Catalytic C-S, C-Se, and C-P cross-coupling reactions mediated by a Cu I/CuIII redox cycle

Article abstract of DOI:10.1021/om3006323

A well-defined macrocyclic aryl-Cu^III complex (1) readily reacts with a series of R-SH, Ar-SH, Ar-SeH, and (RO)₂(O)-PH (R = alkyl) nucleophiles to quantitatively afford the corresponding aryl alkyl thioethers, biaryl thioethers, biaryl selenide, and aryl dialkyl phosphonates, respectively. Competition experiments using bifunctional substrates revealed the important impact of lower pK_a values in order to discriminate between functional groups, although other influencing parameters such as steric effects have been identified. The catalytic version of these reactions is achieved using aryl bromide and aryl chloride model substrates, affording C-S, C-Se, and C-P coupling compounds in excellent to moderate yields. Low-temperature UV-vis and NMR monitoring of the reactions of complex 1 with a variety of nucleophiles support the formation of a ground-state 1-nucleophile adduct. A mechanistic proposal for reaction of 1 with S-nucleophiles involving key nucleophile deprotonation and aryl-nucleophile reductive elimination steps is finally described.

Full text of DOI:10.1021/om3006323

Article
pubs.acs.org/Organometallics
Catalytic C−S, C−Se, and C−P Cross-Coupling Reactions Mediated by
a CuI/CuIII Redox Cycle
Marc Font,† Teodor Parella,‡ Miquel Costas,† and Xavi Ribas*,†
†
́
QBIS Research Group, Departament de Quımica, Universitat de Girona, Campus Montilivi, Girona E-17071, Catalonia, Spain
‡Servei de RMN, Facultat de Cien
̀
cies, Universitat Autonoma de Barcelona, Campus UAB, Bellaterra E-08193, Catalonia, Spain
̀
S
* Supporting Information
ABSTRACT: A well-defined macrocyclic aryl-CuIII complex (1) readily
reacts with a series of R−SH, Ar−SH, Ar−SeH, and (RO)2(O)−PH (R =
alkyl) nucleophiles to quantitatively afford the corresponding aryl alkyl
thioethers, biaryl thioethers, biaryl selenide, and aryl dialkyl phosphonates,
respectively. Competition experiments using bifunctional substrates revealed
the important impact of lower pKa values in order to discriminate between
functional groups, although other influencing parameters such as steric
effects have been identified. The catalytic version of these reactions is
achieved using aryl bromide and aryl chloride model substrates, affording C−
S, C−Se, and C−P coupling compounds in excellent to moderate yields.
Low-temperature UV−vis and NMR monitoring of the reactions of complex 1 with a variety of nucleophiles support the
formation of a ground-state 1−nucleophile adduct. A mechanistic proposal for reaction of 1 with S-nucleophiles involving key
nucleophile deprotonation and aryl-nucleophile reductive elimination steps is finally described.
oxidative addition/reductive elimination process involving a
CuI/CuIII redox catalytic cycle (Scheme 1).24,25 Furthermore,
INTRODUCTION
■
Copper-catalyzed cross-coupling reactions for the formation of
aryl−heteroatom bonds is currently a hot topic, due to the
importance of developing new sustainable synthetic tools for
these transformations and finding new methodologies beyond
those based on palladium.1,2 For the past 10 years many
copper-mediated or -catalyzed procedures have been developed
for Caryl−N and Caryl−O bond formation, usually starting from
aryl halide substrates,3−5 although direct arene C−H
functionalization methodologies have been acquiring more
relevance in the recent years.6−9 Less abundant is the number
Scheme 1. Relevant Mechanistic Proposals for Copper-
Catalyzed Cross-Coupling (Ullmann-Type) Reactions
2
2
of publications devoted to copper-catalyzed Csp −S and Csp −
Se bond formation for the synthesis of biaryl thioether, aryl
alkyl thioether, alkenyl thioether, and alkenyl selenoether
subunits,1,2,10−12 important in pharmaceutical scaffolds, and a
few examples of Caryl−Se or Caryl−P bond formation13−18 and
Calkenyl−S,19,20 Calkenyl−Se,21 or Calkenyl−P22 bond formation
have been reported. The vast majority of copper-based cross-
coupling methodologies rely on the optimization of the
experimental conditions upon the selection of a given auxiliary
ligand. Importantly, a clear understanding of the mechanistic
details of these transformations could help in the rational
design of new methodologies for copper-catalyzed C−
heteroatom bond forming reactions.23−27 However, the use of
insoluble bases and the highly concentrated reaction mixtures
usually preclude mechanistic studies such as spectroscopic
monitoring; thus, several proposals have been made mostly on
the basis of a small amount of experimental evidence and
extensive computational studies. The most often invoked
mechanistic pathways are (a) radical-based single-electron
transfer (SET) involving a CuI/CuII redox pair and (b) an
conclusions based on computational studies have to be
interpreted carefully, because conflicting results have been
reported depending on the DFT functional or basis set
employed.24,25 A very limited number of publications have also
dealt with mass spectrometry monitoring under catalytic
conditions and some information has been extracted, although
the aryl halide activation step remains obscure.28 Therefore, it is
imperative to develop new systems from which an experimental
mechanistic understanding could be extracted. Recently we
have reported a family of well-defined aryl−CuIII−halide
species that proved competent in Caryl−N,29,30 Caryl−O,31,32
Special Issue: Copper Organometallic Chemistry
Received: July 6, 2012
© XXXX American Chemical Society
A
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 2. Copper-Catalyzed C−N Cross-Coupling Reaction Using Model Aryl Halide Substrates, with the Direct Spectroscopic
Observation of Aryl−CuIII−Br Intermediate Species
Scheme 3. Reaction of Aryl−CuIII Complex 1 with Sulfur and Selenium Nucleophiles Resulting in C−S and C−Se Reductive
Elimination Products
and Caryl−halide33 bond forming reactions. The isolated aryl−
CuIII species react at room temperature with amides, phenols,
and carboxylic acids to undergo reductive elimination, affording
the corresponding cross-coupling products and CuI. Impor-
tantly, aryl halide model substrates and catalytic amounts of CuI
in the presence of a given nitrogen or oxygen nucleophile
engage in a catalytic reaction to quantitatively produce the
cross-coupling product with the intermediacy of aryl−CuIII−X
species (Scheme 2), which is formed by aryl halide oxidative
addition at CuI.29 Important mechanistic information has been
gained with the latter systems, since those constitute the first
unequivocal experimental evidence of the CuI/CuIII catalytic
cycle in Ullmann-type reactions,29,31 in which the oxidative
addition occurs rapidly and the halide to nucleophile exchange
or the reductive elimination is rate-limiting.
In the present work we expand the study of the reactivity of
the well-defined macrocyclic aryl−CuIII species with S, Se, and
P nucleophiles, and experimental proof is given for the catalytic
version of these transformations with the intermediacy of aryl−
CuIII−X species. Aromatic and aliphatic thiols, benzeneselenol,
and H-phosphonate diesters are the nucleophiles used, and the
pKa dependence of the nucleophile reactivity is discussed in
detail.
Reactivity of Thiophenols and Alkanethiols in C−S
Bond Formation Reactions. The aryl−CuIII complex 1 reacts
smoothly with HS nucleophiles in acetonitrile at room
temperature to form quantitatively the corresponding C−S
reductive elimination product (Scheme 3). Since both reactants
and products are diamagnetic species, containing either low-
spin CuIII or CuI metal ions, the reaction can be directly
monitored by 1H NMR spectroscopy. Reaction occurs easily at
room temperature using aromatic and aliphatic thiols (Table 1).
The reaction of complex 1 with thiophenols at room
temperature is significantly faster (<10 min) than that with
aliphatic thiols (1.5−3 h to reach completion, as determined by
NMR monitoring) to yield the corresponding diaryl thioethers
and aryl alkyl thioethers, respectively, suggesting that the
reaction rate is pKa dependent (Table 1).31,35 It is worth
pointing out that 1-butanethiol takes about 1.5 h to reach
completion, whereas 2-methyl-2-propanethiol requires about 3
h despite the similar pKa values, indicating that steric effects
also influence the reaction rate (see mechanistic discussion
below). Kinetic studies for the reaction of complex 1 with thiol
nucleophiles were precluded due to the abundant precipitation
of CuI−sulfide compounds upon reaction of the excess thiol
with the CuI formed during the course of the reaction.36,37
Reactivity of Benzeneselenol in C−Se Bond Forming
Reactions. Complex 1 reacts with benzeneselenol in
acetonitrile at room temperature to afford the C−Se coupling
product quantitatively (Scheme 3). The reaction proceeds very
rapidly (approximately 1 min), and 1.5 equiv of benzeneselenol
is needed to displace the reaction to the complete formation of
the biaryl selenide product (Table 1, entry 8). The coupling
product has been characterized by NMR spectroscopy,
including the experimental evidence on the formation of the
C−Se bond by observing a new 77Se NMR signal at −150.7
RESULTS AND DISCUSSION
■
We selected the well-defined aryl−CuIII complex 1 as the
starting point, to test its ability to react with different sulfur,
selenium, and phosphorus nucleophiles and to afford the
corresponding Caryl−heteroatom coupled products.8,34 We
followed a general procedure that consists of mixing complex
1 and the nucleophile (0.9−1.5 equiv) in deuterated
acetonitrile under mild temperatures (25−50 °C) and
1
monitoring the reaction by H NMR spectroscopy.
B
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Table 1. Caryl−S and Caryl−Se Coupling Product Yields from
Table 2. Reaction of Aryl−CuIII Complex 1 with H-
the Reaction of 1 with Thiophenols, Aliphatic Thiols, and
phosphonate Diesters To Yield the Corresponding C−P
a
a
Benzeneselenol
Coupling Product
a
General conditions: [1] = 12 mM, [HS-Nuc] = 11−24 mM, CD3CN.
b
1
Calculated by H NMR spectroscopy using 1,3,5-trimethoxybenzene
c
as internal standard. With respect to limiting nucleophile.
observed but the formed product does not undergo the
aforementioned decomposition pathway.
Competition Experiments Using Bifunctional Sub-
strates. Given the excellent yields obtained for the cross-
coupling reactions with the S, Se, and P nucleophiles tested, we
decided to undertake competition experiments to evaluate the
reactivity of 1 with substrates bearing two distinct nucleophile
moieties capable of undergoing cross-coupling (Scheme 5), and
in particular we selected bifunctional substrates combining (a)
aromatic thiol and alcohol groups (Table 3, entry 1), (b)
aromatic carboxylic acid and thiol groups (Table 3, entry 2),
and (c) aliphatic carboxylic acid and thiol groups (Table 3,
entries 3 and 4).
a
General conditions: [1] = 12 mM, [HS-R] = 12.5 mM, CD3CN in
b
1
0.7 mL of CD3CN at 25 °C. Calculated by H NMR spectroscopy
using 1,3,5-trimethoxybenzene as internal standard. pKa(DMSO)
c
value for 4-bromothiophenol (the 4-chlorothiophenol pKa value is not
tabulated; a value close to that of the 4-bromo species is expected).35
d
Conditions: [1] = 12 mM, [HSe-Ph] = 18 mM, reaction time <1 min.
ppm in the 1H−77Se HMBC spectrum,38 taking benzeneselenol
itself (0 ppm) as the reference.39
The aryl−CuIII complex 1 reacts readily with 4-mercapto-
phenol to yield quantitative cross-coupling with the thiol
moiety (Table 3, entry 1); thus, no reactivity is observed with
the alcohol moiety. In this substrate, the disparate pKa(DMSO)
values (18.0 for phenol and 10.3 for thiophenol) are presumed
to be the most important parameter favoring reactivity toward
the most acidic thiol moiety. On the other hand, reaction with
4-mercaptobenzoic acid affords the C−S coupling product in a
low 45% yield (Table 3, entry 2). The other approximately 50%
of product corresponds to the C−O coupling, which
precipitates out of the solution due to the formation of
insoluble Cu−sulfide species (see IR characterization in the
Supporting Information). In this case, the very similar
pKa(DMSO) values (11.0 for benzoic acid and 10.3 for
thiophenol) allow for a competitive reactivity, affording almost
equimolar amounts of C−S and C−O coupling products.
Finally, we compared the reactivity between aliphatic carboxylic
acid or thiol moieties in the same molecule, and we selected 3-
mercaptopropanoic acid and 11-mercaptoundecanoic acid as
bifunctional nucleophiles (Table 3, entries 3 and 4,
respectively). These competition experiments show that 3-
mercaptopropanoic acid affords better yields (75% in C−S
coupling product) than 11-mercaptoundecanoic acid (51% of
Reactivity of H-phosphonate Diesters in C−P Bond
Forming Reactions. To further investigate the scope of
reactions in which CuI/CuIII redox cycles could be implicated,
we turned our attention to copper-catalyzed C−P bond
forming reactions. The combination of aryl−CuIII complex 1
with H-phosphonate diesters in acetonitrile at 50 °C afforded
the corresponding aryl dialkyl phosphonate products in
moderate to excellent yields (Scheme 4 and Table 2).
Reaction with H-phosphonate dimethyl ester (Table 2, entry
1) is complete after 1.5 h, affording excellent yields of the
corresponding aryl−P coupling product. Similarly, the coupling
product from the reaction of 1 and H-phosphonate dibenzyl
ester is formed quantitatively after 2 h (Table 2, entry 3).
However, in both cases, partial dealkylation and phosphite−
oxide alkylation of the nucleophile occurs (see the Supporting
Information). This phenomenon has been already reported in
the literature,16 and a much faster decomposition of the
nucleophile itself under the reaction conditions is found in the
case of H-phosphonate dibenzyl ester. On the other hand, a
48% yield of the coupling product was obtained when H-
phosphonate dibutyl ester was used as nucleophile (Table 2,
entry 2). In this case, a lower reactivity of the nucleophile is
Scheme 4. Reaction of Aryl−CuIII Complex 1 with Selenium and Phosphorus Nucleophiles Resulting in C−Se or C−P Bond
Coupling
C
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 5. Reaction of Aryl−CuIII Complex 1 with Thiols in Presence of Other Functional Groups
In the case of the catalytic insertion of 4-chlorothiophenol,
the loading of the CuI source was lowered to 0.5 mol %, still
with quantitative yields. Furthermore, when the aryl chloride
substrate L1-Cl was used, an 85% yield of the C−S coupling
product could be obtained with 1 mol % of CuI. On the other
hand, catalysis employing Se nucleophiles and P nucleophiles
proved to be more challenging. It was necessary to increase the
amount of benzeneselenol to 2 equiv to afford the
corresponding diaryl selenide product in 72% yield. For H-
phosphonate dimethyl ester the desired coupling was achieved
in 46% yield upon heating to 50 °C and employing up to 2
equiv of substrate. In all cases slow addition of the substrate
proved to increase the yields of the catalytic reaction either by
preventing the precipitation of the CuI salt with thiolates and
selenolates or by minimizing the dimethyl phosphite
decomposition. As expected, when these reactions were
monitored by UV−visible spectroscopy, the oxidative addition
product aryl−CuIII−Br (2Br) was observed as a steady-state
intermediate (see the Supporting Information for details).29
Mechanistic Insights: Identification of aryl−CuIII···HS−
R Adducts. The detailed mechanism of the interaction of 1
with the HX−Nuc (X = S, Se, P) nucleophiles is still not
completely understood, although a clear parallelism can be
made with the reactivity of 1 with carboxylic acids and
phenols.31 In this regard, we investigated the possibility of
trapping adduct species between 1 and the R−SH nucleophile,
as was previously observed for carboxylic acids and the most
acidic phenol derivatives.31 To test this hypothesis, low-
temperature UV−visible studies were conducted using
substoichiometric amounts of the nucleophile to prevent
precipitation of copper(I)−sulfide species. When the reaction
of complex 1 with 1-butanethiol (nBu-SH), 4-methoxythiophe-
nol, and benzeneselenol was monitored, clear changes in the
UV−vis spectra were observed (see Figure 1). The
Table 3. Aryl-S-Nuc Product Yields from the Reaction of 1
with Bifunctional Substrates
a
a
General conditions: [1] = 12 mM, [HS-Nuc] = 12.5 mM, CD3CN in
b
0.7 mL CD3CN at room temperature. Calculated by 1H NMR
c
spectroscopy using 1,3,5-trimethoxybenzene as internal standard. 6%
of intramolecular C−N reductive elimination product.33
C−S coupling), despite the similarity of pKa(DMSO) values for
the SH and OH moieties, respectively (17 for 1-butanethiol and
12.6 for acetic acid). This noticeable difference in yields
indicates that at least one additional, as yet unidentified factor
in addition to the pKa is also contributing to the reaction. A
possible explanation might consist of the fact that the shorter
chain spacer between functional groups allows the nucleophile
to interact in a proper way through both the carboxylic acid and
the thiol moieties of the molecule, leaving the molecule
oriented to favor the C−S coupling. In contrast, when the alkyl
chain is larger (11-mercaptoundecanoic acid, Table 3, entry 4),
the yield remains at 50%.
Catalytic C−S, C−Se, and C−P Bond Formation
Involving an Aryl−CuIII Complex. The catalytic coupling
of thiophenols, alkanethiols, selenols, and dialkyl phosphites
was achieved by using the model aryl bromide L1-Br substrate
in the presence of catalytic amounts of CuI salt (Scheme 6). A
1.1 equiv amount of both 4-chlorothiophenol and 1-butanethiol
undergo quantitative catalytic cross-coupling with the aryl
bromide L1-Br to afford the corresponding diaryl thioether and
aryl alkyl thioether products in the presence of 10 mol % of
[CuI(CH3CN)4](CF3SO3) at room temperature under a
nitrogen atmosphere.
1
corresponding H NMR monitoring for the reactions with 1-
butanethiol and 4-methoxythiophenol revealed the formation of
transient species that we assign to an adduct between 1 and the
thiol nucleophile (see Figures S51−S53 in the Supporting
Information). Signals that appears within the first 5 min of
reaction are assigned to the adduct species, which show a clear
Scheme 6. Catalytic C−S, C−Se, and C−P Cross-Coupling Reactions
D
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
With all the data presented, a plausible mechanistic proposal
for the reactivity of aryl−CuIII species 1 with thiols and selenols
is disclosed in Scheme 7. First, the formation of the adduct
Scheme 7. Plausible Mechanism for the C−S Cross-Coupling
between 1 and R-SH Nucleophiles
species A, i.e. 1···HS−R, is proposed to occur, in clear similarity
to the reactivity with carboxylic acids.31 The following step is
the rate-limiting deprotonation of the nucleophile by one of the
amines in the complex (possibly a lateral secondary amine),30
and finally Caryl−heteroatom reductive elimination occurs to
yield the corresponding coupled product and CuI. On the other
hand, we cannot rule out the participation of an external base
assisting the deprotonation of the nucleophile, as was reported
for the carboxylic acid mechanistic proposal.31 Indeed, R−SeH
and (RO)2(O)−PH nucleophiles are thought to react by a
similar mechanistic pathway. More mechanistic insights would
be reached if kinetic studies were possible, but the unavoidable
precipitation of noncharacterized [CuI−S−R]n species, possibly
of oligomeric nature, poses a very challenging problem.
Nevertheless, the catalytic versions of the C−S, C−Se, and
C−P couplings reported herein proceed by an initial L1-Br
oxidative addition at CuI to afford the aryl−CuIII−Br
intermediate species, followed by exchange of the axially
coordinated halide by the corresponding nucleophile,33 thus
following the proposal in Scheme 7 at this stage.
Figure 1. Low-temperature UV−vis monitoring of the reaction of 1
with (a) 1-butanethiol, (b) benzeneselenol, and (c) 4-methoxythio-
phenol ,showing the formation of an adduct species. Conditions: [1] =
0.8 mM, [Nuc] = 0.72 mM, CH3CN, 0 °C, except for the reaction of
4-methoxythiophenol, which was performed at −35 °C.
shift upon reaching product formation at the end of the
reaction. Especially distinctive are the aromatic and benzylic
signals of the adduct species in comparison to the same signals
of the starting complex 1 and of the final coupled C−S product.
Therefore, minor but evident changes in the UV−vis (Figure
1) could be correlated with new signals in the 1H NMR
(Figures S51−S53 in the Supporting Information) correspond-
ing to what we propose to be the 1·R−SH adduct. The exact
nature of the 1·R−SH adduct is unclear, but the minor changes
in the electronic spectra seem to exclude the direct
coordination of the deprotonated nucleophile (thiolate), since
strong thiolate to metal charge transfer bands would be
expected. On the other hand, when the sterically more
demanding 2-methyl-2-propanethiol is used as nucleophile,
the reaction proceeds without the formation of any
intermediate species even at low temperature.
Since adduct formation could be experimentally observed for
4-methoxythiophenol and 1-butanethiol despite their different
pKa(DMSO) values (11.2 and 17.0, respectively) but it is not
observed for 2-methyl-2-propanethiol (pKa(DMSO) = 17.9),
we conclude that in the latter case the steric constraints should
destabilize a proper interaction, precluding formation of the
adduct species.
CONCLUSIONS
■
We have presented for the first time conclusive evidence of the
competence of well-defined aryl−CuIII species in cross-coupling
reactions to form new C−S, C−Se, and C−P bonds.
Stoichiometric experiments with the aromatic and aliphatic
thiol, selenol, and phosphite nucleophiles afforded the
quantitative formation of the corresponding C−heteroatom
coupling products. Monitoring experiments by UV−vis and
NMR along with competitive experiments with bifunctional
nucleophiles indicate that the pKa parameter is a key issue but is
not the only parameter that should be be taken into account.
The catalytic version of the reaction has been performed with
R−SH, R−SeH, and (RO)2(O)−PH nucleophiles in excellent
to good yields, and remarkably low catalyst loadings (0.5 mol
%) are achieved for 4-chlorothiophenol with the model
substrate L1-Br. The mechanistic proposal is in line with our
E
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
NMR of the crude reaction mixtures relative to 1,3,5-trimethox-
ybenzene.
previous proposal when carboxylic acids and phenols are used
as nucleophiles. Therefore, this work demonstrates the viability
of the CuI/CuIII redox cycle for C−S, C−Se, and C−P cross-
coupling reactivity in model aryl halide substrates, thus opening
the door to future developments of C−heteroatom bond
forming reactions catalyzed by copper.
General Procedure for Monitoring Kinetics by UV−Vis
Spectroscopy. A UV−visible cuvette equipped with a Teflon
stopcock was dried in an oven and cooled under vacuum. Stock
solutions of the nitrogen nucleophile (21.6 mM) and the aryl−CuIII
complex 1 (4.8 mM) were prepared in dry CH3CN (2 mL). After the
cuvette was back-filled with dry N2, 0.5 mL of the nucleophile stock
solution was added via syringe, and it was diluted with CH3CN to a
total volume of 2.9 mL. The cuvette was inserted into the
spectrophotometer, and the temperature was allowed to equilibrate.
The reaction was initiated by adding the aryl−CuIII stock solution (0.1
mL) to the cuvette followed by rapid mixing of the combined
solutions. Final concentrations: [1] = 0.8 mM, [Nuc] = 0.72 mM.
General Procedure for Monitoring Kinetics by NMR Spec-
troscopy. In an inert-atmosphere glovebox, a stock solution of the
aryl−CuIII complex 1 (7 mM) was prepared in CD3CN (2 mL). A
stock solution of the corresponding nucleophile (50.4 mM) in CD3CN
(1 mL) was prepared. Pulse widths and relaxation times were
determined by using standard methods. To acquire the kinetic data,
0.4 mL of the complex 1 stock solution was added to a NMR tube,
diluted with 0.25 mL of CD3CN, and sealed with a septum. The
sample was placed in the NMR probe and cooled to the corresponding
temperature. The reaction was initiated by addition of 50 μL of the
nucleophile stock solution to the NMR tube via syringe. The solution
was mixed rapidly, and the tube was inserted into the probe to begin
data acquisition. Final concentrations: [1] = 4 mM, [Nuc] = 3.6 mM.
EXPERIMENTAL SECTION
■
Synthesis and Characterization of Aryl Thioethers and
Diaryl Selenide. In an inert-atmosphere glovebox, a sample of the
CuIII−aryl complex 1 (21.4 mg, 42 μmol) was dissolved in CD3CN
(1.6 mL) and 0.4 mL of a solution of 1,3,5-trimethoxybenzene was
added as an internal standard. A portion of this solution (0.4 mL) was
loaded into an NMR tube, and 1.1−1.5 equiv of the corresponding
nucleophile was added to the tube (0.3 mL, 29.2−42 mM). Final
concentrations: [1] = 12 mM and [HNuc] = 12.5−18 mM. The tube
was sealed with a screw cap, and the reaction was allowed to proceed
1
at room temperature and monitored by H NMR spectroscopy until
1
1
1
completion. H, 13C, COSY, NOESY, H−13C HSQC, and H−77Se
HMBC NMR spectra and mass spectrometric analysis were obtained
without isolation of the C nucleophile coupling product. Reaction
1
yields were obtained by integration of the H NMR spectra of the
crude reaction mixtures relative to internal standard.
Synthesis and Characterization of Aryl Dialkyl Phospho-
nates. In an inert-atmosphere glovebox, a sample of the CuIII−aryl
complex 1 (21.4 mg, 42 μmol) was dissolved in CD3CN (1.6 mL) and
0.4 mL of a solution of 1,3,5-trimethoxybenzene was added as an
internal standard. A portion of this solution (0.4 mL), 0.25 mL of
CD3CN, and 0.9−2 equiv of the corresponding dialkyl phosphite
nucleophile were added to the tube (0.05 mL, 0.48−0.34 M). Final
concentrations: [1] = 12 mM and [dialkyl phosphite] = 10.8−24 mM.
The tube was sealed with a screw cap, and the reaction was allowed to
proceed at 50 °C and monitored by 1H NMR spectroscopy until
ASSOCIATED CONTENT
■
S
* Supporting Information
Text and figures giving details of the syntheses and character-
ization data. This material is available free of charge via the
Internet at http://pubs.acs.org.
1
1
completion. 31P, H, COSY, NOESY, H−13C HSQC, and 13C NMR
spectra and mass spectrometric analysis were obtained without
isolation of the C−P coupling product. Reaction yields were obtained
AUTHOR INFORMATION
■
Notes
1
The authors declare no competing financial interest.
by integration of the H NMR spectra of the crude reaction mixtures
relative to internal standard.
Synthesis and Characterization of Products with Bifunc-
tional Groups. In an inert-atmosphere glovebox, a sample of the
CuIII−aryl complex 1 (21.4 mg, 42 μmol) was dissolved in CD3CN
(1.6 mL) and 0.4 mL of a solution of 1,3,5-trimethoxybenzene was
added as an internal standard. A portion of this solution (0.4 mL), 0.25
mL of CD3CN, and 1.1 equiv of the corresponding bifunctional
nucleophile were added to the tube (0.3 mL, 0.48−0.34 M). Final
concentrations: [1] = 12 mM and [Nuc] = 13.2 mM. The tube was
sealed with a screw cap, and the reaction was allowed to proceed at
room temperature and monitored by 1H NMR spectroscopy until
ACKNOWLEDGMENTS
■
We thank Dr. A. Casitas for fruitful discussions. We
acknowledge financial support from the European Research
Council for Project ERC-2011-StG-277801 to X.R., MICINN
of Spain (CTQ2009-08464/BQU to M.C., CTQ2009-08328 to
T.P., and Ph.D. FPI grant to M.F.), Consolider-Ingenio
CSD2010-00065, and the Catalan DIUE of the Generalitat de
Catalunya (2009SGR637). X.R. and M.C. acknowledge
̀
ICREA-Academia awards. We thank STR’s from UdG for
technical support.
1
1
1
reaction completion. H, COSY, NOESY, H−13C HSQC, H−13C
HMBC, and 13C NMR spectra and mass spectrometric analysis were
obtained without isolation of the C−S coupling product. Reaction
1
REFERENCES
yields were obtained by integration of the H NMR spectra of the
■
crude reaction mixtures relative to 1,3,5-trimethoxybenzene.
(1) Beletskaya, I. P.; Cheprakov, A. V. Coord. Chem. Rev. 2004, 248,
2337−2364.
General Procedure for Catalytic Experiments. In an inert-
atmosphere glovebox, a vial was loaded with 0.5 mL of a 30 mM
solution of ligand L1-X (X = Cl, Br) in CH3CN and 0.5−10 mol % of
[CuI(CH3CN)4](CF3SO3) was added (0.2 mL of a 0.75−7.5 mM
stock solution in CH3CN). The colorless solution became slightly red,
indicating that oxidative addition took place, giving the corresponding
aryl−CuIII−X (2X; X = Cl, Br). Then 2.3 mL of a 7.15−13 mM
solution of HS nucleophile in CH3CN was added dropwise. Final
concentrations: [L1-X] = 5 mM, [Cu] = 0.05−0.5 mM, and [HY-
nucleophile] = 5.5−10 mM. After 24 h of stirring the crude mixture,
either at room temperature (for Y = S (thiols) and Se
(benzeneselenol)) or at 50 °C (for Y = P (phosphites)), 150 μL of
3 mM trimethoxybenzene in CH3CN as internal standard was added
and the solvent was removed. The sample was redissolved in 0.5 mL of
(2) Ley, S. V.; Thomas, A. W. Angew. Chem., Int. Ed. 2003, 42, 5400−
5449.
(3) Surry, D. S.; Buchwald, S. L. Chem. Sci. 2010, 1, 13−31.
(4) Monnier, F.; Taillefer, M. Angew. Chem., Int. Ed. 2009, 48, 6954−
6971.
(5) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev. 2008, 108,
3054−3131.
(6) Campbell, A. N.; Stahl, S. S. Acc. Chem. Res. 2012, 45, 851−863.
(7) Hickman, A. J.; Sanford, M. S. Nature 2012, 484, 177−185.
́
(8) Ribas, X.; Calle, C.; Poater, A.; Casitas, A.; Gomez, L.; Xifra, R.;
Parella, T.; Benet-Buchholz, J.; Schweiger, A.; Mitrikas, G.; Sola, M.;
̀
Llobet, A.; Stack, T. D. P. J. Am. Chem. Soc. 2010, 132, 12299−12306.
(9) King, A. E.; Huffman, L. M.; Casitas, A.; Costas, M.; Ribas, X.;
Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 12068−12073.
1
CD3CN, and NMR yields were obtained by integration of the H
F
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(10) Kabir, M. S.; Lorenz, M.; Van Linn, M. L.; Namjoshi, O. A.; Ara,
S.; Cook, J. M. J. Org. Chem. 2010, 75, 3626−3643.
(11) Sperotto, E.; van Klink, G. P. M.; de Vries, J. G.; van Koten, G. J.
Org. Chem. 2008, 73, 5625−5628.
(12) Akkilagunta, V. K.; Kakulapati, R. R. J. Org. Chem. 2011, 76,
6819−6824.
(13) Xu, R.; Wan, J.-P.; Mao, H.; Pan, Y. J. Am. Chem. Soc. 2010, 132,
15531−15533.
(14) Gelman, D.; Jiang, L.; Buchwald, S. L. Org. Lett. 2003, 5, 2315−
2318.
(15) Sperotto, E.; van Klink, G. P. M.; de Vries, J. G.; van Koten, G.
Tetrahedron 2010, 66, 9009−9020.
(16) Zhuang, R.; Xu, J.; Cai, Z.; Tang, G.; Fang, M.; Zhao, Y. Org.
Lett. 2011, 13, 2110−2113.
(17) Gujadhur, R. K.; Venkataraman, D. Tetrahedron Lett. 2003, 44,
81−84.
(18) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596−
1636.
(19) Kao, H.-L.; Lee, C.-F. Org. Lett. 2011, 13, 5204−5207.
(20) Bates, C. G.; Saejueng, P.; Doherty, M. Q.; Venkataraman, D.
Org. Lett. 2004, 6, 5005−5008.
(21) Knapton, D. J.; Meyer, T. Y. J. Org. Chem. 2005, 70, 785−796.
(22) Pirat, J.-L.; Monbrun, J.; Virieux, D.; Cristau, H.-J. Tetrahedron
2005, 61, 7029−7036.
(23) Sperotto, E.; van Klink, G. P. M.; van Koten, G.; de Vries, J. G.
Dalton Trans. 2010, 39, 10338−10351.
(24) Jones, G. O.; Liu, P.; Houk, K. N.; Buchwald, S. L. J. Am. Chem.
Soc. 2010, 132, 6205−6213.
(25) Yu, H.-Z.; Jiang, Y.-Y.; Fu, Y.; Liu, L. J. Am. Chem. Soc. 2010,
132, 18078−18091.
(26) Giri, R.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132, 15860−
15863.
(27) Tye, J. W.; Weng, Z.; Johns, A. M.; Incarvito, C. D.; Hartwig, J.
F. J. Am. Chem. Soc. 2008, 130, 9971−9983.
(28) Cheng, S.-W.; Tseng, M.-C.; Lii, K.-H.; Lee, C.-R.; Shyu, S.-G.
Chem. Commun. 2011, 47, 5599−5601.
(29) Casitas, A.; King, A. E.; Parella, T.; Costas, M.; Stahl, S. S.;
Ribas, X. Chem. Sci. 2010, 1, 326−330.
̀
(30) Casitas, A.; Poater, A.; Sola, M.; Stahl, S. S.; Costas, M.; Ribas,
X. Dalton Trans. 2010, 39, 10458−10463.
(31) Huffman, L. M.; Casitas, A.; Font, M.; Canta, M.; Costas, M.;
Ribas, X.; Stahl, S. S. Chem. Eur. J. 2011, 17, 10643−10650.
(32) Casitas, A.; Ioannidis, N.; Mitrikas, G.; Costas, M.; Ribas, X.
Dalton Trans. 2011, 40, 8796−8799.
(33) Casitas, A.; Canta, M.; Sola,
Chem. Soc. 2011, 133, 19386−19392.
(34) Ribas, X.; Jackson, D. A.; Donnadieu, B.; Mahía, J.; Parella, T.;
Xifra, R.; Hedman, B.; Hodgson, K. O.; Llobet, A.; Stack, T. D. P.
Angew. Chem., Int. Ed. 2002, 41, 2991−2994.
̀
M.; Costas, M.; Ribas, X. J. Am.
(35) Bordwell, F. G. Acc. Chem. Res. 1988, 21, 456−463.
(36) Nguyen, L. M.; Dellinger, M. E.; Lee, J. T.; Quinlan, R. A.;
Rheingold, A. L.; Pike, R. D. Inorg. Chim. Acta 2005, 358, 1331−1336.
(37) Xu, H.; Yip, J. H. K. Inorg. Chem. 2003, 42, 4492−4494.
(38) Berger, S.; Facke, T.; Wagner, R. Magn. Reson. Chem. 1996, 34,
̈
4−13.
(39) Schroeder, T. B.; Job, C.; Brown, M. F.; Glass, R. S. Magn.
Reson. Chem. 1995, 33, 191−195.
G
dx.doi.org/10.1021/om3006323 | Organometallics XXXX, XXX, XXX−XXX