Preventing Pd-NHC bond cleavage and switching from nano-scale to molecular catalytic systems: Amines and temperature as catalyst activators

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ISSN 2044-4761

PAPER

Chaoqiu Chen, Yong Qin et al.

Highly dispersed Pt nanoparticles supported on carbon

nanotubes produced by atomic layer deposition for hydrogen

generation from hydrolysis of ammonia borane

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DOI: 10.1039/C9CY02041A

ARTICLE

Preventing Pd-NHC bond cleavage and switching from nano-scale

to molecular catalytic systems: amines and temperature as

catalyst activators

Received 00th January 20xx,

Accepted 00th January 20xx

Oleg V. Khazipov,^a,cMaxim A. Shevchenko,^a,cDmitry V. Pasyukov,^aAndrey Yu. Chernenko,^a

DOI: 10.1039/x0xx00000x

Alexander V. Astakhov,^a,cVictor A. Tafeenko,^bVictor M. Chernyshev,^a,c*Valentine P. Ananikov,^a,b,c*

www.rsc.org/

ABSTRACT: Many reactions catalyzed by Pd complexes with N-heterocyclic carbene (NHC) ligands are performed in the

presence of amines which usually act as coupling reagents or mild bases. However, amines can react with Pd/NHC

complexes in a number of ways: enhancing molecular catalysis, causing the catalyst deactivation or triggering the

ligandless modes of catalysis by producing NHC-free active palladium species. This study gains insight into conditions

required for the efficient use of amines as activators of molecular Pd/NHC catalysis and preventing the undesirable

reductive cleavage of the Pd-NHC bond in catalytic systems. Reactions of Pd/NHC complexes with various amines within a

temperature range of 25–140 °C and thermal stability of the resulting amino-complexes are examined. The results indicate

the major influence of the amine structure and reaction temperature on the catalyst transformations. In particular,

thermal decomposition of Pd/NHC complexes with aliphatic amine ligands predominantly leads to the reductive Pd-NHC

bond cleavage, while deprotonation of the complexes with primary and secondary aliphatic amine ligands in the presence

of strong bases at 25–60 °C promotes the activation of molecular Pd/NHC catalysis. Efficient Pd-PEPPSI complex – amine

systems suitable for the strong-base-promoted C-S cross-coupling reactions between aryl halides and thiols are suggested

on the basis of these findings.

they are resistant to air and moisture and show superior

catalytic activity in a variety of reactions.^14,18,19The Pd-NHC

backbone is conventionally considered as a highly stable

moiety that secures the catalytic complexes during the

catalysis, while the pyridine is a throw-away ligand eliminated

in the course of Pd-PEPPSI precatalyst activation.

1 Introduction

Palladium holds a dominant position in modern metal complex

catalysis due to its ability to catalyze the widest range of

organic reactions.^1-11N-heterocyclic carbenes (NHCs) are

commonly used as ligands to palladium owing to their

availability, tunable steric and electronic properties and the

high stability of Pd-NHC bonds.^12-17A recently developed

family of Pd/NHC catalysts, Pd-PEPPSI complexes 1, which

comprise N-donor ligands with a pyridine core (PEPPSI stands

for the pyridine-enhanced precatalyst preparation,

stabilization, and initiation)^14,18-22have been a major focus

over the last decade (Scheme 1).^15-17,23-26The Pd-PEPPSI

complexes are easily prepared from available precursors;^27,28

Numerous Pd/NHC catalyzed reactions are performed in the

presence of amines which act as coupling reagents (like in

Buchwald-Hartwig reactions and oxidative C-H aminations)

3,19,29-41

or mild bases (like in Mizoroki-Heck and Sonogashira

reactions, hydrothiolations of alkynes, etc.).⁴²In these

reactions, the pyridine ligands in Pd-PEPPSI complexes can be

substituted with nucleophilic amines to give amino-complexes

2 even under mild conditions (Scheme 1).⁴³The structure of N-

donor ligand can significantly affect the catalytic activity,

especially during the activation stage.^{14,19,29,44-51}The

substitutions of the pyridine ligands with amines shift the

focus to amino-complexes 2,^44-50,52-56which can reportedly

promote a significantly higher activity in certain low-

temperature reactions as compared to corresponding Pd-

PEPPSI complexes with the same NHC ligands.^44-50The

enhancement of catalytic activity may be explained by two

alternative hypotheses, both assuming facilitation of the Pd-N

bond cleavage (Scheme 1, Path A):

^a.Platov South-Russian State Polytechnic University (NPI), Prosveschenya 132,

Novocherkassk, 346428, Russia.

^b.Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, Russian

Federation

^c.Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky

Prospect 47, Moscow, 119991, Russia.

*

Corresponding author. chern13@yandex.ru (Victor M. Chernyshev),

val@ioc.ac.ru (Valentine P. Ananikov)

† Electronic Supplementary Information (ESI) available: additional experimental

data, the details of the theoretical calculations (QTAIM), copies of NMR spectra

and TEM, FE-SEM/EDS data. See DOI: 10.1039/x0xx00000x

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(i) certain amines, e.g. triethylamine, serve as better throw- decomposition of Pd complexes by reductive cleavage of the

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away ligands than pyridines due to the lower strength of Pd-N Pd-C bond with NHC, leading to^DOf^Io^:r¹m^0.1a⁰t³io^9/n^C9Co^Yf⁰²⁰P⁴d^1A⁰

bond, which facilitates their substitution or dissociation at the nanoparticles, azolium salts 3 and bis-NHC complexes 4

activation stage;^44,45,48

(Scheme 1, Path B).⁴²The reductive cleavage of the Pd-NHC

(ii) some amines, e.g. Pd-coordinated morpholine, facilitate bond may deactivate the molecular catalysis or trigger the

intramolecular reduction of Pd^IIto Pd⁰by deprotonation, beta- alternative mode of NHC-free catalysis by highly active

hydride transfer and subsequent reductive elimination.⁵⁰

ligandless palladium species (metal clusters, particles,

On the other hand, despite the high stability of the Pd-NHC etc.).^{20,21,25,26,57,58}

backbone, aliphatic amines can also promote facile

R

N

Path A: cleavage

of the Pd-N bond

Pd⁰

activation of molecular

Pd/NHC catalysis

L

R¹

R²

N

R

R³

N

R

N

R

N

R¹

X

Pd

X

Pd

X

N

R²

N

R'

R³

R

N

R

N

R

N

X^-

N

R

+

X

Pd

X

1

2

H

+

Pd⁰NPs

+

Path B: cleavage

of the Pd-C bond

Pd-PEPPSI

N

R

3

N

R

N

R

4

catalyst deactivation or activation of "ligandless" Pd catalysis

X = Cl, Br, I; R, R' = alkyl, aryl; NR¹R²R³= primary, secondary, tertiary amines

Scheme 1 Transformations of Pd-PEPPSI complexes (1) under the action of aliphatic amines

concerned, we demonstrate that it is not simply coordination

Thus, reactions of Pd-PEPPSI complexes with amines, including of the amine. Rather, it is a unique reactivity with involvement

the substitution of pyridine with amine followed by of reductive Pd-NHC bond cleavage resulting in switching the

transformations of amine complexes 2 (Scheme 1), are highly nature of catalysis (molecular vs. nano-scale).

relevant to Pd/NHC catalysis.⁴²In spite of much importance,

the interplay between the structures of Pd complexes and

amines related to the efficiency of substitution leading to

2 Results and discussion

formation of complexes 2, as well as the stability and catalytic

activity of these complexes, remains understudied. The major

challenge is to find conditions that reliably prevent the

reductive Pd-NHC bond cleavage (Scheme 1, Path B) at the

same time supporting the efficient molecular Pd/NHC catalysis

in these systems (Scheme 1, Path A).

The current study focuses on the reactions of Pd complexes

with various amines at 25–140 °C and the thermal stability of

the resulting complexes 2 against the reductive cleavage of the

Pd-NHC bond. We demonstrate that the outcomes are largely

determined by the structure of amine and the reaction

temperature. Moreover, understanding of the influence of

amine on the low-temperature activation of Pd/NHC

complexes in the presence of a strong base allows us to

suggest efficient Pd-PEPPSI complex – amine systems for

catalytic C-S cross-couplings.

2.1 Reactions of Pd-PEPPSI complexes with aliphatic amines

20

The structures of Pd-PEPPSI complexes (1a-j)

used in the

study are shown in Figure 1.

Bu

I

Pd

I

Br

Pd

Br

I

Pd

I

Pd

I

N

Bu

1a

1b

1c

1d

DiPP

DiPP*Me

Cl

DiPP*OMe

Cl

Br

I

N

Pd

Cl

N

Pd

Br

N

Pd

I

N

Pd

Cl

N

Pd

Cl

N

DiPP

DiPP*Me

DiPP*OMe

1e

1f

1g

1h

1i

Ph

DiPP*Me =

Ph

I

Pd

I

N

OMe

DiPP =

DiPP*OMe =

Ph

1j

b)

Explanation of novelty and significance of this study deserves a

note. One may think that reaction of amines with metal

complexes is an old and well-known topic. However, this

assumption is not particularly valid for the Pd/NHC systems,

where this topic was not comparatively addressed for different

amines. Here we present the first systematic study how to

switch the mechanisms and we are focusing on stabilization of

molecular catalysis pathway. As far as significance is

Fig. 1 Pd-PEPPSI complexes 1a-j used in the study.

At 25–60 °C, the primary and secondary aliphatic amines

reacted selectively by substitution of the pyridine to give

amino-complexes 2 (Scheme 2). After 2 h reactions in CDCl₃at

40 °C, the yields exceeded 95% for all products 2 according to

¹H NMR evaluation (Scheme S1).

2 | J. Name., 2019, 00, 1-3

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R

X

Pd

X

H

N

R'

N

Y

H

N

Pd

X

R''

N

+

N

R'

R''

N

R

1a-j

2a-w

I

N

Pd NH

I

Pd NH

I

Pd NH

I

O

Pd NH

I

N

2b

2c

2d

(88%)

(96%)

(94%)

2a

(94%)

I

N

I

Pd

I

N

Pd NH

I

Pd NH

I

N

Pd NH₂

I

NH₂

N

2e

(93%)

2f

(76%)

2g

(90%)

2h

(78%)

DiPP

Br

I

N

Cl

N

Pd NH

Br

Pd NH

I

Pd NH

I

Pd NH₂

I

Pd NH

Cl

N

DiPP

2m

(77%)

2l

2k

(89%)

(87%)

2i

(89%)

2j

(77%)

DiPP

I

Br

N

Pd NH

Br

DiPP

Pd NH

I

DiPP

Pd NH

Cl

DiPP

O

Pd NH₂

Cl

DiPP

Pd NH₂

Cl

DiPP

N

2o

2p (79%)

2q (84%)

2r

2n

(72%)

(91%)

(74%)

DiPP

DiPP*Me

DiPP*OMe

Cl

N

I

Cl

N

Pd NH

I

Pd NH₂

Pd NH

Cl

Pd NH

N

Cl

DiPP

2s

DiPP

2t

DiPP*Me

DiPP*OMe

2v

(81%)

(80%)

(72%)

2w

(83%)

2u

(78%)

Scheme 2 The synthesis of amine complexes 2a–w from Pd-PEPPSI complexes 1a–j and aliphatic amines. The isolated yields are presented which correspond to the optimized

conditions: heating 1 (0.15 mmol) with amine (0.165 mmol) in 1,4-dioxane (3 mL) at 50 °C for 30 min.

Experiments revealed an overall second order kinetics for

I

NHC Pd

I

H

N

Et

CHCl₃, 25 ^o

C

substitution of pyridine with N,N-diethylamine in complexes

1a, 1d, 1g and 1j (first order with respect to each reactant, see

Figure S1 in Supporting Information). Rate constants

determined for the formation of complexes 2a, 2k, 2o and 2w

in CHCl₃at 25±0.5 °C are 19.7 ± 2.1 М^-1min^-1, 12.6 ± 1.5 М^-

¹min^-1, 2.7 ± 0.3 М^-1min^-1and 15.6 ± 2.1 М^-1min^-1,

respectively. Structural variation of the heterocyclic core in

NHC-ligands has minor influence on the reaction rate

(compare rate constants and kinetic curves for the products

2a, 2k and 2w, Figure 2), by contrast with N-substituents,

which largely define the rate constants apparently by steric

effects (compare rate constants and kinetic curves for the

products 2k and 2o, Figure 2). For instance, reaction of

complex 1d (R = Me) yielding product 2k is ~5 times faster than

reaction of complex 1g (R = DiPP) yielding product 2o. Halogen

ligands X also influence the reaction rate which correlates with

the nature of X as Cl > Br > I (Figure S2). The rate constants

determined for the formation of complexes 2m–o from

complexes 1e–g are 6.1 ± 0.4 М^-1min^-1(X = Cl), 3.6 ± 0.5 М^-

¹min^-1(X = Br) and 2.7 ± 0.3 М^-1min^-1(X = I). This trend may

also be explained by steric factors, as the reaction rate

decreases with an increase in atomic radius of the halogen

ligand X.

NHC Pd

N

Et

1 eq. Et₂NH

I

1a,d,g,j

2a,k,o,w

DiPP

N

NHC =

N

DiPP

Fig. 2 Kinetic plots for the formation of complexes 2a, 2k, 2o and 2w in the

reaction of complexes 1a, 1d, 1g and 1j with Et₂NH. Reaction conditions: 1a, 1d,

1g or 1j (0.05 mmol), Et₂NH (0.05 mmol), CHCl₃(5 mL), 25 °C. The yields of

compounds 2a, 2k, 2o and 2w were determined by HPLC.

Reaction of Pd-PEPPSI complexes 1 with triethylamine is

different. No detectable products were observed upon the

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treatment of complexes 1a, 1d, 1e and 1j with the excess of complexes 1 and TEA complexes is significantly shifted toward

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DOI: 10.1039/C9CY02041A

Et₃N at 40 °C in CDCl₃or DMF. Raising the reaction Pd-PEPPSI complexes 1. For this reason, reaction between

temperature to 60 °C resulted in darkening of the reaction equimolar amounts of TEA complex 2x and pyridine in CDCl₃or

mixtures and slow formation of diethylamine complexes 2a, DMF for 1 day at 40 °C resulted in almost complete conversion

2k, 2m and 2w along with azolium salts 3a–d and trace of 2x into a PEPPSI complex 1e (Scheme 3, reaction i). Second,

amounts of bis-NHC complexes 4a–d (Table 1). Heating the the TEA complexes are thermally unstable and undergo

same complexes 1a, 1d, 1e and 1j with Et₃N in DMF at 100 °C decomposition in solutions at temperatures above 60 °C to

for 1 h increased the yields of the same products (Table 1) and give diethylamine complexes 2 and azolium salts 3 and Pd

promoted precipitation of palladium black. The absence of nanoparticles (Figures 3 and S98, S99) as the main products.

1,2,4-triazolium salt 3d in the reaction mixture can be For instance, complex 2x heated in CHCl₃at 60 °C or in DMF at

explained by instability of 1,2,4-triazolium salts in hot DMF in 100 °C was transformed into compounds 2m and 3c (Scheme

the presence of palladium.⁴²

3, reaction ii). Thus, despite the significantly lower

All attempts to detect anticipated intermediate triethylamine coordination ability of triethylamine as compared with

complexes (NHC)PdX₂NEt₃(TEA complexes) in the reactions of diethylamine and other primary and secondary aliphatic

PEPPSI complexes 1 with triethylamine were unsuccessful. The amines, triethylamine makes a more potent β-hydride donor

elusive behavior of the TEA complexes has two possible under elevated temperatures.

explanations. First, the equilibrium between Pd-PEPPSI

Table 1. Transformations of complexes 1a, 1d, 1e and 1j under the action of Et₃N (in excess).

R

N

+

X^-

X

NHC Pd

X

Et₃N

X

N

NHC Pd NHEt₂

X

NHC Pd NHC

X

+

N

R

3a-d

Py

CDCl₃or DMF

1a,d,e,j

2a,k,m,w

4a-d

DiPP

N

NHC =

N

DiPP

1a,2a,3a,4a 1d,2k,3b,4b 1e,2m,3c,4c 1j,2w,3d,4d

Entry

1

Starting complex

Conditions

CDCl₃, 60 °С^a

DMF, 100 °С^b

CDCl₃, 60 °С^a

DMF, 100 °С^b

CDCl₃, 60 °С^a

DMF, 100 °С^b

CDCl₃, 60 °С^a

DMF, 100 °С^b

Conversion, % ^a,b

Reaction product (yield, %)^a,b

5

2a (4)

2a (9)

2k (14)

2k (22)

3a (trace)

3a (34)

3b (2)

3b (48)

3c (3)

3c (38)

3d (trace)

3d (0)

4a (trace)

4a (18)

4b (trace)

4b (14)

4c (trace)

4d (trace)

4d (9)

1a

65

20

84

10

71

7

2

3

4

1d

1e

1j

2m (6)

2m (33)

2w (trace)

2w (17)

60

^aPd-PEPPSI 1 (0.02 mmol), Et₃N (0.2 mmol), CDCl₃(0.7 mL), 60 °С, 20 h, conversion and yields determined by ¹H NMR.

^bPd- PEPPSI 1 (0.05 mmol), Et₃N (0.5 mmol), DMF (5 mL), 100 °С, 1 h, conversion and yields determined by HPLC.

thermal stability of complexes 2 against the reductive Pd-NHC

bond cleavage must be considered in the protocols for

preparation of these compounds and their potential

applications in catalysis, materials chemistry and life sciences.

Complexes 2 containing primary and secondary aliphatic amine

ligands are quite stable in chloroform, toluene, 1,4-dioxane

and DMF at the temperatures up to ~80–100 °C. For instance,

only 5–8% decreases in the concentrations of complexes 2a, 2l

and 2r were observed after their heating at 100 °C in DMF for

1 h, and only ~5% conversions were observed after their

heating at 80 °C in DMF for 24 h. By contrast, heating

complexes 2a, 2l and 2r, or heating Pd-PEPPSI complexes 1a,

1d and 1e in the presence of corresponding primary and

secondary amines, at 140 °C in DMF resulted in rapid

darkening of the solutions and formation of palladium black,

azolium salts 3 and bis-NHC complexes 4 by reductive cleavage

of Pd-NHC bond (Scheme 1, Path B).⁴²Stability of complexes 2

against the reductive cleavage of Pd-NHC bond significantly

depends on the structure of Pd coordinated amine, steric bulk

DiPP

Py

C

Cl

40 ^o

Cl

N

Pd

N

+

Et₃N

Pd NEt₃

Cl

+

N

(i)

N

Cl

CDCl₃or DMF

DiPP

1e

(~98%)

2x

DiPP

N

DiPP

Cl

Pd

Cl

N

Et₃N

conditions A or B

Pd NHEt₂

Cl

+

Pd⁰

(ii)

Pd NEt₃

Cl

N

DiPP

4c

2m

3c

2x

14% (A)

49% (B)

4% (A)

41% (B)

trace (A)

trace (B)

Conditions A: CDCl₃, 60 ^oC; conditions B: DMF, 100 ^oC.

Scheme 3 Reaction of complex 2x with pyridine (i) and thermal decomposition of 2x in

the presence of Et₃N (ii). The yields in CDCl₃and DMF were determined by ¹H NMR and

HPLC, respectively.

Given their spontaneous formation from Pd/NHC precatalysts

in situ, as well as in various amination reactions, the limited

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of N-substituents in the NHC-ligands and the identity of lower compared to the corresponding diethylamine complex

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DOI: 10.1039/C9CY02041A

halogen ligands X (Table 2).

2m (Table 2, entries 6 and 2).

Table 2. Stability of complexes 2 against the thermally induced reductive cleavage of

Pd-NHC bond.^a

Entry

1

Starting complex

Product (yield)^b

I

H

-

N

I

Pd N Et

I

Et

2k

3b

(95%)

DiPP

Cl H

N

Pd N Et

Cl Et

DiPP

2

3

3c (21%)

N

2m

DiPP

Br H

-

N

Br

Pd N Et

N

Br Et

DiPP

2n

DiPP

(43%)

a)

3e

DiPP

I

H

-

N

I

Pd N Et

Et

4

5

6

N

I

DiPP

2o

DiPP

(60%)

3f

DiPP

Cl H

Pd N ⁿPr

N

-

N

Cl

N

Cl H

DiPP

(18%)

3c

2q

DiPP

Cl Et

N

Pd N Et

Cl Et

3c (56%)

2m (32%)

N

DiPP

2x

^aReaction conditions: 2k,m–o,q,x (0.1 mmol), DMF (2 mL), 140 °C, 21 h.

b)

^bThe yields i were determined by HPLC.

Fig. 3 Transmission electron microscopy (TEM) images of palladium precipitates

isolated from reaction mixtures after heating complex 2x with Et₃N in CDCl₃at

60 ℃ for 20 h (a) and in DMF at 100 ℃ for 1 h (b).

Overall, participation of triethylamine in reactions with Pd-

PEPPSI complexes predominantly leads to the reductive

cleavage of Pd-NHC bond, while secondary and primarily

amines can act as selective nucleophiles at low and moderate

temperatures or cause the reductive cleavage of Pd-NHC bond

at higher temperatures (~100 °C and over).

The observed relationships between the structure of amine

complexes 2 and their stability against the reductive cleavage

of Pd-NHC bond are in good agreement with the recently

proposed reaction mechanism where the amine ligands serve

as intramolecular reductants of palladium, either via the

thermally induced hydride transfer from the N-alkyl group to

the palladium atom (i.e. hydride transfer from the carbon in β-

position relative to the palladium atom) to give (NHC)PdHX

complexes which subsequently undergo H-NHC coupling to

give [NHC-H]⁺, or, alternatively, via the reductive elimination

of HX molecule to give (NHC)Pd⁰complex with its subsequent

dissociation by the Pd-NHC bond cleavage at high

temperature.⁴²

Comparison of the yields of salt 3c formed from complexes

2m, 2q and 2x (Table 2, entries 2, 5 and 6) shows that the

stability of amine complexes against the thermally induced Pd-

NHC bond cleavage significantly correlates with the structure

of amine ligand decreasing as primary amine > secondary

amine > tertiary amine. Besides, the steric bulkiness of N-

substituents is important, as the decomposition rate decreases

with an increase in the steric bulk (compare the yields of

azolium salts 3b and 3f from the complexes 2k and 2o in Table

2, entries 1 and 4). Halogen ligands X also affect the efficiency

of reductive cleavage of Pd-NHC bond (compare the yields of

salts 3c, 3e and 3f from complexes 2m–o in Table 2, entries 2-

4). First-order rate constants of azolium salts 3c, 3e and 3f

formation from complexes 2m–o in DMF at 140 °C are 0.011 ±

0.003 h^-1(X = Cl), 0.023 ± 0.004 h^-1(X = Br), 0.042 ± 0.006 h^-1(X

= I) (the kinetic curves are shown in Figure S3). It is important

to note that thermal stability of triethylamine complex 2x

against the reductive cleavage of Pd-NHC bond is significantly

Considering the significance of amine complexes 2 as effective

catalysts^44-50,52-56and potential antidiabetic and anticholinergic

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agents,⁴³we developed an efficient procedure for preparative

synthesis of complexes 2 from the Pd-PEPPSI complexes 1 and

aliphatic amines. The data clearly indicated that optimal

reaction conditions, while efficiently promoting the synthesis,

should strongly disfavor the reductive cleavage of Pd-NHC

bond to prevent decomposition of the forming complexes. A

recently described synthesis of morpholine complexes with

benzimidazole NHC-ligands in 68–82% yields by reacting Pd

complexes with morpholine in chloroform at 25 °C for 12 h

was taken as a basis for the procedure.⁴³To decrease the

reaction times and increase the yields of amine complexes, we

consistently optimized the reaction conditions (Table S2).

Heating of the Pd-PEPPSI complex with primary or secondary

amine (in 1:1.1 molar ratio) in 1,4-dioxane at 50 °C for 30 min

was found optimal. Complexes 2a–w were obtained in 72–96%

isolated yields under these conditions (Scheme 2).

R

View Article Online

R

X

H

X

Pd

X

N

DOI: 10.1039/C9CY02041A

Y

Pd

X

N

H

Ar

+

N

+ ArNH₂

(i)

N

R

2y-z,aa-ae

1a,d,e,j

I

Pd

I

H

N

H

I

Pd

I

H

N

H

I

Pd

I

H

N

H

N

Ph

O

N

2y

2z

2aa

(83%)

(85%)

(81%)

DiPP

I

Pd

I

H

I

H

N

H

Cl

H

N

H

I

Pd

I

H

N

H

N

H

Ph

Pd

I

Ph

Pd

Cl

Ph

Cl

N

DiPP

2ab

2ac

2ad

2ae

(78%)

(63%)

(82%)

(72%)

Py (2 eq.), DMF

100 ^oC, 10 min

I

Pd

I

Pd

I

H

N

(ii)

N

H

Ph

+

PhNH₂

N

I

In comparison with the previously described methods for

preparation of several amine complexes 2 from halo-bridged

dimeric complexes (NHCPdX₂)₂,^{44,48,50,55,56}the developed

procedure has the advantage of higher availability of the

starting Pd-PEPPSI complexes. Halo-bridged complexes can

2y

1a

(75%)

Scheme 4 Reaction of Pd-PEPPSI complexes 1a, 1d, 1e and 1j with anilines (i) and the

reverse reaction of complex 2x with pyridine (ii). The isolated yields of compounds 2y–z

and 2aa–ae correspond to the following conditions: heating 1a, 1d, 1e or 1j (0.15

mmol) with aromatic amine (1.5 mmol) in DMF (3 mL) at 120 °C for 20 min.

59-63

usually be prepared from azolium salts 3 in lower yields;

alternatively, they can be prepared by protonolysis of Pd-

PEPPSI or similar complexes, which requires an additional

synthetic step.^22,46,47

The data indicate reversibility of the reaction between Pd-

PEPPSI complexes 1 and anilines. Indeed, heating aniline

complex 2y with pyridine (2 eq) at 100 °C afforded complex 1a

in 75% isolated yield (Scheme 4, reaction ii). The coordination

ability of typical arylamines is therefore comparable to that of

pyridine. It means that the reaction of Pd-PEPPSI complexes

with arylamines is of low utility for the preparation of

complexes 2 and has no benefits over the methods based on

the reactions of halo-bridged complexes with arylamines.^64,65

2.2 Reactions of Pd-PEPPSI complexes with aromatic amines

Pd-PEPPSI complexes 1a, 1d, 1e and 1j reacted with anilines

selectively via substitution of pyridine to give aniline

complexes 2y, 2z and 2aa–2ae (Scheme 4, reaction i, Table S3).

No reductive Pd-NHC bond cleavage was observed even at

100 °C. Insignificant decomposition with the formation of

palladium black was observed when the reactions were

performed in DMF at 120–140 °C for 1–2 h. However, the

formation of palladium black in DMF was quite possibly caused

by the products of DMF decomposition at the elevated

temperatures.⁴²The formation of aniline complexes in CDCl₃at

40 °C proceeded very slowly; only 13% and 20% NMR yields of

complexes 2ac and 2ad, respectively, were afforded within 8 h

(Table S3, entries 11 and 13). The reaction significantly

accelerated at 100–120 °C in 1,4-dioxane or DMF; however,

with only a small excess (10–30% mol) of aniline, the yields of

complexes 2 never exceeded 48–56% (Table S3, entries 2–4). A

large excess of aniline (molar ratio of 10:1 with PEPPSI

complex 1) allowed to obtain complexes 2y–2z and 2aa–2ae in

63–85% isolated yields (Table S3, Scheme 4). Complexes 2z

and 2ae were isolated and characterized as stable crystalline

adducts with corresponding anilines (1:1 mol/mol).

2.3 The structure of amino-complexes 2

The structures of the synthesized complexes 2 were confirmed

1

by H and ¹³C NMR spectra, elemental analysis, and single

crystal X-ray diffraction analysis of complexes 2a, 2g, 2k and

2y.

¹H NMR spectra of compounds 2 contained characteristic

signals of Pd-coordinated amines, including signals of NH

groups at 2.8–4.0 ppm (in DMSO-d₆) for the complexes with

aliphatic amines and at 4.6–5.0 ppm (in DMSO-d₆) or 4.0–4.6

ppm (in CDCl₃) for the complexes with aromatic amines. The

NH signals disappeared with the addition of D₂O. The observed

¹³C NMR spectra are similar to the spectra of related amine

complexes described in literature.^43,44,50

Molecular structures of complexes 2a, 2g, 2k and 2y

determined by single crystal X-ray diffraction analysis are

presented in Figure 4. All of the studied complexes adopt the

anticipated slightly distorted square-planar geometry around

the palladium center, with the amine ligand in trans to the

NHC ligand, which is similar to the geometry of related amine

complexes described in literature.^{43,44,50,52-55}Notably, the Pd-N

bonds in the aliphatic amine complexes 2a, 2g and 2k [2.11(1)-

2.125(9) Å, Tables S9, S13, S17] are shorter than in the aniline

complex 2y [2.132(3) Å, Table S21] and triethylamine

complexes described in literature (2.180-2.220 Å).^45,47,66The

6 | J. Name., 2019, 00, 1-3

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bond lengths indicate stronger Pd-N bonding in the complexes 110°, one of the geometrical criterions according _Vt_io_ewt_Ah_re_ticlI_eU_OP_nA_linC_e

68

DOI: 10.1039/C9CY02041A

with primary and secondary aliphatic amines compared to the definition which “should preferably be above 110°”. In

complexes with aromatic amines or Et₃N. The stronger addition, analysis of the electron density topology by means of

character of Pd-N bond in the complexes with secondary “atoms in molecules” theory^69-71revealed no corresponding

aliphatic amines has been previously explained by the bond paths connecting H and I atoms and a (3,–1) critical point

intramolecular NH···X bonding (X = Cl).^44,50Intramolecular between H and I in the structures 2a, 2g and 2k obtained from

NH···I short contacts are observed in complexes 2a, 2g and 2k the X-ray diffraction data (Figures S94-S96). Two similar NH···I

(Figure 4). The H···I distances determined from X-ray structure short contacts are also observed in complex 2y; however, the

analysis (2.963 Å in 2a, 3.014 Å for a shorter contact in 2g and H···I distances determined from X-ray structure analysis (3.133

2.960 Å in 2k) are appreciably shorter than the sum of van der and 3.163 Å) are very close to the sum of van der Waals radii

Waals radii of H and I atoms (3.18 Å).⁶⁷Nevertheless, the N- and no hydrogen bonding was revealed from the analysis of

H···I angle (108.6° in 2a, 102.6° in 2g, 108.6° in 2k) is less than the electron density topology of the structure 2y (Figure S97).

2a

2g

2k

2y

Fig. 4 Molecular structure of complex 2a,g,k,y with ellipsoids drawn at the 50% probability level.

Thus, the presence of reasonably strong H-bonding reactions.^50,72Despite these valuable findings, two important

interactions seems to be unlikely. It is quite probable that questions still remain unanswered:

stronger binding of primary and secondary aliphatic amines to (i) How do the structures of the amine ligand and NHC, as well

palladium in the complexes 2 can be explained by less steric as the reaction temperature and base additives, affect the

bulkiness in comparison with tertiary aliphatic amines and molecular Pd/NHC catalysis in C-S cross-couplings?

higher N-donor ability compared with aromatic amines.

(ii) Can other amines (primary, secondary and tertiary) ensure

efficient activation? For instance, in several base-mediated

2.4 The amine-promoted activation of molecular Pd/NHC catalysis reactions, the tertiary amine ligands were shown to be more

in the C-S cross-coupling between aryl halides and thiols

effective than secondary amines and pyridines.^44-48

To find the answers, we comparatively evaluated the catalytic

activity of complexes 1e, 1h, 1i, 2m-r, 2t-x and 2ad containing

bulky NHC ligands (IPr, IPr* and IPr*OMe, which had

previously proved effective in C-S cross-coupling

reactions)^50,51,72-74and various N-donor co-ligands in the

reaction between 4-bromotoluene (5a) and thiophenol (6a)

under the conditions suggested in literature.⁵⁰We also varied

the conditions of preactivation. In most of the experiments,

preactivation was performed by a standard protocol (stirring

the precatalyst with aryl halide and KO^tBu at 25 °C in toluene

for 5 min before the addition of thiol). We also studied the

effects of higher temperatures and the possibility of thermal

preactivation without KO^tBu. Selected experimental data are

given in Table 3, for the complete data set see Table S4.

IPr complexes 1e, 2t, 2x and 2ad (with, respectively, pyridine,

tert-butylamine, Et₃N and aniline as N-ligands) were inactive at

low temperatures (25–60 °C), after standard preactivation or

without preactivation (Tables 3 and S4). However, IPr

complexes 2m, 2p, 2r and 2q with primary and secondary

aliphatic amine ligands capable to β-hydride transfer showed

significant activity even at 25 °С after standard preactivation

(Tables 3 and S4). The catalytic activity for secondary amine

ligands and benzylamine was slightly higher than for n-

propylamine, apparently due to the higher hydride donation

ability (Table 3). The nature of halogen co-ligands X had

The amine-promoted activation of ligandless catalysis by the

NHC-free active palladium species released from Pd-PEPPSI

complexes in the presence of Et₃N and other aliphatic amines

has been recently investigated for the case of Mizoroki-Heck

reaction.⁴²Herein we consider the conditions required for

efficient activation of molecular Pd/NHC catalysis with amines

as hydrogen donors – reductants of Pd^IIto Pd⁰. The

appropriate conditions that ensure the efficient reduction of

Pd^IIto Pd⁰should provide the retention of Pd-NHC bond, i.e.

suppress the reductive Pd-C_(NHC)bond cleavage via H-NHC

(Scheme 5, A) coupling and other possible pathways.

The Pd/NHC-catalyzed C-S cross-coupling between aryl halides

and aryl thiols affording diaryl sulfides was chosen as a good

model reaction. Organ et al demonstrated the importance of

the activation stage for effective Pd/NHC catalysis of C-S cross-

coupling reactions, especially at low temperatures (23–

70 °C).^50,51,72,73The authors revealed the significant influence

of the N-donor throw-away ligands in Pd/NHC complexes on

both the activation stage and the catalyst deactivation via

formation of the catalytically inactive di- and polythiolate

complexes.^50,51It was demonstrated that morpholine can be

used as an effective N-donor ligand instead of pyridine or

substituted pyridine to provide the rapid reduction of Pd^II/NHC

complexes in the presence of strong bases and the efficient

activation of Pd/NHC precatalysts in C-S cross-coupling

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Journal Name

insignificant effect on the catalytic activity (Table S4, entries washed with water) revealed the formation of_Vip_ewo_Aly_rtt_ich_leio_Ol_na_lit_ne_e

20, 27 and 28).

NHC-containing palladium complexes pr^De^Ovi^Io^{: 1}u⁰s^.1ly⁰³d⁹e^/Cs⁹c^Cri^Yb⁰e²d⁰⁴b^1Ay

It is remarkable that the addition of N,N-diethylamine to Organ et al as the products of catalyst deterioration.^51,73No

complexes 1e, 2x or 2ad at the preactivation stage resulted in such precipitates were formed in the presence of primary and

catalytic activity comparable with the activity of complex 2m secondary aliphatic amines at the activation stage or

(Table 3, compare entries 2, 5, 14 and 16). It is also interesting complexes with primary and secondary aliphatic amine ligands

to note that after the addition of PhSH the reaction mixtures (see Figure S4 for examples). Thus, not only morpholine,⁵⁰but

containing precatalysts 1e, 2x or 2ad looked quite different other primary and secondary aliphatic amines as well, even

from the mixtures containing precatalysts with primary and when applied in combination with Pd-PEPPSI precatalyst at the

secondary aliphatic amines (see for example Figure S4). activation stage, prevent the thiol poisoning of Pd/NHC

Formation of lemon-colored precipitates was observed for catalyst and ensure its efficient activation.

1

precatalysts 1e, 2x and 2ad. Elemental analysis and H NMR

spectra of these precipitates (isolated by centrifugation and

8 | J. Name., 2019, 00, 1-3

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Table 3. Catalytic activity of Pd/NHC complexes in the C-S cross-coupling between compounds 5a and 6a.^a,b

View Article Online

DOI: 10.1039/C9CY02041A

[Pd] (2 mol %)

S

Br HS

+

KO^tBu

toluene

5a

6a

7a

7b

7c

[Pd] precatalysts studied:

DiPP

DiPP*OMe

Cl

DiPP

Cl

N

Pd NH₂

Cl

Pd

N

Pd

Cl

DiPP*OMe

N

Pd NH

Cl

O

N

Cl

DiPP

1e

Cl

DiPP

2p

2r

2m

1i

DiPP

DiPP*OMe

DiPP

Cl

H

N

H

Cl

N

Pd N

Pd

Pd NH₂

Pd NH

Pd NH₂

N

Cl

DiPP

2x

DiPP

DiPP*OMe

DiPP

2ad

2q

2t

2v

Pre-activation

conditions^c

React.

temp.

Product

(GC-MS yield)

7a (0%)

Entry

1

Precatalyst

React. time

1 h

Conv. of 5a

1e

25 °C, 5 min

60 °C, 5 min

25 °C, 5 min

25 °C

60 °C

25 °C

2%

7b (0%)

7c (trace)

7a (79%)

7b (0%)

7c (0%)

7a (0%)

2

3

1e (2 mol %) + Et₂NH (4 mol %)

1 h

16 h

1 h

82%

2%

1i

7b (0%)

7c (trace)

7a (13%)

7b (0%)

4

1i (2 mol %) + Et₂NH (4 mol %)^b

13%

85%

83%

80%

62%

3%

7c (0%)

7a (83%)

7b (trace)

7c (trace)

7a (81%)

7b (trace)

7c (trace)

7a (77%)

7b (trace)

7c (trace)

7a (51%)

7b (trace)

7c (trace)

7a (trace)

7b (trace)

7c (2%)

7a (15%)

7b (0%)

7c (0%)

7a (24%)

7b (trace)

7c (trace)

7a (95%)

7b (trace)

7c (1%)

5

2m

6

2p

7

2r

8

2q

9

2t

10

11

12

13

14

15

16

2v

17%

27%

100%

5%

2v

7a (trace)

7b (0%)

2x

7c (trace)

7a (76%)

7b (trace)

7c (trace)

7a (0%)

2x(2 mol %) + Et₂NH(4 mol %)

2ad

78%

2%

7b (0%)

7c (trace)

7a (71%)

7b (0%)

2ad (2 mol %) + Et₂NH(4 mol %)

74%

7c (trace)

^aOnly selected results are presented. For the complete data set see Table S4.

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^bConditions: Pd precatalyst (2 mol. % relative to 5a), Bu^tOK (0.4 mmol), 5a (0.25 mmol), PhSH (0.26 mmol), toluene (2 mL).

View Article Online

DOI: 10.1039/C9CY02041A

c

Stirring the mixture of a precatalyst (Pd/NHC or Pd/NHC combined with amine) with ArBr (5) and KO^tBu (unless otherwise specified) in toluene at specific

temperature for 5 min before the addition of PhSH.

activity at 25 °C, albeit low in comparison with the

We also revealed an additional important effect of primary corresponding IPr complexes due to the overmuch high steric

and secondary amines on the stability of Pd/NHC catalysts in bulk of IPr* and IPr*OMe ligands (Tables 3 and S2).

the course of strong base-promoted precatalyst activation. It Interestingly, activation of complexes 2u and 2v at a higher

has been recently reported that Pd^II/NHC complexes in the temperature (60 °C) increased the yields of the cross-coupling

presence of strong oxygen bases can undergo cleavage of the product 7a from 14–17% to 24–27% even when the C-S cross-

Pd-NHC bond via O-NHC coupling to give azol-2(5)-ones, the coupling itself was performed at 25 °C (Tables 3 and S4). This

reaction leading to deactivation of molecular Pd/NHC finding indicates that the increase in NHC bulkiness decreases

catalysis.²⁶GC-MS analysis of the reaction mixtures after the the rate of strong base-promoted activation.

KO^tBu-promoted precatalyst activation revealed significantly It should also be noted that all of the studied precatalysts

higher yields of corresponding imidazole-2-one

8 for demonstrated significant catalytic activity at 110 °C

precatalysts 1e and 2x compared to precatalysts with primary independently of the N-ligand (Tables 3 and S4). However, a

and secondary aliphatic amine ligands. The influence of N- significant decrease in the reaction selectivity at so high a

ligand on the undesirable O-NHC coupling reaction was temperature resulted in noticeable yields of side products 7b

especially pronounced at 110 °C (Table 4). Thus, primary and and 7c (Tables 3 and S4). Compounds 7b and 7c were

secondary aliphatic amine ligands capable to β-hydride apparently formed as a result of C-S bond activation in

transfer suppress the O-NHC coupling, at least at the activation compound 7a and PhSH at higher temperatures.^75,76The

stage, apparently due to NH deprotonation and subsequent heating 7a alone, or the equimolar mixture of 7a with PhSH, at

facile beta-hydride transfer leading to (NHC)Pd⁰complexes 110 °C in the presence of 2m and KO^tBu resulted in formation

incapable of participation in the O-NHC coupling.

of compounds 7b and 7c in yields increasing with the duration

of heating (Scheme S2).

Several important inferences from the results are as follows:

(i) At low temperatures (25–60 °C), the structure of N-ligand is

crucial for the catalytic activity. Efficient activation is achieved

for primary and secondary amine ligands containing strong

base-ionizable NH groups and capable to β-hydride transfer. As

has been proposed previously,⁵⁰the activation process starts

with deprotonation of amine complexes via abstraction of a

proton from the NH-group of amine ligand by alkoxide anion

(Scheme 5, B). The deprotonation of amine ligand facilitates

subsequent hydride transfer from the alkyl group of the N-

deprotonated amine ligand of intermediate 9 onto palladium

to give the hydride intermediate 10 which subsequently

undergoes reductive elimination of HX or, alternatively,

deprotonation and dissociation of the Pd-X bond to give the

active (NHC)Pd⁰species 11 that starts the catalytic cycle

(Scheme 5, B). The ligands containing no base-ionizable NH e.g.

pyridine or Et₃N, or no hydrogen atoms capable of β-hydride

transfer e.g. tert-butylamine ligand or aniline ligand, are

inappropriate for activation by this mechanism and cannot

support the strong base-promoted activation.

Table 4. The effect of N-ligand (L) on formation of azolone 8 in the reaction of

complexes (IPr)PdCl₂L with KO^tBu^a

DiPP

KO^tBu

Cl

N

O

Pd

Cl

L

toluene, 110 ^o

1 h

C

N

DiPP

1e,2m,x

8

1e

2m

2x

(L = pyridine)

(L = Et₂NH)

(L = Et₃N)

37%

4%

28%

^aThe yields of 8 were determined by GC-MS

It is also important to note that the attempts of thermal

preactivation at 140 °C in DMF had opposite effects on the

activity of complexes 2m as compared with 2x or 1e + Et₃N

(Table S4, entries 11, 22 and 44). For complex 2m, the activity

decreased after preheating at 140 °C (Table S4, entry 22),

apparently due to partial thermal decomposition of 2m and

formation of palladium black via H-NHC coupling. For the

precatalysts 1e + Et₃N and TEA complex 2x, preheating at

140 °C led to a slight increase in the catalytic activity (Table S4,

entries 11 and 44), apparently due to formation of

diethylamino-complex 2m via the reaction described in Section

2.1 (compound 2m was detected by HPLC in the reaction

mixtures after preheating). The formation of 2m was

apparently responsible for the increase in catalytic activity of

2x or 1e + Et₃N after preheating.

The catalytic behavior of complexes with bulkier ligands IPr*

and IPr*OMe was generally similar to the behavior of IPr

complexes. Complexes 1h and 1i were inactive with or without

preactivation, while complex 1i combined with Et₂NH, as well

as diethylamine complexes 2u and 2v, had detectable catalytic

10 | J. Name., 2019, 00, 1-3

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reaction times are required to provide high yields_Vo_iewf C_Ar-_tS_iclecr_Oo_ns_lins_e-

coupling products with these ligands. Nevertheless, the bulkier

(A) Thermal activation

high temperature, lower basicity

DOI: 10.1039/C9CY02041A

IPr* and IPr*OMe ligands ensure higher selectivity of the C-S

cross-coupling at elevated temperatures.

Ar

-hydride

transfer

Pd⁰

NHC-free

H

N

H-NHC coupling

Pd

L

Nano-Scale

Catalysis

An additional question can also arise concerning the reasons

determining alternative pathways of transformations of

hydride intermediates 10 in the conditions of thermally

induced and strong-base promoted transformations of

complexes 2 with amine ligands (Scheme 5). Indeed, if the key

intermediates are the same, why thermal activation induces

reductive Pd-NHC bond cleavage to give azolium salts and

nanoparticles even in mild conditions (for example, reactions

with Et₃N at 60 °C, Table 1), while strong-base promoted

activation with primary and secondary aliphatic amines leads

to the formation of (NHC)Pd⁰complexes 11 at the same

temperature (Scheme 5)? Formation of complexes 11 in the

presence of Bu^tOK can be suggested based on the results of

catalytic trials (Tables 3, S4 and S5) and was previously

confirmed by trapping experiments.⁵⁰We believe that basicity

of the reaction media as well reaction temperature are the

main factors responsible for switching from nano-scale to

molecular (NHC)Pd⁰/NHC systems. Apparently, the main

pathway from intermediates 10 to nanoscale systems includes

H-NHC coupling (Scheme 5, A).^42,58The H-NHC coupling may be

a facile process which can proceed with a low activation

barrier of ~6.3 kcal/mol.⁵⁸Increase of the hydride intermediate

10 concentration should accelerate H-NHC coupling and

promote formation of nanoscale systems, whereas decrease of

the concentration should retard the H-NHC coupling. Strong

bases like KO^tBu decrease concentration of hydride

intermediates 10 via its fast deprotonation to give (NHC)Pd⁰

complexes uncapable to H-NHC coupling, thus promote

switching to molecular catalysis (Scheme 5, B). In addition,

increase of basicity should suppress reversible protonolysis of

(NHC)Pd⁰complexes and formation of proligands [NHC-H]⁺and

NHC free Pd⁰species. Temperature is the next important

factor. Increase of temperature should accelerate dissociation

of Pd-NHC bond and promote growth of Pd clusters and

nanoparticles. In the absence of strong bases reduction of

Pd^II/NHC complexes with aliphatic amines proceeds at high

temperatures. Therefore, thermally induced activation mode,

which combines high temperature with relatively low basicity

promotes formation of Pd nanoparticles and azolium salts. In

contrast, strong-base induced activation accelerates β-hydride

transfer even at low temperatures due to the deprotonation of

NH groups in amine complexes 2; in addition, high basicity

suppresses H-NHC coupling of hydride intermediates 10 owing

to its deprotonation to form (NHC)Pd⁰complexes and

overwhelm alternative decomposition of the last via

protonolysis (Scheme 5, B). Of course, this is a plausible

explanation only based on the available experimental data and

more detailed mechanistic studies may be further performed.

With new understanding of the main causal links in the amine-

induced activation of Pd/NHC precatalysts, we evaluated the

utility of simple aliphatic amines as activators in the Pd-PEPPSI

catalyzed C-S cross-coupling reaction of aryl bromides and aryl

chlorides with PhSH (Table 5).

N

Ar

X

high

temperature

Ar

X

N

10



H

+ L

N

Ar

3

Ar

H

N

X

Pd

X

N

R'

R

(B) Strong-base promoted activation

Ar

2

(low temperature, high basicity)

B

(strong base)

BH

deprotonation

Ar

H

Ar

H

Pd

X

B

(strong base)

X

Pd

X

N

R'

N

Molecular

Catalysis

Pd⁰

11

L

N

R

L

-hydride

transfer

N

X^-+ ВН

Ar

9

10

Deprotonation of the hydride complex

supresses H-NHC coupling

Scheme 5 Plausible mechanisms of the thermal activation (A) and the strong base-

promoted activation (B) of Pd/NHC complexes with primary and secondary aliphatic

amine ligands. The mechanism of the catalytic C-S cross-coupling is given in Supporting

Information (see Scheme S3).

(ii) Thermal activation in the absence of a strong base (Scheme

5, A) is less effective than the low-temperature strong base-

promoted activation. Preheating of complexes with primary

and secondary aliphatic amines at high temperatures induces

the unwanted reductive cleavage of Pd-NHC bond via H-NHC

coupling thus leading to the catalyst deterioration. However,

for complexes with Et₃N, the preheating can stimulate the

formation of certain amounts of Et₂NH complexes which

subsequently ensure the strong base-promoted activation and

the C-S cross-coupling. Comparison of the results obtained in

this study with the recent results on the amine-promoted

activation of PEPPSI precatalysts in the Mizoroki-Heck

reaction⁴²indicates that tertiary aliphatic amines efficiently

promote the amine-induced thermal activation of NHC-free

catalysis, while primary and secondary aliphatic amines are

more appropriate for the low-temperature strong base-

promoted activation of molecular Pd/NHC catalysis;

(iii) Primary and secondary amines that act as facile reductants

of Pd^II/NHC to Pd⁰/NHC complexes in the strong base-

promoted activation also suppress the formation of inactive

polythiolate complexes and prevent the undesirable reductive

cleavage of the Pd-NHC bond via the O-NHC coupling reaction,

at least at the activation stage;

(iv) At a higher temperature (110 °C), the influence of N-donor

ligand is insignificant, apparently due to the relevance of

another preactivation mechanism under these conditions.^51,77

However, high temperatures lead to a decrease in the C-S

cross-coupling selectivity because of the undesirable activation

of C-S bonds and formation of diarylsulfide by-products;

(v) The excessively bulky NHC-ligands IPr* and IPr*OMe, as

compared with the less bulky IPr ligand, decrease the rates of

both the catalyst activation and the subsequent C-S cross-

coupling. For this reason, higher temperatures and longer

This journal is © The Royal Society of Chemistry 20xx

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Table 5. The yields of diaryl sulfides in the reaction of aryl bromides and aryl chlorides

N,N-diethylamine and morpholine were used as cheap

activators easily separated from the target reaction products.

Pd-PEPPSI complexes 1e and 1i were chosen as precatalysts; in

some cases, amine complexes 2m and 2v were additionally

used for comparison. Optimization of the reaction conditions

(Table S4) revealed that IPr complex 1e (2 mol %) in

combination with diethylamine (4 mol %) or morpholine (4 mol

%) preactivated at 25 °C for 5 min most efficiently catalyzed

the reactions of aryl bromides proceeding at 25 °C for 8–24 h

to afford the target diaryl sulfides in high yields comparable

with the yields obtained by catalysis with diethylamine

complex 2m (Table 5).

With aryl chloride substrates, IPr complexes performed worse:

at temperatures below 60 °C the reactions proceeded too

slowly, while at higher temperatures (60–110 °C) the

selectivity decreased significantly due to the formation of

diaryl sulfide mixtures (Table S5). Significantly better results

for aryl chlorides were obtained with the IPr*OMe complex 1i

(1.5 mol %) in combination with Et₂NH or morpholine (4 mol

%), or with the separately synthesized complex 2v. Due to the

decreased rates of activation and reaction with the bulkier

IPr*OMe ligand, the reaction conditions were optimized

additionally (Table S5). Good yields of target diaryl sulfides

were afforded under the following conditions: preactivation at

60 °C for 5 min, cross-coupling at 60 °C for 12–24 h. The yields

of diaryl sulfides afforded with complex 1i (1.5 mol %) in

combination with Et₂NH (4 mol %) and with the separately

prepared complex 2v (1.5 mol %) are comparable (Table 5).

View Article Online

with PhSH

DOI: 10.1039/C9CY02041A

Conditions A or B

Ar

S

Ph

ArX

PhSH

+

6

7a-p

SPh

7a

1e

7c

1e

7d

1e

a

X = Br, 92% ( + Et₂NH, 12 h) X = Br, 95% ( + morph., 8 h) X = Br, 90% ( + morph., 12 h)

a

b

a

2m

1i

2m

X = Br, 94% ( , 12 h)

X = Cl, 98% ( + Et₂NH, 12 h) X = Br, 89% ( , 12 h)

SPh

Ph

O

7e

7f

1e

7g

1e

b

a

1i

X = Cl, 93% ( + Et₂NH, 16 h)

X = Br, 94% ( + Et₂NH, 8 h)

X = Br, 96% ( + morph., 12 h)

b

2v

1i

X = Cl, 92% ( , 16 h)

X = Cl, 98% ( + Et₂NH, 16 h)

SPh

F

Cl

N

7h

7i

7j

a

1e

X = Br, 93% ( + Et₂NH, 12 h) X = Br, 85% ( + Et₂NH, 12 h) X = Br, 92% ( + Et₂NH, 16 h)

a

2m

X = Br, 96% ( , 12 h)

SPh

H₂N

SPh

H₂N

SPh

H₂N

7k

7l

1i

7m

1i

a

b

1e

X = Br, 89% ( + Et₂NH, 24 h) X = Cl, 80% ( + Et₂NH, 24 h) X = Cl, 83% ( + Et₂NH, 24 h)

a

b

2m

X = Br, 87% ( , 24 h)

2v

X = Cl, 85% ( , 24 h)

O

H₂N

O

SPh

N

Ph

N

7n

7o

1e

7p

a

1i

1e

X = Br, 76% ( + Et₂NH, 24 h) X = Br, 89% ( + Et₂NH, 24 h)

X = Cl, 82% ( + Et₂NH, 24 h)

b

a

2v

2m

X = Cl, 84% ( , 24 h)

X = Br, 84% ( , 24 h)

X = Br, 85% ( , 24 h)

O

N

SPh

7r

7s

a

1e

X = Br, 92% ( + Et₂NH, 24 h)

X = Br, 90% ( + Et₂NH, 24 h)

a

2m

X = Br, 93% ( , 24 h)

2m

X = Br, 88% ( , 24 h)

a

Conditions A: complex 1e (2 mol. %), N,N-diethylamine (Et₂NH, 4 mol %) or

morpholine (morph., 4 mol %), Bu^tOK (0.8 mmol) and aryl bromide (0.5 mmol) in

toluene (2 mL) were stirred at 25 °C for 5 min, then PhSH (0.6 mmol) in toluene (2

mL) was added to the precatalyst solution and the reaction mixture was stirred at

25 °C. When using complex 2m instead of 1e, no Et₂NH or morph. was added. The

isolated yields after chromatography on silica gel correspond to averages of two

runs.

b

Conditions B: complex 1i (1.5 mol. %), N,N-diethylamine (Et₂NH, 4 mol %) or

morpholine (morph., 4 mol %), Bu^tOK (0.8 mmol) and (aryl chloride, 0.5 mmol) in

toluene (2 mL) were stirred at 60 °C for 5 min, then PhSH (0.6 mmol) in toluene (2

mL) was added to the precatalyst solution and the reaction mixture was stirred at

60 °C. When using complex 2v instead of 1i, no Et₂NH or morph. was added. The

isolated yields after chromatography on silica gel correspond to averages of two

runs.

Good yields of C-S cross-coupling products (Table 5) including

the functionally substituted compounds 7k–s demonstrate

high tolerance of Pd-PEPPSI complex – aliphatic amine catalytic

systems in the catalysis of C-S cross-coupling reactions.

3 Conclusions

Pd-PEPPSI complexes can readily react with various aliphatic

and aromatic amines. Depending on the amine structure, as

12 | J. Name., 2019, 00, 1-3

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ARTICLE

well as the temperature and the presence of a strong base, Pd-

PEPPSI complexes that react with amines may undergo

substitution of the pyridine ligand with the amine and

subsequent reduction of Pd^IIto Pd⁰with either the retention

or the cleavage of the Pd-C_(NHC)bond.

(i) In the absence of strong bases, primary and secondary

aliphatic amines at ~25–80 °C react promptly and selectively as

nucleophiles to give amino-complexes (NHC)PdX₂(NHR¹R²) (R¹

= alkyl, R²= H or alkyl) in high yields, while at higher

temperatures the forming amine complexes undergo the

thermally induced Pd-C_(NHC)bond cleavage to give azolium salts

(NHC proligands) and Pd nanoparticles. An optimized simple

procedure suggested for the preparation of amine complexes

in 72–96% isolated yields involves the easily available Pd-

PEPPSI complexes reacting with primary and secondary

aliphatic amines at 50 °C.

The susceptibility of the aliphatic amine complexes to the

thermally promoted reductive cleavage of the Pd-C_(NHC)bond

increases in a primary < secondary < tertiary amine ligand and

a Cl < Br < I halogen co-ligand series. Tertiary aliphatic amines

can be considered as the most efficient activators of ligandless

catalysis by the NHC-free active palladium species in particular

reactions (e.g. the Mizoroki-Heck reaction) as compared with

other amines.

4 Experimental section

4.1 General procedures and reagents

View Article Online

DOI: 10.1039/C9CY02041A

¹H and ¹³C⁷⁸NMR spectra were recorded on a Bruker DRX500

spectrometer at 500 MHz and 125 MHz, respectively, in CDCl₃

1

or DMSO-d₆. H and ¹³C chemical shifts are given in ppm

relative to the residual peak of the solvent signal (δ 7.26 for

CDCl₃, δ 2.50 for DMSO, and δ 5.32 for CD₂Cl₂for ¹H; δ 77.2 for

CDCl₃, δ 39.5 for DMSO-d₆; δ 54.0 for CD₂Cl₂for ¹³C). Elemental

analyses were performed using a Perkin Elmer 2400 elemental

analyzer. High-resolution mass spectra were obtained on a

Bruker maXis Q-TOF instrument equipped with an electrospray

ionization (ESI) ion source in positive (+) MS ion mode (HV

Capillary: 4500 V; Spray Shield: –500 V). HPLC analyses were

performed using an Agilent 1260 Infinity LC system equipped

with a reversed-phase Zorbax SB-C18 column (50 × 4.6 mm)

thermostated at 30 °C, detection wavelength was 260 nm.

Gradient elution with a flow rate of 2 mL min^–1was applied.

The mobile phase A contained 10% MeCN in water, the phase

B was neat MeCN, and the phase C was 0.015 M ammonium

acetate aqueous solution. The gradient conditions were as

follows: ramp over 5 min from 80% A, 18% B and 2% C to 98%

B and 2% C.

For the transmission electron microscopy (TEM)

measurements, carbon coated copper TEM grid (200 mesh)

was placed into analyzed solution for 5 minutes. After that, the

grid was sequentially washed with isopropanol (0.5 mL), water

(0.5 mL) and isopropanol (0.5 mL) followed by drying in air

flow. The observations were carried out using a Hitachi

HT7700 transmission electron microscope. Images were

acquired in bright-field mode at 100 kV accelerating voltage.

Before EDS measurements the copper grid was removed and

carbon film with the sample was mounted on a 25 mm

aluminum specimen stub and fixed by conductive plasticine-

like adhesive. The scanning electron microscopy (SEM) studies

were carried out on the Hitachi SU8000 field-emission

scanning electron microscope (FE-SEM) using Oxford

Instruments X-max 80 EDS system at 10 kV accelerating

voltage.

All synthetic manipulations were conducted under argon or

nitrogen atmosphere using standard Schlenk techniques. Dry

and degassed solvents were used for all manipulations.

Solvents were thoroughly dried and degassed according to the

published procedures.⁷⁹

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-

ylidene)(diiodo)(pyridine)palladium

dibutyl-1,3-dihydro-2H-benzimidazol-2-

ylidene)(pyridine)palladium (1b),²⁰(1,3-dimethyl-1,3-dihydro-

2H-imidazol-2-ylidene)(diiodo)(pyridine)palladium (1d),⁸⁰{1,3-

bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-imidazol-2-

ylidene}(dichloro)(pyridine)palladium

di(propan-2-yl)phenyl]-1,3-dihydro-2H-imidazol-2-

ylidene}(dibromo)(pyridine)palladium

(1f),²⁰

Aromatic amines react with Pd-PEPPSI complexes as weak

nucleophiles to give (NHC)PdX₂(NH₂Ar) complexes in

equilibrium with the starting compounds.

(ii) The conditions of efficient molecular Pd/NHC catalysis in

the Pd-PEPPSI complex – amine systems were determined for

a model reaction of C-S cross-coupling between aryl halides

and thiophenol. The efficient low-temperature activation via

the reduction of Pd^IIto Pd⁰with the retention of Pd-C_(NHC)bond

can be achieved by NH-deprotonation of the complexes with

primary and secondary aliphatic amine ligands in the presence

of strong bases e.g. potassium tert-butoxide. No preliminary

preparation of the aliphatic amine complexes is required since

the efficient activation can be realized in the Pd-PEPPSI –

primary or secondary aliphatic amine – KO^tBu systems. In

general, secondary aliphatic amines are slightly more efficient

activators than primary aliphatic amines. In addition, primary

and secondary aliphatic amines not only serve as facile

reductants of Pd^II/NHC complexes but also help to prevent the

formation of inactive polythiolate complexes and suppress the

unwanted cleavage of the Pd-C_(NHC)bond, which may result

from O-NHC coupling at the activation stage.

(1a),²⁰

dibromo(1,3-

(iii) Efficient catalytic systems Pd-PEPPSI – aliphatic amine

(diethylamine or morpholine) comprising IPr and IPr*OMe

NHC-ligands have been developed for the reactions of thiols

with aryl bromides and aryl chlorides. The combination of

relatively low temperature and bulky NHC ligands allows to

obtain diaryl sulphides in high yields and minimize the

unwanted effects of C-S bond activation.

(1e),⁸¹

{1,3-bis[2,6-

di(propan-2-yl)phenyl]-1,3-dihydro-2H-imidazol-2-

ylidene}(diiodo)(pyridine)palladium (1g),²⁰(2,4-dimethyl-2,4-

dihydro-3H-1,2,4-triazol-3-ylidene)(diiodo)(pyridine)palladium

(1j),²⁰

{1,3-bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-

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added to a solution of compound 1 (0.02 mmol)_Vi_in_ewC_AD_rtiC_cll_e₃_O(_n0_li._n7_e

imidazol-2-ylidene}(dichloro)(N,N-

diethylethanamine)palladium (2x),⁴⁵1,3-dimethyl-1H-3,1- mL) with ТМS (3 µL). The tube was se^Da^Ole^Id^{: 10}w^.1i⁰t³h^9/t^Ch⁹e^CYr⁰u²b⁰b⁴e^1Ar

benzimidazol-3-ium iodide (3a),²⁰1,3-dimethyl-1H-imidazol-3- septa and placed in a thermostated oil bath (40 or 60 °C) atop

ium iodide (3b),⁸²1,3-bis[2,6-di(propan-2-yl)phenyl]-1H- of a magnetic stirrer. After completion of the reaction time (1

imidazol-3-ium chloride (3c),⁸³1,4-dimethyl-4H-1,2,4-triazol-1- or 20 h), the reaction mixture was analyzed by NMR. The yields

ium iodide (3d),⁸²1,3-bis[2,6-di(propan-2-yl)phenyl]-1H- (%) of the reaction products (Table 1, Scheme 3) were

imidazol-3-ium bromide (3e),⁸⁴1,3-bis[2,6-di(propan-2- determined by peak integration for the corresponding protons

yl)phenyl]-1H-imidazol-3-ium iodide (3f),⁸⁴1,3-dibutyl-1H-3,1- in ¹H spectra.

benzimidazol-3-ium bromide (3g),⁸²were synthesized by the

published procedures. Other chemicals were obtained from 4.3 Study of the reaction of Pd-PEPPSI complexes with

commercial sources.

aliphatic amines by HPLC. A 7 mL screw-capped glass tube

(1,3-Dibutyl-1,3-dihydro-2H-benzimidazol-2-

equipped with a magnetic stir bar was charged with a solution

ylidene)(diiodo)(pyridine)palladium (1c). A mixture of 1,3- of compound 1 (0.05 mmol) in appropriate solvent (2.5 mL). A

dibutyl-1H-benzimidazol-3-ium bromide 3g (197 mg, 0.55 solution of aliphatic amine (0.05 – 0.5 mmol) in appropriate

mmol), KI (415 mg, 2.5 mmol), anhydrous K₂CO₃(345 mg, 2.5 solvent (2.5 mL) was added to the reaction tube. The tube was

mmol), PdCl₂(89 mg, 0.5 mmol) and dry pyridine (4 mL) was closed tightly with the screw cap and placed in a thermostated

heated at vigorous stirring for 16 h at 80 °C in a sealed glass oil bath (25 – 100 °C), and that instant was taken as the

vial. After cooling to room temperature, the reaction mixture starting point of the reaction. At the time points indicated in

was diluted with CH₂Cl₂(10 mL) and passed through a short Figure 2, Tables 1 and S2, 10 µL aliquots of reaction mixtures

pad of silica gel eluting with CH₂Cl₂until complete recovery of were sampled from the tubes, diluted with acetonitrile and

the yellow product. The solvent was removed on a rotary analyzed. The yields (%) of products 2-4 (Figure 2, Tables 1, S2)

evaporator under vacuum. The residue obtained was treated were determined by HPLC using corresponding calibration

with hexane (3×5 mL), the precipitate formed was separated curves.

by filtration and recrystallized from CH₂Cl₂-hexane 1:3 mixture.

1

Yield 264 mg (79%), orange prismatic crystals of 1c. H NMR 4.4 General procedure for the synthesis of amino-complexes

(CDCl₃, 500 MHz): δ 1.08 (t, 6H, 2CH₃, J = 7.4 Hz), 1.53-1.62 (m, 2a-w. A mixture of Pd-PEPPSI complex 1 (0.15 mmol), aliphatic

4H, 2CH₂), 2.18-2.25 (m, 4Н, 2CH₂), 4.81 (t, 4H, 2CH₂, J = 8.9 amine (0.165 mmol) and 1,4-dioxane (3 mL) in a screw-capped

Hz), 7.24-7.28 (m, 2H, H_Ar), 7.34-7.41 (m, 4H, H_Ar), 7.74-7.79 tube was stirred at 50 °C for 30 min. Then the mixture was

(m, 1H, H_Ar), 9.05-9.07 (m, 2H, H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ cooled to 20 °C and diluted with water (∼15 mL). The insoluble

14.0, 20.5, 31.2, 48.7, 110.5, 122.9, 124.7, 134.7, 138.0, 152.7, yellow product was collected by filtration, washed with water,

161.5. Anal. calcd. for C₂₀H₂₇I₂N₃Pd (%): C, 35.87; H, 4.06; N, dried and recrystallized from a mixture of CH₂Cl₂with hexane

6.27. Found (%): C, 35.75; H, 3.95; N, 6.16.

(1:3).

{1,3-Bis[2,6-bis(diphenylmethyl)-4-methoxyphenyl]-1,3-

dihydro-2H-imidazol-2-ylidene}(dichloro)(pyridine)palladium

4.4.1

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-

(1i).

A

mixture of 1,3-bis[2,6-bis(diphenylmethyl)-4- ylidene)(N-ethylethanamine)diiodopalladium (2a). Yield 82

1

methoxyphenyl]-1,3-dihydro-2H-imidazol-2-ium bromide (498 mg (94%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ

mg, 0.55 mmol), anhydrous K₂CO₃(345 mg, 2.5 mmol), PdCl₂1.46 (t, 6H, 2CH₃, J = 7.1 Hz); 2.72-2.79 (m, 2Н, СН₂); 2.94-3.03

(89 mg, 0.5 mmol) and dry pyridine (4 mL) was heated at (m, 2Н, СН₂); 3.68-3.72 (m, 1Н, NН); 4.02 (s, 6Н, 2СН₃); 7.33-

vigorous stirring for 16 h at 80 °C in a sealed glass vial. After 7.36 (m, 2Н, H_Ar); 7.64-7.68 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125

cooling to room temperature, the reaction mixture was diluted MHz): δ 15.1; 34.9; 48.3; 110.3; 122.8; 134.4; 164.0. Anal.

with CH₂Cl₂(10 mL) and passed through a short pad of silica calcd. for C₁₃H₂₁I₂N₃Pd (%): C, 26.94; H, 3.65; N, 7.25. Found

gel eluting with CH₂Cl₂until complete recovery of the yellow (%): C, 26.81; H, 3.53; N, 7.14.

product. The solvent was removed on a rotary evaporator

under vacuum. The residue obtained was chromatographed on 4.4.2

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-

silica gel (CH₂Cl₂as an eluent) to give the pure 2v complex. ylidene)(diiodo)[2-methyl-N-(2-methylpropyl)propan-1-

1

Yield 533 mg (81%), yellow powder of 2v. H NMR (CDCl₃, 500 amine]palladium (2b). Yield 84 mg (88%), yellow powder. H

MHz): δ 3.51 (s, 6H, 2CH₃), 4.82 (s, 2Н, 2СН), 6.36 (s, 4Н, H_Ar), NMR (DMSO-d₆, 500 MHz): δ 0.98 (d, 6H, 2CH₃, J = 6.6 Hz),

6.48 (s, 4Н, 4СН), 6.75-6.77 (m, 8H, H_Ar), 7.00-7.08 (m, 12H, 1.08 (d, 6H, 2CH₃, J = 6.6 Hz), 2.55-2.64 (m, 2Н, СН₂), 2.97-3.02

H_Ar), 7.14-7.21 (m, 12H, H_Ar), 7.35-7.38 (m, 2H, H_Ar), 7.44-7.45 (m, 2Н, СН₂), 3.04-3.08 (m, 1Н, NН), 4.00 (s, 6Н, 2СН₃), 7.34-

(m, 8H, H_Ar), 7.77-7.81 (m, 1H, H_Ar), 9.08-9.10 (m, 2H, H_Ar). 7.36 (m, 2Н, H_Ar), 7.65-7.67 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125

¹³C{¹H} (CDCl₃, 125 MHz): δ 51.2, 55.0, 115.6, 124.1, 124.4, MHz): δ 20.3, 20.5, 26.6, 35.0, 60.8, 110.4, 122.9, 134.4, 162.2.

126.2, 126.3, 128.0, 128.3, 129.5, 130.6, 131.0, 143.7, 144.0, Anal. calcd. for C₁₇H₂₉I₂N₃Pd (%): C, 32.12; H, 4.60; N, 6.61.

144.4, 152.0, 158.9. Anal. calcd. for C₇₄H₆₁Cl₂N₃O₂Pd (%):C, Found (%): C, 32.01; H, 4.51; N, 6.52.

73.97; H, 5.12; N, 3.50. Found (%):C, 74.09; H, 5.20; N, 3.58.

4.4.3

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2-

4.2 Study of the reaction of Pd-PEPPSI complexes with ylidene)(diiodo)(morpholine-kN)palladium (2c). Yield 86 mg

1

aliphatic amines by H NMR. Amine (0.06 or 0.2 mmol) was (96%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 2.85-

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2.87 (m, 2Н, СН₂), 3.33-3.38 (m, 2Н, СН₂), 3.58-3.65 (m, 4Н, 165.3. Anal. calcd. for C₁₅H₂₃I₂N₃Pd (%): C, 29.75; H, 3.83; N,

View Article Online

DOI: 10.1039/C9CY02041A

2СН₂), 3.92-3.97 (m, 1Н, NН), 4.00 (s, 6Н, 2СН₃), 7.33-7.35 (m, 6.94. Found (%): C, 29.81; H, 3.91; N, 7.01.

2Н, H_Ar), 7.64-7.66 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ

35.2, 50.0, 66.7, 110.3, 122.9, 134.4, 161.4. Anal. calcd. for 4.4.9

Dibromo(1,3-dibutyl-1,3-dihydro-2H-benzimidazol-2-

C₁₃H₁₉I₂N₃OPd (%): C, 26.31; H, 3.23; N, 7.08. Found (%): C, ylidene)(N-ethylethanamine)palladium (2i). Yield 76 mg

26.19; H, 3.16; N, 7.20.

(89%), yellow powder. ¹H NMR (DMSO-d₆, 500 MHz): δ 0.97 (t,

6H, 2CH₃, J = 7.4 Hz), 1.41-1.49 (m, 4H, 2CH₂), 1.51 (t, 6H, 2CH₃,

4.4.4

(1,3-Dimethyl-2,3-dihydro-2H-benzimidazol-2- J = 7.1 Hz), 2.05-2.11 (m, 4H, 2CH₂), 2.51-2.56 (m, 2Н, СН₂),

ylidene)(diiodo)(piperidine)palladium (2d). Yield 83 mg (94%), 2.85-2.92 (m, 2Н, СН₂), 3.48-3.52 (m, 1Н, NН), 4.69-4.72 (m,

1

yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 1.35-1.42 and 4H, 2CH₂), 7.32-7.35 (m, 2H, H_Ar), 7.68-7.71 (m, 2H, H_Ar).

1.71-1.73 (two m, 2Н, СН₂), 1.49-1.55 (m, 4Н, 2СН₂), 3.02-3.06 ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 13.7, 14.7, 19.7, 30.8, 46.7,

(m, 4Н, 2СН₂), 3.20-3.27 (m, 1Н, NН), 3.99 (s, 6Н, 2СН₃), 7.33- 47.4, 110.7, 122.9, 133.8, 165.6. Anal. calcd. for C₁₉H₃₃Br₂N₃Pd

7.35 (m, 2Н, H_Ar), 7.64-7.66 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 (%): C, 40.06; H, 5.84; N, 7.38. Found (%): C, 40.18; H, 5.75; N,

MHz): δ 23.7, 26.7, 35.2, 50.9, 110.3, 122.9, 134.4, 162.4. Anal. 7.31.

calcd. for C₁₄H₂₁I₂N₃Pd (%): C, 28.42; H, 3.58; N, 7.10. Found

(%): C, 28.30; H, 3.49; N, 7.19.

4.4.10

ylidene)(N-ethylethanamine)diiodopalladium (2j). Yield 77 mg

(1,3-Dimethyl-2,3-dihydro-2H-benzimidazol-2- (77%), yellow powder. ¹H NMR (DMSO-d₆, 500 MHz): δ 0.96 (t,

(1,3-Dibutyl-1,3-dihydro-2H-benzimidazol-2-

4.4.5

ylidene)(diiodo)(2-methylpiperidine)palladium (2e). Yield 85 6H, 2CH₃, J = 7.4 Hz), 1.41-1.47 (m, 10H, 2CH₂+ 2CH₃), 2.03-

1

mg (93%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 2.11 (m, 4H, 2CH₂), 2.73-2.78 (m, 2Н, СН₂), 2.97-3.04 (m, 2Н,

1.32-1.39, 1.55-1.53, 1.59-1.61, 1.70-1.72 (four m, 6Н, 3СН₂), СН₂), 3.70-3.76 (m, 1Н, NН), 4.59-4.63 (m, 4H, 2CH₂), 7.31-7.33

1.44 (d, 3H, CH₃, J = 6.4 Hz), 2.81-2.85 (m, 1H, NН), 2.97-3.05 (m, 2H, H_Ar), 7.66-7.69 (m, 2H, H_Ar). ¹³C{¹H} (DMSO-d₆, 125

(m, 1Н, СН), 3.15-3.18 (m, 2Н, СН₂), 4.01 (s, 6Н, 2СН₃), 7.33- MHz): δ 13.6, 14.9, 19.6, 29.9, 48.0, 48.4, 110.7, 122.8, 134.1,

7.36 (m, 2Н, H_Ar), 7.65-7.67 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 162.2. Anal. calcd. for C₁₉H₃₃I₂N₃Pd (%):C, 34.38; H, 5.01; N,

MHz): δ 23.1, 23.4, 25.7, 33.9, 35.1, 49.8, 55.7, 110.4, 122.9, 6.33. Found (%):C, 34.49; H, 5.12; N, 6.24.

134.4, 162.9. Anal. calcd. for C₁₅H₂₃I₂N₃Pd (%): C, 29.75; H,

3.83; N, 6.94. Found (%): C, 30.01; H, 3.82; N, 6.90.

4.4.11 (1,3-Dimethyl-1,3-dihydro-2H-imidazol-2-ylidene)(N-

ethylethanamine)diiodopalladium (2k). Yield 69 mg (87%),

1

4.4.6

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2- yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 1.41 (t, 6H,

ylidene)(1-ethylpiperazine-kN⁴)diiodopalladium (2f). Yield 71 2CH₃, J = 7.1 Hz), 2.66-2.73 (m, 2Н, СН₂), 2.88-2.97 (m, 2Н,

mg (76%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ СН₂), 3.44-3.48 (m, 1Н, NН), 3.74 (s, 6Н, 2СН₃), 7.33 (s, 2Н,

1

0.97 (t, 3H, CH₃, J = 7.1 Hz), 2.01-2.05 (m, 2Н, СН₂), 2.27 (q, 2H, 2CH). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 15.0, 37.6, 48.2, 123.4,

CH₂, J = 7.1 Hz), 2.67-2.70 (m, 2Н, СН₂), 2.94-2.96 (m, 2Н, СН₂), 147.3. Anal. calcd. for C₉H₁₉I₂N₃Pd (%): C, 20.42; H, 3.62; N,

3.17-3.22 (m, 3Н, СН₂+ NН), 4.00 (s, 6Н, 2СН₃), 7.33-7.35 (m, 7.94. Found (%): C, 20.53; H, 3.51; N, 7.81.

2Н, H_Ar), 7.64-7.66 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ

11.7, 35.2, 49.7, 51.9, 53.4, 110.3, 122.9, 134.4, 161.8. Anal. 4.4.12

(1,3-Dimethyl-1,3-dihydro-2H-imidazol-2-

calcd. for C₁₅H₂₄I₂N₄Pd (%): C, 29.03; H, 3.90; N, 9.03. Found ylidene)(diiodo)(1-phenylmethanamine)palladium (2l). Yield

1

(%): C, 28.91; H, 3.96; N, 9.11.

75 mg (89%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ

3.47-3.50 (m, 2Н, NН₂), 3.67 (s, 6Н, 2СН₃), 3.94-3.97 (m, 2Н,

4.4.7

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2- СН₂), 7.26-7.30 (m, 3Н, H_Ar+2H), 7.33-7.36 (m, 2Н, H_Ar), 7.50-

ylidene)(diiodo)(1-phenylmethanamine)palladium (2g). Yield 7.52 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 37.7, 48.0,

1

83 mg (90%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 123.4, 127.1, 128.1, 128.6, 139.2, 148.0. Anal. calcd. for

3.69-3.71 (m, 2Н, NН₂), 3.92 (s, 6Н, 2СН₃), 4.01-4.03 (m, 2Н, C₁₂H₁₇I₂N₃Pd (%): C, 25.58; H, 3.04; N, 7.46. Found (%): C,

СН₂), 7.29-7.34 (m, 3Н, H_Ar), 7.36-7.39 (m, 2Н, H_Ar), 7.54-7.56 25.42; H, 3.16; N, 7.58.

(m, 2Н, H_Ar), 7.62-7.64 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125

MHz): δ 35.0, 48.2, 110.3, 122.8, 127.2, 128.2, 128.8, 134.4, 4.4.13

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-

139.5, 164.7. Anal. calcd. for C₁₆H₁₉I₂N₃Pd (%): C, 31.32; H, imidazol-2-ylidene}(dichloro)(N-ethylethanamine)palladium

3.12; N, 6.85. Found (%): C, 31.45; H, 3.21; N, 6.73.

(2m). Yield 74 mg (77%), yellow powder. The physical and

spectral characteristics of the product obtained are similar to

4.4.8

(Cyclohexanamine)(1,3-dimethyl-1,3-dihydro-2H- those described in the literature.^42,44

benzimidazol-2-ylidene)diiodopalladium (2h). Yield 71 mg

1

(78%), yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 1.08- 4.4.14

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-

1.15 and 1.54-1.56 (two m, 2Н, СН₂), 1.18-1.24 (m, 4Н, 2СН₂), imidazol-2-ylidene}(dibromo)(N-ethylethanamine)palladium

1

1.70-1.72 (m, 2Н, СН₂), 2.17-2.18 (m, 2Н, СН₂), 2.99-3.02 (m, (2n). Yield 81 mg (74%), orange powder. H NMR (DMSO-d₆,

1Н, СН), 3.18-3.19 (m, 2Н, NН₂), 4.02 (s, 6Н, 2СН₃), 7.33-7.35 500 MHz): δ 0.83 (t, 6H, 2CH₃, J = 7.2 Hz), 1.02 (d, 12H, 4CH₃, J

(m, 2Н, H_Ar), 7.64-7.66 (m, 2Н, H_Ar). ¹³C{¹H} (DMSO-d₆, 125 = 6.9 Hz), 1.34 (d, 12H, 4CH₃, J = 6.9 Hz), 2.08-2.14 (m, 2Н,

MHz): δ 24.5, 25.0, 35.98, 35.04, 53.3, 110.3, 122.8, 134.4, СН₂), 2.40-2.44 (m, 2Н, СН₂), 2.89-2.93 (m, 1Н, NH), 3.09-3.15

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(m, 4Н, 4СН), 7.32-7.34 (m, 4Н, H_Ar), 7.47-7.50 (m, 2 Н, H_Ar), C₃₀H₄₃Cl₂N₃Pd (%): C, 57.84; H, 6.96; N, 6.74. F_Vo_ieu_wn_Ad_rtic(_l%_{e O}):_nliC_ne,

7.73 (s, 2Н, 2CH). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 14.0, 22.7, 57.63; H, 6.28; N, 6.19.

DOI: 10.1039/C9CY02041A

26.2, 28.3, 46.2, 123.3, 126.2, 129.7, 135.3, 146.2, 156.7. Anal.

calcd. for C₃₁H₄₇Br₂N₃Pd (%): C, 51.15; H, 6.51; N, 5.77. Found 4.4.20

(%): C, 51.36; H, 6.82; N, 5.91. imidazol-2-ylidene}(dichloro)(2-methylpropan-2-

amine)palladium (2t). Yield 69 mg (72%), yellow powder. H

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H- NMR (CDCl₃, 500 MHz): δ 1.00 (s, 9H, 3CH), 1.08 (d, 12H, 4CH₃,

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H-

1

4.4.15

imidazol-2-ylidene}(N-ethylethanamine)diiodopalladium (2o). J = 6.7 Hz), 1.42 (d, 12H, 4CH₃, J = 6.8 Hz), 2.00 (s, 2Н, NН₂),

1

Yield 89 mg (72%), orange powder. H NMR (DMSO-d₆, 500 3.04-3.13 (m, 4Н, 4СН), 7.10 (s, 2Н, 2CH), 7.34-7.36 (m, 4H,

MHz): δ 0.82 (t, 6H, 2CH₃, J = 7.0 Hz), 1.02 (d, 12H, 4CH₃, J = 6.5 H_Ar), 7.48-7.51 (m, 2Н, H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ 23.0,

Hz), 1.38 (d, 12H, 4CH₃, J = 6.8 Hz), 2.36-2.42 (m, 2Н, СН₂), 26.6, 28.9, 31.8, 52.5, 123.9, 124.9, 130.3, 135.2, 147.1, 158.0.

2.69-2.75 (m, 2Н, СН₂), 3.25-3.31 (m, 5Н, 2СН₂+ NH), 7.31-7.32 Anal. calcd. for C₃₁H₄₇Cl₂N₃Pd (%): 58.26; H, 7.41; N, 6.58.

(m, 4H, H_Ar), 7.46-7.49 (m, 2Н, H_Ar), 7.75 (s, 2Н, 2CH). ¹³C{¹H} Found (%): 58.43; H, 7.49; N, 6.53.

(DMSO-d₆, 125 MHz): δ 14.3, 23.2, 26.2, 28.8, 47.9, 123.7,

126.7, 129.9, 135.8, 146.0, 155.4. Anal. calcd. for C₃₁H₄₇I₂N₃Pd 4.4.21 {1,3-Bis[2,6-bis(diphenylmethyl)-4-methylphenyl]-1,3-

(%): C, 45.30; H, 5.76; N, 5.11. Found (%): C, 45.16; H, 5.62; N, dihydro-2H-imidazol-2-ylidene}(dichloro)(N-

5.22.

ethylethanamine)palladium (2u). Yield 113 mg (65%), yellow

powder. H NMR (CDCl₃, 500 MHz): δ 1.09 (t, 6H, 2CH₃, J = 7.1

1

4.4.16

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H- Hz), 2.23 (s, 6H, 2CH₃), 2.33-2.38 (m, 3Н, СН₂+ NH), 2.88-2.94

imidazol-2-ylidene}dichloro(morpholine)palladium (2p). Yield (m, 2Н, СН₂), 4.48 (s, 2Н, 2СН), 5.98 (s, 4Н, 4СН), 6.70-6.72 (m,

77 mg (79%), yellow powder. The physical and spectral 8Н, H_Ar), 6.81 (s, 4H, H_Ar), 7.01-7.02 (m, 12H, H_Ar), 7.18-7.21 (m,

characteristics of the product obtained were identical to those 4H, H_Ar), 7.25-7.28 (m, 8H, H_Ar), 7.49-7.50 (m, 8H, H_Ar). ¹³C{¹H}

described in the literature.⁵⁰

(CDCl₃, 125 MHz): δ 14.8, 22.0, 46.5, 51.2, 123.1, 126.1, 126.3,

128.0, 128.1, 129.4, 129.9, 131.2, 134.8, 138.5, 142.7, 143.8,

4.4.17

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H- 145.6, 157.6. Anal. calcd. for C₇₃H₆₇Cl₂N₃Pd (%): C, 75.35; H,

imidazol-2-ylidene}dichloro(1-propylamine)palladium (2q). 5.80; N, 3.61. Found (%): C, 75.49; H, 5.92; N, 3.70.

Yield 78 mg (84%), yellow powder. ¹H NMR (CDCl₃, 500 MHz): δ

0.70 (t, 3H, CH₃, J = 7.3 Hz), 1.08 (d, 12H, 4CH₃, J = 6.9 Hz),

1.26-1.32 (m, 2Н, СН₂), 1.43 (d, 12H, 4CH₃, J = 6.7 Hz), 1.83 (t, 4.4.22

{1,3-Bis[2,6-bis(diphenylmethyl)-4-methoxyphenyl]-

2Н, NН₂, J = 6.5 Hz), 2.40-2.46 (m, 2Н, СН₂), 3.04-3.09 (m, 4Н, 1,3-dihydro-2H-imidazol-2-ylidene}(dichloro)(N-

4СН), 7.09 (s, 2Н, 2CH), 7.35-7.36 (m, 4H, H_Ar), 7.49-7.52 (m, ethylethanamine)palladium (2v). Yield 109 mg (61%), yellow

1

2Н, H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ 11.1, 23.1, 24.8, 26.5, powder. H NMR (CDCl₃, 500 MHz): δ 1.13 (t, 6H, 2CH₃, J = 7.0

28.9, 44.8, 124.0, 124.9, 130.3, 135.2, 146.9, 158.5. Anal. calcd. Hz), 2.34-2.40 (m, 3Н, СН₂+ NH), 2.89-2.97 (m, 2Н, СН₂), 3.55

for C₃₀H₄₅Cl₂N₃Pd (%): C, 57.65; H, 7.26; N, 6.72. Found (%):C, (s, 6H, 2OCH₃), 4.46 (s, 2Н, 2СН), 5.99 (s, 4Н, 4СН), 6.55 (s, 4Н,

57.81; H, 7.38; N, 6.80.

H_Ar), 6.74-6.75 (m, 8H, H_Ar), 7.02-7.04 (m, 12H, H_Ar), 7.19-7.20

(m, 4H, H_Ar), 7.25-7.28 (m, 8H, H_Ar), 7.50-7.51 (m, 8H, H_Ar).

4.4.18

imidazol-2-ylidene}(dichloro)(1-

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H- ¹³C{¹H} (CDCl₃, 125 MHz): δ 15.0, 46.5, 51.4, 55.2, 114.7, 123.2,

126.2, 126.4, 128.07, 128.12, 129.4, 130.3, 131.0, 143.6, 144.6,

phenylmethanamine)palladium (2r). Yield 92 mg (91%), 145.2, 159.3. Anal. calcd. for C₇₃H₆₇Cl₂N₃O₂Pd (%): C, 73.33; H,

1

yellow powder. H NMR (DMSO-d₆, 500 MHz): δ 1.05 (d, 12H, 5.65; N, 3.51. Found (%): C, 73.47; H, 5.73; N, 3.62.

4CH₃, J = 6.6 Hz), 1.31 (d, 12H, 4CH₃, J = 6.9 Hz), 2.98-3.06 (m,

6Н, СН₂+ 4CH), 3.44 (t, 2Н, NH₂, J = 6.6 Hz), 7.11-7.18 (m, 5Н, 4.4.23

(2,4-Dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-

H_Ar), 7.37-7.39 (m, 4Н, H_Ar), 7.53-7.56 (m, 2Н, H_Ar), 7.69 (s, 2Н, ylidene)(N-ethylethanamine)diiodopalladium (2w). Yield 66

1

2CH). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 22.8, 26.0, 28.1, 45.5, mg (83%), orange powder. H NMR (DMSO-d₆, 500 MHz): δ

123.6, 126.1, 126.7, 128.0, 128.1, 129.7, 135.3, 138.9, 146.3, 1.41 (t, 6H, 2CH₃, J = 7.1 Hz), 2.70-2.77 (m, 2Н, СН₂), 2.90-2.99

157.1. Anal. calcd. for C₃₄H₄₅Cl₂N₃Pd (%): C, 60.67; H, 6.74; N, (m, 2Н, СН₂), 3.78-3.81 (m, 1Н, NН), 3.79 (s, 3Н, СН₃), 3.92 (s,

6.24. Found (%): C, 60.45; H, 6.85; N, 6.11.

3Н, СН₃), 8.72 (s, 1Н, CH). ¹³C{¹H} (DMSO-d₆, 125 MHz): δ 15.1,

35.2, 48.5, 144.8, 155.5. Anal. calcd. for C₈H₁₈I₂N₄Pd (%): C,

4.4.19

{1,3-Bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-2H- 18.11; H, 3.42; N, 10.56. Found (%): C, 18.24; H, 3.31; N, 10.43.

imidazol-2-ylidene}dichloro(cyclopropanamine)palladium

1

(2s). Yield 74 mg (80%), yellow powder. H NMR (DMSO-d₆, 4.5 Studies of the formation of azolium salts 3c,e,f from

500 MHz): δ 0.06-0.10 (m, 2H, CH₂), 0.36-0.39 (m, 2H, CH₂), complexes 2k,m-o,q,x heated in DMF. A solution of complex 2

1.01 (d, 12H, 4CH₃, J = 6.8 Hz), 1.31 (d, 12H, 4CH₃, J = 6.8 Hz), (0.1 mmol) and 1,3-diisopropylbenzene (19 µL, 0.1 mmol, an

1.81-1.85 (m, 1Н, СН), 2.92-3.00 (m, 4Н, 4СН), 3.54-3.55 (m, internal standard) in DMF (2 mL) was magnetically stirred at

1Н, NH), 7.32-7.34 (m, 4Н, H_Ar), 7.48-7.51 (m, 2 Н, H_Ar), 7.58 (s, 140 °C in a 7 mL screw-capped glass tube equipped with a

2Н, 2CH). ¹³C{¹H} (DMSO-d₆, 125 MHz): 5.8, 23.1, 25.6, 26.4, septum. At the time points indicated in Table 2 or Figure S3, 5

28.5, 123.9, 126.3, 130.3, 135.6, 146.7, 157.7. Anal. calcd. for µL aliquots of the reaction mixture were sampled with a

16 | J. Name., 2019, 00, 1-3

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syringe (passing a needle through the septum), diluted with 4.98 (s, 2Н, NH₂), 6.47-6.55 (m, 3Н, H_Ar), 6.97-7.01 (m, 2 Н , H_Ar),

View Article Online

13

1

DOI: 10.1039/C9CY02041A

acetonitrile (1 mL) and then analyzed by HPLC. The yields (%) 7.40 (s, 2Н, 2CH). C{ H} (DMSO-d₆, 125 MHz): δ 38.0, 113.8,

were calculated using the corresponding calibration curves.

1

115.6, 124.0, 128.8, 140.8, 148.6. H NMR (CDCl₃, 500 MHz): δ

3.80 (s, 6Н, 2СН₃), 4.47 (s, 2Н, NH₂), 6.87 (s, 2Н, 2CH), 7.12-

4.6 General procedure for the synthesis of complexes 2y-z,aa- 7.15 (m, 1Н, H_Ar), 7.29-7.32 (m, 2Н, H_Ar), 7.44-7.46 (m, 2Н, H_Ar).

ae.A mixture of complex 1a, 1d, 1e or 1h (0.15 mmol), ¹³C{¹H} (CDCl₃, 125 MHz): δ 38.8, 121.6, 123.0, 124.9, 129.0,

aromatic amine (1.5 mmol) and DMF (3 mL) in a screw-capped 139.6, 145.9. Anal. calcd. for C₁₁H₁₅I₂N₃Pd (%): C, 24.04; H,

tube was magnetically stirred at 120 °C for 20 min. Then the 2.75; N, 7.65. Found (%): C, 23.91; H, 2.68; N, 7.71.

solvent was removed in vacuo, the residue was washed three

times with 3 mL of Et₂O-hexane mixture (1:3) and dried at 4.6.6 (Aniline){1,3-bis[2,6-di(propan-2-yl)phenyl]-1,3-dihydro-

45 °С in vacuo. The pure product was obtained after 2H-imidazol-2-ylidene}dichloropalladium (2ad). Yield 71 mg

recrystallization from CH₂Cl₂-hexane (1:3).

(72%), yellow crystals. The physical and spectral characteristics

of the product obtained are similar to those described in the

4.6.1 (Aniline)(1,3-dimethyl-1,3-dihydro-2H-benzimidazol-2- literature.⁸⁵

ylidene)diiodopalladium (2y). Yield 75 mg (83%), orange

1

crystals. H NMR (CDCl₃, 500 MHz): δ 4.02 (s, 6Н, 2СН₃), 4.57 4.6.7

(Aniline)(2,4-dimethyl-2,4-dihydro-3H-1,2,4-triazol-3-

(s, 2Н, NH₂), 7.15-7.18 (m, 2Н, H_Ar), 7.27-7.29 (m, 1Н, H_Ar), ylidene)diiodopalladium (2ae). Yield 64 mg (78%), orange

7.31-7.36 (m, 4Н, H_Ar), 7.49-7.51 (m, 2Н, H_Ar). ¹³C{¹H} (CDCl₃, crystals. ¹H NMR (DMSO-d₆, 500 MHz): δ 3.90 (s, 3Н, СН₃), 4.04

125 MHz): δ 35.8, 110.0, 121.9, 123.1, 125.2, 129.3, 135.2, (s, 3Н, СН₃), 4.97 (s, 2Н, NH₂), 7.53-7.56 (m, 2Н, H_Ar), 7.95-7.98

1

139.8, 165.0. Anal. calcd. for C₁₅H₁₇I₂N₃Pd (%): C, 30.05; H, (m, 1Н, H_Ar), 8.77 (s, 1H, CH), 8.90-8.91 (m, 2Н, H_Ar). H NMR

2.86; N, 7.01. Found (%): C, 29.91; H, 2.79; N, 7.12.

(CDCl₃, 500 MHz): δ 3.84 (s, 3H, CH₃), 4.00 (s, 3H, CH₃), 4.58 (s,

4.6.2 (1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2- 2H, NH₂), 7.14-7.17 (m, 1H, H_Ar), 7.31-7.34 (m, 2H, H_Ar), 7.45-

ylidene)(diiodo)(4-methoxyaniline-kN)palladium (2z). Yield 80 7.47 (m, 2H, H_Ar), 7.89 (s, 1H, CH). ¹³C{¹H} (DMSO-d₆, 125 MHz):

mg (85%), orange crystals. ¹H NMR (CDCl₃, 500 MHz): δ 3.81 (s, δ 35.6, 113.8, 125.0, 128.8, 138.7, 145.0, 153.2 (signals are

3Н, OMe), 4.02 (s, 6Н, СН₃), 4.46 (s, 2Н, NH₂), 6.86-6.87 (m, 2H, partially overlapped). ¹³C{¹H} (CDCl₃, 125 MHz): δ 36.3, 40.8,

H_Ar), 7.26-7.27 (m, 2Н, H_Ar), 7.32-7.33 (m, 2Н, H_Ar), 7.42-7.44 122.0, 125.4, 129.3, 139.6, 143.3, 154.4. Anal. calcd. for

(m, 2H, H_Ar). ¹³C{¹H} (CDCl₃, 126 MHz): δ 35.8, 55.6, 109.9, C₁₀H₁₄I₂N₄Pd (%): C, 21.82; H, 2.56; N, 10.18. Found (%): C,

114.5, 123.0, 123.1, 132.7, 135.2, 157.1, 161.8. Anal. calcd. for 21.70; H, 2.48; N, 10.29.

C₁₆H₁₉I₂N₃OPd (%): C, 30.52; H, 3.04; N, 6.67. Found (%): C,

30.46; H, 2.99; N, 6.73.

4.7 Formation of azolone 8 in reactions of complexes 1e and

2m,x with KO^tBu. In a screw-capped tube, a mixture of the

4.6.3

(1,3-Dimethyl-1,3-dihydro-2H-benzimidazol-2- complex 1e, 2m or 2x (0.005 mmol), KOtBu (45 mg, 0.4 mmol),

2,4,6- 1,3-diisopropylbenzene (0.8 mg, 0.005 mmol, an internal

ylidene)(diiodo)(2,4,6-trimethylaniline)palladium

-

trimethylaniline (1:1) (monosolvate) (2aa). Yield 78 mg (81%), standard) in toluene (2 mL) was magnetically stirred at 110 °C

yellow crystals. ¹H NMR (CDCl₃, 500 MHz): δ 2.16 (s, 6H, CCH₃), for 1 h. After cooling to room temperature, the reaction

2.21 (s, 3H, CCH₃), 2.27 (s, 3H, CCH₃), 2.51 (s, 6H, CCH₃), 3.47 mixture was neutralized with acetic acid and the yield of

(s, 2H, NH₂), 4.04 (s, 2H, NH₂), 4.09 (s, 6H, NCH₃), 6.77 (s, 2H, compound 8 was determined by GC-MS (Table 4).

H_Ar), 6.88 (s, 2H, H_Ar), 7.27-7.28 (m, 2H, H_Ar), 7.33-7.35 (m, 2H,

H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ 17.7, 19.8, 20.5, 20.9, 35.7, 4.8 General procedure for C-S cross-coupling of aryl halides

109.9, 122.0, 123.1, 127.3, 127.9, 129.0, 129.3, 134.0, 135.2, with thiophenol. Method A: Under argon atmosphere, an

137.0, 140.2, 160.4. Anal. calcd. for C₂₇H₃₆I₂N₄Pd (%): C, 41.75; oven-dried vial equipped with a magnetic stir bar and a septa

H, 4.67; N, 7.21. Found (%): C, 41.83; H, 4.54; N, 7.31.

was charged with complex 1e (6.5 mg, 0.01 mmol, 2 mol. %),

aryl bromide (0.5 mmol), Bu^tOK (90 mg, 0.8 mmol) and N,N-

4.6.4

(4-Chloroaniline-kN)(1,3-dimethyl-1,3-dihydro-2H- diethylamine (2.92 mg, 0.04mmol, 4 mol %) or morpholine

benzimidazol-2-ylidene)diiodopalladium

-

4-chloroaniline (3.48 mg, 0.04 mmol, 4 mol %) in toluene (2 mL), the resulting

(1:1) (monosolvate) (2ab). Yield 60 mg (63%), yellow crystals. mixture was stirred at 25 °C for 5 min for the precatalyst

¹H NMR (CDCl₃, 500 MHz): δ 3.65 (s, 2H, NH₂), 4.01 (s, 6H, CH₃), activation. When using complex 2m (6.4 mg, 0.01 mmol, 2 mol.

4.57 (s, 2H, NH₂), 6.60-6.61 (m, 2H, H_Ar), 7.09-7.10 (m, 2H, H_Ar), %) instead of 1e, no Et₂NH or morpholine was added. Then

7.27-7.34 (m, 6H, H_Ar), 7.44-7.46 (m, 2H, H_Ar). ¹³C{¹H} (CDCl₃, PhSH (66 mg, 0.6 mmol) in toluene (2 mL) was added to the

125 MHz): δ 35.9, 110.0, 116.4, 123.1, 123.2, 123.3, 129.3, reaction mixture dropwise with a syringe (passing a needle

129.4, 130.7, 135.2, 138.4, 145.1, 160.6. Anal. calcd. for through the septum) within ~2 min at 25 °С and stirring. The

C₂₁H₂₂Cl₂I₂N₄Pd (%): C, 33.12; H, 2.91; N, 7.36. Found (%): C, resulting mixture was stirred in a sealed vial for 8–24 h at 25 °C

33.08; H, 3.05; N, 7.28.

(Table 5), then treated with 1 M aqueous solution of KOH (2

mL) under argon atmosphere. The organic layer was

4.6.5

(Aniline)(1,3-dimethyl-1,3-dihydro-2H-imidazol-2- separated, the aqueous layer was extracted with diethyl ether

ylidene)diiodopalladium (2ac). Yield 68 mg (82%), yellow (3×1 mL). The organic layer combined with the diethyl ether

1

crystals. H NMR (DMSO-d₆, 500 MHz): δ 3.73 (s, 6Н, 2СН₃), extracts was washed with water (4 mL), then dried over

J. Name., 2019, 00, 1-3 | 17

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Journal Name

anhydrous Na₂SO₄and concentrated under reduced pressure. (2m as precatalyst), colorless oil. The physical and spectral

View Article Online

The resulting products, excluding 7o-s, were purified by flash characteristics of the product obtained^Da^Or^I:e¹⁰s^.1im⁰³i⁹la^/Cr⁹t^Co^Y0t²h⁰o⁴s^1Ae

chromatography on silica gel (hexane as an eluent). described in the literature.⁸⁶

Compounds 7o-s were purified by crystallization from hexane

at ~ -50 °C.

4.8.8 4-Chlorophenyl phenyl sulfide (7i). Yield 94 mg (85%)

Method B: Under argon atmosphere, a screw-capped oven- method A (1e + Et₂NH as precatalyst), colorless oil. The

dried vial equipped with a magnetic stir bar and a septa was physical and spectral characteristics of the product obtained

charged with complex 1i (9 mg, 0.0075 mmol, 1.5 mol. %), aryl are similar to those described in the literature.⁸⁶

chloride (0.5 mmol), Bu^tOK (90 mg, 0.8 mmol) and N,N-

diethylamine (1.46 mg, 0.02mmol, 4 mol %) or morpholine 4.8.9 N,N-Dimethyl-4-(phenylsulfanyl)aniline (7j). Yield 105

(1.74 mg, 0.02 mmol, 4 mol %) in toluene (2 mL). When using mg (92%) method A (1e + Et₂NH as precatalyst), colorless

complex 2v (9 mg, 0.0075 mmol, 1.5 mol. %) instead of 1i, no crystals, mp 63-65 °C. The physical and spectral characteristics

Et₂NH or morpholine was added. The resulting mixture was of the product obtained are similar to those described in the

stirred in a sealed vial at 60 °C for 5 min for the precatalyst literature.⁸⁹

activation. Then PhSH (66 mg, 0.6 mmol) in toluene (2 mL) was

added to the reaction mixture dropwise with a syringe (passing 4.8.10 4-(Phenylsulfanyl)aniline (7k). Yield 89 mg (89%)

a needle through the septum) within ~2 min at stirring. The method A (1e + Et₂NH as precatalyst), 87 mg (87% as

resulting mixture was stirred at 60 °C for 12–24 h (Table 5), precatalyst) method A (2m), colorless crystals, mp 83-85 °C.

then treated as described in the Method A.

The physical and spectral characteristics of the product

obtained are similar to those described in the literature.⁸⁶

4.8.1 4-Methylphenyl phenyl sulfide (7a). Yield 92 mg (92%)

method A (1e + Et₂NH as precatalyst), 94 mg (94%) method A 4.8.11 3-(Phenylsulfanyl)aniline (7l). Yield 80 mg (80%)

(2m as precatalyst), colorless oil. The physical and spectral method B (1i + Et₂NH as precatalyst), colorless oil. The physical

characteristics of the product obtained are similar to those and spectral characteristics of the product obtained are similar

described in the literature.⁸⁶

to those described in the literature.⁹⁰

4.8.2 Diphenyl sulfide (7c). Yield 88 mg (95%) method A (1e + 4.8.12 2-Methyl-5-(phenylsulfanyl)aniline (7m). Yield 89 mg

Et₂NH as precatalyst), 91 mg (98%) method B (1i + Et₂NH as (83%) method B (1i + Et₂NH as precatalyst), 92 mg (85%)

precatalyst), colorless oil. The physical and spectral method B (2v as precatalyst), colorless oil. ¹H NMR (CDCl₃, 500

characteristics of the product obtained are similar to those MHz): δ 2.17 (s, 3H, CH₃), 3.61 (s, 2H, NH₂), 6.73-6.77 (m, 2H,

described in the literature.⁸⁶

H_Ar), 7.01-7.02 (m, 1H, H_Ar), 7.18-7.22 (m, 1H, H_Ar), 7.26-7.32

(m, 4H, H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ 17.2, 118.3, 122.1,

4.8.3 4-tert-Butylphenyl phenyl sulfide (7d). Yield 109 mg 122.5, 126.5, 129.1, 130.1, 131.3, 132.8, 137.2, 145.5. ESI-

(90%) method A (1e + Et₂NH as precatalyst), 108 mg (89%) MS(TOF) calcd for C₁₃H₁₄NS [M + H]⁺216.0841, found

method A (2m as precatalyst), colorless oil. The physical and 216.0833.

spectral characteristics of the product obtained are similar to

those described in the literature.⁸⁷

4.8.13 2-Methoxy-5-(phenylsulfanyl)aniline (7n). Yield 95 mg

(82%) method B (1i + Et₂NH as precatalyst), 97 mg (84%)

4.8.4 2-Methylphenyl phenyl sulfide (7e). Yield 93 mg (93%) method B (2v as precatalyst), colorless oil. ¹H NMR (CDCl₃, 500

method B (1i + Et₂NH as precatalyst), 92 mg (92%) method B MHz): δ 3.82 (s, 2H, NH₂), 3.87 (s, 3H, CH₃), 6.75-6.77 (m, 1H,

(2u as precatalyst), colorless oil. The physical and spectral H_Ar), 6.83-6.835 (m, 1H, H_Ar), 6.87-6.89 (m, 1H, H_Ar), 7.11-7.14

characteristics of the product obtained are similar to those (m, 1H, H_Ar), 7.18-7.25 (m, 4H, H_Ar). ¹³C{¹H} (CDCl₃, 125 MHz): δ

described in the literature.⁸⁶

55.7, 111.1, 120.0, 124.3, 124.7, 125.8, 128.4, 129.0, 137.2,

138.8, 147.7. ESI-MS(TOF) calcd for C₁₃H₁₄NOS [M + H]⁺

4.8.5 1-Methoxy-4-(phenylsulfanyl)benzene (7f). Yield 102 mg 232.0791, found 232.0784.

(94%) method A (1e + Et₂NH as precatalyst), 106 mg (98%)

method B (1i + Et₂NH as precatalyst), colorless oil. The physical 4.8.14 N-[(E)-Phenylmethylidene]-4-(phenylsulfanyl)aniline

and spectral characteristics of the product obtained are similar (7o). Yield 110 mg (76%) method A (1e + Et₂NH as precatalyst),

to those described in the literature.⁸⁶

121 mg (84%) method A (2m as precatalyst), yellow crystals,

mp 70-72 °C. H NMR (CD₂Cl₂, 500 MHz): δ 7.17-7.20 (m, 2Н,

1

4.8.6 1-Phenoxy-4-(phenylsulfanyl)benzene (7g). Yield 133 mg H_Ar), 7.23-7.28 (m, 1Н, H_Ar), 7.29-7.36 (m, 4Н, H_Ar), 7.39-7.42

(96%) method A (1e + morpholine as precatalyst), colorless oil. (m, 2H, H_Ar), 7.47-7.52 (m, 3H, H_Ar), 7.88-7.92 (m, 2H, H_Ar), 8.48

The physical and spectral characteristics of the product (s, 1Н, CH). ¹³C{¹H} (CD₂Cl₂, 125 MHz): 122.4, 127.4, 129.3,

obtained are similar to those described in the literature.⁸⁸

129.4, 129.8, 131.0, 132.1, 133.0, 133.2, 136.8, 137.0, 151.9,

161.0. ESI-MS(TOF) calcd for C₁₉H₁₆NS [M + H]⁺290.0998,

4.8.7 4-Fluorophenyl phenyl sulfide (7h). Yield 95 mg (93%) found 290.0997.

method A (1e + Et₂NH as precatalyst), 98 mg (96%) method A

18 | J. Name., 2019, 00, 1-3

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4.8.15

ARTICLE

4-methoxy-N-{(E)-[3- 1867867 (2a), 1867866 (2g), 1907428 (2y) and are available

View Article Online

DOI: 10.1039/C9CY02041A

(phenylsulfanyl)phenyl]methylidene}aniline (7p). Yield 142 online: www.cdc.cam.ac.uk.

mg (89%) method B (1e + Et₂NH as precatalyst), 136 mg (85%)

method B (2m as precatalyst), yellow crystals, mp 67-69 °C. ¹H

NMR (CD₂Cl₂, 500 MHz): δ 3.82 (s, 3H, CH₃), 6.91-6.95 (m, 2Н,

H_Ar), 7.20-7.24 (m, 2Н, H_Ar), 7.28-7.37 (m, 3Н, H_Ar), 7.39-7.43

Acknowledgements

(m, 4H, H_Ar), 7.74-7.79 (m, 1H, H_Ar), 7.85-7.86 (m, 1H, H_Ar), 8.43

(s, 1Н, CH). ¹³C{¹H} (CD₂Cl₂, 125 MHz): 56.0, 114.9, 122.8,

127.6, 128.0, 129.9, 130.1, 131.1, 132.0, 133.5, 135.7, 137.5,

138.2, 145.0, 157.6, 159.1. ESI-MS(TOF) calcd for C₂₀H₁₈NOS [M

+ H]⁺320.1104, found 320.1109.

This work was financially supported by the Russian Foundation

for Basic Research, RFBR Grants no. 19-03-01053 (synthesis of

metal complexes) and 16-29-10786 (transformations of metal

complexes). The authors are grateful to Dr. Ilya E. Chikunov for

performing some NMR experiments in the studies of the

reactions between Pd-PEPPSI complexes and amines. The

authors also thank the Shared Research Center

“Nanotechnologies” of the Platov South-Russian State

Polytechnic University and the Department of Structural

Studies of Zelinsky Institute of Organic Chemistry for analytical

services.

4.8.16

N-[(E)-(4-methoxyphenyl)methylidene]-4-

(phenylsulfanyl)aniline (7r). Yield 147 mg (92%) method B (1e

+ Et₂NH as precatalyst), 149 mg (93%) method B (2m as

precatalyst), yellow crystals, mp 79-81 °C. ¹H NMR (CD₂Cl₂, 500

MHz): δ 3.87 (s, 3H, CH₃), 6.98-7.01 (m, 2Н, H_Ar), 7.15-7.17 (m,

2Н, H_Ar), 7.20-7.25 (m, 1H, H_Ar), 7.28-7.32 (m, 4Н, H_Ar), 7.38-

7.42 (m, 2H, H_Ar), 7.83-7.86 (m, 2H, H_Ar), 8.40 (s, 1Н, CH).

¹³C{¹H} (CD₂Cl₂, 125 MHz): 56.0, 114.7, 122.4, 127.3, 129.71,

129.74, 130.7, 131.1, 132.2, 133.4, 137.3, 152.4, 160.3, 163.1.

ESI-MS(TOF) calcd for C₂₀H₁₈NOS [M + H]⁺320.1104, found

320.1123.

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DOI: 10.1039/C9CY02041A

ARTICLE

Graphical Abstract

R

Molecular catalysis

R

N

X

Pd

X

N

Pd⁰

Base

L

N

R

+

R

N

Temperature

-

+

X

Alkyl

Pd⁰NPs

H N

H

+

N

Alkyl(H)

Nano-scale catalysis

R

J. Name., 2019, 00, 1-3 | 22

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Article Doi

Preventing Pd-NHC bond cleavage and switching from nano-scale to molecular catalytic systems: Amines and temperature as catalyst activators

DOI: 10.1039/c9cy02041a

Source and publish data:

Authors:

Article abstract of DOI:10.1039/c9cy02041a

Full text of DOI:10.1039/c9cy02041a

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