A new family of nucleophiles for photoinduced, copper-catalyzed cross-couplings via single-electron transfer: Reactions of thiols with aryl halides under mild conditions (O C)

Article abstract of DOI:10.1021/ja404050f

Building on the known photophysical properties of well-defined copper-carbazolide complexes, we have recently described photoinduced, copper-catalyzed N-arylations and N-alkylations of carbazoles. Until now, there have been no examples of the use of other families of heteroatom nucleophiles in such photoinduced processes. Herein, we report a versatile photoinduced, copper-catalyzed method for coupling aryl thiols with aryl halides, wherein a single set of reaction conditions, using inexpensive CuI as a precatalyst without the need for an added ligand, is effective for a wide range of coupling partners. As far as we are aware, copper-catalyzed C-S cross-couplings at 0 C have not previously been achieved, which renders our observation of efficient reaction of an unactivated aryl iodide at -40 C especially striking. Mechanistic investigations are consistent with these photoinduced C-S cross-couplings following a SET/radical pathway for C-X bond cleavage (via a Cu(I)-thiolate), which contrasts with nonphotoinduced, copper-catalyzed processes wherein a concerted mechanism is believed to occur.

Full text of DOI:10.1021/ja404050f

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Article
A New Family of Nucleophiles for Photoinduced, Copper-
Catalyzed Cross-Couplings via Single-Electron Transfer:
Reactions of Thiols with Aryl Halides Under Mild Conditions (0 °C)
Christopher Uyeda, Yichen Tan, Gregory C. Fu, and Jonas Christopher Peters
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/ja404050f • Publication Date (Web): 23 May 2013
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A New Family of Nucleophiles for Photoinduced, Copper-Catalyzed
Cross-Couplings via Single-Electron Transfer: Reactions of Thiols
with Aryl Halides Under Mild Conditions (O °C)
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Christopher Uyeda, Yichen Tan, Gregory C. Fu,* and Jonas C. Peters*
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California, 91125,
United States
ABSTRACT: Building on the known photophysical properties of well-defined copper–carbazolide complexes, we
have recently described photoinduced, copper-catalyzed N-arylations and N-alkylations of carbazoles. Until now, there
have been no examples of the use of other families of heteroatom nucleophiles in such photoinduced processes. Herein,
we report a versatile photoinduced, copper-catalyzed method for coupling aryl thiols with aryl halides wherein a single
set of reaction conditions, using inexpensive CuI as a precatalyst without the need for an added ligand, is effective for a
wide range of coupling partners. As far as we are aware, copper-catalyzed C–S cross-couplings at 0 °C have not previ-
ously been achieved, which renders our observation of efficient reaction of an unactivated aryl iodide at –40 °C espe-
cially striking. Mechanistic investigations are consistent with these photoinduced C–S cross-couplings following an
SET/radical pathway for C–X bond cleavage (via a Cu(I)–thiolate), which contrasts with non-photoinduced, copper-
catalyzed processes wherein a concerted mechanism is believed to occur.
adduct is accessible and sufficiently reducing to partici-
pate in SET with an electrophilic coupling partner.
INTRODUCTION
Transition metal-catalyzed cross-coupling reactions
that furnish carbon–heteroatom bonds are a powerful
tool for the synthesis of fine chemicals, pharmaceuticals,
and materials.1,2,3 The use of thiols as the nucleophilic
coupling partner affords access to sulfides (and therefore
sulfoxides), important families of target molecules.4,5
Cross-couplings catalyzed by palladium provide a useful
approach to C–S bond construction,6 although the cost of
palladium and of the ligands that are typically required
to achieve efficient catalysis has stimulated the develop-
ment of complementary catalysts based on copper.
Noteworthy progress has been described in copper-
catalyzed C–S cross-couplings with aryl halides, alt-
hough an elevated reaction temperature (≥50 °C) is al-
most always necessary.6a,6b,7,8
We have recently reported photoinduced, copper-
catalyzed C–N bond-forming reactions of carbazoles,
specifically, N-phenylations and N-alkylations.9 We hy-
pothesize that these couplings may proceed via single
electron transfer (SET) from an excited state of a Cu(I)–
carbazolide complex to the organic electrophile (Figure
1).
X
[LnCu(Nu)]
hν
Nu
*
[LnCuX]
[LnCu(Nu)]
electron
transfer
R
X
Nu
R
[LnCu(Nu)]
+ R
X
Figure 1. Outline of a possible mechanism for photoin-
duced, copper-catalyzed cross-coupling reactions. For the
sake of simplicity, the copper complex that undergoes exci-
tation ([LnCu(Nu)]) is depicted as uncharged.
In this report, we establish for the first time that pho-
toinduced, copper-catalyzed cross-couplings can be ac-
complished with heteroatom nucleophiles other than
carbazoles. Specifically, we demonstrate that C–S bond
formation between thiols and aryl halides can be
achieved using a simple method with an inexpensive pre-
catalyst (CuI) under unusually mild conditions (0 °C or
below) (eq 1). Our mechanistic observations are con-
sistent with the pathway outlined in Figure 1, involving
SET and a radical intermediate, thereby supporting the
suggestion that this strategy for effecting cross-coupling
may have substantial generality.
One of the attractive features of photoinduced, copper-
catalyzed C–N coupling reactions is that they can pro-
ceed at an unusually low temperature; for example, in
the case of the phenylation of carbazole with iodoben-
zene, we observed several turnovers upon photolysis at –
40 °C. In our initial investigations of photoinduced, cop-
per-catalyzed cross-couplings, we focused on the use of
carbazoles as nucleophiles, due to our knowledge of the
photophysical properties of well-defined Cu(I)–
carbazolide complexes.10 Nevertheless, we hoped that
this photoinduced SET strategy for copper-catalyzed
cross-coupling might be generalizable to other nucleo-
philes for which an excited state of a Cu(I)–nucleophile
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Page 2 of 6
could be cross-coupled (entries 7–9). The method is
10% CuI
hν (100-watt Hg lamp)
1
2
3
4
compatible with a wide range of functional groups, in-
cluding an aryl fluoride, a primary aniline, a nitro group,
a nitrile, an ether, a pyridine, an indole, and a thio-
phene.12
H
X
Ar1
ArS Ar1
(1)
ArS
1.0 equiv NaOt-Bu
0 °C, CH3CN
1.0 equiv 1.0 equiv
X = I, Br
5
6
7
8
Table 2. Photoinduced, Copper-Catalyzed C–S
Couplings: Scope with Respect to the Aryl Iodide
RESULTS AND DISCUSSION
Under our standard conditions, thiophenol and 1-iodo-
3,5-dimethylbenzene underwent C–S cross-coupling in
good yield (85%) upon irradiation with a 100-watt Hg
lamp for five hours at 0 °C in the presence of 10% CuI
(Table 1, entry 1). A variety of control reactions estab-
lished the importance of the copper catalyst and of the
light (entries 2–6).11 Essentially no cross-coupling was
observed in the absence of NaOt-Bu (entry 7), whereas
the identity of the alkali-metal cation associated with the
t-butoxide base had a rather small impact on C–S bond
formation (entries 8 and 9). Use of Cs2CO3 as the
Brønsted base resulted in a significant amount of the
desired product (entry 10), although the coupling was
less efficient than with NaOt-Bu. When CuCl2 was em-
ployed in place of CuI, the formation of PhSSPh, possibly
due to sacrificial oxidation of the thiolate to reduce the
Cu(II) pre-catalyst, accompanied the generation of the
diaryl sulfide (entry 11). Use of 5%, rather than 10%, CuI
led to a lower yield of the coupling product (entry 14).
see eq 1
PhS
H
I
Ar1
PhS Ar1
5–8 h
9
10
11
12
13
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15
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60
entry
I
Ar1
yield (%)a
Me
1
2
3
88
82
78
I
I
Me
F
I
H2N
4
5
6
75
78
73
I
Table 1. Photoinduced, Copper-Catalyzed C–S
Couplings: Effect of Reaction Parameters
Me
Me
Me
I
I
Me
Me
Me
see eq 1
5 h
PhS
H
I
PhS
Me
Me
entry variation from the standard conditions
yield (%)a
I
I
I
NO2
7
8
9
90
79
79
1
2
none
85
10
<1
<1
<1
no CuI
CN
3
no light
4
no CuI and no light
ambient light
OMe
5
6
100-watt Hg lamp, filtering out wavelengths <500 nm <1
N
7
no NaOt-Bu
<1
69
72
39
65
25
80
57
10
11
82
63
I
I
8
LiOt-Bu instead of NaOt-Bu
KOt-Bu instead of NaOt-Bu
Cs2CO3 instead of NaOt-Bu
CuCl2 instead of CuI
9
10
11
12
13
14
N
H
I
I
Cu powder instead of CuI
[Cu5(SPh)7][Na(12-crown-4)2]2 (1)b instead of CuI
5% CuI
12
13
71
65
S
a
Yield obtained via calibrated GC analysis with the aid of
an internal standard (average of two experiments). Scale of
reaction: 0.33 mmol of each coupling partner. b 10% loading
of copper-atom equivalents.
S
a
Yield of purified product (average of two experiments).
Scale of reaction: 1.0 mmol of each coupling partner.
This mild, photoinduced method for C–S cross-
coupling has broad scope. With respect to the aryl iodide,
1-iodonaphthalene and ortho-substituted electrophiles
were suitable substrates (Table 2, entries 2–6), including
a very hindered 2,6-disubstituted compound (entry 6).
Furthermore, both activated and deactivated aryl iodides
With respect to the aryl thiol, a diverse array of nucle-
ophiles serve as suitable cross-coupling partners. Thus,
hindered, electron-rich, electron-poor, and heterocyclic
thiols reacted with an aryl iodide to generate a C–S bond
in good yield (Table 3).
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Table 3. Photoinduced, Copper-Catalyzed C–S
Couplings: Scope with Respect to the Aryl Thiol
1
Table 4. Photoinduced, Copper-Catalyzed C–S
2
3
4
5
6
7
8
9
Couplings: Aryl Bromides as Coupling Partners
see eq 1
ArS
H
I
Ph
ArS Ph
see eq 1
5–8 h
PhS
entry
1
H
Br Ar1
PhS Ar1
yield (%)a
73
12–24 h
entry
yield (%)a
ArS
H
Br Ar1
F
Br
1
2
SH
SH
SH
73
71
Me
Me
Me
10
11
12
13
14
15
16
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19
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2
3
4
Br
Br
Br
59
70
64
CF3
3
MeO
MeO
81
OMe
a
Yield of purified product (average of two experiments).
4
5
SH
SH
65
74
Scale of reaction: 1.0 mmol of each coupling partner.
As discussed above, from the outset we were interested
in determining the generality of the proposed
SET/radical-based pathway for photoinduced, copper-
catalyzed cross-couplings (Figure 1) in the case of nucle-
ophiles other than carbazoles. For the C–S couplings
described herein, our working hypothesis is that a Cu(I)–
thiolate is likely undergoing excitation. In fact, the pho-
tophysical properties of Cu(I)–thiolates have previously
been explored by others, due in part to the occurence of
such motifs in metal-binding proteins;14 furthermore,
polynuclear copper clusters bearing anionic sulfur lig-
ands have been observed to exhibit luminescence that is
susceptible to quenching by outer-sphere oxidants.15
In order to identify copper species that might be rele-
vant to the mechanism of photoinduced C–S cross-
couplings, an aliquot from the reaction of thiophenol
with 1-iodo-3,5-dimethylbenzene was analyzed by ESI–
MS after one hour of irradiation at 0 °C. Two prominent
negatively charged ion signals, corresponding to
[Cu(SPh)2]– and [Cu2(SPh)3]–, were observed.16
N
a
Yield of purified product (average of two experiments).
Scale of reaction: 1.0 mmol of each coupling partner.
For the sake of convenience, we routinely conduct the-
se photoinduced, copper-catalyzed cross-couplings of
thiols with aryl iodides at 0 °C. However, we have deter-
mined that a very good yield of the desired product could
also be obtained at –40 °C (eq 2). This observation
stands in contrast to other copper-catalyzed C–S cou-
plings, which are almost always carried out at ≥50
°C.6a,6b,7,8
Me
Me
10% CuI
hν (100-watt Hg lamp)
(2)
PhS
H
I
PhS
80%
1.0 equiv NaOt-Bu
–40 °C, CH3CN
12 h
Me
Me
1.0 equiv 1.0 equiv
By combining equimolar amounts of CuI, PhSH, and
NaOt-Bu in CH3CN, followed by filtration and the addi-
tion of excess 12-crown-4, we were able to obtain pale-
In copper-catalyzed cross-coupling reactions, aryl
bromides are often significantly less reactive than the
corresponding iodides.13 Nevertheless, we have deter-
mined that, under the same conditions that we employed
for aryl iodides, an array of bromides underwent pho-
toinduced, CuI-catalyzed cross-coupling with aryl thiols
(Table 4); not unexpectedly, the reaction times were
somewhat longer for bromides than for iodides (12–24
versus 5–8 hours). Hindered, electron-poor, and elec-
tron-rich aryl bromides reacted with thiophenol upon
irradiation at 0 °C. We are not aware of previous reports
of copper-catalyzed couplings of thiols with aryl bro-
mides that proceed below 60° C.
yellow crystals of
a
Cu(I)–thiolate complex,
[Cu5(SPh)7][Na(12-crown-4)2]2 (1). The X-ray crystal
structure revealed a distorted tetrahedral arrangement of
four Cu centers, with a fifth Cu inserted along one edge
(Figure 2a).17 All of the thiolates occupy bridging posi-
tions.
Solutions of copper complex 1 in CH3CN exhibited the
same two predominant ESI–MS signals ([Cu(SPh)2]– and
[Cu2(SPh)3]–) as observed under the catalytic reaction
conditions, suggestive of solution equilibria that lead to a
Cu(I)–thiolate speciation that differs from the solid-state
structure. Although solutions of complex 1 in CH3CN
were not visibly luminescent, an emissive state is acces-
sible upon excitation at short wavelengths in the visible
spectrum (excitation maximum at 418 nm; Figure 2b).
Consistent with these photophysical properties, no C–S
coupling was observed when a filter that blocked wave-
lengths less than 500 nm was applied to the light source
(Table 1, entry 6).
Furthermore, photoinduced coupling of a thiol with an
activated aryl chloride could be achieved at 0 °C (eq 3).
To the best of our knowledge, such electrophiles have not
been reported to participate in copper-catalyzed C–S
cross-couplings at a temperature below 60 °C.
see eq 1
PhS
H
Cl
CN
PhS
CN (3)
12 h
77%
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PhSH
+
D
D
SPh
SPh
1
2
3
4
H
I
H
see eq 1
5 h
(5)
O
O
O
D
4a
4b
2-d
1
:
1
5
6
7
8
9
Further support for a mechanism involving one-
electron reduction of the aryl halide, as opposed to con-
certed oxidative addition, was obtained from a competi-
tion experiment between 1-bromonaphthalene and 4-
chlorobenzonitrile. While selective activation of the
weaker C–Br has been viewed as supporting a concerted
mechanism for oxidative addition, the opposite selectivi-
ty is expected for an SET pathway, based on the relative
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outer-sphere reduction potentials (–2.03
V for 4-
Figure 2. (a) Representation of the solid-state structure of
[Cu5(SPh)7][Na(12-crown-4)2]2 (1). (b) Excitation spectrum
at 635 nm emission (dotted line) and emission spectrum at
418 nm excitation (solid line) for 1 in CH3CN at room tem-
perature.
chlorobenzonitrile and –2.17 V for 1-bromonaphthalene
vs. SCE in DMF).20
Under our conditions for photoinduced C–S coupling,
the ratio of products in this competition experiment was
2.6:1 in favor of activation of the C–Cl bond (eq 6), con-
sistent with the expectation for an SET mechanism.21 In
Under our standard C–S cross-coupling conditions,
copper complex 1 served as a competent pre-catalyst
(Table 1, entry 13). Furthermore, upon irradiation at 0
°C, it reacted directly with 1-iodo-3,5-dimethylbenzene
(7.0 equiv with respect to 1) to provide 2.5 equiv of the
coupled product.
a
previous report of a non-photoinduced, copper-
mediated C–S cross-coupling (DMSO, 110 °C), exclusive
reaction of 1-bromonaphthalene was observed in the
presence of 4-chlorobenzonitrile.7a
Br
The possible intermediacy of an aryl radical (R• in
Figure 1) in these photoinduced C–S couplings was as-
sessed with aid of an aryl iodide bearing a pendant olefin
(eq 4).7a,9a The radical generated by cleavage of the C–I
bond of compound 2 has been reported to rapidly cyclize
to the dihydrobenzofuran with a unimolecular rate con-
stant of 9.6 × 109 s–1 in DMSO.18 Whereas reaction of aryl
iodide 2 with PhSH in the dark at 60 °C for 72 hours fur-
nished only the uncyclized product (3) in low yield,19 the
photoinduced coupling provided cyclized product 4 with
high selectivity. The observation of cyclization under
photochemical conditions not only has mechanistic im-
plications, but it also underscores the potential of SET-
initiated reactions to access tandem processes that com-
plement non-photoinduced pathways.
SPh
5
6
19%
50%
1.0 equiv PhSH
see eq 1
5.0 equiv
+
(6)
+
10 h
SPh
Cl
NC
NC
5.0 equiv
CONCLUSION
We have described a mild and versatile photoinduced,
copper-catalyzed method for cross-coupling aryl thiols
with aryl halides. This study provides the first evidence
that the approach that we have recently reported for
photoinduced N-phenylation and N-alkylation of carba-
zoles is viable for other nucleophiles. Key features of the
present method include the use of a single set of reaction
conditions for the efficient coupling of a broad range of
aryl thiols with a wide array of functionalized aryl halides
(iodides and bromides), including hindered, electron-
poor, electron-rich, and heterocyclic partners, at 0 °C
with a 1:1:1 stoichiometry of thiol:halide:base. To the
best of our knowledge, copper-catalyzed C–S cross-
couplings at 0 °C have not previously been described; in
this respect, our observation that we can achieve a pho-
toinduced reaction of an unactivated aryl iodide at –40
°C is especially striking. A simple and inexpensive pre-
catalyst (CuI) is employed, and no ligand co-additive is
necessary. A series of mechanistic studies are consistent
with these photoinduced C–S couplings proceeding
through the proposed SET/radical pathway (via a Cu(I)–
thiolate), in contrast with previously reported non-
photoinduced reactions, wherein C–X bond cleavage is
generally believed to occur via concerted oxidative addi-
tion to copper. Ongoing studies are directed at develop-
SPh
PhSH
+
SPh
10% CuI
(4)
I
1.0 equiv NaOt-Bu
O
O
CH3CN
3
4
O
dark (60 °C, 72 h): 16%
0%
2
hν (100-watt Hg lamp; 0 °C, 5 h): 3%
57%
Aryl iodide 2-d, a monodeuterated variant of 2, react-
ed to form a 1:1 mixture of diastereomeric dihydrobenzo-
furans 4a and 4b (eq 5), as expected for the putative
radical intermediate generated upon addition of the aryl
radical to the pendant olefin. On the other hand, a path-
way involving only concerted oxidative addition, syn β-
migratory insertion, and then reductive elimination
would be expected to yield a single diastereomer (4a).9a
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Journal of the American Chemical Society
ing other photoinduced coupling reactions and elucidat-
ing the mechanism of these processes.
1
2
3
4
EXPERIMENTAL SECTION
Hartwig, J. F. Acc. Chem. Res. 2008, 41, 1534–1544. (d) Mura-
ta, M.; Buchwald, S. L. Tetrahedron 2004, 60, 7397–7403.
(7) For a recent discussion and leading references, see: (a)
Chen, C.; Weng, Z.; Hartwig, J. F. Organometallics 2012, 31,
8031–8037. (b) Kwong, F. Y.; Buchwald, S. L. Org. Lett. 2002,
4, 3517–3520.
(8) For exceptions, see: (a) Huang, Y.-B.; Yang, C.-T.; Yi, J.;
Deng, X.-J.; Liu, L. J. Org. Chem. 2011, 76, 800–810. In the
presence of 2 equiv of the aryl iodide, 20% CuI, 40% 1,10-
phenanthroline, and 1.5 equiv of a resin-bound Brønsted base,
seven diaryl sulfides were synthesized in 42–69% yield at room
temperature. (b) Xu, H.-J.; Liang, Y.-F.; Zhou, X.-F.; Feng, Y.-
S. Org. Biomol. Chem. 2012, 10, 2562–2568. In the presence of
1.5% CuI nanoparticles and 3 equiv of n-Bu4NOH, diphenyl
sulfide was synthesized in 51% yield at room temperature.
(9) (a) Creutz, S. E.; Lotito, K. J.; Fu, G. C.; Peters, J. C. Sci-
ence 2012, 338, 647–651. (b) Bissember, A. C.; Lundgren, R. J.;
Creutz, S. E.; Peters, J. C.; Fu, G. C. Angew. Chem. Int. Ed.
2013, 52, 5129–5133.
(10) Lotito, K. J.; Peters, J. C. Chem. Commun. 2010, 46,
3690–3692.
(11) Bunnett, J. F.; Creary, X. J. Org. Chem. 1974, 39, 3173–
3174.
(12) (a) On a gram-scale (1.40 g of product), the coupling il-
lustrated in entry 1 of Table 2 proceeded in 82% yield. (b) In
preliminary experiments under our standard conditions, a ke-
tone was compatible with the reaction conditions, but an ester
and an aldehyde were not.
Representative procedure: Under an atmosphere
of N2, a borosilicate glass tube was charged in turn with
CuI (0.10 mmol, 10%), NaOt-Bu (1.0 mmol, 1.0 equiv),
CH3CN (3.0 mL), the aryl halide (1.0 mmol, 1.0 equiv),
and the aryl thiol (1.0 mmol, 1.0 equiv). The tube was
sealed with a rubber septum, and then the heterogene-
ous reaction mixture was stirred at 0 °C, irradiating with
a 100-watt Hg lamp. After 5–24 h, the volatiles were re-
moved under reduced pressure. The residue was sus-
pended in Et2O, and the mixture was filtered through a
short plug of Celite. The filtrate was concentrated, and
the residue was purified by column chromatography.
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ASSOCIATED CONTENT
Experimental procedures and product characterization data.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
gcfu@caltech.edu; jpeters@caltech.edu
Notes
The authors declare no competing financial interest.
(13) For leading references, see: Beletskaya, I. P.; Cheprakov,
A. V. Organometallics 2012, 31, 7753–7808.
ACKNOWLEDGMENTS
(14) For example, see: (a) Beltramini, M.; Lerch, K. FEBS
Letters 1981, 127, 201–203. (b) Li, Y. J.; Weser, U. Inorg.
Chem. 1992, 31, 5526–5533. (c) Green, A. R.; Presta, A.;
Gasyna, Z.; Stillman, M. J. Inorg. Chem. 1994, 33, 4159–4168.
(15) For example, see: (a) Yam, V. W.-W.; Lo, K. K.-W.;
Wang, C.-R.; Cheung, K.-K. J. Phys. Chem. A 1997, 101, 4666–
4672. (b) Yam, V. W.-W.; Lam, C.-H.; Fung, W. K.-M.; Cheung,
K.-K. Inorg. Chem. 2001, 40, 3435–3442.
(16) [Cu(SPh)2]– has also been detected in ESI–MS studies of
the non-photoinduced, CuI/1,10-phenanthroline-catalyzed C–S
cross-coupling of thiophenol with iodobenzene (120 °C in tolu-
ene): Cheng, S.-W.; Tseng, M.-C.; Lii, K.-H.; Lee, C.-R.; Shyu,
S.-G. Chem. Commun. 2011, 47, 5599–5601.
This work was supported in part by the Gordon and Betty
Moore Foundation. Insightful discussions with Kenneth J.
Lotito, as well as assistance with X-ray crystallography from
Larry M. Henling, are gratefully acknowledged.
REFERENCES
(1) For leading references, see: (a) Metal-Catalyzed Cross-
Coupling Reactions; de Meijere, A., Diederich, F., Eds.; Wiley–
VCH: Weinheim, 2004. (b) Handbook of Organopalladium
Chemistry for Organic Synthesis; Negishi, E.-i., Ed.; Wiley–
Interscience: New York, 2002. (c) Cross-Coupling Reactions: A
Practical Guide, Topics in Current Chemistry Series 219;
Miyaura, N., Ed.; Springer, New York: 2002.
(2) (a) Catalyzed Carbon–Heteroatom Bond Formation;
Yudin, A. K., Ed.; Wiley–VCH: Weinheim, 2011. (b) Yin, J. In
Applications of Transition Metal Catalysis in Drug Discovery
and Development; Crawley, M. L., Trost, B. M., Eds.; John
Wiley and Sons: Hoboken, 2012; pp 97–163.
(3) (a) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2011, 2, 27–
50. (b) Hartwig, J. F.; Shekhar, S.; Shen, Q.; Barrios–Landeros,
F. In Chemistry of Anilines, Vol. 1; Rapaport, Z., Ed.; John
Wiley & Sons: New York, 2007; pp 455–536.
(4) SeroquelTM, NexiumTM, and SingulairTM are examples of
bioactive sulfides/sulfoxides.
(17) While the X-ray data were of sufficient quality to estab-
lish the connectivity of copper complex 1, the structure suffered
from a high degree of disorder in one of the thiolate ligands and
in the encapsulated sodium cations.
A directly analogous
[Cu5(SPh)7]2– complex has been structurally characterized with
Me4N+ counterions: Dance, I. G. J. Chem. Soc., Chem. Com-
mun. 1976, 103–104.
(18) Annunziata, A.; Galli, C.; Marinelli, M.; Pau, T. Eur. J.
Org. Chem. 2001, 1323–1329.
(19) Similarly, Hartwig has reported that the reaction of a
Cu(I)–thiolate with aryl iodide 2 in DMSO at 110 °C afforded
only acyclic products, suggesting that an aryl radical is not an
intermediate (ref. 7a).
(20) Enemaerke, R. J.; Christensen, T. B.; Jensen, H.; Daas-
bjerg, K. J. Chem. Soc., Perkin Trans. 2 2001, 1620–1630.
(21) In the case of a photoinduced C–N coupling of a Cu(I)–
carbazolide complex, the corresponding competition experi-
ment furnished 1.8:1 selectivity favoring reaction of 4-
chlorobenzonitrile in preference to 1-bromonaphthalene (ref.
9a).
(5) For leading references on aryl sulfides, see: Rakitin, O. A.
In Science of Synthesis; Georg Thieme Verlag: New York, 2007;
Vol. 31a, pp 975–1000.
(6) For reviews and examples, see: (a) Beletskaya, I. P.;
Ananikov, V. P. Chem. Rev. 2011, 111, 1596–1636. (b) Bichler,
P.; Love, J. A. Top. Organomet. Chem. 2010, 31, 39–64. (c)
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10% CuI
hν (100-watt Hg lamp)
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X = I, Br
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