Synthesis, structure, and applications of pyridiniophosphines

Article abstract of DOI:10.1002/anie.201401073

A new family of cationic ligands, N-alkyl/aryl pyridiniophosphines, has been synthesized through a short, scalable, and highly modular route. Evaluation of their electronic properties evidenced weak σ-donor and quite strong π-acceptor character when used

Full text of DOI:10.1002/anie.201401073

Angewandte
Chemie
DOI: 10.1002/anie.201401073
Cationic Phosphines
Hot Paper
Synthesis, Structure, and Applications of Pyridiniophosphines**
Hendrik Tinnermann, Christian Wille, and Manuel Alcarazo*
Dedicated to Professor Walter Thiel on the occasion of his 65th birthday
Abstract: A new family of cationic ligands, N-alkyl/aryl
pyridiniophosphines, has been synthesized through a short,
scalable, and highly modular route. Evaluation of their
electronic properties evidenced weak s-donor and quite
strong p-acceptor character when used as ancillary ligands.
These attributes confer a substantially enhanced p-acidity to
the PtII and AuI complexes thereof derived and, as result, they
depict an improved ability to activate alkynes towards nucle-
ophilic attack. This superior performance has been demon-
strated along several mechanistically diverse PtII- and AuI-
catalyzed transformations.
ligands depict. Moreover, taking advantage of these proper-
ties, we have been able to develop new AuI and PtII catalysts
that exhibit an unmatched ability to activate alkynes toward
hydroarylation reactions.[2]
However, the specific use of di(isopropylamino) cyclo-
propenium substituents compromises to some extend the
independent fine tuning of steric and electronic properties in
the resulting phosphines owing to the synthetic and geometric
restrictions that these cationic groups impose.[3,4] Moreover,
the best catalytic performances are often obtained by the
employment of di- or tricationic catalysts that, because of
their highly charged nature, depict low solubility in typical
organic solvents. For these reasons, the use of alternative
positively charged substituents, which are more amenable to
stereoelectronic modification, seems to be adequate to
further expand the still limited repertoire of extreme p-
acceptor ligands and their applications in metal catalysis.[5]
Given these considerations, we envisaged that N-(alkyl/
arylpyridinium)-substituted phosphines might be a potentially
very useful family of strong p-acceptor ligands owing to the
simultaneous confluence of tree beneficial factors: a) The
low-lying p* orbitals of the pyridinium moiety should
effectively interact with the lone pair at phosphorus making
the resulting phosphines very poor donating ligands; b) the
fine stereoelectronic tuning of the resulting phosphines can be
achieved by an appropriate selection of the other two R
groups at phosphorus and additionally, by introduction of
substituents on the pyridinium ring (Figure 1); and c) the
reaction of 1-alkyl/aryl-2-chloropyridinium salts with differ-
ent secondary phosphines offers a short, effective and highly
modular synthetic route to the target ligands.[6]
F
or the design of an effective metal-catalyzed process, the
choice of the ancillary ligand is crucial; in fact, it can be as
critical as the choice of the metal itself. This is due to the
extraordinary control that ligands exert over the reactivity of
the resulting catalysts and, not less important, over the
product selectivity of the catalyzed process. The selection of
the most appropriate ligand for each particular transforma-
tion must then consider among others, the nature of the rate
determining step and the plausible (not desired) reaction
pathways.
In this context where ligands that depict different proper-
ties are necessary, phosphines play a prominent role because
both their donor ability and steric requirements can be easily
adjusted at convenience by modification of the substituents
attached to the phosphorus atom. Specifically, if strong Lewis
acidity is required at the metal, poor electron-releasing
phosphites or polyfluorinated phosphines are the ligands of
choice. This is often the case in Pt and Au catalysis.[1]
Very recently, we developed an alternative strategy for the
synthesis of even weaker electron donor phosphines consist-
ing of the direct attachment of up to three cationic bis(di-
alkylamino) cyclopropenium substituents to the central P-
atom. The positive charges thus introduced account for the
poor s-donor and excellent p-acceptor abilities that these
To put our design concept into practice, we first prepared
pyridinium-substituted phosphines 12–19 in good to excellent
yields through a two-step sequence. N-alkylation of readily
available 2-chloropyridines 1–4 with trimethyl- or triethyl-
oxonium tetrafluoroborates afforded the corresponding pyr-
[*] H. Tinnermann, C. Wille, Dr. M. Alcarazo
Max-Planck-Institut fꢀr Kohlenforschung
Kaiser Wilhelm Platz 1, 45470- Mꢀlheim an der Ruhr (Germany)
E-mail: alcarazo@mpi-muelheim.mpg.de
[**] Generous financial support from the Fonds der Chemischen
Industrie (Dozentenstipendium to M.A.), the European Research
Council (ERC Starting Grant to M.A.), and the Deutsche For-
schungsgemeinschaft (AL 1348/4-1) is gratefully acknowledged. We
also thank Prof. A. Fꢀrstner for constant support of our research
programs and the assistance from our NMR spectroscopy and X-ray
crystallography departments.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201401073.
Figure 1. Structural features of pyridinium-substituted phosphines and
their impact on the donor properties of the resulting ligand.
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idinium salts 6, 8–11 in excellent yields. 1-Aryl substituted 2-
chloropyridinium salts such as 7 could be also obtained
through an alternative procedure consisting on an Ullmann
coupling between pyridone 5 and iodoarenes[7] followed by
treatment with oxalyl chloride.[8] Subsequently, the unprece-
dented condensation of 2-chloropyridinium salts 6–11 with
a range of secondary phosphines efficiently afforded the
desired pyridiniophosphines 12–19 in moderate to good yields
(see Scheme 1 and the Supporting Information).
At this point we tried to evaluate the donor endowment of
the new cationic phosphines by analysis of the CO stretching
frequencies in trans-[RhCl(CO)L2] complexes 20–25 (Table 1
and Scheme 2). However, these data were misleading and
certainly should be taken with caution. For example, ligand 19
that bears five CF3 groups seems to be a stronger electron
donor than 16 that shares the same skeleton but carries only
one CF3 substituent (Table 1, entries 3 and 6). This clearly
indicates that in Rh complexes 20–25, the CO stretching
frequencies may not only be determined by the electronic
properties of the ligands on Rh, but also influenced by small
geometric changes around the metal owing to steric factors or
Table 1: Carbonyl stretching frequencies in [RhCl(CO)L2](BF4)2 com-
plexes in the solid state and electrochemical redox potential of the
ligands. The values of commonly used phosphorus ligands are also
included for comparison.
Ep(ox)[b]
[a]
˜
nCO
Entry
Ligand
[RhCl(CO)L2](BF4)2
1
2
3
4
5
6
7
8
9
12
15
16
17
18
19
26
27
1996
1994
2004
1982
1974
2001
1971
–
1.398
1.355
1.436
1.297
1.269
1.578[c]
1.207
1.541
0.687
1.287
Scheme 1. Synthesis of pyridinium-substituted phosphines. Reagents
and conditions (yields): a) Me3OBF4 or EtOBF4, CH2Cl2, RT; 6 (91%);
8 (99%); 9 (99%); 10 (98%); 11 (89%); b) 5 (1.2 equiv), iodobenzene
(1 equiv), CuBr (10 mol%), Cs2CO3 (2.1 equiv), DMSO, 608C, (95%);
c) oxalyl chloride (3 equiv), Cl(CH2)2Cl, and then NaBF4 (4 equiv),
(71%); d) diaryl/dialkylphosphine (2 equiv), THF, 658C; 1–3 days; 12
(70%), 13 (80%); 14 (71%); 15 (43%); 16 (60%); 17 (77%); 18
(89%); 19 (30%).
Ph3P
(MeO)3P
1979
2011
10
[a] Values in cmÀ1. [b] Oxidation peak potentials reported in V. Calibrated
versus ferrocene/ferrocenium (E1/2 =0.24 V), Bu4NPF6 (0.1m) in CH2Cl2.
[c] Measured in CH3CN.
Figure 2 depicts the structure of 12 in the solid state. The
À
P1 C1 distance (1.8551(7) ꢀ) is only slightly longer than the
À
À
À
other two C P bonds (P1 C7, 1.8260(7) ꢀ; P1 C13,
1.8244(7) ꢀ), which is probably due to the increased steric
hindrance of the N-methylpyridinium group when compared
with the two phenyl rings.[9] Furthermore, the degree of
pyramidalization at phosphorus (61.3%) is even slightly
higher than that observed for PPh3 (56.7%).[10] These
parameters suggest retention of the nonbonding electron
pair at the phosphorus atom.
Scheme 2. Synthesis of Rh complexes and crystal structure of 23.
Hydrogen atoms and BF4 anions were omitted for clarity; ellipsoids
are set at 50% probability.[11] Reagent and conditions (yields):
a) [{RhCl(CO)2}2] (0.25 equiv), CH2Cl2, RT; 20 (99%); 21 (77%); 22
(57%); 23 (78%); 24 (74%).
Figure 2. Crystal structure of 12. Hydrogen atoms and the BF4 anion
were omitted for clarity; ellipsoids are set at 50% probability.[11]
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through-space interactions between CO and the other
ligands.[12,13] For this reason the oxidation potential Ep(ox)
determined by cyclic voltammetry was chosen as a more
reliable parameter to rank the electronic properties of
phosphines 12–19.[14] These data followed the expected
tendency and suggest that ligands 17 and 18, both decorated
with two cyclohexyl substituents, depict donor abilities similar
to that of (MeO)3P, while 12, 15, 16, and 19 are even weaker
donors than this phosphite (Table 1).
process.[16] In fact, increases in rate of reactions were observed
when (C6F5)3P was employed as ancillary ligand or if higher
oxidized Pt species such as PtCl4 were used as catalysts.[17]
Figure 3 also shows the conversion versus time plot for
precatalysts 28 and 29 under otherwise identical conditions
(2 mol% Pt, 808C). Their vastly superior performances,
The Ep(ox) for cyclopropenium substituted phosphines 26
and 27 are also shown for comparison purposes.[2a,c] These
values support the notion that pyridinium substituents are
more effective electron withdrawing groups than di(alkyl-
amino)cyclopropenium rings (compare entries 1 and 7), and
also indicate that if appropriately substituted, pyridiniophos-
phines can reach donor abilities characteristic of dicationic
ligands (entries 3, 6, and 8).
Encouraged by this analysis, we decided to test the
viability of pyridiniophosphines in catalysis and prepared
a set of PtII and AuI complexes in which salts 12–19 were used
as ligands (Scheme 3). Compounds 28–34 were obtained as
air-stable solids by addition of K2PtCl4 or (Me2S)AuCl to
solutions of the corresponding ligands. Moreover, crystals of
28 and 31 were obtained and their structure determined by X-
ray diffraction confirming the expected connectivity.[15]
To compare the catalytic performance of complexes 28
and 29 with standard Pt catalysts, the hydroarylation of
propargyl aryl ether 35 to chromene 36 was chosen as first
model reaction because the proposed mechanism for this
Figure 3. Ligand effect on the Pt-catalyzed hydroarylation of propargyl
aryl ether 35 to chromene 36. Reagents and conditions: a) 35 (0.05m),
Pt precatalysts (2 mol%), AgSbF6 (2 mol%), (CH2)2Cl2, 808C. Conver-
sions determined by gas chromatography.
transformation suggests that
enhanced cationic character should facilitate the whole
a
platinum catalyst with
which clearly surpass the other catalytic mixtures, beautifully
demonstrate the exquisite ability of pyridiniophosphine
ligands to increase the p-acidity of Pt centers. Moreover,
a qualitative correlation between the reactivity depicted by
catalysts 28 and 29 and the measured oxidation potentials
Ep(ox) for their corresponding free ligands could be estab-
lished. This also supports the use of cyclic voltammetry as an
adequate technique to characterize the electronic properties
of P-based ligands.
Interestingly, other synthetically useful and mechanisti-
cally more complex PtII-promoted transformations also
responded to the strong p-acceptor properties of ligands 12–
19. Specifically, the cycloisomerization of enyne 37 to cyclo-
butene 38 was chosen as additional model because this
process is known to be accelerated when performed under
CO atmosphere (1 atm).[18] Thus, the study of this reaction
allows a direct comparison between pyridiniophosphines and
the archetypical p-acceptor ligand. Figure 4 shows the kinetic
profiles compiled for a set of different catalytic systems under
otherwise identical conditions (2 mol% Pt, 808C). It can be
appreciated that CO performed better in terms of reactivity
than any the other p-acceptor ligands tested: (PhO)3P and
(C6F5)3P. However, the activity exhibited by catalysts 28 and
29 has no rival, and cyclobutene 38 could be obtained in
excellent yields after only few minutes (Figure 4).
Scheme 3. Synthesis of Pt and Au complexes and crystal structure of
28 and 31. Hydrogen atoms, solvent molecules and BF4 anions were
omitted for clarity; ellipsoids are set at 50% probability.[11] Reagent
and conditions (yields): a) K2PtCl4 (1.0 equiv), CH3CN, RT; 28 (80%);
29 (40%); b) (Me2S)AuCl (1.0 equiv), CH2Cl2, RT; 30 (97%); 31
(69%); 32 (98%); 33 (98%); 34 (51%).
Finally, the Au-catalyzed hydroarylation of phenylacety-
lene (39) with mesitylene (40) served as preliminary probe to
test the utility of pyridiniophosphines beyond Pt chemistry.[19]
It has been reported that typical catalytic systems such as
Ph3PAuCl/AgBF4 are ineffective in this particular transfor-
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enhance the Lewis acidity of the metals they coordinate. The
beneficial effects of this property in the area of homogeneous
catalysis are demonstrated along three mechanistically
diverse PtII- and AuI-catalyzed reactions.
Received: January 31, 2014
Published online: && &&, &&&&
Keywords: cationic ligands · homogeneous catalysis ·
.
hydroarylation · ligand design · p-acids
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Figure 4. Ligand effect on the Pt-catalyzed cycloisomerization of enyne
37 to cyclobutene 38. Reagents and conditions: a) 37 (0.05m), Pt
precatalysts (2 mol%), AgSbF6 (2 mol%), (CH2)2Cl2, 808C Conversions
determined by gas chromatography.
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ligands 12–19 render Au particularly electrophilic in com-
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superior. Note however, that the high activities observed
rapidly decay after some minutes and complete conversions
of the starting materials into alkene 41 could never be
achieved even by using catalyst loads of up to 5 mol%
(Figure 5). The design of longer-lived active species for this
and other processes is currently under investigation in our
laboratories.
In summary, we outlined herein the preparation of a new
family of bench stable cationic phosphines, pyridiniophos-
phines, through a short and highly modular synthesis. When
used as ligands, these compounds depict excellent p-acceptor
properties, and as a consequence, a remarkable ability to
[4] Furthermore, we have observed catalyst decomposition in some
cases through nucleophilic attack at the C1 carbon of the
cyclopropenium rings in the presence of alcohols.
[5] Imidazolium-substituted phosphines have been studied; how-
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rings. Moreover, the synthesis of 2-chloroimidazolium precur-
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[9] The same effect is observed in (o-tol)PPh2 metal complexes; see:
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Figure 5. Ligand effect on the Au-catalyzed hydroarylation of alkyne 39
with arene 40. Reagents and conditions: a) 39 (0.05m), 40 (4 equiv;
0.2m) AuI precatalysts (5 mol%), AgBF4 or AgSbF6 (5 mol%),
(CH2)2Cl2, 608C. Conversions determined by gas chromatography.
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´
ˆ
´
[10] Z. B. Maksic, B. Kovacevic, J. Chem. Soc. Perkin Trans. 2 1999,
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ities of their Pt centers.
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[13] Steric factors are probably responsible for the Cl1-Rh1-C1 angle
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Communications
Cationic Phosphines
Be positive! Pyridinium-substituted
phosphines carry a positive charge
directly attached to the phosphorus atom.
This makes them weak s-donor but
excellent p-acceptor ligands. Their syn-
thesis and their remarkable effect in Pt
and Au catalysis are described.
H. Tinnermann, C. Wille,
M. Alcarazo*
&&&& — &&&&
Synthesis, Structure, and Applications of
Pyridiniophosphines
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