of the evolving free amine might influ-
ence the decarboxylation rate in DMF.
by A. Sharma et al.[15c]
Kinetic data for the decarboxylation of compound 1 in
1
DMSO and in DMF were determined by H NMR spectro-
1
scopy. Multiple consecutive H NMR spectra were recorded
at 258C, displaying the formation of product signals and the
disappearance of starting material signals. To ensure that in-
tegrals were reliable, relaxation times were determined (see
the Supporting Information). The decarboxylation kinetics
differ for DMSO and DMF as solvents (Figure 3). In the
In a modified experimental set-up, the decarboxylation
rate was quantified under an atmospheric pressure of
1
carbon dioxide. The H NMR kinetics showed that the rate
of decarboxylation was strongly retarded under a carbon di-
oxide atmosphere. Changing the atmosphere resulted in an
enhancement in the half-life of amino acid 1 in DMSO from
5 h (argon, 1 bar) to 17 h (carbon dioxide, 1 bar) (Figure 4,
left side). The linear dependence of ln(cACHTNUTRGNEUNG[reagent]) on time
(Figure 4, right side) indicates that decarboxylation follows
a first-order rate law both under argon and carbon dioxide
atmosphere and that there is no change in mechanism.
Major and Gao calculated that for the decarboxylation of
picolinic acid there is only a very small inherent barrier for
recombination of carbanion and carbon dioxide.[37] This pro-
vides an explanation for the observed decrease in decarbox-
ylation rate of 1 under carbon dioxide atmosphere. Increas-
Figure 3. Kinetic 1H NMR measurements of the decarboxylation of 1 in
DMSO (continuous curve) and DMF (dotted curve); left side: formation
rate of decarboxylated product; right side: ln(cACTHNUGRTNEUNG[reagent]) versus time.
case of DMSO, the kinetic data for decarboxylation conform
to first-order rate dependence (Figure 3, continuous
curve). The linear dependence of ln(c[reagent]) on time
a
AHCTUNGTRENNUNG
(Figure 3, right side) is in accordance with an SE1 mecha-
nism. This mechanism has been found for substrates with
electron-withdrawing groups at the a-carbon atom,[36] for
which carbon-carbon bond cleavage is rate-determining. In
the case of DMF as solvent, however, the decarboxylation
rate is constant over the first 10 h (Figure 3, dotted curve).
Since decarboxylation almost always starts from a free
carboxylate ion, and since compound 1 favors a dimeric
form, the initial step should be breaking of the hydrogen
bonds in a pre-equilibrium to generate free carboxylate ions
Figure 4. Kinetic 1H NMR measurements of the decarboxylation of 1 in
DMSO under argon atmosphere (continuous curve) and carbon dioxide
atmosphere (dotted curve); left side: formation rate of decarboxylated
product; right side: ln(cACTHNUTRGNEUGN[reagent]) versus time.
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Zwitterionic N,N-Dimethylisotryptammonium Carboxylate
FULL PAPER
ing partial pressure of carbon dioxide increases the rate of
recombination, thereby resulting in a decreased overall de-
carboxylation rate.
The influence of carbon dioxide on the enzymatic decar-
boxylation rate has been explained by Kluger.[3c,30d] His key
assumption was that re-carboxylation of the intermediate
carbanion strongly influences the reaction rate. The decar-
boxylation produces a molecule of carbon dioxide and a re-
active carbanion in the immediate vicinity of one another.
The barrier for recombination of the carbanion and carbon
dioxide can be considered to be near to or lower than that
for diffusion.[37] This is supported by the fact that decarboxy-
lation is retarded under carbon dioxide atmosphere. The in-
ternal return of carbon dioxide is probable and a significant
component in the overall reaction rate.[3c,30d,38] To retard the
reverse reaction, the products have to separate rapidly or
react with another species, for example, an adjacent protic
fragment in the active site of the enzyme. For the decarbox-
ylation of compound 1, the carbanion has to be protonated
by an ammonium moiety of a second amino acid 1. The
linker between the carbanion and ammonium fragment is
too rigid to allow for an intramolecular process. Thus, exter-
nal CO2 has ample time to compete with the slow intermo-
lecular, irreversible protonation of the highly reactive car-
banion.
Scheme 8. Syntheses of silicon- and tin-containing spiro compounds 4–6.
Single-crystal X-ray analysis revealed that both silicon deriv-
atives 4 and 5 are monomeric species having a pseudo-tetra-
hedral coordination environment at silicon (Figure 5).
We were interested in stabilizing the carboxylic fragment.
Substitution of the indole core at the C2 position seemed to
be promising. The use of n-butyllithium led to unselective
deprotonation of the indole core, whereas the use of tert-bu-
tyllithium resulted in decomposition of the starting material.
However, reaction of compound 1 with two equivalents of
methyllithium in diethyl ether resulted in precipitation of
the corresponding dilithium salt 3 as a yellow solid. The co-
ordination of lithium apparently stabilizes the carboxylate
fragment. The deprotonation yield was determined by treat-
ing the reaction mixtures with deuterium oxide and integrat-
1
ing the respective signals in the H NMR spectra. Lithium
Figure 5. ORTEP plots of the molecular structures of silanes 4 and 5. El-
lipsoids are drawn at the 50% probability level; hydrogen atoms have
been omitted for clarity; left: compound 4: selected bond lengths [ꢂ]:
salt 3 yielded the C2-deuterated compound d1-1. The steric
demand of methyllithium might be decisive for the deproto-
nation, since the adjacent carboxylate and N,N-dimethylami-
noethyl groups only leave a small gap for the attacking base.
This limits the size of an introduced functional group that
may be introduced to stabilize the carboxylic moiety. We in-
troduced silicon- and tin-containing fragments to utilize the
strength of the arising silicon-oxygen and tin-oxygen bonds.
Transmetallations of dilithium salt 3 with dichlorodimethyl-
silane, dichlorodiphenylsilane, and dibutyltin dichloride
yielded the corresponding spiro compounds 4, 5, and 6
(Scheme 8).
À
À
Si1 C6 1.838, Si1 O2 1.672, angles [8]: C6-Si1-O2 99.6, Si1-O2-C3 134.4,
O2-Si1-C8 107.4, dihedral angles [8]: C5-C4-C3-O2 À19.9, C5-C6-Si1-O2
À0.4, C6-N7-C41-C42 101.1; right: compound 5: selected bond lengths
À
À
[ꢂ]: Si1 C6 1.835, Si1 O2 1.672, angles [8]: C6-Si1-O2 99.9, Si1-O2-C3
134.1, O2-Si1-C8 108.3, dihedral angles [8] C5-C4-C3-O2 À17.7, C5-C6-
Si1-O2 À11.2, C6-N7-C41-C42 À89.3.
The spiro compound 6 forms a hypervalent pentacoordi-
nated tin species. Single-crystal X-ray analysis revealed a
trigonal-bipyramidal coordination environment at the tin
atom (Figure 6).
These spiro compounds are stable with regard to decar-
boxylation. The silicon derivatives 4 and 5 show no sign of
decomposition even at 3008C. Tin derivative 6 starts to lose
carbon dioxide at 1888C. The three spiro compounds are
stable in DMSO or DMF solution and under basic condi-
tions at room temperature. Besides their enhanced stability
towards decarboxylation, the spiro compounds 4–6 have dif-
ferent coordination numbers of the silicon and tin atoms.
The indolyl ligand and the two n-butyl ligands are situated
in equatorial positions. According to Bentꢃs rule, the less
electron-donating ligands are situated in the apical posi-
tions.[39]
Carboxylate rearrangement—methylation reaction: In initial
attempts to synthesize compound 1, we were unable to iso-
late it after work-up with aqueous sodium chloride solution.
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B. F. Straub et al.
Figure 6. ORTEP plot of the molecular structure of stannane 6. Ellipsoids
are drawn at the 50% probability level; hydrogen atoms have been omit-
Figure 7. ORTEP plot of the molecular structure of the rearrangement
product 8; ellipsoids are drawn at the 50% probability level; selected
À
À
ted for clarity; selected bond lengths [ꢂ]: Sn1 C6 2.125, Sn1 O2 2.156,
À
À
bond lengths [ꢂ]: C3 C10 1.486, C10 O10 1.220; angles [8]: C3-C10-C11
118.7, C3-C10-O10 120.5; dihedral angles [8]: C2-C3-C10-C11 À42.7, N4-
C3-C10-O10 À38.42.
À
Sn1 N43 2.400, angles [8]: C6-Sn1-O2 84.1, Sn1-O2-C3 122.6, O2-Sn-C8
91.5, O2-Sn1-N43 171.3, dihedral angles [8] C5-C4-C3-O2 À36.1, C5-C6-
Sn1-O2 5.3.
Instead, we obtained a colorless solid that turned yellow in
air within minutes. The H NMR spectrum nearly matched
There are well investigated compounds in which combina-
tions of lithium and potassium/sodium ions play a crucial
role, for example Schlosserꢃs reagent LICKOR.[40] In the
Lochmann–Schlosser, a combination of tert-butyllithium and
potassium tert-butoxide, the high oxophilicity of lithium
leads to a superbase. In the present case, a similar effect can
explain the formation of the rearrangement product 8. A
possible rearrangement mechanism based on a method for
preparing ketones from organolithium reagents and carbox-
ylic acids,[41] explaining the formation of 8, is shown in
Scheme 10.
1
that of compound 1, except for the slightly shifted proton
signals of the N,N-dimethylaminoethyl group. This yellow
compound gave decreased yields in the syntheses of spiro
compounds, but one additional side-product. The elemental
analysis matched that of a mixture of a sodium carboxylate
and sodium chloride in a 1:1 ratio (Scheme 9).
Compound 8 was synthesized directly by treating sodium
carboxylate 7 with an excess of methyllithium in diethyl
ether. The first mechanistic step is a selective deprotonation
at the C2 position. Driven by the higher oxophilicity of lithi-
Scheme 9. Synthesis of sodium carboxylate 7.
Knowing the nature of the double salt 7, we investigated
the identity of the by-product in the syntheses of spiro com-
pounds 4–6. To avoid separation problems, the reaction mix-
ture was quenched with water instead of with alkyl silicon
and alkyl tin chlorides after deprotonation. An acetyl deriv-
ative 8 was easily separated from the starting material by
column chromatography. Its structure was confirmed by
single-crystal X-ray analysis (Figure 7). The former carbox-
ylic group had been shifted and transformed into an acetyl
group situated at the C2 indole carbon atom. Normally, a
coplanar arrangement of the indole core and the acetyl
group would be expected, maximizing the p-interaction be-
tween the indole p-system and the carbonyl group. Due to
steric crowding at the C2 position, the acetyl group is dis-
torted by roughly 408 towards the indole plane.
Scheme 10. Mechanism of the rearrangement–methylation sequence lead-
ing to 2-acetylindole 8.
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Zwitterionic N,N-Dimethylisotryptammonium Carboxylate
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um, a lithium carboxylate is formed, leaving a sodium 2-in-
dolate ion. The negative charge at the indole core is much
less shielded by the sodium ion than it was before by the
lithium ion. This provides a more distinct ionic character, re-
sulting in nucleophilic attack on the carboxylate carbon
atom, thereby yielding a cyclobutanediolate intermediate.
Ring opening forms an indole-2-carboxylate. In the follow-
ing step, the lithium carboxylate is attacked by another mol-
ecule of methyllithium, thereby forming a dilithium diolate.
The dilithium intermediate, which is more stable than other
metal dialkoxides,[41a] precipitates as a bright-yellow solid.
To release the final product 8, water was added to the reac-
tion mixture. Similarly, deuterium oxide was used as a mech-
anistic probe. The obtained monodeuterium species d1-8
contained a non-deuterated COCH3 group and a tertiary C-
D moiety. Thus, the mechanistic alternative of intramolecu-
lar protonation of the triaryl carbanion by the acetyl group
to give an enolate can be ruled out.
two nearly equidistant hydrogen bonds. Breaking of these
strong hydrogen bonds in DMSO and DMF is responsible
for destabilizing the sterically shielded carboxylate frag-
ment. Thus, a highly basic carbanion was released that was
competitively trapped by external CO2.
Stable derivatives have been obtained by bridging the car-
boxylate and the 2-position of the indole moiety with sily-
lene or stannylene moieties. These spiro compounds show
high thermal stability even in basic media.
The sodium salt undergoes a carboxylate walk upon de-
protonation of the adjacent 2-indolyl fragment with an
excess of methyllithium. The stoichiometric presence of
both counterions lithium and sodium is mandatory for car-
boxylate transfer to the 2-indolide fragment. The rearrange-
ment is followed by a nucleophilic attack of methyllithium.
In summary, we have presented a carboxylic acid that un-
dergoes facile deprotonation, features a re-carboxylation
mechanism of the resulting carbanionic intermediate, and is
prone to intramolecular transfer of the carboxylate to give a
2-indolide fragment.
A positive effect of NaCl and water on the rearrangement
reaction was ruled out (Table 1). The stoichiometric pres-
ence of the sodium carboxylate appears to be essential.
Table 1. Effect of water and sodium chloride addition on the rearrange-
ment of amino acid 1 to acetyl derivative 8.
Experimental Section
Starting materials[a]
Detection of 8[b]
Materials and methods: All starting materials and deuterated solvents
were obtained from commercial suppliers (Acros Organics, Sigma–Al-
drich, Scientific-Fisher, Deutero, euriso-top) and were used without fur-
ther purification unless otherwise noted. Dry tetrahydrofuran was taken
from an MBRAUN MB SCS-800 solvent purification system and kept
under nitrogen. Dry diethyl ether was obtained by distillation from
sodium and benzophenone and kept under nitrogen. Air- and moisture-
sensitive reactions were conducted in oven-dried glassware by using
standard Schlenk or dry-box techniques under an inert atmosphere of
dry nitrogen or dry argon.
compound 1
–
–
–
+ +
+
compound 1, 1 equiv H2O
compound 1, 1 equiv NaCl
compound 7
compound 7, compound 1 (1:5 ratio)
[a] Conditions: suspension in diethyl ether, r.t., 4.2 equiv methyllithium,
16 h. [b] Work-up: addition of water, extraction with dichloromethane,
compound 8 was detected using TLC (– not detected, + detected (small
amount), + + detected (large amount)).
1
Physical and spectroscopic measurements: H NMR spectra were record-
ed on Bruker ARX-250 (250 MHz), Bruker Avance 300 (300 MHz), and
Bruker Avance 500 (500 MHz) spectrometers. 13C NMR spectra were re-
corded on Bruker Avance 300 (75 MHz) and Bruker Avance 500
(125 MHz) spectrometers. Chemical shifts are reported in parts per mil-
lion (ppm) and were calibrated to the residual signals of the deuterated
The compositions of the product mixtures derived from
the comparative experiments were determined by thin-layer
chromatography. Neither the addition of sodium chloride
nor of water to compound 1 before adding methyllithium
led to the formation of the rearranged product 8. A possible
influence of water or sodium chloride on the rearrangement
can thus be ruled out. The fact that a mixture of sodium car-
boxylate 7 and the protonated acid 1 gives low yields of the
rearrangement product 8 supports our proposed mechanism.
A stoichiometric amount of sodium carboxylate is necessary
for full conversion. The rearrangement is apparently not cat-
alyzed by sodium salts.
solvents
[dH
G
dH([D6]DMSO)=2.50 ppm,
dH([D8]THF)=1.72 and 3.58 ppm]. Selected NMR spectra are available
in the Supporting Information. ESI mass spectra were obtained on a
JEOL JMS-700 instrument. IR spectra were recorded on
a Bruker
Vector 22 FTIR instrument. Melting points were determined using a Gal-
lenkamp hot-stage microscope and are uncorrected.
X-ray structure analyses: Single-crystal X-ray diffraction data sets were
collected at 200(2) K on a Bruker Smart CCD diffractometer for 5-hy-
droxy-10,11-dihydro-5H-dibenzoACHTUNTRGNEU[GN a,d]cycloheptene-5-carboxylic acid, 1,
and 8, or on a Bruker APEX diffractometer for 4, 5, and 6, both equip-
ped with a CCD area detector and a standard sealed tube MoKa (l=
0.71073 ꢂ) radiation source. 0.38 omega scans covering a whole sphere in
reciprocal space were taken in each case, and an empirical absorption
correction was applied using SADABS based on the Laue symmetry of
the reciprocal space.[42] Structures were solved by direct methods and re-
fined against F2 with a full-matrix least-squares algorithm using the
SHELXTL-PLUS (6.10) software package.[43] The Supporting Informa-
tion or CCDC-792003 (for 5-hydroxy-10,11-dihydro-5H-dibenzo-
Conclusion
We have synthesized a carboxylic acid derived from N,N-di-
methylisotryptamine that features a unique set of reactivity
patterns. The carboxylate zwitterion is stable in the solid
state but quantitatively decarboxylates in polar aprotic sol-
vents even at room temperature. A single-crystal X-ray
analysis revealed dimerization of the amino acid through
AHCTUNGERTG[NNUN a,d]cycloheptene-5-carboxylic acid), CCDC-792002 (for 1), CCDC-
792004 (for 4), CCDC-792006 (for 5), CCDC-792005 (for 6), and CCDC-
792007 (for 8) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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B. F. Straub et al.
1-[2-(N,N-Dimethylamino)ethyl]indole: Under an atmosphere of nitro-
gen, 2-(dimethylamino)ethyl chloride hydrochloride (85 g, 0.59 mol) was
slowly added to a mixture of potassium hydroxide (129 g, 2.30 mol),
indole (60 g, 0.51 mol), and dimethyl sulfoxide (300 mL) at 08C. After
stirring at room temperature for 48 h, water was added and the product
was extracted three times with diethyl ether. The combined extracts were
washed with water, dried over magnesium sulfate and concentrated in
vacuo to afford a brown oil. Distillation gave the title compound as a col-
orless liquid (80.8 g, 429 mmol). Yield: 84%; b.p. 1008C (1 mbar);
1H NMR (300 MHz, CDCl3, 258C): d=7.86–7.82 (m, 1H; 4-Hindole), 7.53–
7.49 (m, 1H; 7-Hindole), 7.44–7.38 (m, 1H; 6-Hindole), 7.34–7.28 (m, 1H; 5-
tallized from chloroform/diethyl ether to give the title compound as a
colorless powder. Residual chloroform in the solid could be removed by
stirring in diethyl ether, filtering, and drying in vacuo (34.2 g, 80.8 mmol).
Yield: 84%; m.p. 1548C (decomposition, gas evolution); 1H NMR
(500 MHz, [D6]DMSO/1% CF3COOD, 258C): d=7.55–7.53 (m, 1H;
Hindole), 7.34 (s, 1H; 2-Hindole), 7.16–7.13 (m, 2H; Haryl), 7.11–7.05 (m, 5H;
1 ꢁ Hindole, 4 ꢁ Haryl), 6.95–6.92 (m, 2H; Haryl), 6.74–6.70 (m, 1H; Hindole),
6.52–6.49 (m, 1H; Hindole), 4.62 (t, 3J
(CH3)2), 3.53 (t, 3J
(H,H)=7.5 Hz, 2H; CH2N
CH2), 2.87 ppm (s, 6H;
(CH3)2); 1H NMR (300 MHz, [D6]DMSO,
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
NACHTUNGTRENNUNG
258C): d=7.43–7.41 (m, 1H; Hindole), 7.25 (s, 1H; Hindole), 7.14–6.97 (m,
7H; 1 ꢁ Hindole, 6 ꢁ Haryl), 6.91–6.89 (m, 2H; Haryl), 6.66–6.64 (m, 1H;
3
3
Hindole), 7.25 (d, J
G
ACHTUNGTREN(NUNG H,H)=3.0 Hz,
1H; 3-Hindole), 4.28 (t, 3J
E
G
H ACHTUTGNENRNUG
indole), 6.46–6.44 (m, 1H; Hindole), 4.30 (t, 3J
3J
A
N
N
G
CH2CH2N
N
ACHTUNGTRENNUNG
13C{1H} NMR (75 MHz, CDCl3, 258C): d=135.7 (7a-Cindole), 128.3 (3a-
A
ACHTUNGTRENNUNG
Cindole), 127.7 (2-Cindole), 121.1 (6-Cindole), 120.7 (4-Cindole), 119.0 (5-Cindole),
[D6]DMSO/1% CF3COOD, 258C): d=175.5 (CO2H), 141.7 (Caryl), 139.9
(Caryl), 136.4 (Cindole), 132.2 (CHaryl), 130.0 (CHaryl), 128.4 (CHindole), 126.9
(Cindole), 126.8 (CHaryl), 125.2 (CHaryl), 121.8 (CHindole), 121.5 (CHindole),
108.9 (7-Cindole), 100.9 (3-Cindole), 58.6 (CH2N
ACHTUNTGRNENGU(CH3)2), 45.4 (NACHUTGNTREN(NUGN CH3)2),
44.3 ppm (CH2CH2N(CH3)2); IR (KBr): n˜ =3055 (w), 2972 (m), 2943 (s),
ACHTUNGTRENNUNG
2860 (w), 2821 (m), 2770 (s), 1617 (w), 1512 (s), 1481 (m), 1463 (s), 1361
(w), 1334 (m), 1316 (s), 1257 (w), 1223 (w), 1171 (w), 1154 (w), 1055 (w),
1042 (w), 763 (m), 740 (s), 716 cmÀ1 (m); MS (EI+): m/z (%): 188.1 (35)
120.2 (Cindole), 119.1 (CHindole), 110.0 (CHindole), 65.0 (C
ACHTUNGTRENNUNG
signal), 55.2 (CH2N(CH3)2), 42.8 (N(CH3)2), 40.7 (CH2CH2NACHTUNGTRENNUNG
A
U
34.8 ppm (CH2); IR (KBr): n˜ =3440 (br), 3016 (m), 2939 (m), 2894 (m),
2836 (m), 2771 (w), 2710 (w), 1705 (m), 1161 (br), 1481 (s), 1466 (s), 1367
(m), 1340 (m), 1326 (m), 1256 (m), 1233 (m), 1212 (m), 1161 (m), 1017
(w), 779 (s), 751 (s), 739 (s), 719 (s), 647 (w), 640 (w), 531 cmÀ1 (w); MS
(ESI+): m/z (%): 425.4 (100) [M+H+], 353.3 (7) [MÀCH2CH2N-
[M+], 130.1 (5) [M+ÀCH2N
(CH3)2+]; elemen-
ACHTUTGNREN(NUG CH3)2], 58.1 (100) [CH2NCAHTUNGTRENNGUN
tal analysis calcd (%) for C12H16N2: C 76.55, H 8.57, N 14.88; found: C
76.40, H 8.60, N 14.94; alternative procedures for the synthesis have been
published previously.[32]
AHCTUNGTRENNUNG
(CH3)2+H+], 214.9 (21) [C15H12+Na+], 211.8 [C12H16N2+Na+]; HRMS
5-Hydroxy-10,11-dihydro-5H-dibenzoACTHNUGTRNEUNG[a,d]cycloheptene-5-carboxylic
(ESI+): calcd (m/z) for C28H29N2O2+: 425.22235; found: 425.22274; ele-
mental analysis calcd (%) for C28H28N2O2: C 79.22, H 6.65, N 6.60, O
7.54; found: C 79.07, H 6.64, N 6.66. For X-ray structure determination, a
single crystal was obtained by recrystallization from chloroform.
acid·0.5 (1,4-dioxane): Under an atmosphere of nitrogen, dibenzosuber-
one (100 g, 466 mmol) was dissolved in dry tetrahydrofuran (800 mL) and
sodium lumps (29.3 g, 1.27 mol, 2.7 equiv) were slowly added. The yellow
solution turned dark blue within minutes. Carbon dioxide was continu-
ously passed into the solution, changing the color to red. The reaction
mixture was heated under reflux conditions for 8 h at 708C, stirred over-
night at room temperature, and heated again for 8 h at 708C. Excess
sodium metal was quenched by carefully (!) adding water. Tetrahydrofur-
an was removed from the aqueous reaction mixture by rotary evapora-
tion. The remaining alkaline aqueous layer was extracted with diethyl
ether to remove any remaining dibenzosuberone, and then glacial acetic
acid (1 L) was added. The acidic aqueous solution was extracted with di-
ethyl ether. The organic extracts were washed with water, dried over
magnesium sulfate, and concentrated in vacuo to give the yellow crude
product. Recrystallization from 1,4-dioxane containing a small amount of
water gave the title compound as white crystals (containing 0.5 equiva-
lents of 1,4-dioxane in the crystal) (98.4 g, 330 mmol). Yield: 71%; m.p.
2328C (decomposition); 1H NMR (300 MHz, [D6]DMSO, 258C): d=
12.85 (s, 1H; CO2H), 7.78–7.73 (m, 2H; Haryl), 7.20–7.12 (m, 4H; Haryl),
7.12–7.07 (m, 2H; Haryl), 6.89 (s, 1H; OH), 3.55 (s, 4H; dioxane), 3.34–
3.20 (m, 2H; CH2), 2.94–2.80 ppm (m, 2H; CH2); 13C{1H} NMR
(75 MHz, [D6]DMSO, 258C): d=174.2 (CO2H), 142.0 (Caryl), 137.4 (Caryl),
129.7 (CHaryl), 127.1 (CHaryl), 125.1 (CHaryl), 124.7 (CHaryl), 78.0 (C(OH)),
31.6 ppm (CH2); IR (KBr): n˜ =3441 (br), 3018 (br), 2935 (br), 2888 (br),
2610 (m), 1706 (s), 1484 (m), 1257 (s), 1243 (s), 1217 (s), 1166 (m), 1114
(s), 1078 (s), 1041 (s), 863 (s), 758 (s), 748 (s), 718 (s), 709 (s), 656 (s),
613 cmÀ1 (s); MS (ESI+): m/z (%): 747.2 (100) [3MÀ2H2O+Na+], 495.2
(61) [2MÀ2H2O+Na+], 299.1 (8) [MÀH+2Na+], 259.1 (26)
[MÀH2O+Na+]; elemental analysis calcd (%) for C16H14O3·0.5C4H8O2:
C 72.47, H 6.08; found: C 72.40, H 6.14. For X-ray structure determina-
tion, a single crystal was obtained by recrystallization from 1,4-dioxane;
alternative procedures for analogous syntheses have been reported in the
literature.[33]
5-{1-[2-(N,N-Dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-dibenzo-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
(549 mg, 1.29 mmol) was heated in a small crucible to 2008C for 30 s
until the evolution of gas was complete. The hot melt was poured into a
mold made of aluminum foil. The mold was then cooled, whereupon a
dark glassy mass solidified. The product was pounded in a cooled mortar.
Without further purification, the title compound was obtained as a brown
powder (490 mg, 1.29 mmol); yield: 99%. Method (b): 5-{1-[2-(N,N-Di-
methylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-dibenzo-
AHCTUNGERTG[NNUN a,d]cycloheptene-5-carboxylic acid (466 mg, 1.10 mmol) was stirred in
DMSO (20 mL) overnight. Water (300 mL) was then added to the yellow
reaction mixture. The aqueous solution was extracted three times with di-
ethyl ether. The combined organic extracts were washed with water,
dried over magnesium sulfate, and concentrated in vacuo to give a brown
glassy solid, pounding of which in a cooled mortar gave the title com-
pound as
a brown powder (410 mg, 1.08 mmol). Yield: 98%; m.p.
47.58C; 1H NMR (300 MHz, [D6]DMSO, 258C): d=7.51–7.46 (m, 2H;
Haryl), 7.37–7.35 (m, 1H; Hindole), 7.22–7.16 (m, 4H; Haryl), 7.14–7.09 (m,
2H; Haryl), 7.03–7.00 (m, 1H; Hindole), 6.93–6.91 (m, 1H; Hindole), 6.77–6.75
(m, 1H; Hindole), 6.45 (s, 1H; Hindole), 5.44 (s, 1H; CH), 4.12 (t, 3J
ACHTUNGTRENNUNG
6.6 Hz, 2H; CH2CH2NACHTUNGTRENNUNG
3
2H; CH2), 2.45 (t, J
N
ACHTUNGTRENNUNG
NACHTUNGTRENNUNG
139.6 (Caryl), 136.4 (Cindole), 130.4 (CHaryl), 130.4 (CHaryl), 127.5 (CHindole),
126.9 (CHaryl), 126.0 (Cindole), 125.9 (CHaryl), 120.8 (CHindole), 119.6
(CHindole), 118.5 (CHindole), 117.8 (Cindole), 109.6 (CHindole), 58.6 (CH2N-
ACHNUTTGERG(NUNN CH3)2), 51.0 (CH), 45.2 (NACHNUTRGTE(UNNGN CH3)2), 43.5 (CH2CH2NACHTNGUTRENUN(NG CH3)2), 31.2 ppm
(CH2); IR (KBr): n˜ =3450 (br), 3058 (w), 3015 (w), 2932 (w), 2864 (w),
2819 (w), 2767 (w), 1635 (w), 1611 (w), 1491 (w), 1480 (w), 1465 (m),
1455 (m), 1360 (w), 1329 (w), 1158 (w), 773 (s), 753 (s), 739 (s), 587 (w),
425 cmÀ1 (w); MS (ESI+): m/z (%): 381.2 (100) [M+H+], 395.2 (15),
775.4 (8); HRMS (ESI+): calcd (m/z) for C27H29N2+: 381.23253; found:
381.23263; elemental analysis calcd (%) for C27H28N2: C 85.22, H 7.42, N
7.36; found: C 84.77, H 7.24, N 7.19.
5-{1-[2-(N,N-Dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-dibenzo-
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
96.0 mmol) in glacial acetic acid (200 mL ) was heated under reflux con-
ditions for 12 min at 1188C, and then rapidly cooled to room tempera-
ture. Water (500 mL) was added to the red solution, and the product was
extracted with dichloromethane. The combined organic layers were
washed with water and dried over magnesium sulfate. The organic sol-
vent was removed by rotary evaporation. The crude product was recrys-
Lithium 5-(2-lithio{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl})-10,11-di-
hydro-5H-dibenzo
methylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-dibenzo
heptene-5-carboxylic acid (631 mg, 1.45 mmol) and diethyl ether (5 mL)
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
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ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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Zwitterionic N,N-Dimethylisotryptammonium Carboxylate
FULL PAPER
were placed in a 20 mL flask under an argon atmosphere. A solution of
methyllithium in diethyl ether (2.71 mL, 1.6m, 4.34 mmol) was slowly
added. After stirring for 16 h, the yellow precipitate was collected by fil-
tration, washed three times with diethyl ether, and dried in vacuo. The
5.85. For X-ray structure determination, a single crystal was obtained by
recrystallization from methanol.
Spiro[10,11-dihydro-5H-dibenzo
oxa-4’-silacyclohexan-2’-one[4’a,9’b-b’]-5’-[2“-(N,N-dimethylamino)eth-
yl]indole})] (5): A 100 mL Schlenk flask was charged with a suspension
ACHTUNGTREN[NUNG a,d]cycloheptene-5,1’-(4’,4’-diphenyl{3’-
title compound was obtained as
a yellow, highly moisture-sensitive
AHCTUNGTRENNUNG
powder (574 mg, 1.32 mmol). Yield: 95%.
of
dibenzo
5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-
[a,d]cycloheptene-5-carboxylic acid (2.0 g, 4.7 mmol) in diethyl
5-(2-Deutero{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl})-10,11-dihydro-
U
5H-dibenzo
lithio{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl})-10,11-dihydro-5H-
dibenzo[a,d]cycloheptene-5-carboxylate (100 mg, 229 mmol) and diethyl
ether (2 mL) were placed in a 10 mL flask under an argon atmosphere.
Addition of D2O (1 mL) to the yellow suspension led to the precipitation
of a colorless solid, which was collected by filtration, washed with water
and diethyl ether, and dried in vacuo. The product was obtained as a col-
orless powder (92.7 mg, 217 mmol). Yield: 95%; 1H NMR (250 MHz,
[D6]DMSO/1% F3CCOOD, 258C): d=7.53–7.51 (m, 1H; Hindole), 7.20–
[a,d]cycloheptene-5-carboxylic acid ([D1]1): Lithium 5-(2-
ether (20 mL) under an argon atmosphere. A solution of methyllithium
in diethyl ether (6.50 mL, 1.6m, 10.4 mmol, 2.2 equiv) was slowly added
by means of a syringe. The reaction mixture was stirred for 16 h at room
temperature. The resulting yellow suspension was cooled to À788C,
ACHTUNGTRENNUNG
whereupon
a pre-cooled solution of dichlorodiphenylsilane (2.98 g,
2.48 mL, 11.8 mmol) in THF (30 mL) was injected into the flask. The re-
action mixture was stirred and allowed to warm to room temperature
overnight, yielding a violet suspension. The colorless precipitate was re-
moved by filtration. The remaining violet solution was concentrated in
vacuo to give the crude product as a viscous oil. Purification by column
chromatography on silica gel (dichloromethane/methanol, 9:1) yielded a
yellow solid. It was recrystallized from dichloromethane/methanol and
the title compound was obtained as light-yellow crystals (1.29 g,
2.13 mmol). Yield: 45%; Rf =0.70 (CH2Cl2/MeOH, 9:1); m.p. 2398C;
1H NMR (500 MHz, [D6]DMSO, 258C): d=7.75–7.73 (m, 4H; Hphenyl),
7.70–7.67 (m, 2H; Hphenyl), 7.63–7.59 (m, 4H; Hphenyl), 7.48–7.45 (m, 1H;
7-Hindole), 7.25–7.23 (m, 2H; Haryl), 7.13–7.07 (m, 3H; 6-Hindole, Haryl),
6.98–6.96 (m, 2H; Haryl), 6.87–6.84 (m, 2H; Haryl), 6.74–6.70 (m, 1H; 5-
6.89 (m, 9H; 1 ꢁ Hindole, 8 ꢁ Haryl), 6.73–6.69 (m, 1H; Hindole), 6.49–6.45
3
(m, 1H; Hindole), 4.61 (t, J
N
ACHTUGNTREN(UNNG CH3)2), 3.51 (t,
3J
(s, 6H; N
Spiro[10,11-dihydro-5H-dibenzo
oxa-4’-silacyclohexan-2’-one[4’a,9’b-b’]-5’-[2“-(N,N-dimethylamino)eth-
yl]indole})] (4): A 100 mL Schlenk flask was charged with a suspension
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTREGUN[NN a,d]cycloheptene-5,1’-(4’,4’-dimethyl{3’-
ACHTUNGTRENNUNG
of
dibenzo
5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-
[a,d]cycloheptene-5-carboxylic acid (2.0 g, 4.7 mmol) in diethyl
U
Hindole), 6.59–6.57 (m, 1H; 4-Hindole), 4.29 (t, 3J
CH2CH2N(CH3)2), 3.63–3.57 (m, 2H; CH2), 3.20–3.14 (m, 2H; CH2), 2.22
(t, 3J
(H,H)=7.0 Hz, 2H; CH2NACHTUNGTRENN(UG CH3)2), 1.92 ppm (s, 6H; NACHTUNGTRENNUNG(CH3)2);
ACHTUNGTREN(NGNU H,H)=7.0 Hz, 2H;
ether (20 mL) under an argon atmosphere. A solution of methyllithium
in diethyl ether (6.5 mL, 1.6m, 10 mmol, 2.2 equiv) was slowly added by
means of a syringe. The reaction mixture was stirred for 16 h at room
temperature. The resulting yellow suspension was cooled to À788C,
AHCTUNGTRENNUNG
G
1H NMR (250 MHz, CDCl3, 258C): d=7.80–7.75 (m, 4H; Hphenyl), 7.61–
7.44 (m, 6H; Hphenyl), 7.35 (d, 3JH,H =8.3 Hz, 1H; Hindole), 7.20–7.02 (m,
whereupon
a pre-cooled solution of dichlorodimethylsilane (1.8 g,
7H; Hindole/aryl), 6.86–6.67 (m, 4H; Hindole/aryl), 4.35 (t, 3J
ACHTUNGTRENNUNG
1.7 mL, 14 mmol) in THF (30 mL) was injected into the flask. The reac-
tion mixture was stirred at room temperature overnight. The solvent was
then removed in vacuo. Diethyl ether was added to the initially orange
crude product, stirred for a few hours, and filtered. This process was re-
peated twice more. The nearly colorless powder was recrystallized from
methanol to afford the title compound as colorless crystals (1.71 g,
3.55 mmol). Yield: 76%; m.p. 2048C; 1H NMR (300 MHz, [D6]DMSO,
258C): d=7.51–7.48 (m, 1H; 7-Hindole), 7.23–7.19 (m, 2H; Haryl), 7.08–7.04
(m, 3H; 5-Hindole, Haryl), 7.00–6.85 (m, 4H; Haryl), 6.70–6.64 (m, 1H; 6-
2H; CH2CH2N
ACHTUNGTRENNUNG
2.35 (t, 3J
G
1H NMR (250 MHz, [D8]THF, 258C): d=7.82–7.78 (m, 4H; Hphenyl),
7.62–7.45 (m, 6H; Hphenyl), 7.39–7.34 (m, 1H; Hindole), 7.17–7.13 (m, 2H;
Hindole/aryl), 7.08–6.97 (m, 5H; Hindole/aryl), 6.79–6.71 (m, 2H; Hindole/aryl),
6.66–6.63 (m, 2H; Hindole/aryl), 4.32 (t, 3J
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
A
R
NACHTUNGTRENNUNG
13C{1H} NMR (125 MHz, [D6]DMSO, 258C): d=170.4 (CO2), 143.2
(Caryl), 140.1 (7a-Cindole), 139.8 (Caryl), 135.1 (CHphenyl), 133.5 (3-Cindole),
132.2 (CHphenyl), 131.8 (CHaryl), 130.5 (CHaryl), 129.9 (Cphenyl), 128.9
(CHphenyl), 127.5 (2-Cindole), 127.1 (CHaryl), 125.9 (CHaryl), 125.6 (3a-Cindole),
123.7 (6-CHindole), 120.7 (4-CHindole), 119.5 (5-CHindole), 110.6 (7-CHindole),
Hindole), 6.55–6.51 (m, 1H; 4-Hindole), 4.44 (t, 3J
CH2CH2N(CH3)2), 3.62–3.54 (m, 2H; CH2), 3.19–3.11 (m, 2H; CH2), 2.81
(t, 3J
(H,H)=6.3 Hz, 2H; CH2N(CH3)2), 2.36 (s, 6H; N(CH3)2), 0.77 ppm
(s, 6H; Si
(CH3)2); 1H NMR (250 MHz, CDCl3, 258C): d=7.34–7.32 (m,
ACHTUNGTREN(NGNU H,H)=6.3 Hz, 2H;
ACHTUNGTRENNUNG
A
R
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
1H; Hindole), 7.18–7.03 (m, 5H; 1 ꢄ Hindole, 4 ꢄ Haryl), 6.91–6.83 (m, 4H;
Haryl), 6.73–6.71 (m, 1H; Hindole), 6.63–6.61 (m, 1H; Hindole), 4.47 (t, 3J-
63.9 (C
ACTHGNUTERN(UGNN CO2)), 57.8 (CH2NAHCTNUREGTN(GNUN CH3)2), 46.0 (CH2CH2NACHTNUGTREN(NUGN CH3)2), 45.1 (N-
AHCTNUGTREN(GUNN CH3)2), 36.0 ppm (CH2); IR (KBr): n˜ =3450 (br), 3050 (w), 3019 (w),
A
ACHTUNGTRENNUNG
2942 (w), 2822 (w), 2771 (w), 1733 (s), 1489 (m), 1447 (w), 1430 (m),
1359 (m), 1326 (w), 1174 (s), 1120 (s), 1110 (s), 977 (s), 885 (m), 825 (w),
740 (s), 719 (m), 700 (s), 611 (w), 513 (s), 493 cmÀ1 (m); MS (ESI+): m/z
(%): 722.5 (9), 605.3 (100) [M+H+]; MS (ESI-): m/z (%): 635.3 (44)
[MÀ+MeO], 623.3 (62), 591.3 (27), 283.3 (54), 255.2 (100); HRMS
(ESI+): calcd (m/z) for C40H37N2O2Si+: 605.26227; found: 605.26243; ele-
mental analysis calcd (%) for C40H36N2O2Si: C 79.43, H 6.00, N 4.63;
found: C 79.14, H 6.04, N 4.70. For X-ray structure determination, a
single crystal was obtained by recrystallization from dichloromethane/
methanol.
G
ACHTUNGTRENNUNG
N
A
ACHTUNGTRENNUNG
[D8]THF, 258C): d=7.40–7.36 (m, 1H; Hindole), 7.16–7.11 (m, 2H; Hindole/
aryl), 7.06–6.93 (m, 5H; Hindole/aryl), 6.84–6.78 (m, 2H; Hindole/aryl), 6.65–6.58
(m, 2H; Hindole/aryl), 4.39 (t, 3J
A
ACHTUGNRTNE(NUNG CH3)2),
AHCTUNGTRENNUNG
E
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
142.9 (Caryl), 140.2 (Caryl), 139.5 (7a-Cindole), 131.7 (CHaryl), 131.7 (3a-
Cindole), 130.4 (2-Cindole), 130.2 (CHaryl), 126.7 (CHaryl), 125.9 (CHaryl), 125.3
(3-Cindole), 123.0 (4-CHindole), 120.3 (5-CHindole), 119.2 (6-CHindole), 110.2 (7-
Spiro[10,11-dihydro-5H-dibenzoACHTNUTRGNEUNG[a,d]cycloheptene-5,1’-(4’,4’-di-nbutyl{3’-
CHindole), 63.4 (C
(CO2)), 57.8 (CH2N
E
E
oxa-4’-stannacyclohexan-2’-one[4’a,9’b-b’]-5’-[2“-(N,N-dimethylamino)-
ethyl]indole})] (6): A 150 mL Schlenk flask was charged with a suspen-
sion of 5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-
45.2 (N(CH3)2), 36.0 (CH2), 0.9 ppm (SiACTHUNGTRENNUNG
A
3056 (w), 3016 (w), 2941 (br), 2895 (w), 2822 (w), 2772 (w), 1727 (s),
1636 (w), 1487 (m), 1449 (m), 1359 (m), 1326 (w), 1258 (s), 1207 (br), 981
(s), 889 (s), 851 (s), 799 (s), 776 (s), 753 (s), 742 (s), 690 cmÀ1 (w); MS
(ESI+): m/z (%): 967.5 (41) [2M+Li+], 961.5 (30) [2M+H+], 519.2 (11)
[M+K+], 487.2 (100) [M+Li+], 481.4 (63) [M+H+], 425.2 (2) [1+H]+;
MS (ESI-): m/z (%): 719.2 (13) [M+3·(Si(Me)2O)+OHÀ], 645.2 (37)
[M+2·(Si(Me)2O)+OHÀ], 571.2 (65) [M+(Si(Me)2O)+OHÀ], 497.3 (99)
[M+OHÀ], 423.3 (100) [MÀÀ(Si(Me)2)+H]; HRMS (ESI+): calcd (m/z)
for C30H33N2O2Si+: 481.23058; found: 481.23112; elemental analysis calcd
(%) for C30H32N2O2Si: C 74.96, H 6.71, N 5.83; found: C 75.05, H 6.80, N
dibenzoACTHUNRTGNEUNG[a,d]cycloheptene-5-carboxylic acid (4.0 g, 9.4 mmol) in diethyl
ether (40 mL) under an argon atmosphere. A solution of methyllithium
in diethyl ether (13.0 mL, 1.6m, 20.7 mmol, 2.2 equiv) was slowly added
by means of a syringe. The reaction mixture was stirred for 16 h at room
temperature. The resulting yellow suspension was cooled to À788C,
whereupon a pre-cooled solution of dibutyltin dichloride (3.7 g, 12 mmol)
in THF (60 mL) was injected into the flask. The reaction mixture was
stirred and allowed to warm to room temperature overnight, and then
the solvent was removed in vacuo. Diethyl ether was added to the orange
Chem. Eur. J. 2012, 00, 0 – 0
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B. F. Straub et al.
crude product, stirred for a few hours, and filtered. This process was re-
peated twice more. The nearly colorless powder was recrystallized from
methanol to afford the title compound as colorless crystals (4.8 g,
7.3 mmol). Yield: 77%; m.p. 1888C (decomposition); 1H NMR
(300 MHz, [D6]DMSO, 258C): d=7.31–7.29 (m, 1H; 7-Hindole), 7.08–7.05
(m, 2H; Haryl), 7.04–7.00 (m, 2H; Haryl), 6.94–6.87 (m, 3H; 6-Hindole, Haryl),
6.77–6.69 (m, 2H; Haryl), 6.56–6.53 (m, 2H; 4-Hindole, 5-Hindole), 4.51–4.49
yllithium in diethyl ether (6.30 mL, 1.6m, 10.3 mmol, 4.6 equiv) was
slowly added by means of a syringe. The reaction mixture was stirred for
16 h at room temperature and then water (5 mL) was added. The result-
ing suspension was stirred for 15 min and then poured into water
(50 mL). The aqueous suspension was extracted three times with di-
chloromethane. The combined organic layers were washed with brine
and dried over magnesium sulfate. Dichloromethane was removed by
rotary evaporation. The crude product was purified by column chroma-
tography (dichloromethane/methanol, 7:1) and recrystallized from tol-
uene. The title compound was obtained as slightly yellow crystals
(248 mg, 0.587 mmol). Yield: 24%; Rf =0.48 (CH2Cl2/MeOH, 7:1); m.p.
1438C; 1H NMR (300 MHz, CDCl3, 258C): d=7.44–7.40 (m, 1H; 7-
Hindole), 7.32–7.24 (m, 3H; 6-Hindole, Haryl), 7.22–7.12 (m, 4H; Haryl), 7.09–
(m, 2H; CH2CH2N
CH2N(CH3)2), 3.10–3.02 (m, 2H; CH2), 2.50 (s, 6H; N
(m, 4H; SnCH2), 1.43–1.25 (m, 8H; SnCH2CH2CH2), 0.82 ppm (t, 3J-
(H,H)=7.2 Hz, 6H, SnCH2CH2CH2CH3); 1H NMR (250 MHz, CDCl3,
258C): d=7.22–7.15 (m, 1H; Hindole), 7.10–6.90 (m, 7H; Hindole/aryl), 6.80–
6.65 (m, 4H; Hindole/aryl), 4.45–4.37 (m, 2H; CH2CH2N(CH3)2), 3.83–3.70
(m, 2H; CH2), 3.32–3.25 (m, 2H; CH2N(CH3)2), 3.19–3.07 (m, 2H; CH2),
2.57 (s, 6H; N(CH3)2), 1.76–1.59 (m, 4H; SnCH2), 1.43–1.29 (m, 8H;
SnCH2CH2CH2), 0.85 ppm (t, 3J
ACTHNUGENRT(NGU H,H)=7.3 Hz, 6H; SnCH2CH2CH2CH3);
ACHTUNGTRENNUNG
A
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
7.03 (m, 2H; Haryl), 6.97–6.94 (m, 2H; 4-Hindole, 5-Hindole), 6.15 (s, 1H;
AHCTUNGTRENNUNG
3
CH), 4.33 (t, J
G
R
ACHTUNGTRENNUNG
3
CH2), 2.63 (t, J
ACHTUNGTRENNUNG
2.17 ppm (s, 3H; (CO)CH3); 13C{1H} NMR (75 MHz, CDCl3, 258C): d=
197.6 (CO), 140.5 (Caryl), 140.4 (Caryl), 137.2 (7a-Cindole), 136.4 (2-Cindole),
130.4 (CHaryl), 130.3 (CHaryl), 127.5 (3-Cindole), 127.2 (CHaryl), 125.9
(CHaryl), 124.0 (6-CHindole), 123.4 (4-CHindole), 120.2 (5-CHindole), 119.5 (3a-
1H NMR (250 MHz, [D8]THF, 258C): d=7.30–7.28 (m, 2H; Hindole/aryl),
7.23–7.21 (m, 1H; Hindole), 7.00–6.98 (m, 2H; Hindole/aryl), 6.85–6.66 (m,
6H; Hindole/aryl), 6.42–6.40 (m, 1H; Hindole), 5.03–5.01 (m, 2H; CH2CH2N-
ACHTUNGTRENNUNG
Cindole), 110.1 (7-CHindole), 58.9 (CH2N
ACHTUNTGRENGU(N CH3)2), 47.9 (CH), 45.7 (NACHTUNGTRENNUNG(CH3)2),
N
ACHTUNGTRENNUNG
42.9 (CH2CH2N(CH3)2), 33.1 (CH2), 31.8 ppm ((CO)CH3); IR (KBr): n˜ =
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
SnCH2CH2CH2CH3); 13C{1H} NMR (75 MHz, [D6]DMSO, 258C): d=
175.4 (CO2), 143.7 (Caryl), 142.2 (Caryl), 140.1 (7a-Cindole), 134.8 (3-Cindole),
132.5 (CHaryl), 129.2 (CHaryl), 126.9 (3a-Cindole), 125.0 (CHaryl), 124.7
(CHaryl), 121.0 (4-CHindole), 120.3 (6-CHindole), 118.2 (5-CHindole), 109.2 (7-
3433 (br), 3058 (w), 3016 (w), 2940 (w), 2822 (w), 2784 (w), 1667 (s),
1524 (w), 1485 (w), 1458 (m), 1403 (w), 1349 (m), 1336 (w), 1261 (w),
1206 (w), 1153 (w), 1105 (w), 1029 (w), 769 (m), 751 cmÀ1 (s); MS
(ESI+): m/z (%): 423.2 (100) [M+H+], 391.3 (4), 108.2 (6); HRMS
(ESI+): calcd (m/z) for C29H31N2O+: 423.24309; found: 423.24304; ele-
mental analysis calcd (%) for C29H30N2O: C 82.43, H 7.16, N 6.63; found:
C 81.97, H 7.09, N 6.80. For X-ray structure determination, a single crys-
tal was obtained by recrystallization from toluene.
CHindole), 65.9 (C
ACHTUNGTRENNUNG(CO2)), 57.4 (CH2NAHCTNUTREGG(NNNU CH3)2), 45.2 (NACHTNUGTREN(NUGN CH3)2), 41.7
(CH2CH2N(CH3)2), 36.2 (CH2), 27.7 (SnCH2), 26.4 (SnCH2CH2), 26.4
ACHTUNGTRENNUNG
(SnCH2CH2CH2), 13.6 ppm (SnCH2CH2CH2CH3), (2-CindoleSn) not visi-
ble; 119Sn{1H} NMR (112 MHz, CDCl3, 258C): d=À142.5 ppm;
119Sn{1H} NMR
(112 MHz,
CD2Cl2,
258C):
d=À148.8 ppm;
5-{2-Acetyl-1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-(5-deutero)-10,11-
119Sn{1H} NMR (112 MHz, [D6]DMSO, 258C): d=À166.2 ppm;
119Sn{1H} NMR (112 MHz, [D5]pyridine, 258C): d=À167.2 ppm;
119S{1H} NMR (112 MHz, [D8]THF, 258C): d=À174.6 ppm; IR (KBr):
n˜ =3426 (br), 3048 (w), 2954 (s), 2924 (s), 2869 (m), 2854 (m), 1644 (s),
1485 (s), 1465 (s), 1353 (s), 1318 (m), 1281 (s), 1176 (w), 1160 (w), 1016
(w), 813 (m), 779 (w), 752 (s), 738 (s), 720 cmÀ1 (m); MS (ESI+): m/z
(%): 868.5 (7), 695.2 (33) [M+K+], 679.2 (28) [M+Na+], 657.3 (100)
[M+H+]; HRMS (ESI+): calcd (m/z) for C36H45N2O2Sn+: 657.24975;
found: 657.25331; elemental analysis calcd (%) for C36H44N2O2Sn: C
65.97, H 6.77, N 4.27; found: C 65.28, H 6.83, N 4.15. For X-ray structure
determination, a single crystal was obtained by recrystallization from
benzene.
dihydro-5H-dibenzo
was charged with a suspension of sodium 5-{1-[2-(N,N-dimethylamino)e-
thyl]indol-3-yl}-10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylate
ACHTUNGTRENN[UGN a,d]cycloheptene ([D1]8): A 25 mL Schlenk flask
AHCTUNGTRENNUNG
(333 mg, 0.751 mmol) in diethyl ether (5 mL) under an argon atmos-
phere. A solution of methyllithium in diethyl ether (2.10 mL, 1.6m,
3.36 mmol, 4.6 equiv) was slowly added by means of a syringe. The reac-
tion mixture was stirred for 16 h at room temperature. Deuterium oxide
(2 mL) was then added. The resulting suspension was stirred for 15 min
and then poured into water (20 mL). The aqueous suspension was ex-
tracted three times with dichloromethane. The combined organic layers
were washed with brine and dried over magnesium sulfate. The dichloro-
methane was removed by rotary evaporation. The crude product was pu-
rified by column chromatography (dichloromethane/methanol, 7:1) to
afford the title compound as slightly yellow crystals (105 mg,
0.248 mmol). Yield: 33%; Rf =0.49 (CH2Cl2/MeOH, 7:1); 1H NMR
(250 MHz, CDCl3, 258C): d=7.44–7.38 (m, 1H; 7-Hindole), 7.31–7.21 (m,
3H; 6-Hindole, Haryl), 7.18–7.10 (m, 4H; Haryl), 7.08–7.00 (m, 2H; Haryl),
Disodium chloride 5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-di-
hydro-5H-dibenzo
[2-(N,N-dimethylamino)ethyl]indole (2.00 g, 10.6 mmol) and 5-hydroxy-
10,11-dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylic acid·0.5(1,4-di-
ACHTUNGTRENNUNG[a,d]cycloheptene-5-carboxylate (7): A mixture of 1-
AHCTUNGTRENNUNG
oxane) (3.17 g, 10.6 mmol) in glacial acetic acid (30 mL) was heated
under reflux conditions for 12 min at 1188C and then cooled rapidly to
room temperature. Brine (50 mL) was added to the red solution, and the
mixture was stirred for 30 min. The product was extracted with dichloro-
methane. The combined organic layers were washed five times with
brine, and then dried over magnesium sulfate. The organic solvent was
removed by rotary evaporation leaving the crude product. Recrystalliza-
tion from chloroform/diethyl ether gave the title compound as a light-
brown powder. The chloroform incorporated into the solid could be re-
moved from the product by stirring in diethyl ether, filtering, and drying
in vacuo (3.12 g, 7.35 mmol). Yield: 69%; 1H NMR (250 MHz,
[D6]DMSO/1% CF3COOD, 258C): d=7.60–7.53 (m, 1H; Hindole), 7.31 (s,
1H; 2-Hindole), 7.18–6.98 (m, 7H; Haryl, Hindole), 6.97–6.87 (m, 2H; Haryl
Hindole), 6.75–6.66 (m, 1H; Hindole), 6.51–6.42 (m, 1H; Hindole), 4.71–4.59
(m, 2H; CH2CH2N(CH3)2), 3.54–3.39 (m, 2H; CH2N(CH3)2), 3.21–2.98
(m, 4H; CH2), 2.83 (s, 3H; N(CH3)2), 2.81 ppm (s, 3H; N(CH3)2); ele-
mental analysis found (%): C 65.68, H 5.39, N 5.15.
5-{2-Acetyl-1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-dihydro-5H-
dibenzo[a,d]cycloheptene (8): A 50 mL Schlenk flask was charged with a
suspension of sodium 5-{1-[2-(N,N-dimethylamino)ethyl]indol-3-yl}-10,11-
dihydro-5H-dibenzo[a,d]cycloheptene-5-carboxylate (1.00 g, 2.24 mmol)
in diethyl ether (15 mL) under an argon atmosphere. A solution of meth-
6.97–6.92 (m, 2H; 4-Hindole
CH2CH2N
(CH3)2), 3.23–2.99 (m, 4H; CH2), 2.62 (t, 3J
2H; CH2NACHTGUNRTNEUN(NG CH3)2), 2.28 (s, 6H; NACHTNGUTERN(NUG CH3)2), 2.16 ppm (s, 3H; (CO)CH3);
, ACHTUTGNENRNUG
5-Hindole), 4.32 (t, 3J
A
ACHTUNGTRENNUNG
MS (ESI+): m/z (%): 675.7 (33), 424.2 [M+H+], 338.3 (49); HRMS
(ESI+): calcd (m/z) for C29H30DN2O+: 424.24937; found: 424.24901.
Acknowledgements
,
Financial support from the Ruprecht-Karls-Universitꢀt Heidelberg, the
SFB 623 (Molecular Catalysts: Structure and Functional Design), and the
Fonds der Chemischen Industrie (FCI) is gratefully acknowledged.
G
ACHTUNGTRENNUNG
G
ACHTUNGTRENNUNG
G
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ACHTUNGTRENNUNG
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Chem. Eur. J. 2012, 00, 0 – 0
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B. F. Straub et al.
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Received: June 28, 2012
Published online: && &&, 0000
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These are not the final page numbers!

Zwitterionic N,N-Dimethylisotryptammonium Carboxylate
FULL PAPER
Carboxylate Transformations
A. Hꢀußermann, F. Rominger,
B. F. Straub* .................. &&&& — &&&&
CO2 on a Tightrope: Stabilization,
Room-Temperature Decarboxylation,
and Sodium-Induced Carboxylate
Migration
To balance or to unbalance—that is
CO2ꢂs question: A facile decarboxyla-
tion at room temperature of a zwitter-
ionic amino acid has been observed.
The re-carboxylation influences the
reaction kinetics (middle to left X-ray
structure). Stable silicon and tin spiro
derivatives are reported. The detailed
mechanism of a carbon chain rear-
rangement from the sodium carboxy-
late and excess methyllithium is
reported (middle to right structure).
Chem. Eur. J. 2012, 00, 0 – 0
ꢁ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
&
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&
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These are not the final page numbers!