Dimerisation, rhodium complex formation and rearrangements of N-heterocyclic carbenes of indazoles

Article abstract of DOI:10.3762/bjoc.10.79

Deprotonation of indazolium salts at low temperatures gives N-heterocyclic carbenes of indazoles (indazol-3-ylidenes) which can be trapped as rhodium complexes (X-ray analysis). In the absence of Rh, the indazol-3-ylidenes spontaneously dimerize under ring cleavage of one of the N,N-bonds and ring closure to an indazoleindole spiro compound which possesses an exocyclic imine group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present results of a single crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating of the indazoleindole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray analysis). Results of DFT calculations are presented.

Full text of DOI:10.3762/bjoc.10.79

Dimerisation, rhodium complex formation
and rearrangements of N-heterocyclic carbenes
of indazoles
Zong Guan1, Jan C. Namyslo1, Martin H. H. Drafz1, Martin Nieger2
and Andreas Schmidt*1
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2014, 10, 832–840.
1Clausthal University of Technology, Institute of Organic Chemistry,
Leibnizstrasse 6, D-38678 Clausthal-Zellerfeld, Germany and
2University of Helsinki, Laboratory of Inorganic Chemistry,
Department of Chemistry, P.O. Box 55 (A.I. Virtasen aukio 1),
FIN-00014 University of Helsinki, Finland
doi:10.3762/bjoc.10.79
Received: 25 January 2014
Accepted: 21 March 2014
Published: 10 April 2014
Email:
Associate Editor: C. Stephenson
Andreas Schmidt* - schmidt@ioc.tu-clausthal.de
© 2014 Guan et al; licensee Beilstein-Institut.
License and terms: see end of document.
* Corresponding author
Keywords:
E/Z isomerism; indazol-3-ylidene; mesomeric betaine; pyrazole;
quinazoline; Rh complex
Abstract
Deprotonation of indazolium salts at low temperatures gives N-heterocyclic carbenes of indazoles (indazol-3-ylidenes) which can
be trapped as rhodium complexes (X-ray analysis). In the absence of Rh, the indazol-3-ylidenes spontaneously dimerize under ring
cleavage of one of the N,N-bonds and ring closure to an indazole–indole spiro compound which possesses an exocyclic imine
group. The E/Z isomers of the imines can be separated by column chromatography when methanol is used as eluent. We present
results of a single crystal X-ray analysis of one of the E-isomers, which equilibrate in solution as well as in the solid state. Heating
of the indazole–indole spiro compounds results in the formation of quinazolines by a ring-cleavage/ring-closure sequence (X-ray
analysis). Results of DFT calculations are presented.
Introduction
As a result of their biochemical and pharmacological signifi- In view of the rapid development of the class of N-heterocyclic
cance, there has been a considerably growing interest in inda- carbenes (NHC) [6-12] it is not unexpected, that attention was
zoles in recent years, which is reflected in several book chap- also directed towards the NHCs of indazole which have been
ters and review articles dealing with syntheses [1-4], synthetic generated and applied in heterocyclic synthesis (vide infra) as
potentials [4], and biological activities [4,5] of this ring system. well as in complex chemistry [13]. Undoubtedly the N-hetero-
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Beilstein J. Org. Chem. 2014, 10, 832–840.
cyclic carbenes of imidazole, imidazoline and the triazoles play
the most important roles as ligands in metal-organic chemistry
[14] or as organocatalysts [15,16]. The N-heterocyclic carbenes
of indazole (and pyrazole [17,18]), however, have a chemistry
of their own which set them apart from the NHCs of the afore-
mentioned ring systems. Portions of that field have been
covered in recent review articles [18,19]. The N-heterocyclic
carbene of indazole 3 has been generated by thermal decarboxy-
lation of indazolium-3-carboxylates 1 [20] which belong to the
class of pseudo-cross-conjugated heterocyclic mesomeric
betaines (Scheme 1). Its properties have been calculated [20,21]
and examined by means of vibrational spectroscopy [21]. It was
shown that pseudo-cross-conjugated mesomeric betaines decar-
boxylate readily in the absence of stabilizing effects such as
hydrogen bonds to protic solvents or water of crystallization
[18,19]. Thus, the Gibbs free energy difference for the decar-
boxylation of 1,2-dimethylindazolium-3-carboxylate under
standard conditions (25 °C, 1 atm) was found to be 3.4 kcal/mol
[20]. Alternatively, indazolium salts 2 can be deprotonated by
various bases to give indazol-3-ylidenes 3 [22].
Scheme 2: Reaction products of indazol-3-ylidenes in heterocycle syn-
thesis.
The chemistry of indazol-3-ylidene, which is a singlet carbene,
is due to the considerable donor strength of the carbene atom
which has a calculated Mulliken charge of 0.009 [20]. More-
over, the ability to cleave the N–N single bond, which was carbene can be trapped by elemental sulfur, isocyanates, and
calculated to have a bond length of 144.6 pm in 1,2-dimethylin- isothiocyanates which form indazolethione 4, indazolium-3-
dazol-3-ylidene [20] (N–N1H-indazole = 138.4 pm [3]) and a amidate 5, and indazolium-3-thioamidate 6, respectively [23]
stretching force constant of 4.23 mdyn Å−1 [21], opens the (Scheme 2). Aliphatic ketones surprisingly give stable 1:1
access to several heterocyclic transformation products (vide adducts 7 [20,24]. α-Bromo acetophenones induce an unex-
infra). Finally, the synthetic potential is governed by the elec- pected ring enlargement to cinnolines 8 [25]. New ring systems
trophilic properties of the iminium group of indazolium salts such as 9 [25] and 10 [26] were prepared on treatment of
which result from protonation of the carbene. As a conse- indazol-3-ylidene with acetylenes.
quence, the synthetic potential of indazol-3-ylidene not only
strongly depends on the choice of potential reaction partners, Indazol-3-ylidenes which possess an aryl ring at N1 rearrange
but also on its substitution pattern and the reaction conditions. to give substituted acridines by a ring-cleavage/pericyclic ring-
As examples, when N1 is substituted with a methyl group, the closure reaction sequence (2→A→B→11) (Scheme 3). It
Scheme 1: Generation of indazol-3-ylidenes.
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Beilstein J. Org. Chem. 2014, 10, 832–840.
Scheme 3: Syntheses of acridines from indazol-3-ylidenes.
proved to be advantageous to start these rearrangements from 14a,c,d, respectively, equilibrated slowly in chloroform solu-
indazolium salts which are readily available by copper- tions to give stable ratios after several days at rt. These results
catalyzed aryl couplings or Buchwald–Hartwig reactions [22]. are summarized in Table 1.
Pyrazol-3-ylidenes rearrange similarly to quinolines [17].
Table 1: Equilibrium between 13a–d and 14a–d in chloroform.
We report here on two unexpected rearrangements of indazol-3-
ylidene, and trapping reactions of the N-heterocyclic carbene
Compounds
Ratioa
Time (d)
with rhodium.
13a/14a
13b/14b
13c/14c
13d/14d
10 : 7
5 : 1
12
2
Results and Discussion
1 : 1
18
9
On trying to deprotonate the indazolium salts 12a–e with potas-
sium 2-methylbutan-2-olate in anhydrous dichloromethane at
−80 °C to the N-heterocyclic carbene I in the absence of trap-
ping reagents we unexpectedly obtained a mixture of two com-
pounds which are in equilibrium, when the reaction was
10 : 9
aRatios determined by 1H NMR spectroscopy in CDCl3 at rt.
allowed to warm to room temperature (Scheme 4). From the The isomers 13a–e and 14a–e gave identical IR spectra, but the
NMR spectra of the mixture it was apparent that neither the NMR spectra differ considerably (Figure 1). In the NMR
3,3'-biindazolylidene II nor its trans isomer had formed, as
signals between δ = 91.7 ppm and 94.0 ppm were detected by
13C NMR spectroscopy which are neither in agreement with
structure II nor with its trans isomer. Mass spectrometric exam-
inations, however, clearly showed the peaks of dimerized
species of the carbene I, because the molecular peaks corres-
pond to twice the mass of the salts 12a–e minus two hydrogen
atoms, respectively. We were able to separate the mixtures of
the reactions of 12a,c,d by column chromatography employing
methanol as eluent, and to characterize the separated species.
The species in equilibrium proved to be spiro[indazole-3,2'-
indolines], the exocyclic imine groups of which form Z- and
E-isomers 13a–e and 14a–e, respectively. The equilibration of
14b is too fast so that a separation of a pure sample failed. The
iodo derivative 13e gave low yields and despite of intense
Figure 1: Diagnostic 1H and 13C NMR chemical shifts of the Z and E
configuration isomer in CDCl3.
efforts we were not able to obtain the compounds in pure form.
Solutions of pure samples of the E/Z-isomers 13a–d and
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Beilstein J. Org. Chem. 2014, 10, 832–840.
Scheme 4: Dimerisation of indazol-3-ylidenes to spiro compounds.
spectra the Z-isomers 13a–e show two distinct methyl groups at The following scheme presents diagnostic peak assignments of
δ = 3.27 ppm and δ = 2.60 ppm in CDCl3, respectively, as well the 1H and 13C NMR spectra, taken at 400 and 100 MHz in
as two different phenyl rings. The methyl groups of the CDCl3, respectively.
isomeric spiro compounds 14a,c,d appear at δ = 3.74 ppm and –
as overlapped signal – at δ = 2.60 ppm in the 1H NMR spectra According to DFT calculations the conversion of 13a to 14a
measured in CDCl3. On conversion of the exocyclic imine requires an activation energy of ΔG# = +79 kJ/mol (ΔE = +89
groups from the Z- into the E-configuration (13 → 14), the kJ/mol) while the two species do not differ in energy (ΔE < 1
methyl groups move from a position above the plane of the kJ/mol). In comparison the inversions of the two nitrogen atoms
indazole ring into a position in the plane of the indole ring. This within the indazole ring (vide infra) require less than 50 kJ/mol.
change from vertical to horizontal interactions of aromatics on Transition with such low activation energies are not inhibited at
the methyl groups explains the considerable downfield shift of room temperature, so the last mentioned inversions are not
their 1H NMR resonance frequencies on Z→E isomerisation. observable in NMR spectra at standard temperature conditions.
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Beilstein J. Org. Chem. 2014, 10, 832–840.
The spiro compound 14c crystallized from a saturated solution equilibrium between the free N-heterocyclic carbene I and its
in n-hexane so that we were able to perform a single crystal dimers II or III. A closer inspection of the structures reveals
X-ray analysis. The compound crystallized monoclinic. As that the intermediary betaines III are representatives of the
expected, neither the pyrrole ring nor the pyrazole ring is planar aforementioned class of pseudo-cross-conjugated heterocyclic
as evidenced by the dihedral angles C9–N10–C11–C16 = mesomeric betaines. Thus the intermediates III are related to
−159.47(12)° and C9–N1–N2–C3 = 15.22(13)° (crystallo- indazolium-3-carboxylates, -amidates, and -thioamidates shown
graphic numbering; Figure 2). The pyramidalization of the in Scheme 1 and Scheme 2. The neutralization of the charges in
nitrogen atoms N1 and N10 cause an anti conformation of the cross-conjugated as well as in pseudo-cross-conjugated
methyl group attached to N1 and the 3-chlorophenyl ring at- mesomeric betaines by inter- or intramolecular cycloadditions
tached to N10. The latter is twisted with respect to the indole are typical reactions [18,19].
moiety [C11–N10–C27–C28 = 41.85(18)°]. As N2 is also pyra-
midalized, the methyl group at N1 and the 3-chlorophenyl ring To prove the initial formation of an N-heterocyclic carbene in
at N2 adopt an anti conformation as well. The exocyclic imine this reaction we tried trapping reactions starting from 12a and
has a bond length of 127.13(17) pm and this value corresponds 12e with carbonylbis(triphenylphosphine)rhodium(I) chloride
to a typical Csp2=N imine bond. Correspondingly, the dihedral under otherwise unchanged reaction conditions. Indeed, stable
angle C16–C17–N18–C19 is only −1.3(2)°. The dihedral angle complexes were formed as yellow crystals in either case which
C15–C16–C17–N18, however, is 6.3(3)° so that the imine were fully characterized (Scheme 5). The carbene atom of 15e
group is slightly twisted out of the plane of the indole´s phenyl was detected at 191.4 ppm by 13C NMR spectroscopy. A com-
ring. In the single crystal of 14c, the imine adopts an E con- parison of the stretching frequencies of the CO ligands (15a:
figuration as already predicted by the NMR investigations.
2009 cm−1, 15e: 1994 cm−1) indicated very strong donor
strengths of these indazol-3-ylidenes as already postulated
earlier on comparing different stretching frequencies of selected
5-membered NHCs [27] or 13C NMR resonance frequencies of
several palladium carbene complexes [28].
Figure 2: Molecular structure of 14c, displacement parameters are
drawn at 50% probability level.
Scheme 5: Rhodium complex formation.
The mechanism of this new rearrangement can be either postu-
lated by dimerization of the N-heterocyclic carbene I to give II
followed by ring-cleavage of one of the indazole rings to III We were able to obtain single crystals of 15e to perform an
(pathways A and C, Scheme 4), or as nucleophilic attack of the X-ray analysis (Figure 3). Suitable single crystals were obtained
carbene I to the iminium group of the salts 12a–e followed by by slow evaporation of a concentrated solution in
ring-cleavage and deprotonation to give betaine III (pathway dichloromethane/iPrOH. The complex crystallized monoclinic.
B). As a matter of fact, cross-experiments between 13a and the The Rh–Ccarbene and Rh–CCO bond lengths [Rh1–C1 and
chlorophenyl derivative 13b failed in refluxing THF for 4 h as Rh1–C10; crystallographic numbering] were determined to be
well as in refluxing chloroform under irradiation for 8 h, as no 206.0(2) pm and 186.3(3) pm, respectively. The p-iodophenyl
monochloro compound was detectable. Obviously, once the substituent is twisted by −50.7(4)° from the plane of the inda-
dimerized species is formed under these conditions, there is no zole ring [C4–N2–C1–C53].
836

Beilstein J. Org. Chem. 2014, 10, 832–840.
1,7-H-shift from the mesomeric betaine III, followed by ring
cleavage of the indazole ring and subsequent ring-closure of the
resulting 1,6-dipole to give the quinazolines 16a–d.
Single crystals of 16b suitable for an X-ray analysis were
obtained by slow evaporation of a saturated solution in
methanol. This compound crystallized monoclinic. A molec-
ular structure is shown in Figure 4. In the single crystal the NH
group of the aniline (N18–H) forms a hydrogen bond to the
imine group (N25) so that an almost planar six-membered ring
is formed. The dihedral angle C11–C12–C17–N18 (crystallo-
graphic numbering) was determined to be 0.5(2)°. This six-
membered ring is almost perpendicularly twisted in relation to
the quinazoline ring [N1–C10–C11–C12 = −92.65(17)°].
Figure 3: Structure of the cation of 15e, displacement parameters are
drawn at 50% probability level.
Another type of rearrangement occurred on heating the dimer-
ized carbenes 13a–d/14a–d in xylene, as the substituted quina-
zolines 16a–d were isolated in reasonable yields (Scheme 6).
The mechanism can be rationalized by formation of an ylide by
Figure 4: Molecular structure of 16b, displacement parameters are
drawn at 50% probability level.
Scheme 6: Rearrangement of the spiro compounds on heating.
837

Beilstein J. Org. Chem. 2014, 10, 832–840.
Conclusion
remaining degrees of freedom. Torsion angles were modified in
The N-heterocyclic carbene of indazole, indazol-3-ylidene, steps of 10°.
displays a chemistry of its own which differs from the chem-
istry of N-heterocyclic carbenes of other ring systems. At low Thermodynamic corrections were estimated from unscaled
temperatures it can be trapped as a rhodium complex. Without frequencies, using standard formulae in the ideal gas harmonic
trapping reagents it dimerizes under ring-cleavage to form two oscillator approximation as implemented in Jaguar, and refer to
isomeric spiro compounds possessing E- and Z-configurated a standard state of 298.15 K and 1 mol/dm3 concentration.
methylimine groups. Heating of the carbene dimer results in the
Crystal structure determinations of 14c, 15e,
formation of novel quinazolines.
16b
Experimental
The single-crystal X-ray diffraction study was carried out on a
General considerations: All reactions for the dimerisation and Bruker-Nonius Kappa-CCD at 123(2) K using MoKα radiation
the rearrangement were carried out under an atmosphere of (λ = 0.71073 Å). Direct Methods (SHELXS-97) [30] were used
nitrogen in oven-dried glassware. Flash-chromatography was for structure solution and refinement was carried out using
performed with silica gel 60 (0.040–0.063 mm). Nuclear SHELXL-2013 [30] (full-matrix least-squares on F2). Hydrogen
magnetic resonance (NMR) spectra were obtained with a atoms were localized by difference electron density determin-
Bruker Avance 400 and Bruker Avance III 600 MHz. 1H NMR ation and refined using a riding model (H(N) free). Semi-empir-
spectra were recorded at 400 MHz or 600 MHz. 13C NMR ical absorption corrections were applied. In 15e one of the 3
spectra were recorded at 100 MHz or 150 MHz, with the solvent molecules CH2Cl2 is disordered. For more information
solvent peak or tetramethylsilane used as the internal reference. see the Supporting Information File 1.
Multiplicities are described by using the following abbrevia-
tions: s = singlet, d = doublet, t = triplet, q = quartet, and m = 14c: yellow, C25H22Cl2N4, M = 485.39, crystal size 0.45 × 0.25
multiplet. FTIR spectra were obtained on a Bruker Vector 22 in × 0.15 mm, monoclinic, space group P21/c (no. 14): a =
the range of 400 to 4000 cm−1. The mass spectra were 13.522(1) Å, b = 14.131(1) Å, c = 12.306(1) Å, β = 94.16(1)°, V
measured with a Varian 320 MS Triple Quad GC–MS/MS with = 2345.2(3) Å3, Z = 4, ρ(calc) = 1.375 Mg m−3, F(000) = 1008,
a Varian 450-GC. The electrospray ionization mass spectra µ = 0.302 mm−1, 38867 reflections (2θmax = 55°), 5367 unique
(ESIMS) were measured with an Agilent LCMSD series HP [Rint = 0.028], 309 parameters, R1 (for 4546 I > 2σ(I)) = 0.032,
1100 with APIES. Melting points are uncorrected and were wR2 (all data) = 0.086, GOOF = 1.05, largest diff. peak and
determined in an apparatus according to Dr. Tottoli (Büchi). hole 0.339 / −0.294 e Å−3.
The HRMS spectra were measured on a Bruker Daltonik Tesla-
Fourier transform-ion cyclotron resonance mass spectrometer 15e: yellow, C51H41IN2OP2Rh+ –PF6− · 3CH2Cl2, M =
with electrospray ionisation. Yields are not optimized. Com- 1389.36, crystal size 0.35 × 0.25 × 0.15 mm, monoclinic, space
pounds 12a, 12b, 12c and 12e were described in an earlier group P21/n (no. 14): a = 14.314(1) Å, b = 26.691(2) Å, c =
publication [22]. 1-(4-Bromophenyl)-1H-indazole was prepared 15.045(1) Å, β = 99.43(1)°, V = 5670.3(7) Å3, Z = 4, ρ(calc) =
by the method B which we described earlier [22] and was 1.627 Mg m−3, F(000) = 2768, µ = 1.273 mm−1, 91339 reflec-
isolated in better yield (85%) than in the literature (40%) [29]. tions (2θmax = 55°), 12976 unique [Rint = 0.021], 685 parame-
All density-functional theory (DFT)-calculations were carried ters, 70 restraints, R1 (for 11838 I > 2σ(I)) = 0.032, wR2 (all
out by using the Jaguar 7.7.107 software running on Linux data) = 0.086, GOOF = 1.09, largest diff. peak and hole
2.6.18-238.el5 SMP (x86_64) on two AMD Phenom II X6 1.473/−1.377 e Å−3.
1090T processor workstations (Beowulf-cluster) parallelized
with OpenMPI 1.3.4. MM2 optimized structures were used as 16b: colourless, C28H22Cl2N4, M = 485.39, crystal size 0.30 ×
starting geometries. Complete geometry optimizations were 0.24 × 0.06 mm, monoclinic, space group P21/n (no. 14): a =
carried out on the implemented LACVP* (Hay–Wadt effective 14.690(1) Å, b = 7.488(1) Å, c = 21.484(2) Å, β = 90.75(1)°, V
core potential (ECP) basis on heavy atoms, N31G6* for all = 2363.0(4) Å3, Z = 4, ρ(calc) = 1.364 Mg m−3, F(000) = 1008,
other atoms) basis set and with the B3LYP density functional. µ = 0.300 mm−1, 36379 reflections (2θmax = 55°), 5408 unique
All calculated structures were proven to be true minima by the [Rint = 0.034], 311 parameters, 1 restraints, R1 (for 4414 I >
absence of imaginary frequencies or transition states by the 2σ(I)) = 0.040, wR2 (all data) = 0.093, GOOF = 1.05, largest
occurrence of one negative frequency. Plots were obtained diff. peak and hole 0.325/−0.278 e Å−3.
using Maestro 9.1.207, the graphical interface of Jaguar. Inver-
sion barriers have been calculated fully relaxed, fixating one Crystallographic data (excluding structure factors) for the struc-
torsion angle around the inverted center, and optimizing all tures reported in this work have been deposited with the
838

Beilstein J. Org. Chem. 2014, 10, 832–840.
Cambridge Crystallographic Data Centre as supplementary 697, 681, 480 cm−1; ESIMS: m/z (%) = 417 [M + H+];
publication no. CCDC-972482 (14c), CCDC-972481 (15e), and HRESIMS: C28H25N4 calcd for 417.2079; found: 417.2075.
CCDC-972483 (16b). Copies of the data can be obtained free of
General procedure for the preparation of the
charge on application to The Director, CCDC, 12 Union Road,
Cambridge DB2 1EZ, UK (Fax: int.code+(1223)336-033; rhodium complexes 15
e-mail: deposit@ccdc.cam.ac.uk).
A solution of 0.2 mmol of the indazolium salts 12a
and 12e, respectively, and 0.2 mmol of carbonylbis(triph-
enylphosphine)rhodium(I) chloride in 20 mL of THF was
cooled to −80 °C. Then, 0.1 mL of a 2 M solution of potassium
General procedure for the preparation of the
indazole carbene dimers 13/14
A solution of 2.0 mmol of the indazolium salts 12a–e in 20 mL 2-methylbutan-2-olate in THF was added dropwise. The reac-
of dichloromethane was cooled to −80 °C. Then 1.2 mL of a tion mixture was then stirred overnight at room temperature.
2 M solution of potassium 2-methylbutan-2-olate in THF was Yellow solids formed which were filtered off, washed with
added dropwise within 30 minutes. The reaction mixture was 2 mL of ethylacetate, and dried in vacuo.
then evaporated to dryness and extracted twice with 20 mL of
Carbonyl-bis(triphenylphosphine)(2-methyl-1-
petroleum ether, respectively. After evaporation of the solvent
phenyl-1H-indazole-3-ylidene)rhodium(I)
hexafluorophosphate (15a)
in vacuo the crude reaction product was purified by flash
column chromatography (silica gel; methanol) and dried in
vacuo. The isomers 13 and 14 have Rf values of approximately
0.4 and 0.2 on silica gel in MeOH, respectively.
Yield: 73 mg (36%) of yellow crystals; dec. 240 °C; 1H NMR
(400 MHz, DMSO-d6) δ 7.67 (d, J = 8.3 Hz, 1H), 7.62–7.60 (m,
3H), 7.56–7.39 (m, 31H), 7.04–6.97 (m, 3H), 6.77 (d, J = 8.3
Hz, 1H), 3.23 (s, 3H) ppm; 13C NMR (150 MHz, DMSO-d6) δ
139.2, 133.5 (t, J = 6.0 Hz), 132.4 (t, J = 23.0 Hz), 132.3, 132.1,
131.0, 130.9, 130.3, 128.9 (t, J = 4.3 Hz), 128.7, 127.7, 126.2,
(Z)-N-(2-Methyl-1,1'-diphenyl-1,2-dihy-
drospiro[indazole-3,2'-indolin]-3'-
ylidene)methanamine (13a)
Yield: 152 mg (37%) of a yellow solid; mp 74–75 °C; 1H NMR 122.2, 109.6, 40.2 ppm; IR (ATR): 2009, 1498, 1479, 1436,
(400 MHz, CDCl3) δ 7.68 (dd, J = 7.5, 0.6 Hz, Ar-H, 1H), 1308, 1095, 861, 833, 741, 641, 557, 498 cm−1; ESIMS: m/z
7.29–7.25 (m, 2H, Ar-H), 7.23–7.06 (m, 9H, Ar-H), 6.96 (dd, J (%) = 863 [M +]; HRESIMS: C51H42N2OP2Rh calcd for
= 8.6, 1.2 Hz, 2H, Ar-H), 6.89–6.83 (m, 2H, Ar-H), 6.71 (d, J = 863.1827; found: 863.1827.
8.1 Hz, 1H, Ar-H), 6.58 (d, J = 8.1 Hz, 1H, Ar-H), 3.27 (s, 3H,
General procedure for the rearrangements of
the indazole carbene dimers to 16
CH3), 2.60 (s, 3H, CH3) ppm; 13C NMR (100 MHz, CDCl3) δ
166.5, 153.5, 149.0, 145.8, 140.7, 133.0, 129.4, 129.1, 129.0,
127.6, 125.8, 125.7, 124.9, 124.5, 123.7, 123.5, 122.5, 121.9,
119.2, 110.1, 109.5, 91.8, 39.8, 35.1 ppm; IR (ATR): 3051,
2952, 2891, 2855, 1655, 1605, 1590, 1450, 1354, 1312, 1271,
1191, 1151, 1000, 922, 856, 697, 681, 480 cm−1; ESIMS: m/z
(%) = 417 [M + H+]; HRESIMS: C28H25N4 calcd for 417.2079;
found: 417.2075.
A solution of 1.0 mmol of the dimers of the indazole carbenes
13a/13b/13d in 20 mL of xylene was stirred at reflux
temperature for 3 hours. After the solvent was distilled off in
vacuo, the crude product was purified by flash column chroma-
tography (petroleum ether: ethyl acetate = 3:1) and dried in
vacuo.
(E)-N-(2-Methyl-1,1'-diphenyl-1,2-dihy-
2-((Methylimino)(1-phenyl-1,2-dihydroquina-
drospiro[indazole-3,2'-indolin]-3'-
zolin-4-yl)methyl)-N-phenylaniline 16a
ylidene)methanamine 14a
Yield 233 mg (56%) of yellow crystals; mp 146–147 °C. 1H
NMR (400 MHz, CDCl3) δ 11.74 (bs, 1H, NH), 7.46–7.42 (m,
2H, Ar-H), 7.38–7.28 (m, 8H, Ar-H), 7.24–7.16 (m, 3H, Ar-H),
7.11–7.05 (m, 2H, Ar-H), 6.97 (d, J = 8.3 Hz, 1H, Ar-H), 6.77
(t, J = 7.6 Hz, 1H, Ar-H), 6.65 (t, J = 7.6 Hz, 1H, Ar-H), 5.51
(s, 2H, CH2), 3.41 (s, 3H, CH3) ppm; 13C NMR (100 MHz,
CDCl3) δ 169.4, 164.6, 146.7, 145.1, 144.1, 141.8, 133.3,
132.1, 129.7, 129.4, 127.3, 124.9, 123.5, 122.8, 122.2, 120.1,
119.2, 118.6, 116.9, 116.0, 114.0, 66.6, 40.1 ppm; IR (ATR):
3025, 2968, 2856, 1714, 1589, 1524, 1482, 1448, 1319, 1174,
740, 693, 638, 518 cm−1. ESIMS: m/z (%) = 417 [M + H+].
HRESIMS: C28H25N4 calcd for 417.2079; found: 417.2080.
Yield: 106 mg (25%) of a yellow solid; mp 79–80 °C; 1H NMR
(400 MHz, CDCl3) δ 7.81 (d, J = 7.5 Hz, 1H, Ar-H), 7.30–7.27
(m, 1H, Ar-H), 7.25–7.21 (m, 2H, Ar-H), 7.19–7.13 (m, 6H,
Ar-H), 7.10–7.06 (m, 2H, Ar-H), 6.97–6.95 (m, 2H, Ar-H), 6.91
(ddd, J = 7.4, 7.4, 0.8 Hz, 1H, Ar-H), 6.83–6.77 (m, 2H, Ar-H),
6.62 (d, J = 8.0 Hz, 1H, Ar-H), 3.75 (s, 3H, CH3), 2.59 (s, 3H,
CH3) ppm; 13C NMR (100 MHz, CDCl3) δ 168.1, 155.3, 149.1,
147.0, 140.2, 133.2, 129.4, 129.0, 128.9, 128.8, 128.1, 127.7,
126.1, 125.3, 124.3, 123.8, 121.8, 118.3, 118.1, 111.1, 109.6,
93.8, 40.7, 35.8 ppm; IR (ATR): 3034, 2950, 2888, 2858, 1655,
1605, 1590, 1450, 1355, 1312, 1272, 1192, 1152, 999, 921, 857,
839

Beilstein J. Org. Chem. 2014, 10, 832–840.
20.Schmidt, A.; Merkel, L.; Eisfeld, W. Eur. J. Org. Chem. 2005,
2124–2130. doi:10.1002/ejoc.200500032
Supporting Information
21.Schmidt, A.; Snovydovych, B.; Casado, J.; Quirante, J. J.;
López Navarrete, J. T.; Ramírez, F. J. Phys. Chem. Chem. Phys. 2009,
11, 341–348. doi:10.1039/b812597j
Supporting Information File 1
Synthetic procedures, characterization data, X-ray data and
NMR spectra.
22.Guan, Z.; Wiechmann, S.; Drafz, M.; Hübner, E.; Schmidt, A.
Org. Biomol. Chem. 2013, 11, 3558–3567. doi:10.1039/c3ob40379c
23.Schmidt, A.; Beutler, A.; Habeck, T.; Mordhorst, T.; Snovydovych, B.
Synthesis 2006, 1882–1894. doi:10.1055/s-2006-942367
24.Schmidt, A.; Habeck, T.; Snovydovych, B.; Eisfeld, W. Org. Lett. 2007,
9, 3515–3518. doi:10.1021/ol0713739
[http://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-10-79-S1.pdf]
Acknowledgements
Dr. Gerald Dräger, University of Hannover, Germany, is thank-
25.Schmidt, A.; Snovydovych, B.; Gjikaj, M. Synthesis 2008, 2798–2804.
doi:10.1055/s-2008-1067215
26.Schmidt, A.; Snovydovych, B.; Hemmen, S. Eur. J. Org. Chem. 2008,
4313–4320. doi:10.1002/ejoc.200800456
fully acknowledged for measuring the HRESIMS spectra.
27.Jothibasu, R.; Huynh, H. V. Chem. Commun. 2010, 46, 2986–2988.
doi:10.1039/b925977e
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