Achieving Nickel Catalyzed C-S Cross-Coupling under Mild Conditions Using Metal-Ligand Cooperativity

Article abstract of DOI:10.1021/acs.joc.9b00075

A simple and efficient approach of C-S cross-coupling of a wide variety of (hetero)aryl thiols and (hetero)aryl halides under mild conditions, mostly at room temperature, catalyzed by well-defined singlet diradical Ni(II) catalysts bearing redox noninnocent ligands is reported. Taking advantage of ligand centered redox events, the high-energetic Ni(0)/Ni(II) or Ni(I)/Ni(III) redox steps were avoided in the catalytic cycle. The cooperative participation of both nickel and the coordinated ligands during oxidative addition/reductive elimination steps allowed us to perform the catalytic reactions under mild conditions.

Full text of DOI:10.1021/acs.joc.9b00075

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Article
Achieving Nickel Catalyzed C-S Cross Coupling under
Mild Conditions using Metal-Ligand Cooperativity
Rina Sikari, Suman Sinha, Siuli Das, Anannya Saha, Gargi Chakraborty, Rakesh Mondal, and Nanda D. Paul
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00075 • Publication Date (Web): 11 Mar 2019
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Achieving Nickel Catalyzed C-S Cross Coupling under Mild
Conditions using Metal-Ligand Cooperativity
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Rina Sikari,† Suman Sinha,† Siuli Das,† Anannya Saha,‡ Gargi Chakraborty,† Rakesh Mondal,†
and Nanda D. Paul†,*
†Department of Chemistry, Indian Institute of Engineering Science and Technology, Shibpur,
Botanic Garden, Howrah 711103, India
‡Department of Chemical Sciences, Indian Institute of Science Education and Research Kolkata,
Mohanpur 741246, India
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ABSTRACT: A simple and efficient approach of C−S cross coupling of a wide variety of
(hetero)aryl thiols and (hetero)aryl halides under mild conditions, mostly at room temperature;
catalyzed by well defined singlet di-radical Ni(II)-catalysts bearing redox noninnocent ligands is
reported. Taking advantage of ligand centered redox events; the high-energetic Ni(0)/Ni(II) or
Ni(I)/Ni(III) redox steps were avoided in the catalytic cycle. The cooperative participation of
both nickel and the coordinated ligands during oxidative addition/reductive elimination steps
allowed us to perform the catalytic reactions under mild conditions.
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INTRODUCTION. Formation of C−S bonds remains one of the most important challenges in
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organic synthesis because of the prevalence of aromatic thioethers in a wide spectrum of natural
and synthetic organic compounds (Figure 1).1 Over the decades, notable progress have been
made in developing catalytic and stoichiometric C − S bond forming reactions via direct
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functionalization of aryl halides, paricularly aryl bromides and iodides (Scheme 1).1-6 Majority of
the already developed transition metal catalyzed strategies for C−S cross coupling reactions are
based on expensive and relatively less abundant palladium based catalysts which requires typical
ligand design to achieve efficient catalysis.2,3
In recent years photoredox catalysis has emerged as a powerful alternative method for
carrying out wide variety of reactions under mild conditions, including C−S bond formation.4
However, these methods are associated with expensive ruthenium or iridium based photo-
sensitizers which may introduce a bar in terms of sustainability and scalability of these methods.
Figure 1. Selected examples of medicinally and biologically important thioethers.
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In this perspective, the use of catalysts based on cheap and abundant base-metals is
especially beneficial for large-scale and industrial applications, where the paucity and cost of the
noble metals like palladium, iridium or ruthenium can be problematic. However, the base metals
tend to react via single electron transfer process and the corresponding two-electron transfer
processes are mostly enegetically uphill requiring high temperatures.7 In recent yeras,
notwworthy progress has also been achieved with cheap copper1d,5 and nickel6 catalysts, however
these protocols almost always requires high temperatures for the reaction to proceed.
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Scheme 1
Previous work
S
Pd Catalyst
+
X
HS
HS
R
R
Base, Solvent
R'
R'
R
R'
R'
expensive & scarce catalyst
S
Cu or Ni Catalyst
Base, Solvent
+
X
R
required elevated temperature
works best with aryl bromides and iodides
Photoredox
S
catalysis
+
X
HS
HS
R
Base, Solvent
R'
R'
R
R'
RT
required expensive photo-catalyst
Present work
NiII Catalyst
S
X
+
R
Base, Solvent
R
cheap & earth abundant catalyst
easy to prepare; air stable
R'
X=I, Br, Cl
efficient with aryl iodides and bromides
moderate with aryl chlorides
mild reaction conditions
RT (for X = Br, I); 550 C (for X = Cl)
broad substrate scope (> 40)
The use of redox noninnocent ligands in combination with the base-metals has emerged
as an attractive alternative.7,8 The ability of redox noninnocent ligands to store and release
electrons when required, allows multi-electron transformations (mostly preferred for noble
metals like palladium) with inexpensive 3d-base metals. In recent times, using the redox
noninnocent properties of imine, diamine and aminophenol based scaffolds, various new
stoichiometric and catalytic reactions were developed where these organic scaffolds were found
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to participate actively during electron transfer processes involved during catalytic turnover.8
However, no systematic studies were carried out to explore catalytic C−S coupling reactions
using transition metal complexes of redox noninnocent ligands.
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Herein we report the synthesis of a wide variety (47 examples) of aromatic thioethers via
cross coupling of (hetero)aryl halides(ArX, where X = I, Br, or Cl) and (hetero)aryl thiols
catalyzed coordinatively unsaturated Ni(II)-complexes containing redox noninnocent diamine
ligands where the redox processes are expected to be in part (or entirely) ligand centered. To
avoid high-energy Ni(0)/Ni(II) or Ni(I)/Ni(III) redox steps during catalysis we wanted to (partly)
utilize the low enegy ligand centered redox processes, by either leaving nickel in the +II
oxidation state throughout the entire catalytic cycle or enabling less energetic nickel(II)-
nickel(III) oxidative addition/reductive elimination steps. Notably, the reactions were found to
proceed efficiently at room temperature with aryl bromides and iodides affording the
corresponding thioethers in moderate to good yields. With aryl chlorides, the C-S corss coupling
reaction did nor proceed at room temperature. At slightly higher temparture (55 °C) the desired
products were obtained in moderate yields wheras the highest yield was obtained at 80 °C (Table
2, entry 1) with aryl chlodide.
RESULT AND DISCUSSION. Three tetracoordinate singlet di-radical Ni(II)-complexes, 1-3
featuring two antiferromagnetically coupled one-electron oxidized redox noninnocent dimaine
type ligands {(L1-3)•-} with the valence configuration of [NiII{(L1-3)•-}2] (1-3) were employed to
study the above mentioned C−S cross coupling reactions (Figure 2).9 In all the three catalysts,
the central Ni(II)-center is coordinated by two o-diiminosemiquinonato type ligands in a
distorted square planner geometry. In catalyst 1, and 2, the Ni(II) ion is bound to two one
electron oxidized o-phenylenediamine (L1) and two N-phenyl-o-phenylenediamine (L2) ligands
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respectively, whereas in catalyst 3, two one electron oxidized tridentate N-(2-
aminophenyl)benzene-1,2-diamine (L3) ligands are bound to the Ni(II) centre in a bidentate
mode with one uncoordinated amine arm from each of the ligands.9c
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Figure 2. Catalysts used in this study.
During transition metal catalyzed cross coupling of thiols with aryl halides, mostly aryl
iodides, and bromides are used and the use of aryl chlorides as the substrate is limited because of
their poor reactivity.6a,b Therefore, during our initial studies we focused on the possibility of
cross coupling of thiols with chloro-, bromo- and iodobenzene separately. The reactions of
thiophenol (4a) with chloro- (5a'), bromo- (5a") and iodobenzene (5a) were performed
independently under various reaction conditions to obtain the optimal conditions and to check
the effects of ligands and solvents during the catalytic C−S bond formation reactions using
Ni(II)-complexes, 1-3 as catalysts.
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Table 1: Optimization of the Reaction Conditions.a-d
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S
Ni-Catalyst (mol%)
SH
I
Base, Solvent
Temperature (oC)
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(6aa)
(4a)
(5a)
Entry
1
Ni-catalyst (mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
3 (5.0mol%)
2 (5.0mol%)
1 (5.0mol%)
L3
Solvent
DMF
Base
Time (h) Yield (%)
NaOtBu
NaOH
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24
24
24
24
24
24
24
24
24
24
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24
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24
24
24
24
24
24
24
24
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24
68
28
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3
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5
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16
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN
Cs2CO3
K2CO3
K3PO4
KOH
KOtBu
NR
NR
NR
NR
78
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
NaOtBu
87
69
Trace
NR
NR
NR
67
NR
NR
<10
NR
<10
Trace
NR
NR
NR
NR
Toluene
Dioxane
THF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
CH3CN/DMF
17d Ni(COD)2/DPPF
18d Ni(COD)2/Xanthphos
19d Ni[P(OPh)3]4/DPPF
20d Ni[P(OPh)3]4/Xanthphos
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22
23
24
Ni(ClO4)2.6H2O (10.0 mol%)
NiCl2.6H2O (10.0 mol%)
3(5.0 mol%) + 2 equiv. TEMPO
3(5.0 mol%) + 2 equiv. DPPH
aStoichiometry: thiol (4a) (1.0 mmol; 1.0 equiv.) and aryl halide (5a) (1.2 mmol; 1.2 equiv). b1.0
equiv of base. cTemperature: RT. dNickel salts: 10 mol%; ligands: 20mol%.
Using 3 as the catalyst, the cross-coupling reactions of thiophenol (4a) with bromo- (5a")
and iodobenzene (5a) are found to proceed efficiently at room temperature in CH3CN/DMF (5:1)
solvent mixture. Among the series of bases tested, NaOtBu was found to be most efficient. At
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room temperature, using iodobenzene a maximum of 87% of diphenylsulfide (6aa) was isolated
with 5.0 mol% of catalyst loading in presence 1.0 mmol of NaOtBu as base (Table 1, entry 8)
whereas bromobenzene afforded 60% of 6aa. However, chlorobenzene requires slightly higher
temperature, at 55°C, diphenylsulfide (6aa) was isolated in 51% yield. Interestingly, with
increase in the reaction temperature, the yield of 6aa increases with bromo- and chlorobenzene.
With bromobenzene, at 50°C, the yield of 6aa increases to 75%. However, a maximum of 70%
6aa was isolated at 80°C using chlorobenzne as the electrophile (Table 2, entry 1). In all the
cases, the yield of 6aa decreases significantly upon lowering the catalyst loading below 5.0
mol%, however, no significant increase of yields were noticed with higher catalyst loading.
Among the three different Ni(II)-catalysts studied, best results were obtained with catalyst 3,
whereas using catalyst 2 only 67% of the desired C−S coupled product was obtained (Table 1,
entry 14) at room temperature starting from thiophenol (4a) and iodobenzene (5a).
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Control experiments were performed to check the role of base as well as role of the
coordinated redox active ligands during the catalytic C-S cross coupling. In absence of catalyst, 3
and NaOtBu, no desired C-S coupled product was obtained. In absence of 3, when the reactions
were carried out in presence of only NaOtBu, no C−S coupled products were obtained while
using unsubstituted aryl halides or aryl halides containing electron donating groups. However,
with aryl halides having electron withdrawing substituents the corresponding C−S coupled
products were isolated in trace amount (<10%) at RT in presence of only NaOtBu under our
optimized reaction conditions. No desired products were also obtained only in presence of the
ligand L3. Other Ni-salts like NiCl2.6H2O, Ni(ClO4)2.6H2O, Ni(COD)2 and Ni[P(OPh)3]4 when
used as the catalyst, no desired C−S coupled products were obtained at room temperature under
our optimal reaction conditions. No desired C−S coupled products were also obtained when the
cross coupling of thiophenol (4a) and iodobenzene (5a) were carried out using these nickel salts
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in presence of ligands like DPPF and Xantphos under our optimized conditions. Using these
ligands, reactions also did not proceed at room temperature under the optimized reaction
conditions reported by Stewart and co-workers (Table 1, entries 17-20).6a Literature data reveals
that with other nickel catalysts containing various redox non-active phosphines, N-heterocyclic
carbene based ligands almost always require high temperature (1100C-800C) for C-S cross-
coupling reactions (Figure 1).6a-i Interestingly, C−S cross coupling reactions requires high
temperature to proceed even with nickel complexes bearing redox active ligands such as
bipyridine,6k diiminopyridine,6l etc where the C−S cross coupling involves only the nickel
centered redox events and the coordinated ligands remain as spectator.6j-l Literature data reveals
that irrespective of the nature of the coordinated ligands (redox active or redox non-active) the
nickel catalyzed C-S cross coupling reactions which involve only the nickel centered redox
events (Ni(0)/Ni(II) or Ni(I)/Ni(III)) almost always require high temperature (Figure 3).6
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S
Ni-Catalyst
SH
X
Base, Solvent
X=Cl, Br
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8
9
Ligand
Pre-Catalyst type
Ligand
Pre-Catalyst type
[L/NiCl2]
NiBr2-bpy
N
N
O
O
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PR2
PR2
Condition
110oC
Additive
Zn
R=Ph, Me, iPr, tBu
Reference : 6e
Reference : 6h
Condition
80oC
Ligand
Ligand
Pre-Catalyst type
Pre-Catalyst type
[L/Ni(COD)2]
Reference : 6c
[L/NiX2]
Cl-
O
N
N
P
P
O
H
H
O
Ph
Ph
Reference : 6d
Condition
110oC
Condition
80oC
Pre-Catalyst type
[L/NiCl2]
Pre-Catalyst type
[L/NiCl2]
Ligand
Ligand
N
H
N
Reference : 6i
Reference : 6g
R2P
PR2
N
N
Arf
Arf
R=Ph, Cy, tBu
Condition
Condition
800C
110oC-160oC
Pre-Catalyst type
Ligand
Ligand
Pre-Catalyst type
L/Ni[P(Op-Tolyl)3]4
L/Ni[P(Op-Tolyl)3]4
Ph2P
PPh2
O
Condition
110oC
Additive
Zn
Reference : 6a
PR2
R=Ph,tBu
PR2
Reference : 6a
Condition
110oC
Figure 3. Examples of some nickel catalyzed C−S cross-coupling reactions involving metal
(Ni)-centered redox events.
Having the optimized conditions in hand, we studied the substrate scope of this nickel
catalyzed C−S cross coupling reactions. A diverse range of thiophenols bearing electron
donating, withdrawing, and heterocyclic functionalities were reacted with iodo-, bromo- and
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chlorobenzene separately. It is worth mentioning that the reactions of iodobenzene with thiols
were performed at room temperature while the reactions of bromo- and chlorobenzenes were
carried out at two different temperatures and the results are summarized in Table 2.
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Aryl thiols containing both electron donating and withdrawing functionalities were found
to be effective in the catalytic C−S cross coupling reactions with aryl halides (X = I, Br, Cl)
affording the corresponding C−S-coupled products in moderate to good yields. S−arylated
products were obtained in higher yield with aryl halides bearing electron donating groups at the
ortho-, para- or meta- positions (Table 2, entries 2-5). At room temperature the reaction of iodo-
and bromobenzene with ortho-, meta-, and para-thiocresol produced the corresponding
diarylsulfides (6ab-ad) in 67%, 78% and 82% (with iodobenzene) and 45%, 61% and 63% (with
bromobenzene) yields respectively. The same reactions with bromo- (at 50°C) and
chlorobenzene (at 55°C) afforded the corresponding diarylsulfides in 54%, 69% and 71% (with
bromobenzene) and 42%, 58% and 65% (with chlorobenzene) yields respectively.
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Table 2: Substrate Scope of Thiols with Aryl Chlorides/Bromides/Iodides.a-g
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Aryl thiols containing electron withdrawing groups were also found to be suitable,
although the corresponding S−arylated products were obtained in moderate to good yield (Table
2, entries 10-12). It is worth to mention that aryl thiols bearing free amine or hydroxyl groups
were also tolerated under the optimal conditions (Table 2, entry 6, 8, 9). Excellent
chemoselectivity was observed when ortho- and para-hydroxy thiols were reacted with aryl
iodide and bromide under the optimized reaction conditions; only the C−S coupled product was
formed, and no C−O bond formation was observed. However, with chlorobenzene at 80°C, other
than C−S, small amount of C−O coupled product was also isolated. 2-naphthalenethiol was also
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found to be compatible, affording the desired C−S coupling product in 65% isolated yield at RT
with iodobenzene (Table 2, entry 13). Heterocyclic functionalities were also tolerated under the
optimized reactions conditions producing the corresponding diarylsulfides in moderate to good
isolated yields (Table 2, entries 14, 15). The C−S cross coupling reactions also proceeded with
alkyl thiols and iodobenzene (Table 2, entry 16).
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To further substantiate the substrate scope, various aryl iodides, bromides and chlorides
were used as the electrophile to couple with thiophenol. Aryl halides bearing different electronic
functionalities were all found to be suitable yielding the corresponding diarylsulfides in good to
moderate yields (Table 3). Both activated and unactivated aryl halides are equally effective
affording the corresponding diarylsulfides in almost comparable yields. At room temperature, the
reactions of aryl iodides containing electron donating groups at ortho-, para-, and meta-
positions produced the corresponding diarylsulfides in 63-85% yields (Table 3, entries 17-20).
Almost identical yields were obtained with aryl bromides at 50°C, whereas slightly lower yields
were obtained with chlorobenzene even at 80°C. Napthyl and pyrene iodides were also found to
be compatible, yielding the corresponding diarylsulfides in 61 and 65% yields at room
temperature (Table 3, entries 34-36) respectively. Heterocyclic iodides such as, 2-iodothiophene,
3-iodopyridine produced the corresponding diarylsulfides in 60% and 65% yields respectively
(Table 3, entries 37, 38). Long chain alkyl iodides were also tolerated under our optimal
conditions (Table 3, entry 39).
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Table 3: Substrate Scope aryl Chlorides/Bromides/Iodides.a-g
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Since arylthioethers are ubiquitous in various pharmaceuticals, we explored the potential
of our methodology to bring about late stage thiolation of some selected pharmaceutically
relevent molecules such as Hydrochlorothiazide, Fenofibrate, Monoclobemide and Indometacin
under our optimized reaction conditions. To our delight the desired thiolated compounds (Table
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4, entries 40-45) were obtained in 52%−72% yield. We also synthesized the key structure of 11β-
HSD1 inhibitors (Table 4, entry 46) in 50% yield via the reaction of 2-chlorothiophenol and 4-
bromoacetophenone under our optimized reaction conditions.
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Table 4: Late Stage Functionalization of Some Pharmaceutically Relevant Molecules.
Finally to understand the mechanism of the developed catalytic methodology and to
confirm our hypothesis of using ligand centered redox events avoiding Ni(0)/Ni(II) or
Ni(I)/Ni(III) redox couples during catalytic turnover, some control experiments were carried out.
Since the catalysts used in this study are all redox active and the redox processes are expected to
occur at the ligand centers generating organic radicals upon oxidation or reduction, we decided to
check the catalytic reaction in presence of a radical inhibitor to confirm the involvement of
ligand centered redox as well as to check the involvement of any organic radicals during catalytic
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turnover. Interestingly, no C−S coupled product was obtained in presence of TEMPO or DPPH
(∼2.0 equiv with respect to the catalyst; TEMPO = 2,2,6,6-tetramethyl piperidinoxyl; DPPH =
2,2-diphenyl-1-picrylhydrazyl; Table 1, entries 19-20).
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An immediate change of color of the catalysts 2 and 3 was observed upon addition of
NaOtBu. Since, alkali metal tertiary butoxides, other than acting as base can also act as a
reducing agent,10 the observed color change may lead to confusion whether it is due to
deprotonation of any of the −NH group of the coordinated ligand or it is due to the reduction of
the coordinated ligands. Recently, in our work with catalysts 2 and 3, we revealed that in
presence of KOtBu the catalysts 2 and 3 undergo simple deprotonation.9d Our present
experimental results in presece of NaOtBu also indicates that the base seems to act as a base
(deprotonating agent) rather than a reducing agent in these reactions and the deprotonated
complex [3]─ possibly plays the role of the active catalyst. Interestingly, when the stoichiometric
reaction of iodobenzene and thiophenol was performed in absence of any added base using the
preformed [3]─ as the catalyst, 80% of diphenylthiol (6aa) was isolated confirming the active
participation of [3]─ during catalysis.
Next, to explore the feasibility of single electron transfer from [3]─ to the aryl halide,
generating aryl radicals, a control reaction was carried out with thiophenol (4a) and 1-(allyloxy)-
2-iodobenzene (5y) under the optimized reaction conditions (Scheme 2).4b Characterization of
the reaction mixture confirms the formation of the C−S coupling product 9-(2-(allyloxy)phenyl)-
thiophenol (6ya) and no intramolecular cyclization product (that would have been formed if the
reaction proceeds through single electron transfer pathway) was found. 9-(2-(allyloxy)phenyl)-
thiophenol (6ya) was isolated in 52% yield and ~44% of unreacted 1-(allyloxy)-2-iodobenzene
(5y) was recovered from the reaction mixture. This result indeed eliminates mechanistic
pathways involving single electron transfer from the catalyst to the aryl halides and it was also
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conclude that our catalyst was efficient to from C-S coupled product when iodo substrate was 1-
(allyloxy)-2-iodobenzene.
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SPh
Catalyst 3 (5.0 mol%)
I
NaOtBu (1.0 equiv.)
O
O
47
O
CH3CN/DMF (5:1)
RT, 24h
O
Unreacted starting materials
(5y)
SPh
(6ya)
52%
Scheme 2. Control experiment to check the possibility of single electron transfer pathway.
For further understanding of the reaction mechanism and to check the role of the ligand
centered redox events, DFT studies were carried out at the B3LYP level using LANL2DZ basis-
set for Ni, 6-311+G(d) basis-set for N and the 6-31G(d,p) basis-set for C, H. (see experimental
section and the Supporting Information for details).12-17 Broken-symmetry calculations were
performed following the formalism as introduced by Noodleman18 to achieve the spin-polarized
symmetry-broken solutions for all the intermediates involved in the catalytic reactions.19,20
Efforts were given to understand the plausible electronic structures of the reaction intermediates
as well as to reveal the involvement of the redox couples involved in the oxidative
addition/reductive elimination steps. Computed low-energy barriers are displayed in Figure 4.21
As evident from the experimental results described above, it seems that in presence of
NaOtBu, the complex 3 undergoes deprotonation9d and the deprotonated complex [3]─ plays the
role of the active catalyst. Therefore, electronic structure of [3]─ was first studied. As was
reported with 3,9 the deprotonated complex [3]─ was also found to be singlet di-radical species
containing two one electron oxidized semiquinone radicals coupled antiferromagnetically with
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an electronic structure description of [NiII(L3)•−{(L3)−}•−]− (one extra negetive charge is for the
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initial deprotonation of L3) (See SI).
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The activation of the Ar-I bond was then studied. Upon introduction of PhI moiety to 3 in
presence of tBuO─, the catalyst 3 undergoes deprotonation to form the active species [3]─ which
then losses its square plannar geometry and both the ligand become orthogonal to each other
which indeed creates some extra space for PhI to aproach close to [3]─ and its C–I bond gets
activated in transition state (3ATS). The transition state 3ATs for oxidative addition was found to
have a barrier of 26.3 kcalmol-1 relative to 3. The intermediate 3B, formed after oxidative
addition was found to be penta-coordinate with one iodide anion at a distance of 4.5 Å from the
nickel center. Formation of 3B is exergonic by –12.8 kcalmol-1 relative to 3. Transition state
barrier was also calculated starting with the deprotonated species [3]─ to check the feasibility of
the step-wise deprotonation of 3 to form [3]─ followed by oxidative addtion of PhI on the
preformed [3]─ (Figure S6). In both the cases the activation of Ph-I goes through the same
activation energy of 26.3 kcalmol-1 relative to 3, however, with respect to the preformed [3]─, the
transition state barrier was found to be slightly higher 29.2 kcalmol-1. On the other hand, the
direct activation (oxidative addition) of Ph-I on 3, goes through a transition state (3ATS') energy
barrier of 29.1 kcalmol-1 (Figure S7). This indeed indicates that the base (tBuO─) plays an
important role during catalysis and upon deprotonation the oxidative addition is favored.
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Figure 4. The relative free energy profile with scehmatic presentation for C–S crosscoupling
reaction of PhI and PhSH catalyzed by 3.
It is important to note that during oxidative addition the two electron transfer from the
catalyst can occur either involving energetically demanding exclusively nickel centered redox-
couple, Ni(II)/Ni(IV) or both Ni(II) and one of the coordinated ligand can participate in a
synergistic way by loosing one electron each, thus leading to comparitively low energy
Ni(II)/Ni(III) and {(L3)•−}/{(L3)0} or {(L3)•2−}/{(L3)−}(extra negative charge results from the
initial deprotonation) redox couples. The possibility of two electron transfer from the two
coordinated ligands can also not be excluded. Therefore, to understand the possible redox
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couples involved during the oxiative addition, the electronic structures of 3ATs and the
intermediate (3B) obtained after the oxidative addition were analysed throughly. In the transition
state 3ATs, the nickel center possesses +1.44 spin and the deprotonated ligand contains –0.16
spin whereas –0.82 spin resides over the other ligand.
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Analysis of eletronic configuration of 3B reveals following facts: i) +0.83 spin is located
on the nickel center which supports the +3 oxidation state of nickel suggesting the involvement
of the Ni(II)/Ni(III) redox couple during oxidative addition, (ii) the deprotonated ligand contains
only +0.11 spin, indicating the existence of fully oxidized quinone form [(L3)]− of the ligand
indicating involvement of {(L3)•2−}/{(L3)−} redox couple during oxidative addition, here extra
negative charge results from the initial deprotonation (iii) the other ligand contains –0.87 spin
which supports monoanionic semiquinone radical oxidation state [(L3)•−] (See SI, Figure S6, S8).
The electronic configuration of 3B can be expressed as {[NiIII{(L3)•−}{(L3)−}(Ph)]I}−. Thus DFT
study indicates that oxidative addition involves Ni(II)/Ni(III) and {(L3)•2−}/{(L3)−} redox
couples demonstrating metal-ligand cooperative catalysis. Therefore, computational studies
t
reveal that oxidative addition is favored upon ligand -NH deprotonatio by BuO−. Possibly,
because of deprotonation, the coordinated ligand becomes more electron rich which makes it
more susceptible towards oxidation and that in turn promotes the C–I bond activation under mild
conditions in combination with Ni(II)/Ni(III) redox couple.
In the next step, the nucleophile PhSH coordinates to Ni(III) center as PhS– and the
proton is transferred to the doubly oxidized ligand leading to 3C which is exergonic by –16.0
kcalmol-1 compared to 3B. The energy difference for the step 3B to 3C was calculated as (3C+I–)
– (3B + PhSH). In 3C, nickel center remains in +3 oxidation state as evident from +0.70 spin on
nickel. No substantial amount of spin (0.01) was found on the fully oxidized quinone form of the
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ligand, as expected. The other ligand contains –0.88 spin indicating its monoanionic
semiquinone radical oxidation state [(L3)•−] as was there in 3B.
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Next, attention was paid to understand the reductive elimination step. Reductive
elimination was found to pass through the transition state 3CTS with energy barrier of 8.3
kcalmol−1. The TS energy barrier for the non-catalyzed C–S coupling reaction is calculated to be
29.9 kcalmol−1 which is 21.6 kcalmol−1 higher than the catalyzed reaction. It is important to note
that the transition state energy barrier (26.3 kcalmol−1) for oxidative addition is larger than the
energy barrier for reductive elimination (8.3 kcalmol−1). This suggests that the oxidative addition
is the rate determining step for this reaction.
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After reductive elimination it leads to an intermediate 3D where nickel center is reduced
to Ni(II) as revealed from its spin population of +1.47. Along with metal center reduction, the
deprotonated doubly oxidized ligand in 3D also gets reduced to its monoanionic radical state
(spin population is –0.73) during C–S coupling. This also supports synergestic metal-ligand
participation in the catalytic cycle. The coupled product diphenylsulfide is released in this
process. 3D was found to be exergonic by –28.9 kcalmol−1 relative to 3C.
Thus, computational study performed herein reinforces the following facts; i) initial
tBuO− mediated ligand NH deprotonation facilitates the activation of Ph–I via oxidative addition
under mild conditions, ii) the catalytic cycle utilizes combined ligand and Ni(II)/Ni(III) redox
events, iii) the oxidative addition was found to be rate limiting step in the catalytic cycle.
Based on the above experimental results and available literature a plausible mechanism is
t
outlined in Scheme 3. The reaction is supposed to progress via BuO– mediated ligand -NH
deprotonation of catalyst 3 followed by oxidative addition of Ph-I to form the intermediate 3B.
The increased electron density in [3]─ likely enables the oxidative addition of the ArI substrate
under mild conditions. During oxidative addition the nickel center is oxidized by one electron to
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Ni(III) and another electron is provided by the deprotonated ligand. In the next step PhSH
coordinate to Ni(III) center as PhS– and the proton is transferred to the doubly oxidized ligand to
form intermediate 3C which upon reductive elimination produce the diarylsulfide.
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Na+
-
R
H
N
R
N
II
Ni
NaOtBu
H
N
N
N
II
Ni
I
- tBuOH
N
H
N
N
R
R
[3]-
3
R = H, NH2
S
NaOtBu
-
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N
R
III
Ni
III
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NH
NH
N
N
H
3B
N
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R
R
SH
Scheme 3. Proposed Mechanism.
Conclusion. In summary, we have reported a simple and efficient approach of C–S bond
formation of a wide variety of (hetero)aryl thiols and (hetero)aryl halides under mild conditions
mostly at room temperature (with aryl iodides/bromides), catalyzed by simple, well defined, easy
to prepare and cheap Ni(II)-catalysts bearing redox noninnocent ligands. Taking advantage of
ligand centered redox events; high-energetic Ni(0)/Ni(II) or Ni(I)/Ni(III) redox steps were
avoided in the catalytic cycle via synergistic participation of both nickel and the coordinated
ligands during oxidative addition/reductive elimination steps. As revealed from DFT studies,
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both nickel and one of the coordinated ligand undergo one electron trasfer during oxidative
addition/reductive elimination. The successful development of similar approaches avoiding high
energetic Ni(I)/Ni(III) redox couple is expected to open many new research avenues aimed at the
future replacement of expensive noble metal catalysts in various cross-coupling reactions. Our
studies in this area is in progress and will be reported in due course.
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EXPERIMENTAL SECTION
General Information. Unless otherwise stated, all the reactions were performed under argon
atmosphere using standard Schlenk technique. All the solvents were dried following standard
drying procedure. Aryl halides and substitutedthiophenols werepurchased from Sigma-Aldrich,
TCI and used without further purification. Analytical TLC was performed on a Merck 60 F254
silica gel plate (0.25mm thickness) and column chromatography was performed on Merck 60
silica gel (60-120 mesh).NMR spectra were recorded on a Bruker DPX-300(300 MHz), Bruker
DPX-400(400 MHz) and Bruker DPX-500(500 MHz) spectrometers. TMS (tetramethylsilane)
was used as an internal standard.
Catalyst Synthesis. The catalysts 1-3 were synthesized following the available literature
procedures.9
General Procedure for Catalytic C-S Coupling. Under argon atmosphere, Ni-catalyst (5.0 mol
%) and NaOtBu (1.0 equiv.) were added to an oven dried 25mL Schlenk tube containing a Teflon
coated magnetic stir-bar. To this Schlenk tube, respective aryl halides (1.10 mmol) and
thiophenols (1.0 mmol) were added via syringe. A mixture of solvent CH3CN/DMF (5:1) was
added to the reaction vessels through a syringe. Using a rubber septum the Schlenk tube was
capped and was tightly wrapped with Teflon. The reaction mixture was then degassed with argon
for 10 min and the reaction mixture was kept for stirring at room temperature for 24 hours. The
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reaction was monitored using TLC. After the reaction was completed, the solvent was removed
through vacuum and the product was purified through column chromatography using a mixture
of petroleum ether and hexane as an eluent.
9
Computational Studies. All DFT calculation were done using theGaussian 16 package11 with
the Lee–Yang–Parr correlation function (B3LYP).12-13 Grimme’s D3-dispersion correction14 was
employed for the dispersion correction. For Ni and iodide, the Hay and Wad basis-set LANL2DZ
pseudopotential15 was used, 6-311+G(d)16 basis-set was employed for N and the 6-31G(d,p)17
basis-set was used for C, H. For all the optimized structures, broken-symmetry states were found
to be lower in energy compared to their corresponding high-spin states. Broken-symmetry
calculations were performed following the formalism as introduced by Noodleman18 to achieve
the spin-polarized symmetry-broken solutions.19,20 For complex 3, two unpaired electrons on
both the ligands could not be separated by broken-symmetry. This could be due to strong anti-
ferromagnetic coupling between both the ligands in square planar geometry. For all other
structures, broken-symmetry solutions were obtained as expected. The nature of the ground-state
geometries of each optimized structure, were evaluated by frequency calculations at the same
level of theory, as that of geometry optimization. No imaginary frequency was obtained for the
intermediates whereas transition states have only one imaginary frequency. The intrinsic reaction
coordinate (IRC) calculations revealed that the transition states connect to the right minima. All
energies reported in the reaction coordinate are Gibbs free energy. All the optimization of the
intermediates and transition states were performed with CPCM polarizable conductor calculation
model22 employing acetonitrile as solvent. Spin-density plots were made using the Chemcraft
Visualization program.
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Characterization Data of the Isolated Compounds.
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Diphenylsulfane (6aa).4h,5d Eluent: petroleum ether. Colorless oil. Yield c87% (162 mg, for X =
5
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8
d
e
f
I); c60% & 75% (112 mg & 140 mg, for X = Br); 51% & 70% (95mg & 130mg, for X=Cl).
1HNMR (400 MHz, CDCl3): δ = 7.36-7.25 (m, 10H). 13C{1H} NMR (100 MHz, CDCl3) = 135.0,
130.7, 129.0, 127.1.
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Phenyl (o-tolyl)sulfane (6ab).4g,5d,6c Eluent: petroleum ether. Colorless oil. Yield c67% (134 mg,
c
d
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for X = I), 45% & 54% (90 mg & 108 mg, for X = Br); 42% (84 mg, for X = Cl). HNMR
13
(400 MHz, CDCl3): δ = 7.38-7.10 (m, 9H), 2.46 (s, 3H). C{1H} NMR (100 MHz, CDCl3) =
139.9, 138.9, 136.1, 133.8, 133.0, 131.2, 131.0, 130.6, 129.7, 129.3, 129.1, 127.9, 127.2, 127.0,
126.79, 126.7, 126.3, 21.0.
Phenyl (m-tolyl)sulfane (6ac).4h,5d,6c Eluent: petroleum ether. Colorless oil. Yield c78% (156 mg,
for X = I), c61% & d69% (122 mg & 138 mg, for X = Br); e58% (116 mg, for X = Cl). 1HNMR
(400 MHz, CDCl3): δ = 7.33-7.26 (m, 4H), 7.23-7.12 (m, 4H), 7.05 (d, 1H, J = 6.8 Hz). 13C{1H}
NMR (100 MHz, CDCl3) = 139.0, 136.1, 135.2, 131.9, 130.8, 129.2, 129.1, 128.4, 128.1, 126.9,
21.3.
Phenyl (p-tolyl)sulfane (6ad).4h,5d,6c Eluent: petroleum ether. Colorless oil. Yield c82% (164 mg,
for X = I), c63% & d71% (126 mg & 142 mg, for X = Br); e65% (130 mg, for X = Cl). 1H NMR
(400 MHz, CDCl3): δ = 7.29-7.26 (m, 2H), 7.25-7.20 (m, 4H), 7.20-7.13 (m, 1H), 7.11 (d, J = 4
13
Hz, 2H), 2.23 (s, 3H). C{1H} NMR (100 MHz, CDCl3) = 137.6, 137.2, 132.3, 131.3, 130.1,
129.8, 129.1, 126.4, 21.2.
4-(methoxyphenyl) (phenyl)sulfane (6ae).4e,4h,5d Eluent: petroleum ether/ethyl acetate (50:1).
Light yellow solid. Yield c85% (184 mg, for X = I), c61% & d72% (132 mg, 156 mg, for X = Br);
e65% (141 mg, for X = Cl). 1H NMR (400 MHz, CDCl3): δ = 7.42 (d, J = 6.4 Hz, 2H), 7.23-7.13
(m, 5H), 6.88 (d, J = 8.4 Hz, 2H), 2.83 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) = 160.2,
138.8, 135.5, 129.1, 128.4, 126.0, 124.4, 115.2, 55.5.
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4-(Phenylthio)benzenamine (6af).4e Eluent: petroleum ether/ethyl acetate (50:1). White solid.
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6
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Yield c83% (167 mg, for X = I). H NMR (400 MHz, CDCl3): δ = 7.17 (dd, J1 = 12 Hz, J2 = 8
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Hz, 2H), 7.05 (t, J = 8 Hz, 2H), 7.00 (d, J = 8 Hz, 2H), 6.95 (t, J = 8 Hz, 1H), 6.47 (d, J = 8 Hz,
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2H), 3.60 (br, s, 2H). C{1H} NMR (100 MHz, CDCl3) = 147.3, 139.9, 136.3, 129.0, 127.3,
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125.4, 120.1, 116.0.
Methyl 2-(phenylthio)benzoate (6ag).4h Eluent: petroleum ether/ethyl acetate (50:1). Yellow oil.
c
c
d
e
Yield 52% (127 mg, for X = I), 39% & 45% (96 mg & 110 mg, for X = Br); 41%
(101 mg, for X = Cl). 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 7.91 Hz, 1H), 7.56-7.53 (m,
2H), 7.43-7.41 (m, 3H), 7.23 (t, J = 8.26 Hz, 1H), 7.14 (t, J = 7.90 Hz, 1H), 6.83 (d, J = 8.25 Hz,
1H), 3.95 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3) = 167.1, 143.7, 134.7, 132.8, 132.4, 131.5,
130.0, 129.2, 127.5, 127.2, 124.7, 52.0.
2-(phenylthio)phenol (6ah).6h Eluent: petroleum ether/ethyl acetate (50:1). Yellow oil. Yield
c57% (115 mg, for X = I), 37% & 43% (75 mg & 87 mg, for X = Br); 40% (81 mg, for X =
c
d
e
Cl). 1H NMR (400 MHz, CDCl3): δ = 7.47-7.45 (m, 1H), 7.33-7.28 (m, 1H), 7.18-7.14 (m, 2H),
7.09-7.05 (m, 1H), 7.02-6.99 (m, 3H), 6.90-6.86 (m, 1H), 6.45 (s, 1H). C{1H} NMR (100
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MHz, CDCl3) = 157.2, 136.9, 135.8, 132.3, 129.2, 126.8, 126.1, 121.3, 116.2, 115.5.
4-(phenylthio)phenol (6ai).4e,5d Eluent: petroleum ether/ethyl acetate(40:1). Yellow oil. Yield
c69% (140 mg, for X = I), c47% & d60% (95 mg & 122 mg, for X = Br), e52% (106 mg, for X =
Cl). 1H NMR (400 MHz, CDCl3): δ = 7.43-7.35 (m, 2H), 7.27-7.13 (m, 5H), 6.86-6.82 (m, 2H),
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4.98 (br, s, 1H). C{1H} NMR (100 MHz, CDCl3) = 156.0, 138.7, 135.7, 129.0, 128.8, 125.8,
124.5, 116.5.
4-(nitrophenyl)(phenyl)sulfane (6aj).4g,4h Eluent: petroleum ether (50:1). Yellow solid. Yield
c55% (128 mg, for X = I), c35% & d45% (81 mg & 104 mg, for X = Br), e25% (58 mg, for X =
Cl). 1H NMR (400 MHz, CDCl3): δ = 7.94-7.91 (m, 2H), 7.43-7.40 (m, 2H), 7.36-7.32 (m, 3H),
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7.06-7.03 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3) = 148.5, 145.4, 134.8, 130.4, 130.0, 129.7,
126.6, 124.0.
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4-(chlorophenyl)(phenyl)sulfane (6ak).5d,6c Eluent: petroleum ether. Colorless oil. Yield 59%
(131 mg, for X = I), c35% & d42% (78 mg & 93 mg, for X = Br), e30% (67 mg, for X = Cl). 1H
NMR (400 MHz, CDCl3): δ = 7.33-7.31 (m, 6H), 7.28-7.25 (m, 3H). 13C{1H} NMR (100 MHz,
CDCl3) = 135.3, 134.8, 133.1, 132.2, 131.5, 129.5, 129.5, 127.6.
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4-(bromophenyl)(phenyl)sulfane (6al).6c Eluent: petroleum ether. Colorless oil. Yield c61% (162
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e
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mg, for X = I), 43% & 49% (114 mg & 130 mg, for X = Br), 35% (93 mg, for X = Cl). H
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NMR (400 MHz, CDCl3): δ = 7.36-7.31 (m, 6H), 7.29-7.21 (m, 3H). C{1H} NMR (100 MHz,
CDCl3) = 135.3, 134. 9, 133.3, 132.3, 131.6, 129.5, 129.5, 127.6.
(Napthalen-6-yl)(Phenyl)sulfane (6am).4h,5d,6c Eluent: petroleum ether/ethyl acetate (50:1).
c
c
d
Yellow solid. Yield 65% (154 mg, for X = I), 40% & 55% (95 mg & 130 mg, for X = Br),
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e50% (118 mg, for X = Cl). H NMR (400 MHz, CDCl3): δ = 7.80-7.63 (m, 4H), 7.40-7.33 (m,
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5H), 7.30-7.15 (m, 3H). C{1H} NMR (100 MHz, CDCl3) = 136.0, 133.9, 133.2, 132.4, 131.1,
130.0, 129.4, 129.0, 128.9, 127.9, 127.6, 127.2, 126.8, 126.4.
2-(phenylthio)pyridine (6an).4h,5d Eluent: petroleum ether/ethyl acetate (10:1). Yellow oil. Yield
c
d
e
c55% (103 mg, for X = I), 40% & 45% (75 mg & 85 mg, for X = Br), 15% (28 mg, for X =
1
Cl). H NMR (400 MHz, CDCl3): δ = 8.33 (d, J = 4 Hz, 1H), 7.51-7.48 (m, 2H), 7.37-7.30 (m,
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4H), 6.90-6.87 (m, 1H), 6.78 (d, J = 8.4 Hz, 1H). C{1H} NMR (100 MHz, CDCl3) = 161.5,
149.5, 136.8, 135.0, 131.0, 129.6, 129.1, 121.3, 119.9.
2-(phenylthio)benzo[d] thioazole (6ao).4e,5d Eluent: petroleum ether/ethyl acetate (40:1). White
solid. Yield c53% (129 mg, for X = I), c40% & d45% (98 mg, 110 & for X = Br), e40% (98 mg,
for X = Cl). 1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 13 Hz, 1H), 7.66 (d, J = 9.6 Hz, 2H),
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7.54 (d, J = 9.6 Hz, 1H), 7.42-7.20 (m, 4H), 7.17 (t, J = 5.6 Hz, 1H). 13C{1H} NMR (100 MHz,
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CDCl3) = 169.6, 153.9, 135.6, 135.3, 130.1, 129.9, 126.6, 124.7, 121.9, 120.9.
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Benzyl(phenyl)sulfane (6ap).3h Eluent: petroleum ether. Yellow solid. Yield 66% (132 mg, for
X = I), d60% (120 mg, for X = Br), e47% (94 mg, for X = Cl). 1H NMR (400 MHz, CDCl3): δ =
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7.31-7.17 (m, 10H), 4.10 (s, 2H). C{1H} NMR (100 MHz, CDCl3) = 138.5, 137.7, 129.8,
129.4, 129.2, 128.8, 127.7, 127.3, 39.5.
2-(methoxyphenyl)(phenyl)sulfane (6ba).4h,5d Eluent: petroleum ether/ethyl acetate (50:1).
Yellow oil. Yield c63% (137 mg, for X = I). 1H NMR (400 MHz, CDCl3): δ = 7.32-7.26 (m, 4H),
7.26-7.20 (m, 2H), 7.07-7.01 (m, 1H), 6.90-6.85 (m, 2H), 3.71 (s, 3H). C{1H} NMR (100
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MHz, CDCl3) = 157.3, 134.7, 131.2, 130.5, 130.3, 128.1, 127.3, 125.1, 120.9, 109.8, 54.7.
3, 5-dimethylphenyl(phenyl)sulfane (6ea).4g,4h,5d Eluent: petroleum ether. Colorless oil. Yield
c75% (161 mg, for X = I). H NMR (400 MHz, CDCl3): δ = 7.30-7.28 (m, 2H), 7.25-7.21 (m,
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2H), 7.18-7.14 (m, 1H), 6.98 (s, 2H), 6.85 (s, 1H), 2.22 (s, 6H). C{1H} NMR (100 MHz,
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CDCl3) = 137.8, 135.4, 133.7, 129.4, 128.1, 125.6, 20.1.
Ethyl 4-(phenylthio)benzoate (6fa).5i Eluent: petroleum ether. Colorless oil. Yield 81% (210
c
1
mg, for X = I). H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 4.4 Hz, 2H), 7.47-7.45 (m, 2H),
7.38-7.35 (m, 3H), 7.21 (d, J = 4 Hz, 2H), 4.31-4.26 (q, J = 7.2 Hz, 2H), 1.34-1.29 (m, 3H).
13C{1H} NMR (100 MHz, CDCl3) = 166.1, 144.0, 133.5, 132.5, 130.0, 129.5, 128.6, 127.9,
127.6, 60.9, 14.3.
1-(2-(phenylthio)phenyl)ethanone (6ga).4h Eluent: petroleum ether/ethyl acetate (50:1). Yellow
solid. Yield c52% (119 mg, for X = I). 1H NMR (400 MHz, CDCl3): δ = 7.82 (d, J = 8.8 Hz, 2H),
7.54-7.50 (m, 2H), 7.44-7.40 (m, 3H), 7.26-7.17 (m, 2H), 6.88 (d, J = 7.6 Hz, 1H). C{1H}
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NMR (100 MHz, CDCl3) = 199.8, 142.9, 135.0, 134.8, 133.2, 132.5, 130.4, 129.7, 129.0, 128.2,
124.4, 29.4.
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1-(3-(phenylthio)phenyl)ethanone (6ha).3c Eluent: petroleum ether/ethyl acetate (50:1). Yellow
solid. Yield c70% (160 mg, for X = I), d50% (114 mg, for X = Br). 1H NMR (400 MHz, CDCl3):
δ = 7.81 (s, 1H), 7.71 (d, J = 7.6 Hz, 1H), 7.38 (d, J = 8.0 Hz, 1H), 7.31-7.17 (m, 6H), 2.46 (s,
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3H). C{1H} NMR (100 MHz, CDCl3) = 197.5, 137.9, 137.5, 134.6, 134.4, 131.9, 130.0, 129.5,
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129.4, 127.8, 126.6, 26.7.
1-(4-(phenylthio)phenyl)ethanone (6ia).5d,6h Eluent: petroleum ether/ethyl acetate (30:1). Yellow
solid. Yield c75% (172 mg, for X = I), d67% (153 mg, for X = Br). 1H NMR (400 MHz, CDCl3):
δ = 7.80 (d, J = 7.6 Hz, 2H), 7.51-7.47 (m, 2H), 7.41-7.38 (m, 3H), 7.20 (d, J = 5.6 Hz, 2H),
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2.54 (s, 3H). C{1H} NMR (100 MHz, CDCl3) = 197.2, 145.0, 134.6, 134.0, 132.3, 129.8,
129.0, 128.9, 127.6, 26.7.
4-(phenylthio) benzoic acid (6ja).5d Eluent: petroleum ether. Colorless oil. Yield c82% (189 mg,
for X = I), d,e65% (150 mg, for X = Br & Cl). 1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8Hz,
2H), 7.35-7.33 (m, 2H), 7.25-7.21 (m, 4H), 7.19-7.15 (m, 2H). 13C{1H} NMR (100 MHz,
CDCl3) = 171.0, 145.9, 135.0, 131.9, 130.7, 129.0, 127.9, 127.1, 126.5.
2-(phenylthio)benzenamine (6la).4g Eluent: petroleum ether. Colorless oil. Yield c65% (131 mg,
for X = I), e57% (115 mg, for X = Cl). 1H NMR (400 MHz, CDCl3): δ = 7.36 (d, J = 7.6Hz, 1H),
7.15-7.10 (m, 3H), 7.02-6.98 (m, 3H), 6.68-6.63 (m, 2H), 4.18 (br, s, 2H). C{1H} NMR (100
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MHz, CDCl3) = 148.9, 137.5, 136.8, 131.2, 129.0, 126.5, 125.4, 118.8, 115.4, 114.3.
2-(nitrophenyl)phenylsulfane (6ma).6h Eluent: petroleum ether/ethyl acetate (50:1). Colorless
oil. Yield c69% (160 mg, for X = I), e53% (123 mg, for X = Cl). 1H NMR (400 MHz, CDCl3): δ
= 7.46-7.40 (m, 1H), 7.24-7.11 (m, 3H), 7.10-7.01 (m, 3H), 6.76-6.69 (m, 2H). C{1H} NMR
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(100 MHz, CDCl3) = 148.9, 137.4, 136. 9, 130.9, 129.3, 126.7, 125.3, 118.9, 114.6.
4-(fluorophenyl) (phenyl)sulfane (6oa).3h,5d,6h Eluent: petroleum ether(50:1). Colorless oil. Yield
c75% (154 mg, for X = I). H NMR (400 MHz, CDCl3): δ = 7.36-7.32 (m, 2H), 7.29-7.20 (m,
1
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