PNN ruthenium pincer complexes based on phosphinated 2,2′- dipyridinemethane and 2,2′-oxobispyridine. metal-ligand cooperation in cyclometalation and catalysis

Article abstract of DOI:10.1021/om400194w

The synthesis of novel PNN ruthenium pincer complexes based on 2,2′-dipyridinemethane phosphine derivatives, as well as on 2,2′-oxobispyridine phosphine ligands, and their reactivity toward dearomatization and cyclometalation are described. The dearomatized compounds 7a,b undergo cyclometalation to yield complexes 8a,b. In order for cyclometalation to proceed, the coordination sphere around the Ru center has to rearrange, and this depends on the flexibility of the system, showing that the cyclometalation is qualitatively faster in the case of the dimethyl derivative 7a than in the case of the spyrocyclopentyl derivative 7b. The cyclometalation occurs diastereoselectively and leads to only one diastereomer of the cyclometalated compounds. In the case of the 2,2′-oxobispyridine complex 6c, the dearomatized complex was too unstable to be isolated; however it was possible to isolate and characterize a stable dicarbonyl-dearomatized ruthenium(II) complex, 9c, when the deprotonation was performed under a CO atmosphere. Dearomatization of 6a under CO also led to dicarbonyl-dearomatized ruthenium(II) complex 9a, which slowly rearranged into the dicarbonyl-aromatized ruthenium(0) complex 10a. These complexes were tested in catalytic alcohol-amine coupling, esterification of primary alcohols, and hydrogenation of secondary amides. Moderate activity was observed in hydrogenation of amides to alcohols and amines and low activity in the other transformations, owing mainly to the formation of stable cyclometalated compounds.

Full text of DOI:10.1021/om400194w

Article
pubs.acs.org/Organometallics
PNN Ruthenium Pincer Complexes Based on Phosphinated 2,2′-
Dipyridinemethane and 2,2′-Oxobispyridine. Metal−Ligand
Cooperation in Cyclometalation and Catalysis
Rigoberto Barrios-Francisco,† Ekambaram Balaraman,† Yael Diskin-Posner,‡ Gregory Leitus,‡
Linda J. W. Shimon,‡ and David Milstein*,†
†Department of Organic Chemistry and ‡Department of Chemical Research Support, Weizmann Institute of Science, Rehovot 76100,
Israel
S
* Supporting Information
ABSTRACT: The synthesis of novel PNN ruthenium pincer
complexes based on 2,2′-dipyridinemethane phosphine de-
rivatives, as well as on 2,2′-oxobispyridine phosphine ligands,
and their reactivity toward dearomatization and cyclo-
metalation are described. The dearomatized compounds 7a,b
undergo cyclometalation to yield complexes 8a,b. In order for
cyclometalation to proceed, the coordination sphere around
the Ru center has to rearrange, and this depends on the
flexibility of the system, showing that the cyclometalation is
qualitatively faster in the case of the dimethyl derivative 7a
than in the case of the spyrocyclopentyl derivative 7b. The cyclometalation occurs diastereoselectively and leads to only one
diastereomer of the cyclometalated compounds. In the case of the 2,2′-oxobispyridine complex 6c, the dearomatized complex
was too unstable to be isolated; however it was possible to isolate and characterize a stable dicarbonyl-dearomatized
ruthenium(II) complex, 9c, when the deprotonation was performed under a CO atmosphere. Dearomatization of 6a under CO
also led to dicarbonyl-dearomatized ruthenium(II) complex 9a, which slowly rearranged into the dicarbonyl-aromatized
ruthenium(0) complex 10a. These complexes were tested in catalytic alcohol−amine coupling, esterification of primary alcohols,
and hydrogenation of secondary amides. Moderate activity was observed in hydrogenation of amides to alcohols and amines and
low activity in the other transformations, owing mainly to the formation of stable cyclometalated compounds.
diols and diamines,2m and the synthesis of peptides2f and
INTRODUCTION
■
pyrroles2n from amino alcohols.
Our group has developed a new mode of metal−ligand
cooperation involving dearomatization/aromatization of pyr-
In continuation of this work, we have now synthesized novel,
more flexible, expanded PNN-type pincer ruthenium com-
plexes. These complexes undergo dearomatization upon
deprotonation, followed by an unusual cyclometalation
reaction, involving metal−ligand cooperation, resulting in
rearomatization, with retention of the metal oxidation state.
idine-based PNN and PNP pincer complexes, which were
employed in the activation of C−H,1 O−H,2 N−H,3 and H−
H4 bonds and in catalytic, environmentally friendly organic
transformations.5 Among these complexes, the bipyridine-based
pincer complex 1 (Figure 1), which exhibits excellent catalytic
activity, such as in the hydrogenation of secondary amides to
alcohols and amines,4b hydrogenation of urea derivatives4c and
carbamates4e into amines and methanol, hydrogenation of
organic carbonates, formates, and biomass derived cyclic
These complexes were also evaluated as catalysts in the
coupling of alcohols with amines, dehydrogenation of alcohols
to esters, and hydrogenation of secondary amides. Cyclo-
metalated compounds6,7 have been utilized in organic
synthesis,6a,b catalysis,8 asymmetric synthesis,6g and photo-
chemistry.6h,i
diesters,4 the synthesis of polyamides by direct coupling of
i
RESULTS AND DISCUSSION
■
Synthesis of 2,2′-Dibipyridinemethane-Based PNN
Ligands. Ligands 2a and 2b were prepared according to
Scheme 1. Reaction of 2,6-lutidine with 2-fluoropyridine and n-
BuLi in THF resulted in the methyl bipyridinemethane
Received: March 10, 2013
Figure 1. Complex 1.
© XXXX American Chemical Society
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Scheme 1
Scheme 2
compound 3. Alkylation of the bridging methylene group was
performed by deprotonation with n-BuLi and dropwise
addition of a slight excess of iodomethane in THF two times,
to obtain 4a, or 1,4-diiodobuthane in an intramolecular process
to give compound 4b. Phosphination of 4a,b took place by
using a slight excess of n-BuLi and ClP(t-Bu)2 to obtain ligands
2a and 2b.
Complexes 6a−c were the single products of each reaction.
Table 1 summarizes the characteristic signals in multinuclear
NMR of each complex.
a
Table 1
31P
1H NMR
(hydride)
1H NMR (methylene
arm)
13C NMR
(CO)
complex NMR
Ligand 2c, bearing a bridging oxygen atom, was prepared
using the methodology reported by Buchwald9 for the coupling
of 6-methyl-2-hydroxypyridine and 2-bromopyridine in the
presence of a catalytic amount of CuI in DMF to give the
oxobispyridine compound 5 in good yield. Reaction of 5 with a
slight excess of n-BuLi and ClP(t-Bu)2 resulted in ligand 2c
(Scheme 2).
Synthesis of PNN-RuHCl(CO) Complexes. The PNN-Ru
complexes 6a−c were prepared following the methodology
described in the literature for the corresponding bipyridyl-
phosphine derivatives, by reacting the [RuHCl(CO)(PPh3)3]
precursor with a slight excess of the electron-rich PNN ligands
2a−c in THF at 65 °C for 4 h under a N2 atmosphere (Scheme
3).4b
2
6a
6b
6c
108.5
(s)
−14.5 (d, JPH 4.1 (dd, JPH = 7.8 Hz, 207.1 (d, JPC
= 26.1 Hz)
JHH = 16.5 Hz)
= 17.7 Hz)
3.6 (dd, JPH = 12.0
Hz, JHH = 16.8 Hz)
2
108.9
(s)
−14.5 (d, JPH 4.1 (dd, JPH = 7.8 Hz, 207.2 (d, JPC
= 26.1 Hz)
JHH = 16.8 Hz)
= 17.4 Hz)
3.6 (dd, JPH = 11.7
Hz, JHH = 17.1 Hz)
2
112.8
(s)
−14.5 (d, JPH 3.8 (dd, JPH = 8.9 Hz, 206.4 (d, JPC
= 23.6 Hz)
JHH = 16.2 Hz)
= 17.2 Hz)
3.4 (dd, JPH = 10.4
Hz, JHH = 16.1 Hz)
a
NMR experiments were recorded at room temperature using CD2Cl2
as solvent. Chemical shifts are given in ppm.
There are no significant differences between the NMR
spectra of complexes 6a−c, and the chemical shifts of these
complexes are quite similar to the previously reported complex
1.4b Structures of complexes 6a and 6b were also confirmed by
single-crystal X-ray diffraction studies. These complexes display
distorted octahedral geometries around the ruthenium center
with the PNN pincer ligand coordinated in a meridional
fashion, the CO ligand being located trans to the central
pyridine nitrogen, and the hydride trans to chloride (Figure 2).
Dearomatization Reactions. Upon treatment of complex
6a with a slight excess of t-BuOK in THF at −35 °C, a dark
Scheme 3
1
green solution was obtained. The H NMR spectrum of the
reaction mixture at room temperature in benzene-d6 revealed
the presence of two new hydride complexes. One complex
B
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with the PNC system coordinated in a pseudomeridional
fashion, the terminal pyridine ring occupies the apical position
trans to hydride, and the CO is coordinated trans to the
nitrogen of the central pyridine ring (Figure 3).
Figure 3. ORTEP drawing of PNN-Ru complex 8a at 50% probability.
Hydrogen atoms (except hydride) are omitted for clarity. Selected
bond distances (Å): Ru1−C27 1.823(2), Ru1−N3 2.1014(15), Ru1−
C11 2.1369(19), Ru1−N4 2.2325(16), Ru1−P2 2.3321(5), Ru1−H1
1.58(2). Selected angles (deg): C27−Ru1−N3 175.52(8), C27−Ru1−
C11 104.68(8), N3−Ru1−C11 76.80(7), C27−Ru1−N4 100.97(8),
N3−Ru1−N4 83.49(6), C11−Ru1−N4 74.72(7), C27−Ru1−P2
96.67(6), N3−Ru1−P2 81.13(4), C11−Ru1−P2 156.08(5), N4−
Ru1−P2 111.98(4), C27−Ru1−H1 87.2(9), N3−Ru1−H1 88.6(9),
C11−Ru1−H1 90.0(9), N4−Ru1−H1 164.0(9), P2−Ru1−H1
80.3(9).
Figure 2. ORTEP drawing of PNN-Ru complexes 6a and 6b at 50%
probability. Hydrogen atoms (except hydride) are omitted for clarity.
exhibited the presence of a hydride ligand as a doublet at −22.1
ppm (2JPH = 29.1 Hz) and a phosphine singlet at 102.3 ppm in
the 31P{1H} NMR spectrum, corresponding to the expected
dearomatized complex 7a. The second complex, 8a, exhibited a
hydride signal as a doublet at −12.1 ppm (2JPH = 20.4 Hz) and
a phosphine singlet at 108.2 ppm in the 31P{1H} NMR
spectrum. Compound 8a was obtained as the sole product of
this reaction after 4 h at −35 °C. Upon workup, 8a was
characterized as the cyclometalated complex, which was formed
by C−H activation of one of the methyl groups between the
pyridine rings in the dearomatized complex 7a (Scheme 4).
Upon treatment of complex 6a with KHMDS (potassium
hexamethyldisilazide) at −35 °C in toluene-d8 in an NMR tube,
the dearomatized compound 7a was observed as the sole
product. Upon warming to room temperature, 7a transformed
to the cyclometalated RuH complex 8a, indicating that 7a is an
intermediate in the formation of 8a.
This type of cyclometalation via metal−ligand cooperation is
uncommon. It involves intramolecular diastereoselective C−H
activation, with aromatization of the pyridine moiety and no
change in metal oxidation state. Intermolecular C−H activation
by metal−ligand cooperation, involving aromatizaion of pincer
ligands, has been reported by our group.1
Crystals of complex 8a suitable for X-ray diffraction were
grown from a saturated benzene solution. The geometry
around the ruthenium center is a highly distorted octahedron
Significantly, only one diastereoisomer of complex 8a was
formed, as indicated by the 1H and 31P{1H} NMR spectra. The
chirality in the complex is conferred by the chiral Ru1 and C10
centers in the complex. Complex 8a has very low solubility in
most of the common solvents (benzene, toluene, THF,
acetone, and MeOH). It is very stable and unreactive in
these solvents even at high temperatures or in the solid state
(up to 130 °C).
Complex 6b is expected to have a lower tendency toward
cyclometalation since it is more difficult for a C−H bond of the
spirocyclopentyl group to approach the metal center. In this
case, unlike the case of 7a, the dearomatized compound 7b was
isolated as a single product, and it was stable in solution at
room temperature for several hours; nevertheless, conversion to
the cyclometalated product 8b was observed after 2 days and
was complete at room temperature after 5 days, forming 8b as a
single product (Scheme 5).
Cyclometalation of complex 7b is slower than that of the
dimethyl analogue 7a (which formed the cyclometalated
1
compound after 4 h, as described above). Figure 4 shows H
NMR follow-up of this transformation, expanded in the hydride
region. It is remarkable that only one diastereomer is formed
1
along the reaction (on the basis of H and 31P NMR), despite
the formation of three chiral centers. Interestingly complex 8b
is soluble in common solvents, unlike the very insoluble 8a.
Scheme 4
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Scheme 5
1
Figure 4. H NMR follow-up of the cyclometalation of 7b in benzene-d6 showing the hydride region.
Scheme 6
Similar treatment of the oxygen-bridged complex 6c with
1.02 equivalents of t-BuOK in THF at −35 °C led to a mixture
of unidentified compounds. Several attempts to obtain the
expected dearomatized compound were performed, including
use of less polar solvents such as toluene or benzene or using
KHMDS as the base, but mixtures of several unidentified
products were obtained. The low stability of the expected
dearomatized compound could be attributed to the presence of
the donor oxygen atom directly linked to the pyridine rings,
which increases the electron density of these ligands and
destabilizes the deprotonated complex.
remained unreactive and did not undergo cyclometalation,
indicating that an unsaturated metal center is required for
cyclometalation, as expected. Interestingly, after 19 h at room
temperature the dicarbonyl dearomatized Ru(II) complex 9a
underwent rearrangement to the PNN-Ru(0) complex 10a.
The presence of two diastereomeric methyl groups in 1H NMR
confirmed the cis coordination of the two CO ligands in
complex 10a (Scheme 6).
Figure 5 shows the 1H NMR of the dearomatized dicarbonyl-
Ru(II) complex 9a (top) and the rearomatization of the
pyridinic moiety and formation of the dicarbonyl-Ru(0)
complex 10a (bottom). It is worth noting the absence of the
hydride around −4.3 ppm and the appearance of the
methylenic arm as a multiplet at 2.7 ppm in the product, as
well as the modification of the aromatic and aliphatic regions
due to the aromatization process.
While attempts at dearomatization of the oxobispyridine
complex 6c led to mixtures, as described above, performing the
deprotonation under CO afforded the corresponding dicar-
bonyl-dearomatized Ru(II) complex 9c as a single product
(Scheme 7). Interestingly, in contrast to complex 9a,
rearrangement to the corresponding Ru(0) complex was not
Dearomatization Reaction in the Presence of CO and
Formation of Ru(0) Complexes. Upon deprotonation of
complex 6a in the presence of CO, the dearomatized PNN-
1
Ru(II) complex 9a was formed as a single product. The H
NMR spectrum of the dearomatized compound exhibits the
hydride ligand at −4.3 ppm (d, 2JHP = 18.8 Hz), downfield from
the chemial shift of the hydride of complex 6a (−22.1 ppm),
which is consistent with coordination of a CO ligand trans to
the hydride. Methyl and tert-butyl groups in complex 9a are
diastereotopic, indicating a cis coordination of the CO groups
in the Ru center. Significantly, the methyl groups of the ligand
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Figure 5. 1H NMR of the dearomatized dicarbonyl-Ru(II) complex 9a (top) and the rearomatization of the pyridinic moiety and formation of the
dicarbonyl-Ru(0) complex 10a (bottom).
Scheme 7
conditions described in entry 1 of Table 2, but extending the
reaction time (72 h), resulted in an increased yield of 63% of
ethanol and 65% of aniline (entry 3, Table 2).
This reaction was also tested with other amides such as N-
benzyl-benzylamide and N-phenyl-benzylamide, obtaining
moderate yields of the corresponding alcohols and amines
(entries 4 and 5, Table 2). Hydrogenation of amides to alcohols
and amines is a difficult transformation, and only very few
examples for this reaction were reported.4b,10
The catalytic activity of the new PNN-Ru complexes was also
tested in several reactions, including coupling of alcohols with
amines and esterification of primary alcohols (see Supporting
Information). The results are compared with the parent
pyridine- and bipyridine-based catalysts and found that PNN-
Ru complexes (6a−c, 7b, 8a, and 9c) showed less activity
toward catalysis.2b,c,o The low activity and selectivity of these
bridged-bipyridine-based PNN-Ru(II) complexes in this
reaction is likely a result of the cyclometalation of the active
species 7a and 7b, which is detrimental to the catalysis. The low
stability of the expected dearomatized complex formed by
deprotonation of 6c was also detrimental to catalysis. Hence,
these PNN complexes are much less active than the previously
reported amine-pyridine-based PNN and PNP-Ru(II) com-
plexes, which presented high activity and selectivity toward
amidation2c and imine synthesis2d reactions, respectively.
Thus, it is clear that the low activity of the PNN-Ru
complexes evaluated in this work is directly related to the
cyclometalation of the dearomatized complexes. In previous
reports,1−5 it was shown that these transformations involve
dearomatized, pyridine- and bipyridine- based catalysts, which
are able to add alcohols, followed by hydride elimination and
liberation of dihydrogen as key steps. With the cyclometalated
observed under these conditions. Formation of 9c suggests that
deprotonation of 6c in the absence of CO does lead to the
dearomatized complex, which is probably unstable and reacts
further; coordination of an additional CO ligand to form a
coordinatively saturated complex stabilizes it. The unobserved
rearrangement of the Ru(II) complex 9c to the corresponding
Ru(0) complex may be due to the electron-donating bridging
oxygen atom, which results in stabilization of the higher metal
oxidation state.
Catalytic Activity. The catalytic activity of the new PNN-
Ru complexes was tested in the hydrogenation of secondary
amides. Better results were obtained with these complexes, and
the results are presented in Table 2.
Hydrogenation of secondary amides afforded primary
alcohols and primary amines in moderate yields. When 1 mol
% of the dearomatized complex 7b was utilized as catalyst for
the reduction of N-phenylacetamide, the corresponding ethanol
and aniline were obtained in 52% and 57% yields, respectively
(entry 1, Table 2). When the cyclometalated complex 8b was
employed for the hydrogenation of N-phenylacetamide, lower
yields of ethanol (22%) and aniline (25%) were obtained (entry
2, Table 2). It is clear that the cyclometalation is again
detrimental for the catalysis. An additional experiment using the
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Table 2.
a
Reaction procedure: A Fischer−Porter tube was charged with 1 mmol of amide, 0.01 mmol of catalytic precursor, 10 atm of H2, 1 mmol of
b
mesitylene as internal standard in each experiment, and 2 mL of THF as solvent, and the solution was heated at 110 °C for 48 h. Conversions were
determined by CG and GC-MS. Reaction time: 72 h.
c
Atmospheres glovebox equipped with an MO 40-2 inert gas purifier or
using standard Schlenk techniques. All solvents were reagent grade or
better. All nondeuterated solvents were refluxed over sodium/
benzophenone ketyl and distilled under an argon atmosphere.
Deuterated solvents were used as received. All solvents were degassed
with argon and kept in the glovebox over 4 Å molecular sieves. Most of
the chemicals used in catalysis reactions were purified according to
standard procedures (or by vacuum distillation/sublimation). RuHCl-
(PPh3)3(CO)11 was prepared according to literature procedures.
Thin-layer chromatography (TLC) was performed on Merck
1.05554 aluminum sheets precoated with silica gel 60 F254, and the
spots were visualized with UV light at 254 nm or under iodine.
Column chromatography purifications were performed by flash
compounds, these reactions are inhibited due to the rear-
omatization of the pyridine ring and the saturation of the
ruthenium center. In addition, the hydride ligand of complexes
8a and 8b is located trans to the terminal pyridine ligand,
rendering the hydride less hydridic and thus hampering the
liberation of the required dihydrogen (by hydride coupling with
a proton from the “arm”), and as a consequence catalysis is
retarded. The much better results for hydrogenation of amides
may be a consequence of the reversibility of the cyclometalation
process under hydrogen pressure.
CONCLUSION
■
1
chromatography using Merck silica gel 60 (0.063−0.200 mm). H,
New pincer-ligand systems and complexes are described here.
The reported diastereoselective cyclometalation reactions of the
dearomatized complexes lead to novel complexes and provide
another example of facile bond activation by metal−ligand
cooperation, based on the concept of aromatization−dearoma-
tization of the ligand. However, the intramolecular C−H
activation process hinders intermolecular bond activation and
has a negative impact on catalytic dehydrogenation reactions,
but less so on catalytic hydrogenation; thus the rare
hydrogenation of amides proceeds fairly well, probably as a
result of reversal of the cyclometalation process.
13C{1H}, and 31P{1H} NMR spectra were recorded at 300, 75, and 122
MHz, respectively, using Bruker AMX-300 and AMX-500 NMR
1
spectrometers. H and 13C{1H} NMR chemical shifts are reported in
ppm downfield from tetramethylsilane. 31P{1H} NMR chemical shifts
are reported in parts per million downfield from H3PO4 and
referenced to an external 85% solution of phosphoric acid in D2O.
Abbreviations used in the NMR follow-up experiments: br, broad; s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; dd, doublet of
doublets. Mass spectra were recorded on a Micromass Platform LCZ
4000, using electrospray ionization (ESI) mode. GC was performed
using a Carboxen 1000 column on a HP 690 series GC system.
b. Synthesis of 2-Methyl-6-(pyridin-2-ylmethyl)pyridine (3).
A dried three-neck round-bottom flask equipped with a stirring bar
and connected to a vacuum-argon line, equipped with two rubber
septa, was charged with 5 g (46.6 mmol, 1.0 equiv) of 2,6-lutidine and
10 mL of anhydrous THF. The flask was placed into a dry ice/acetone
bath at −75 °C. Then 34.2 mL of a solution of n-BuLi (1.5 M in
EXPERIMENTAL SECTION
a. General Experimental Procedures. Unless otherwise noted,
all experiments with metal complexes and phosphine ligands were
carried out under an atmosphere of purified nitrogen in a Vacuum
■
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hexanes, 51.3 mmol, 1.1 equiv) was added dropwise at this
temperature during 20 min. After this time 5.43 g (56 mmol, 1.2
equiv) of 2-fluoropyridine was added dropwise during 20 min at −75
°C and stirred for an additional hour. The solution was allowed to
warm at room temperature and stirred for 5 h at this temperature. A 5
mL amount of an aqueous solution of NH4Cl was added at 0 °C to
quench the reaction, and the solvent was removed under vacuum.
Then 10 mL of ethyl acetate was added, and the organic phase was
washed three times with 10 mL of an aqueous solution of NaHCO3.
The solvent was removed under vacuum, and the compound was
purified on a column of neutral alumina using a mixture of hexanes/
ethyl acetate (9.5:0.5) as eluent. Product 3 was obtained as a yellow oil
in 80% yield (6.9 g).
31P{1H} NMR (C6D6): 39.5 (s). 13C{1H} NMR (C6D6): 168.1 (s, Py),
166.1 (s, Py), 161.0 (d, JP−C = 13.8 Hz, Py), 148.4 (s, Py), 135.7 (s,
Py), 135.2 (s, Py), 121.6, (s, Py), 121.2 (d, JP−C = 8.8 Hz, Py), 120.6
(s, Py), 117.8 (s, Py), 32.3 (d, JP−C = 26.4 Hz, Py-CH2-P), 31.7 (d,
JP−C = 23.8 Hz, P-CMe3), 29.7 (d, JP−C = 13.8 Hz, CMe3), 28.7 (s,
Me2C).
e. Synthesis of Complex 6a. A Schlenk vessel equipped with a
stopcock, Rotaflo cap, and a stirring bar was charged with 817 mg
(0.85 mmol, 1 equiv) of RuHCl(CO)(PPh3)3 and 300 mg of the PNN
ligand 2a (0.87 mmol, 1.02 equiv), which were then dissolved in 5 mL
of THF. The reaction was set up into a thermostated oil bath at 65 °C
for a period of 6 h. After this time, the solution was transferred to a vial
and the solvent was concentrated under vacuum to 1 mL, and then 5
mL of pentane was added to precipitate the product. The solid was
filtered off, washed with 5 mL of pentane (three times), and dried
under vacuum for 4 h. The product 6a was obtained as a light yellow
solid in 89% yield (0.39 g).
1H NMR (CDCl3): 8.49 (d, J = 5.0 Hz, 1H, Py), 7.6 (t, J = 7.5 Hz,
1H, Py), 7.4 (t, J = 7.5 Hz, 1H, Py), 7.1 (d, J = 8.0 Hz, 1H, Py), 7.0 (m,
1H, Py), 6.9 (m, 2H, Py), 4.4 (s, 2H, Py-CH2-Py), 2.5 (s, 3H, CH3-
Py). MS (EI+): 184 (M+).
1H NMR (CD2Cl2): 9.5 (d, J = 5.4 Hz, 1H, Py), 7.77 (m, 3H, Py),
7.6 (d, J = 8.4 Hz, 1H, Py), 7.4 (d, J = 7.8 Hz, 1H, Py), 7.2 (t, J = 6.6
Hz, 1H, Py), 4.1 (dd, JP−H = 7.8 Hz, Jgem = 16.5 Hz, 1H, Py-CH2-P),
3.6 (dd, JP−H = 12.0 Hz, Jgem= 16.8 Hz, 1H, Py-CH2-P), 2.3 (s, 3H,
Me2C), 2.0 (s, 3H, Me2C), 1.5 (d, JP−H = 13.2 Hz, 9H, t-Bu2P), 1.2 (d,
c. Synthesis of 2-Methyl-6-(2-(pyridin-2-yl)propan-2-yl)-
pyridine (4a). A dried three-neck round-bottom flask equipped
with a stirring bar and connected to a vacuum-argon line, equipped
with two rubber septa, was charged with 3 g (16.2 mmol, 1.0 equiv) of
2-methyl-6-(pyridin-2-ylmethyl)pyridine (3) and 15 mL of anhydrous
THF. The flask was placed into a dry ice/acetone bath at −75 °C.
Then 11.88 mL of a solution of n-Bu-Li (1.5 M in hexanes, 17.8 mmol,
1.1 equiv) was added dropwise at this temperature during 20 min.
After this time 1.14 mL (2.52 mg, 17.8 mmol, 1.1 equiv) of methyl
iodide was added dropwise during 15 min at −75 °C, and the solution
was stirred for an additional hour. Then 11.9 mL of additional n-BuLi
was added slowly, and the solution was stirred for a period of 1 h.
Then 3.0 mL (6.9 mg, 48.6 mmol, 3 equiv) of methyl iodide was
added with a syringe during 30 min, and the reaction was stirred for 2
h at −75 °C. The reaction mixture was allowed to warm to room
temperature and stirred for 1 h at this temperature. A 5 mL sample of
an aqueous solution of NH4Cl was added at 0 °C to quench the
reaction, followed by removal of the solvent under vacuum. A 10 mL
portion of ethyl acetate was added, and the organic phase was washed
three times with 10 mL of aqueous NaHCO3. The solvent was
removed under vacuum, and the compound was purified on a column
of neutral alumina using a mixture of hexanes/ethyl acetate (9.5:0.5) as
eluent. The product 5a was obtained as a colorless solid in 86% yield
(2.9 g).
JP−H = 12.6 Hz, 9H, t-Bu2P), −14.5 (d, JP−H = 26.1 Hz, 1H, Ru-H). 31
P
NMR (CD2Cl2): 108.5 (s). 13C NMR (CD2Cl2): 207.1 (d, JP−C = 17.7
Hz, CO), 163.6 (d, JP−C = 5.3 Hz, Py), 163.2 (s, Py), 163.1 (s, Py),
158.3 (d, JP−C = 2.03 Hz, Py), 137.7 (s, Py), 137.3 (s, Py), 122.3 (s,
Py), 121.8 (d, JP−C = 9.2 Hz, Py), 121.6 (d, JP−C = 2.9 Hz, Py), 119.3
(s, Py), 47.1 (s, Py-C-Py), 36.3 (d, JP−C = 16.1 Hz, Py-CH2-P), 36.4 (d,
JP−C = 22.4 Hz, P-CMe3), 36.0 (d, JP−C = 22.6 Hz, P-CMe3), 30.2 (d,
JP−C = 3.21 Hz, CMe3), 29.7 (s, Me2C), 28.3 (d, JP−C = 3.5 Hz, CMe3),
26.1 (s, Me2C). MS (ESI, MeOH): 488 (100%, (M − Cl)+).
f. Synthesis of Complex 7a by Dearomatization of 6a. An 18
mg (0.036 mmol, 1.0 equiv) portion of the PNN-Ru complex 6a was
suspended in 0.5 mL of toluene-d8 into a vial, and the suspension was
cooled at −35 °C for 15 min. Then 7 mg (0.036 mmol, 1.0 equiv) of
potassium hexamethyldisilazane (KHMDS) was dissolved in 0.5 mL of
toluene-d8 and cooled at −35 °C for 15 min. The base was added
slowly to the suspension of complex 6a, resulting in an inmediate
formation of a dark green solution. The solution was inmediatelly
transferred into an NMR tube, and the NMR spectra of the
dearomatized complex 7a were inmediatly recorded at −35 °C.
1H NMR (tol-d8): 8.6 (d, J = 4.8 Hz, 1H, Py), 6.8 (t, J = 7.5 Hz, 1H,
Py), 6.7 (d, J = 7.8 Hz, 1H, Py), 6.2 (m, 3H, Py), 5.3 (d, J = 6.3 Hz,
1H, Py), 3.5 (d, JP−H = 1.8 Hz, 1H, P-CH), 1.45 (d, JP−H = 8.1 Hz,
9H, t-Bu2P), 1.39 (d, JP−H = 7.5 Hz, 9H, t-Bu2P), 1.2 (s, 3H, Me2C),
0.3 (s, 3H, Me2C), −22.1 (d, JP−H = 29.1 Hz, 1H, Ru-H). 31P NMR
(tol-d8): 102.3 (s).
1H NMR (CDCl3): 8.5 (d, J = 5.0 Hz, 1H, Py), 7.5 (t, J = 7.5 Hz,
1H, Py), 7.4 (t, J = 7.5 Hz, 1H, Py), 7.2 (d, J = 8.0 Hz, 1H, Py), 7.1 (m,
1H, Py), 6.9 (m, 2H, Py), 2.5 (s, 3H, CH3-Py), 1.8 (s, 6H, Me2C). MS
(EI+): 212 (M+).
d. Synthesis of the Pincer-Type PNN Ligand 2a. A dried three-
neck round-bottom flask equipped with a stirring bar and connected to
a vacuum-argon line, equipped with two rubber septa, was charged
with 1.18 g (5.5 mmol, 1.0 equiv) of 2-methyl-6-(2-(pyridin-2-
yl)propan-2-yl)pyridine (4a) and 15 mL of anhydrous diethyl ether.
The flask was placed into a dry ice/acetone bath at −75 °C under a
constant flow of argon. Then 4.45 mL of a solution of n-BuLi (1.5 M
in hexanes, 6.6 mmol, 1.1 equiv) was added dropwise at this
temperature during 20 min. After this time a solution of 1.2 g (6.67
mmol, 1.1 equiv) of chlorodi-tert-butylphosphine in 3 mL of ether was
transferred via cannula into the flask and stirred at this temperature for
a period of 3 h. The reaction mixture was allowed to warm to room
temperature and stirred overnight under argon. The reaction mixture
was quenched with 3 mL of deionized and deoxygenated water, the
organic phase was transferred via cannula into a dried Schlenk flask
connected to the vacuum-argon line, and the solvent was removed
under vacuum. The resulting oil was transferred to a glovebox and
dissolved in 10 mL of pentane, and the solution was dried over
anhydrous Na2SO4. The pentane solution was passed through a
column of neutral alumina, and the pentane was removed under
vacuum. The product 2a was obtained as a yellow oil in 93% yield (1.8
g).
g. Formation of Complex 8a by Cyclometalation. A 24 mg
(0.0459 mmol, 1 equiv) amount of the PNN-Ru complex 6a was
suspended in 2 mL of THF in a vial and cooled at −35 °C for 15 min.
Then 5.6 mg (0.0505 mmol, 1.1 equiv) of t-BuOK was dissolved in 1
mL of THF and cooled at −35 °C for 15 min. The base was added
dropwise into the suspension at −35 °C and stirred for a period of 30
min at this temperature, resulting in a dark green solution. The dark
combined solution was stirred at room temperature during 4 h until
the appearance of a yellow suspension of compound 8a. The solution
was concentrated under vacuum to a volume of 1 mL, and 5 mL of
pentane was added to precipitate the product. The solid was washed
with 5 mL of pentane (three times) and dried under vacuum for 4 h.
The product was obtainded as a yellow solid in 97% (21 mg) yield. It
is poorly soluble and nonreactive in benzene, toluene, acetone, MeOH,
and THF.
1H NMR (C6D6): 8.9 (d, J = 5.4 Hz, 1H, Py), 6.9 (t, J = 7.5 Hz, 2H,
Py), 6.8 (t, J = 7.8 Hz, 1H, Py), 6.6 (d, J = 7.8 Hz, 1H, Py), 6.3 (d, J =
7.8 Hz, 1H, Py), 6.2 (t, J = 6.0 Hz, 1H, Py), 3.1 (dd, JP−H = 6.0 Hz, Jgem
= 16.2 Hz, 1H, Py-CH2-P), 2.9 (m, 2H, C-CH2-Ru), 2.4 (dd, JP−H
=
5.7 Hz, Jgem= 10.2 Hz, 1H, Py-CH2-P), 1.7 (s, 3H, MeC), 1.5 (d, JP−H
= 12.0 Hz, 9H, t-Bu2P), 0.9 (d, JP−H = 11.4 Hz, 9H, t-Bu2P), −12.1 (d,
JP−H = 20.4 Hz, 1H, Ru-H). 31P NMR (C6D6): 108.2 (s). 13C NMR
(C6D6): the very low solubility of this complex in most of the solvents
1H NMR (C6D6): 8.5 (d, J = 4.5 Hz, 1H, Py), 7.1 (m, 4H, Py), 6.8
(d, J = 7.2 Hz, 1H, Py), 6.6 (m, 1H, Py), 3.1 (d, JP−H = 2.4 Hz, 2H, Py-
CH2-P), 2.0 (s, 6H, Me2C), 1.0 (d, JP−H = 10.8 Hz, 18H, t-Bu2P).
G
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did not allow the observation of the quaternary carbons even at longer
periods of adquisition; 155.0 (s, Py), 134.7 (s, Py), 134.4 (s, Py), 119.8
(s, Py), 119.5 (s, Py), 117.2 (d, JP−C = 7.83 Hz, Py), 116.6 (s, Py), 48.9
(d, JP−C = 62.4 Hz, Ru-CH2-C), 37.3 (d, JP−C = 13.4 Hz, Py-CH2-P),
31.1 (d, JP−C = 5.4 Hz, CMe3), 29.1 (d, JP−C = 7.9 Hz, CMe3), 26.4 (d,
JP−C = 7.5 Hz, MeC). MS (ESI, MeOH): 486 (100%, (M)+).
h. Synthesis of 2-Methyl-6-(1-(pyridin-2-yl)cyclopentyl)-
pyridine (4b). A dried three-neck round-bottom flask equipped
with a stirring bar and connected to a vacuum-argon line, equipped
with two rubber septa, was charged with 1 g (5.4 mmol, 1.0 equiv) of
2-methyl-6-(pyridin-2-ylmethyl)pyridine (3) and 10 mL of anhydrous
freshly distilled THF. The flask was placed in a dry ice/acetone bath at
−75 °C, and 3.96 mL of a solution of n-BuLi (1.5 M in hexanes, 5.94
mmol, 1.1 equiv) was added dropwise at this temperature during 20
min. After this time, 0.752 mL (1.76 g, 5.7 mmol, 1.05 equiv) of 1,4-
diiodobutane was added dropwise during 15 min at −75 °C and stirred
for an additional hour. After this time, an additional 3.96 mL of n-BuLi
was added slowly and stirred for 1 h at −75 °C. The solution was
allowed to warm to room temperature and stirred for 3 h at this
temperature. Then 5 mL of an aqueous solution of NH4Cl was added
at 0 °C to quench the reaction, and the solvent was removed under
vacuum. A 10 mL sample of ethyl acetate was added to the mixture,
and the organic phase was washed with 3 × 10 mL of aqueous
NaHCO3. The solvent was removed under vacuum, and the residue
was purified using a column of neutral alumina using hexanes/ethyl
acetate (9.5:0.5) as eluent. The product 4b was obtained as a colorless
solid in 75% yield (1.0 g).
mL of pentane (three times) and dried under vacuum for 4 h. The
product 6b was obtained as a light yellow solid in 94% yield (0.135 g).
1H NMR (CD2Cl2): 9.4 (d, J = 5.1 Hz, 1H, Py), 7.7 (m, 2H, Py),
7.5 (d, J = 8.1 Hz, 1H, Py), 7.4 (d, J = 8.1 Hz, 1H, Py), 7.2 (m, 1H,
Py), 7.1 (m, 1H, Py), 4.1 (dd, JP−H = 7.8 Hz, Jgem = 16.8 Hz, 1H, Py-
CH2-P), 3.6 (dd, JP−H = 11.7 Hz, Jgem = 17.1 Hz, 1H, Py-CH2-P), 3.5
(m, 1H, −CH2−), 3.0 (m, 1H, −CH2−), 2.6 (m, 3H, −CH2−), 1.9
(m, 3H, −CH2−), 1.5 (d, JP−H = 13.5 Hz, 9H, t-Bu2P), 1.2 (d, JP−H
=
12.9 Hz, 9H, t-Bu2P), −14.5 (d, JP−H = 26.1 Hz, 1H, Ru-H). 31P NMR
(CD2Cl2): 108.9 (s). 13C NMR (CD2Cl2): 207.2 (d, JP−C = 17.4 Hz,
CO), 163.5 (d, JP−C = 4.8 Hz, Py), 158.3 (d, JP−H = 1.8 Hz, Py), 137.4
(d, JP−C = 1.2 Hz, Py), 137.1 (s, Py), 134.4 (t, JP−C = 5.6 Hz, Py),
127.4 (d, JP−C = 4.7 Hz, Py), 122.2 (d, JP−C = 1.2 Hz, Py), 122.0 (d,
JP−C = 2.6 Hz, Py), 121.6 (d, JP−C = 9.6 Hz, Py), 119.8 (s, Py), 59.6
(bd, CH2-P), 36.5 (s, −CH2−), 36.1 (m, −CH2−, CMe3), 30.2 (d,
JP−C = 3.2 Hz, CMe3), 29.3 (d, JP−C = 3.2 Hz, CMe3), 22.5 (s,
−CH2−), 22.1 (s, −CH2−). MS (ESI, MeOH): 514 (100%, (M −
Cl)+).
k. Synthesis of the Dearomatized Complex 7b. A 27 mg
(0.049 mmol, 1 equiv) amount of the PNN-Ru complex 6b was
suspended in 2 mL of THF in a vial and cooled at −35 °C for 15 min.
A solution of t-BuOK (5.6 mg, 0.0501 mmol, 1.1 equiv) in 1 mL of
THF was cooled at −35 °C for 15 min and then added dropwise to
the suspension of 6b at −35 °C during 30 min, and the solution was
stirred at this temperature for 2 h. The solution was filtered over
Celite, and the Celite was washed with 2 mL of cold THF. The
combined solvent was removed under vacuum, and the sample was
dried under vacuum for a period of 4 h. The product 7b was obtainded
as a dark green solid in 94% yield (23 mg).
1H NMR (CDCl3): 8.5 (d, J = 4.2 Hz, 1H, Py), 7.5 (t, J = 7.5 Hz,
1H, Py), 7.4 (t, J = 7.5 Hz, 1H, Py), 7.2 (d, J = 8.1 Hz, 1H, Py), 7.0 (m,
1H, Py), 6.9 (d, J = 7.8 Hz, 1H, Py), 6.8 (d, J = 7.5 Hz, 1H, Py), 2.6
(m, 4H, −CH2−), 2.5 (s, 3H, Me-Py), 1.7 (m, 4H, −CH2−). MS
(EI+): 238 (M+).
1H NMR (C6D6): 8.5 (d, J = 5.08 Hz, 1H, Py), 6.9 (m, 1H, Py), 6.8
(t, J = 7.7 Hz, 1H, Py), 6.7 (d, J = 7.79 Hz, 1H, Py), 6.3 (m, 1H, Py),
6.2 (m, 2H, Py), 5.3 (d, J = 6.3 Hz, 1H, Py), 3.5 (d, JP−H = 2.24 Hz,
1H, CH-P), 2.0 (m, 1H, −CH2−), 1.6 (m, 3H, −CH2−), 1.4 (d,
JP−H = 9.8 Hz, 9H, t-Bu2P), 1.39 (d, JP−H = 9.7 Hz, 9H, t-Bu2P), 1.2
(m, 2H, −CH2−), 0.8 (m, 1H, −CH2−), 0.2 (m, 1H, −CH2−), −21.9
(d, JP−H = 29.2 Hz, 1H, Ru-H). 31P NMR (C6D6): 102.7 (s). 13C NMR
(C6D6): 214.7 (d, JP−C = 13.3 Hz, CO), 167.0 (d, JP−C = 7.01 Hz, Py),
166.4 (d, JP−C = 1.28 Hz, Py), 162.7 (d, JP−C = 8.67 Hz, Py), 154.5 (s,
Py), 135.2 (s, Py), 134.2 (s, Py) 119.7 (d, JP−C = 11.04 Hz, Py), 118.3
(s, Py) 117.2 (d, JP−C = 7.5 Hz, Py), 76.6 (d, JP−C = 2.4 Hz, Py), 67.2
(d, JP−C = 65.9 Hz, CH-P), 37.5 (d, JP−C = 13.06 Hz, −CH2−), 36.5
(s, spiro-C), 36.4 (s, −CH2−), 34.2 (d, JP−C = 10.7 Hz, −CH2−), 31.6
(d, JP−C = 6.12 Hz, CMe3), 31.1 (d, JP−C = 5.09 Hz, CMe3), 29.0 (d,
JP−C = 8.2 Hz, CMe3), 26.2 (d, JP−C = 7.12 Hz, CMe3). MS (ESI,
MeCN): 513 (100%, (M + 1)+).
I. Synthesis of Ligand 2b. A dried three-neck round-bottom flask
equipped with a stirring bar and connected to a vacuum-argon line,
equipped with two rubber septa, was charged with 0.262 g (1.1 mmol,
1.0 equiv) of 2-methyl-6-(1-(pyridin-2-yl)cyclopentyl)pyridine (4b)
and 10 mL of anhydrous and freshly distilled diethyl ether. The flask
was placed in a dry ice/acetone bath at −75 °C under a constant flow
of argon. Then 0.88 mL of a solution of n-BuLi (1.5 M in hexanes,
1.32 mmol, 1.1 equiv) was added dropwise at this temperature during
20 min. A solution of ClP(t-Bu)2 (0.238 mg, 1.32 mmol, 1.2 equiv) in
3 mL of ether was transferred via cannula into the flask and stirred at
−75 °C for a period of 3 h. The reaction was allowed to warm to room
temperature and stirred overnight under argon flow. The reaction was
quenched with 3 mL of deionized and deoxygenated water, the organic
phase was transferred via cannula into a dried Schlenk tube connected
to a vacuum-argon line, and the solvent was removed under vacuum.
The resulting oil was dissolved in 10 mL of pentane in a glovebox and
dried with anhydrous Na2SO4. The pentane solution was passed
through a column of neutral alumina, and the pentane was removed
under vacuum during 4 h. The product 2b was obtained as yellow oil
in 94% (0.395 g) yield.
l. Synthesis of Complex 8b. A 23 mg (0.044 mmol) portion of
the dearomatized compound 7b was dissolved in 0.7 mL of benzene-d6
and introduced into an NMR tube. The reaction was monitored via 1H
and 31P NMR until disappearance of the starting material after 5 days.
1H NMR (C6D6): 8.8 (d, J = 5.21 Hz, 1H, Py), 6.9 (d, J = 7.6 Hz,
1H, Py), 6.8 (t, J = 7.5 Hz, 1H, Py), 6.7 (d, J = 7.5 Hz, 1H, Py), 6.7 (d,
J = 7.6 Hz, 1H, Py), 6.3 (d, J = 7.3 Hz, 1H, Py), 6.2 (t, J = 6.4 Hz, 1H,
Py), 3.0 (dd, JP−H = 6.0 Hz, Jgem = 16.2 Hz, 1H, Py-CH2-P), 2.8 (dd,
JP−H = 8.0 Hz, Jgem = 15.9 Hz, 1H, Py-CH2-P), 2.6 (m, 1H, −CH2−),
2.4 (m, 1H, −CH2−), 1.9 (m, 1H, CH2-CH-Ru), 1.7 (m, 4H,
−CH2−), 1.4 (d, JP−H = 11.8 Hz, 9H, t-Bu2P), 0.8 (d, JP−H = 11.3 Hz,
9H, t-Bu2P), −12.5 (d, JP−H = 19.9 Hz, 1H, Ru-H). 31P NMR (C6D6):
109.4 (s). 13C NMR (C6D6): 214.69 (d, JP−C = 8.3 Hz, CO), 166.9 (d,
JP−C = 9.5 Hz, Py), 166.4 (s, Py), 162.8 (d, JP−C = 8.7 Hz, Py), 154.5
(s, Py), 135.1 (s, Py), 134.2 (s, Py) 119.8 (s, Py), 119.7 (s, Py), 118.3
(s, Py), 117.2 (d, JP−C = 7.6 Hz, Py), 76.6 (d, JP−C = 2.8 Hz, Py-C-Py),
67.2 (d, JP−C = 66.2 Hz, CH2-CH-Ru), 37.3 (d, JP−C = 13.05 Hz, 
CH-P), 36.5 (d, JP−C = 10.8 Hz, CMe3), 36.4 (s, −CH2−), 34.2 (d,
JP−C = 10.8 Hz, CMe3), 31.6 (d, JP−C = 6.09 Hz, −CH2−), 31.1 (d,
1H NMR (C6D6): 8.4 (d, J = 4.2 Hz, 1H, Py), 7.1 (t, J = 7.8 Hz, 1H,
Py), 7.09 (t, J = 5.4 Hz, 1H, Py), 6.9 (m, 3H, Py), 6.5 (m, 1H, Py), 3.0
(d, JP−H = 2.4 Hz, 2H, Py-CH2-P), 2.8 (m, 4H, −CH2−), 1.8 (m, 4H,
−CH2−), 1.1 (d, JP−H = 10.5 Hz, 18H, t-Bu2P). 31P NMR (C6D6):
39.5 (s). 13C{1H} NMR (C6D6): 168.0 (s, Py), 166.2 (s, Py), 161.1 (d,
JP−C = 12.9 Hz, Py), 148.4 (s, Py), 135.1 (s, Py), 134.7 (s, Py), 121.6
(s, Py), 121.4 (d, JP−C = 7.6 Hz, Py), 119.9 (s, Py), 117.6 (s, Py), 32.5
(d, JP−C = 26.8 Hz, Py-CH2-P), 31.6 (d, JP−C = 23.5 Hz, P-CMe3), 29.5
(d, JP−C = 13.4 Hz, CMe3), 22.4 (s, −CH2−), 22.1 (s, −CH2−).
j. Synthesis of Complex 6b. A Schlenk vessel equipped with a
stopcock, a Rotaflo cap, and a stirring bar was charged with 300 mg
(0.31 mmol, 1 equiv) of RuHCl(CO)(PPh3)3 and 131 mg of the PNN
ligand 2b (0.34 mmol, 1.1 equiv) dissolved in 5 mL of THF. The
reaction was set up in an oil bath at 65 °C for a period of 6 h. After this
time, the solution was transferred into a vial, the solvent was removed
up to 1 mL, and then 5 mL of pentane was added, allowing the
precipitation of the product. The solid was filtered and washed with 5
JP−C = 5.2 Hz, CMe3), 29.0 (d, JP−C = 7.9 Hz, CMe3), 26.2 (d, JP−C
=
7.4 Hz, −CH2−). MS (ESI, MeOH): 513 (100%, (M + 1)+).
m. Synthesis of 2-Methyl-6-(pyridin-2-yloxy)pyridine (5). A
Schlenk vessel equipped with a stopcock, a Rotaflo cap, and a stirring
bar was charged with 300 mg (1.91 mmol, 1 equiv) of 2-
bromopyridine, 250 mg (2.29 mmol, 1.2 equiv) of 6-methyl-2-
H
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hydroxypyridine, 530 mg (3.85 mmol, 2 equiv) of K2CO3, 33.2 mg
(0.28 mmol, 0.15 equiv) of N,N,N′,N′-tetramethylethylenediamine, 18
mg (0.095 mmol, 0.05 equiv) of CuI, and 5 mL of anhydrous DMF.
The solution was stirred and heated at 110 °C for a period of 48 h.
After this time, 15 mL of ethyl acetate was added to the solution, and it
was washed with 50 mL of a saturated aqueous solution of sodium
chloride three times. The organic phase was dried with anhydrous
Na2SO4, and the solvent was removed under vacuum. The product was
purified by chromatography on a column of neutral alumnia using a
mixture of hexane/ethyl acetate (90:10) as eluent. Product 5 was
obtained as a yellow oil in 81% (287 mg) yield.
p. Dearomatization in the Presence of CO. Synthesis of
Complexes 9a and 10a. A 20 mL vial equipped with a cap with a
septum was charged with 25 mg (0.047 mmol, 1 equiv) of complex 6a
and 1 mL of C6D6. The suspension in the vial was stirred and bubbled
with CO, and then a solution of KHMDS (10 mg, 0.05 mmol, 1.05
equiv) in 0.5 mL of C6D6 was injected with a syringe into the reaction
mixture at room temperature. A red solution of complex 9a appeared
immediately. The solution was introduced into an NMR tube and
characterized. The conversion of 9a into 10a was followed at room
temperature by 1H and 31P NMR for a period of 19 h until complex 9a
completely disappeared.
1H NMR (CDCl3): 8.24 (d, J = 4.2 Hz, 1H, Py), 7.7 (t, J = 7.38 Hz,
1H, Py), 7.6 (t, J = 7.71 Hz, 1H, Py), 7.1 (m, 2H, Py), 6.9 (d, J = 7.47
Hz, 1H, Py), 6.8 (d, J = 8.2 Hz, 1H, Py), 2.5 (s, 3H, CH3-Py). 13C
NMR (CDCl3): 162.3 (s, Py), 160.7 (s, Py), 157.82 (s, Py), 147.7 (s,
Py), 139.6 (s, Py), 139.4 (s, Py), 119.7 (s, Py), 119.3 (s, Py), 113.2 (s,
Py), 111.18 (s, Py), 24.1 (s, CH3-Py). MS (EI+): 186 (M+).
Complex 9a: 1H NMR (C6D6): 8.8 (d, J = 5.73 Hz, 1H, Py), 6.8 (d,
J = 6.8 Hz, 1H, Py), 6.7 (t, J = 7.44 Hz, 1H, Py), 6.5 (t, J = 7.44 Hz,
1H, Py), 6.4 (d, J = 8.6 Hz, 1H, Py), 6.1 (t, J = 6.3 Hz, 1H, Py), 5.7 (d,
J = 6.7 Hz, 1H, Py), 3.6 (d, JP−H = 2.6 Hz, 1H, CH-P), 2.1 (s, 3H,
CH3-C), 1.5 (d, JP−H = 13.7 Hz, 9H, t-Bu2P), 1.4 (d, JP−H = 13.5 Hz,
9H, t-Bu2P), 1.37 (s, 3H, CH3-C), −4.34 (d, JP−H = 18.8 Hz, 1H, Ru-
H). 31P NMR (C6D6): 99.32 (s).
n. Synthesis of Phosphine Ligand 2c. A dried three-neck round-
bottom flask equipped with a stirring bar and connected to a vacuum-
argon line, equipped with two rubber septa, was charged with 250 mg
(1.3 mmol, 1.0 equiv) of 2-methyl-6-(pyridin-2-yloxy)pyridine (5) and
15 mL of anhydrous diethyl ether. The flask was placed in a dry ice/
acetone bath at −75 °C under a constant flow of argon. The 1 mL of a
solution of n-BuLi (1.5 M in hexanes, 1.4 mmol, 1.1 equiv) was added
dropwise at this temperature during 20 min. After this time a solution
of ClP(t-Bu)2 (266 mg, 1.4 mmol, 1.1 equiv) in 3 mL of ether was
transferid via cannula into the flask, and the resulting solution was
stirred at −75 °C for 3 h. The reaction was allowed to warm to room
temperature and stirred overnight under argon. After this time the
reaction was quenched with 3 mL of deionized and deoxygenated
water, the organic phase was transferred via cannula into a dried
Schlenk tube connected to a vacuum-argon line, and the solvent was
removed under vacuum. The resulting oil was dissolved in 10 mL of
pentane in a glovebox and dried with anhydrous Na2SO4. The pentane
solution was passed through a column of neutral alumina, and the
pentane was removed under vacuum during 4 h. The product 2c was
obtained as yellow oil in 76% (338 mg) yield.
1
Complex 10a: H NMR (C6D6): 8.1 (br s, 1H, Py), 7.5 (t, J = 7.2
Hz, 1H, Py), 6.6 (t, J = 7.7 Hz, 1H, Py), 6.4 (d, J = 7.8 Hz, 1H, Py), 6.2
(d, J = 7.7 Hz, 1H, Py), 6.0 (m, 2H, Py), 2.7 (m, 2H, Py-CH2-P), 2.2
(s, 3H, CH3-C), 1.3 (s, 3H, CH3-C), 1.1 (d, JP−H = 13.37 Hz, 9H, t-
Bu2P), 0.94 (d, JP−H = 12.7 Hz, 9H, t-Bu2P). 31P NMR (C6D6): 100.8
(s).
q. Dearomatization in the Presence of CO. Synthesis of
Complex 9c. A 20 mL vial equipped with a cap with a septum was
charged with 25 mg (0.05 mmol, 1 equiv) of complex 6c and 1 mL of
C6D6. Then 10.5 mg (0.052 mmol, 1.05 equiv) of KHMDS was
dissolved in 0.5 mL of C6D6 and charged in a syringe. The suspension
in the vial was stirred and bubbled with CO, and then the KHMDS
solution was injected into the reaction mixture at room temperature.
An orange solution of complex 9c appeared immediately. The solution
was introduced into an NMR tube and characterized. The product was
1
stable in solution for several days according to H and 31P NMR.
1H NMR (C6D6): 8.17 (brd, JP−H = 6.0 Hz, 1H, Py), 6.54 − 6.58
(m, 2H, Py), 6.42 (brd, JP−H = 9.0 Hz, 1H, Py), 6.35 (d, JP−H = 9.0 Hz,
1H, Py), 5.90 (d, JP−H = 6.0 Hz, 1H, Py), 5.50 (d, JP−H = 6.0 Hz, 1H,
Py), 3.73 (d, JP−H = 3.0 Hz, 1H, =CH-P), 1.48 (d, JP−H = 15.0 Hz, 9H,
tBu2P), 1.27 (d, JP−H = 15.0 Hz, 9H, tBu2P), −4.41 (d, JP−H = 24.0 Hz,
1H, Ru-H). 31P NMR (C6D6): 99.32 (s). 13C NMR (C6D6): 204.0 (d,
1H NMR (C6D6): 8.6 (d, J = 4.4 Hz, 1H, Py), 7.1 (t, J = 7.2 Hz, 1H,
Py), 7.0 (t, J = 7.7 Hz, 1H, Py), 6.8 (d, J = 8.3 Hz, 1H, Py), 6.7 (m, 2H,
Py), 6.5 (t, J = 6.5 Hz, 1H, Py), 2.8 (d, JP−H = 2.9 Hz, 2H, Py-CH2-P),
1.0 (d, JP−H = 10.9 Hz, 18H, t-Bu2P). 31P NMR (C6D6): 39.2 (s). 13
C
NMR (C6D6): 161.5 (s, Py), 161.4 (s, Py), 161.3 (s, Py), 147.8 (s, Py),
138.8 (s, Py), 138.4 (s, Py), 119.7 (d, JP−C = 9.46 Hz, Py), 118.9 (s,
Py), 113.7 (s, Py), 110.5 (d, JP−C = 8.8 Hz, Py), 31.6 (d, JP−C = 3.9 Hz,
P-CMe3), 31.3 (d, JP−C = 5.9 Hz, P-CMe3), 29.4 (d, JP−C = 13.8 Hz,
CMe3), 27.5 (d, JP−C = 17.0 Hz, P-CH2-Py).
J
P−C = 16.5 Hz, Ru-CO(a)), 169.7 (d, JP−C = 18.0 Hz, Ru-CO(b)), 161.3
(s, Py-C(quart)), 158.1 (s, Py-C(quart)), 153.7 (s, Py-C), 140.1 (s, Py-C),
133.4 (s, Py-C), 120.1 (s, Py-C), 116.4 (s, Py-C), 112.1 (s, Py-C),
111.9 (s, Py-C), 88.3 (s, Py-C=CH-), 64.5 (d, JP−C = 70.5 Hz, =CH-
P), 38.2 (d, JP−C = 22.5 Hz, C(a)(CH3)3), 34.7 (brs, C(b)Me3), 31.2 (d,
JP−C = 4.5 Hz, C(C(a)H3)3), 29.0 (d, JP−C = 6.0 Hz, C(C(b)H3)3).
r. Hydrogenation of Amides to Corresponding Alcohols and
Amines. A 100 mL Fischer−Porter tube was charged under nitrogen
with the ruthenium catalyst (0.01 mmol), an amide (1.0 mmol), and
THF (2 mL). The nitrogen present in the Fischer−Porter (100 mL)
was replaced by H2 (three times with 30 psi) at room temperature;
then it was filled with H2 (10 atm). The solution was heated at 110 °C
(bath temperature) with stirring for 48 h or longer. After cooling to
room temperature, the H2 was vented off carefully and the products
were determined by GC with mesitylene as internal standard, using a
Carboxen 1000 column on an HP 690 series GC system.
s. X-ray Crystal Structure Determination of Complexes 6a,
6b, and 8a. Crystals were placed in Paratone oil (Hampton
Research), mounted in a MiTeGen loop, and flash frozen in a
nitrogen stream at 100 K. Data were collected on a Bruker APEX-II
Kappa CCD diffractometer mounted on a FR590 generator equipped
with a sealed tube with Mo Kα radiation (λ = 0.71073 Å), MiraCol
optics, and a graphite monochromator. The data were processed and
scaled using the Bruker Apex2 SAINT suite. The structures were
solved using direct methods with SHELXS-97 based on F2. CIF files
are included as separate files.
o. Synthesis of Complex 6c. A Schlenk vessel equipped with a
stopcock, a Rotaflo cap, and a stirring bar was charged with 524 mg
(0.55 mmol, 1 equiv) of RuHCl(CO)(PPh3)3 and a solution of 200
mg of the PNN ligand 2c (0.6 mmol, 1.1 equiv) in 5 mL of THF. The
solution was heated in an oil bath at 65 °C for a period of 6 h. After
this time, the solution was transferred into a vial, the solvent was
concentrated to 1 mL, and then 5 mL of pentane was added, allowing
the precipitation of the product. The solid was filtered off, washed with
3 × 5 mL of pentane, and dried under vacuum for 4 h. The product 6c
was obtained as a light yellow solid in 91% yield (0.275 g).
1H NMR (CD2Cl2): 8.9 (d, J = 5.8 Hz, 1H, Py), 7.8 (m, 2H, Py),
7.4 (d, J = 7.4 Hz, 1H, Py), 7.3 (d, J = 8.3 Hz, 1H, Py), 7.2 (t, J = 6.6
Hz, 1H, Py), 7.12 (d, J = 8.1 Hz, 1H, Py), 3.8 (dd, JP−H = 8.87 Hz,
Jgem= 16.21 Hz, 1H, Py-CH2-P), 3.4 (dd, JP−H = 10.43 Hz, Jgem = 16.1
Hz, 1H, Py-CH2-P), 1.5 (d, JP−H = 13.24 Hz, 9H, t-Bu2P), 1.2 (d, JP−H
= 12.9 4 Hz, 9H, t-Bu2P), −14.48 (d, JP−H = 23.56 Hz, 1H, Ru-H). 31
P
=
NMR (CD2Cl2): 112.8 (s). 13C NMR (CD2Cl2): 206.4 (d, JP−C
17.19 Hz, CO), 162.0 (d, JP−C = 4.6 Hz, Py), 158.5 (s, Py), 158.3 (s,
Py), 154.5 (d, JP−C = 1.68 Hz, Py), 140.66 (s, Py), 140.22 (s, Py),
121.1 (d, JP−C = 1.10 Hz, Py), 119.5 (d, JP−C = 8.6 Hz, Py), 115.6 (d,
JP−C = 1.62 Hz, Py), 112.4 (s, Py), 36.9 (d, JP−C = 17.24 Hz, CMe3)
35.8 (d, JP−C = 23.12 Hz, CMe3), 35.7 (d, JP−C = 16.87 Hz, P-CH2-Py),
29.7 (d, JP−C = 3.6 Hz, CMe3), 28.9 (d, JP−C = 3.2 Hz, CMe3). MS
(ESI, MeOH): 562 (100%, (M − Cl)+).
I
dx.doi.org/10.1021/om400194w | Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
2721. (h) Balaraman, E.; Ben-David, Y.; Milstein, D. Angew. Chem., Int.
Ed. 2011, 50, 11702. (i) Balaraman, E.; Fogler, E.; Milstein, D. Chem.
Commun. 2012, 48, 1111.
(5) (a) Milstein, D. Top. Catal. 2010, 53, 915. (b) Gunanathan, C.;
Milstein, D. Acc. Chem. Res. 2011, 44, 588.
ASSOCIATED CONTENT
* Supporting Information
Catalytic experiments, copies of NMR spectra of complexes 6a,
6b, 6c, 7a, 7b, 8a, 8b, and 9c, and CIF files giving X-ray data for
6a, 6b, and 8a are included. This material is available free of
charge via the Internet at http://pubs.acs.org.
■
S
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AUTHOR INFORMATION
Corresponding Author
*E-mail: david.milstein@weizmann.ac.il.
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This research was supported by the European Research Council
under the FP7 framework (ERC No. 246837). R.B.-F. thanks
Conacyt and Mr. Armando Jinich for a postdoctoral fellowship.
D.M. is the holder of the Israel Matz Professorial Chair of
Organic Chemistry.
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dx.doi.org/10.1021/om400194w | Organometallics XXXX, XXX, XXX−XXX