s-Block-Metal-Mediated Hydroamination of Diphenylbutadiyne with Primary Arylamines Using a Dipotassium Tetrakis(amino)calciate Precatalyst

Article abstract of DOI:10.1021/acs.organomet.5b00449

(Chemical Equation Presented). The hydroamination of diphenylbutadiyne with primary arylamines requires a reactive catalyst. In the presence of heterobimetallic K₂[Ca{N(H)Dipp}₄] (Dipp = 2,6-diisopropylphenyl) the performance of this

Full text of DOI:10.1021/acs.organomet.5b00449

Article
pubs.acs.org/Organometallics
s‑Block-Metal-Mediated Hydroamination of Diphenylbutadiyne with
Primary Arylamines Using a Dipotassium Tetrakis(amino)calciate
Precatalyst
Fadi M. Younis, Sven Krieck, Helmar Gorls, and Matthias Westerhausen*
̈
Institute of Inorganic and Analytical Chemistry, Friedrich-Schiller-University, Humboldtstraße 8, D-07743 Jena, Germany
S
* Supporting Information
ABSTRACT: The hydroamination of diphenylbutadiyne with primary
arylamines requires a reactive catalyst. In the presence of heterobimetallic
K2[Ca{N(H)Dipp}4] (Dipp = 2,6-diisopropylphenyl) the performance of this
reaction in THF yields 2-tert-butyl-6,7,10,11-tetraphenyl-9H-cyclohepta[c]-
quinoline (1a) and 2-fluoro-6,7,10,11-tetraphenyl-9H-cyclohepta[c]quinoline
(1b) within 3 days at room temperature when 4-tert-butyl- and 4-
fluoroaniline, respectively, have been used. During this catalysis o-CH
activation occurs and quinoline derivatives are formed. Blocking the o-CH
positions by methyl groups and use of 2,4,6-trimethylaniline under similar
reaction conditions leads to the formation of N-mesityl-7-(E)-((mesitylimino)(phenyl)methyl)-2,3,6-triphenylcyclohepta-1,3,6-
trienylamine (2) containing a β-diketimine unit with a N−H···N hydrogen bridge. NMR experiments with labeled 4-tert-
butylaniline verify the transfer of N-bound hydrogen atoms to the newly formed cycloheptatriene ring. If the s-block-metal-
mediated hydroamination of diphenylbutadiyne is performed in refluxing THF for 6 days, N-aryl-2,5-diphenylpyrroles 3a−d (3a,
R = tBu, R′ = H; 3b, R = F, R′ = H; 3c, R = R′ = Me; 3d, R = R′ = H) are obtained regardless of the substitution pattern of the
arylamines.
by deprotonation and formation of the much more aggressive
and nucleophilic amides (R2N−) or even imides (RN2−) of
early transition metals or s-block metals. The disadvantageous
entropy value can be minimized by an intramolecular
hydroamination reaction, leading to cyclic amines.
INTRODUCTION
■
Metal-mediated hydroamination of CC and CC multiple
bonds with amines (Scheme 1) represents an atom-economical
Scheme 1. Hydroamination of Alkenes (Top) and Alkynes
Alkali-metal and alkaline-earth-metal complexes represent
less common catalysts for diverse reasons. Organometallics of
these s-block metals contain very heteropolar metal−carbon or
metal−nitrogen bonds, and saltlike ionic contributions
dominate the reaction pattern. In contrast to covalent bonds,
electrostatic forces are nondirectional and hence control of
stereochemistry has to be performed with a definite and
particularly designed ligand sphere. The larger alkaline-earth-
metal ions are isoelectronic with trivalent ions of the scandium
group as well as tetravalent ions of the titanium group, and such
d0 metal ions are able to use d orbitals in bonding situations.2
Due to this fact, the heavier alkaline-earth metals combine the
advantageous properties of typical s-block metals (strongly
ionic and highly heteropolar bonds, high reactivity, and
nucleophilicity) and early transition metals (d orbital
participation, Lewis acidity, catalytic behavior), with calcium
being the ideal element because it is also globally abundant,
available worldwide, inexpensive, and nontoxic.3−5
(Bottom) Yielding Alkylamines and E/Z-Alkenylamines
procedure to prepare substituted amines by addition of N−H
bonds to alkenes or alkynes.1 Generally, this process has to
overcome certain challenges such as unfavorable entropic
effects, electrostatic repulsion between a strongly Lewis basic
amine and an electron-rich multiple bond, and lack of
significant exothermic reaction enthalpy. Due to these facts
several strategies have been developed to support the addition
of N−H functionalities to C−C multiple bonds. On the one
hand, activation of alkenes and alkynes often succeeds in the
vicinity of late transition metals by back-donation of charge
from the metal-centered d orbitals into π* orbitals of the
alkenes and alkynes, in agreement with the Dewar−Chatt−
Duncanson model. On the other hand, the amines can be
activated by oxidative addition to transition-metal complexes or
For about ten years, intramolecular calcium-mediated
hydroamination of alkenes has been investigated intensely by
several research groups, often employing heteroleptic com-
Received: May 7, 2015
© XXXX American Chemical Society
A
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plexes with one bulky protecting anion in order to partially
shield the catalyst.6−13 Intermolecular hydroamination reac-
tions catalyzed by calcium-based complexes are much more
challenging. Therefore, amines have been added to activated
alkenes such as styrenes14,15 or carbodiimides16 as well as
alkynes14,17,18 catalyzed by amidocalcium species. These studies
showed that the reactivity of the catalyst can be enhanced by
using heterobimetallic potassium tetrakis(amido)calciates of the
type K2[Ca(NRR′)4] in ethereal solvents. However, side
-products have been observed that result from an o-hydrogen
activation and abstraction followed by C−C bond formation
(Figure 1, top).18 Thus, the addition of diphenylamine to
The copper-catalyzed addition of primary amines to
diphenylbutadiyne gives pyrroles in high yields. This reaction
requires high catalyst loads such as 25 mol % of copper(I)
halide and enhanced reaction temperatures.19
These results initiated a detailed investigation of the reaction
of primary anilines with diphenylbutadiyne in the presence of
the same approved precatalyst K2[Ca{N(H)Dipp}4] under
variation of the reaction conditions and the substitution pattern
of the primary arylamine. We decided to maintain this
precatalyst because (i) its preparation is straightforward from
the metathesis reaction of KN(H)Dipp with CaI2 (eq 1) and
(ii) its purification easily succeeds by recrystallization.
Furthermore, (iii) this compound crystallizes free of solvent,
thus avoiding aging of the solid by uncontrolled loss of solvent
molecules; hence, stoichiometric requirements (addition of a
specified mole percent of K2[Ca{N(H)Dipp}4] to the
substrates) can easily be achieved.
+Cal2
4KN(H)Dipp ⎯−⎯⎯2⎯K⎯→l K2[Ca{N(H)Dipp]4
(1)
RESULTS AND DISCUSSION
■
Synthesis. In a typical procedure, equimolar amounts of
diphenylbutadiyne and substituted amine were combined in
tetrahydrofuran (THF) in the presence of 5 mol % of
K2[Ca{N(H)Dipp}4] and stirred for 3 days at room temper-
ature. Depending on the substitution pattern, different reaction
pathways have been observed. The use of 4-tert-butylaniline in
this reaction and a hydrolytic workup procedure yields product
1a regardless of the applied stoichiometry. This product is
based on α-deprotonation steps of 4-tert-butylaniline and
formation of a C−C bond leading to 2-tert-butyl-6,7,10,11-
tetraphenyl-9H-cyclohepta[c]quinoline (1a); very poor yields
were obtained under similar reaction conditions for the reaction
of diphenylbutadiyne with 4-fluoroaniline leading to 2-fluoro-
6,7,10,11-tetraphenyl-9H-cyclohepta[c]quinoline (1b). The
fluoro substituent withdraws electron density via the aromatic
ring from the nitrogen atom, reducing the nucleophilicity of the
amino functionality. Compensation of reduced reactivity by
more drastic reaction conditions proved to be disadvantageous
because at raised temperatures another reaction pathway was
observed as discussed below, yielding a pyrrole. Nevertheless,
derivatives 1a,b both represent quinoline derivatives with
annelated seven-membered rings. The reaction is depicted in eq
2, and only hydrogen atoms that are involved in the conversion
are explicitly shown.
Figure 1. Products of the s-block-metal-mediated hydroamination of
diphenylbutadiyne with N-diisopropylaniline (top) and 2,6-diisopro-
pylaniline (bottom; only the formerly N-bound H atoms are depicted),
containing 2 equiv of butadiyne (yellow and green) and 1 equiv of
amine (C, gray; N, blue).
diphenylbutadiyne required a heterobimetallic s-block-metal
catalyst, whereas the addition of more nucleophilic N-
isopropylaniline to this butadiyne can be promoted by
homometallic s-block-metal amides. In contrast to this “simple”
addition of a N−H bond of a secondary amine to
diphenylbutadiyne, the reaction of primary 2,6-diisopropylani-
line with diphenylbutadiyne at room temperature in the
presence of catalytic amounts of K2[Ca{N(H)Dipp}4] (Dipp
= 2,6-diisopropylphenyl) proceeds via multiple reaction steps
involving ring expansion of the 2,6-diisopropylphenyl ring to a
seven-membered-ring system (Figure 1, bottom).17 Here, 2
equiv of diphenylbutadiyne (distinguished by the colors yellow
and green) react with 1 equiv of H2N-Dipp, regardless of the
applied stoichiometry.
The reaction of 2,4,6-trimethylaniline with diphenylbuta-
diyne must proceed via a different pathway, because the ortho
positions are blocked by methyl groups. In this case, a 1:1 ratio
of both substrates was observed at room temperature in THF
with a precatalyst load of 5 mol % of K2[Ca{N(H)-Dipp}4]
according to eq 3, yielding N-mesityl-7-(E)-((mesitylimino)-
B
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Scheme 2. Proposed Mechanism of the s-Block-Metal-
Mediated Hydroamination of Diphenylbutadiyne with
Primary Arylamines at High Temperatures Yielding N-Aryl-
2,5-diphenylpyrroles
(phenyl)methyl)-2,3,6-triphenylcyclohepta-1,3,6-trienylamine
(2). Only those hydrogen atoms are depicted that were bound
at the nitrogen atom of the amine substrate. Again, a seven-
membered cycloheptatriene moiety was found; however, the
mesityl substituents remain intact during this transformation, in
contrast to earlier findings with 2,6-diisopropylaniline yielding
product B (Figure 1, bottom).17
In order to study the influence of the reaction temperature,
in a typical procedure diphenylbutadiyne was dissolved in THF
and an equimolar amount of arylamine and 5 mol % of the
catalyst K2[Ca{N(H)Dipp}4] were added. This reaction
mixture was stirred and refluxed for 3 days. Then another 5
mol % of K2[Ca{N(H)Dipp}4] was added and heating was
continued for a further 3 days. A standard workup procedure
including hydrolysis with distilled water, extraction with diethyl
ether, drying with sodium sulfate, and recrystallization from
pentane or toluene at 5 °C yielded colorless crystals of N-aryl-
2,5-diphenylpyrroles 3 according to eq 4 (3a, R = tBu, R′ = H;
3b, R = F, R′ = H; 3c, R = R′ = Me; 3d, R = R′ = H).
heterobimetallic catalyst system.17,18 E/Z isomerization is
possible via the cumulene isomer A′, which can isomerize to
either a trans (A) or a cis orientation (A″) of the anionic site
and the remaining alkyne moiety. Such cumulene systems have
also been suggested during calcium-mediated hydrophospha-
nylation of diphenylbutadiyne with diphenylphosphane in order
to explain isomer mixtures.20 After the initial reaction step,
intramolecular metalation transfers the N-bound hydrogen to
the alkenyl moiety and amide B is formed. During the high-
temperature route an intramolecular addition to the second
alkyne unit occurs and the pyrrole derivative C is formed. The
reaction of this intermediate species with another arylamine
regenerates the catalyst, and the formation of pyrroles 3a−d is
completed.
In contrast to this straightforward pathway for the synthesis
of pyrroles 3a−d, the low-temperature route proceeds via an
insertion of another diphenylbutadiyne molecule into the
metal−carbon bond of the primary reaction product
(carbometalation step, Scheme 3) yielding intermediate D.
For the sake of clarity the diphenylbutadiyne units are
distinguished by different colors in this scheme. An intra-
molecular metalation reaction forms amide E. Now, two
reaction routes seem to be feasible to explain the formation of 1
(via o-CH activation) and 2 (via addition of a second
arylamine). These compounds are depicted in Figure 2, also
clarifying the origin of the structural moieties. The closed-shell
ionic mechanism involves the formation of the 1,2,4,6-
cycloheptatetraene intermediate F. Such species exhibit ring
strain; nevertheless, unsaturated ring systems of this kind have
already been studied in a solid matrix21 and by quantum
chemical investigations, also considering other isomers such as
phenylcarbene, bicyclo[3.2.0]hepta-1,3,6-triene, bicyclo[3.2.0]-
hepta-3,6-diene-2-ylidene, bicyclo[3.2.0]hepta-2,3,6-triene, and
bicyclo[4.1.0]heptatriene.22 Furthermore, a cyclotetramer of
such a strained cycloheptatetraene derivative has been
characterized by an X-ray crystal structure determination.23
Despite the fact that ring strain is present in cycloheptate-
Proposed Mechanism. In all cases, with the exception of
1b, moderate to good yields were obtained. The precatalyst
K2[Ca{N(H)Dipp}4] reacts with the primary aniline substrate,
and NMR spectroscopic investigations of THF solutions
containing K2[Ca{N(H)-Dipp}4] and the 4-fold stoichiometric
amount of 2,4,6-trimethylaniline verified the quantitative ligand
exchange and formation of 2,6-diisopropylaniline. A 1:2 ratio of
K2[Ca{N(H)Dipp}4] and mesitylamine led to heteroleptic
calciates of the general formula K2[Ca{N(H)Dipp}4−x{N(H)-
Mes}x]. Due to the fact that all aniline derivatives might exhibit
comparable pKa values, it can be concluded that the bulkier
amide is replaced by the smaller amide in order to minimize
intramolecular strain of the calciate anion mainly provoked by
the ortho substituents.
The catalytic reaction starts with the addition of a metal−
nitrogen bond to one CC triple bond as shown in Scheme 2
(nucleophilic attack of an amide at an alkyne) yielding
intermediate A. In this scheme, M symbolizes the s-block
metal and hence the anionic site. The reactivity of
homometallic calcium amides is not sufficient to mediate this
hydroamination. Therefore, we employed the already known
strategy to significantly enhance the reactivity by formation of a
traenes, these derivatives also represent 4n π-Mobius aromatic
̈
systems.24 Intermolecular metalation by an arylamine regener-
ates the catalyst and leads to the formation of G.
In this bicyclic intermediate G the allene moiety attacks the
o-CH group leading to compound 1. Absence of o-CH
C
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Scheme 3. Proposed Mechanism of the s-Block-Metal-
Mediated Hydroamination of Diphenylbutadiyne with
Primary Arylamines at Room Temperature via a 1,2,4,6-
Cycloheptatetraene Intermediate and via a Bergman
a
Cyclization Route
Figure 2. Stick-and-ball presentations of 1 (top) and 2 (bottom). The
structural building blocks are distinguished by different colors: the
initial diphenylbutadiyne moieties are shown in yellow and green and
the arylamines in gray (C atoms) and blue (N atom). Only those H
atoms are drawn (light gray) that are involved in chemical
transformations or are bound at a nitrogen atom.
Scheme 4. Proposed Final Mechanistic Steps for the
Formation of 2 Starting from I or G′a
a
The diphenylbutadiyne units are distinguished by the colors orange
and green.
fragments and bulkier N-bound aryl groups favor the formation
of isomer G′ (Scheme 4), leading to an alternative reaction
pattern. Here, the 1,4-addition of an arylamine to the
cycloheptatetraene ring leads to the formation of compound 2.
An alternative pathway contains the Bergman cyclization
leading to diradical H. Again the catalyst is re-formed by an
intermolecular reaction with an arylamine yielding intermediate
I. This radical can attack either at a o-CH group (yielding 1)
orin the case that such a functionality is absentanother
amine substrate, leading to compound 2 as shown in Scheme 4.
a
G′ is the E isomer of G.
The fact that homometallic calcium bis(amide) does not
mediate these hydroamination reactions raises the question of
the cooperation of potassium and calcium in the catalyst
system. In the solid state K2[Ca{N(H)Dipp}4] forms a
coordination polymer consisting of [Ca{N(H)Dipp}4]2−
anions interconnected by potassium cations.17 It can be
assumed that in solution the calciate anions are maintained.
D
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In these calciate anions electrostatic repulsion between the
amido substituents enhances the Ca−N bond lengths and,
hence, the nucleophilicity and reactivity of the amido groups.
This consideration suggests that M in the schemes might be a
calciate fragment. The role of the potassium ions remains
unclear and speculative. Potassium ions are considered as soft
Lewis acids, being able to coordinate to rather hard (such as
ethers) and preferably to soft Lewis bases such as aromatics and
extended π systems. Nevertheless, it remains speculative to
what extent this coordination behavior of K+ supports the
catalytic hydroamination via coordination to any of the
reported intermediates. Due to the fact that rather high yields
of the products were obtained and that cycloheptatetraene
derivatives have already been accessible experimentally, we
favor the mechanism via the cycloheptatetraene intermediates.
In addition, we would expect diverse derivatives for the radical
mechanism due to reactions of the radical with solvent
molecules and still present arylamine substrates.
1
NMR Experiments. The H NMR spectrum of 1a (R =
tBu) clearly shows a characteristic ABX coupling pattern for the
hydrogen atoms at the seven-membered ring leading to three
doublets of doublets (Figure 3) with a pseudotriplet for the CH
Figure 4. 1H NMR spectrum of the CH fragment of the seven-
membered ring of partially deuterated 1a (top), with assignment to
differently deuterated derivatives (bottom).
tert-butylphenyl group to the seven-membered ring yielding the
methylene group.
Compound 2 represents a β-diketimine derivative with an
annelated unsaturated seven-membered ring. This structural
fragment gives rise to a low-field-shifted resonance for the N−
H···N hydrogen bridge with a chemical shift of δ 12.85 ppm. In
Figure 5 the 1H NMR spectrum of the methyl region is
Figure 3. 1H NMR resonances of the newly formed methylene unit of
the seven-membered ring of compound 1a. The coupling pattern
clearly verifies the magnetic nonequivalence of the H atoms.
resonance at δ 6.41 ppm due to very similar vicinal coupling
constants. The H atoms of the methylene fragment are
magnetically inequivalent with a geminal coupling constant of
2JHH = 11.6 Hz, verifying the nonplanarity of the cyclo-
heptatriene unit.
In order to support the reaction mechanism, we repeated the
preparation of this compound with partially N-deuterated 4-
tert-butylaniline with a deuteration degree of 75%. This
approach should yield 1a in addition to its partially deuterated
1
derivatives. The coupling pattern in the H NMR spectrum at
Figure 5. 1H NMR resonances of the methyl substituents of the
mesityl groups, showing that the 2,6-positions are magnetically
nonequivalent, which suggests a hindered rotation of the mesityl
groups around the N−C bonds.
the CH signal at δ = 6.41 ppm enables the assignment and
determination of the positions of deuterium atoms (Figure 4).
The coupling pattern of the endocyclic CH−CH2− fragment
allows the assignment to the moieties CH−CH2, CH−CHD,
and CH−CDH. The intensity ratio of the resonances excludes
the formation of CH−CD2 units, which would suggest a
bimolecular reaction mechanism. This coupling pattern and the
resonances of the neighboring methylene group (see the
Supporting Information) clearly show that there exists no
preference for deuteration at either position and hence no
stereocontrol for the transfer of the o-hydrogen atom of the 4-
depicted. All methyl groups are chemically different, which has
been explained by hindered rotation around the C−N bonds.
The nonequivalence of the o-methyl groups of each mesityl
substituent is a consequence of the chiral carbon atom of the
seven-membered cycloheptatriene ring.
E
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Molecular Structures. The molecular structure and
numbering scheme of N-mesityl-2,5-diphenylpyrrole (3c) are
depicted in Figure 6. Due to steric reasons the N-bound aryl
Figure 7. Molecular structure and numbering scheme of 1a. The
ellipsoids represent a probability of 30%, Hand atoms are shown with
arbitrary radii. Selected bond lengths are given in Table 1.
Figure 6. Molecular structure and numbering scheme of 3c. The
ellipsoids represent a probability of 30%, and H atoms are shown with
arbitrary radii. Selected bond lengths (pm): N1−C1 139.1(2), N1−C4
139.3(2), N1−C11 144.4(2), C1−C2 138.1(2), C2−C3 140.7(2),
C3−C4 137.8(2), C1−C20 147.6(2), C4−C5 146.8(2). Selected bond
angles (deg): C1−N1−C4 109.0(1), N1−C1−C2 107.5(1), C1−C2−
C3 107.9(1), C2−C3−C4 108.4(1), N1−C4−C3 107.3(1), C1−N1−
C11 125.6(1), C4−N1−C11 125.1(1), N1−C1−C20 124.7(1), C2−
C1−C20 127.8(1), N1−C4−C5 125.3(1), C3−C4−C5 127.4(1).
group is oriented nearly perpendicular to the pyrrole ring with
an angle of 69.2° between these planes. Expectedly, the π
system of the pyrrole ring leads to short bonds and charge
delocalization to a large extent. Endocyclic C1−C2, C2−C3,
and C3−C4 bond lengths differ by less than 3 pm and have an
average value of 138.9 pm. The exocyclic C1−C20 and C4−C5
bond lengths, with an average distance of 147.2 pm, are
characteristic for single bonds between sp2-hybridized carbon
atoms. 1,2,5-Triphenylpyrrole (3d) exhibits crystallographic C2
symmetry and shows very similar structural parameters (see the
Supporting Information). This measurement at −140 °C leads
to results very similar to those of the crystal structure
determination at room temperature.25
Figure 8. Molecular structure and numbering scheme of 1b. The
ellipsoids represent a probability of 30%, and H atoms are shown with
arbitrary radii. Selected bond lengths are given in Table 1.
Verification of the compositions of 1a,b and 2 as shown in
Figure 2 was also successful by X-ray diffraction experiments on
single crystals. Molecular structures and numbering schemes of
1a,b are presented in Figures 7 and 8, respectively. The
numbering schemes of both compounds are identical, and a
comparison of selected bond lengths is given in Table 1. These
compounds are built from two butadiyne molecules (atoms
C1A−C16A and C1B−C16B) and one 4-tert-butylaniline
(N1A, C17A−C26A) or 4-fluoroaniline molecule (N1A, F1A,
C17A−C22A), respectively. The quinoline fragments show
balanced bond lengths which are comparable to those of
unsubstituted quinoline.26 Substituents at the quinoline nucleus
of 1a,b lead to a slight lengthening between those carbon atoms
carrying substituents. The phenyl groups are oriented nearly
perpendicular to the ring systems; hence, no interaction
between the aromatic phenyl groups and the π-systems of the
seven-membered ring can be expected and characteristic C−C
single bond values around 149 pm were observed.
as well as N1B and C17B−C25B). Compound 2 contains the
chiral C4B atom, but due to the centric monoclinic space group
the crystalline state consists of a racemate. The structure-
dominating moiety is the N1A−C1B−C2B−C3B−N1B frag-
ment with significant charge delocalization and a N1B−H···
N1A hydrogen bridge (N1A···N1B distance 265.7(3) pm). The
C1A−C2B bond length shows a characteristic single-bond
value for sp2-hybridized carbon atoms excluding π interaction
between the β-diketimine unit and the remaining π bonds of
the seven-membered ring. This hydrogen bridge also explains
why only the E isomer of the N1AC1B imine unit is
observed.
CONCLUSION
■
The s-block-metal-mediated hydroamination of diphenylbuta-
diyne with primary amines in THF requires the presence of 5−
10 mol % of heterobimetallic K2[Ca{N(H)Dipp}4]; homo-
metallic calcium bis(amides) did not initiate the hydro-
amination under similar reaction conditions. The substitution
pattern of the arylamines and the reaction conditions strongly
influence the reaction pathway. At high temperatures in
The molecular structure and numbering scheme of
compound 2 are shown in Figure 9. This compound is built
from two butadiyne (atoms C1A−C4A and C1B to C4B) and
two 2,4,6-trimethylaniline molecules (N1A and C17A−C25A
F
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These highly reactive intermediates attack o-CH functionalities
of the arylamine unit, leading to a quinoline derivative with a
2:1 ratio of butadiyne to arylamine. If o-CH groups are not
available, another reaction pathway is pursued and the reactive
intermediate traps another 1 equiv of arylamine, yielding a β-
diketimine derivative which is annelated to a seven-membered
ring. This β-diketimine crystallizes in the ene−amine form with
a N−H···N hydrogen bridge and shows no significant
conjugation with the attached multiple bonds of the annelated
seven-membered ring. The performance of this s-block-metal-
mediated hydroamination of diphenylbutadiyne at room
temperature allows the synthesis of quinolone derivatives in
the presence of o-CH functionalities.
Special attention has to be given to the advantageous
properties of the catalyst system. The reaction of 4 equiv of
KN(H)Dipp with calcium iodide in THF yields solvent-free
K2[Ca{N(H)Dipp}4].17 The potassium ions bind to the amido
anions and to the π systems of the aryl groups, leading to a
coordination polymer in the solid state. Nevertheless, this
complex is soluble in ethers. On the one hand, the rather bulky
isopropyl groups in ortho positions prevent formation of ether
adducts which commonly tend to slowly lose these neutral
coligands upon standing and handling. Partial loss of coligands
leads to weathering of the crystalline material and makes it
difficult to exactly meet the stoichiometry. On the other hand,
these isopropyl groups enhance intramolecular steric strain
which can be released by a ligand exchange reaction and,
therefore, in solution a fast substitution of the 2,6-
diisopropylanilide anion by smaller amide ligands occurs. This
initial amide exchange, which is much faster than the addition
to the alkyne moieties, is the reason that K2[Ca{N(H)Dipp}4]
represents an ideal precatalyst for any hydroamination of
diphenylbutadiyne with sterically less demanding primary
arylamines. It is a common observation that heterobimetallic
s-block-metal compounds often adopt reactivities different from
those of their homometallic constituents.5,27−30 These mixed-
metal complexes form metalates27,28 which are in some cases
addressed as inverse crowns29 and turbo Grignard or turbo
Hauser reagents.30
Table 1. Comparison of Selected Bond Lengths (pm) of 2-
tert-Butyl-6,7,10,11-tetraphenyl-9H-cyclohepta[c]quinoline
(1a) and 2-Fluoro-6,7,10,11-tetraphenyl-9H-
cyclohepta[c]quinoline (1b)
bond
1a (R = tBu)
1b (R = F)
N1A−C1A
N1A−C17A
C17A−C18A
C17A−C22A
C18A−C19A
C19A−C20A
C20A−C21A
C20A−R
C21A−C22A
C1A−C2A
C1A−C11A
C2A−C3A
C2A−C4B
C3A−C4A
C3A−C22A
C4A−C5A
C4A−C1B
C1B−C2B
C1B−C11B
C2B−C3B
C3B−C4B
C4B−C5B
131.4(2)
137.1(2)
140.8(2)
141.6(2)
137.0(2)
141.4(2)
138.5(2)
153.2(2)
141.6(2)
144.4(2)
149.1(2)
139.5(2)
148.6(2)
149.2(2)
144.6(2)
149.4(2)
135.6(2)
151.8(2)
149.0(2)
150.3(2)
133.8(2)
149.0(2)
131.4(3)
138.0(3)
141.5(3)
141.5(3)
137.5(4)
138.7(4)
136.4(3)
136.3(3)
141.9(3)
144.2(3)
149.6(3)
139.5(3)
148.3(3)
148.6(3)
146.2(3)
149.4(3)
135.8(3)
151.1(3)
149.3(3)
150.5(3)
132.8(3)
149.2(3)
In conclusion, thermodynamic control (in boiling THF) of s-
block-metal-mediated hydroamination of diphenylbutadiyne
with primary arylamines employing K2[Ca{N(H)Dipp}4] yields
N-aryl-2,5-diphenylpyrroles regardless of the bulkiness of the
N-bound aryl groups, whereas kinetic control (at room
temperature) leads to rather complex reaction pathways
depending on the ortho substituents of the arylamines, where
the formation of unsaturated seven-membered rings represents
a key feature.
Figure 9. Molecular structure and numbering scheme of 2. The
ellipsoids represent a probability of 30%, and selected H atoms are
shown with arbitrary radii. Selected bond lengths (pm): N1A−C17A
142.9(3), N1A−C1B 129.5(3), N1B−C17B 143.2(3), N1B−C3B
135.7(3), N1B−H 88(3), C1A−C2A 135.8(3), C1A−C2B 147.2(3),
C1A−C11A 149.0(3), C2A−C3A 143.9(3), C3A−C4A 134.7(3),
C4A−C5A 148.4(3), C4A−C4B 152.8(3), C1B−C2B 146.9(3),
C1B−C11B 150.6(3), C2B−C3B 139.1(3), C3B−C4B 151.6(3),
C4B−C5B 153.9(3).
EXPERIMENTAL SECTION
■
General Remarks. All manipulations were carried out under an
inert nitrogen atmosphere using standard Schlenk techniques. The
solvent was dried over KOH and subsequently distilled over sodium/
benzophenone under a nitrogen atmosphere prior to use. Deuterated
solvents were dried over sodium, degassed, and saturated with
refluxing THF the formation of N-aryl-2,5-diphenylpyrroles
succeeds with moderate to high yields. A 2-fold addition of
metal−nitrogen bonds to both CC triple bonds yields
pyrrole rings with an aromatic character.
1
nitrogen. The yields given are not optimized. H and 13C{1H} NMR
spectra were recorded on Bruker AC 400 and AC 600 spectrometers.
Chemical shifts are reported in parts per million relative to SiMe4 as an
external standard. The residual signals of the deuterated solvents
[D8]THF and CD2Cl2 were used as internal standards. The solvent-
free and recrystallized precatalyst K2[Ca{N(H)Dipp}4] was prepared
according to a literature procedure.17 A specific amount of this
compound was dissolved in anhydrous THF, and aliquots of this
solution were added to the reaction mixtures. This procedure allowed
In contrast to the high-temperature route, the s-block-metal-
mediated reaction of diphenylbutadiyne with arylamines at
room temperature strongly depends on the substituents in
ortho positions. During this reaction an amide reacts with two
diphenylbutadiyne molecules. Cyclization leads either to a
cyclohepta-1,2,4,6-tetraene intermediate or, via Bergman
cyclization, to a methylidene−cycloheptatrienediyl radical.
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DOI: 10.1021/acs.organomet.5b00449
Organometallics XXXX, XXX, XXX−XXX

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Article
us to easily add definite amounts of precatalyst to the substrates under
strictly anaerobic conditions. All substrates were purchased from
Sigma-Aldrich, Merck, or Alfa Aesar and used without further
purification.
General Procedure for the Synthesis of 2-Substituted
6,7,10,11-Tetraphenyl-9H-cyclohepta[c]quinolone (1; R = tBu,
F). A 2 equiv amount of diphenylbutadiyne was dissolved in THF.
Thereafter, 1 equiv of 4-tert-butylaniline and 5 mol % (with respect to
the butadiyne) of the catalyst K2[Ca{N(H)Dipp}4]∞ were added. This
solution was stirred for 3 days at room temperature. After hydrolysis
with distilled water, extraction with diethyl ether, drying with sodium
sulfate, and recrystallization from a mixture of dichloromethane and
pentane at 5 °C, colorless crystals were isolated from an orange
mother liquor.
Synthesis of 2. Diphenylbutadiyne (0.3 g 1.48 mmol) was
dissolved in 15 mL of THF. Then, 0.21 mL of 2,4,6-trimethylaniline
(0.2 g, 1.48 mmol) and 5 mol % of the calciate catalyst
K2[Ca{N(H)Dipp}4]∞ were added. This reaction mixture was stirred
for 3 days at oom temperature. A standard workup procedure included
hydrolysis with 15 mL of distilled water, extraction with diethyl ether,
drying with sodium sulfate, and recrystallization from a mixture of
dichloromethane and pentane at 5 °C, yielding colorless crystals in a
reddish brown mother liquor. Yield: 0.4 g, 0.59 mmol, 80%.
General Procedure for the Synthesis of N-Aryl-2,5-diphe-
nylpyrroles 3. Diphenylbutadiyne (0.3 g 1.48 mmol) was dissolved in
17 mL of THF before 4-fluoraniline (0.164 g, 1.48 mmol) and 10 mol
% of the calciate K2[Ca{N(H)Dipp}4]∞ (5 mol % at the beginning
and 5 mol % after 3 days) were added, and the reaction mixture was
heated for 6 days at 60 °C. Thereafter, the solution was hydrolyzed
with 15 mL of distilled water and extracted with diethyl ether and the
separated ether phase dried with sodium sulfate. Recrystallization from
pentane at 5 °C yielded a colorless solid (0.40 g, 1.27 mmol, 85.8%) in
an orange mother liquor.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This paper is dedicated to Professor Manfred Scheer on the
occasion of his 60th birthday. We appreciate the financial
support of the Fonds der Chemischen Industrie im Verband
der Chemischen Industrie e.V. (FCI/VCI, Frankfurt/Main,
Germany). F.M.Y. thanks the German Academic Exchange
Service (DAAD, Bonn, Germany) for a generous Ph.D. stipend.
REFERENCES
■
(1) (a) Hydrofunctionalization; Ananikov, V. P., Tanaka, M., Eds.;
Springer: Heidelberg, Germany, 2013; Topics in Organometallic
Chemistry 43. (b) Behr, A.; Neubert, P.: Applied Homogeneous
Catalysis; Wiley-VCH: Weinheim, Germany, 2012; Chapter 30, pp
455−472. (c) Catalyzed Carbon-Heteroatom Bond Formation; Yudin,
A. K., Ed.; Wiley-VCH: Weinheim, Germany, 2011. (d) Muller, T. E.;
̈
Hultzsch, K. C.; Yus, M.; Foubelo, F.; Tada, M. Chem. Rev. 2008, 108,
3795−3892. (e) Catalytic Heterofunctionalization: From Hydroamina-
tion to Hydrozirconization; Togni, A., Grutzmacher, H., Eds.; Wiley-
VCH: Weinheim, Germany, 2001.
(2) (a) Kaupp, M. In Anorganische Chemie: Prinzipien von Struktur
und Reaktivitat; Huheey, J. E., Keiter, E. A., Keiter, R. L., Eds.; De
Gruyter: Berlin, Boston, 2012. (b) Kaupp, M. Angew. Chem., Int. Ed.
2001, 40, 3534−3565.
̈
̈
(3) Harder, S. Chem. Rev. 2010, 110, 3852−3876.
(4) (a) Crimmin, M. R.; Hill, M. S. Top. Organomet. Chem. 2013, 45,
191−241. (b) Barrett, A. G. M.; Crimmin, M. R.; Hill, M. S.;
Procopiou, P. A. Proc. R. Soc. London, Ser. A 2010, 466, 927−963.
(5) Westerhausen, M.; Langer, J.; Krieck, S.; Glock, C. Rev. Inorg.
Chem. 2011, 31, 143−184.
X-ray Structure Determination. The intensity data for the
compounds were collected on a Nonius KappaCCD diffractometer
using graphite-monochromated Mo Kα radiation. Data were corrected
for Lorentz and polarization effects; absorption was taken into account
on a semiempirical basis using multiple scans.31−33 The structures
were solved by direct methods (SHELXS)34 and refined by full-matrix
(6) (a) Romero, N.; Rosç a, S.-C.; Sarazin, Y.; Carpentier, J.-F.;
Vendier, L.; Mallet-Ladeira, S.; Dinoi, C.; Etienne, M. Chem. - Eur. J.
2015, 21, 4115−4125. (b) Liu, B.; Roisnel, T.; Carpentier, J.-F.;
Sarazin, Y. Chem. - Eur. J. 2013, 19, 13445−13462. (c) Liu, B.; Roisnel,
T.; Carpentier, J.-F.; Sarazin, Y. Chem. - Eur. J. 2013, 19, 2784−2802.
(7) (a) Mathia, F.; Zalupsky, P.; Szolcsanyi, P. Targets Heterocycl.
Systems 2012, 16, 309−370. (b) Mathia, F.; Zalupsky, P.; Szolcsanyi, P.
Targets Heterocycl. Systems 2011, 15, 226−262.
least-squares techniques against Fo (SHELXL-97).34 The hydrogen
2
atoms (with the exception of methyl groups C24, C25, and C26 of 1a
and 2) were located by difference Fourier synthesis and refined
isotropically. All non-hydrogen atoms were refined anisotropically.34
Crystallographic data as well as structure solution and refinement
details are summarized in the Supporting Information. The programs
XP (Siemens Analytical X-ray Instruments, Inc.)35 and POV-Ray36
were used for structure representations.
(8) (a) Nixon, T. D.; Ward, B. D. Chem. Commun. 2012, 48, 11790−
11792. (b) Wixey, J. S.; Ward, B. D. Dalton Trans. 2011, 40, 7693−
7696. (c) Wixey, J. S.; Ward, B. D. Chem. Commun. 2011, 47, 5449−
5451.
(9) (a) Jenter, J.; Koeppe, R.; Roesky, P. W. Organometallics 2011,
30, 1404−1413. (b) Panda, T. K.; Hrib, C. G.; Jones, P. G.; Jenter, J.;
Roesky, P. W.; Tamm, M. Eur. J. Inorg. Chem. 2008, 2008, 4270−4279.
(c) Datta, S.; Garner, M. T.; Roesky, P. W. Organometallics 2008, 27,
1207−1213. (d) Datta, S.; Roesky, P. W.; Blechert, S. Organometallics
2007, 26, 4392−4394.
(10) (a) Arrowsmith, M.; Crimmin, M. R.; Barrett, A. G. M.; Hill, M.
S.; Kociok-Kohn, G.; Procopiou, P. A. Organometallics 2011, 30,
1493−1506. (b) Crimmin, M. R.; Arrowsmith, M.; Barrett, A. G. M.;
Casely, I. J.; Hill, M. S.; Procopiou, P. A. J. Am. Chem. Soc. 2009, 131,
9670−9685. (c) Arrowsmith, M.; Hill, M. S.; Kociok-Kohn, G.
Organometallics 2009, 28, 1730−1738. (d) Barrett, A. G. M.; Crimmin,
M. R.; Hill, M. S.; Hitchcock, P. B.; Kociok-Kohn, G.; Procopiou, P. A.
Inorg. Chem. 2008, 47, 7366−7376. (e) Crimmin, M. R.; Casely, I. J.;
Hill, M. S. J. Am. Chem. Soc. 2005, 127, 2042−2043.
(11) (a) Mukherjee, A.; Nembenna, S.; Sen, T. K.; Sarish, S. P.;
Ghorai, P. K.; Ott, H.; Stalke, D.; Mandal, S. K.; Roesky, H. W. Angew.
Chem., Int. Ed. 2011, 50, 3968−3972. (b) Roesky, P. W. Angew. Chem.,
Int. Ed. 2009, 48, 4892−4894.
(12) Neal, S. R.; Ellern, A.; Sadow, A. D. J. Organomet. Chem. 2011,
696, 228−234.
(13) Buch, F.; Harder, S. Z. Naturforsch. 2008, 63b, 169−177.
ASSOCIATED CONTENT
■
S
* Supporting Information
Text, figures, a table, and CIF files giving preparative details and
physical data of all reported compounds and crystallographic
data of the crystal structure determinations as well as the NMR
spectra of all new compounds. The Supporting Information is
available free of charge on the ACS Publications website at
DOI: 10.1021/acs.organomet.5b00449. Crystallographic data
(excluding structure factors) have also been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publications CCDC-1062187 for 1a, CCDC-1062188 for 1b,
CCDC-1062189 for 2, CCDC-1062190 for 3c, and CCDC-
1062191 for 3d. Copies of the data can be obtained free of
charge on application to the CCDC, 12 Union Road,
Cambridge CB2 1EZ, U.K. (e-mail deposit@ccdc.cam.ac.uk).
AUTHOR INFORMATION
■
Corresponding Author
*M.W.: fax, +49 (0) 3641 9-48132; e-mail, m.we@uni-jena.de.
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Article
(14) (a) Reid, S.; Barrett, A. G. M.; Hill, M. S.; Procopiou, P. A. Org.
Lett. 2014, 16, 6016−6019. (b) Brinkmann, C.; Barrett, A. G. M.; Hill,
M. S.; Procopiou, P. A. J. Am. Chem. Soc. 2012, 134, 2193−2207.
(15) Barrett, A. G. M.; Brinkmann, C.; Crimmin, M. R.; Hill, M. S.;
Hunt, P.; Procopiou, P. A. J. Am. Chem. Soc. 2009, 131, 12906−12907.
(33) SADABS 2.10, Bruker-AXS Inc., Madison, WI, USA, 2002.
(34) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.
2008, 64, 112−122.
(35) XP; Siemens Analytical X-ray Instruments Inc., Karlsruhe,
Germany, 1990, and Madison, WI, USA, 1994.
(36) POV-Ray, Persistence of Vision Raytracer: Victoria, Australia,
2007.
(16) (a) Al-Shboul, T. M. A.; Volland, G.; Gorls, H.; Westerhausen,
̈
M. Z. Anorg. Allg. Chem. 2009, 635, 1568−1572. (b) Lachs, J. R.;
Barrett, A. G. M.; Crimmin, M. R.; Kociok-Kohn, G.; Hill, M. S.;
Mahon, M. F.; Procopiou, P. A. Eur. J. Inorg. Chem. 2008, 2008, 4173−
4179.
(17) Glock, C.; Younis, F. M.; Ziemann, S.; Gorls, H.; Imhof, W.;
̈
Krieck, S.; Westerhausen, M. Organometallics 2013, 32, 2649−2660.
(18) Glock, C.; Gorls, H.; Westerhausen, M. Chem. Commun. 2012,
̈
48, 7094−7096.
(19) Dudnik, A. S.; Gevorgyan, V. In Catalyzed Carbon-Heteroatom
Bond Formation; Yudin, A. K., Ed.; Wiley-VCH: Weinheim, Germany,
2011; Chapter 8, pp 227−316.
(20) Al-Shboul, T. M. A.; Pal
́
fi, V. K.; Yu, L.; Kretschmer, R.;
Wimmer, K.; Fischer, R.; Gorls, H.; Reiher, M.; Westerhausen, M. J.
̈
Organomet. Chem. 2011, 696, 216−227.
(21) (a) McKee, M. L.; Reisenauer, H. P.; Schreiner, P. R. J. Phys.
Chem. A 2014, 118, 2801−2809. (b) Warmuth, R.; Marvel, M. A.
Chem. - Eur. J. 2001, 7, 1209−1220. (c) Matzinger, S.; Bally, T. J. Phys.
Chem. A 2000, 104, 3544−3552.
(22) (a) Yang, Z. Y.; Wang, X. L.; Wang, J.; Zhang, J. C.; Cao, W. L.
Chin. Chem. Lett. 2005, 16, 1417−1420. (b) Patterson, E. V.;
McMahon, R. J. J. Org. Chem. 1997, 62, 4398−4405.
(23) Mahlokozera, T.; Goods, J. B.; Childs, A. M.; Thamattoor, D. M.
Org. Lett. 2009, 11, 5095−5097.
(24) Martin-Santamaria, S.; Lavan, B.; Rzepa, H. S. Chem. Commun.
2000, 1089−1090.
(25) Feng, X.; Tong, B.; Shen, J.; Shi, J.; Han, T.; Chen, L.; Zhi, J.;
Lu, P.; Ma, Y.; Dong, Y. J. Phys. Chem. B 2010, 114, 16731−16736.
(26) Davies, J. E.; Bond, A. D. Acta Crystallogr., Sect. E: Struct. Rep.
Online 2001, 57, o947−o949.
(27) (a) Deagostino, A.; Prandi, C.; Tabasso, S.; Venturello, P. Curr.
Org. Chem. 2011, 15, 2390−2412. (b) Westerhausen, M. Dalton Trans.
2006, 4755−4768.
(28) (a) Harford, P. J.; Peel, A. J.; Chevallier, F.; Takita, R.; Mongin,
F.; Uchiyama, M.; Wheatley, A. E. H. Dalton Trans. 2014, 43, 14181−
14203. (b) Tilly, D.; Chevalier, F.; Mongin, F.; Gros, P. C. Chem. Rev.
2014, 114, 1207−1257. (c) Harrison-Marchand, A.; Mongin, F. Chem.
Rev. 2013, 113, 7470−7562. (d) Mongin, F.; Harrison-Marchand, A.
Chem. Rev. 2013, 113, 7563−7727. (e) Mulvey, R. E.; Robertson, S. D.
Top. Organomet. Chem. 2013, 45, 103−139. (f) Linton, D. J.; Schooler,
P.; Wheatley, A. E. H. Coord. Chem. Rev. 2001, 223, 53−115.
(29) (a) Mulvey, R. E. Dalton Trans. 2013, 42, 6676−6693.
(b) Mulvey, R. E. Acc. Chem. Res. 2009, 42, 743−755. (c) Mulvey,
R. E.; Mongin, F.; Uchiyama, M.; Kondo, Y. Angew. Chem., Int. Ed.
2007, 46, 3802−3824. (d) Mulvey, R. E. Organometallics 2006, 25,
1060−1075. (e) Mulvey, R. E. Chem. Commun. 2001, 1049−1056.
(f) Mulvey, R. E. Chem. Soc. Rev. 1998, 27, 339−346.
(30) (a) Dagousset, G.; Francois, C.; Leon, T.; Blanc, R.; Sansiaume-
Dagousset, E.; Knochel, P. Synthesis 2014, 46, 3133−3171. (b) Klatt,
T.; Markiewicz, J. T.; Saemann, C.; Knochel, P. J. Org. Chem. 2014, 79,
4253−4269. (c) Knochel, P.; Barl, N. M.; Werner, V.; Saemann, C.
Heterocycles 2014, 88, 827−844. (d) Hevia, E.; Mulvey, R. E. Angew.
Chem., Int. Ed. 2011, 50, 6448−6450. (e) Manolikakes, S. M.; Barl, N.
M.; Saemann, C.; Knochel, P. Z. Naturforsch., B: J. Chem. Sci. 2013,
68b, 411−422. (f) Knochel, P.; Schade, M. A.; Bernhardt, S.;
Manolikakes, G.; Metzger, A.; Piller, F. M.; Rohbogner, C. J.;
Mosrin, M. Beilstein J. Org. Chem. 2011, 7, 1261−1277. (g) Haag, B.;
Mosrin, M.; Ila, H.; Malakhov, V.; Knochel, P. Angew. Chem., Int. Ed.
2011, 50, 9794−9824.
(31) COLLECT, Data Collection Software; Nonius BV, Dordrecht,
The Netherlands, 1998.
(32) Otwinowski, Z.; Minor, W. In Methods in Enzymology; Carter, C.
W., Sweet, R. M., Eds.; Academic Press: New York, 1997; Vol. 276
(Macromolecular Crystallography, Part A), pp 307−326.
I
DOI: 10.1021/acs.organomet.5b00449
Organometallics XXXX, XXX, XXX−XXX