Rhodium-Catalyzed Selective Partial Hydrogenation of Alkynes

Article abstract of DOI:10.1021/acs.organomet.5b00322

The cationic rhodium complex [Rh(P^cPr₃)₂(η⁶-PhF)]⁺[B{3,5-(CF₃)₂C₆H₃}₄]^- (P^cPr₃ = triscyclopropylphosphine, PhF = fluorobenzene) was used as a catalyst for the hydrogenation of the charge-tagged alkyne [Ph₃P(CH₂)₄C₂H]⁺[PF₆]^-. Pressurized sample infusion electrospray ionization mass spectrometry (PSI-ESI-MS) was used to monitor reaction progress. Experiments revealed that the reaction is first order in catalyst and first order in hydrogen, so under conditions of excess hydrogen the reaction is pseudo-zero order. Alkyne hydrogenation was 40 times faster than alkene hydrogenation. The turnover-limiting step is proposed to be oxidative addition of hydrogen to the alkyne (or alkene)-bound complex. Addition of triethylamine caused a dramatic reduction in rate, suggesting a deprotonation pathway was not operative. (Graph Presented).

Full text of DOI:10.1021/acs.organomet.5b00322

Article
pubs.acs.org/Organometallics
Rhodium-Catalyzed Selective Partial Hydrogenation of Alkynes
Jingwei Luo,† Robin Theron,† Laura J. Sewell,‡ Thomas N. Hooper,‡ Andrew S. Weller,‡ Allen G. Oliver,§
and J. Scott McIndoe*,†
†Department of Chemistry, University of Victoria, P.O. Box 3065, Victoria, BC V8W3 V6, Canada
‡Department of Chemistry, University of Oxford, Mansfield Road, Oxford, OX1 3TA, U.K.
§Molecular Structure Facility, Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556,
United States
S
* Supporting Information
ABSTRACT: The cationic rhodium complex [Rh(PcPr3)2(η6-PhF)]+[B-
{3,5-(CF3)2C6H3}4]− (PcPr3 = triscyclopropylphosphine, PhF = fluo-
robenzene) was used as a catalyst for the hydrogenation of the charge-
tagged alkyne [Ph3P(CH2)4C2H]+[PF6]−. Pressurized sample infusion
electrospray ionization mass spectrometry (PSI-ESI-MS) was used to
monitor reaction progress. Experiments revealed that the reaction is first
order in catalyst and first order in hydrogen, so under conditions of excess
hydrogen the reaction is pseudo-zero order. Alkyne hydrogenation was 40
times faster than alkene hydrogenation. The turnover-limiting step is
proposed to be oxidative addition of hydrogen to the alkyne (or alkene)-
bound complex. Addition of triethylamine caused a dramatic reduction in
rate, suggesting a deprotonation pathway was not operative.
(PR3)2]+ precursors8 was further increased to the hydro-
INTRODUCTION
■
genation of imines,9 and since then, the hydrogenations of
Hydrogenation of alkynes and alkenes mediated by rhodium
complexes is a classic catalytic organometallic reaction.1 First
prochiral imines for the production of a chiral amines has
introduced by Wilkinson,2 the eponymous catalyst Rh-
become a promising route for synthesis of chiral nitrogen-
containing compounds.10 DFT studies have become increas-
(PPh3)3Cl has been widely employed, thanks to the mild
conditions it operates under and its selectivity for C−C
ingly popular for the unravelling of mechanistic details of these
systems.11
multiple bonds over other unsaturated sites.3 The mechanism
of the reaction has been studied by a wide range of
approaches.4 It may well be the most well-studied organo-
metallic catalytic reaction. It is relatively complicated, with off-
cycle equilibria between catalyst monomer and dimer (and
hydrogenated versions thereof) and between di- and
triphosphine species. Cationic rhodium complexes are known
for the hydrogenation of alkynes from Schrock and Osborn’s
work,5 and since then, these types of complexes have served as
precursors in various studies of homogeneous catalysis.
Bis(ditertiaryphosphine) chelate complexes of rhodium(I)
were studied as catalytic hydrogenators of methylenesuccinic
acid, and cationic and hydrido versions of the complex were
found to be more active than corresponding chloro versions,
with activity increasing with increasing chain length of the
diphosphine.6a Semihydrogenation of internal alkynes such as
diphenylacetylene has also been developed with good selectivity
with use of trinuclear cationic rhodium complexes.6b Innately
linked to cationic rhodium hydrogenation is catalytic
asymmetric synthesis to produce enantiomerically pure
compounds due to the possibility of introducing a degree of
chirality in the ligands on the metal center. Extensive work has
been done in this area with rhodium and more recently with
iridium and ruthenium complexes.7 The scope of [Rh(diene)-
We have examined rhodium-catalyzed hydrogenation pre-
viously using electrospray ionization mass spectrometry (ESI-
MS), wherein we doped in substoichiometric quantities of a
charged phosphine ligand,12 [Ph2P(CH2)4PPh2Bn]+[PF6]− (Bn
= benzyl), into a reaction mixture consisting of an alkene,
hydrogen, and Wilkinson’s catalyst, using chlorobenzene as a
solvent.13 We observed a large variety of rhodium complexes
consistent with the known speciation of this reaction mixture.
However, because ESI-MS operates only on ions, the overall
progress of the reaction was not tracked, and therefore the
concentration of metal−ligand intermediates cannot be
matched to activity. As such, establishing whether or not an
observed species is an intermediate, a resting state, or a
decomposition product is not easy. We later reexamined the
reaction, where we added a charged tag to the substrate (in this
case an alkyne) rather than the catalyst.14 This paper confirmed
that the turnover-limiting step was ligand dissociation from the
precatalyst to generate the unsaturated, 14-electron species
Rh(PPh3)2Cl. However, since all steps involving the alkyne on
Received: April 16, 2015
Published: June 9, 2015
© 2015 American Chemical Society
3021
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
ature, 90 °C; desolvation temperature, 180 °C; cone gas flow, 100 L/
h; desolvation gas flow, 100 L/h; collision voltage, 2 V (for MS
experiments); collision voltage, 2−80 V (for MS/MS experiments);
MCP voltage, 2700 V. Mass spectrometric interpretation was aided by
ChemCalc.25
the metal were relatively fast, we saw no metal-containing
intermediates during the reaction.
ESI-MS is increasingly popular as a method of establishing
solution speciation in organometallic reactions.15 It has been
used on systems with inherently charged catalysts,16 with
neutral catalysts that become charged via oxidation17 or
protonation,18 and with catalysts with deliberately charged
ligands.19 Use of charged substrates is somewhat rarer, as is
continuous monitoring of reaction solutions, but we favor this
approach thanks to the complete picture of speciation it
provides.20 Here, for the first time, we combine a charged
substrate with a charged catalyst to allow simultaneous
examination of the abundance and identity of all charged
species in solution. Real-time monitoring of the charged species
in solution was achieved using pressurized sample infusion ESI-
MS (Figure 1).21
ESI-MS Reaction Monitoring Using Pressurized Sample
Infusion. A Schlenk flask was used for these experiments, as shown
in Figure 1. A 10 mL fluorobenzene solution of 2[PF6] (10−20 mg,
2.1−4.2 mM) was monitored using the pressurized sample infusion
electrospray ionization mass spectrometry (PSI-ESI-MS) setup. The
Schlenk flask was pressurized to 3 psi using 99.999% purity hydrogen
gas. [Rh(PcPr3)2(η6-FPh)]+[BArF ]− (1.0−6.0 mg, 0.75−4.5 μmol, 1−
4
20% catalyst loading) was dissolved in 1 mL of fluorobenzene and
injected into the well-stirred Schlenk flask via a septum. The solution
end of the PEEK tubing was protected with a standard cannula filter
system to avoid the tube being blocked by any insoluble byproducts.
Data were processed by normalizing the abundance of each species to
the total ion count of all species identified as containing the tag. No
smoothing of the data was performed. The triethylamine reaction was
conducted using 2.2 mM of the charged alkyne, 0.22 mM of the
catalyst, and 1.12 mM of NEt3. The reaction with D2 used the same
overpressure as for H2.
1[BArF ]: [Rh(PcPr3)2(η6-C6H5F)]+[BArF ]−. [RhCl(PcPr3)2]2 was
4
4
prepared by the procedure described by Goldman et al.26 [RhCl-
(PcPr3)2]2 (0.100 g, 0.112 mmol) and Na[BArF ] (0.203 g, 0.229
4
mmol) were added to a Schlenk flask, and fluorobenzene (5 cm3) was
added. After stirring for 1 h the solution was filtered, and the volume
was reduced in vacuo to approximately 2 cm3. This solution was
layered with n-pentane (20 cm3), and storage at room temperature
gave [Rh(PcPr3)2(η6-C6H5F)][BArF ] as brown crystals (0.200 g, 65%)
4
after 48 h. 1H NMR (C6H5F, 500 MHz): 8.38 (s, 8H, BArF ), 7.69 (s,
4
4H, BArF ), 6.20 (m, 2H, C6H5F), 6.12 (m, 2H, C6H5F), 5.68 (m, 1H,
4
c
c
C6H5F), 0.60 (br m, 24H, Pr CH2), 0.36 (br m, 6H, Pr CH) ppm.
31P{1H} NMR (C6H5F, 202 MHz): 41.4 (d, JPRh = 206 Hz) ppm.
1
Anal. Calcd for C56H47BF25P2Rh (1370.60 g mol−1): C, 49.07; H, 3.46.
Found: C, 48.84; H, 3.39. ESI-MS(+) (C6H5F, 60 °C): m/z 507.12.
2[I]: [Ph3P(CH2)4C2H]+[I]−, Hex-5-yn-1-yltriphenylphospho-
nium Iodide. Triphenylphosphine (5.00 g, 19.0 mmol) was dissolved
into 10 mL of toluene in a Schlenk flask at 75 °C, and 6-iodo-1-hexyne
(1.00 g, 4.81 mmol) added dropwise over 10 min. The mixture was
stirred for 72 h, before the product was filtered off, washed with
toluene, and dried under high vacuum. Final product was a white
powder (2.22 g, 4.72 mmol, 98%). Crystals for X-ray crystallographic
analysis were grown by vapor diffusion of hexane into a chloroform
solution. ESI-MS(+): m/z 343.1. ESI-MS(−): m/z 126.9.
Figure 1. Pressurized sample infusion ESI-MS. The glassware used
consisted of a Schlenk flask modified to incorporate a reflux condenser.
The cationic catalyst [Rh(PcPr3)2(η6-PhF)]+[B{3,5-
(CF3)2C6H3}4]− (1[BArF ]; PcPr3 = triscyclopropylphosphine,
4
2[PF6]: [Ph3P(CH2)4C2H]+[PF6]−, Hex-5-yn-1-yltriphenylphos-
phonium Hexafluorophosphate(V). Sodium hexafluorophosphate
(0.56 g, 2.12 mmol) was dissolved in 5 mL of water, and 5 mL of a
methanol/water mixed solution of [Ph3P(CH2)4C2H]+[I]− (0.5 g 1.06
mmol) was added dropwise with stirring. The product was filtered and
washed with water and dried under high vacuum for a week. Final
PhF = fluorobenzene) was used, for which similar systems have
been shown to be effective for both amine−borane
dehydrocoupling reactions22,23 and alkene hydroboration.24
Cationic rhodium complexes are well known to be excellent
selective hydrogenators of alkynes, from the classic work of
Schrock and Osborn from the 1970s.5 The charged alkyne
substrate was [Ph3P(CH2)4C2H]+[PF6]− (2[PF6]), which was
hydrogenated over the course of the reaction to the alkene
[Ph3P(CH2)4C(H)CH2]+[PF6]− (3[PF6]) and eventually
the alkane [Ph3P(CH2)5CH3]+[PF6]− (4[PF6]). A slightly
different alkene, [Ph3P(CH2)3C(H)CH2]+[PF6]− (5[PF6]),
was also prepared for a competition study.
1
product was a white powder (0.55 g, 1.12 mmol, 53%). H NMR
(CDCl3 300 MHz): δ (ppm) 7.81 (m, 3H, PPh3); 7.70 (m, 12H,
PPh3); 3.22 (m, 2H, PPh3CH2); 2.29 (m, 2H, CH2C2H); 1.86, (t, 1H,
CH2CH2CH2C2H); 1.81 (m, 3H, CH2CH2CH2C2H); 1.26 (s, 1H,
C2H). ESI-MS(+): m/z 343.1. ESI-MS(−): m/z 145.0.
5[I]: [Ph3P(CH2)3C(H)CH2]+[PF6]−, Pent-4-en-1-yltriphenyl-
phosphonium Bromide. Triphenylphosphine (5.5 g, 20.1 mmol)
was dissolved into 10 mL of toluene in a Schlenk flask at 75 °C, and 5-
bromo-1-pentene (2.1 g, 13.4 mmol) added dropwise over 10 min.
The mixture was stirred for 72 h, before the product was filtered off,
washed with toluene, and dried under high vacuum. Final product was
a white powder (0.50 g, 1.2 mmol, 9%). ESI-MS(+): m/z 331.1. ESI-
MS(−): m/z 78.9.
EXPERIMENTAL SECTION
■
Fluorobenzene was freshly distilled from P2O5 before use. All other
solvents were dispensed from an MBraun solvent purification system
immediately before use. All reactions were under a nitrogen or argon
atmosphere. Chemicals and solvents were purchased from Aldrich and
used without subsequent purification. The charged alkyne was
prepared by a previously published method.1 All mass spectra were
collected by using a Micromass Q-Tof Micro mass spectrometer in
positive ion mode using pneumatically assisted electrospray ionization:
capillary voltage, 3000 V; extraction voltage, 0.5 V; source temper-
5[PF6]: [Ph3P(CH2)3C(H)CH2]+[PF6]−, Pent-4-en-1-yltriphe-
nylphosphonium Hexafluorophosphate(V). Sodium hexafluoro-
phosphate (0.50 g, 3.0 mmol) was dissolved in 5 mL of water, and 5
mL of a water solution of [Ph3P(CH2)3C2H3]+[I]− (0.50 g, 1.2 mmol)
was added dropwise with stirring. The product was filtered and washed
with water and dried under high vacuum for a week. Final product was
3022
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
a white powder (0.52 g, 1.1 mmol, 91%). 1H NMR (CDCl3 300
MHz): δ (ppm) 7.80 (m, 3H, PPh3); 7.68 (m, 12H, PPh3); 5.68 (m,
1H, −CH2CH2); 5.05 (m, 2H, −CH2CH2); 3.13 (m, 2H, PPh3CH2);
2.30 (m, 2H, −CH2CH2CH2); 1.71 (m, 2H, PPh3CH2CH2). ESI-
MS(+): m/z 331.1. ESI-MS(−): m/z 145.0.
RESULTS AND DISCUSSION
■
Cationic rhodium(I) complexes are, as already mentioned,
known to be active hydrogenation catalysts27 and are readily
detected by ESI-MS. Used here was [Rh(PcPr3)2(η6-
FPh)]+[BArF ]− (ArF = 3,5-bis(trifluoromethyl)phenyl)
4
(1[BArF ]),15 as the phosphine is small, tied-back, and unlikely
Figure 3. PSI-ESI-MS trace for hydrogenation of the alkyne 2[PF6]
4
under 3 psi of H2, with 13.3% of 1[BArF ] as catalyst at room
temperature with FPh as solvent. Inset: Relative intensity vs time plot
exhibiting behavior of [Rh(PcPr3)2(η6-FPh)]+ (1+) and [Rh(PcPr3)2]+
(1a+).
to partake in C−H activation or intramolecular dehydrogen-
ation reactions that would complicate the mass spectral
analysis. The charged substrate used was [Ph3P-
(CH2)4C2H]+[PF6]− (2[PF6]), which proved to have the
right combination of solubility, high ESI-MS response factor,
and lack of reactivity of the tag for the purposes of reaction
analysis.14 The product alkane, [Ph3P(CH2)5CH3][PF6]
(4[PF6]), was isolated and crystallized to establish that the
reactivity of the charge-tagged alkyne duplicates that of a
regular terminal alkyne; the resulting structure of the
triphenyhexylphosphonium salt was entirely unremarkable
(Figure 2).
4
substrate is not involved in the turnover-limiting step (vide
infra). This suggests that the alkyne (alkene) coordination to
the Rh complex is fast and lies a long way toward the alkyne (or
alkene) complex, but that the alkyne still substantially
outcompetes the alkene. The reaction is sensitive to the
temperature it is run at (Figure 4), confirming that the reaction
is taking place in solution rather than being some sort of artifact
of the ESI-MS ionization process.28
The reaction is first order in catalyst concentration (see
Supporting Information), there is no induction period, and no
Figure 2. Alkane hydrogenation product 4[PF6]. Key bond lengths
and angles: C5−C6 1.499(3) Å; C4−C5−C6 113.86(19)°.
The kinetic profile of the alkyne hydrogenation reaction
proved to be very different from that catalyzed by Wilkinson’s
catalyst, Rh(PPh3)3Cl.1 For Wilkinson’s catalyst, the rate of
alkyne hydrogenation was only 3 times faster than the rate of
alkene hydrogenation, and the turnover-limiting step was
phosphine dissociation from the Rh(PPh3)3Cl precatalyst to
generate the reactive 14-electron species Rh(PPh3)2Cl.
However, for the cationic rhodium catalyst studied here,
hydrogenation of the alkyne 2+ was 40× faster than
hydrogenation of the corresponding alkene, [Ph3P-
(CH2)4CHCH2]+ (3+), and production of both appeared
to be essentially zero order in alkyne (alkene). No
intermediates were observed that included both rhodium
complex and the charged tag, and the only observed
rhodium-containing species were [Rh(PcPr3)2(η6-FPh)]+ (1+)
and [Rh(PcPr3)2]+ (1a+). These features are summarized in
Figure 3.
Figure 4. PSI-ESI-MS traces for (top) the disappearance of alkyne 2+
at 23, 38, and 49 °C (fast at all temperatures); (middle) appearance
and consumption of alkene 3+; (bottom) appearance of alkane 4+.
The selectivity for alkyne over alkene is striking at the early
stages of reaction (at least 40:1), but because the reaction is
(close to) zero order in alkynes (alkene), we suspect that this
3023
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
di- or polynuclear rhodium species are observed, suggesting
that the reaction involves a mononuclear rhodium species as
catalyst. Hydrogen was present in large excess during the
preliminary catalytic runs, so another experiment was carried
out to establish whether the reaction profile changed under
stoichiometric conditions. The experiment was reexamined
using a single equivalent of H2 (170 μL); the (well-stirred, to
avoid diffusion effects) reaction was much slower, and the
overall reaction displayed first-order characteristics (Figure 5).
or the alkene needs justifying. We can do so on several
grounds:
(a) Monodentate alky(e)nes are difficult to characterize by
ESI-MS at the best of times because they are generally weakly
bound and easily lost during the desolvation process.13 This is
exacerbated for a cationic metal complex binding a cationic
alky(e)ne, as the charges repel each other.
(b) Addition of octyne to 1[BArF ] displaces the
4
fluorobenzene and produces the ions [Rh(PcPr3)2(octyne)n]+
(n = 1 or 2; see Supporting Information). This observation
suggests that fluorobenzene is a relatively weakly bound
ligand32 and is easily displaced by alkynes. Interestingly, with
different, chelating, ligands and CH2Cl2 solvent PhF dissocia-
tion is slow.33
(c) We never observe ions of the form [Rh(PcPr3)(H)2]+ in
the mass spectrometer in the presence of H2, suggesting that
addition of H2 to the catalyst is either slow or lies a long way in
the wrong direction (hydrides are readily observed by ESI-
MS).34 We examined complex 1[BArF ] with H and 31P{1H}
1
4
NMR spectroscopy under a pressure of ∼4 atm of H2 in PhF
solvent, and there were no observable changes at room
temperature (storage of this solution under H2 overnight led to
Figure 5. PSI-ESI-MS traces for the selective hydrogenation of the
charge-tagged alkyne 2+ in the presence of 1.1 equiv of H2. Inset: ln[x]
vs time plot exhibiting first-order behavior.
the appearance of a doublet of multiplets at δ 4.33 ppm (2JHF
=
48.8 Hz) and several multiplets from δ 1.68 to 0.73 ppm
characteristic of fluorocyclohexane35 from the hydrogenation of
fluorobenzene, a process that has been shown previously to
proceed via a colloidal Rh catalytic route36). By contrast,
The reaction rate doubled if two equivalents of H2 were used
instead of one (see the Supporting Information), suggesting the
reaction is not limited by mass transport under these
experimental conditions.
Given that the turnover-limiting step seemed to involve
hydrogen, it was reasonable to assume that a primary kinetic
isotope effect (KIE)29 may be detectable in the reaction. As
such, the reaction was examined using D2 instead of H2, and we
found the alkene → alkane reduction to be appreciably faster
for H2, by a factor of kH/kD = 2.1 0.2 (Figure 6). This value is
addition of alkyne (1-octyne) to a PhF solution of 1[BArF ] at
4
1
5 mol % loadings resulted in complex 31P{1H} and H NMR
spectra that showed many species to be present. No distinctive
1
signals at high field in the H NMR spectrum that would
indicate Rh−H species were observed. Addition of 1-octyne to
a sample of 1[BArF ] under 4 atm of H2 led to very similar
4
1
31P{1H} and H NMR spectra, suggesting similar speciation
under H2. 1-Octene was also observed, consistent with catalytic
turnover. These NMR data suggest that H2 addition is the
limiting rate, and thus the complex speciation observed by
solution NMR spectroscopy represents the resting state of the
system.
Osborn and Schrock outlined three possible mechanisms for
the hydrogenation of alkenes by cationic rhodium complexes
(Scheme 1).5
Path A involved addition of H2 to [RhLn]+, then
deprotonation to form an active neutral catalyst of the form
HRhLn. Alkene coordination, migration, H2 addition, and
reductive elimination of alkane followed. Path B involved
addition of H2, then coordination of alkene to [RhLn]+,
followed by migration and reductive elimination of the product
alkane. Path C is the same as path B, except the order of H2 and
alkene addition is reversed. Osborn and Schrock considered
path A to predominate in the polar solvents acetone, 2-
methoxyethanol, and tetrahydrofuran, except where binding of
the alkene was particularly strong, such as in the selective
hydrogenation of dienes.5 THF is capable of deprotonating
metal hydrides.37
Halpern and co-workers studied hydrogenation of 1-hexene
and other substrates using a variety of [Rh(PP)]+ (PP =
chelating bisphosphine) complexes as catalysts under mild
conditions in methanol (ambient temperature and 1 atm of
H2).38 They found that oxidative addition of H2 to [Rh(PP)-
(alkene)]+ was rate-determining, consistent with pathway C
being operative. They found that the bis(triphenylphosphine)
complex seemed to proceed via pathway B, with the slow steps
Figure 6. PSI-ESI-MS traces for the reduction of alkyne 2+ to alkane
4+ using H2 (blue/yellow) vs D2 (green/red).
consistent with oxidative addition (OA) being the slow step,
since concerted OA requires the breaking of a H−H (D−D)
bond. This KIE is larger than expected if hydride insertion or
reductive elimination was rate-determining.30 We cannot
discount that equilibrium isotope effects are operating prior
to such a step, and reactions involving small molecules such as
H2 can generate isotope effects that are highly dependent on
system and temperature.31 However, other evidence points to
H2 addition after alkyne (or alkene) binding being turnover-
limiting (vide infra).
So while the kinetics point to the oxidative addition of H2
being turnover-limiting, the fact we are unable to identify
intermediates by ESI-MS containing the charge-tagged alkyne
3024
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
Scheme 1. Pathways for Alkene Hydrogenation, after Schrock and Osborn5
being addition of the alkene to [H2Rh(PPh3)2]+ and
elimination of the alkane, but that the observed kinetics were
also consistent with pathway C if oxidative addition of H2 was
fast and the equilibrium lay a long way to the product.39
We considered all three mechanisms as possible candidates
to explain our observations, but ultimately settled on path C,
for the following reasons:
(d) The solvent used, fluorobenzene, is inimical to
deprotonation compared to the polar solvents used by Schrock
and Osborn (tetrahydrofuran, acetone, 2-methoxyethanol).
(e) The numerical modeling (vide infra) proved most
tractable for path C, providing excellent correlation with
experimental data. Neither path A nor path B provided sensible
solutions. This evidence is circumstantial given that the fit of
eight rate constants is underdetermined, but nonetheless it
confirms that there exist plausible sets of rate constants for path
C that fit nicely to the experimental data. Path C has been
redrawn in Scheme 2 and elaborated to include the alkyne and
the alkene on the same plot.
(a) Neither HRhLn (path A) nor [H2RhLn]+ (path B) could
be detected by 1H NMR spectroscopy when examining
[RhP2(η6-FPh)]+ in the presence of H2, nor could [H2RhLn]+
(path B) be observed by ESI-MS. If path B is operative, the
equilibrium must lie a long way toward the left.
(b) If path A was operative, any of the intermediates
HRhP2(alkene), RhRP2, and RhH2RP2 would be expected to be
observable as monocations using ESI-MS, due to the charged
tag. None of these species were in fact observed. If this path
was operative, at least one (the resting state) should be seen.
(c) Addition of bases such as NEt3 ought to accelerate
reactions proceeding through a fast path A, due to the
deprotonation equilibrium being perturbed in the direction of
RhHP2. However, no such acceleration was observed. Indeed,
the reaction was slowed in the presence of NEt3 (Figure 7), and
the reaction became much less selective for the alkyne.
a
Scheme 2. Mechanism of Alkyne/Alkene Hydrogenation
a
Figure 7. PSI-ESI-MS traces showing the effect of NEt3 on the rate
and selectivity of hydrogenation.
P = P(cyclopropyl)3.
Using the cycle in Scheme 2, we constructed a numerical
model and used the program COPASI40 to generate a set of
rate constants compatible with the results that we observe. We
then tested a variety of optimization methods and starting
points. Given the number of independent parameters (if all
steps in the cycle were reversible, there are 18 rate constants to
consider), we simplified the picture by assuming hydride
migration and reductive elimination steps were fast and (quasi)
irreversible, leaving a more tractable 10 rate constants to
optimize. Two out of these 10 rate constants, 1+ → 1a+ and 1a+
The reaction reached a maximum of 50% in alkene only, very
similar to the degree of selectivity exhibited by Wilkinson’s
catalyst.1 Addition of NEt3 to [RhP2]+ in the presence of H2
resulted in disappearance of [RhP2]+ and the appearance of
[HNEt3]+ (see the Supporting Information), suggesting the
formation of neutral RhHP2 and the operation of the slower
and less alkyne-selective path A.
3025
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
Figure 8. Direct comparison between simulated (colored lines) and experimental results (black, from PSI-ESI-MS) for path C and, in the inset, paths
A and B.
→ 1+, can be approximated based on the experimental
measurements. These showed that a stable amount of 1a+
exists in the reacting solution. After we fix these values to
produce the roughly equivalent amounts of 1+ and 1a+ as seen
in the ESI-MS traces, the remaining eight rate constants can be
optimized by COPASI by using a variety of mathematical
methods (see the Supporting Information). All these methods
generated similar rate constants and high-quality matches for
the experimental data for path C. Similar procedures carried out
with paths A and B produce significantly worse matches, being
unable to replicate the close to zero-order behavior or the
significant quantities of 1+ and 1a+ present throughout the
reaction (Figure 8).
The lack of any initiation time suggested that fluorobenzene
dissociation (1+ → 1a+) was fast. As such, trying to model this
dissociation step added complexity to the model without
adding anything to our understanding of the productive part of
the cycle. Accordingly, we inspected the catalyst behavior over
the course of the reaction and selected rate constants that
reflected the relative abundances of 1+ and 1a+. These values
were approximated to 10 min−1 and 0.1 min−1 mmol−1 L,
respectively. All models predicted that binding of the alkene to
1a+ was slower than the binding of the alkyne to 1a+ (1a+ →
X+) by a factor of at about 40, but that both were relatively fast.
However, this factor appeared to be just part of the reason for
the selectivity for alkyne over alkene. Oxidative addition of
hydrogen (X+ → Y+) seems to be turnover-limiting, as
predicted by the stoichiometric H2 addition, the overall zero-
order kinetics, and the primary KIE established from the D2
experiment. As expected, the numerical modeling is in
agreement: this step is slow and, especially so for the alkene,
by a factor of about 40 compared to the alkyne. No attempt was
made to model the migration and reductive elimination (Y+ →
Z+ and Z+ → 1a+) steps. Y+ and Z+ are indistinguishable by MS
because they are isomers, and the fact that neither could be
observed makes it unlikely that they are resting states.
[Ph3P(CH2)3CHCH2]+ was perhaps due to a small
electronic effect due to the greater proximity of the charged tag.
Examination of catalyst behavior showed that the ratio of 1+
to 1a+ stayed fairly constant and fairly similar in intensity
throughout the reaction (see the Supporting Information). The
absolute intensity reached a maximum soon after catalyst
addition, and the intensity drops as the reaction proceeds,
stabilizing at the completion of the reaction. We attribute this
behavior to a competitive catalyst decomposition pathway
stemming from a reaction intermediate (if the decomposition
was from a catalyst precursor, the decomposition ought to
continue after the cessation of the reaction). We could not
identify any charged rhodium-containing species that could
account for the disappearance of signal, suggesting that the
decomposition product is neutral. RhP2H is one such
possibility; there was no color change that might indicate the
formation of metallic rhodium.
CONCLUSIONS
■
Analysis of alkyne hydrogenation using a charge-tagged alkyne
and a cationic rhodium catalyst revealed the catalyst to be a
highly efficient partial hydrogenator, with a rate of alkyne
hydrogenation in excess of 40 times faster than alkene
hydrogenation. The mechanism was shown by a combination
of ESI-MS, NMR, kinetic isotope effects, and numerical
modeling methods to most likely have a turnover-limiting
step of oxidative addition of hydrogen following alkyne/alkene
binding. Using a stoichiometric amount of hydrogen was shown
to be an effective means of enabling selective hydrogenation to
the alkene.
ASSOCIATED CONTENT
■
S
* Supporting Information
Numerical modeling, further kinetic data, mass spectra, X-ray
crystal structure data for precatalyst 1[BArF ]. The Supporting
4
Information is available free of charge on the ACS Publications
website at DOI: 10.1021/acs.organomet.5b00322.
Further confirmation of the mechanism came through
competition experiments. We took the charge-tagged alkyne
2[PF6] and a similar charge-tagged alkene, 5[PF6], and
conducted an excess H2 reduction competitively. Neither
alkene (3[PF6] as derived from 2[PF6] or 5[PF6]) reacted
until practically all of the alkyne 2[PF6] was consumed, at
which point the observed rates of alkene consumption were
fairly similar to each other (Supporting Information): 3.2 ×
10−4 mol L−1 min−1 for 5[PF6] + H2 and 2.5 × 10−4 mol L−1
min−1 for 3[PF6] + H2. The fractionally faster rate for
AUTHOR INFORMATION
■
Corresponding Author
*Fax: +1 (250) 721-7147. Tel: +1 (250) 721-7181. E-mail:
mcindoe@uvic.ca.
Notes
The authors declare no competing financial interest.
3026
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
J. E.; Knochel, P.; Koszinowski, K. J. Org. Chem. 2010, 75, 6848−6857.
(j) Jansen, H.; Samuels, M. C.; Couzijn, E. P. A.; Slootweg, J. C.;
Ehlers, A. W.; Chen, P.; Lammertsma, K. Chem.Eur. J. 2010, 16,
1454−1458. (k) dos Santos, M. R.; Coriolano, R.; Godoi, M. N.;
Monteiro, A. L.; de Oliveira, H. C. B.; Eberlin, M. N.; Neto, B. A. D.
New J. Chem. 2014, 38, 2958−2963. (l) Medeiros, G. A.; da Silva, W.
A.; Bataglion, G. A.; Ferreira, D. A. C.; de Oliveira, H. C. B.; Eberlin,
M. N.; Neto, B. A. D. Chem. Commun. 2014, 50, 338−340.
(m) Oliveira, F. F. D.; dos Santos, M. R.; Lalli, P. M.; Schmidt, E.
M.; Bakuzis, P.; Lapis, A. A. M.; Monteiro, A. L.; Eberlin, M. N.; Neto,
B. A. D. J. Org. Chem. 2011, 76, 10140−10147.
(16) (a) Banu, L.; Blagojevic, V.; Bohme, D. K. J. Phys. Chem. B 2012,
116, 11791−11797. (b) Polyansky, D. E.; Muckerman, J. T.; Rochford,
J.; Zong, R.; Thummel, R. P.; Fujita, E. J. Am. Chem. Soc. 2011, 133,
14649−14665.
(17) Bridgewater, J. D.; Lim, J.; Vachet, R. W. Anal. Chem. 2006, 78,
2432−2438.
ACKNOWLEDGMENTS
■
J.S.M. thanks the Natural Sciences and Engineering Research
Council (NSERC) of Canada, the Canada Foundation for
Innovation (CFI), the British Columbia Knowledge Develop-
ment Fund (BCKDF), and the University of Victoria for
instrumentation and operational funding. A.S.W. thanks the
University of Oxford and the EPSRC (EP/J02127X/1).
REFERENCES
■
(1) (a) James, B. R. Homogeneous Hydrogenation; Wiley: New York,
1973. (b) Hartwig, J. F. OrganoTransition Metal Chemistry; University
Science Books: Sausalito, CA, 2010.
(2) Young, J. F.; Osborn, J. A.; Jardine, F. H.; Wilkinson, G. Chem.
Commun. 1965, 131−132.
(3) Osborn, J. A.; Jardine, F. H.; Young, J. F.; Wilkinson, G. J. Chem.
Soc. A 1966, 1711−1732.
(18) Wu, Z.-J.; Luo, S.-W.; Xie, J.-W.; Xu, X.-Y.; Fang, D.-M.; Zhang,
G.-L. J. Am. Soc. Mass Spectrom. 2007, 18, 2074−2080.
(19) (a) Jackson, S. M.; Chisholm, D. M.; McIndoe, J. S.; Rosenberg,
L. Eur. J. Inorg. Chem. 2011, 327−330. (b) Beierlein, C. H.; Breit, B.;
Paz Schmidt, R. A.; Plattner, D. A. Organometallics 2010, 29, 2521−
2532.
(4) (a) Halpern, J.; Okamoto, T.; Zakhariev, A. J. Mol. Catal. 1977, 2,
65−68. (b) Cabrera, M. I.; Zgolicz, P. D.; Grau, R. J. Appl. Catal. A:
Gen. 2008, 334, 291−303. (c) Nelson, D. J.; Li, R.; Brammer, C. J. Org.
Chem. 2004, 70, 761−767. (d) Bowker, M.; Gland, J.; Joyner, R.; Li,
Y.; Slin’ko, M.; Whyman, R. Catal. Lett. 1994, 25, 293−308. (e) Koga,
N.; Daniel, C.; Han, J.; Fu, X. Y.; Morokuma, K. J. Am. Chem. Soc.
1987, 109, 3455−3456. (f) Wink, D.; Ford, P. C. J. Am. Chem. Soc.
1985, 107, 1794−1796. (g) Wink, D. A.; Ford, P. C. J. Am. Chem. Soc.
1987, 109, 436−442. (h) Duckett, S. B.; Newell, C. L.; Eisenberg, R. J.
Am. Chem. Soc. 1993, 115, 1156−1157. (i) Duckett, S. B.; Newell, C.
L.; Eisenberg, R. J. Am. Chem. Soc. 1994, 116, 10548−10556.
(5) Schrock, R. R.; Osborn, J. A. J. Am. Chem. Soc. 1976, 98, 2143−
2147.
(20) Henderson, M. A.; Luo, J.; Oliver, A.; McIndoe, J. S.
Organometallics 2011, 30, 5471−5479.
(21) (a) Vikse, K. L.; Woods, M. P.; McIndoe, J. S. Organometallics
2010, 29, 6615−6618. (b) Vikse, K. L.; Ahmadi, Z.; Luo, J.; van der
Wal, N.; Daze, K.; Taylor, N.; McIndoe, J. S. Int. J. Mass Spectrom.
2012, 323−324, 8−13.
(22) Sewell, L. J.; Lloyd-Jones, G. C.; Weller, A. S. J. Am. Chem. Soc.
2012, 134, 3598−3610.
(6) (a) James, B. R.; Mahajan, D. Can. J. Chem. 1979, 57, 180−187.
(23) Dallanegra, R.; Robertson, A. P. M.; Chaplin, A. B.; Manners, I.;
Weller, A. S. Chem. Commun. 2011, 47, 3763−3765.
(b) Kohrt, C.; Wienhofer, G.; Pribbenow, C.; Beller, M.; Heller, D.
̈
ChemCatChem 2013, 5, 2818−2821.
(24) Sewell, L. J.; Chaplin, A. B.; Weller, A. S. Dalton Trans. 2011, 40,
7499−7501.
(7) (a) James, B. R.; Wang, D. K. W. Can. J. Chem. 1980, 58, 245−
250. (b) Knowles, W. S. Adv. Synth. Catal. 2003, 345, 3−13. (c) Cipot,
J.; McDonald, R.; Ferguson, M. J.; Schatte, G.; Stradiotto, M.
(25) Patiny, L.; Borel, A. J. Chem. Inf. Model. 2013, 53, 1223−1228.
(26) Wang, K.; Goldman, M. E.; Emge, T. J.; Goldman, A. S. J.
Organomet. Chem. 1996, 518, 55−68.
Organometallics 2007, 26, 594−608. (d) Bell, S.; Wustenberg, B.;
Kaiser, S.; Menges, F.; Netscher, T.; Pfaltz, A. Science 2006, 311, 642−
̈
(27) (a) Doran, S.; Achard, T.; Riera, A.; Verdaguer, X. J. Organomet.
Chem. 2012, 717, 135−140. (b) Cadierno, V.; Díez, J.; García-Garrido,
S. E.; Gimeno, J.; Pizzano, A. Polyhedron 2010, 29, 3380−3386.
(c) Ahlquist, M.; Gustafsson, M.; Karlsson, M.; Thaning, M.; Axelsson,
O.; Wendt, O. F. Inorg. Chim. Acta 2007, 360, 1621−1627. (d) Burk,
M. J.; Harper, T. G. P.; Lee, J. R.; Kalberg, C. Tetrahedron Lett. 1994,
35, 4963−4966.
644.
(8) Chan, A. S. C.; Pluth, J. J.; Halpern, J. Inorg. Chim. Acta 1979, 37,
L477−L479.
(9) (a) James, B. R. Catal. Today 1997, 37, 209−221. (b) Kobayashi,
S.; Ishitani, H. Chem. Rev. 1999, 99, 1069−1094.
(10) Longley, C. J.; Goodwin, T. J.; Wilkinson, G. Polyhedron 1986,
5, 1625−1628.
(28) Muller, T.; Badu-Tawiah, A.; Cooks, R. G. Angew. Chem., Int. Ed.
̈
(11) (a) Landis, C. R.; Hilfenhaus, P.; Feldgus, S. J. Am. Chem. Soc.
1999, 121, 8741−8754. (b) Imamoto, T.; Tamura, K.; Zhang, Z.;
Horiuchi, Y.; Sugiya, M.; Yoshida, K.; Yanagisawa, A.; Gridnev, I. D. J.
Am. Chem. Soc. 2012, 134, 1754−1769. (c) Donald, S. M. A.; Vidal-
Ferran, A.; Maseras, F. Can. J. Chem. 2009, 87, 1273−1279. (d) Reetz,
M. T.; Meiswinkel, A.; Mehler, G.; Angermund, K.; Graf, M.; Thiel,
W.; Mynott, R.; Blackmond, D. G. J. Am. Chem. Soc. 2005, 127,
10305−10313.
2012, 51, 11832−11835.
(29) (a) Bernskoetter, W. H.; Lobkovsky, E.; Chirik, P. J. J. Am.
Chem. Soc. 2005, 127, 14051−14061. (b) Janak, K. E.; Parkin, G. J. Am.
Chem. Soc. 2003, 125, 13219−13224.
́
(30) Zuidema, E.; Escorihuela, L.; Eichelsheim, T.; Carbo, J. J.; Bo,
C.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Chem.Eur. J. 2008,
14, 1843−1853.
(31) Zhu, G.; Janak, K. E.; Parkin, G. Chem. Commun. 2006, 2501−
2503.
(12) Chisholm, D. M.; McIndoe, J. S. Dalton Trans. 2008, 3933−
3945.
(32) Pike, S. D.; Pernik, I.; Theron, R.; McIndoe, J. S.; Weller, A. S. J.
(13) Chisholm, D. M.; Oliver, A. G.; McIndoe, J. S. Dalton Trans.
2010, 39, 364−373.
Organomet. Chem. 2015, 784, 75−83.
(33) Hooper, J. F.; Young, R. D.; Weller, A. S.; Willis, M. C. Chem.
Eur. J. 2013, 19 (9), 3125−3130.
(14) Luo, J.; Oliver, A. G.; McIndoe, J. S. Dalton Trans. 2013, 42,
11312−11318.
(34) Brayshaw, S. K.; Harrison, A.; McIndoe, J. S.; Marken, F.;
Raithby, P. R.; Warren, J. E.; Weller, A. S. J. Am. Chem. Soc. 2007, 129,
1793−1804.
́
́
(15) (a) Hyvl, J.; Roithova, J. Org. Lett. 2013, 16, 200−203.
(b) Chen, P. Angew. Chem., Int. Ed. 2003, 42, 2832−2847. (c) Torker,
S.; Merki, D.; Chen, P. J. Am. Chem. Soc. 2008, 130, 4808−4814.
(d) Santos, L. S. Eur. J. Org. Chem. 2008, 2008, 235−253. (e) Eberlin,
M. Eur. J. Mass Spectrom. 2007, 13, 19−28. (f) Robinson, P. S. D.;
Khairallah, G. N.; da Silva, G.; Lioe, H.; O’Hair, R. A. J. Angew. Chem.,
Int. Ed. 2012, 51, 3812−3817. (g) Ryzhov, V.; Lam, A. Y.; O’Hair, R. J.
J. Am. Soc. Mass Spectrom. 2009, 20, 985−995. (h) Vikse, K. L.;
Ahmadi, Z.; Manning, C. C.; Harrington, D. A.; McIndoe, J. S. Angew.
Chem., Int. Ed. 2011, 50, 8304−8306. (i) Schade, M. A.; Fleckenstein,
(35) Lambert, J. B.; Greifenstein, L. G. J. Am. Chem. Soc. 1974, 96,
5120−5124.
(36) (a) Yang, H.; Gao, H.; Angelici, R. J. Organometallics 1999, 18,
2285−2287. (b) Blum, J.; Rosenfeld, A.; Gelman, F.; Schumann, H.;
Avnir, D. J. Mol. Catal. A: Chem. 1999, 146, 117−122.
(37) Ingleson, M. J.; Mahon, M. F.; Weller, A. S. Chem. Commun.
2004, 2398−2399.
3027
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028

Organometallics
Article
(38) Halpern, J.; Riley, D. P.; Chan, A. S. C.; Pluth, J. J. J. Am. Chem.
Soc. 1977, 99, 8055−8057.
(39) Landis, C. R.; Halpern, J. J. Organomet. Chem. 1983, 250, 485−
490.
(40) Hoops, S.; Sahle, S.; Gauges, R.; Lee, C.; Pahle, J.; Simus, N.;
Singhal, M.; Xu, L.; Mendes, P.; Kummer, U. Bioinformatics 2006, 22,
3067−3074.
3028
DOI: 10.1021/acs.organomet.5b00322
Organometallics 2015, 34, 3021−3028