Synthesis and structure elucidation of allyl Pd(II) complexes of NHC ligands derived from substituted imidazo[1,5-a]quinolin-1(2H)-ylidene

Article abstract of DOI:10.1016/j.jorganchem.2017.09.036

Nine Pd(II) complexes involving N-heterocyclic carbenes (NHCs) derived from 2-substituted and 2- and 7-substituted imidazo[1,5-a]quinolin-1(2H)-ylidene with auxiliary allylic ligands were synthesized and characterized. The structure and configuration of the complexes were elucidated on the basis of combination of dynamic NMR and DFT studies. Conformational studies in respect of hindered rotation around Pd-C bond and η³-η¹-η³ pseudo allyl rotation were performed. The results from dynamic NMR and DFT studies confirmed the mechanism of selective η³-η¹-η³ isomerization, whose energy barriers are affected by steric hindrance of substituents at nitrogen atom. Energy barriers of isomerization (16.7–18.8 kcal/mol) are slightly influenced by the electronic nature of substituents at seventh position in imidazo[1,5-a]quinolin-1(2H)-ylidene moiety. The results from DFT calculations were in good agreement with the experimental energy barriers.

Full text of DOI:10.1016/j.jorganchem.2017.09.036

Accepted Manuscript
Synthesis and structure elucidation of allyl Pd(II) complexes of NHC ligands derived
from substituted imidazo[1,5-a]quinolin-1(2H)-ylidene
Rumen Lyapchev, Petar Petrov, Miroslav Dangalov, Nikolay G. Vassilev
PII:
S0022-328X(17)30556-9
10.1016/j.jorganchem.2017.09.036
JOM 20111
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 6 July 2017
Revised Date: 13 September 2017
Accepted Date: 22 September 2017
Please cite this article as: R. Lyapchev, P. Petrov, M. Dangalov, N.G. Vassilev, Synthesis
and structure elucidation of allyl Pd(II) complexes of NHC ligands derived from substituted
imidazo[1,5-a]quinolin-1(2H)-ylidene, Journal of Organometallic Chemistry (2017), doi: 10.1016/
j.jorganchem.2017.09.036.
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ACCEPTED MANUSCRIPT
Synthesis and Structure elucidation of Allyl Pd(II) Complexes of NHC
Ligands Derived from Substituted Imidazo[1,5-a]quinolin-1(2H)-ylidene
Rumen Lyapchev a, Petar Petrov a, Miroslav Dangalov b, Nikolay G. Vassilev b,*
a Department of Organic Chemistry, Faculty of Chemistry and Pharmacy, Sofia University St. Kliment Ohridsky,
1, James Bourchier Blvd., 1164, Sofia, Bulgaria
b Institute of Organic Chemistry with Center of Phytochemistry, Bulgarian Academy of Sciences, Acad. G.
Bonchev Str. Bl. 9, 1113 Sofia, Bulgaria
ABSTRACT: Nine Pd(II) complexes involving N-heterocyclic carbenes (NHCs) derived from 2-substituted and
2- and 7-substituted imidazo[1,5-a]quinolin-1(2H)-ylidene with auxiliary allylic ligands were synthesized and
characterized. The structure and configuration of the complexes were elucidated on the basis of combination of
dynamic NMR and DFT studies. Conformational studies in respect of hindered rotation around Pd-C bond and
η3-η1-η3 pseudo allyl rotation were performed. The results from dynamic NMR and DFT studies confirmed the
mechanism of selective η3-η1-η3 isomerization, whose energy barriers are affected by steric hindrance of
substituents at nitrogen atom. Energy barriers of isomerization (16.7 – 18.8 kcal/mol) are slightly influenced by
the electronic nature of substituents at seventh position in imidazo[1,5-a]quinolin-1(2H)-ylidene moiety. The
results from DFT calculations were in good agreement with the experimental energy barriers.
Keywords: NHC, Palladium, Allyl Complexes, Dynamic NMR Spectroscopy, DFT calculations
1. Introduction
N-heterocyclic carbenes (NHC) are state of the art ligands in organometallic chemistry [1-6] and
catalysis [7-11]. The nitrogen atoms in the heterocycle offer possibilities for tuning of the ligand structure;
through change in the N substituents, steric demands and electronic properties of the ligand can be modified to
provide complexes with enhanced catalytic performances [12-15]. The extension of aromatic system by
annulation of imidazole-2-yliden moiety provides another possibility for tuning of electronic and steric
properties of NHC ligands. Polyaromatic-fused NHCs derivative of phenanthrene [16], acenaphtene [17], pyrene
[18], heterocycles [19-21] demonstrate fertile catalytic properties and interesting photophysical features [22-24].
Various functional groups can be introduced, resulting in complexes with wider applications [25, 26]. The
introduction of a suitable donor group can lead to versatile structures in ditopic complexes or enhanced catalytic
* Corresponding author. Tel.: +359 2 9606172; fax: +359 2 8700225
E-mail: niki@orgchm.bas.bg (N. G. Vassilev)
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performance of complexes with hemilabile ligands [27-32]. In addition, complexes of bifunctional ligands can be
immobilized or their solubilities altered by suitable functionalization to afford recoverable catalysts [33-37].
O
n-Bu
O
N
N
N
R2
R1
N
N
n-Bu
R
Pd
Cl
Pd
Cl
previous work
R3 this work
Scheme 1. Structures of η3-allyl palladium complexes with fused NHC ligands
As part of our current research interests we report the preparation of novel N-heterocyclic carbene
ligands fused with quinolin moiety (Scheme 1). The focus of this work is the synthesis and full characterization
of palladium NHC complexes derived from substituted imidazo[1,5-a]quinolin-1(2H)-ylidene with auxiliary
allylic ligands. Organometallic η3-allyl complexes are characterized by fluxional behaviour in solution which has
been studied for more than 40 years [38, 39] and it may be substantially affected by the electronic or steric
properties of ligands. Three principal scenarios might be distinguished with participation of NHC ligands (Fig.
1). The first one involves exchange of syn and anti-proton positioning from the allyl moiety, which operates
through π−σ−π (η3−η1−η3) mechanism [40-42]. The second one is an allyl rotation [43, 44], which exchanges
the syn-syn protons on the one side and anti-anti protons on the other side and has an alias “syn-syn, anti-anti
exchange”. The third possibility is a rotation around the NHC-metal bond, which, if hindered may give raise to
pairs of rotamers [15, 45-47].
Figure 1. The three possible mechanisms of allyl fluxuanality and corresponding exchanges in 1H NMR spectra:
(A) η3-η1-η3 (π-σ-π) allyl rearrangement, (B) allyl rotation and (C) rotation around the Pd-Ccarbene bond.
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Preliminary results obtained in our research group led to design and synthesis of unsymmetrical N-
heterocyclic carbene-fused benzoimidazoisoquinoline and their η3-allyl palladium complexes, which
demonstrate dynamic behaviour in solution governed by hindered rotation around the M-Ccarbene bond. All new
synthesized complexes 1-9 (Fig. 2) also show fluxionality occurred in solution at rates that were slow on the
NMR time scale. In order to elucidate the NMR spectra, to find out the exchange routes and the origin of the
observed exchanges, the complexes were studied by combination of dynamic NMR and DFT calculations. This
protocol including combination of dynamic NMR spectroscopy and DFT calculation was successfully applied
recently for studying the structure and exchange mechanism of hindered rotation along the M-Ccarbene bond for
M(NHC)(η3-R-allyl)Cl] complexes [47]; also for ortho-diphenylphosphinobenzenecarboxamide ligands [40] and
atropisomers of 2,20 -diaryl-1,10 -binaphthalenes containing three stereogenic axes [41].
Figure 2. Molecular structure of studied complexes 1-10 and designation of H and C atoms.
2. Results and Discussion
2.1. Synthesis of imidazoquinolinium salts.
The synthesis of imidazoquinolinium salts is depicted in Scheme 2. It was carried out in several stages.
Firstly were synthesized quinolines a1-3 [48], bearing different substituents in their sixth position affecting the
quinoline structure by electronic effects. The prepared quinolines were brominated with NBS. For this step of the
synthesis photochemical [49, 50] and thermal activation [51, 52] were tested. The thermally activated reactions
required less dilution, they are more convenient and resulted in higher yields, so they were preferred. 2-
bromomethylquinolines b1-3 were reacted directly with an excess of n-butyl- or tert-butylamine in inert solvent
at room temperature and amines c1-5 were obtained in virtually pure form. They are unstable in air - that's why
c1-5 were formylated with a solution of the mixed anhydride [53] to formamides d1-5 immediately after
isolation without further purification. The same approach has proved unsuitable to provide the formamides with
adamantyl and 2,6-diisopropyl substituent, and the corresponding formamides d6-8 were prepared by reaction of
bromomethylquinoline and N-adamantyl or N-(2,6-diisopropylphenyl)formamide, in the presence of sodium
hydride [54] at room temperature. The reactions involving N-adamantylformamide proceed slowly at room
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temperature,; increasing of the temperature led to formation of difficult to remove byproducts. The resulting N-
quinolinylmethylformamides d1-8 were cyclized [54, 55] by phosphorous oxychloride under anhydrous
conditions. The resulting imidazoquinolinium salts e1-8 were treated in aqueous solution with ammonium
tetrafluoroborate or potassium hexafluorophosphate in order to enhance their solubility in organic solvents.
Scheme 2. Synthesis of imidazoquinolinium salts. Conditions: i - NBS in C6H6 or CCl4 (R1 = H, MeO, F), reflux;
ii-R2NH2 in Et2O or CH3CN (R2 = n-Bu, tert-Bu), room temperature; iii – R2NHCHO/NaH in THF, room
temperature (R2 = Ad, dipp); iv- HCOOH/(CH3CO)2O in THF, room temperature; v – 1) POCl3 in toluene, 80oC;
2) NH4BF4 or KPF6 in water (X = BF4, PF6).
2.2. Synthesis of allyl Pd(II) NHC complexes
The synthesis of allyl complexes 1-9 is depicted in Scheme 3. The corresponding imidazoquinolinium
salt e1-8 was deprotonated with K2CO3 in situ and the resulting free N-heterocyclic carbene was trapped with a
suitable dimeric η3-allyl palladium complex [56]. The use of weak base provides mild conditions, low
concentration of free carbene and does not lead to degradation of the dimeric allyl complex at room temperature
- heating led to the formation of palladium black. Complex 10 was not obtained (R1 = CH3O, R2 = 2,6-
diisopropylphenyl), because it and its corresponding imidazoquinolinium salt are unstable on silica gel, which
makes the monitoring of the reaction and purification of the product impossible.
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Scheme 3. Synthesis of allyl complexes.
2.3. Structure elucidation of allyl Pd(II) NHC complexes
1
The H and 13C spectra of all nine new complexes 1-9 show two sets of signals for every inequivalent
nuclei in the ratios 1 : (0.65 ÷ 0.95), all lines seem comparatively sharp at room temperature. 2D 1H-1H NOESY
and ROESY spectra reveal exchange between two isomers. The assignment of chemical shifts of hydrogen and
carbon for η3-allyl signals were performed using the obtained NMR data, together with literature data [42, 57-59]
and the magnitudes of JHH coupling in allyl moiety. All 8 complexes with η3-(C4H7) structure fragment exhibit
ABCD spin pattern, excluding complex 9, which η3-(C3H5) structure fragment demonstrates ABCDX spin
system. As in other allylic systems, syn-protons are arranged at higher frequency than anti ones [60]. The syn
protons (pseudo-trans towards carbene) are more deshielded and shift to a higher frequency, compared to all
other allyl protons, due to stronger trans effect of the carbene ligand than Cl; analogous results were observed
for the corresponding carbon signals (Fig. 2, Table 1.). Carbene carbon signals were assigned from their three
bond correlation with the allyl pseudo-trans anti-protons in the HMBC spectrum. The carbene signals fall in the
range of 172-177 ppm, which is comparable with chemical shifts of carbene carbon for unsaturated NHC [61,
62]. The substituents at 7th position, with different electronic effects (H; -OMe; F), in imidazo[1,5-a]quinolin-
1(2H)-ylidene moiety have no significantly influence on chemical shifts of carbene carbon.
Table 1. Selected lH and 13C NMR chemical shifts of the studied η3-allyl complexes.
1H
13C
Complex
HsC
HaC
HsCl
HaCl
ap
CC
CCl
Cmeso
ap
CNHC
ap
sp
ap
sp
ap
sp
ap
sp
sp
ap
sp
ap
sp
sp
1
2
3
4
5
6
7
8
9
4.26
4.24
4.23
4.19
4.22
4.21
4.19
3.92
4.34
4.19
4.18
4.17
4.14
4.17
4.18
4.17
4.06
4.13
3.29
3.28
3.35
3.32
3.34
3.48
3.46
3.23
3.03
3.44
3.42
3.48
3.44
3.44
3.34
3.33
2.82
3.42
3.16
3.15
3.11
3.08
3.11
3.08
3.07
2.98
3.45
3.16
3.15
3.07
3.04
3.07
3.01
2.99
3.17
3.34
2.38
2.37
2.25
2.22
2.24
2.38
2.36
2.33
1.66
2.41
2.39
2.41
2.37
2.38
2.25
2.24
1.62
2.50
70.9
70.8
69.6
69.6
69.8
69.3
69.4
70.2
73.1
70.3
70.2
68.7
68.7
69.0
68.8
68.8
71.5
70.3
50.3
50.4
51.8
51.4
51.8
51.8
51.6
50.0
50.2
50.5
50.5
51.7
51.6
51.7
51.8
51.6
50.1
50.9
130.0
130.1
129.5
129.3
129.5
129.9
128.8
129.0
114.2
128.7
129.0
128.8
128.9
128.9
129.8
128.7
129.3
113.6
173.7
171.8
172.7
171.9
173.3
172.3
171.3
178.0
176.8
173.7
171.8
172.6
171.8
173.2
172.6
171.1
177.5
176.7
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The molecular structures of all complexes in solution are governed by chemical exchange which
determines the presence of two conformers, evident by two sets of 1H and 13C signals (see Supp. Info). At room
temperature the signals are still well resolved in contrast with the intermediate chemical exchange in spectra of
previously reported Pd complexes of NHC ligands derived from substituted 1,8-naphtalimides [47]. The
intermediate chemical exchange was observed at 50°C and resulted in broad and not well-resolved signals. The
attempt to reach the fast exchange limit in C2D2Cl4 provokes sample decomposition at 80°C.
Experimental assignment of major and minor signals as synperiplanar (sp) and antiperiplanar (ap)
conformers was performed using observed ROE effects in measured ROESY spectra of studied complexes at
slow exchange. Sp and ap conformers differ in orientation of R3 substituent in respect to the quinolin moiety.
Therefore the observed ROE between H-9 and CH3(or H)-meso-allyl signals in only one of the conformers,
which confirms the sp assignment of the conformer. In this way the major species for 1-5 were assigned as sp
conformers. Typical ROE between H-9 and CH3-meso-allyl signals of major conformer was presented in Fig. 3.
According to the observed ROE in 6-7 minor species, they were assigned as sp conformers. The observed ROE
between H-9 and CH3(or H)-meso-allyl signals in the major species of 8-9 prove their sp assignment.
Calculated and experimental thermodynamic parameters at standard conditions are compared in Table
1
11S. Experimental data for complexes 1-9 were acquired based on VT H NMR spectra in chloroform-d1 and
were evaluated using the Van't Hoff equation (Tables 1-3S, 2-3S, 3-3S, 4-3S, 5-3S, 6-3S, 7-3S, 8-3S and 9-3S).
Calculated relative enthalpy values for particular conformers at B3LYP/ECP (LanL2DZ for Pd and 6-
31G* for other atoms) level including SMD exhibit almost correct tendency for all investigated complexes 1–9
(Table 11S) except for complexes 3, 5-7, in which the predicted relative enthalpy has false sign. Seeing that the
enthalpy differences are very low (0.01 – 0.56 kcal mol-1), the differences in entropy may play significant role on
the position of final thermodynamic equilibrium. Trends in entropy were correctly predicted for complexes 1 and
2 only. The final ∆G° values accumulate computational errors both in enthalpy and in entropy and the population
distributions were predicted satisfactory only for complexes 1, 2 and 9.
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Figure 3. 2D ROESY spectrum of complex 1 in CDCl3 at 263K using mixing time of 0.6 s showing correlation
between H-9 and CH3-meso-allyl signal in major(sp) conformer.
The DFT calculations can help in the conformers assignment by predicting the populations and NMR
chemical shifts of sp and ap conformers of studied complexes. Unfortunately the experimental populations are
close to 1 to 1 and the DFT calculations at the chosen level of theory were not so precise to reproduce them
(Table 11S). The difference in chemical shifts in sp and ap conformers were of order of the expected errors
1
(recent estimate at higher level of theory of mean absolute error values: <0.2 ppm for H resonances and <~6.0
ppm for 13C resonances [63]) in DFT predicted NMR chemical shifts (Table 2). Nevertheless the trend of shifting
the H-9 resonances, which are most sensitive to allyl rearrangement, depending on sp/ap allyl arrangement was
correctly predicted for all studied complexes except complex 8. Either DFT calculated population or DFT
calculated chemical shifts cannot undoubtedly prove the sp and ap assignment of experimentally observed
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conformers of studied complexes. Having reliable assignment of sp and ap conformers by ROESY spectra at
slow exchange, an increasing the level of theory and/or changing the basis set used for DFT calculations just
only to reproduce experimental values was pointless use of computer resources.
Table 2. Experimental and calculated 1H chemical shifts using DFT calculated geometries in CDCl3.a
Conformers
H-9
exp./calc.
9.99/10.44
H-9 (current-major)
exp./calc.
0/0
1-major/sp-GS
1-minor/ap-GS 10.19/10.87
2-major/sp-GS 9.89/10.24
0.20/0.43
0/0
2-minor/ap-GS 10.08/10.52
3-major/sp-GS 10.49/10.91
3-minor/ap-GS 10.77/11.24
4-major/sp-GS 10.37/10.69
4-minor/ap-GS 10.65/11.14
5-major/sp-GS 10.51/10.79
5-minor/ap-GS 10.78/11.38
6-major/ap-GS 10.80/11.37
6-minor/sp-GS 10.49/10.77
7-major/ap-GS 10.71/11.13
7-minor/sp-GS 10.40/10.68
8-major/sp-GS 10.34/10.50
8-minor/ap-GS 10.16/10.69
9-major/sp-GS 10.05/10.36
0.19/0.28
0/0
0.28/0.33
0/0
0.28/0.45
0/0
0.27/0.59
0/0
-0.31/-0.60
0/0
-0.31/-0.45
0/0
-0.18/0.19
0/0
9-minor/ap-GS 10.42/10.73
Experimental H NMR chemical shifts are measured at 0°C for 1-2 and 20°C for 3-9. The PCM//B3LYP/6-
0.37/0.37
a
1
311++G(d,p) calculated 1H NMR chemical shifts use TMS as a reference system.
2.3.1. Conformational studies of complexes 1-9 in solution
1H and 13C NMR spectra reveal dynamic behaviour in solution of all studied complexes. Three possible
pathways could be responsible for the respective fluxionality of complexes 1-9 (Fig. 1). The first mechanism is
η3-η1-η3 (π-σ-π) allyl isomerization, which would lead to syn-anti exchange in the allyl moiety, due to stronger
trans effect of NHC ligand; this rearrangement is selective, and proceeds only on one side of allyl ligand, and
could be driven under electronic or steric control; the second one is an allyl rotation, this process would govern
an anti-anti and syn-syn exchange for the allyl protons; the third is hindered rotation of the NHC ligand around
the Pd-Ccarbene bond, producing two rotamers.
2D ROESY spectra were obtained to explain the observed mechanism of exchange. All complexes
show syn-anti exchange only between protons on carbon CCl and the other side anti-anti and syn-syn exchange
between protons on carbon CC at 293 K, which excludes mechanisms of allyl rotation and hindered rotation
around the Pd-Ccarbene bond, and correspond precisely with selective η3-η1-η3 isomerization. The mechanism
proceeds through breaking of the pseudotrans toward the carbene C-atom bond, then the η1-allyl intermediate
undergoes rotation around the C-C single bond followed by η1-η3 isomerization, leading to re-formed η3-allyl
complex (Fig. 4).
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The rate constants for all complexes were determined for qualitative estimation of detected chemical
exchange using raw volume intensities of diagonal and cross peaks for the H9-quinoline signals, in the 10-11
ppm range, in 2D EXSY spectra in CDCl3 at various temperatures (Fig. 1-2S, 2-2S, 3-2S, 4-2S, 5-2S, 6-2S, 7-2S,
8-2S and 9-2S). These signals were chosen because they are very sensitive to the chemical exchange and in these
complexes they don’t overlap with other signals and can be integrated precisely. The activation thermodynamic
parameters (∆G≠, ∆H≠ and ∆S≠) were calculated from determined temperature dependence of rate constants
applying the Eyring equation. Linear dependences of ln(k/T) vs 1000/T for all studied complexes showed R2
values in range from 0.9999 to 0.9957 that showed reasonable precision of collected experimental data (Figs. 1-
3S, 2-3S, 3-3S, 4-3S, 5-3S, 6-3S, 7-3S, 8-3S, and 9-3S). The barriers of isomerization, ∆G≠, are in the range of
16.7-18.8 kcal/mol, complexes 1 and 2, with n-butyl substituent at N-atom, expectedly demonstrate the lowest
barriers, 16.7-17.1 kcal/mol, whereas complex 8, the most rigid one with 2,6-diisopropylphenyl substituent at the
N-atom, shows the highest barrier with 18.8 kcal/mol. Unsurprisingly the complexes with tert-butyl and
adamantyl substituents exhibit almost equal values. The presence of methyl group at meso position in the allyl
ligand of complex 8, influences the isomerization with 1 kcal/mol higher by comparison with complex 9 with
unsubstituted allyl ligand. The substituents at seventh position in the imidazo[1,5-a]quinolin-1(2H)-ylidene
moiety, which differ in their electronic effects, respectively hydrogen, methoxy group and fluorine (complexes 3,
4 and 5), show little impact on the energy barrier of selective η3-η1-η3 isomerization.
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Figure 4. 2D ROESY spectrum of allyl moiety of complex 1 in CDCl3 at 293K using mixing time of 0.3 s.
Exchange correlations are shown in black, NOE correlations are shown in red. The mechanism of η3-η1-η3 allyl
isomerization involves allyl dissociation of the side pseudotrans to the carbene (CC in Fig. 2) and rotation around
CCl- Cmeso bond (Fig. 2) resulting in indicated exchanges in 2D ROESY sprectrum.
2.3.2. DFT study of complexes 1-10 in solution
The study of exchange processes between the conformers was performed computationally by DFT
calculations of ground state (GS) η3- and η1-structures and transition state (TS) η3-, η1- and η1η3-structures of
the studied complexes 1-10 (Fig. 5 and Fig. 6). The conformational search of GS structures produce two GS
structures in which the chlorine atom and the allyl group are perpendicularly oriented to the plane of
imidazoquinoline: sp-GS(η3) (synperiplanar GS) and ap-GS(η3) (antiperiplanar GS), which differ in the
orientation of R3 substituent with respect to the quinoline group. The sp-GS(η3) structures are more stable in all
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studied complexes except in complex 3, in which ap-GS is the preferred one (Table 11S.). The GS structures sp-
GS(η1) and ap-GS(η1) are the intermediate species in η3-η1-η3 allyl isomerization. The energy of GS(η1)
structures is between 6 and 10 kcal/mol higher then the GS(η3) structures and their populations are practucally
close to zero. Therefore the thermodynamic parameters of GS(η1) structures are not included in Table 11S. The
localized sp-TS (synperiplanar TS) and ap-TS (antiperiplanar TS) also differ in orientation of the R3 substituent
in respect to the quinoline group. The sp-TS(η3) and ap-TS(η3) structures are localized during the rotation
around the Pd-Ccarbene bond. The sp-TS(η1) and ap-TS(η1) structures are localized during the C-C bond rotation.
The sp-TS(η1η3) and ap-TS(η1η3) structures are localized during the η3 to η1 rearrangement.
As it is seen in Table 3, the DFT calculated barrier of hindered rotation along the Pd-Ccarbene bond is much
higher than the experimental values. The DFT calculated barrier of selective η3-η1-η3 allyl isomerization is in a
good agreement with the experimental values. Only the DFT calculated energy barriers in complexes 8-10 are
underestimated. Most probably the used level of theory underestimates the steric influence of 2,6-diisopropyl
substituent.
The DFT calculated effective free energy of activation reproduce very well the experimental values and
reveal the mechanism of exchange in studied complexes as selective η3-η1-η3 allyl isomerization, which is in
agreement with the interpretation of ROESY spectra of the complexes. Better agreement between the
experimental and DFT activation parameters can be achieved by increasing the basis sets, using better DFT
functional wich describe well pure dispersion interactions [64], but this is out of the scope of the current study.
We managed to solve the problems of assignment of conformers and reveal the exchange mechanism at the
possible reasonable computational cost.
The bond length of CCl-CMeso single bond, around which the rotation occurs, is most sensitive to the selective
η3-η1-η3 allyl isomerization. In GS(η3) structures the bond length is 1.43 Ǻ, in TS(η1η3) structures it is 1.48 Ǻ, in
GS(η1) structures it is 1.48 Ǻ and in TS(η1) structures it is 1.50 Ǻ. The NBO calculated bond order in GS(η3)
structures is 1.108, in TS(η1η3) structures it is 0.974, in GS(η1) structures it is 0.966 and in TS(η1) structures it is
0.923. These results are in agreement with the available theoretical studies of the η3-η1-η3 allyl isomerization and
with the today concept of the selective η3-η1-η3 allyl isomerization in Pd complexes [65, 66].
The mechanism of exchange in studied complexes is selective η3-η1-η3 allyl isomerization, while the
mechanism of exchange in previously reported Pd complexes of NHC ligands derived from substituted 1,8-
naphtalimides is Pd-C restricted rotation and the energetical barrier of η3-methallyl complex is 13.2 kcal/mol
only [47]. It is obvious that in the studied Pd complexes of NHC ligands derived from 2-substituted and 2- and 7-
substituted imidazo[1,5-a]quinolin-1(2H)-ylidene the allylic ligands are in more ridig and bulkier environment.
The allyl group influences more steric repulsion of either R2 substitutent in NHC and quinoline group (which can
be regarded as 1,5-fused NHC) compare to previously reported 4,5-fused NHC. As a result the mechanism is
changed from Pd-C restricted rotation to selective η3-η1-η3 allyl isomerization and the energy barrier is
increasing by more then 3.5 kcal/mol.
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Table 3. Activation parameters for rotational barriers of studied complexes at 298 K.
Compound
Process
∆H‡
∆S‡
∆G‡ (a)
∆G‡ (b)
[kcal mol-1]
∆G‡ (c)
[kcal mol-1]
[kcal mol-1] [cal K-1 mol-1] [kcal mol-1]
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
major → minor
minor → major
13.7(0.6)
13.7(0.5)
13.0(0.4)
12.8(0.4)
14.0(0.5)
14.1(0.4)
15.4(0.6)
15.2(0.6)
15.2(0.8)
14.9(0.7)
15.2(0.5)
15.1(0.5)
14.1(0.6)
14.0(0.6)
18.5(0.7)
18.4(0.8)
14.8(0.7)
14.6(0.7)
-11.5(1.8)
-10.7(1.8)
-12.8(1.5)
-13.0(1.5)
-13.4(1.7)
-12.6(1.6)
-8.6(2.2)
-8.7(1.9)
-9.3(2.3)
-9.8(2.2)
-9.4(1.5)
-9.8(1.6)
-12.4(1.7)
-12.5(1.6)
-1.0(1.8)
-1.3(2.7)
-9.2(2.4)
-9.0(2.4)
17.1(0.1)
16.9(0.1)
16.9(0.1)
16.7(0.1)
18.0(0.1)
17.9(0.1)
17.9(0.1)
17.8(0.1)
18.0(0.1)
17.8(0.1)
18.0(0.1)
18.0(0.1)
17.8(0.1)
17.7(0.1)
18.8(0.1)
18.7(0.1)
17.6(0.1)
17.3(0.1)
18.6
18.5
18.6
19.5
21.3
23.0
21.4
20.5
20.6
20.8
22.0
21.1
22.1
22.9
19.8
18.9
22.0
19.8
20.7
20.0
15.5
15.4
15.8
16.7
17.1
18.8
18.1
17.1
17.6
17.8
17.0
17.1
16.8
17.6
14.7
13.9
15.0
12.8
15.3
14.7
1
2
3
4
5
6
7
8
9
10
1
[a] based on volume of diagonal and cross peaks in VT H NOESY NMR. Quoted errors in parentheses
combine either the statistical errors based on scattering of the data points around Eyring straight line, and the
errors computed using error propagation equations (see the experimental part for details); [b] theoretical
calculations of effective ∆G‡ (taking into accound the rate constats throw the two TS) at the B3LYP/ECP
(LanL2DZ for Pd and 6-31G* for other atoms) level including SMD solvation model for Pd-C rotation; [c]
theoretical calculations of effective ∆G‡ (taking into accound the rate constats throw the two TS) at the same
level of theory for η3-η1-η3 exchange.
12

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R3
Cl
N
N
=
R1
R2
Cl
Pd
R3
3
3
sp-GS(
)
ap-GS( )
Cl
Cl
Cl
Cl
R3
R3
ap-GS(
R3
ap-TS(
R3
sp-TS(
1
1
sp-GS(
)
)
1
3
1
3
)
)
R3
Cl
Cl
Cl
Cl
R3
R3
R3
ap-TS( )
1
1
3
3
sp-TS(
)
sp-TS(
)
ap-TS(
)
Figure 5. The calculated ground state (GS) η3- and η1-structures and transition state (TS) η3-, η1- and η1η3-
structures (Newman projectrions along the Pd-Ccarbene bond) of the studied complexes 1-10. In GS(η1) and
TS(η1) structures the Cl atom is located in front of Pd atom.
13

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Figure 6. Part of the calculated Gibbs free energy profile for Pd-NHC η3-η1-η3 allyl rearrangement in complex 1.
All values and structures correspond to local minima or transition states optimized at the B3LYP/ECP
(LanL2DZ for Pd and 6-31G* for other atoms) level including SMD solvation model, and energies are reported
with respect to the lowest energy conformer sp-GS. The projections were choosen to be along carbene Pd-C
bond and the aromatic ring is perpendicular to the plane of the paper.
3. Conclusion
We have synthesized nine new NHC complexes involving allylic ligands. Conformational studies of the
hindered rotation around Pd-C bond and selective η3−η1−η3 isomerization were performed. The conformations
of the newly prepared complexes were elucidated on the base of NMR and DFT studies. In solution of the
complexes two conformers were revealed and proved to originate from selective η3−η1−η3 isomerization, whose
energy barriers are affected by steric hindrance of substituents at nitrogen atom. Energy barriers of isomerization
are slightly influenced by the electronic nature of substituents at seventh position in imidazo[1,5-a]quinolin-
1(2H)-ylidene moiety. The results from DFT calculations were in good agreement with the experimental energy
barriers.
4. Experimental Section
4.1. General
14

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All reactions were performed under argon atmosphere unless noted otherwise using standard Schlenk
techniques. Reagents purchased from commercial suppliers were used without any further purification.
Dichloromethane was dried over anhydrous CaCl2 and distilled. THF, dioxane and toluene were distilled from
sodium/benzophenone and stored under argon. Flash chromatography was performed on Silica Gel 0.035-0.070
mm, 60 A from Acros Organics. Reactions were monitored using TLC silica gel 60 F254 on aluminum sheets
from Merck. The NMR spectra were recorded on a Bruker Avance III 600 (600.13 for 1H NMR and 150.92
MHz for 13C NMR) spectrometer with TMS as internal standard for proton and carbon chemical shifts (δ, ppm).
Elemental analyses were performed by the Microanalytical Service Laboratory of the Faculty of Chemistry and
Pharmacy, University of Sofia, using Vario EL3 CHNS(O) and the Microanalytical service Laboratory of the
Institute of Organic Chemistry, Bulgarian Academy of Science.
4.2. Dynamic NMR studies
1
VT H NMR spectra of complexes 1-9 were recorded on a Bruker II+ 600 instrument (BBO probe) at
600.13 MHz in steps of 10 K between 223 and 323 K in CDCl3. Temperature calibration was done with B-VT
3000 unit (it was checked and calibrated with methanol and ethylene glycol reference samples). 1H NMR spectra
were acquired using a spectral width of 10 kHz, an acquisition time of 3.4 s and 32 scans, zerofilled to 64k
datapoints (0.15 Hz per point) and processed without apodization.
1
VT H EXSY NMR spectra of complexes 1–9 were recorded on a Bruker II+ 600 instrument (BBO
probe). The spectra were acquired at particular conditions given in Table 4, using a spectral width of 0.8 kHz,
2048 x 256 complex time domain datapoints, with 2 scans in about 48 min. Linear prediction (32 coefficients
and 256 points) in F1 was applied. The spectra were zerofilled to 1024 x 1024 datapoints and processed with a
shifted square sine bell apodization in both dimensions. Populations and exchange rates were obtained from
diagonal- and crosspeak integrals using EXSYCalc [67]. The program EXSYCalc does a quantitative analysis of
the experimental intensities of the NMR peaks in EXSY experiments to calculate the exchange rates [68, 69].
Alternative program for quantitative analysis of experimental intensities in EXSY spectra is D2DNMR [70].
2
ES2 + EkT
The errors Etot, quoted in Table 3 are calculated according to the expression:
, where ES
Etot
=
is the statistical error based on scattering of the data in the Eyring plot while EkT is computed using error
propagation equations as derived by Binsch in [71] and Heinzer and Oth [72], in which errors due to both the
calculated rate constants and the measured temperature are taken into account. The absolute error in temperature
is assumed to be not more than ±0.5 K. The relative errors in k are estimated to be not more than ±10% at all
temperatures according the precision of the volume integration of peaks. The errors analysis was performed
using self-made computer program using the cited equations.
Table 4. Experimental conditions for measurement of 1H NOESY NMR spectra.
Compond
Temp. region
(temp. step)
Mixing time range
273 - 323 K (5 K)
263 - 323 K (5 K)
263 - 323 K (5 K)
263 - 323 K (5 K)
0.03 – 1.0 s
0.03 – 1.0 s
0.03 – 1.0 s
0.03 – 1.0 s
1
2
3
4
15

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263 - 323 K (5 K)
263 - 323 K (5 K)
263 - 323 K (5 K)
283 - 323 K (5 K)
283 - 323 K (5 K)
0.03 – 1.0 s
0.03 – 1.0 s
0.03 – 1.0 s
0.03 – 1.5 s
0.03 – 1.0 s
5
6
7
8
9
4.3. DFT calculations
The DFT calculations were carried out on MADARA cluster (http://madara.orgchm.bas.bg) using
program package GAUSSIAN 09 [73]. Geometry optimizations were performed by using density functional
theory [74-76] with B3LYP functionals [77, 78]. As for the basis sets, we used 6-31G(d) sets for C, H, N, O and
Cl [78]. For Pd, we used LANL2DZ basis sets [79], whose core parts were represented by effective core
potentials (ECP). Solvent was included implicitly to the optimizations via the SMD [80] model with the built in
parameters for solvent CHCl3. The nature of all critical points was confirmed by means of the vibrational
analysis, and ZPV energies were evaluated. The thermal and entropy corrections to Gibbs free energy to 298.15
K have been calculated for all minima from unscaled vibrational frequencies obtained at the same level. The ∆H,
∆S and ∆G values were calculated for T = 293.15 K at the given level of theory including zero-point energy and
1
vibrational, rotational and translational thermal energy corrections. The H NMR chemical shifts of the 1-10
conformers in solvent environment (SMD) were calculated using B3LYP functional with 6-311++G(d,p) basis
sets for C, H, N, O and Cl and LANL2DZ basis sets for Pd.
4.4. Synthesis of allyl complexes
4.4.1. Synthesis of precursors
The formylating solution (solution of acetic formic anhydride) [53] was obtained by mixing and
stirring for 2 hours at room temperature equal volumes of 98% formic acid and acetic anhydride. The solution
was used immediately. N-adamantylformamide and N-(2,6-diisopropylphenyl)formamide were prepared by
formilating the corresponding amines following general procedure А for the synthesis of formamides d1-5.
Melting points, NMR spectra and elemental analyses of the already known compounds (N-adamantyl- and N-
(2,6-diisopropylphenyl)formamide [81, 82], quinolines a1-3 and 2-bromomethylquinolines b1-3 are in
accordance with the values in the cited literature.
General procedure for the synthesis of quinaldines (a1-3).
In air, a mixture of aniline and 6M hydrochloric acid (500 ml per mol) was heated to reflux and
crotonaldehyde (1.1-2 eqv) was added dropwise for 30 min. After consumption of the starting aniline the
reaction mixture was cooled to room temperature, washed with diethyl ether (3x50ml) and anhydrous ZnCl2 (1
eqv) was added. The solution was stirred for 30 min at room temperature and then for 20 min in an ice bath. The
resulting precipitate was filtered, washed with cold 3M hydrochloric acid and cold water and was transferred to a
beaker with isopropanol. The resultng suspension was stirred for 10 min and filtered. Yellow solid was obtained
and washed with isopropanol to nearly colorless washings, and then with ether. After drying, the complex was
transfered to a beaker with conc. aqueous ammonia. The product was extracted with ethyl acetate, the combined
16

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extracts were dried over Na2SO4 and the solvent was evaporated to dryness. The resulting quinaldine was
purified by passing through short column with silica, distilled under reduced presure or used directly.
4.4.1.1. 2-methylquinoline (a1): Prepared following the general procedure from 18.63 g (0.2 mol) aniline, 100 ml
6M hydrochloric acid and 21 ml (17.77 g, 0.253 mol) crotonaldehyde. The mixture was heated for two hours.
Yield – 11.1 g (39%) dark oil. 1H NMR (600 MHz, CDCl3) δ 8.04 (d, J = 8.4 Hz, 1H, H4), 8.03 (dd, J = 1.1, 8.4
Hz, 1H, H5), 7.77 (dd, J = 1.2, 8.1 Hz, 1H, H8), 7.68 (ddd, J = 1.2, 6.9, 8.4 Hz, 1H, H6), 7.48 (ddd, J = 1.1, 6.9,
8.1 Hz, 1H, H7), 7.28 (d, J = 8.4 Hz, 1H, H3), 2.75 (s, 3H, CH3). 13C NMR (151 MHz, CDCl3) δ 159.07 (4C2),
147.86 (4C8a), 136.33 (C4), 129.55 (C6), 128.64 (C5), 127.58 (C8), 126.56 (4C4a), 125.78 (C7), 122.11 (C3),
25.44 (CH3).
4.4.1.2. 6-methoxy-2-methylquinoline (a2): Prepared from 30 g (0.244 mol) of 4-methoxyaniline, 123 ml 6M
hydrochloric acid and 40.5 ml (34.26 g, 0.489 mol) crotonaldehyde. The mixture was heated for 2 hours. Yield
24.6 g (58%) dark slowly solidifying oil, purified by passing through short column. 1H NMR (600 MHz, CDCl3)
δ 7.92 (d, J = 8.4 Hz, 1H, H4), δ 7.91 (d, J = 9.1 Hz, 1H, H8), δ 7.32 (dd, J = 9.1, 2.8 Hz, 1H, H7), 7.22 (d, J =
8.4 Hz, 1H, H3), 7.02 (d, J = 2.8 Hz, 1H, H5), 3.89 (s, 3H, CH3O), 2.69 (s, 3H, CH3). 13C NMR (151 MHz,
CDCl3) δ 157.29 (4C6), 156.42 (4C2), 143.84 (4C8a), 135.30 (C4), 130.02 (C8), 127.44 (4C4a), 122.38 (C3),
122.10 (C7), 105.31 (C5), 55.63 (CH3O), 25.10 (CH3).
4.4.1.3. 6-fluoro-2-methylquinoline (a3): Prepared from 10 g (0.090 mol) 4-fluoroaniline, 45 ml of 6M
hydrochloric and 8.3 ml crotonaldehyde. The mixture was heated for 3 hours. Yield 7.24 g (50%) yellow
1
crystals. H NMR (600 MHz, CDCl3) δ 8.00 (dd, J = 5.1, 9.0 Hz, 1H, H8), 7.98 (d, J = 8.4 Hz, 1H, H4), 7.44
(ddd, J = 2.8, 8.8, 9.0 Hz, 1H, H7), 7.37 (dd, J = 2.8, 8.8 Hz, 1H, H5), 7.29 (d, J = 8.4 Hz, 1H, H3), 2.73 (s, 3H,
CH3). 13C NMR (151 MHz, CDCl3) δ 160.06 (d, 1JC-F = 246.6 Hz, 4C6), 158.41 (d, J = 2.9 Hz, 4C8a), 144.97 (s,
4C2), 135.69 (d, J = 5.1 Hz, C4), 131.08 (d, J = 9.0 Hz, C8), 127.08 (d, J = 9.8 Hz, 4C4a), 122.89 (C3), 119.62
(d, J = 25.5 Hz, C5), 110.65 (d, J = 21.6 Hz, C7), 25.33 (CH3)
General procedure for the synthesis of 2-(bromomethyl)quinolones (b1-3).
The respective 2-methylquinoline (14-20 mmol) was dissolved in carbon tetrachloride or benzene (1.3-
13.5 ml per mmol) and N-bromosuccinimide (1.1 eqv) was added. The mixture was refluxed in the presence of
benzoyl peroxide (0.8-1.7 mmol) for the indicated below amount of time. After cooling to room temperature, the
precipitated succinimide was filtered off and after evaporation af the volatiles under vacuum, the product was
purified by flash chromatography.
4.4.1.4. 2-(bromomethyl)quinoline (b1): Prepared following the general procedure from 2.8 g (19.6 mmol) of
quinaldine a1, 25 ml carbon tetrachloride, 3.86 g (21.7 mmol) NBS and 0.411 g (1.7 mmol) benzoyl peroxide.
1
Refluxed for 5 hours. Yield 2.27 g pink crystals (52%). H NMR (600 MHz, CDCl3) δ 8.19 (d, J = 8.4 Hz, 1H,
H4), 8.09 (dd, J = 1.2, 8.4 Hz, 1H, H5), 7.82 (dd, J = 1.4, 8.1 Hz, 1H, H8), 7.74 (ddd, J = 1.5, 6.9, 8.4 Hz, 1H,
H6), 7.58 (d, J = 8.4 Hz, 1H, H3), 7.56 (ddd, J = 1.2, 6.9, 8.1 Hz, 1H, H7), 4.73 (s, 2H, CH2). 13C NMR (151
MHz, CDCl3) δ 157.00 (4C2), 147.48 (4C8a), 137.62 (C4), 130.22 (C6), 129.27 (C5), 127.69 (C8), 127.48
(4C4a), 127.26 (C7), 121.36 (C3), 34.38 (CH2).
17

ACCEPTED MANUSCRIPT
4.4.1.5. 2-(bromomethyl)-6-methoxyquinoline (b2): Prepared from 1.025 g (5.92 mmol) 6-methoxyquinaldine a2,
0.215 g (0.89 mmol) benzoyl peroxide and 1.159 g (6.5 mmol) NBS in 80 ml benzene. Refluxed for 3.5 hours.
Yield – 0,955 g (64 %) pale yellow crystals. 1H NMR (600 MHz, CDCl3) δ 7.92 (d, J = 8.4 Hz, 1H, H4), δ 7.91
(d, J = 9.1 Hz, 1H, H8), δ 7.32 (dd, J = 9.1, 2.8 Hz, 1H, H7), 7.22 (d, J = 8.4 Hz, 1H, H3), 7.02 (d, J = 2.8 Hz,
1H, H5), 3.89 (s, 3H, CH3O), 2.69 (s, 3H, CH3).
4.4.1.6. 2-bromomethyl-6-fluoroquinoline (b3): Prepared from 2.5 g (15,5 mmol) 2-methyl-6-fluoroquinoline a3,
3.04 g (17 mmol) N-bromosuccinimide and 0.185 g (0.76 mmol) of dibenzoyl peroxide in 80 ml of benzene.
1
Refluxed for 21 hours. Yield - 1.94 g (52%) beige crystals. H NMR (600 MHz, CDCl3) δ 8.18 (d, J = 8.6 Hz,
1H, H4), 8.16 (dd, J = 5.3, 9.1 Hz, 1H, H8), 7.62 (d, J = 8.6 Hz, 1H, H3), 7.52 (ddd, J = 2.8, 9.1, 8.5 Hz, 1H,
1
H7), 7.45 (dd, J = 2.8, 8.5Hz, 1H, H5), 4.75 (s, 2H, CH2). 13C NMR (151 MHz, CDCl3) δ 161.00 (d, JC-F
=
4
250.0 Hz, C6), 156.15 (d, J = 2.8 Hz, C2), 143.68 (bs, 4C8a), 137.64 (C4), 131.16 (d, J = 8.8 Hz, C8), 128.21
(d, J = 10.1 Hz, 4C4a), 122.27 (C3), 120.85 (d, J = 25.8 Hz, C7), 110.89 (d, J = 21.9 Hz, C5), 33.27 (CH2).
General procedure А for the synthesis of formamides d1-5.
In air, 2-(bromomethyl)quinoline was suspended in diethyl ether or acetonitrile (2.5-5.1 ml per mmol).
Excess of tert-butyl or n-butylamine (10-26 eqv) was added in one portion. The mixture was stirred at room
temperature until the starting halide was consumed. Аfter that the volatiles were evaporated and the resulting oil
was basified with saturated aqueous NaOH. The suspension was extracted with ether, the organic layer was dried
with Na2SO4 and the solvent was removed. The resulting oil was dissolved in THF or diethyl ether (1.3-3.4 ml
per mmol), cooled in an ice bath and precooled formylating solution (0.5-2 ml per mmol) was added. The
resulting reaction mixture was stirred in an ice bath, and then at room temperature until the starting amine was
consumed. Then the mixture was neutralized with saturated aqueous K2CO3 and extracted with ethyl acetate. The
crude formamide was purified by flash chromatography.
4.4.1.7. N-butyl-N-(quinolin-2-ylmethyl)formamide (d1): Prepared following general procedure A reacting 1,186
g (5,34 mmol) 2-bromomethyl quinoline b1 and 10 ml of n-butylamine in 20 ml diethyl ether at room
temperature for 3 h. After work up amine c1 was dissolved in 15 ml of THF, cooled, treated with 4 ml cold
1
formylating solution and stirred for 15 hours. Yield 1.268 g (98%) orange oil. H NMR (600 MHz, CDCl3, two
conformers in ratio 1:0.54 ) Major δ 8.26 (bs, 1H, CHO), 8.13 (d, J = 8.5 Hz, 1H, H4), 8.06 (d, J = 8.4 Hz, 1H,
H8), 7.81 (d, J = 8.2 Hz, 1H, H5), 7.72-7.70 (m, 1H, H7), 7.55 – 7.52 (m, 1H, H6), 7.42 (d, J = 8.5 Hz, 1H, H3),
4.85 (bs, 2H, CH2), 3.27 (t, J = 7.3 Hz, 2H, NCH2CH2), 1.56-1.51 (m, 2H, CH2CH2CH2), 1.29-1.20 (m, 2H,
CH2CH3), 0.86 (t, J = 7.3, 3H, CH2CH3); Minor 1H NMR (600 MHz, CDCl3) δ 8.37 (s, 1H, CHO), 8.18 (d, J =
8.5 Hz, 1H, H4), 8.05 (d, J = 8.5 Hz, 1H, H8), 7.83 (d, J = 8.1 Hz, 1H, H5), 7.75 – 7.72 (m, 1H, H7), 7.57 –
7.55 (m, 1H, H6), 7.32 (d, J = 8.5 Hz, 1H, H3), 4.69 (bs, 2H, CH2), 3.31 (t, J = 7.3 Hz, 2H, NCH2CH2), 1.52-
1.47 (m, 2H, CH2CH2CH2), 1.30-1.23 (m, 2H, CH2CH3), 0.85 (t, J = 7.4 Hz, 3H, CH2CH3). 13C NMR (151
MHz, CDCl3, two conformers in ratio 1:0.54) Major δ 163.24 (CHO), 157.45 (4C2), 147.52 (4C8a), 137.29 (C4),
129.88 (C7), 129.03 (C8), 127.75 (C5), 127.52 (4C4a), 126.67 (C6), 120.31 (C3), 48.48 (CH2), 47.71
(NCH2CH2), 30.48 (CH2CH2CH2), 19.71 (CH2CH3), 13.70 (CH2CH3); Minor δ 163.48 (CHO), 156.97 (4C2),
147.87 (4C8a), 137.48 (C4), 130.21 (C7), 129.20 (C8), 127.81 (C5), 127.54 (4C4a), 126.95 (C6), 118.99 (C3),
18

ACCEPTED MANUSCRIPT
53.92 (CH2), 42.68 (NCH2CH2), 29.12 (CH2CH2CH2), 20.16 (CH2CH3), 13.85 (CH2CH3). C15H18N2O
(242.32): calcd. C, 74.35; H, 7.49; N, 11.56, found: C, 74.41; H, 7.58; N, 11.49.
4.4.1.8. N-butyl-N-((6-methoxyquinolin-2-yl)methyl)formamide (d2): 0.987 g (3,92 mmol) 2-bromomethyl-6-
methoxyquinoline b2 and 4 ml of n-butylamine were reacted in 10 ml of diethyl ether for 2.5 hours. After work
up amine c2 was dissolved in 10 ml of THF, cooled, treated with 4 ml cold formylating solution and stirred for
15 hours. Yield - 0.99 g (93%) yellow oil. 1H NMR (600 MHz, CDCl3, two conformers in ratio 1:0,6): Major δ =
8.23 (bs, 1H, CHO), 8.01 (d, J = 8.4 Hz, 1H, H4), 7.93 (d, J = 9.3 Hz, 1H, H8), 7.36 (d, J=8.4 Hz, 1H, H3), 7.35
(dd, J = 2.8, 9.2, 1H, H7), 7.05 (d, J = 2.8 Hz, 1H, H5), 4.79 (bs, 2H, CH2), 3.91 (bs, 3H, CH3O), 3.25 (t, J = 7.2
Hz, 2H, NCH2), 1.54-1.48 (m, 2H, CH2CH2CH2), 1.28-1.21 (m, 2H, CH2CH3), 0.84 (t, J = 7.4 Hz, 3H,
CH2CH3); Minor δ = 8.36 (s, 1H, CHO), 8.06 (d, J = 8.4 Hz, 1H, H4), 7.94 (d, J = 9.2 Hz, 1H, H8), 7.37 (dd, J
= 2.8, 9.2,1H, H7), 7.25 (d, J=8.4 Hz, 1H, H3), 7.07 (d, J = 2.8 Hz, 1H, H5), 4.64 (s, 2H, CH2), 3.92 (bs, 3H,
CH3O), 3.28 (t, 2H, NCH2), 1.49-1.45 (m, 2H, CH2CH2CH2), 1.28-1.21 (m, 2H, CH2CH3), 0.85 (t, J = 7.4 Hz,
3H, CH2CH3). 13C NMR (151 MHz, CDCl3, two conformers in ratio 1:0,6): Major δ = 163.03 (CHO), 157.69
(4C6), 154.66 (4C2), 143.76 (4C8a), 135.83 (C4), 130.25 (C8), 128.33 (4C4a), 122.32 (C7), 120.49 (C3), 105.04
(C5), 55.50 (CH3O), 48.14 (CH2), 47.47 (NCH2), 30.29 (CH2CH2CH2), 19.52 (CH2CH3), 13.52 (CH2CH3);
Minor δ = 163.26 (CHO), 157.89 (4C6), 154.09 (4C2), 143.40 (4C8a), 135.97 (C4), 130.39 (C8), 128.40 (4C4a),
122.76 (C7), 119.18 (C3), 104.99 (C5), 55.53 (CH3O), 53.61 (CH2), 42.42 (NCH2), 28.95 (CH2CH2CH2), 19.98
(CH2CH3), 13.68 (CH2CH3). C16H20N2O2 (272.35): calcd. C, 70.56; H, 7.40; N, 10.29, found: C, 70.48; H, 7.51;
N, 10.31.
4.4.1.9. N-tert-butyl-N-(quinolin-2-ylmethyl)formamide (d3): 2 g (9 mmol) of 2-(bromomethyl)quinoline b1 and
25 ml of tert-butylamine were reacted in 25 ml acetonitrile for 20 hours. After work up amine c3 was dissolved
in 12 ml of THF, cooled, treated with 10 ml cold formylating solution and stirred for 15 hours. Yield: 2.12 g
1
(97%) orange-brown oil. H NMR (600 MHz, CDCl3) δ 8.72 (s, 1H, CHO), 8.09 (d, J = 8.5 Hz, 1H, H4), 8.01
(dd, J = 1.2, 8.4 Hz, 1H, H8), 7.78 (dd, J = 1.2, 8.0 Hz, 1H, H5), 7.69 (ddd, J = 1.4, 6.9, 8.4 Hz, 1H, H7), 7.50
(ddd, J = 1.2, 6.9, 8.0 Hz, 1H, H6), 7.37 (d, J = 8.5 Hz, 1H, H3), 4.94 (s, 2H, CH2), 1.36 (s, 9H, tert-Bu). 13C
NMR (151 MHz, CDCl3) δ 162.59 (CHO), 159.44 (4C2), 147.51 (4C8a), 136.91 (C4), 129.68 (C7), 128.88 (C8),
127.68 (C5), 127.28 (4C4a), 126.33 (C6), 119.71 (C3), 56.35 (4C-tert-Bu), 47.08 (CH2), 30.04 (tert-Bu).
C15H18N2O (242.32): calcd. C, 74.35; H, 7.49; N, 11.56, found: C, 74.28; H, 7.33; N, 11.59.
4.4.1.10. N-tert-butyl-N-((6-methoxyquinolin-2-yl)methyl)formamide (d4): 1 g (3.97 mmol) 2-bromomethyl-6-
methoxyquinoline b2 and 10 ml tert-butylamine were reacted in 15 ml of acetonitrile for 24 hours. After work up
amine c4 was dissolved in 6 ml of THF, cooled, treated with 5 ml cold formylating solution and stirred for 16
1
hours. Yield 0.982 g (91%) yellow oil. H NMR (600 MHz, CDCl3) δ 8.70 (s, 1H, CHO), 7.97 (d, J = 8.6 Hz,
1H, H4), 7.89 (d, J = 9.2 Hz, 1H, H8), 7.36 (dd, J = 2.8, 9.2 Hz, 1H, H7), 7.35 (d, J = 8.6 Hz, 1H, H3), 7.03 (d,
J = 2.8 Hz, 1H, H5), 4.89 (s, 2H, CH2), 3.89 (s, 3H, CH3O), 1.34 (s, 9H, tert-Bu). 13C NMR (151 MHz, CDCl3)
δ 162.58 (CHO), 157.83 (4C6), 156.70 (4C2), 143.05 (4C8a), 136.19 (C4), 129.87 (C8), 128.30 (4C4a), 122.62
(C3), 120.16 (C7), 105.21 (C5), 56.38 (4C-tert-Bu), 55.68 (CH3O), 46.55 (CH2), 30.05 (tert-Bu).C16H20N2O2
(272.35): calcd. C, 70.56; H, 7.40; N, 10.29, found: C, 70.68; H, 7.28; N, 10.25.
19

ACCEPTED MANUSCRIPT
4.4.1.11. N-tert-butyl-N-((6-fluoroquinolin-2-yl)methyl)formamide (d5): 0.700 g (2.92 mmol) of 2-bromomethyl-
6-fluoroquinoline b3 and 5 ml tert-butylamine were reacted in 15 ml diethyl ether for 22 hours. After work up
amine c5 was dissolved in 10 ml of diethyl ether, cooled, treated with 1.5 ml cold formylating solution and
o
1
stirred for 20 hours. Yield 0.694 g (91%) beige powder with m.p. 101 – 102 C. H NMR (600 MHz, CDCl3) δ
8.71 (s, 1H, CHO), 8.04 (d, J = 8.7 Hz, 1H. H4), 8.02 (dd, J = 5.3, 9.1 Hz, 1H, H8), 7.46 (ddd, J = 2.8, 8.4, 9.1
Hz, 1H, H7), 7.40 (d, J = 8.7 Hz, 1H, H3), 7.40 (dd, J = 2.8, 8.8 Hz, 1H, H5), 4.92 (s, 2H, CH2), 1.37 (s, 3H,
tert-Bu). 13C NMR (151 MHz, CDCl3) δ 162.60 (CHO), 160.40 (d, 1JC-F = 247.8 Hz, C6), 158.77 (d, J = 3.2 Hz,
4
4C2), 144.51 (4C8a), 136.32 (d, J = 5.3 Hz, C8), 131.29 (d, J = 9.0 Hz, C4), 127.86 (d, J = 10.0 Hz, C4a),
120.59 (s, C3), 119.86 (d, J = 25.7 Hz, C7), 110.72 (d, J = 21.8 Hz, C5), 56.37 (4C-tert-Bu), 46.91 (CH2), 30.05
(tert-Bu). C15H17FN2O (260.31): calcd. C, 69.21; H, 6.58; N, 10.76; N, 10.29, found: C, 69.31; H, 6.70; N,
10.71.
General procedure B for the synthesis of formamides (d6-8).
N-alkyl or N-arylformamide (1 eqv) was dissolved in THF (3.3-3.9 ml per mmol) and the resulting
solution was cooled in an ice bath. To the cold solution was added NaH (50% in mineral oil) (1.3 eqv) and the
suspension was stirred for 1 hour. Then the corresponding 2-(bromomethyl)quinoiline (1 eqv) was added and the
reaction mixture was stirred at room temperature until full consumption of the starting 2-
(bromomethyl)quinoiline. The solvent was removed under reduced pressure, small amount of water was added
and the suspension was extracted with DCM or ethyl acetate. The crude product was purified by recrystallization
or by flash chromatography.
4.4.1.12. N-(adamantan-1-yl)-N-(quinolin-2-ylmethyl)formamide (d6): Prepared following general procedure B
by deprotonating 0.978 g (5.46 mmol) N-adamantylformamide with 0.341 g 50% suspension of NaH in mineral
oil (7.09 mmol) in 21 ml dry THF. After 1 hour 1.212 g (5.46 mmol) 2-(bromomethyl)quinoline (b1) was added.
Stirred for 4 days. Yield after purification – 1.53 g (88%) pale yellow slowly solidifying oil with m.p. 142-143
1
oC. H NMR (600 MHz, CDCl3) δ 8.75 (s, 1H, CHO), 8.10 (d, J = 8.5 Hz, 1H, H4), 8.04 (dd, J = 1.0, 8.5 Hz,
1H, H8), 7.79 (dd, J = 1.2, 8.2 Hz, 1H, H5), 7.70 (ddd, J = 1.2, 6.9, 8.5 Hz, 1H, H7), 7.51 (ddd, J = 1.0, 6.9, 8.2
Hz, 1H, H6), 7.38 (d, J = 8.5 Hz, 1H, H3), 4.95 (s, 2H, CH2), 2.10 (bs, 3H, CH-adamantyl), 1.94 (d, J = 2.7 Hz,
6H, CH2-adamantyl), 1.67-1.60 (m, 6H, CH2-adamantyl).13C NMR (151 MHz, CDCl3) δ 162.33 (CHO), 159.69
(4C2), 147.39 (4C8a), 136.95 (C4), 129.75 (C7), 128.78 (C8), 127.73 (C5), 127.29 (4C4a), 126.34 (C6), 119.70
(C3), 57.28 (4C-adamantyl), 45.93 (CH2), 42.50 (CH2-adamantyl), 35.96 (CH2-adamantyl), 29.55 (CH-
adamantyl). C21H24N2O (320.44): calcd. C, 78.71; H, 7.55; N, 8.74, found: C, 78.62; H, 7.43; N, 8.78.
4.4.1.13. N-(adamantan-1-yl)-N-((6-methoxyquinolin-2-yl)methyl)formamide (d7): Prepared following general
procedure B by deprotonating 1.067 g (5.95 mmol) N-adamantyl formamide with 0.371g 50 % suspension of
NaH in mineral oil (7.74 mmol) in 23 ml dry THF. After 1 hour 1.5 g (5.95 mmol) of 2-bromomethyl-6-
methoxyquinoline was added. Stirred for 4 days. Yield after purification – 1.77 g (85%) pale yellow slowly
solidifying oil with m. p. 143-144oC. 1H NMR (600 MHz, CDCl3) δ 8.72 (s, 1H, CHO), 7.99 (d, J = 8.5 Hz, 1H,
H4), 7.93 (d, J = 9.1 Hz, 1H, H8), 7.34 (dd, J = 2.8, 9.1 Hz, 1H, H7), 7.34 (d, J = 8.5 Hz, 1H, H3),7.04 (d, J =
2.8 Hz, 1H, H5), 4.91 (s, 2H, CH2), 3.90 (s, 3H, CH3O), 2.08 (s, 3H, CH-adamantyl), 1.91 (d, J = 2.5 Hz, 6H,
20

ACCEPTED MANUSCRIPT
CH2-adamantyl), 1.65-1.58 (m, 6H, CH2-adamantyl). 13C NMR (151 MHz, CDCl3) δ 162.10 (CHO), 157.51
(4C2), 156.88 (4C8a), 143.14 (4C6), 135.63 (C4), 129.92 (C8), 128.05 (4C4a), 122.22 (C7), 119.89 (C3), 105.06
(C5), 57.06 (4C-adamantyl), 55.50 (CH3O), 45.50 (CH2), 42.31 (CH2-adamantyl), 35.79 (CH2-adamantyl),
29.38 (CH-adamantyl). C22H26N2O2 (350.46): calcd. C, 75.40; H, 7.48; N, 7.99, found: C, 75.54; H, 7.39; N,
7.95.
4.4.1.14. N-(2,6-diisopropylphenyl)-N-(quinolin-2-ylmethyl)formamide (d8): Prepared following general
procedure B by deprotonating 1.849 g (9 mmol) N-(2,6-diisopropylphenyl)formamide with 0.983g (11.7 mmol)
50% suspension of NaH in oil in 30 ml dry THF. After 30 min 2 g (9 mmol) 2-bromomethylquinoline was
added. Stirred for 19 hours. Yield after work up and recrystallization (cyclohexane) - 2.53 g (81%) of beige
powder with m.p. 131-132 oC. 1H NMR (600 MHz, CDCl3) δ 8.20 (s, 1H, CHO), 8.16 (d, J = 8.5 Hz, 1H, H4),
7.95 (d, J = 8.4 Hz, 1H, H8), 7.80 (d, J = 8.5 Hz, 1H, H3 and dd, J = 1.1, 8.1, 1H, H5), 7.66 (ddd, J = 1.1, 6.9,
8.4 Hz, 1H, H7), 7.52 (ddd, J = 1.1, 6.9, 8.1 Hz, 1H, H6), 7.33 (t, J = 7.8 Hz, 1H, 4H-2,6-diisopropylphenyl),
7.14 (d, J = 7.8 Hz, 2H, 3,5-H-2,6-diisopropylphenyl), 5.07 (s, 2H, CH2), 2.80 (sep, J = 6.8 Hz, 2H, CH-
isopropyl), 1.07 (d, J = 6.8 Hz, 6H, CH3-isopropyl), 0.82 (d, J = 6.8 Hz, 6H, CH3-isopropyl). 13C NMR (151
MHz, CDCl3) δ 163.97 (CHO), 156.81 (4C2), 147.84 (2,6-4C-2,6-diisopropylphenyl), 147.39 (4C8a), 136.92
(C4), 135.74 (1-4C-2,6-diisopropylphenyl), 129.69 (4-C-2,6-diisopropylphenyl), 129.63 (C7), 129.24 (C8),
127.58 (C5), 127.54 (4C4a), 126.72 (C6), 124.54 (3,5-C-2,6-diisopropylphenyl), 122.55 (C3), 54.63 (CH2),
28.54 (CH-isopropyl), 25.41 (CH3-isopropyl), 23.31 (CH3-isopropyl). C23H26N2O (346.47): calcd. C, 79.73; H,
7.56; N, 8.09, found: C, 79.79; H, 7.63; N, 8.00.
General procedure for the synthesis of imidazoquinolinium salts (e1-8).
The corresponding formamide d1-8 (1 eqv) was dissolved in dry toluene (6-12 ml per mmol of
formamide). The solution was stirred for 10 minutes at 80oC and POCl3 (1.1 eqv) was added. Heating at 80oC
was continued until full consumption of the starting material and after that the volatiles were removed under
reduced pressure. The resulting solid was dissolved in a minimum amount of boiling water, the solution was
filtered while still hot and thereto was added dropwise, with stirring, saturated aqueous solution of NH4BF4 (1.5
eqv) or KPF6 (1.2 eqv). The resulting suspension was stirred for 30 min, cooled and filtered. The white
precipitate was washed with water and dried in a vacuum desiccator over P4O10.
4.4.1.15. 2-butylimidazo[1,5-a]quinolin-2-ium hexafluorophosphate (e1): Prepared from 0.908 g (3.75 mmol) d1
and 0.454 ml (4.87 mmol) POCl3 in 25 ml dry toluene at 80oC for 2 hours. Treated with water solution of 0.897
o
g (4.87 mmole) KPF6. Yield after drying - 1.3 g (94%) white powder with m. p. 163 C (decomposition). 1H
NMR (600 MHz, DMSO) δ 10.55 (bs, 1H, H1), 8.43 (d, J = 8.4 Hz, 1H, H9), 8.32 (d, J = 1.3 Hz, 1H, H3), 8.02
(dd, J = 1.2, 7.8 Hz, 1H, H6), 7.87 (ddd, J = 1.2, 7.1, 8.4 Hz, 1H, H8), 7.74 (ddd, J = 1.2, 7.1, 7.8 Hz, 1H, H7),
7.70 (d, J = 9.7 Hz, 1H, H4), 7.67 (d, J = 9.7 Hz, 1H, H5), 4.47 (t, J = 7.2 Hz, 2H, NCH2), 1.98-1.94 (m, 2H,
CH2CH2CH2), 1.39-1.32 (m, 2H, CH2CH3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3). 13C NMR (151 MHz, DMSO) δ
130.26 (C8), 129.61 (C6), 129.15 (4C9a), 128.54 (C7), 128.38 (C1), 128.20 (4C3a), 126.20 (C5), 124.15 (4C5a),
116.65 (C9), 115.48 (C4), 115.36 (C3), 50.05 (NCH2), 31.50 (CH2CH2CH2), 18.90 (CH2CH3), 13.37 (s,
CH2CH3). C15H17F6N2P (370.28): calcd. C, 48.66; H, 4.63; N, 7.57, found: C, 48.48; H, 4.72; N, 7.42.
21

ACCEPTED MANUSCRIPT
4.4.1.16. 2-butyl-7-methoxyimidazo[1,5-a]quinolin-2-ium hexafluorophosphate (e2): Prepared from 0.860 g
(3.56 mmol) d2 and 0.383 ml (4.1 mmol) POCl3 in 20 ml dry toluene for 2.5 hours at 80oC. Treated with water
o
solution of 0.756 g (4.1 mmol) KPF6. Yield after drying - 0.985 g (69%) white powder with m. p. 164 C
(decomposition). 1H NMR (600 MHz, DMSO) δ 10.44 (bs, 1H, H1), 8.35 (d, J = 8.8 Hz, H9), 8.29 (bs, 1H, H3),
7.68 (d, J = 9.6 Hz, 1H, H5), 7.61 (d, J = 9.6 Hz, 1H, H4), 7.56 (d, J = 2.6 Hz, 1H, H6), 7.47 (dd, J = 2.6, 8.8
Hz, 1H, H8), 4.44 (t, J = 7.2 Hz, 2H, NCH2), 3.91 (s, 3H, CH3O), 1.96-1.93 (b, 2H, CH2CH2CH2), 1.36-1.33
(m, 2H, CH2CH3), 0.95 (t, J = 7.4 Hz, 3H, CH2CH3). 13C NMR (151 MHz, DMSO) δ 158.70 (4C7), 127.78
(4C3a), 127.56 (C1), 126.12 (C4), 125.70 (4C9a), 123.15 (4C5a), 118.34 (C8), 118.14 (C9), 115.72 (C5), 115.49
(C3), 111.42 (C6), 55.89 (CH3O), 49.95 (NCH2), 31.52 (CH2CH2CH2), 18.92 (CH2CH3), 13.38 (CH2CH3).
C16H19F6N2OP (400.31): calcd. C, 48.01; H, 4.78; N, 7.00, found: C, 48.15; H, 4.82; N, 6.91.
4.4.1.17. 2-(tert-butyl)imidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e3): Prepared from 1.13 g (4.66 mmol)
of d3 and 0.478 ml (5.13 mmol) POCl3 in 50 ml dry toluene for 12 hours at 80°C. Treated with water solution of
0.733 g (6.99 mmol) NH4BF4. Yield after drying – 1.14 g (71%) white powder with m. p. 252 oC
1
(decomposition). H NMR (600 MHz, DMSO) δ 10.42 (d, J = 1.4 Hz, 1H, H1), 8.69 (d, J = 8.4 Hz, 1H, H9),
8.54 (d, J = 1.4 Hz, 1H, H3), 8.03 (dd, J = 1.2, 7.6 Hz, 1H, H6), 7.87 (ddd, J = 1.2, 7.1, 8.4 Hz, 1H, H8), 7.74
(ddd, J = 1.2, 7.1, 7.6 Hz, 1H, H7), 7.68 (d, 1H, J = 9.5, H5), 7.64 (d, 1H, J = 9.5, H4), 1.76 (s, 9H, tert-Bu). 13
C
NMR (151 MHz, DMSO) δ 130.14 (C8), 129.58 (C6), 129.31 (4C9a), 128.52 (C7), 128.28 (4C3a), 126.85 (C1),
126.27 (C5), 124.13 (4C5a), 117.07 (C9), 115.27 (C4), 113.44 (C3), 61.20 (4C-tert-Bu), 29.35 (tert-Bu).
C15H17BF4N2 (312.12): calcd. C, 57.72; H, 5.49; N, 8.98, found: C, 57.58; H, 5.61; N, 8.81.
4.4.1.18. 2-(tert-butyl)-7-methoxyimidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e4): Prepared from 0.963 g
(3.54 mmol) of d4 and 0.363 ml (3.89 mmol) POCl3 in 24 ml dry toluene for 12 hours at 80°C. Treated with
water solution of 0.556 g (5.304 mmol) NH4BF4. Yield after drying – 1.114 g (92%) white powder with m. p. 253
oC (decomposition). 1H NMR (600 MHz, DMSO) δ 10.33 (d, J = 1.5 Hz, 1H, H1), 8.60 (d, J = 9.2 Hz, 1H, H9),
8.50 (d, J = 1.5 Hz, 1H, H3), 7.64 (d, 1H, J = 9.5, H5), 7.61 (d, 1H, J = 9.5, H4), 7.56 (d, J = 2.8 Hz, 1H, H6),
7.47 (dd, J = 2.8, 9.2 Hz, 1H, H8), 3.92 (s, 3H, CH3O), 1.75 (s, 9H, tert-Bu). 13C NMR (151 MHz, DMSO) δ
158.70 (4C7), 127.90 (4C3a), 126.22 (C5), 126.09 (C1), 125.71 (4C5a), 123.32 (4C9a), 118.58 (C9), 118.20 (C8),
115.66 (C4), 113.44 (C3), 111.44 (C6), 61.04 (4C-tert-Bu), 55.90 (CH3O), 29.39 (tert-Bu). C16H19BF4N2O
(342.14): calcd. C, 56.17; H, 5.60; N, 8.19, found: C, 56.03; H, 5.72; N, 8.35.
4.4.1.19. 2-(tert-butyl)-7-fluoroimidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e5): Prepared from 0.694 g
(2.67 mmol) of d5 and 0.323 ml (3.47 mmol) POCl3 in 20 ml dry toluene for 1 hour at 80°C. Treated with water
o
solution of 0.419 g (4 mmol) NH4BF4. Yield after drying - 0.850 g (97%) white powder with m. p. 258 C
(decomposition). 1H NMR (600 MHz, DMSO) δ 10.42 (d, J = 1.3, 1H, H1), 8.75 (dd, J = 4.4, 9.1, Hz, 1H, H9),
8.56 (d, J = 1.3, 1H, H3), 7.92 (dd, J = 2.7, 9.0, Hz, 1H, H6), 7.80 (td, J = 2.7, 9.1, Hz, 1H, H8), 7.71 (d, J = 9.6
Hz, 1H, H4), 7.63 (d, J = 9.6 Hz, 1H, H5), 1.76 (s, 9H, tert-Bu). 13C NMR (151 MHz, DMSO) δ 160.77 (d, 1JC-F
= 245.8 Hz, 4C7), 128.05 (4C3a), 127.54 (C1), 126.16 (d, J = 9.7 Hz, 4C5a), 126.08 (d, J = 1.6 Hz, 4C9a), 125.50
(d, J = 2.4 Hz, C5), 119.76 (d, J = 9.1 Hz, C9), 117.90 (d, J = 24.7 Hz, C8), 116.62 (C4), 114.74 (d, J = 23.6 Hz,
C6), 113.82 (C3), 61.27 (4C-tert-Bu), 29.33 (tert-Bu). C15H16BF5N2 (330.11): calcd. C, 54.58; H, 4.89; N, 8.49,
found: C, 54.42; H, 4.81; N, 8.53.
22

ACCEPTED MANUSCRIPT
4.4.1.20. 2-adamantanylimidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e6): Prepared from 0.8 g (2.5 mmol) of
d6 and 0.256 ml (2.75 mmol) POCl3 in 27 ml dry toluene for 12 hours at 80°C. Treated with water solution of
0.393 g (3.74 mmol) NH4BF4. Yield after drying - 0.835 g (86%) white powder with m. p. 260 oC
1
(decomposition). H NMR (600 MHz, DMSO) δ 10.45 (d, J = 1.5 Hz, 1H, H1), 8.68 (dd, J = 1.0, 8.3 Hz, 1H,
H9), 8.57 (d, J = 1.5 Hz, 1H, H3), 8.03 (dd, J = 1.4, 8.5 Hz, 1H, H6), 7.87 (ddd, J = 1.2, 7.1, 8.3, 1H, H8), 7.74
(ddd, J = 1.4, 7.1, 8.5, 1H, H7), 7.68 (d, J = 9.6 Hz, 1H, H5), 7.65 (d, J = 9.6 Hz, 1H, H4), 2.31 (bs, 9H,
adamantyl), 1.82 – 1.74 (m, 6H, CH2-adamantyl). 13C NMR (151 MHz, DMSO) δ 130.18 (C8), 129.59 (C6),
129.36 (4C9a), 128.54 (C7), 128.21 (4C3a), 126.83 (C1), 126.63 (C5), 124.15 (4C5a), 117.05 (C9), 115.33 (C4),
112.56 (C3), 60.84 (4C-adamantyl), 41.94 (CH2-adamantyl), 34.96 (CH2-adamantyl), 29.04 (CH-adamantyl).
C21H23BF4N2 (390.23): calcd. C, 64.64; H, 5.94; N, 7.18, found: C, 64.72; H, 5.81; N, 7.03
4.4.1.21. 2-adamantanyl-7-methoxyimidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e7): Prepared from 1.7 g
(4.85 mmol) of d7 and 0.497 ml (5.34 mmol) POCl3 in 60 ml dry toluene for 12 hours at 80°C. Treated with
water solution of 0.763 g (7.28 mmol) NH4BF4. Yield after drying - 1.64 g (80%) white powder with m. p. 292
1
oC (decomposition). H NMR (600 MHz, DMSO) δ 10.37 (bs, 1H, H1), 8.60 (d, J = 9.1 Hz, 1H, H9), 8.53 (bs,
1H, H3), 7.64 (d, J = 9.6, 1H, H5), 7.61 (d, J = 9.6, 1H, H4), 7.55 (d, J = 2.8 Hz, 1H, H6), 7.47 (dd, J = 2.8, 9.1,
Hz, 1H, H8), 3.92 (s, 3H, CH3O), 2.29 (s, 9H, adamantyl), 1.80-1.75 (m, 6H, adamantyl). 13C NMR (151 MHz,
DMSO) δ 158.69 (4C7), 127.80 (4C3a), 126.18 (C5), 125.70 (4C5a), 125.62 (C1), 123.34 (4C9a), 118.52 (C9),
118.18 (C8), 115.68 (C4), 112.54 (C3), 111.44 (C6), 60.65 (4C-adamantyl), 55.88 (CH3O), 41.96 (CH2-
adamantyl), 34.97 (CH2-adamantyl), 29.03 (CH-adamantyl). C22H25BF4N2O (420.26): calcd. C, 62.88; H, 6.00;
N, 6.67, found: C, 62.99; H, 6.16; N, 6.62.
4.4.1.22. 2-(2,6-diisopropylphenyl)imidazo[1,5-a]quinolin-2-ium tetrafluoroborate (e8): Prepared from 3.118 g
(9 mmol) of d8 and 1,1 ml (11.8 mmol) POCl3 in 80 ml dry toluene for 12 hours at 80°C. Treated with water
o
solution of 1.416 g (13.5 mmol) NH4BF4. Yield after drying – 2.855 g (76%) white powder with m. p. 240 C
1
(decomposition). H NMR (600 MHz, DMSO) δ 10.87 (d, J = 1.0 Hz, 1H, H1), 8.60 (d, J = 1.0 Hz, 1H, H3),
8.52 (dd, J = 1.9, 8.5 Hz, 1H, H9), 8.12 (dd, J = 1.0, 7.9 Hz, 1H, H6), 7.91 (ddd, J = 1.0, 7.3, 8.5 Hz, 1H, H8),
7.83 (d, J = 9.6 Hz, 1H, H5), 7.81 (ddd, J = 0.9, 7.3, 7.9 Hz, 1H, H7), 7.79 (d, J = 9.6 Hz, 1H, H4), 7.72 (t, J =
7.9 Hz, 1H, 4H-2,6-diisopropylphenyl), 7.54 (d, J = 7.9 Hz, 2H, 3,5-H-2,6-diisopropylphenyl), 2.38 (sep, J = 6.7
Hz, 2H, CH-isopropyl), 1.19 (d, J = 6.7 Hz, 6H, CH3-isopropyl), 1.16 (d, J = 6.7 Hz, 6H, CH3-isopropyl). 13C
NMR (151 MHz, DMSO) δ = 145.28 (1-4C-2,6-diisopropylphenyl), 131.79 (4C-2,6-diisopropylphenyl), 130.89
(2,6-C-2,6-diisopropylphenyl), 130.33 (C6), 129.61 (C8), 129.61 (C1), 129.42 (C9a), 128.94 (C3a), 128.93 (C7),
127.16 (C5), 124.54 (C5a), 124.48 (3,5-C-2,6-diisopropylphenyl), 117.73 (C3), 117.20 (C9), 115.33 (C4), 27.78
(CH-isopropyl), 24.16 (CH3-isopropyl), 23.91 (CH3-isopropyl). C23H25BF4N2 (416.27): calcd. C, 66.36; H, 6.05;
N, 6.73, found: C, 66.42; H, 6.00; N, 6.58.
General procedure for the synthesis of allyl complexes.
In a Schlenk tube were placed 0.3-0.4 mmol of the corresponding imidazoquinolinium salt (2.1 eqv),
dimeric allyl palladium complex (1 eqv) and finely powdered anhydrous K2CO3 (6 eqv). 2-3 ml dry THF or
dioxane were added. The resulting suspension was stirred at room temperature until full consumption of the
23

ACCEPTED MANUSCRIPT
starting materials and then the solvent was removed under reduced pressure. The crude product was purified by
flash chromatography.
4.4.2. Complex 1
Prepared from 0.150 g (0.4 mmol) e1, 0.076 g (0.19 mmol) [(Me-allyl)PdCl]2 and 0.160 g (1.16 mmol) K2CO3 in
3 ml of dry dioxane for 21 hours. Purified by flash chromatography (hexanes:acetone = 4:1). Yield - 0.115 g
o
1
(71%) pale yellow powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two conformers in
ratio 1:0.72, 273 K) Major δ = 9.99 (dd, J = 1.1, 8.4 Hz, 1H, H9), 7.53 (dd, J = 1.6, 7.4 Hz, 1H, H6), 7.43 (ddd, J
= 1.6, 7.6, 8.4 Hz, 1H, H8), 7.38 (ddd, J = 1.1, 7.4, 7.6 Hz, 1H, H7), 7.35 (bs, 1H, H3), 7.11 (d, J = 9.5 Hz, 1H,
H4), 7.05 (d, J = 9.4 Hz, 1H, H5), 4.89-4.84 (m, 1H, b-NCH2-butyl), 4.56-4.51 (m, 1H, a-NCH2-butyl), 4.26 (d,
J = 3.0 Hz, 1H, HsC), 3.29 (bs, 1H, HaC), 3.16 (dd, J = 1.5, 3.0 Hz, 1H, HsCl), 2.38 (d, J = 1.5 Hz, 1H, HaCl), 2.13
(s,3H, CH3-metallyl), 1.98-1.91 (m, 1H, b-CH2CH2CH3-butyl), 1.89-1.83 (m, 1H, a-CH2CH2CH3-butyl), 1.48-
1.43 (m, 2H, CH2CH3-butyl), 0.99 (t, J=7.4 Hz, 3H, CH3-butyl); Minor δ = 10.19 (d, J = 8.4 Hz, 1H, H9), 7.55
(ddd, J = 1.6, 7.6, 8.4 Hz, 1H, H8), 7.54 (dd, J = 1.6, 7.4 Hz, 1H, H6), 7.39 (ddd, J = 1.1, 7.4, 7.6 Hz, 1H, H7),
7.32 (bs, 1H, H3), 7.11 (d, J = 9.5 Hz, 1H, H4), 7.03 (d, J = 9.4 Hz, 1H, H5), 4.64-4.58 (m, 1H, b-NCH2-butyl),
4.35-4.30 (m, 1H, a-NCH2-butyl), 4.19 (d, J = 3.0 Hz, 1H HsC), 3.44 (bs, 1H, HaC), 3.16 (dd, J = 1.5, 3.0 Hz, 1H,
HsCl), 2.41 (d, J = 1.5 Hz, 1H, HaCl), 2.05 (s,3H, CH3-metallyl), 2.08-2.01 (m, 1H, b-CH2CH2CH3-butyl), 1.98-
1.91 (m, 1H, a-CH2CH2CH3-butyl), 1.43-1.37 (m, 2H, CH2CH3-butyl), 0.97 (t, J=7.4 Hz, 3H, CH3-butyl). 13C
NMR (151 MHz, CDCl3, two conformers in ratio 1:0.72, 273 K) Major δ = 173.74 (4CNHC), 134.34 (4C9a),
131.04 (4C3a), 130.03 (4Cmeso), 128.30 (C6), 128.25 (C8), 125.99 (C7), 124.66 (4C5a), 124.04 (C5),118.34 (C9),
115.32 (C4), 113.35 (C3), 70.87 (CC), 53.20 (NCH2-butyl), ), 50.31 (CCl), 33.18 (CH2CH2CH3-butyl), 23.41
(CH3-metallyl), 19.97 (CH2CH3-butyl), 13.81 (CH3-butyl) Minor δ = 173.72 (4CNHC), 134.43 (4C9a), 131.01
(4C3a), 128.72 (4Cmeso), 128.36 (C6), 128.25 (C8), 125.99 (C7), 124.75 (4C5a), 124.17 (C5), 118.53 (C9), 115.25
(C4), 113.25 (C3), 70.28 (CC), 53.22 (NCH2-butyl), 50.46 (CCl), 33.22 (CH2CH2CH3-butyl), 23.43 (CH3-
metallyl), 20.06 (CH2CH3-butyl), 13.77 (CH3-butyl). C19H23ClN2Pd (421.28): calcd. C, 54.17; H, 5.50; N, 6.65,
found: C, 54.01; H, 5.62; N, 6.69.
4.4.3. Complex 2
Prepared from 0.150 g (0.38 mmol) of e2, 0.070 g (0.18 mmol) [(Me-allyl)PdCl]2 and 0.148 g (1.07 mmol)
K2CO3 in 3 ml of dry dioxane for 24 hours. Purified by flash chromatography (hexanes:acetone = 10:3). Yield –
light brown oil (quantitative yield). 1H NMR (600 MHz, CDCl3, two conformers in ratio 1:0.72, 273 K) Major δ
= 9.89 (d d, J = 8.9 Hz, 1H, H9), 7.32 (bs, 1H, H3), 7.11-7.08 (m, 1H, H4), 6.99-6.97 (m, 3H, H5, H6 and H8),
4.89-4.83 (m, 1H, b-NCH2-butyl), 4.52-4.47 (m, 1H, a-NCH2-butyl), 4.24 (d, J = 2.8 Hz, 1H, HsC), 3.86 (s, 3H, -
OMe), 3.28 (bs, 1H, HaC), 3.15 (bs, 1H, HsCl), 2.37 (d bs, 1H, HaCl), 2.11 (s, 3H, CH3-metallyl), 1.96-1.88 (m,
1H, b-CH2CH2CH3-butyl), 1.87-1.79 (m, 1H, a-CH2CH2CH3-butyl), 1.46-1.41 (m, 2H, CH2CH3-butyl), 0.97 (t,
J=7.4 Hz, 3H, CH3-butyl); Minor δ = 10.08 (d, J = 8.9 Hz, 1H, H9), 7.29 (bs, 1H, H3), 7.11-7.08 (m, 2H, H4
and H8), 6.99-6.97 (m, 2H, H5 and H6), 4.62-4.57 (m, 1H, b-NCH2-butyl), 4.30-4.26 (m, 1H, a-NCH2-butyl),
4.18 (d, J = 2.8 Hz, 1H HsC), 3.87 (s, 3H, -OMe), 3.42 (bs, 1H, HaC), 3.15 (bs, 1H, HsCl), 2.39 (bs, 1H, HaCl),
2.05 (s,3 H, CH3-metallyl), 2.08-2.00 (m, 1H, b-CH2CH2CH3-butyl), 1.96-1.88 (m, 1H, a-CH2CH2CH3-butyl),
24

ACCEPTED MANUSCRIPT
1.41-1.36 (m, 2H, CH2CH3-butyl), 0.95 (t, J=7.4 Hz, 3H, CH3-butyl). 13C NMR (151 MHz, CDCl3, two
conformers in ratio 1:0.72, 273 K) Major δ = 171.8 (4CNHC), 157.02 (4C7), 130.50 (4C3a), 130.05 (4Cmeso),
128.32 (4C5a), 125.82 (4C9a), 123.70 (C5), 119.47 (C9), 115.84 (C4), 115.39 (C8), 113.35 (C3), 110.82 (C6),
70.83 (CC), 55.53 (-OMe), 52.97 (NCH2-butyl), 50.35 (CCl), 33.19 (CH2CH2CH3-butyl), 23.47 (CH3-metallyl),
19.90 (CH2CH3-butyl), 13.87 (CH3-butyl); Minor δ = 171.84 (4CNHC), 157.00 (4C7), 130.45 (4C3a), 129.04
(4Cmeso), 128.40 (4C5a), 125.80 (4C9a), 123.83 (C5), 119.61 (C9), 115.75 (C4), 115.66 (C8), 113.28 (C3), 110.50
(C6), 70.23 (CC), 55.53 (-OMe), 53.00 (NCH2-butyl), 50.46 (CCl), 33.28 (CH2CH2CH3-butyl), 23.47 (CH3-
metallyl), 20.01 (CH2CH3-butyl), 13.84 (CH3-butyl). C20H25ClN2OPd (451.30): calcd. C, 53.23; H, 5.58; N, 6.21,
found: C, 53.10; H, 5.67; N, 6.19.
4.4.4. Complex 3
Prepared from 0.120 g (0.39 mmol) e3, 0.072 g (0.18 mmol) [(Me-allyl)PdCl]2, 0.152 g (0.11 mmol) K2CO3 in 3
ml of dry THF for 17 hours. Purified by flash chromatography (hexanes:acetone = 4:1). Yield 0.067 g (44%)
o
1
light brown powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two conformers in ratio
1:0.82, 293 K) Major δ = 10.49 (dd, J = 1.1, 8.7 Hz, 1H, H9), 7.58 (bs, 1H, H3), 7.53 (dd, J = 1.5, 7.7 Hz, 1H,
H6), 7.47 (ddd, J = 1.5, 7.3, 8.7 Hz, 1H, H8), 7.39 (ddd, J = 1.1, 7.3, 7.7 Hz, 1H, H7), 7.11 (d, J = 9.4 Hz, 1H,
H4), 7.04 (d, J = 9.4 Hz, 1H, H5), 4.23 (d, J = 3.1 Hz, 1H, HsC), 3.35 (bs, 1H, HaC), 3.11 (dd, J = 1.5, 3.1 Hz,
1H, HsCl), 2.25 (d, J = 1.5 Hz, 1H, HaCl), 2.05 (bs, 3H, CH3-metallyl), 2.05 (s, 9H, tert-Bu); Minor δ = 10.77 (d,
J = 8.7 Hz, 1H, H9), 7.57 (ddd, J = 1.5, 7.3, 8.7 Hz, 1H, H8), 7.56 (dd, J = 1.5, 7.7 Hz, 1H, H6), 7.55 (s, 1H,
H3), 7.42 (ddd, J = 1.1, 7.3, 7.7 Hz, 1H, H7), 7.12 (d, J = 9.4 Hz, 1H, H4), 7.06 (d, J = 9.4 Hz, 1H, H5), 4.17 (d,
J = 3.1 Hz, 1H HsC), 3.48 (bs, 1H, HaC), 3.07 (dd, J = 1.5, 3.1 Hz, 1H, HsCl), 2.41 (d, J = 1.5 Hz, 1H, HaCl), 2.05
(bs, 3H, CH3-metallyl), 1.94 (s, 9H, tert-Bu). 13C NMR (151 MHz, CDCl3, two conformers in ratio 1:0.82, 293
K) Major δ = 172.69 (4CNHC), 134.58 (4C9a), 129.97 (4C3a), 129.49 (4Cmeso), 128.35 (C8), ,128.19 (C6), 125.93
(C7), 125.01 (4C5a), 123.92 (C5), 118.98 (C9), 115.38 (C4), 112.39 (C3), 69.55 (CC), 59.65 (4C-tert-Bu), 51.81
(CCl), 32.07 (tert-butyl), 23.55 (CH3-metallyl); Minor δ = 172.64 (4CNHC), 134.43 (4C9a), 129.81 (4C3a), 128.80
(4Cmeso), 128.39 (C8), 128.27 (C6), 125.91 (C7), 125.17 (4C5a), 123.99 (C5), 119.17 (C9), 115.38 (C4), 112.13
(C3), 68.73 (CC), 59.23 (4C-tert-Bu), 51.70 (CCl), 31.79 (tert-butyl), 22.96 (CH3-metallyl). C19H23ClN2Pd
(421.28): calcd. C, 54.17; H, 5.50; N, 6.65, found: C, 54.01; H, 5.45; N, 6.67.
4.4.5. Complex 4
Prepared from 0.050 g (0.146 mmol) e4, 0.029 g (0.073 mmol) [(Me-allyl)PdCl]2, 0.050 g (0.365 mmol) K2CO3
in 2 ml of dry THF for 48 hours. Purified by flash chromatography (cyclohexane : acetone = 4:1). Yield 0.056 g
o
1
(85%) of pale yellow powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, 293 K): 1:0.84
mixture of rotamers; signals for major conformer: δ = 10.37 (d, J=9.2 Hz, 1H, H9), 7.54 (s, 1H, H3), 7.09 (d,
J=9.4 Hz, 1H, H4), 7.00 (dd, J=3.0, 9.2 Hz, 1H, H8), 6.98 (d, J=3.0 Hz, 1H, H6), 6.97 (d, J=9.4 Hz, 1H, H5),
4.19 (d, J=3.0 Hz, 1H, HsC), 3.84 (s, 1H, OCH3), 3.32 (bs, 1H, HaC), 3.08 (dd, J=1.8, 3.0 Hz, 1H, HsCl), 2.22 (d,
J=1.8 Hz, 1H, HaCl), 2.03 (s, 3H, CH3-metallyl), 2.01 (s, 9H, tert-Bu). Signals for minor conformer: δ = 10.65
(d, J=9.2 Hz, 1H, H9), 7.50 (s, 1H, H3), 7.10 (dd, J=3.0, 9.2 Hz, 1H, H8), 7.08 (d, J=9.4 Hz, 1H, H4), 6.96 (d,
J=9.4 Hz, 1H, H5), 6.95 (d, J=3.3 Hz, 1H, H6), 4.14 (d, J= 3.0 Hz, 1H, HsC), 3.85 (s, 3H, OCH3), 3.44 (bs, 1H,
25

ACCEPTED MANUSCRIPT
HaC), 3.04 (dd, J=1.8, 3.3 Hz, 1H, HsCl), 2.37 (d, J=1.8 Hz, 1H, HaCl), 2.03 (s, 3H, CH3-metallyl), 1.90 (s, 9H,
tert-Bu). 13C NMR (150.9 MHz, CDCl3, 293 K): signals for major conformer: δ = 171.88 (4CNHC), 157.19 (4C7),
129.56 (4C3a), 129.33 (4Cmeso), 128.66 (4C9a), 126.38 (4C5a), 123.79 (C5), 120.59 (C9), 115.91 (C4), 115.15
(C8), 112.40 (C3), 110.86 (C6), 69.57 (CC), 59.55 (4C-tert-Bu), 55.51 (OCH3), 51.44 (CCl), 32.11 (tert-Bu),
23.48 (CH3-metallyl); signals for minor conformer: δ = 171.83 (4CNHC), 157.19 (4C7), 129.56 (4C3a), 128.90
(4Cmeso), 128.77 (4C9a), 126.54 (4C5a), 123.73 (C5), 120.77 (C9), 115.91 (C4), 115.05 (C8), 112.15 (C3), 111.23
(C6), 68.74 (CC), 59.13 (4C-tert-Bu), 55.51 (OCH3), 51.56 (CCl), 31.85 (tert-Bu), 22.88 (CH3-metallyl).
C20H25ClN2OPd (451.30): calcd. C, 53.23; H, 5.58; N, 6.21, found: C, 53.35; H, 5.47; N, 6.25.
4.4.6. Complex 5
Prepared from 0.100 g (0.3 mmol) e5, 0.057 g (0.14 mmol) [(Me-allyl)PdCl]2, 0.120 g (0.87 mmol) K2CO3 in 3
ml of dry dioxane for 29 hours. Purified by flash chromatography (hexanes:EtOAc=2:3). Yield - 0.105 g (83%)
beige powder with m.p. 120 oC (decomposition). 1H NMR (600 MHz, CDCl3, two conformers in ratio 1:0.8, 293
K) Major δ = 10.51 (dd, J = 4.8, 9.3 Hz, 1H, H9), 7.59 (s, 1H, H3), 7.19 (dd, J = 2.9, 8.5 Hz, 1H, H6), 7.14 (d, J
= 9.4 Hz, 1H, H4), 7.14 (ddd, J = 2.9, 7.8, 9.3 Hz, 1H, H8), 6.97 (d, J = 9.4 Hz, 1H, H5). 4.22 (d, J = 3.1 Hz,
1H, HsC), 3.34 (bs, 1H, HaC), 3.11 (dd, J = 1.5, 3.1 Hz, 1H, HsCl), 2.24 (d, J = 1.5 Hz, 1H, HaCl), 2.03 (bs, 3H,
CH3-metallyl), 2.03 (s, 9H, tert-Bu); Minor δ = 10.78 (dd, J = 4.8, 9.3 Hz, 1H, H9), 7.56 (s, 1H, H3), 7.25 (ddd,
J = 2.9, 7.8, 9.3 Hz, 1H, H8), 7.22 (dd, J = 2.9, 8.5 Hz, 1H, H6), 7.15 (d, J = 9.4 Hz, 1H, H4), 6.98 (d, J = 9.4
Hz, 1H, H5), 4.17 (d, J = 3.1 Hz, 1H HsC), 3.44 (bs, 1H, HaC), 3.07 (dd, J = 1.5, 3.1 Hz, 1H, HsCl), 2.38 (d, J =
1.5 Hz, 1H, HaCl), 2.04 (bs, 3H, CH3-metallyl), 1.92 (s, 9H, tert-Bu). 13C NMR (151 MHz, CDCl3, two
conformers in ratio 1:0.8, 293 K) Major δ = 173.31 (4CNHC), 160.19 (d, 1JC-F = 247.0 Hz, 4C7), 130.99 (d, JC-F
=
4
4
2.6 Hz, C5a), 129.82 (4C3a), 129.46 (4Cmeso), 126.92 (d, JC-F = 8.5 Hz, C9a), 123.11 (d, JC-F = 2.5 Hz, C5),
121.16 (d, J = 8.0 Hz, C9), 116.79 (C4), 115.31 (d, JC-F = 23.0 Hz, C8), 113.47 (d, JC-F = 22.8 Hz, C7), 112.89
(C3), 69.84 (CC), 59.87 (4C-tert-Bu), 51.79 (CCl), 32.13 (tert-butyl), 23.51 (CH3-metallyl); Minor δ = 173.21
1
4
4
(4CNHC), 160.19 (d, JC-F = 247.0 Hz, C7), 131.15 (d, JC-F = 2.6 Hz, C5a), 129.68 (4C3a), 128.97 (4Cmeso),
127.04 (d, JC-F = 8.5 Hz, 4C9a), 123.18 (d, JC-F = 2.5 Hz, C5), 121.35 (d, J = 8.0 Hz, C9), 116.79 (C4), 115.54 (d,
JC-F = 23.0 Hz, C8), 113.57 (d, JC-F = 22.8 Hz, C7), 112.64 (C3), 69.02 (CC), 59.45 (4C-tert-Bu), 51.74 (CCl),
31.87 (tert-butyl), 22.90 (CH3-metallyl). C19H22ClFN2Pd (439.27): calcd. C, 51.95; H, 5.05; N, 6.38, found: C,
52.11; H, 4.98; N, 6.27.
4.4.7. Complex 6
Prepared from 0.150 g (0.384 mmol) of e6, 0.072 g (0.183 mmol) [(Me-allyl)PdCl]2, 0.152 g (0.11 mmol)
K2CO3 in 2 ml of dry THF for 48 hours. Purified by flash chromatography (hexanes: acetone = 4:1). Yield -
o
1
0.098 g (54%) of pale brown powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two
conformers in ratio 1:0.72, 293 K) Major δ = 10.80 (d, J = 8.5 Hz, 1H, H9), 7.56 (s, 1H, H3), 7.53 (ddd, J = 1.5,
7.7, 8.5 Hz, 1H, H8), 7.51 (dd, J = 1.5, 7.7 Hz, 1H, H6), 7.39 (ddd, J = 1.0, 7.8, 8.3 Hz, 1H, H7), 7.11 (d, J = 9.3
Hz, 1H, H4), 7.04 (d, J = 9.3 Hz, 1H, H5), 4.18 (d, J = 2.9 Hz, 1H, HsC), 3.34 (bs, 1H, HaC), 3.01 (dd, J = 1.5,
2.9 Hz, 1H, HsCl), 2.61-2.60 (m, 6H, CH2-adamantyl), 2.29-2.27 (m, 3H, CH-adamantyl), 2.25 (d, J = 1.5 Hz,
1H, HaCl), 2.05 (bs, 3H, CH3-metallyl), 1.78-1.74 (m, 6H, CH2-adamantyl); Minor δ = 10.49 (d, J = 8.5 Hz, 1H,
26

ACCEPTED MANUSCRIPT
H9), 7.61 (s, 1H, H3), 7.55 (dd, J = 1.5, 7.7 Hz, 1H, H6), 7.44 (ddd, J = 1.5, 7.7, 8.5 Hz, 1H, H8), 7.37 (ddd, J =
1.0, 7.8, 8.3 Hz, 1H, H7), 7.10 (d, J = 9.3 Hz, 1H, H4), 7.02 (d, J = 9.3 Hz, 1H, H5), 4.21 (d, J = 2.9 Hz, 1H,
HsC), 3.48 (bs, 1H, HaC), 3.08 (dd, J = 1.5, 2.9 Hz, 1H, HsCl), 2.77-2.71 (m, 6H, CH2-adamantyl), 2.38 (d, J = 1.5
Hz, 1H, HaCl), 2.34-2.32 (m, 3H, CH-adamantyl), 2.04 (bs, 3H, CH3-metallyl), 1.83-1.77 (m, 6H, CH2-
adamantyl). 13C NMR (151 MHz, CDCl3, two conformers in ratio 1:0.92, 293 K) Major δ = 172.56 (4CNHC),
134.83 (4C9a), 129.81 (4Cmeso), 128.71 (4C3a), 128.31 (C6), 128.29 (C8), 125.93 (C7), 125.38 (4C5a), 123.88
(C5), 119.43 (C9), 115.51 (C4), 111.37 (C3), 68.84 (CC), 59.34 (4C-adamantyl), 51.76 (CCl), 43.90 (CH2-
adamantyl), 35.81 (CH2-adamantyl), 29.90 (CH-adamantyl), 22.98 (CH3-metallyl); Minor δ = 172.34 (4CNHC),
134.64 (4C9a), 129.91 (4Cmeso), 129.26 (4C3a), 128.22 (C6), 128.14 (C8), 125.93 (C7), 125.20 (4C5a), 123.82
(C5), 119.16 (C9), 115.52 (C4), 111.55 (C3), 69.33 (CC), 60.39 (4C-adamantyl), 51.76 (CCl), 44.22 (CH2-
adamantyl), 35.89 (CH2-adamantyl), 30.03 (CH-adamantyl), 23.46 (CH3-metallyl). C25H29ClN2Pd (499.39):
calcd. C, 60.13; H, 5.85; N, 5.61, found: C, 60.01; H, 5.73; N, 5.69.
4.4.8. Complex 7
Prepared from 0.141 g (0.336 mmol) e7, 0.063 g (0.16 mmol) [(Me-allyl)PdCl]2, 0.133 g (0.96 mmol) K2CO3 in
2 ml of dry THF for 48 hours. Purified by flash chromatography (hexanes: acetone = 4:1). Yield 0.142 g (84%)
o
1
beige powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two conformers in ratio 1:0.95,
293 K) Major δ = 10.71 (d, J = 9.0 Hz, 1H, H9), 7.54 (s, 1H, H3), 7.11 (dd, J = 2.9, 9.0 Hz, 1H, H8), 7.10 (d, J =
9.4 Hz, 1H, H4), 6.99 (d, J = 2.9 Hz, 1H, H6), 6.97 (d, J = 9.7 Hz, 1H, H5), 4.17 (d, J = 2.9 Hz, 1H, HsC), 3.86
(s, 3H, -OMe), 3.33 (bs, 1H, HaC), 3.99 (dd, J = 1.5, 2.9 Hz, 1H, HsCl), 2.60-2.59 (m, 6H, CH2-adamantyl), 2.28-
2.26 (m, 3H, CH-adamantyl), 2.24 (d, J = 1.5 Hz, 1H, HaCl), 2.03 (bs, 3H, CH3-metallyl), 1.78-1.74 (m, 6H,
CH2-adamantyl); Minor δ = 10.40 (d, J = 9.0 Hz, 1H, H9), 7.59 (s, 1H, H3), 7.09 (d, J = 9.4 Hz, 1H, H4), 7.01
(dd, J = 2.9, 9.0 Hz, 1H, H8), 6.96 (d, J = 2.9 Hz, 1H, H6), 6.95 (d, J = 9.7 Hz, 1H, H5), 4.19 (d, J = 2.9 Hz, 1H,
HsC), 3.85 (s, 3H, -OMe), 3.46 (bs, 1H, HaC), 3.07 (dd, J = 1.5, 2.9 Hz, 1H, HsCl), 2.76-2.69 (m, 6H, CH2-
adamantyl), 2.36 (d, J = 1.5 Hz, 1H, HaCl), 2.33-2.31 (m, 3H, CH-adamantyl), 2.05 (bs, 3H, CH3-metallyl), 1.83-
1.77 (m, 6H, CH2-adamantyl). 13C NMR (151 MHz, CDCl3, two conformers in ratio 1:0.95, 293 K) Major δ =
171.07 (4CNHC), 157.21 (4C7), 129.39 (4C3a), 128.65 (4Cmeso), 129.19 (4C5a), 126.63 (4C9a), 123.63 (C5), 120.79
(C9), 116.04 (C4), 114.96 (C8), 111.40 (C3), 110.88 (C6), 68.83 (CC), 59.75 (4C-adamantyl), 55.54 (-OMe),
51.58 (CCl), 43.91 (CH2-adamantyl), 35.81 (CH2-adamantyl), 29.89 (CH-adamantyl), 22.98 (CH3-metallyl);
Minor δ = 171.27 (4CNHC), 157.21 (4C7), 130.45 (4C3a), 128.84 (4Cmeso), 129.02 (4C5a), 126.45 (4C9a), 123.57
(C5), 120.59 (C9), 116.04 (C4), 115.09 (C8), 111.57 (C3), 111.27 (C6), 69.35 (CC), 60.20 (4C-adamantyl), 55.54
(-OMe), 51.63 (CCl), 44.23 (CH2-adamantyl), 35.90 (CH2-adamantyl), 30.02 (CH-adamantyl), 23.49 (CH3-
metallyl). C26H31ClN2OPd (529.42): calcd. C, 58.99; H, 5.90; N, 5.29, found: C, 58.89; H, 5.99; N, 5.32.
4.4.9. Complex 8
Prepared from 0.150 g (0.36 mmol) of e8, 0.068 g (0.172 mmol) [(Me-allyl)PdCl]2, 0.142 g (1,03 mmol) K2CO3
in 3 ml of dry THF for 24 hours. Purified by flash chromatography (hexanes:EtOAc = 5:2). Yield - 0.175 g
o
1
(97%) beige powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two conformers in ratio
1:0.92, 293 K) Major δ = 10.34 (d, J = 8.5 Hz, 1H, H9), 7.65 (ddd, J = 1.4, 7.2, 8.5 Hz, 1H, H8), 7.61 (dd, J =
27

ACCEPTED MANUSCRIPT
1.4, 7.8 Hz, 1H, H6), 7.47-7.44 (m, 1H, 4H-2,6-diisopropylphenyl), 7.43 (ddd, J = 0.9, 7.4, 7.6 Hz, 1H, H7),
7.37 (dd, J = 1.4, 7.9 Hz, 1H, 3,5-H-2,6-diisopropylphenyl), 7.32 (s, 1H, H3), 7.23 (dd, J = 1.4, 7.9 Hz, 1H, 3,5-
H-2,6-diisopropylphenyl), 7.18 (d, J = 9.4 Hz, 1H, H4), 7.17 (d, J = 9.4 Hz, 1H, H5), 3.92 (d, J = 3.2 Hz, 1H,
HsC), 3.23 (bs, 1H, HaC), 3.27-3.21 (m, 1H, CH-isopropyl), 3.11-3.06 (m, 1H, m, 1H, CH-isopropyl), 2.98 (dd, J
= 1.3, 3.2 Hz, 1H, HsCl), 2.33 (bs, 1H, HaCl), 1.40 (, J = 6.8 Hz, 3H, CH3-isopropyl), 1.31 (, J = 6.8 Hz, 3H, CH3-
isopropyl), 1.12 (s, 3H, CH3-metallyl), 1.03 (, J = 6.8 Hz, 3H, CH3-isopropyl), 0.97 (, J = 6.8 Hz, 3H, CH3-
isopropyl); Minor δ = 10.16 (d, J = 8.5 Hz, 1H, H9), 7.58 (dd, J = 1.5, 7.7 Hz, 1H, H6), 7.53 (ddd, J = 1.4, 7.2,
8.5 Hz, 1H, H8), 7.47-7.44 (m, 1H, 4H-2,6-diisopropylphenyl), 7.46 (ddd, J = 0.9, 7.4, 7.6 Hz, 1H, H7), 7.35 (s,
1H, H3), 7.34 (dd, J = 1.4, 7.8 Hz, 1H, 3,5-H-2,6-diisopropylphenyl), 7.28 (dd, J = 1.4, 7.8 Hz, 1H, 3,5-H-2,6-
diisopropylphenyl), 7.18 (d, J = 9.4 Hz, 1H, H4), 7.16 (d, J = 9.4 Hz, 1H, H5), 4.06 (d, J = 3.2 Hz, 1H, HsC),
3.17 (dd, J = 1.3, 3.2 Hz, 1H, HsCl), 2.82 (bs, 1H, HaC), 2.27-2.22 (m, 2H, CH-isopropyl), 2.02 (s, 3H, CH3-
metallyl), 1.62 (bs, 1H, HaCl), 1.30 (d, J = 6.8 Hz, 3H, CH3-isopropyl), 1.24 (, J = 6.8 Hz, 3H, CH3-isopropyl),
1.12 (, J = 6.8 Hz, 3H, CH3-isopropyl), 1.10 (, J = 6.8 Hz, 3H, CH3-isopropyl). 13C NMR (151 MHz, CDCl3, two
conformers in ratio 1:0.92, 293 K) Major δ = 177.98 (4CNHC), 144.82 (2,6-4C-2,6-diisopropylphenyl), 144.68
(2,6-4C-2,6-diisopropylphenyl), 137.06 (1-4C-2,6-diisopropylphenyl), 134.29 (4C9a), 130.58 (4C3a), 130.03 (4-
C-2,6-diisopropylphenyl), 128.97 (4Cmeso), 128.93 (C8), 128.25 (C6), 126.35 (C7), 125.19 (C5), 124.97 (4C5a),
124.56 (3,5-C-2,6-diisopropylphenyl), 123.17 (3,5-C-2,6-diisopropylphenyl), 119.80 (C9), 116.95 (C3), 115.07
(C4), 70.18 (CC), 50.03 (CCl), 28.10 (CH-isopropyl), 28.08 (CH-isopropyl), 26.40 (CH3-isopropyl), 26.21 (CH3-
isopropyl), 23.06 (2*CH3-isopropyl), 21.84 (CH3-metallyl)Minor δ = 177.54 (4CNHC), 147.69 (2,6-4C-2,6-
diisopropylphenyl), 147.64 (2,6-4C-2,6-diisopropylphenyl), 137.18 (1-4C-2,6-diisopropylphenyl), 134.25 (4C9a),
130.73 (4C3a), 130.13 (4-C-2,6-diisopropylphenyl), 129.34 (4Cmeso), 128.52 (C8), 128.28 (C6), 126.30 (C7),
125.04 (C5), 124.92 (4C5a), 124.31 (3,5-C-2,6-diisopropylphenyl), 122.88 (3,5-C-2,6-diisopropylphenyl), 119.37
(C9), 116.89 (C3), 115.13 (C4), 71.53 (CC), 51.05 (CCl), 28.35 (CH-isopropyl), 28.16 (CH-isopropyl), 27.02
(CH3-isopropyl), 26.84 (CH3-isopropyl), 22.47 (CH3-isopropyl), 22.30 (CH3-isopropyl), 23.38 (CH3-metallyl).
C27H31ClN2Pd (525.43): calcd. C, 61.72; H, 5.95; N, 5.33, found: C, 61.65; H, 5.89; N, 5.37.
4.4.10. Complex 9
Prepared from 0.150 g (0.36 mmol) of e8, 0.063 g (0.172 mmol) [(allyl)PdCl]2 and 0.166 g (0.12 mmol) K2CO3
in 3 ml of dry THF for 24 hours. Purified by flash chromatography (hexanes:EtOAc = 5:1). Yield - 0.170 g
O
1
(97%) beige powder with m.p. 120 C (decomposition). H NMR (600 MHz, CDCl3, two conformers in ratio
1:0.65, 293 K) Major δ = 10.05 (d, J = 8.3 Hz, 1H, H9), 7.65-7.59 (m, 1H, H8), 7.61-7.59 (m, 1H, H6), 7.56-
7.52 (m, 1H, 4H-2,6-diisopropylphenyl), 7.52-7.49 (m, 1H, H7), 7.44-7.43 (m, 1H, 3,5-H-2,6-
diisopropylphenyl), 7.44 (s, 1H, H3), 7.31-7.29 (m, 1H, 3,5-H-2,6-diisopropylphenyl), 7.26 (d, J = 9.4 Hz, 1H,
H4), 7.25 (d, J = 9.4 Hz, 1H, H5) 5.44-5.37 (m, 1H, Hmeso), 4.34 (dd, J = 2.1, 7.4 Hz, 1H, HsC), 3.45 (d, J = 6.7
Hz, 1H, HsCl), 3.34 (m, 1H, CH-isopropyl), 3.03 (d, J = 13.5 Hz, 1H, HaC), 2.32 (m, 1H, CH-isopropyl), 1.66 (d,
J = 12.0 Hz, 1H, HaCl), 1.49 (d, J = 6.7 Hz, 1H, CH3-isopropyl), 1.31 (d, J = 6.7 Hz, 1H, CH3-isopropyl), 1.19
(d, J = 6.7 Hz, 1H, CH3-isopropyl), 1.12 (d, J = 6.7 Hz, 1H, CH3-isopropyl); Minor δ = 10.42 (d, J = 8.3 Hz, 1H,
H9), 7.70-7.67 (m, 1H, H8), 7.69-7.37 (m, 1H, H6), 7.56-7.52 (m, 1H, 4H-2,6-diisopropylphenyl), 7.55-7.52 (m,
1H, H7), 7.41-7.49 (m, 1H, 3,5-H-2,6-diisopropylphenyl), 7.40 (s, 1H, H3), 7.33-7.31 (m, 1H, 3,5-H-2,6-
28

ACCEPTED MANUSCRIPT
diisopropylphenyl), 7.28 (d, J = 9.4 Hz, 1H, H4), 7.27 (d, J = 9.4 Hz, 1H, H5), 4.90-4.84 (m, 1H, Hmeso), 4.13
(dd, J = 2.1, 7.4 Hz, 1H, HsC), 3.42 (d, J = 13.5 Hz, 1H, HaC), 3.34 (d, J = 6.7 Hz, 1H, HsCl), 3.01 (m, 1H, CH-
isopropyl), 2.50 (d, J = 12.0 Hz, 1H, HaCl), 2.38 (m, 1H, CH-isopropyl), 1.41 (d, J = 6.7 Hz, 1H, CH3-isopropyl),
1.30 (d, J = 6.7 Hz, 1H, v), 1.16 (d, J = 6.7 Hz, 1H, CH3-isopropyl), 1.06 (d, J = 6.7 Hz, 1H, CH3-isopropyl). 13
C
NMR (151 MHz, CDCl3, two conformers in ratio 1:0.65, 293 K) Major δ = 176.79 (4CNHC) , 147.66 (2,6-4C-2,6-
diisopropylphenyl), 144.89 (2,6-4C-2,6-diisopropylphenyl), 137.07 (1-4C-2,6-diisopropylphenyl), 134.16 (4C9a),
130.64 (4C3a), 130.22 (4-C-2,6-diisopropylphenyl), 128.68 (C8), 128.23 (C6), 126.35 (C7), 125.19 (C5), 124.87
(4C5a), 124.31 (3,5-C-2,6-diisopropylphenyl), 122.92 (3,5-C-2,6-diisopropylphenyl), 119.56 (C9), 116.83 (C3),
115.02 (C4), 114.23 (Cmeso), 73.10 (CC), 50.24 (CCl), 28.39 (CH-isopropyl), 28.10 (CH-isopropyl), 26.80 (CH3-
isopropyl), 26.44 (CH3-isopropyl), 23.10 (CH3-isopropyl), 22.33 (CH3-isopropyl); Minor δ = 176.67 (4CNHC),
147.26
(2,6-4C-2,6-diisopropylphenyl),
144.50
(2,6-4C-2,6-diisopropylphenyl),
136.47
(1-4C-2,6-
diisopropylphenyl), 134.38 (4C9a), 130.52 (4C3a), 130.17 (4-C-2,6-diisopropylphenyl),128.98 (C8), 128.43 (C6),
126.43 (C7), 125.04 (C5), 125.00 (4C5a), 124.31 (3,5-C-2,6-diisopropylphenyl), 122.92 (3,5-C-2,6-
diisopropylphenyl), 119.29 (C9), 117.25 (C3), 115.14 (C4), 113.62 (Cmeso), 70.34 (CC), 50.93 (CCl), 28.37 (CH-
isopropyl), 28.07 (CH-isopropyl), 26.59 (CH3-isopropyl), 26.48 (CH3-isopropyl), 22.68 (CH3-isopropyl), 22.33
(CH3-isopropyl). C26H29ClN2Pd (511.40): calcd. C, 61.06; H, 5.72; N, 5.48, found: C, 60.95; H, 5.83; N, 5.45.
Acknowledgement
The financial support by the Bulgarian Science Fund (Projects UNA-17/2005, RNF01/0110 and DRNF-
02/13), the Program for career development of young scientists-BAS (DFNP-130/2016) and the Sofia University
Research Fund (143/05.2010 and 093/05.2014) is gratefully acknowledged.
Appendix A. Supplementary data
Supplementary data related to this article (copies of the 1H and 13C NMR spectra of the new complexes,
details of dynamic NMR studies and DFT calculations) are provided.
References
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