Half-sandwich (η5-Cp?)Rh(iii) complexes of pyrazolated organo-sulfur/selenium/tellurium ligands: Efficient catalysts for base/solvent free C-N coupling of chloroarenes under aerobic conditions

Article abstract of DOI:10.1039/d0ob00538j

Three new pyrazolated chalcogenoether ligated Rh(iii) half-sandwich complexes (1-3) were synthesised by the thermal reaction of chalcogenoether (S, Se and Te) substituted 1H-pyrazole ligands (L1-L3) and [(η⁵-C₅Me₅)RhCl]₂ in methanol. The complexes were fully characterised by various spectroscopic techniques, and the molecular structures of complexes 1 and2 were also established through single crystal X-ray crystallographic analysis, which indicates a pseudo-octahedral half-sandwich piano-stool geometry around the rhodium metal. All three complexes were found to be thermally stable and insensitive towards air and moisture. One mol% of Rh(iii) complexes (1-3) along with 10 mol% of Cu(OAc)₂ were explored for the Buchwald-Hartwig type C-N coupling reactions of amine and aryl chloride. Good to excellent yields (89-92%) of the coupling products were obtained with seleno- and thio-ether functionalised pyrazolated Rh(iii) complexes (1 and 2), while an average yield (39%) was obtained with the telluro-ether functionalised complex (3). In contrast to the previously reported C-N coupling reactions the present reaction works under solvent- and base-free conditions, and the coupling reaction is accomplished in just 6 h with a high yield of the coupling product. The present methodology was also found to be efficient for a wide variety of functionalised aryl halides, and aliphatic or aromatic amines (1° and 2°). Moreover, the reaction also enables the C-N coupling of electron-withdrawing substrates and base-sensitive functionalities.

Full text of DOI:10.1039/d0ob00538j

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DOI: 10.1039/D0OB00538J
ARTICLE
Half-Sandwich (η5-Cp*)Rh(III) Complex of Pyrazolated Organo-
Sulfur/Selenium/Tellurium Ligands: Efficient Catalysts for Base/
Solvent Free C−N Coupling of Chloroarenes under Aerobic
Conditions
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
Charu Sharma,[a] Avinash Kumar Srivastava,[a] Kamal Nayan Sharma*[b] Raj Kumar Joshi*[a]
Three new pyrazolated chalcogenoether ligated Rh(III) half-sandwich complexes (1-3) were synthesised by the thermal
reaction of chalcogenoether (S, Se and Te) substituted 1H-pyrazole ligand (L1-L3) and [(η5-C5Me5)RhCl]2 in methanol. The
complexes were fully characterised by various spectroscopic techniques, and the molecular structures of the complex (1-2)
were also established through the single crystal X-ray crystallographic analysis, which indicates a pseudo-octahedral half
sandwich piano-stool geometry around rhodium metal. All three complexes were found thermally stable and insensitive
towards the air and moisture. One mol% of Rh(III) complexes (1-3) along with 10 mol% of Cu(OAc)2 were explored for the
Buchwald-Hartwig type C−N coupling reactions of amine and aryl chloride. The good to excellent yields (89-92%) of the
coupling products were obtained with seleno- and thio-ether functionalised pyrazolated Rh(III) complexes (1 and 2), while
an average yield (39%) was obtained with telluro-ether functionalised complex (3). In contrast to the previously reported
C−N coupling reactions the presented reaction works under a solvent and base free conditions, and the coupling reaction
accomplished in just 6 h with high yield of coupling product. The present methodology was also found to be efficient for
the wide variety of functionalised aryl halides, and aliphatic or aromatic amines (1° and 2°). Moreover, the reaction also
enables the C−N coupling of electron-withdrawing substrates and base sensitive functionalities.
Ag, Au, Al, Ni, Rh, Pd and Cu metals either in the form of their
salts or complexes.2 But, none of these catalytic methodologies
Introduction
works in the absence of base, moreover, Cu in its various
forms found active for the Ullman type aryl-aryl coupling
reactions, which is generally performed under elevated
temperatures with a stoichiometric amounts of Cu catalyst.3
While it was also reported that toluene and dioxane are the
most suitable solvents for C-N coupling reactions, but due to
the low solubility of strong bases in these aprotic solvents
restricted the formation of deprotonated amines.4 To enhance
the solubility of bases in aprotic solvents, and reduce the
reaction duration some additional ingredient the diamine
ligands has been used4 but some unwanted interference and
complexity into the reaction was observed. Further, the
literature suggests both Cu(I) and Cu(II) are known for C-N
coupling reactions. The Cu(I) is more active than the Cu(II); this
fact is supported through the mechanistic studies of Ullman
type coupling reactions.5,6 Cu(II) in the form of Cu(OAc)2 had
received notable attention till early 90’s as a potential
substitute of expensive Pd catalyst.7,8 But, Cu(OAc)2 is not
found substantially active for the aryl halides. However, it
shows excellent activity in a variety of reactions which includes
the organolead, bismuth, antimony, iodo, silicon, tin and
phenylboronic acids compounds with aryl or aliphatic amines.8-
Catalysis is an indispensable technology in the present
scenario. In the realm of catalytic synthesis, mono-metallic
catalysis and classical methodologies had offered vast array
applications for the laboratory to commercial synthesis and a
variety of chemical compounds.1 These well-known strategies
are based on the unique catalyst substrate interactions.
However, in recent past, various multi-metallic catalytic
strategies had influenced the establishment of previously
known catalytic methodologies. Four different multi-metallic
mechanisms are accepted yet: bi-functional, cascade, double
activation and synergistic catalysis.1 This classification is mainly
based on the nature of insitu complex formation or the
generation of electrophile and nucleophile. For the C-N
coupling
reaction
various
mono-metallic
catalytic
methodologies are known. These methodologies use La, Fe,
a. Department of Chemistry, Malaviya National Institute of Technology, Jaipur –
302017, Rajasthan, INDIA.
Email: rkjoshi.chy@mnit.ac.in
b. Department of Chemistry, Amity School of Applied Sciences, Amity University
Haryana, Manesar, Gurugram 122413, Haryana, India.
Email: kamalnayaniitd@gmail.com
† Footnotes relating to the title and/or authors should appear here.
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
10
The scheme 1 depicts that there are earlier known methods
for the synthesis of aromatic amines. Initially the nitration,
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followed by reduction and further alkylation was the most restricted to the liquid substrates only and presence of strong
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DOI: 10.1039/D0OB00538J
common method followed for the synthesis of aromatic base in these reactions usually restricts the applicability of the
amines. However, nitration is the multistep process and methodology for the base sensitive functionalities.19
suffers poor step economy, other strategies like aromatic Present Work
Rh cat. (1 mol%)
R2 Cu(OAc)2 (10 mol%)
R1
N
nucleophilic substitutions (SnAr) requires aromatic substrates
with strong electron withdrawing groups.11 The other catalyst
based strategies, the Ullman and Cham-Lam coupling serves
the better alternatives for the laboratory synthesis. But usually
it requires stoichiometric amounts of Cu catalyst with base and
Cl
R1
N
H
+
R
R2
110 oC, 6h
X
R
R1 - H, Aliphatic
R2 - Aliphatic, Benzene, benzylic
R = EWG, Me
X = C, N
very high reaction temperatures. The most recent Scheme 2. Base and solvent free C-N coupling reaction.
methodological upgrade in this area is known as Buchwald- This script aims to the design, synthesis and application of a
Hartwig coupling which is performed with Pd catalyst and base novel Rh(III)-chalcogenoether (S/Se/Te) complexes in
at comparatively milder reaction temperature.3, 11
association with Cu(OAc)2 for the C-N coupling reactions under
aerobic and solvent free reaction conditions (Scheme 2). The
reaction also works well in toluene solvent and shows similar
results. The present bimetallic strategy does not require any
base for activation, which makes it more suitable for base
sensitive functionalities. Moreover, the reaction is also found
suitable for variety of aryl and alkyl amines and halides (Cl, Br
and I). Exceptional results were obtained at very low catalyst
loading of Rh and Cu and the desired coupling products does
not require any chromatographic separation for their
isolations.
Ullman and Chan-Lam
coupling
Buchwald-Hartwig
CN coupling
Pd cat., Base
Cu cat., base
rt - 250 oC
Solvent, rt - 100 oC
R1
N
R1 - H, Aliphatic
R - Aliphatic, Aromatic
R
1. Nitration
2. NO2 Reduction
3. Alkylation
For EWG only
Aromatic
Amines
Multistep Process
Aromatic Nucleophilic
Substitution (SnAr)
Results and Discussion
Scheme 1. Earlier known strategies for the synthesis of
aromatic amines.
Synthesis of pyrazolated selenoether Rh(III) half-sandwich
Nitrogen containing compounds have great commercial complex: The ligands (L1-L3) and Rh(III) complex (1-3) were
value.12 Synthesis of such nitrogen containing organic synthesized by using the methodology illustrated in Scheme 3.
compounds are highly desirable for their innumerable A previously reported method was used to prepare the
applications. As per the survey of GMP (Good Manufacturing pyrazole based organosulphur (L1), organoselenium (L2) and
Practices) bulk reactions during the year 1985-2002 in various organotellurium (L3) ligands.20-23 The half-sandwich (η5-
research facilities at the Pfizer-Groton shows 15% involvement Cp*)Rh(III) complexes (1-3) were prepared by reacting [(η5-
of C-N bond forming reactions.13 Moreover, in last two Cp*)RhCl(μ-Cl)]2 with a methanolic solution of L1, L2 or L3
decades intensive research over C-N coupling reactions has under ambient reaction conditions. The complexes 1-3 were
been conducted by various research groups, however, the fully characterized by using the multinuclei NMR, HR-MS, and
1
Ullman-Goldeberg, Chan-Evan-Lam and Buchwald-Hartwig FT-IR techniques. The H and 13C NMR (SI, Figures S1-S9) and
reactions had provided a comparatively mild conditions to mass spectra of complexes 1, 2 and 3 were found fully
perform C-N couplings.14 But performing base free C-N consistent with the proposed molecular structures mentioned
coupling reactions is still difficult and rare to find in in Scheme 3. The deshielded NMR signals were appeared in 1H
literature.15 Moreover, since, an amine acts as one of the and 13C{1H} spectra of complex 1, 2 and 3 as compared to the
reactant, hence, a strong base is highly desired for the free ligand, corroborating the coordination of ligand with
reaction. The t-BuOK and t-BuONa bases are frequently used in Rh(III) in a bidentate chelate mode. The -CH2- protons of
1
combination with aryl chlorides and bromides, which lead to chelate ring were appeared as four different peaks in H NMR
the formation of their K/Na salts as by-product.16 Due to the spectra of both the complexes 1 and 2, which further confirms
low solubility of these salts most of the methodologies does diastereotopic nature of these protons arises due to the
not implemented in flow reactors.16 For bulk scale these chelate ring formation and chiral asymmetric molecular
reactions are generally performed on batch reaction process. structure.
1. NaOH, EtOH
reflux, 10 min,
But, the literature indicates the cost of production raised up to
45% due to chemical required for the bulk production and
N2 atm
PhEH
2.Br
E = S
prolonged reaction times (typically 24-48 h).17 Hence, there is
an strong desire of the catalyst which can produce high yields
at low catalyst loading, under base free conditions and
complete the reaction in adequate time duration. All the
previous literature related to solvent free C-N coupling shows
the use of Pd catalysts and base (mostly t-BuOK and t-
BuONa).18 Most of the solvent free methodologies are
Cl
N
1. [(n5-Cp*)RhCl2
]
2
N
Br
PF6
Br
8
methanol, rt
2
EtOH, reflux
12 h, N2 atm
2. NH4PF6, rt, 5 h
Rh
E
7
3
N
1
-
Cl
5
N
9
4
N
N
E
6
1. NaBH4, EtOH
reflux, 10 min,
N2 atm
E = S, Se, Te
L1 - L3
1
2 or 3
,
Ph2E2
2.Br
E = Se, Te
Cl
N
N
EtOH, reflux
12 h, N2 atm
2 | J. Name., 2012, 00, 1-3
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Scheme 3. Syntheses of ligands (L1-L3) and Rh(III) complexes continuous monitoring the reaction, shows the formation of a
View Article Online
DOI: 10.1039/D0OB00538J
product which was identified as the desired C-N coupled
(1-3).
These prepared complexes 1, 2 and 3 were found to be soluble product. Similar results were observed when K3PO4, K2CO3 and
in CH3CN, DMF, and DMSO while sparingly soluble in CH2Cl2, KOH bases were used for the reaction. Surprisingly, the
CHCl3, and CH3OH and insoluble in diethyl ether and n-hexane, reaction is keep on producing the similar results even in the
hence, crystals for X-ray crystallographic analysis were grown absence of base. Herein, the bimetallic catalysis is enabled to
in CH3CN:CH3OH (3:1) solution under ambient conditions. The obtain the Buchwald coupling product even in the absence of
summary of crystallographic data and structural refinements base.
are outlined in Table 1(SI). The molecular structures of
complex 1 and 2 obtained by crystallographic analysis is
depicted in Figure 1 and 2. The bidentate coordination mode
of ligand (L1-L3) through sulphur, selenium and tellurium and
nitrogen of the pyrazole moiety resulted a six membered
chelate ring with Rh(III) metal to forms a pseudo-octahedral
half-sandwich “pianostool” geometry along the Rh metal. The
Rh−S and Rh−Cl bond distances obtained at 2.381(3) and
2.385(3) Å; Rh−Se and Rh−Cl bond distances obtained at
2.5134(7) and 2.3920(13) Å, respectively and have close
agreement with respect to the reported Rh(III) complex of
organoselenium ligand.24
Figure 2. The molecular structure diagram (thermal ellipsoids
at 30% probability level) of half-sandwich (η5-Cp*)Rh(III)
complex (1); Hexafluorophosphate anion and hydrogen atoms
are not shown for the sake of clearness; Key crystallographic
distances [Å]: Rh−Se 2.5134(7), Rh−N(2) 2.108(4), Rh−Cl
2.3920(13); Bond angles [°] N(2)−Rh−Se 85.23(11), N(2)−Rh−Cl
88.34(11), Cl−Rh−Se 91.30(4).
Now, the further reactions were optimised in absence of base.
Figure 1. The molecular structure diagram (thermal ellipsoids In another reaction, only Cu acetate (10 mol%) was taken and
at 30% probability level) of half-sandwich (η5-Cp*)Rh(III) reaction mixture was refluxed for 36 h. As expected, the yield
complex (1); Hexafluorophosphate anion and hydrogen atoms of C-N coupling product was reduced to 25% (Table 1, Entry 1).
are not shown for the sake of clearness; Key crystallographic In contrast, when only Rh complex (1 mol%) was used, the
distances [Å]: Bond angles [°]: Rh(1)−S(1) 2.381(3), Rh(1)−N(1) reaction failed to mimic the desired C-N coupling and does not
2.127(9), Rh(1)−Cl(1) 2.385(3); Bond angles [°] N(1)−Rh(1)−S(1) produce the product even in trace (Table 1, Entry 2). Reducing
91.4(2), N(1)−Rh(1)−Cl(1) 84.9(2), Cl(1)−Rh(1)−S(1) 95.41(10).
the quantity of Cu(OAc)2 and Rh complex (1 mol% of each)
Catalysis and reaction optimisation. Innumerable applications does not bring any change in the course of the reaction, an
of Rhodium complexes as a homogeneous catalyst has been sizeable yield was recorded in 12 h. Furthermore, during the
reported.25,26 In recent the Rh complexes with Cu(OAc)2 had solvent optimizations, it was observed that present reaction
evolved as
a potential catalytic composition for C-H shows excellent transformation of desire product in solvent
activations.27 Only two reports which shows the use of Rh(I) free conditions. Moreover, in absence of solvent, the reaction
and Cu for C-N coupling of aryl aldimines and internal time reduces to its half (Table 1, Entry 3). Hence, next few
alkynes12,29 via the hydrogen borrowing from phenol to reactions were performed under solvent free conditions and
aniline28 are the only reports available in literature. The results also at gram scale (Table 1, Entry 4 and 5). Reducing the
from the literature encouraged to use this combination for the quantity of Rh catalyst to 0.4 mol% (reaction performed at
various nature of C-N coupling reactions. Buchwald type C-N gram scale) shows considerable loss in the productivity of the
coupling was the very first choice, exception to all in the initial reaction. Further going down to 0.1 mol% (reaction performed
reactions of pyrrolidine with bromobenzene and at gram scale) of Rh catalyst shows imperceptible yields of the
chlorobenzene separately, using the prepared Rh complex (1 desired products in 6 h (Table 1, Entry 6). Replacing the Rh-Se
mol%), Cu(OAc)2 (10 mol%) and tBuOK (1 equiv) in toluene catalyst with their other chalcogen analogues Rh-S and Rh-Te
solvent. Refluxing the mixture for several hours with shows deviation in the product yield. Rh-S complex shows a
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
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substantially similar transformation in comparison to the Rh-Se Following the optimised reaction conditions, tVhieew AsruticblestOrnalitnee
DOI: 10.1039/D0OB00538J
analogue but the Rh-Te is producing comparatively less yields. scope for various amines and aryl halides was explored (Table
The different electron donor properties of different chalcogen
2 and 3). Initially aryl chlorides were subjected to
which leads to the difference in electron density over the benzylamines, (Table 2, 1a-1i) in general all the reactions
central metal atom could be the reason for the different produces excellent yields. However, there is a slight variation
catalytic activity.30
Table 1. Reaction Optimisation
of the yield observed with the change in the electronic
properties due to para- or ortho- substitution of functional
groups. Electron donating and withdrawing functionalities also
produce subtle effects on product yields. The initial reaction of
chlorobenzene and benzylamine produces an excellent 87%
yield of the C-N coupled product (1a).
Rh Complex (1 mol%)
Cu(OAc)2 (10 mol%)
Cl
N
+
110 C, 6h
N
H
Rh
Catalyst
mol%
Toluene Nil
Table 2. Substrate scope for benzylic amine and
chlorobenzenes
Cu(OAc)2
mol%
Temp. Time Yielda
Entry Solvent
[°C]
[h]
%
Rh cat. (1 mol%)
X
Cl
R
Cu(OAc)2 (10 mol%)
110 oC, 6 h
NH2
R1
1.
10
110
110
110
110
110
110
110
110
110
110
110
40
36
24
12
6
25
nd
89
92
46
nd
89
39
32
nd
38
nd
12
43
82
91
+
R
N
H
X
R1
2.
Toluene
Toluene
1
1
Nil
R = EWG, p-Me
R1 = H, Me
X = C, N
3.
10
4.
Nil
Nil
1(RhSe)
0.4b
10
H
N
H
H
N
N
5.
10
6
O2N
Nil
Nil
Nil
Nil
Nil
Nil
Nil
Nil
Nil
Nil
Nil
6.
0.1b
10
6
1a, 87%
1b, 84%
1c, 75%
7.
1(RhS)
10
6
NO2
H
N
8.
1(RhTe)
10
6
H
N
H
N
9.
1(RhCl3)
10
6
F3C
NC
10.
11.
12.
13.
14.
15.
16.
1
1
1
1
1
1
1
10 (CuCl2)
10 (CuI)
10
6
1d, 88%
1e, 83%
1f, 66%
6
36
6
H
N
H
N
H
N
N
N
10
60
O2N
10
80
6
1g, 71%
1h, 83%
1i, 74%
10
100
6
Reaction Conditions: Benzylamine (1 mmol), Arylhalide (1
mmol), Rh cat. (1 mol%), Cu(OAc)2 (10 mol%), Temperature
110 °C, Time 6 h
10
110
6
aIsolated Yields, Optimised conditions: Pyrrolidine (1 mmol),
Chlorobenzene (1 mmol), Rh complex (1 mol%), Cu(OAc)2 (10
mol%), Temp. 110 °C, Time 6 h, bGram scale reactions, nd = not
detected
Substrates with electron-withdrawing functionalities at para-
position
shows
comparatively
slight
increase
in
transformation. The reaction of para-nitrochlorobenzene with
benzylamine shows an effective 84% transformation of desired
product (1b), while reaction with para-methylchlorobenzene
produces 75% yield of corresponding amine (1c). The
withdrawing groups, para-cyano chlorobenzene and para-
triflourochlorobenzene, undergoes excellent transformation
and result the 88% and 83% yields of corresponding coupling
product (1d and 1e). In case of the ortho-nitrochlorobenzene,
a 66% yield was recorded when it was coupled with
benzylamine (1f), perhaps, steric reasons could be the possible
factors. Reaction with 2-chloropyridine yields a substantial
71% yield of the desired product (1g). Further reaction of a
withdrawing group para-nitro substituted chlorobenzene and
donor group para-methyl substituted benzylamine shows a
sizeable 83% transformation of desired product (1h). The
reaction of 2-chloropyridine and para-methylbenzylamine
found equally efficient and produces 74% product yield.
Therefore, it is comprehended that the product yields are not
much affected by the substitutions on aromatic ring of the
benzylic amine.
Replacing the Rh complex with RhCl3 and performing reactions
at 1 mol% loading shows 30% yield of C-N coupled product
(Table 1, Entry 9). Replacing Cu acetate with CuCl2 shows no
catalytic activity for the desired conversion but, with CuI forms
the mediocre yield in 6 h (Table 1, Entry 8 and 9). This is most
probably due to novel structural features of Cu acetate and
high reactivity resulted by acetate ligand for such reactions.31-
34
During optimisation of reaction temperature, it was found
that reaction does not initiate at room temperature. However,
increasing temperature to 60 °C shows an insignificant
formation of desired product. While, a gradual increase in
temperature to 80 °C brings the product yield close to the
average. A further rise in the temperature up to 110 °C shows
an excellent yield of the desired coupling product (Table 1,
Entry 10-14). It was also observed that the present coupling
reaction found to be constant in air and N2 atmosphere, as
there was hardly any change in the yield of the desired
coupling product and all the reactions were conducted in air
atmosphere.
4 | J. Name., 2012, 00, 1-3
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The scope of various amine for the reaction was also explored decrease in the yield was recorded VwiewithArticlepOanrliane-
DOI: 10.1039/D0OB00538J
(Table 3, 2a – 2h). Initially the reaction of aniline and methylchlorobenzene, 77% (3c).
chlorobenzene produces a significant 82% yield of the di-aryl The reaction of para-triflourochlorobenzene and pyrrolidine
amine (2a). Similar to the previous trend, electron- produces a substantial 86% yield of the corresponding tertiary
withdrawing group with functionalised chlorobenzenes were amine (3d). Ortho- substitution of nitro with chlorobenzene as
found more active for current transformation. While the expected shows a reduced reactivity and produces 79% yield
difference in yields of para- and ortho-substituted (3e). 3-methylchlorobenzene shows a low yield of 69% (3f).
chlorobenzene is comparatively lower than that of observed in Reactions of piperidine with para-nitrochlorobenzene and
the case of benzylic amines. However, the present coupling para-triflourochlorobenzene show a significant transformation
method failed to activate the halide substituted anilines for of 81% and 85% (3g and 3h). The additional reaction of 2-
the desired coupling.
Table 3. Substrate Scope for aniline and chlorobenzenes
nitrochlorobenzene yields 82% of corresponding amine (3i).
Further reaction of para-nitrochlorobenzene with di-
ethylamine yields 76% (3j) and 73% (3k) transformation was
recorded in a reaction of para-cyanochlorobenzene and
propylamine.
Rh cat. (1 mol%)
H
Cl
NH2
Cu(OAc)2 (10 mol%)
110 oC, 6 h
N
X
+
R
R
X
R = EWG, Me
X = C, N
Table 4. Substrate Scope for aliphatic amines and
chlorobenzenes
H
N
H
H
N
N
Rh cat. (1 mol%)
Cu(OAc)2 (10 mol%)
R1
Cl
R1
R
N
N
H
F3C
O2N
+
R
R
110 oC, 6h
R
2a, 82%
2b, 83%
2c, 85%
H
N
R = EWG, Me
R1 - H, Aliphatic
R - Aliphatic, Aromatic
H
H
N
N
N
O
N
N
N
2d, 76%
2e, 81%
2f, 85%
NO2
H
N
H
N
O2N
3a, 92%
3b,84%
3c, 77%
NO2
N
2g, 79%
2h,74%
N
N
Reaction Conditions: Aniline (1 mmol), Arylhalide (1 mmol), Rh
cat. (1 mol%), Cu(OAc)2 (10 mol%), Temperature 110 °C, Time
6 h
F3C
3d, 86%
3e, 79%
3f, 69%
The papa substituted electron withdrawing group’s i.e. the
para-nitrochlorobenzene and para-triflourochlorobenzene
shows 83% (2b) and 85% (2c) transformation respective
coupling product. While a slightly reduced yield was obtained
with the para substituted electron donating groups, the para-
NO2
N
N
N
O2N
F3C
3g, 81%
3h, 85%
3i, 82%
H
N
methylchlorobenzene
and
para-methoxychlorobenzene
N
formed 76% (2d) and 81% (2e) yield of the desired product
respectively. The reaction of 2-chloropyridine and aniline
furnished the corresponding CN coupled product with 85% (2f)
NC
O2N
3j, 76%
3k, 73%
yield.
Reactions
of
2-nitrochlorobenzene
and
2-
Reaction Conditions: amine (1 mmol), Arylhalide (1 mmol), Rh
cat. (1 mol%), Cu(OAc)2 (10 mol%), Temperature 110 °C, Time
6 h
methylchlorobenzene with aniline show slight deviation in the
trend and yields were limited to 79% and 72% (2g and 2h)
respectively.
Plausible Mechanism: No intermediate has been isolated
Subsequently, substrate scope was further extended to
aliphatic amines (Table 4, 3a – 3k). However, methodology was
not found suitable for the aliphatic halides. Reactions of
secondary cyclic aliphatic amines, pyrrolidine and piperidine
with chlorobenzenes show beneficial transformations. While
slightly reduced yields were recorded for electron donating
substituted chlorobenzenes. Non-cyclic secondary and primary
amines also show a negative trend in the product yield. The
reaction of pyrrolidine and chlorobenzene was found highly
efficient, and a 92% yield was recorded through this reaction
(3a). Para-nitrochlorobenzene with the same reactant yields
84% of the desired product (3b). Comparatively, a minute
during the present catalytic reaction, but,
a plausible
mechanism has been proposed on the basis of the available
literature evidences (Scheme 2). Here, the reaction initiated by
the formation of adduct (2) between Rh(III) complex (1) and
the 1° or 2° amine, and the successive loss of HCl produces
another intermediate (3).35-38 Adjacently, the added Cu(OAc)2
interacts with aryl halide to forms an activated intermediate
(4)33 which reacts with intermediate (3) and oxidatively added
to yield the intermediate (5) and regenerate the Cu(OAc)2.
During the oxidative addition Rh(III) intermediate undergo
oxidations and transforms into a Rh(V), as it is reported earlier
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Journal Name
as a thermodynamically favourable transformations.35 The refinements. Olex2 was employed for theViewfinAratilcle Odnalitnae
DOI: 10.1039/D0OB00538J
intermediate (5) undergoes rearrangement to produce presentation and structure plots. Non-hydrogen atoms were
intermediate (6) which reductively eliminate the desired C-N refined with anisotropic thermal parameters. Hydrogen atoms
coupling product and regenerate the Rh catalyst (1) back into were included in idealized position with isotropic thermal
the reaction.
parameters set at 1.2 times that of the carbon atom to which
they are attached. The structure was refined (weighted least
squares refinement on F2) to convergence.
R
N
Synthesis of half-sandwich (η5-Cp*)Rh(III) complex (1-3).
Pyrazolated chalcogenoether ligands (L1-L3) were prepared by
using a reported method.20-23 Ligand (L1) (0.056 g, 0.2 mmol),
(L2) (0.066 g, 0.2 mmol), or (L3) (0.076 g, 0.2 mmol) solid
[Rh(η5-Cp*)Cl2]2 (0.062 g, 0.1 mmol) and methanol (25 mL)
were taken in a round bottom flask and stirred overnight
under ambient reaction conditions. The resulting reaction
mixture was filtered, and the volume of the filtrate was
reduced to 5 mL at rotary evaporator. It was mixed with solid
NH4PF6 (0.032 g, 0.2 mmol) and further stirred at rt for 5 h. The
resulting orange coloured precipitated solid was filtered,
washed with 5 mL of chilled methanol, and dried in vacuo. The
complex 1 was isolated as orange solid (82%, mp: 127 ± 2 °C).
complex 2 was isolated as orange solid (89%, mp: 121 ± 2 °C)
and complex 3 was isolated as orange solid with an excellent
yield of (80%, mp: 180 ± 2 °C). Single crystals of the complexes
were grown by slow evaporation of a solution of 1 and 2 made
in acetonitrile: methanol (3:1).
R1
R1
R
Cl
N
H
Rh
Cp*
R1 - H, Aliphatic
R - Aliphatic, Aromatic
1
Cl
Rh Catalyst
R1
R
Rh
N
*Cp
N
R1
H
Rh
2
R
6
Cl
*Cp
Cu(OAc)2
Cl
HCl
(AcO)2Cu
Cl
4
Rh
R1
Cl
N
Rh
*Cp
R1
N
*Cp
R
3
R
5
Cu(OAc)2
1
Complex 1: NMR (CD3CN, δ/ppm): H (400 MHz) 7.98 (s, 1H),
Scheme 4. A plausible mechanism for the Rh, Cu co-catalysed 7.77 (s, 1H), 7.29 – 7.39 (m, 5H), 4.85 – 4.81 (d, 1H), 3.95 –
C-N coupling reaction
3.88 (t, 1H), 3.81 – 3.79 (d, 1H), 3.00 – 2.94 (t, 1H), 2.13 (s,
15H). 13C{1H} (100 MHz): 145.28, 136.86, 131.75, 130.42,
129.75, 129.08, 117.44, 100.28, 97.99, 96.37, 49.54, 35.49. IR
(cm−1, powder film): 458, 553, 831, 1021, 1372, 1468, 1738;
Mass (CH3CN) [(M – PF6]+ (m/z) Found: 554.9711, Calc. Value
Experimental Section
Chemicals and Instruments
Chemicals and instrumentation. The common chemicals and for [C21H27BrClN2RhS]+: 554.9714
1
reagents which were available commercially within the Complex 2: NMR (CD3CN, δ/ppm): H (400 MHz) 8.03 (s, 1H,
country were used as received. RhCl3.xH2O, Ph2Se2, NaBH4, and H9), 7.80 (s, 1H, H7), 7.55 (s, 1H, H8), 7.32 – 7.30 (m, 1H, H1),
4-bromopyrazole were procured from Sigma-Aldrich (USA). 7.24 – 7.21 (m, 2H, H2), 6.90 – 6.89 (m, 2H, H3), 4.99 – 4.95 (m,
Pyrazolated organochalcogen ligands (L1-L3) and Rh(III)-dimer; 1H, H6), 3.95 – 3.94 (m, 2H, H6, H5), 2.87 – 2.81 (m, 1H, H5),
[Rh(η5-Cp*)Cl(μ-Cl)]2, were prepared by previously reported 1.59 (s, 15H, CH3 of Cp*); 13C{1H} (100 MHz) 145.3 (C9), 136.9
methods. Standard methods were used for drying and (C7), 132.3 (C3), 129.9 (C1), 129.2 (C2), 125.15 (C4), 117.5 (CH3 of
distillation of the solvents. Silica gel (100-200 and 60-120 Cp*), 99.6 (C of Cp*), 96.4 (C8), 50.7 (C6), 30.9 (C5). IR (cm−1,
mesh) and sheets for TLC (silica gel 60F254) used in column powder film): 457, 556, 831, 1018, 1369, 1469, and 1743; Mass
chromatography, were procured from Fisher Scientific and (CH3CN) [(M – PF6]+ (m/z) Found: 602.9187; Calc. Value for
Merck, respectively. The melting point of solid compounds [C21H27BrClN2RhSe]+: 602.9188.
were determined in an open capillary and reported as such. All Complex 3: NMR (CDCl3, δ/ppm): 1H (400 MHz) 7.93 – 7.91 (d,
the reaction products were vacuum dried for several hours 2H), 7.31 (s, 1H), 7.16 – 7.13 (t, 2H), 6.74 – 6.72 (d, 2H), 5.30 –
prior to being analyzed and weighted as well. JEOL ECS-400 5.27 (d, 1H), 4.15 – 4.11 (m, 2H), 2.52 – 2.44 (m, 1H), 1.75 (s,
1
spectrometer operating at 400 MHz and 101 MHz for H and 15H); 13C{1H} (100 MHz) 145.51, 136.54, 136.30, 134.94,
13C nuclei, respectively were used to record the NMR spectra 131.29, 130.77, 129.80, 99.89, 99.61, 52.45, 9.69, 9.17. IR
of all the compounds synthesized. FT-IR spectra were recorded (cm−1, powder film): 456, 556, 831, 1018, 1299, 1433, 1627,
on a Perkin-Elmer 10.4.00 FT-IR spectrometer within the range Mass (CH3CN) [(M – PF6]+ (m/z) Found: 652.2506; Calc. Value
4000-400 cm-1 using KBr pellets of the sample. High-Resolution for [C21H27BrClN2RhTe]+: 652.9085.
Electron Impact Mass Spectra (HR-EIMS) were obtained with General procedure for the catalytic synthesis. In a reaction
Xevo G2-S Q-Tof (Waters, USA). The diffraction data on a single tube, 1 mmol of each primary/secondary amine and aryl halide
crystal of 1 was collected on a Bruker AXS SMART Apex CCD were taken. Then a mixture of prepared Rh catalyst (1/2/3),
Diffractometer using Mo-Kα (0.71073 Å) radiation at 298(2) K. Cu(OAc)2 (10 mol%) as catalyst was added and the reaction
The SADABS program was used for absorption correction and mixture was continuous stirred at 110 °C for 6 h. After
SHELXTL for space group, structure determination, and completion, the reaction mixture was allowed to cool to room
6 | J. Name., 2012, 00, 1-3
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Organic & Biomolecular Chemistry
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ARTICLE
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temperature and the organic layer was separated through
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rotatory evaporator. The desired products were separated
through column chromatography.
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Conclusion
Some novel pyrazolated chalcogenoether Rh(III) half sandwich
complexes as efficient catalysts for the C-N coupling reaction
have been designed and synthesised. The combination of
Rh(III) complex together with Cu(OAc)2 works as bimetallic
catalytic system and produced an excellent yields of the C-N
coupled products. Moreover, this methodology work under
the solvent and base free conditions and bring the desired
transformations in just six hours. In conclusion, this
methodology enables to perform C-N coupling with electron-
withdrawing and base sensitive functionalities. This
methodology is exceptionally efficient for wide variety of
functionalised aryl halides and 1° and 2° aliphatic or aromatic
amines. Moreover, we are the first to report bimetallic
catalytic methodology for the Buchwald type C-N coupling
reaction.
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Conflicts of interest
“There are no conflicts to declare”.
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Acknowledgements
Raj K. Joshi thanks to CSIR (01(2996)/19/EMR-II) for financial
assistance. Charu Sharma and Avinash K. Srivastava thank to
MNIT for the research fellowships. Authors also acknowledge
the MRC, MNIT for providing characterisation facilities.
Notes and references
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via
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CB21EZ,
UK;
Fax:
(+44)1223-336-033;
or
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