Synthesis and reactivity of cationic iridium aminocarbenes derived from terminal alkynes and 2-aminopyridines

Article abstract of DOI:10.1021/om400326c

The reaction of a terminal alkyne (RCCH) and 2-aminopyridine (R′C₅NH₃NH₂) with the dinuclear species [Cp*IrCl₂]₂ afforded the cationic aminocarbene derivatives Cp*Ir(Cl)[ =C(CH₂R)NHC₅NH ₃R′] via a hydroamination and a ligand substitution. The reaction pathway has been examined through computational studies.

Full text of DOI:10.1021/om400326c

Article
pubs.acs.org/Organometallics
Synthesis and Reactivity of Cationic Iridium Aminocarbenes Derived
from Terminal Alkynes and 2‑Aminopyridines
Elumalai Kumaran, Kai Tong Sonia How, Rakesh Ganguly, Yongxin Li, and Weng Kee Leong*
Division of Chemistry and Biological Chemistry, Nanyang Technological University, 21 Nanyang Link, Singapore 637371
S
* Supporting Information
ABSTRACT: The reaction of a terminal alkyne (RCCH) and 2-
aminopyridine (R′C5NH3NH2) with the dinuclear species [Cp*IrCl2]2
afforded the cationic aminocarbene derivatives Cp*Ir(Cl)[ C-
(CH2R)NHC5NH3R′] via a hydroamination and a ligand substitution.
The reaction pathway has been examined through computational
studies.
INTRODUCTION
RESULTS AND DISCUSSION
■
■
Even though several methodologies have been developed,1
nucleophilic attack at the α-carbon of a vinylidene intermediate
is one of the best and most attractive synthetic routes to
transition-metal carbenes. Transition-metal vinylidenes are
susceptible to a wide number of nucleophiles, including
amines,2,3 water,4 alcohols,5 thiols,6 phosphines,7 and even
fluoride.8 A large variety of Fischer-type transition-metal
carbenes have been made available using this methodology,
including, alkoxy-,5 thio-,6 and aminocarbenes.3 We have also
recently utilized this method toward the synthesis of a variety of
ortho-metalated iridium aminocarbene derivatives, with the
reaction of [Cp*IrCl2]2 (1) with a terminal alkyne (2) and an
aniline as the nucleophile.
The reaction of 1 with the terminal alkyne 2 and the 2-
aminopyridine 3 afforded an iridium aminocarbene complex of
the type [Cp*Ir(C(NHC5NH3R′)(CH2R))Cl]Cl (4·Cl) in
59−82% yields (Scheme 1). A wide variety of aminopyridines
Scheme 1
In this report, we wish to report our attempt at extending this
methodology to the use of a 2-aminopyridine (3) as the
nucleophile. Two possible products, of structure I or II, may be
expected a priori (Figure 1), and the outcome should be
and terminal alkynes can be employed; the reaction proceeded
smoothly with both aliphatic and aromatic terminal alkynes but
failed to afford aminocarbenes with internal alkynes (dipheny-
lacetylene and prop-1-ynylbenzene), and both electron-with-
drawing and -donating substituents on the 2-aminopyridine can
be tolerated.
The products have all been characterized completely by
spectroscopy, elemental analysis, and, in the case of 4c·Cl, by a
single-crystal X-ray crystallographic study as well; an ORTEP
plot of the cation 4c is shown in Figure 2. Similar iridacycles
which have been structurally characterized include TpPhIr(H)-
(CHNMePy),9a [Ir(H)2{C(Me)NEtPy}(PPh3)2]+,9b and
[Ir(H)2{C(CH2CH2CH2Ph)NMePy}(PPh3)2]+.9c The 1H
NMR spectra of the aminocarbene complexes were charac-
terized by two doublet resonances arising from the diaster-
eotopic CH2 protons and a resonance at ∼242 ppm in the
13C{1H} NMR spectra which is typical for a transition-metal
carbene.
Figure 1. Possible products from the reaction of [Cp*IrCl2]2 (1) with
a terminal alkyne (2) and a 2-aminopyridine (3).
dictated by the feasibility of C−H activation versus ligand
substitution. Literature on transition-metal aminocarbenes
having the aminopyridine moiety is extensive for ruthenium.3
However, there has been much less work carried out with
iridium and that mainly involved double C−H activation of the
corresponding N-alkyl-2-aminopyridines.1a,9
Received: April 17, 2013
© XXXX American Chemical Society
A
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Scheme 3
binding of the alkyne followed displacement of a chloride. The
energetics for this pathway were comparable to that outlined
above and hence could not be confidently excluded, but such a
pathway may not be favored in a relatively nonpolar
environment such as that employed here.
It was also found that 4, which contains a benzylic group α to
the carbene moiety, was susceptible to aerial oxidation to form
complexes 5; those with aliphatic substituents, such as 4c, were
resistant to oxidation under similar conditions (Scheme 4).
These oxidation products have also been characterized
completely; 5e·Cl has been characterized by a single-crystal
X-ray structural study as well.
Figure 2. ORTEP plot (50% probability thermal ellipsoids) showing
the molecular structure of the cation 4c. H atoms are omitted for
clarity.
Scheme 4
The proposed reaction pathway to 4 (Scheme 2) is similar to
that which we have proposed earlier for the ortho-metalated
Scheme 2
In both 4 and 5, the NH proton is expected to be acidic.
Indeed, treatment with triethylamine afforded the neutral
cyclometalated species 6 and 7, respectively (Scheme 3). The
reaction is reversible, as treatment of 6 with HBF4 afforded
t
[Cp*(Cl)IrC(CH2 Bu)NHPy]BF4 (4c·BF4); the chloride
salt, 4c·Cl, could be obtained by treatment with concentrated
HCl.
In addition to 4c·Cl and 5e·Cl, the complexes 4c·BF4, 5g·Cl,
6b, and 7e have also been characterized crystallographically.
Selected bond parameters for the six structures are given in
Table 1.
aminocarbene complexes and differs only in the final step;3j the
Gibbs free energies (in kJ mol−1) for each step have also been
evaluated computationally with DFT and are shown.
The Ir−C(4) bond lengths in the cationic species are
comparable to or shorter than the corresponding bond lengths
in the ortho-metalated aminocarbenes3j and hence are clearly
indicative of IrC double-bond character. The corresponding
bond in the neutral species (6b and 7e) is longer but not
appreciably so, suggesting some double-bond character as well.
Indeed, the C−N bond lengths for all six crystals show similar
variations, suggesting similar delocalization of electrons about
the metallacycles. This is corroborated by the 13C NMR
spectra, which show a distinct downfield peak at ∼225−245
ppm for all of the complexes in this study, both cationic and
neutral. The structures of 5e,g and 7e suggest that the ketone
functionality in these complexes is not conjugated to the
metallacycle; the dihedral angle between the Ir−C(4)−N(3)
and C(4)−CO planes ranges from about 68 to 79°.
However, the infrared spectroscopic data (νCO bands are
1659, 1654, 1653, and 1651 cm−1 for 5e,5g and 7e,g,
respectively, in comparison to 1686 cm−1 in acetophenone)
suggests that in solution there is conjugation.
Deuterium labeling experiments involving phenylactylene-d
with 1 and 2-amino-6-bromopyridine and phenylacetylene with
1 and 2-amino-6-bromopyridine in the presence of D2O
afforded 4e with no deuterium and two deuteriums,
respectively, incorporated at the diastereotopic CH2 protons.
This is consistent with the alkyne−vinylidene rearrangement
from A to B via intermolecular proton transfer with
adventitious water. Nucleophilic attack by the aniline
functionality at the vinylidene α-carbon followed by proton
transfer would afford the aminocarbene intermediate C. From
there, ligand displacement of a chloride by the pyridyl N would
result in 4; the alternative ortho metalation to afford the neutral
aminocarbene 4′ that was observed with aniline3j is energeti-
cally less favorable (Scheme 3). An alternative pathway which
we have also examined computationally involved the formation
of a cationic intermediate early in the pathway, in which
B
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Scheme 5
a
Table 1. Selected Bond Parameters for 4c·Cl, 4c·BF4, 5e,g, 6b, and 7e
a
The two sets of values given for 5e,g are for the two crystallographically independent molecules found in the crystals.
spectrometer. [Cp*IrCl2]2 (1) was prepared according to the
published method.10 Elemental analyses were performed by the
microanalytical laboratory at NTU.
Reaction of 1 with Alkyne and 2-Aminopyridine. In a 50 mL
Carius tube, a dichloroethane solution (5 mL) of [Cp*IrCl2]2 (40 mg,
50 μmol), 3,3-dimethyl-1-butyne (125 μL, 1 mmol), and 2-
aminopyridine (10 mg, 100 μmol) was stirred at 40 °C for 24 h.
The reaction solvent was then removed under reduced pressure,
followed by recrystallization from dichloromethane/diethyl ether to
give pure 4a·Cl (45 mg, 80%).
Aerial Oxidation of 4e·Cl and 4g·Cl. In a 50 mL round-
bottomed flask, 4e·Cl (20 mg, 29.7 μmol) was dissolved in
dichloromethane (5 mL) and hexane (15 mL) and the reaction
mixture was refluxed in the open at 50 °C overnight. The solvent was
then removed under reduced pressure, followed by recrystallization
from dichloromethane/diethyl ether to give pure 5e·Cl (15 mg, 74%).
Reversible Deprotonation of 4. To a solution of 4a·Cl (20 mg,
34.8 μmol) in dichloromethane (5 mL) was added triethylamine (6
μL, 42 μmol), the mixture was stirred at RT room temperature for 15
min and filtered through silica gel, and the solvent was evaporated
under reduced pressure to afford pure 6a. A similar procedure was
used for 6b,c. The reversible protonation of 6c (20 mg, 32.5 μmol) in
dichloromethane (5 mL) with HBF4·OEt2 (5 μL, 39 μmol) afforded
4c·BF4 (22 mg, 96%).
CONCLUSION
■
In this report, we have described a synthetic route to cationic
aminocarbene complexes of iridium(III) by the reaction of 1
with aminopyridines and terminal alkynes. They can undergo
reversible deprotonation at the NH moiety, and those
containing a benzylic group at the metallacycle can readily
undergo aerial oxidation. These are characteristic of electron
delocalization within, and hence aromaticity in, the metallacycle
and is also corroborated by the structural and NMR parameters
for these complexes.
EXPERIMENTAL SECTION
■
General Considerations. All reactions and manipulations, except
for TLC separations, were performed under argon by using standard
Schlenk techniques. All other reagents were from commercial sources
and used without further purification. 1H NMR and 13C NMR spectra
were recorded on a JEOL ECA400 or ECA400-SL NMR spectrometer
as CDCl3 solutions; chemical shifts reported were referenced against
the residual proton signals of the solvent at 7.26 and 77.24 ppm for 1H
and 13C{1H} NMR, respectively. ESI/MS were recorded in EI mode
on a MATLCQ spectrometer. High-resolution mass spectra (HRMS)
were recorded in ESI mode on a Waters UPLC-Q-TOF mass
C
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X-ray Crystallographic Studies. Crystals were grown from
dichloromethane/hexane solutions and mounted on quartz fibers. X-
ray data were collected on a Bruker AXS APEX system, using Mo Kα
radiation, with the SMART suite of programs.11 Data were processed
and corrected for Lorentz and polarization effects with SAINT12 and
for adsorption effects using SADABS.13
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The structures were solved by direct methods to locate the heavy
atoms, followed by difference maps for the light, non-hydrogen atoms.
Hydrogen atoms were placed in calculated positions and refined with a
riding model. There were two formula units per asymmetric unit for
5e·Cl and 5g·Cl. Dichloromethane solvates were found in the crystals
of 4c·Cl, 5e·Cl, and 5g·Cl. For the last two crystals, four sites were
found for the solvates, which were modeled with various occupancies,
and with 5e·Cl, one of the solvates was modeled as disordered with
two alternative positions for one of the Cl atoms. The crystal of 4c·BF4
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t
respectively. The crystal of 6b exhibited disorder of the CH2 Bu group,
which was modeled with two alternative sites with their occupancies
summed to unity. Appropriate restraints on the bond and thermal
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and Lee−Yang−Parr’s gradient-corrected correlation function
(B3LYP).15 The LanL2DZ (Los Alamos effective core potential
double-ζ) basis set together with an f polarization function was
employed for the Ir atom, and the 6-311+G(2d,p) basis set was used
for all other atoms. Spin-restricted calculations were used for geometry
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ASSOCIATED CONTENT
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S
* Supporting Information
Tables, figures, and CIF files giving crystallographic data,
experimental details and characterization data for the
complexes, and optimized geometries of all computed
structures. This material is available free of charge via the
Internet at http://pubs.acs.org.
(10) Ball, R. G.; Graham, A. G.; Heinekey, D. M.; Hoyano, , J. K.;
McMaster, A. D.; Mattson, B. M.; Michel, S. T. Inorg. Chem. 1990, 29,
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(11) SMART version 5.628; Bruker AXS Inc., Madison, WI, 2001.
(12) SAINT+ version 6.22a; Bruker AXS Inc., Madison, WI, 2001.
AUTHOR INFORMATION
■
(13) Sheldrick, G. M. SADABS; University of Gottingen, Gottingen,
̈
̈
Notes
Germany, 1996.
(14) Becke, A. D. J. Chem. Phys. 1993, 98, 568−5652.
The authors declare no competing financial interest.
(15) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B 1998, 37, 785−789.
(16) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.;
Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.;
Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.;
Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J.
B.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev,
O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.;
Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.;
Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.;
Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman,
J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.;
Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.;
Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.;
Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen,
W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03; Gaussian
Inc., Wallingford, CT, 2004.
ACKNOWLEDGMENTS
■
This work was supported by Nanyang Technological University
and the Ministry of Education (Research Grant No.
M4011017). E.K. thanks the university for a Research
Scholarship.
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