Design of highly selective alkyne hydrothiolation RhI-NHC catalysts: Carbonyl-triggered nonoxidative mechanism

Article abstract of DOI:10.1021/acs.organomet.7b00251

New Rh^I-IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-carbene) complexes bearing an N,O-pyridine-2-methanolato (N-O) bidentate ligand have been prepared. The carbonyl complex Rh(N-O)(IPr)(CO) efficiently catalyzes the hydrothiolation of

Full text of DOI:10.1021/acs.organomet.7b00251

Article
pubs.acs.org/Organometallics
Design of Highly Selective Alkyne Hydrothiolation RhI‑NHC Catalysts:
Carbonyl-Triggered Nonoxidative Mechanism
Laura Palacios,† Yoann Meheut,† María Galiana-Cameo,† María Jose Artigas,† Andrea Di Giuseppe,†
́
Fernando J. Lahoz,† Victor Polo,‡ Ricardo Castarlenas,*,† Jesus J. Perez-Torrente,† and Luis A. Oro†,§
́
́
†Departamento de Química Inorgan
C/Pedro Cerbuna 12, 50009 Zaragoza, Spain
́
ica-Instituto de Síntesis Química y Catal
́
isis Homogen
́
ea-ISQCH, Universidad de Zaragoza-CSIC,
‡Departamento de Química Física, Universidad de Zaragoza, C/Pedro Cerbuna 12, 50009 Zaragoza, Spain
§Center of Research Excellence in Petroleum Refining and Petrochemicals, King Fahd University of Petroleum and Minerals, 31261
Dhahran, Saudi Arabia
S
* Supporting Information
ABSTRACT: New RhI-IPr (IPr = 1,3-bis(2,6-diisopropylphenyl)imidazolin-
2-carbene) complexes bearing an N,O-pyridine-2-methanolato (N-O)
bidentate ligand have been prepared. The carbonyl complex Rh(N-
O)(IPr)(CO) efficiently catalyzes the hydrothiolation of a range of alkynes
with high selectivity to α-vinyl sulfides. Reactivity studies and DFT
calculations have revealed a new nonoxidative catalytic pathway, passing
through RhI catalytic intermediates, which is driven by the interplay between
the pyridine-2-methanolato and carbonyl ligands. The basic alkoxo ligand
promotes the deprotonation of the thiol to generate the RhI active species,
whereas the π-acceptor character of the carbonyl ligand hinders the oxidative
addition process. In addition, the stereochemistry of the key thiolate-π-alkyne
intermediate, which is determined by the electronic preference of the
carbonyl ligand to coordinate cis to IPr, facilitates the rate-limiting alkyne
thiometalation step.
Scheme 1. Rhodium-Based Alkyne Hydrothiolation
Mechanisms
INTRODUCTION
■
Vinyl sulfides constitute an interesting group of organic
molecules with valuable biological applications1 and remarkable
versatility as synthetic intermediates.2 Although several
approaches have been described,3 the addition of a S−H
bond of a thiol across a C−C triple bond, known as alkyne
hydrothiolation, is one of the more straightforward and atom-
economical preparative methods.4 While this process can be
initiated by radical,5 basic,6 or acid7 promoters, transition-metal
catalysis represents a more flexible approach to control the
regioselectivity.8 Particularly, rhodium catalysts behave as
chameleonic species, since subtle tuning of the ancillary ligands
strongly influences the catalytic outcome.9 It becomes evident
that, in order to obtain the desired product, an in-depth
understanding of the mode of action of the catalyst is essential.
In this context, the more common mechanism for rhodium-
based catalysts starts with the oxidation of the RhI metal
precursor to RhIII by addition of the S−H bond of the thiol
(Scheme 1). Subsequent 1,2- or 2,1-alkyne insertion into Rh−
H or Rh−S bonds generates four pathways which, followed by
reductive elimination, affords α-(E)- or β-(E)-vinyl sulfides. As
a viable alternative, the nonoxidative route entails the
deprotonation of the thiol by an internal base present in the
catalytic precursor to generate a Rh-thiolate species. Then,
alkyne insertion and protonolysis by an external thiol or a
protonated hemilabile ligand preferentially afford the branched
vinyl sulfides and regenerate RhI-SR active species.9m Vinyl-
Received: April 4, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
idene intermediates or external attack of thiol to a coordinated
alkyne are less prevalent in rhodium systems. The complexity of
the process entails a rational design of the catalytic precursors
to channel the reactive intermediates through the desired
reaction pathway.
Our group has recently disclosed that rhodium(I)-N-
heterocyclic carbene (NHC) catalysts efficiently perform alkyne
hydrothiolation under mild conditions (Scheme 2).9f Addition
for the branched alkenyl isomer, thus resulting in high
Markovnikov selectivity.
Despite the success attained in the design of Rh-NHC-based
hydrothiolation catalysts, further improvements are still
desirable. We now revisit our idea that RhI-thiolate species
could be potential Markovnikov-selective alkyne hydrothiola-
tion catalysts.9h In view of the experience gained in catalyst
design, the new catalysts must fulfill several requirements: (i) a
bulky and powerful electron-donor NHC ligand provides
stability to active species as well as control over the
coordination position of the labile ligands and substrates and
hence over selectivity outcome,10 (ii) the catalyst precursor
must contain an internal base to deprotonate the thiol and
generate a thiolate ligand without change in the oxidation state
of the metal, (iii) the presence of a chelate ligand should
control the potential equilibrium between mononuclear−
dinuclear species (indeed, we have observed that a pyridine
moiety provides stability and flexibility to the catalytic system),
and (iv) the introduction of a π-acceptor ligand would disfavor
the oxidative addition to RhI-thiolate intermediates. With these
prerequisites established, we envisage the potential of the
pyridine-2-methanolato ligand due to the presence of the basic
alkoxo group and the pyridine moiety that enable a chelate
coordination.11 In addition, a carbonyl ligand may play the role
of a π-acceptor ligand.
Scheme 2. Quest for Improved Markovnikov-Selective Rh-
NHC-Based Catalysts
Herein, we report on the synthesis of Rh-NHC-CO
complexes bearing a chelate pyridine-2-methanolato ligand as
efficient catalysts for Markovnikov-selective alkyne hydro-
thiolation. Stoichiometric studies supported by DFT calcu-
lations suggest a nonoxidative mechanism pathway, thus
confirming our previous expectations.
RESULTS AND DISCUSSION
■
Synthesis of Catalysts. We have previously observed that
the dinuclear derivative [Rh(μ-OH)(IPr)(η2-coe)]2 (1; IPr =
1,3-bis(2,6-diisopropylphenyl)imidazolin-2-carbene, coe = cy-
clooctene) is a suitable precursor for the preparation of alkoxo
complexes by deprotonation of the corresponding alcohol by
the basic hydroxo ligand. Thus, reaction of 1 with 2-
hydroxymethylpyridine at 40 °C for 2 h resulted in the
formation of Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(η2-coe) (2),
which was isolated as a yellow solid in 70% yield (Scheme
3). Alternatively, the olefin-alkoxo derivative 2 can be prepared
in 74% yield from the chlorido-bridged dinuclear complex
of pyridine remarkably increased the selectivity toward the
more valuable Markovnikov-type adducts.2b A complex inter-
play among carbene, pyridine, and hydride ligands within the
active species accounts for 1,2-insertion of the alkyne into a
Rh−S bond as the rate-limiting and selectivity-determining
step. In the quest for an improvement of Markovnikov
selectivity, we hypothesized that introduction of an internal
base in the catalyst precursor should prevent the formation of
hydride species, thereby suppressing the hydrometalation
pathways.9h However, the resulting thiolate-RhI intermediates
are inactive and undergo a subsequent thiol addition to
generate hydride-bis(thiolate)-RhIII species that show selectivity
similar to that of its chloride counterparts. As an alternative
approach, we envisaged the shift of the dinuclear−mononuclear
equilibrium by the anchoring of the pyridine moiety through a
bidentate quinolinolate ligand.9l Interestingly, the reaction
proceeds through a hydrometalation mechanism with reductive
elimination as the rate-limiting step. In addition, the selectivity
was increased up to 97% after addition of pyridine. It has been
determined that stabilization gained by pyridine coordination
into linear rhodium-alkenyl intermediates increases the
reductive elimination energy barrier, which is not operative
Scheme 3. Formation of Alkoxopyridine−Rhodium
Complexes
B
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
[Rh(μ-Cl)(IPr)(η2-coe)]2 (3), the precursor of 1, by treatment
with the potassium salt of pyridine-2-methanolate. In contrast
to the similar 8-quinolinolate-coe complex Rh{κ2-O,N-
(C9H6NO)}(η2-coe)(IPr),9l only one structural isomer having
the pyridine moiety trans to IPr was observed for the pyridine-
2-methanolato compound, as inferred from selective 1D-
1
NOESY H NMR experiments and DFT calculations (see the
Supporting Information). Complex 2 is highly air sensitive. In
fact, the dioxygen adduct Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(O2)
(4) was obtained as a violet solid in 85% yield after bubbling air
through a solution of 2. Interestingly, the carbonyl complex
Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(CO) (5) was prepared by
treatment of 1 with 2 equiv of 2-hydroxymethylpyridine for 4 h
at 80 °C and isolated in 76% yield. Likely, the carbonyl ligand
of 5 arises from decarbonylation of the alkoxypyridine via a
rhodium-hydride-piconylaldehyde intermediate that releases
pyridine and molecular hydrogen (see the Supporting
Information for the proposed mechanism).12 In fact, pyridine
was detected by GC-MS in the mother liquor, which supports
the proposed mechanism. As could be expected, bubbling of
carbon monoxide through a solution of 2 or 4 also affords 5.
Figure 1. X-ray structures of 4 and 5. For complex 4, only the most
abundant disordered complex (0.874(3) occupancy) is represented
and geometrical data refer only to this specimen. Selected bond
lengths (Å) and angles (deg): 4, Rh−C(1) 1.977(5), Rh−N(2)
2.078(4), Rh−O(1) 1.922(4), Rh−O(2) 1.973(3), O(2)−O(2)′
1.375(7), C(1)−Rh−N(2) 174.1(2), C(1)−Rh−O(1) 91.53(19),
C(1)−Rh−O(2) 92.17(16), N(2)−Rh−O(1) 82.57(18), N(2)−Rh−
O(2) 93.36(14), O(1)−Rh−O(2) 159.25(10); 5, Rh−C(8) 1.996(5),
Rh−N(1) 2.089(4), Rh−O(1) 2.017(4), Rh−C(7) 1.826(6), C(8)−
Rh−N(1) 170.84(18), C(8)−Rh−O(1) 89.95(18), C(8)−Rh−C(7) =
92.0(2), N(1)−Rh−O(1) 80.89(16), N(1)−Rh−C(7) 97.1(2),
O(1)−Rh−C(7) 178.03(19).
1
Complex 2 presents a fluxional behavior in the H NMR
spectrum at room temperature due to the rotation of IPr, which
is resolved at −40 °C. The spectrum displays the typical set of
resonances for a substituted pyridine ring. The H6 proton
adjacent to the nitrogen atom appears at δ 8.36 ppm as a small
doublet (5.5 Hz), whereas the resonances corresponding to the
remaining pyridinic protons appeared between 6.60 and 6.07
ppm. The methylene group shows a singlet at 5.67 ppm.
Coordination of coe is confirmed by the presence of a
resonance at 2.68 ppm. The more representative signals in the
13C{1H}-APT NMR spectrum of 2 are two doublets at δ 185.9
(JC−Rh = 61.2 Hz) and 51.2 ppm (JC−Rh = 12.9 Hz),
corresponding to the carbene and the coordinated olefin,
respectively. Complex 4 also displays rotation of the IPr ligand
that is faster than that of 2, as previously presented for the
similar complexes RhCl(IPr)(py)L.13h The carbene carbon
atom resonates in the 13C{1H}-APT NMR spectrum at δ 179.7
as a doublet with JC−Rh = 58.4 Hz.
methoxo and dioxygen moieties (see the Experimental
Section).
Both complexes present a slightly distorted square planar
environment around the rhodium atom. The distortions
fundamentally arise from the chelate coordination of the
N,O-bidentate ligand (82.57(18)° in 4 vs 80.89(16)° in 5). A
trans relative situation of the pyridinic nitrogen atom to the IPr
ligand has been also observed (174.1(2)° (4) vs 170.84(18)°
(5)). The rhodium−carbene separations (1.977(5) (4) and
1.996(5) Å (5)) lie in the typical range for a Rh−IPr single
bond.13 The O−O separation of the coordinated molecular
oxygen fits well with the description of a {1O2} ligand (O(2)−
O(2)′ 1.383.5 Å).13h The higher trans influence of the carbonyl
group in comparison to that of the η2-O2 dioxygen ligand is
reflected in the longer Rh−O bond distance observed in 5
(2.017(4) Å), relative to the significantly shorter distance
determined in 4 (1.922(4) Å). Similarly to previous described
RhI-NHC complexes, the wingtips of the carbene adopt an out-
of-plane disposition from the square-planar metal environment.
Catalytic Activity in Alkyne Hydrothiolation. The
catalytic activity of pyridine-2-methanolato complexes for
alkyne hydrothiolation was evaluated. The addition of
thiophenol to phenylacetylene in a 1/1 ratio was chosen as a
benchmark reaction. Catalytic reactions were monitored in
NMR tubes containing 0.5 mL of C6D6 and a catalyst loading of
2 mol %. Catalytic results are compiled in Table 1. The catalytic
activity of complex 2 in alkyne hydrothiolation is similar to that
of related Rh-quinolinolate-coe catalysts.9l Formation of α-vinyl
sulfide is favored, but the selectivity is not very high (entry 1).
The η2-O2 derivative 4 is also active, reaching 92% conversion
after 26 h at room temperature with 73% selectivity to the
Markovnikov-type product (entry 2). The catalytic activity in
alkyne hydrothiolation of a rhodium-η2-O2 complex has been
previously reported.9j Gratifyingly, complex 5 is much more
efficient. Selectivity toward α-vinyl sulfide reaches 97% at room
temperature, with an 80% conversion after 15 h (entry 3). In
this case, addition of pyridine is not essential for the control of
the selectivity, although an increase of the Markovnikov
1
Regarding 5, the H NMR spectrum displays the typical
signals for IPr and pyridine-2-methanolato ligands. The
presence of a CO ligand in 5 is corroborated by a doublet at
δ 193.0 ppm (JC−Rh = 70.3 Hz) in the 13C{1H}-APT NMR
spectrum, whereas the carbene carbon atom of IPr appears at
1
186.1 ppm as a doublet with JC−Rh = 57.3 Hz. The H−15N
HMBC spectrum is indicative of coordination of a nitrogen
atom, since a cross peak appears at 257.3 ppm, significantly
more shielded than the signal corresponding to free 2-
hydroxymethylpyridine at 301.2 ppm. In addition, the IR
spectrum shows a strong carbonyl stretching absorption band at
1909 cm−1. This low-frequency value is indicative of the high
electron richness of the RhI center that bears IPr, pyridine, and
alkoxo as strong electron-releasing ligands.
The structures of 4 and 5, in the solid state, have been
determined by two single-crystal X-ray diffraction analyses
(Figure 1). Single crystals were grown by slow diffusion of n-
hexane into a toluene (4) or C6D6 (5) solution of the
complexes. Both compounds exhibit a crystallographically
imposed planar symmetry, making just half of the molecule
independent; the symmetry plane contains the rhodium, the
whole pyridine-2-methanolato ligand, and, in 5, the carbonyl
group. In 4, a minor static disorder in the metal coordination
sphere was identified, implying a positional exchange of the
C
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
a
Table 1. Phenylacetylene Hydrothiolation with Thiophenol
Table 3. Thiophenol Addition to Several Alkynes Catalyzed
by 5
a
b
c
entry
catalyst
additive
time (h)
conversion (%)
α/β-E
1
2
3
4
5
6
2
4
5
5
6
7
24
26
15
12
13
21
83
92
80
25
30
d
69/31
73/27
97/3
pyridine
99/1
75/25
a
Conditions: 0.5 mL of C6D6 with 2 mol % of catalyst, [alkyne] =
b
c
[thiol] = 1.0 M at 25 °C. 10 equiv. Relative to phenylacetylene.
Calculated by NMR integration. Poly(phenylacetylene) was formed.
d
product up to 99% was observed, albeit with a reduction in the
activity (entry 4). In order to disclose the effect of the carbonyl
ligand over catalytic activity,9g,m the performances of the known
a
complexes RhCl(IPr)(CO)(py)13h (6) and RhCl(IPr)-
Conditions: 0.5 mL of C6D6 with 2 mol % of catalyst, [alkyne] =
b
13d
[thiol] = 1.0 M at 50 °C. Relative to the corresponding alkyne.
Calculated by NMR integration. β-Z vinyl sulfide.
(CO)2
(7) was studied. Catalyst 6, containing CO and
c
pyridine ligands, shows activity but is less active and selective
than 5 (entry 5). In contrast, complex 7 is not effective as an
alkyne hydrothiolation catalyst, since only poly-
(phenylacetylene) was recovered (entry 6).
The scope of catalyst 5 was studied for a set of thiols and
alkynes. Table 2 shows the results of catalytic alkyne
conversion of 99% with excellent selectivity (entries 1 and 2).
The enyne 1-ethynylcyclohexene reacted preferentially by the
triple bond, reaching a 97% selectivity (entry 3). In contrast, 2-
ethynylpyridine displayed a totally different behavior, since a
70/30 ratio of β-(Z)-/β-(E)-vinyl sulfides was observed (entry
4). Coordination of the pyridine fragment of the substrate must
play an important role in this case. Finally, the internal alkyne
3-hexyne gave the β-(E)-vinyl sulfide as a result of a syn
addition of the thiol over the alkyne.
Table 2. Phenylacetyene Hydrothiolation with Several
a
Thiols Catalyzed by 5
Mechanistic Studies. With the aim of shedding light on
the operative mechanism for alkyne hydrothiolation and the
role played by the pyridine-2-methanolato and carbonyl ligands,
several stoichiometric reactions were carried out. Complex 5
did not react with phenylacetylene after one night at 50 °C.
However, addition of 1 equiv of benzylthiol to a toluene-d8
solution of 5 in an NMR tube at −30 °C cleanly afforded the
RhI-thiolate complex Rh(SCH2Ph){η1-N-[2-(HOCH2)py]}-
(IPr)(CO) (8) (Scheme 4). Formation of 8 results from the
Scheme 4. Formation of Rhodium−Thiolate Complex 8
a
Conditions: 0.5 mL of C6D6 with 2 mol % of catalyst, [alkyne] =
b
[thiol] = 1.0 M at 50 °C. Relative to phenylacetylene. Calculated by
NMR integration. 1/2 thiol/alkyne ratio. Ratio between α/α and β-
E/α.
c
d
hydrothiolation of phenylacetylene with different thiols. The
reactions were performed at 50 °C with 2 mol % catalyst
loading. As a general trend, high selectivity to α-vinyl sulfides
was attained: over 87% for all cases. Interestingly, the reaction
with 1-butanethiol proceeded more quickly, although with
slightly lower selectivity in comparison to thiophenol (entry 2).
Other aliphatic thiols such as benzylthiol or a doubly protected
cysteine, N-tert-butoxycarbonyl (Boc) and methyl ester, reacted
more slowly but with excellent regioselectivity up to 96% in the
second example (entries 3 and 4). The terminal bis-mercaptan
1,6-hexanedithiol reacts with two molecules of alkyne to form a
bis-vinyl sulfide (entry 5), whereas 2-thiolpyridine is not
efficient as a hydrothiolation partner (entry 6).
protonation of the alkoxo ligand of 5 by the thiol and
coordination of the resulting thiolate. However, alternative
mechanisms such as oxidative addition of thiol to the RhI center
to form a rhodium-hydride-thiolate intermediate and sub-
sequent hydride-alkoxo reductive elimination or a σ-bond
metathesis process should not be discarded. In this regard, it is
worth noting that no hydride resonances could be detected.
Attempts to isolate 8 in the solid state failed.
The NMR spectra of 8 are in accordance with the proposed
structure. A set of three signals at δ 6.17, 5.44, and 4.18 ppm in
1
1
Table 3 shows the results of the hydrothiolation of a range of
alkynes with thiophenol. In all cases selectivity to α-vinyl
sulfides is higher than that previously obtained for related Rh-
NHC catalysts.9f,h Aliphatic alkynes such as 1-hexyne and
propargyl methyl ether required 21−24 h to achieve a
the H NMR spectrum at −30 °C related by H−1H COSY
cross peaks are ascribed to the protons of the hydroxymethyl
group (Figure 2). The absence of a correlation peak for the
signal at 6.17 ppm in the 13C−1H HSQC experiment, in
addition to an interaction between the resonances at 5.44 and
D
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
by 5 gives rise to the formation of the thiolate-η1-N-
hydroxypyridine intermediate I similar to 8. From this point,
two plausible pathways are conceivable: (i) activation of the
alkyne in a RhI intermediate or (ii) oxidative addition of the
thiol. In the first case, the nonoxidative cycle starts by exchange
of alkyne and pyridine ligands to form II. In this intermediate
1,2-thiolate insertion is more likely to afford the thioalkenyl
unsaturated species III, in which a molecule of thiol can
coordinate to form IV. Subsequent sequential thiol oxidative
addition−reductive elimination or protonolysis and addition of
the pyridine ligand regenerates I.
The second cycle (Scheme 6, left) starts by the oxidative
addition of a thiol molecule to form the bis(thiolate)-hydride-
RhIII intermediate V. Oxidative addition of the alkyne on I is
possible but unlikely, since thiol is more acidic. The next step is
alkyne coordination to the vacant site of V located trans to the
higher trans-influence hydride ligand to yield VI, and therefore
1,2-thiolate insertion results in the formation of VII.
Subsequent hydride-thioalkenyl reductive elimination gives
rise to the branched vinyl sulfide, thus regenerating the
catalytically active species by oxidative addition of thiol on the
resulting unsaturated species. The stoichiometric results
described above point to the nonoxidative mechanism being
operative. It seems reasonable that the oxidative addition of
thiol in I is hampered by the presence of a π-acceptor carbonyl
ligand, which contrasts with the reactivity previously observed
for the intermediate Rh(SR)(IPr)(η2-coe)(py), lacking such a
strong electron-acceptor ligand.9h
Theoretical Calculations on the Mechanism. A detailed
DFT computational analysis on the mechanism of alkyne
hydrothiolation promoted by 5 has been carried out. The
B3LYP method including dispersion correction has been used
throughout the study. Full IPr, pyridine-2-methanolato,
thiophenol, and phenylacetylene have been explicitly consid-
ered. All energies are relative to the starting point A
(compound 5) and the corresponding reactants. The first
process studied is the deprotonation of the thiol by the alkoxo
ligand (Figure 3). Approximation of a thiol molecule to A by
formation of a hydrogen bond stabilizes the complex by 8.3 kcal
mol−1 (A′). From this point, protonation of the alkoxo group
by the external thiol takes places via B-TS to generate C, which
is 13.7 kcal mol−1 more stable than A. An alternative pathway
via oxidative addition of thiol to A is unfeasible, as the resuting
hydride-thiolate-RhIII species C′ is located at 0.3 kcal mol−1.
Compound C may evolve by the two pathways described in
Scheme 6. Both routes were computed and presented in
Figures 4−7. The first step in the nonoxidative pathway is the
pyridine−alkyne exchange to yield the RhI-π-alkyne inter-
mediate D, which is 8.2 kcal mol−1 less stable than C, which
reflects the affinity of the catalytic system for pyridine ligands.
Due to the two possible orientations for the coordinated alkyne
to the metallic center, the route bifurcates to yield α-vinyl
sulfides (E−G, red line) via 1,2-thiolate insertion or β-(E)-vinyl
sulfides via 2,1-thiolate insertion (E′−G′, blue line). The
Markovnikov-type addition pathway is less energetically
demanding, showing a barrier of 30.2 kcal mol−1 via E-TS, in
contrast to 31.6 kcal mol−1 computed for the linear vinyl sulfide
via E′-TS. These transition states evolve to the thiometallacy-
clobutane intermediates F and F′ in which, after an
isomerization process, the sulfur atom is located trans to IPr.
Subsequent decoordination of the sulfur atom allows free access
to a new molecule of thiol to generate G and G′.
Figure 2. 1H NMR spectra of 8 at −30 °C (top) and −60 °C
(bottom).
4.18 ppm with the same carbon atom at 60.0 ppm, confirms
that the more deshielded doublet corresponds to the −OH
proton. Moreover, this signal shifts to 6.38 ppm at −60 °C.
Coordination of a sulfur atom to rhodium results in
diastereotopic methylene protons appearing at 2.77 and 2.51
ppm, displaying a scalar coupling of 12.5 Hz. The more relevant
signals of the 13C{1H}-APT spectrum are two doublets at δ
188.6 (JC−Rh = 72.1 Hz) and 184.1 ppm (JC−Rh = 53.6 Hz)
corresponding to CO and IPr ligands, respectively. The
nitrogen atom of the η1-N-2-hydroxypyridine ligand resonates
at δ 254.0 ppm.
Thereafter, the reactivity of 8 toward alkynes was studied.
Thus, treatment of a freshly prepared sample of 8 with
phenylacetylene at −30 °C showed no reaction. However,
heating the sample to room temperature gave rise to the
formation of the α-vinyl sulfide product resulting from
hydrothiolation and a mixture of unidentified rhodium species.
In addition, no reaction was observed after treatment of 8 with
a second equivalent of benzylthiol at low temperature, although
the sample slowly decomposed at room temperature.
A competitive hydrothiolation experiment between phenyl-
acetylene and phenylacetylene-d1 was performed in order to
evaluate the kinetic isotope effect kH/kD (Scheme 5).14 A syn
Scheme 5. KIE Measurement for Hydrothiolation Reaction
addition of the thiol across the triple bond is confirmed, since
only (E)-deuterostyrene was obtained. A secondary KIE value
of 1.28 0.03 is calculated, which indicates that a C−D bond is
not breaking in the rate-determining step and agrees with a
turnover-limiting alkyne migratory insertion mechanism.15
In view of these results, a mechanistic proposal is presented
in Scheme 6. In the first step, the activation of a thiol molecule
E
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Scheme 6. Mechanistic Proposal for Alkyne Hydrothiolation Mediated by 5
Figure 3. Computed energies (ΔG in kcal mol−1) for the protonation
of the alkoxo ligand by the external thiol.
Figure 4. DFT calculations (ΔG in kcal mol−1) along the energy
surface for the formation of vinyl sulfides through a nonoxidative
process. Structures E−G correspond to α-vinyl sulfide formation (R1 =
Ph, R2 = H, red line), and structures E′−G′ lead to β-(E)-vinyl sulfides
(R1 = H, R2 = Ph, blue line).
The next step of the nonoxidative pathway is the release of
vinyl sulfide from G and G′. Two possibilities have been
computed (Figure 5). In the first one, oxidative addition of a
molecule of thiol on G and G′ generates hydride-thiolate-RhIII
intermediates I and I′ via H-TS and H′-TS. Subsequent
reductive elimination through J-TS and J′-TS yields K and K′,
respectively. The second pathway consists of the direct
formation of K and K′ by protonolysis within G and G′ via
L-TS and L′-TS. Both pathways show very similar energetic
barriers. In fact, oxidative addition−reductive elimination is the
preferred pathway for the formation of α-vinyl sulfide (3.3 vs
5.4 kcal mol−1), whereas protonolysis is more favorable for the
formation of β-(E)-vinyl sulfide (8.2 vs 8.7 kcal mol−1).
Nevertheless, in both cases lower energetic barriers relative to
those found in the migratory insertion step have been
computed.
thiol (Figure 6). The thiol replaces 2-hydroxymethylpyridine to
form M, which is destabilized by 10.4 kcal mol−1 with regard to
C. From this intermediate activation of the S−H bond takes
place via N-TS located at 10.1 kcal mol−1 relative to A, to form
the hydride-bis(thiolate) compound O′, which isomerizes to
the more stable complex O with both thiolate ligands disposed
mutually trans and the carbonyl moiety located trans to IPr.
After formation of O the catalytic cycle may follow the
hydrometalation or thiometalation pathway (Figure 7).
Coordination of the alkyne in the vacant site of O generates
P, which is destabilized by 1.0 kcal mol−1. Then insertion of the
alkyne into the Rh−S bond takes place via Q-TS and Q′-TS.
Taking into account that we are under Curtin−Hammett
On the other hand, the first step in the process that implies
oxidation of the metallic center is the oxidative addition of the
F
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
alkyne ligands have to be disposed mutually cis. Intermediates
R and R′ are 17.7 and 17.5 kcal mol−1 higher in energy than O,
respectively. After this point, insertion of alkyne into the Rh−H
bond goes through transition states S-TS and S′-TS with
energetic barriers from C of 33.9 and 37.0 kcal mol−1,
respectively.
In all pathways studied, migratory insertion is the rate-
limiting step. The lower barrier is found for the nonoxidative
process (30.2 kcal mol−1), whereas the routes that involve RhIII
intermediates show 31.6 and 33.9 kcal mol−1 for the
thiometalation and hydrometalation pathways, respectively.
These results are in agreement with the calculated KIE and the
low activity observed at room temperature. However, catalyst 5
displays selectivity higher than that of the previously reported
Rh-NHC catalysts, without the need for addition of pyridine. It
is worth mentioning that the operative mechanism for catalyst
precursor 5, which proceeds through RhI catalytic intermedi-
ates, is markedly different from that observed for related Rh-
NHC catalytic systems that involve RhIII active species. The key
point is the presence of an internal base such as the alkoxo
ligand. This requisite was already present in Rh(μ-OH)(IPr)-
(η2-olefin)/py catalytic systems. However, the carbonyl ligand
in 5 plays an important role. Theoretical studies over Rh-NHC
square-planar systems have revealed that pyridine has a
tendency to coordinate trans to IPr, whereas π-acceptor ligands
are prone to bind cis to IPr.13h This coordination affinity results
in a mutually trans disposition of thiolate and alkyne in the key
intermediate species for the pyridine-based catalysts, whereas
these ligands are mutually cis in the CO-based systems,
facilitating the rate-limiting alkyne thiometalation step.
Figure 5. DFT calculations (ΔG in kcal mol−1) along the energy
surface for the formation of vinyl sulfides through oxidative addition−
reductive elimination (H-TS to K) or protonolysis (L-TS). Structures
G−K correspond to α-vinyl sulfide formation (R1 = Ph, R2 = H, red
line), and structures G′−K′ lead to β-(E)-vinyl sulfides (R1 = H, R2 =
Ph, blue line).
CONCLUSIONS
■
In summary, a new RhI-NHC-CO complex bearing a pyridine-
2-methanolato ligand is an efficient catalyst for alkyne
hydrothiolation with high selectivity toward the Markovnikov
product. The rational catalyst design has resulted in an
improvement in the selectivity with regard to previously
reported Rh-NHC systems without the need for addition of
pyridine. Reactivity studies and DFT calculations have revealed
a new nonoxidative catalytic pathway passing through RhI
catalytic intermediates. The basic alkoxo ligand assists the
deprotonation of the incoming thiol to generate the RhI active
species. On the other hand, the carbonyl ligand plays an
essential role, as its π-acceptor capacity hampers the oxidative
addition processes. Indeed, its affinity to coordinate cis to the
IPr ligand opens the way for a cis thiolate-π-alkyne
intermediate, which favors the rate-limiting migratory insertion
step. These results prompt us to apply the underlying principles
to the design of improved catalysts for C−C and C−
heteroatom bond forming catalytic reactions.
Figure 6. DFT calculations (ΔG in kcal mol−1) for the oxidative
addition of thiol to intermediate C.
Figure 7. DFT calculations (ΔG in kcal mol−1) along the energy
surface for the formation of vinyl sulfides through hydrometalation and
thiometalation processes. Structures P−S correspond to α-vinyl sulfide
formation (R1 = Ph, R2 = H, red line), and structures P′−S′ lead to β-
(E)-vinyl sulfides (R1 = H, R2 = Ph, blue line).
EXPERIMENTAL SECTION
■
General Considerations. All reactions were carried out with
rigorous exclusion of air using Schlenk-tube techniques. The reagents
were purchased from commercial sources and used as received, except
for phenylacetylene, which was distilled and stored over molecular
sieves. Organic solvents were dried by standard procedures and
distilled under argon prior to use or obtained oxygen and water free
from a Solvent Purification System (Innovative Technologies). The
organometallic precursors 19h and 313a were prepared as previously
described. Chemical shifts (expressed in parts per million) are
referenced to residual solvent peaks (1H, 13C{1H}) or liquid NH3
(15N). Coupling constants, J, are given in hertz. Spectral assignments
conditions (see Figure 6), the energetic barriers from C to the
transition states are 31.6 and 35.2 kcal mol−1, respectively, both
being higher than that computed for the rate-limiting step in
the nonoxidative cycle, making further analysis of that pathway
impractical. In contrast to thiometalation, an isomerization after
coordination of the alkyne is necessary in order for the
hydrometalation process to be operative, as hydride and π-
1
were achieved by combination of H−1H COSY, 13C{1H}-APT, and
G
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
1H−13C HSQC/HMBC experiments. H, C, and N analyses were
carried out in a PerkinElmer 2400 CHNS/O analyzer. GC-MS
analyses were recorded on an Agilent 5973 mass selective detector
interfaced to an Agilent 6890 series gas chromatograph system, using a
HP-5MS 5% phenyl methyl siloxane column (30 m × 250 mm with a
0.25 mm film thickness). The organic products were identified by
comparison with the previously reported data: phenyl 1-phenylvinyl
CHMeIPr). 13C{1H}-APT NMR (75.1 MHz, C6D6, 298 K): δ 193.0 (d,
JC−Rh = 70.3, CO), 186.1 (d, JC−Rh = 57.3, Rh−CIPr), 174.1 (s, C2‑py),
149.7 (s, C6‑py), 146.7 (s, Cq‑IPr), 137.1 (s, CqN), 133.7 (s, C4‑py), 129.6
and 123.7 (both s, CPh‑IPr), 123.6 (s, CHN), 120.3 (s, C5‑py), 117.8
(s, C3‑py), 78.1 (s, CH2O), 28.9 (s, CHMeIPr), 25.9 and 23.0 (both s,
1
CHMeIPr). H−15N NMR HMBC (40.1 MHz, toluene-d8, 243 K): δ
257.3 (Npy), 192.0 (NIPr).
In Situ Formation of Rh(SCH2Ph){η1-N[2-(HOCH2)py]}(IPr)-
(CO) (8). A toluene-d8 solution of 3 (20 mg, 0.032 mmol) in an NMR
tube at 243 K was treated with benzylthiol (3.8 μL, 0.032 mmol).
sulfide,3 butyl 1-phenylvinyl sulfide,16 benzyl 1-phenylvinyl sulfide,9c
g
phenyl S-(1-phenylvinyl)-N-Boc-L-cysteine-methyl ester,9f 1,6-bis((1-
phenylvinyl)thio)hexane,9f phenyl hex-1-en-2-yl sulfide,17 phenyl 3-
methoxyprop-1-en-2-yl sulfide,8b phenyl 1-(cyclohex-1-en-1-yl)vinyl
sulfide,9c 2-(2-(phenylthio)vinyl)pyridine,8h and (E)-3-(phenylthio)-
hex-3-ene.5b
1
NMR spectra were recorded immediately at 243 K. H NMR (400
MHz, toluene-d8, 243 K): δ 8.17 (d, J H−H = 5.2, 1H, H6‑Opy), 7.5−7.1
(m, 11H, HPh), 6.68 (s, 2H, CHN), 6.48 (br, 2H, H3‑py and H4‑py),
6.17 (d, JH−H = 10.0, 1H, HOCH2py), 5.96 (dd, JH−H = 8.7, 5.2, 1H,
H5‑py), 5.44 (d, JH−H = 10.7, 1H, HOCH2py), 4.18 (dd, JH−H = 10.7,
10.0, 1H, HOCH2py), 3.41 and 3.29 (both br, 4H, CHMeIpr), 2.77 and
2.51 (both d, JH−H = 12.5, 2H, PhCH2S), 1.66, 1.60, 1.13, and 1.11 (all
br, 24H, CHMeIpr). 13C{1H}-APT NMR (100.6 MHz, toluene-d8, 243
K): δ 188.6 (d, JC−Rh = 72.1, CO), 184.1 (d, JC−Rh = 53.6, Rh−CIPr),
162.9 (s, C2‑py), 152.8 (s, C6‑py), 145.4 (s, CqCH2S), 137.2 (s, CqN),
136.1 (s, C4‑py), 129.9, 128.9, 128.6, 127.6, and 125.5 (all s, CHPh),
124.0 (s, C3‑py), 121.9 (s, C5‑py), 121.7 (s, CHN), 60.0 (s,
HOCH2py), 30.7 (s, PhCH2S), 28.4 and 28.2 (both s, CHMeIPr), 26.7,
Preparation of Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(η2-coe) (2).
Method a. A yellow solution of 1 (100 mg, 0.08 mmol) in 10 mL
of toluene was treated with 2-hydroxymethylpyridine (15 μL, 0.16
mmol) and stirred at 313 K for 2 h. Then, the solution was
concentrated to ca. 1 mL and n-hexane added to induce the
precipitation of a yelow solid, which was washed with n-hexane (3 ×
3 mL) and dried in vacuo. Yield: 78.3 mg (70%).
Method b. A solution of 2-hydroxymethylpyridine (35 μL, 0.36
mmol) in 5 mL of THF was treated with potassium tert-butoxide (42
mg, 0.37 mmol) and stirred at room temperature for 30 min. Then,
this solution was poured over a solution of 3 (215 mg, 0.17 mmol) in
5 mL of THF and stirred at room temperature for 1.5 h. Afterward, the
solution was concentrated to ca. 1 mL and n-hexane was added to
induce the precipitation of a yellow solid, which was washed with n-
hexane (3 × 1 mL) and dried in vacuo. Yield: 178 mg (74%).
1
26.3, and 22.6 (all s, CHMeIPr). H−15N NMR HMBC (40.1 MHz,
toluene-d8, 243 K): δ 254.0 (Npy), 192.0 (NIPr).
Standard Conditions for Catalytic Hydrothiolation of
Alkynes. An NMR tube containing a solution of 0.01 mmol of
catalyst in 0.5 mL of C6D6 was treated with 0.5 mmol of thiol and 0.5
1
1
mmol of alkyne. The reaction was monitored by H NMR at the
Satisfactory elemental analysis could not be obtained. H NMR (500
required temperature, and the conversion was determined by
integration of the corresponding resonances of the alkyne and the
products. The final reaction products were analyzed by GC-MS
techniques.
KIE Determination. A NMR tube containing a solution of 0.01
mmol of catalyst in 0.5 mL of C6D6 was treated with 0.5 mmol of
thiophenol, 0.25 mmol of phenylacetylene, and 0.25 mmol of
phenylacetylene-d. The reaction was monitored by 1H NMR (500
MHz) at 298 K, and the conversion was determined by integration of
the corresponding resonances of the thiol and the products.
MHz, toluene-d8, 233 K): δ 8.36 (d, JH−H = 5.5, 1H, H6‑py), 7.3−7.0
(m, 6H, HPh‑IPr), 6.60 (m, 2H, H4‑py, H3‑py), 6.50 (s, 2H, CHN),
6.07 (dd, JH−H = 6.8, 5.5, 1H, H5‑py), 5.67 (s, 2H, CH2O), 4.61 and
2.52 (both sept, JH−H = 6.8, 4H, CHMeIPr), 2.68 (m, 2H, = CHcoe),
1.9−1.0 (m, 12H, CH2coe), 1.62, 1.46, 1.14, and 1.04 (all d, JH−H = 6.8,
24H, CHMeIPr). 13C{1H}-APT NMR (75.1 MHz, toluene-d8, 233 K):
δ 185.9 (d, JC−Rh = 61.2, Rh−CIPr), 175.0 (s, C2‑py), 150.5 (s, C6‑py),
148.0 and 145.4 (both s, Cq‑IPr), 137.6 (s, CqN), 133.0 (s, C4‑py), 129.2,
124.3, and 122.5 (all s, CHPh‑IPr), 123.6 (s, CHN), 119.4 (s, C5‑py),
117.8 (s, C3‑py), 79.2 (s, CH2O), 51.2 (d, JC−Rh = 12.9, CHcoe), 30.7,
30.6, and 26.4 (all s, CH2‑coe), 28.7 and 28.5 (both s, CHMeIPr), 26.6,
26.4, 23.5, and 22.7 (all s, CHMeIPr).
Crystal Structure Determinations. Single crystals for X-ray
diffraction studies were grown by slow diffusion of n-hexane into a
toluene (4) or C6D6 (5) solution of the complexes. X-ray diffraction
data were collected at 100(2) K on a Bruker APEX DUO CCD
diffractometer with graphite-monochromated Mo Kα radiation (λ =
0.71073 Å) using narrow ω rotations (0.3°). Intensities were
integrated and corrected for absorption effects with SAINT-PLUS18
and SADABS19 programs, both included in the APEX2 package. The
structures were solved by Patterson methods with SHELXS-9720 and
refined by full-matrix least squares on F2 with SHELXL-2014.21 In
both cases, the crystallographically imposed symmetry causes only half
of the complex to be asymmetric, the metal, the carbene carbon atom,
and the pyridine-2-methanolato ligand being on the symmetry plane.
Both structures were refined first with isotropic and later with
anisotropic displacement parameters for nondisordered non-H atoms.
Specific relevant details on each structure are described below.
Crystal data for 4: C33H42N3O3Rh; Mr = 631.60; brown prism 0.114
× 0.126 × 0.131 mm3; orthorhombic, Pnma; a = 17.597(4), b =
17.206(4), c = 9.999(2) Å; Z = 4; V = 3027.5(11) Å3; Dc = 1.386 g
cm−3; μ = 0.601 mm−1; min and max absorption correction factors
0.855 and 0.946; 2θmax = 50.05°; 22854 reflections collected, 2768
unique (Rint = 0.0462); number of data/restraints/parameters 2768/
17/247; final GOF 1.119; R1 = 0.0345 (2159 reflections, I > 2σ(I));
wR2(F2) = 0.0967 for all data. After anisotropic refinement of all non-
hydrogen atoms, an anomalous, very intense residual was present in
close proximity of the metal; at the same time some hydrogen atoms of
the carbene ligand became clearly apparent in the difference Fourier
maps. Detailed inspection of the electron density around the metal-
coordinated atoms also showed weak residuals in the proximity of both
independent oxygen atoms: methoxy group and dioxygen ligand. All of
these residuals have been interpreted by assuming a minor disorder of
Preparation of Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(O2) (4). Air was
bubbled through a toluene solution (10 mL) of 2 (100 mg, 0.141
mmol) for 15 min at room temperature Then, the solvent was
evaporated to dryness and the residue stirred with n-hexane to give a
violet solid, which was washed with n-hexane (4 × 2 mL) and dried in
vacuo. Yield: 76 mg (85%). Anal. Calcd for C33H42N3O3Rh: C, 62.75;
1
H, 6.70; N, 6.65. Found: C, 62.51; H, 6.72; N, 6.48. H NMR (400
MHz, C6D6, 298 K): δ 7.64 (dd, JH−H = 5.4, 1H, H6‑py), 7.2−7.3 (m,
6H, HPh), 6.73 (s, 2H, CHN), 6.52 (vt, NH−H = 15.4, 1H, H4‑py),
6.23 (dd, JH−H = 7.7, 5.4, 1H, H5‑py), 6.20 (d, JH−H =7.5, 1H, H3‑py),
4.81 (s, 2H, CH2O), 3.28 (sept, JH−H = 6.7, 4H, CHMeIPr), 1.58 and
1.17 (d, JH−H = 6.7, 12H, CHMeIPr). 13C{1H}-APT NMR (100.6 MHz,
C6D6, 298 K): δ 179.7 (d, JC−Rh = 58.4, Rh−CIPr), 169.1 (d, JC−Rh = 3,
C2‑py), 147.2 (s, C6‑py), 147.1 (s, Cq‑IPr), 136.7 (s, CqN), 134.8 (s,
C4‑py), 129.5 and 123.5 (s, CHm‑p‑IPr), 124.0 (s, CHN), 120.9 (s,
C5‑py), 116.2 (s, C3‑py), 81.8 (s, CH2O), 28.9 (s, CHMeIPr), 25.9 and
23.2 (s, CHMeIPr).
Preparation of Rh{κ2-O,N-[2-(OCH2)py]}(IPr)(CO) (5). A yellow
solution of 1 (100 mg, 0.08 mmol) in 10 mL of toluene was treated
with 2-hydroxymethylpyridine (30 μL, 0.32 mmol) and stirred at 353
K for 4 h. Then, the solution was concentrated to ca. 1 mL and n-
hexane added to induce the precipitation of a yellow solid, which was
washed with n-hexane (3 × 3 mL) and dried in vacuo. Yield: 75.4 mg
(76%). Anal. Calcd for C34H42N3O2Rh: C, 65.07; H, 6.75; N, 6.70.
Found: C, 64.92; H, 6.92; N, 6.62. 1H NMR (300 MHz, C6D6, 298 K):
δ 8.22 (d, JH−H = 4.0, 1H, H6‑py), 7.3−7.0 (m, 6H, HPh‑IPr), 6.81 (s, 2H,
CHN), 6.57 (vt, NH−H = 14.6, 1H, H4‑py), 6.42 (d, JH−H = 7.8, 1H,
H3‑py), 5.98 (t, JH−H = 5.9, 1H, H5‑py), 5.37 (s, 2H, CH2O), 3.52 (sept,
JH−H = 6.7, 4H, CHMeIPr), 1.73 and 1.27 (both d, JH−H = 6.5, 24H,
H
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
these two ligands being interchanged at both sides of the metal. The
second disordered coordination of the methoxy/dioxygen moieties is
present in the crystal in a very small fraction (relative occupancy of
0.126 vs 0.874(3)), this being the reason that only one significant
residual close to the metal atom was observed. Hydrogens have been
included only for those nondisordered atoms, in some cases (when
clearly observed) as free isotropic atoms, and in other cases (for
terminal methyl groups) in calculated positions. Final residuals were all
well under 1 e/Å3.
Crystal data for 5: C34H42N3O2Rh·2C6D6; Mr = 783.86; orange
prism 0.195 × 0.185 × 0.082 mm3; orthorhombic, Pnma; a =
17.857(5), b = 21.917(6), c = 10.326(3) Å; Z = 4; V = 4041.3(18) Å3;
Dc = 1.288 g cm−3; μ = 0.463 mm−1; min and max absorption
correction factors 0.845 and 0.948; 2θmax = 54.20°; 45624 reflections
collected, 4570 unique (Rint = 0.0640); number of data/restraints/
parameters 4570/0/320; final GOF 1.105; R1 = 0.0568 (3914
reflections, I > 2σ(I)); wR2(F2) = 0.1162 for all data. A benzene
solvent molecule was observed in the crystal structure. Hydrogens
were observed from difference Fourier maps and refined as free
isotropic atoms, except for those bonded to the terminal methyl
groups. Two residual peaks slightly above 1 e/Å3 were observed in the
final difference map, but they have no chemical sense.
2010, under the Project MULTICAT (CSD2009-00050) are
gratefully acknowledged. A.D.G. thanks the Spanish Ministerio
́
de Economıa y Competitividad (MINECO) for the post-
doctoral grant Juan de la Cierva - Incorporacion 2015 (IJCI-
2015-27029).
́
REFERENCES
■
(1) (a) Brooks, G.; Coleman, K.; Davies, J. S.; Hunter, P. A. J.
Antibiot. 1988, 41, 892. (b) Johannesson, P.; Lindeberg, G.; Johansson,
A.; Nikiforovich, G. V.; Gogoll, A.; Synnergren, B.; LeGrev
̀
es, M.;
Nyberg, F.; Karlen, A.; Hallberg, A. J. Med. Chem. 2002, 45, 1767.
́
(c) Sader, H. S.; Johnson, D. M.; Jones, R. N. Antimicrob. Agents
Chemother. 2004, 48, 53. (d) Tian, Y.; Li, J.; Zeng, X.; Wang, D.; Liu,
Q.; Niu, X.; Huang, X.; Xu, N.; Li, Z. Chem. Sci. 2016, 7, 3325.
(2) (a) Trost, B. M.; Lavoie, A. C. J. Am. Chem. Soc. 1983, 105, 5075.
(b) Schaumann, E. Top. Curr. Chem. 2007, 274, 1. (c) Liu, T.; Zhao,
X.; Lu, L.; Cohen, T. Org. Lett. 2009, 11, 4576. (d) Quinet, C.;
́
Sampoux, L.; Marko, I. E. Eur. J. Org. Chem. 2009, 2009, 1806. (e) Cui,
Y.; Floreancing, P. E. Org. Lett. 2012, 14, 1720. (f) Kiemele, E. R.;
Watier, M.; Bichler, P.; Love, J. A. Org. Lett. 2016, 18, 492.
(3) (a) Russell, G. A.; Ngoviwatchai, P.; Tashtoush, H. I.; Pla-
Dalmau, A.; Khanna, R. K. J. Am. Chem. Soc. 1988, 110, 3530. (b) Han,
L.-B.; Tanaka, M. J. Am. Chem. Soc. 1998, 120, 8249. (c) Kuniyasu, H.;
Yamashita, F.; Hirai, T.; Ye, J.-H.; Fujiwara, S.-i.; Kambe, N.
Organometallics 2006, 25, 566. (d) Silveira, C. C.; Santos, P. C. S.;
Mendes, S. R.; Braga, A. R. J. Organomet. Chem. 2008, 693, 3787.
Computational Details. All DFT theoretical calculations have
been carried out using the Gaussian program package.22 The B3LYP
method23 has been employed, including the D3 dispersion correction
scheme developed by Grimme24 for both energies and gradient
calculations and the “ultrafine” grid. The def2-SVP basis set25 has been
selected for all atoms. The nature of the stationary points has been
confirmed by analytical frequency analysis. We have reported in the
Supporting Information the computational results, including the
Cartesian coordinates (in Å), absolute energies (in au), and graphical
representation.
́
(e) Hooper, J. F.; Chaplin, A. B.; Gonzalez-Rodríguez, C.; Thompson,
A. L.; Weller, A. S.; Willis, M. C. J. Am. Chem. Soc. 2012, 134, 2906.
(f) Feng, J.; Lu, G.; Lv, M.; Cai, C. Asian J. Org. Chem. 2014, 3, 77.
(4) (a) Bichler, P.; Love, J. A.; Vigalok, A. Top. Organomet. Chem.
2010, 31, 39. (b) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011,
́
111, 1596. (c) Castarlenas, R.; Di Giuseppe, A.; Perez-Torrente, J. J.;
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.7b00251.
■
Oro, L. A. Angew. Chem., Int. Ed. 2013, 52, 211. (d) Ogawa, A.;
Ananikov, V. P.; Tanaka, M. Top. Organomet. Chem. 2011, 43, 325.
(e) Dondoni, A.; Marra, A. Eur. J. Org. Chem. 2014, 2014, 3955.
(f) Orlov, N. V. ChemistryOpen 2015, 4, 682. (g) Di Giuseppe, A.;
Castarlenas, R.; Oro, L. A. Top. Organomet. Chem. 2016,
DOI: 10.1007/3418_2016_171.
S
Experimental procedures, KIE determination, and NMR
spectra for complexes (PDF)
Cartesian coordinates for theoretical calculations (XYZ)
(5) (a) Griesbaum, K. Angew. Chem., Int. Ed. Engl. 1970, 9, 273.
(b) Benati, L.; Montevecchi, P. C.; Spagnolo, P. J. Chem. Soc., Perkin
Trans. 1 1991, 2103. (c) Lo Conte, M.; Pacifico, S.; Chambery, A.;
Marra, A.; Dondoni, A. J. Org. Chem. 2010, 75, 4644. (d) Chun, S.;
Chung, J.; Park, J. E.; Chung, Y. K. ChemCatChem 2016, 8, 2476.
(e) Wang, H.; Lu, Q.; Chiang, C.-W.; Luo, Y.; Zhou, J.; Wang, G.; Lei,
A. Angew. Chem., Int. Ed. 2017, 56, 595.
Accession Codes
CCDC 1550180−1550181 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(6) (a) Ipatieff, V. N.; Pines, H.; Friedman, B. S. J. Am. Chem. Soc.
1938, 60, 2731. (b) Screttas, C. G.; Micha-Screttas, M. J. Org. Chem.
1979, 44, 713. (c) Weïwer, M.; Coulombel, L.; Dunach, E. Chem.
̃
Commun. 2006, 332. (d) Kucin
Hreczycho, G. Chem. - Eur. J. 2015, 21, 4940.
́ ́
ski, K.; Pawluc, P.; Marciniec, B.;
(7) (a) Truce, W. E.; Simms, J. A.; Boudakian, M. M. J. Am. Chem.
Soc. 1956, 78, 695. (b) Kondoh, A.; Takami, K.; Yorimitsu, H.;
Oshima, K. J. Org. Chem. 2005, 70, 6468. (c) Truong, V. X.; Dove, A.
P. Angew. Chem., Int. Ed. 2013, 52, 4132. (d) Kumar, R.; Saima; Shard,
A.; Andhare, N. H.; Richa; Sinha, A. K. Angew. Chem., Int. Ed. 2015, 54,
828.
(8) (a) Kuniyasu, H.; Ogawa, A.; Sato, K.-I.; Ryu, I.; Kambe, N.;
Sonoda, N. J. Am. Chem. Soc. 1992, 114, 5902. (b) Ananikov, V. P.;
Malyshev, D. A.; Beletskaya, I. P.; Aleksandrov, G. G.; Eremenko, I. L.
Adv. Synth. Catal. 2005, 347, 1993. (c) Kondoh, A.; Yorimitsu, H.;
Oshima, K. Org. Lett. 2007, 9, 1383. (d) Munro-Leighton, C.; Delp, S.
A.; Alsop, N. M.; Blue, E. D.; Gunnoe, T. B. Chem. Commun. 2008,
111. (e) Weiss, C. J.; Wobser, S. D.; Marks, T. J. J. Am. Chem. Soc.
2009, 131, 2062. (f) Ananikov, V. P.; Gayduck, K. A.; Orlov, N. V.;
Beletskaya, I. P.; Khrustalev, V. N.; Antipin, M. Y. Chem. - Eur. J. 2010,
16, 2063. (g) Weiss, C. J.; Marks, T. J. J. Am. Chem. Soc. 2010, 132,
10533. (h) Gerber, R.; Frech, C. M. Chem. - Eur. J. 2012, 18, 8901.
AUTHOR INFORMATION
Corresponding Author
*E-mail for R.C.: rcastar@unizar.es.
ORCID
Andrea Di Giuseppe: 0000-0002-3666-5800
Fernando J. Lahoz: 0000-0001-8054-2237
Ricardo Castarlenas: 0000-0003-4460-8678
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support from the Spanish Ministerio de Economıa y
Competitividad (MINECO/FEDER) under the Projects
■
́
CTQ2013-42532-P and CTQ2016-75884-P, the Diputacion
General de Aragon (E07) and CONSOLIDER INGENIO-
́
́
(i) Cabrero-Antonino, J. R.; Leyva-Per
́
ez, A.; Corma, A. Adv. Synth.
I
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
Catal. 2012, 354, 678. (j) Yang, Y.; Rioux, R. M. Green Chem. 2014,
(14) Gom
́
ez-Gallego, M.; Sierra, M. A. Chem. Rev. 2011, 111, 4857.
16, 3916. (k) Cadu, A.; Watile, R. A.; Biswas, S.; Orthaber, A.; Sjober,
(15) Weiss, C. J.; Wobser, S. D.; Marks, T. J. Organometallics 2010,
29, 6308.
(16) Ikehira, H.; Tanimoto, S.; Oida, T. Bull. Chem. Soc. Jpn. 1983,
56, 2537.
(17) Fiandanese, V.; Marchese, G.; Naso, F.; Ronzini, L. Synthesis
1987, 1987, 1034.
̈
P. J. R.; Samec, J. S. M. Org. Lett. 2014, 16, 5556. (l) Degtyareva, E. S.;
Burykina, J. V.; Fakhrutdinov, A. N.; Gordeev, E. G.; Khrustalev, V. N.;
Ananikov, V. P. ACS Catal. 2015, 5, 7208. (m) Modem, S.; Kankala,
S.; Balaboina, R.; Thirukovela, N. S.; Jonnalagadda, S. B.; Vadde, R.;
Vasam, C. S. Eur. J. Org. Chem. 2016, 2016, 4635.
(18) SAINT+, version 6.01: Area-Detector Integration Software; Bruker
AXS, Madison, WI, USA, 2001.
(9) See for example: (a) Ogawa, A.; Ikeda, T.; Kimura, K.; Hirao, J. J.
Am. Chem. Soc. 1999, 121, 5108. (b) Burling, S.; Field, L. D.; Messerle,
B. A.; Vuong, K. Q.; Turner, P. Dalton Trans. 2003, 4181. (c) Cao, C.;
Fraser, L. R.; Love, J. A. J. Am. Chem. Soc. 2005, 127, 17614.
(d) Misumi, Y.; Seino, H.; Mizobe, Y. J. Organomet. Chem. 2006, 691,
3157. (e) Shoai, S.; Bichler, P.; Kang, B.; Buckley, H.; Love, J. A.
Organometallics 2007, 26, 5778. (f) Di Giuseppe, A.; Castarlenas, R.;
Perez-Torrente, J. J.; Crucianelli, M.; Polo, V.; Sancho, R.; Lahoz, F. J.;
́
Oro, L. A. J. Am. Chem. Soc. 2012, 134, 8171. (g) Kankala, S.; Nerella,
S.; Vadde, R.; Vasam, C. S. RSC Adv. 2013, 3, 23582. (h) Palacios, L.;
(19) Sheldrick, G. M. SADABS program; University of Gottingen,
̈
Gottingen, Germany, 1999.
̈
(20) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.
1990, 46, 467.
(21) Sheldrick, G. M. Acta Crystallogr., Sect. C 2015, C71, 3.
(22) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.;
Robb, M. A.; Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci,
B.; Petersson, G. A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.
P.; Izmaylov, A. F.; Bloino, J.; Zheng, G.; Sonnenberg, J. L.; Hada, M.;
Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima,
T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J. A., Jr.;
Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin,
K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.; Rega,
N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.;
Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.;
Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Martin, R. L.;
Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.; Salvador, P.;
́
Artigas, M. J.; Polo, V.; Lahoz, F. J.; Castarlenas, R.; Perez-Torrente, J.
J.; Oro, L. A. ACS Catal. 2013, 3, 2910. (i) Pritzius, A. B.; Breit, B.
Angew. Chem., Int. Ed. 2015, 54, 3121. (j) Kleinhans, G.; Guisado-
Barrios, G.; Liles, D. C.; Bertrand, G.; Bezuidenhout, D. I. Chem.
Commun. 2016, 52, 3504. (k) Kennemur, J. L.; Kortman, G. D.; Hull,
K. L. J. Am. Chem. Soc. 2016, 138, 11914. (l) Palacios, L.; Di Giuseppe,
A.; Artigas, M. J.; Polo, V.; Lahoz, F. J.; Castarlenas, R.; Per
Torrente, J. J.; Oro, L. A. Catal. Sci. Technol. 2016, 6, 8548.
(m) Strydom, I.; Guisado-Barrios, G.; Fernandez, I.; Liles, D. C.; Peris,
́
ez-
́
E. Bezuidenhout. Chem. - Eur. J. 2017, 23, 1393.
̈
Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas, O.;
(10) (a) Herrmann, W. Angew. Chem., Int. Ed. 2002, 41, 1290.
(b) Lappert, M. F. J. Organomet. Chem. 2005, 690, 5467. (c) Díez-
Gonzalez, S.; Marion, N.; Nolan, S. P. Chem. Rev. 2009, 109, 3612.
́
(d) Arduengo, A. J., III; Iconaru, L. I. Dalton Trans. 2009, 6903.
(e) Hopkinson, M. N.; Richter, C.; Schedler, M.; Glorius, F. Nature
2014, 510, 485. (f) Mata, J. A.; Hahn, F. E.; Peris, E. Chem. Sci. 2014,
5, 1723.
(11) (a) Canovese, L.; Cattalini, L.; Marangoni, G.; Tobe, M. J.
Chem. Soc., Dalton Trans. 1985, 731. (b) Cooper, D. A.; Rettig, S. J.;
Storr, A. Can. J. Chem. 1986, 64, 566. (c) Darensbourg, D. J.; Fontal,
B.; Chojnacki, S. S.; Klausmeyer, K. K.; Reibenspiesl, J. H. Inorg. Chem.
Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09,
revision A.1; Gaussian, Inc., Wallingford, CT, 2004.
(23) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. Rev. B: Condens. Matter
Mater. Phys. 1988, 37, 785. (b) Becke, A. D. J. Chem. Phys. 1993, 98,
1372. (c) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(24) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys.
2010, 132, 154104.
(25) Weigend, F.; Ahlrichs, R. Phys. Chem. Chem. Phys. 2005, 7, 3297.
1994, 33, 3526. (d) Martos-Calvente, R.; de la Pena O’Shea, V. A.;
̃
́
Campos-Martin, J. M.; Fierro, J. L. G.; Gutierrez-Puebla, E. J. Mol.
Catal. A: Chem. 2004, 214, 269. (e) Telfer, S. G.; Parker, N. D.;
Kuroda, R.; Harada, T.; Lefebvre, J.; Leznoff, D. B. Inorg. Chem. 2008,
́
47, 209. (f) Fandos, R.; Gallego, B.; Lopez-Solera, M. I.; Otero, A.;
Rodríguez, A.; Ruiz, M. J.; Terreros, P.; van Mourik, T. Organometallics
2009, 28, 1329. (g) Icsel, C.; Yilmaz, V. T.; Golcu, A.; Ulukaya, E.;
Buyukgungor, O. Bioorg. Med. Chem. Lett. 2013, 23, 2117.
(h) Carmona, D.; Lamata, P.; Sac
Ramírez, P.; Lahoz, F. J.; García-Orduna, P.; Oro, L. A. Organometallics
2014, 33, 4016. (i) Monakhov, K. Y.; Lop
́
hez, A.; Pardo, P.; Rodríguez, R.;
̃
́
ez, X.; Speldrich, M.; van
Leusen, J.; Kogerler, P.; Braunstein, P.; Poblet, J. M. Chem. - Eur. J.
̈
2014, 20, 3769.
(12) Vaska, L.; DiLuzio, J. W. J. Am. Chem. Soc. 1961, 83, 2784−
2785.
(13) (a) Yu, X.-Y.; Patrick, B. O.; James, B. R. Organometallics 2006,
́
25, 4870. (b) Gois, P. M. P.; Trindade, A. F.; Veiros, L. F.; Andre, V.;
Duarte, M. T.; Afonso, C. A. M.; Caddick, S.; Cloke, G. N. Angew.
Chem., Int. Ed. 2007, 46, 5750. (c) Praetorius, J. M.; Wang, R.;
Crudden, C. M. Eur. J. Inorg. Chem. 2009, 2009, 1746. (d) Zenkina, O.
V.; Keske, E. C.; Kochhar, G. S.; Wang, R.; Crudden, C. M. Dalton
Trans. 2013, 42, 2282. (e) Palacios, L.; Di Giuseppe, A.; Opalinska, A.;
Castarlenas, R.; Per
Organometallics 2013, 32, 2768. (f) Azpíroz, R.; Rubio-Per
Giuseppe, A.; Passarelli, V.; Lahoz, F. J.; Castarlenas, R.; Per
́
ez-Torrente, J. J.; Lahoz, F. J.; Oro, L. A.
ez, L.; Di
ez-
́
́
Torrente, J. J.; Oro, L. A. ACS Catal. 2014, 4, 4244. (g) Keske, E. C.;
Moore, B. D.; Zenkina, O. V.; Wang, R.; Schatte, G.; Crudden, C. M.
Chem. Commun. 2014, 50, 9883. (h) Palacios, L.; Di Giuseppe, A.;
́
Castarlenas, R.; Lahoz, F. J.; Perez-Torrente, J. J.; Oro, L. A. Dalton
Trans. 2015, 44, 5777. (i) Buhl, H.; Ganter, C. J. Organomet. Chem.
2016, 809, 74.
J
DOI: 10.1021/acs.organomet.7b00251
Organometallics XXXX, XXX, XXX−XXX