Effects of hindrance in N-pyridyl imidazolylidenes coordinated to iridium on structure and catalysis

Article abstract of DOI:10.1021/om400758b

The unhindered N-pyrid-2-yl imidazolidene NHC ligand has been shown to chelate to a CpIr fragment (1). With the goal of weakening the coordination of the pyridyl substituent and enabling its role as pendant base or hemilabile ligand, a tert-butyl group at C-6 next to the pyridyl N was installed. Attempted coordination of the newly synthesized carbene ligand avoided N-coordination entirely, but led to unexpected C-metalation at C-3 by the CpIr center. Successful formation of a weakly N-coordinated analogue was achieved by synthesizing a ligand with a second tert-butyl group at C-4. The complexes were studied using X-ray crystallography and NMR spectroscopy. The X-ray crystal structure of di-tert-butyl analogue 6 showed that in the solid the complex existed as a chloride-bridged dimer, with the pyridyl nitrogen uncoordinated. In solution, ¹⁵N chemical shift information revealed that 6 existed with the pyridyl substituent N-coordinated, presumably as a monomer, but that addition of an amine ligand readily opened the chelate. Finally, 6 was used as a catalyst for intramolecular hydroamination of primary and secondary alkenylamines. Comparing (heteroaryl)NHC species, each with a tert-butyl group next to the nitrogen, which enables hydroamination, the rate differences are very modest but increase in the order imidazolyl < pyridyl < pyrimidyl, which may be an effect of basicity but because of the similarity in rates is better ascribed to counterbalancing of more than one factor, including hemilability. The (4,6-di-tert-butyl)pyridyl species 6 was shown to be much more effective compared to parent compound 1 without the tert-butyl groups, in which the chelating group was more tightly bound.

Full text of DOI:10.1021/om400758b

Article
pubs.acs.org/Organometallics
Effects of Hindrance in N‑Pyridyl Imidazolylidenes Coordinated to
Iridium on Structure and Catalysis
Zephen G. Specht,† Douglas B. Grotjahn,*,† Curtis E. Moore,‡ and Arnold L. Rheingold‡
†Department of Chemistry and Biochemistry, San Diego State University, 5500 Campanile Drive, San Diego, California 92182-1030,
United States
‡Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0358, United States
S
* Supporting Information
ABSTRACT: The unhindered N-pyrid-2-yl imidazolidene NHC ligand has
been shown to chelate to a Cp*Ir fragment (1). With the goal of weakening
the coordination of the pyridyl substituent and enabling its role as pendant
base or hemilabile ligand, a tert-butyl group at C-6 next to the pyridyl N was
installed. Attempted coordination of the newly synthesized carbene ligand
avoided N-coordination entirely, but led to unexpected C-metalation at C-3
by the Cp*Ir center. Successful formation of a weakly N-coordinated
analogue was achieved by synthesizing a ligand with a second tert-butyl
group at C-4. The complexes were studied using X-ray crystallography and
NMR spectroscopy. The X-ray crystal structure of di-tert-butyl analogue 6
showed that in the solid the complex existed as a chloride-bridged dimer,
with the pyridyl nitrogen uncoordinated. In solution, 15N chemical shift information revealed that 6 existed with the pyridyl
substituent N-coordinated, presumably as a monomer, but that addition of an amine ligand readily opened the chelate. Finally, 6
was used as a catalyst for intramolecular hydroamination of primary and secondary alkenylamines. Comparing (heteroaryl)NHC
species, each with a tert-butyl group next to the nitrogen, which enables hydroamination, the rate differences are very modest but
increase in the order imidazolyl < pyridyl < pyrimidyl, which may be an effect of basicity but because of the similarity in rates is
better ascribed to counterbalancing of more than one factor, including hemilability. The (4,6-di-tert-butyl)pyridyl species 6 was
shown to be much more effective compared to parent compound 1 without the tert-butyl groups, in which the chelating group
was more tightly bound.
(pyrimidyl)NHC complexes, it was less clear what role was
played by basicity of the heteroaryl group. (Imidazolyl)NHC
species 2 was somewhat less active than 4, but this could be due
to increased pendant basicity or because of altered ligand−
metal bond strength because of different geometry imposed by
the five-membered imidazole ring. Therefore, we decided to
study pyridyl analogues of pyrimidyl species 4 because the ring
size would be constant. Because protonated pyrimidine and
pyridine are of different basicity (pKa = 1.3 and 5.2,
respectively),13,14 in complexes such as 4−6, the related
pendant bases could be expected to have very different
coordination and catalytic properties.
INTRODUCTION
■
N-Heterocyclic carbene (NHC) complexes have been shown to
be extremely versatile and stable catalysts for a wide range of
reactions such as olefin metathesis, transfer hydrogenation, and
C−C coupling reactions.1−3 These NHCs are attractive ligands
due to their relative air, moisture, and thermal stability4−6
because of their strong σ-donating ability and poor back-
bonding of their complexes.7−11
In 2011 our group reported a series of iridium-based NHC
ligands that feature a potential pendant base as a substituent.12
Several of the examples (including 4, Chart 1) featured a
pyrimidine nitrogen, with one example of an imidazolyl
nitrogen (2), bound to the iridium metal. The Ir−N bond
was shown through variable-temperature NMR studies and X-
ray crystallography to weaken significantly as more steric bulk
was added around the nitrogen atoms on the pyrimidine ring.
The most reactive complex (4) featured a tert-butyl group next
to each heteroaryl nitrogen atom and was able to perform
intramolecular hydroamination of alkenes by primary and
secondary amine groups. In summary, controlling ligand sterics
near the nitrogen−iridium bond lowered the energy required to
break the bond and increased catalytic activity.
(Pyridyl)NHC complex 1 was made in 200815 and would be
expected to have a very strong Ir−N bond, as we determined to
be the case for unhindered pyrimidine analogue 3.16 Structures
5 and 6 (Chart 1) show the desired pyridine-based compounds
targeted in the study reported here. Although a few iridium
(pyridyl)NHC ligand catalysts have been reported in recent
years,15,17−19 as far as we are aware, none of these feature
sterically hindered pendant pyridines such as the ones reported
here.
Although our study conclusively demonstrated that greater
catalyst activity resulted from increased steric bulk on
Received: July 30, 2013
Published: October 14, 2013
© 2013 American Chemical Society
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elimination using the sodium salt of imidazole, producing 8 in
high yield. Subsequent N-methylation of the more nucleophilic
and less hindered imidazole ring proceeded without incident,
giving 9, and after anion exchange, 10. However, as described
below, due to unexpected metalation of the pyridine ring at a
ring carbon, producing 22, inclusion of a second tert-butyl
group as in 6 was proposed to suppress metalation.
Chart 1. Cp*Ir Complexes Considered in This Study
Including Published Species 1,15 2,12 3,16 and 412
In order to create the di-tert-butyl pyridyl imidazolium salt
19, and thus form compound 6, first alkynyl ketone 12 was
created using a method published by Grotjahn et al.20
Streitwieser’s published method was used to make pyrancar-
boxylate 13.21 The oxygen in the ring was then exchanged for a
nitrogen atom using ammonia, and then the methyl ester group
was removed by hydrolysis and decarboxylation using strong
acid and heat to give 15. Phosphorus pentachloride chlorinated
15 to form 16 in good yield, after which a copper-catalyzed
displacement reaction was used to form 17. It should be noted
here that the methods used to form compound 8 were first
used to try to create 17. However, the reaction failed to go to
completion, even at higher temperatures and longer reaction
times. The final steps of precursor synthesis followed the
previously listed methods for methylation and anion exchange,
converting 17 into 18 and then 19. The salts were characterized
1
by elemental analysis and NMR spectroscopy, where the H
NMR spectra showed a very low field resonance in the range δ
9.28−11.62 ppm, characteristic of the NCHN imidazolium
proton.
Air-stable ionic (bis-NHC)silver hexafluorophosphate com-
plexes were prepared in yields above 95% following the method
reported by Wang and Lin,22 except that no added phase
transfer agent was needed. Lack of added quaternary
ammonium salt simplified isolation to partitioning the mixture
between water and CH2Cl2 in a separatory funnel. Trans-
formations of the imidazolium salts to their corresponding
RESULTS AND DISCUSSION
■
Synthesis. As mentioned in the Introduction, in order to
change the basicity of the substituent in pyrimidyl NHC
systems without changing chelate geometry, pyridyl NHCs
were attractive targets. We embarked on the synthesis of 5,
Chart 1. Starting material 7 was subjected to addition−
Scheme 1. Syntheses of Ligands
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Scheme 2. Syntheses of Silver and Iridium Complexes and Monomer−Dimer Equilibrium of 6
silver-NHC complexes led to downfield shifts of the C-2 carbon
from 133.8 ppm to 135.0 ppm to 181.2 ppm, respectively. The
13C NMR signal for the carbene carbon attached to silver
appeared as two doublets, for example in the case of 21, at δ
181.2 ppm, with JC−Ag‑109 = 214.9 Hz and JC−Ag‑107 = 185.7
Hz, as noted by Arduengo et al.23 and subsequently
others.22,24,25 The isolated silver compounds were air stable,
and only a small amount of degradation was seen in a vial filled
with air in a closed drawer after months.
X-ray Diffraction and Raman and NMR Spectroscopic
Analysis of 6 and 23 and Related Species. Full comparison
of the structure of 6 in the solid state and solution gave
interesting results, as described here. The crystal structures for
both 6 and 23 were obtained, with the crystallographic data
listed in Table S1. The molecular structures are shown in
Figures 1 and 2 for compounds 23 and 6, respectively. Figure 1
1
1
Graphical summaries of 2D NMR data and assignments of all
proton and carbon resonances for compounds 6, 9, 10, 14−17,
19−21, and 23 are given in the Supporting Information.
The isolated Ag complexes were used for transmetalation by
[Cp*Ir(μ-Cl)Cl]2 and sufficient AgPF6. The mixtures were
stirred for 12−18 h and then filtered through Celite, followed
by concentration under vacuum. In the case of attempted
synthesis of compound 5, analysis of the product mixture after
1
workup by H NMR spectroscopy suggested that only two
mutually coupled protons were left on the pyridyl ring, as
evidenced by two sharp doublets at 8.54 and 7.26 ppm (J = 7.6
Hz). A downfield broad one-proton signal was seen near 12.6
ppm, suggesting the presence of an NH and the formation of
22 rather than 5. In confirmation of this alternative structure,
addition of base allowed the isolation of neutral species 23 by
crystallization of the crude mixture as a red-orange solid in
moderate yield.
Figure 1. ORTEP diagram of 23, confirming metalation of the pyridyl
substituent at carbon.
Efforts were made to see if target complex 5 was formed at
early stages during the synthesis, which ultimately led to 22 and
23. An NMR tube reaction conducted in CD2Cl2 by mixing 20,
[Cp*Ir(μ-Cl)Cl]2, and AgPF6 showed a somewhat complicated
mixture, with evidence even in the first hour of reaction of a
downfield NH proton resonance associated with 22. Our
conclusion was that simple changes in reaction conditions alone
would not allow one to make 5, because of fast, competitive
metalation at carbon of the pyridyl ring. Cyclometalations by
Cp*Ir fragments are well known; for one example, see Li et
al.26
shows that the mono-tert-butyl pyridine ring metalated at the
C3 carbon (labeled C5 in Figure 1), forming unexpected
product 23, as previously shown in Scheme 2. Metalation at
carbon can be prevented by steric hindrance of the di-tert-butyl
pyridine ring.
Interestingly, the X-ray crystallographic data for 6 (Figure 2)
revealed that in the crystalline state the compound is dimer
(6)2, forming through bridging chlorides, rather than the
expected monomer with a chelate and an Ir−N bond.
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stretch at 280.2 cm−1, and 1-PF6 also with a terminal Ir−Cl
bond showed a single stretch at 282.8 cm−1. In our hands, the
dimer [Cp*Ir(μ-Cl)Cl]2 also showed a peak at 280.3 (terminal
Ir−Cl), but also a stretch at 254.9 cm−1, previously assigned as
due to the bridging Cl.27−30 The spectrum of 6 showed a peak
at 289.8 cm−1, and no peak between there and 177.2 cm−1.
More direct and conclusive evidence for the bonding of the
heteroaryl substituent was sought, particularly in the solution
phase, where catalysis would occur. Appreciable 15N chemical
shift changes accompanying coordination, hydrogen bonding,
or protonation of a sp2-hybridized heteroaryl nitrogen have
previously given us a uniquely diagnostic tool for determining
bonding changes of bifunctional catalysts,31−34 and the work
here is no exception. In order to study how 6 behaves in
Figure 2. ORTEP diagram of the (di-tert-butylpyridyl)NHC complex
as dimer (6)2 with bridging chloride ligands and an intact, unmetalated
ligand.
1
solution, 15N chemical shift data were gathered by H−15N
HMBC spectra (Table 1) on unlabeled compound 6 and the
product of benzylamine binding, 6-BA (Scheme 3), as we had
done previously for species 2 and 4 and their benzylamine
adducts also shown in Scheme 3.12
Comparing the Ir−C or Ir−N bond distances of the pyrimidine
compounds 3 and 4 to that of the pyridine-based compounds 5
and 6 is not possible due to the fact that 23 rather than 5
formed and that dimer (6)2 formed in the solid state rather
than the chelating monomer. Apparently the Ir−Cl bridging
interaction and the Ir−N interactions must have relatively
similar strengths and can be reversibly formed, supporting the
notion of Ir−N bonds weakened by steric destabilization.
To begin to study the relationship of 6 and dimer (6)2,
attempts were made to identity the bridging chloride dimer
using Raman spectra of solid samples (spectra shown in the
Supporting Information). Complex 23 showed a terminal Ir−Cl
In addition to looking at 6 and 6-BA, to provide models for
the 15N chemical shift in the absence of coordination, synthetic
precursors 19 and 21 were also examined (Table 1, entries 11
to 14). One can see from entries 11 and 12 that chemical
changes remote from a pendant heteroaryl nitrogen, such as
conversion of an imidazolium salt to its corresponding silver-
NHC complex, do not lead to appreciable chemical shift
changes (no more than 5 ppm) for the pendant heteroaryl
nitrogen. The same conclusion is reached when looking at data
for three different heteroaryl groups (di-tert-butylpyridyl, its
a
Table 1. 15N NMR Chemical Shift Data for Complexes and Model Compounds
15N NMR chemical shifts
heteroaryl
imidazolium or imidazolylidene
temp (o
C)
N1 (N-
Me)
N-3 (with
heteroaryl)
coordinated
PhCH2NH2
entry
heteroaryl group
imidazole
compound
solvent
N free
N interacting
b
b
1
2
acetone-d6
CD2Cl2
CD2Cl2
CD2Cl2
acetone-d6
CD2Cl2
CD3CN
CDCl3
30
−239.2
−226.8
−125.7
−125.4
−128.6
−100.6
−224.4 (coord)
−135.3 (H-bond)
−203.0
−189.8
−204.1
−195.4
−201.8
−192.4
−203.1
−205.7
−195.7
−210.0
−205.9
−196.0
−204.0
−191.5
−193.7
−195.9
−182.3
−171.2
−177.7
−170.0
−178.7
−183.5
−171.6
−164.6
−183.2
−171.0
−178.8
−170.4
b
2
2-BA
24
−90
30
−385.2
b
3
pyrimidine
b
4
X = N, R = t-Bu
25
30
b
5
4
−18
−90
30
−191.2 (coord)
−118.0 (H-bond)
−176.9 (coord)
b
c
6
4-BA
−388.4
d
7
pyridine
1-PF6
8
pyridine
10
20
23
19
21
6
30
−98.5
−93.2
−113.8
−104.5
−99.9
9
X = CH, R = H
CD2Cl2
CDCl3
30
10
11
12
13
14
30
pyridine
CDCl3
30
X = CH, R = t-Bu
CD2Cl2
CD2Cl2
CD2Cl2
30
−40
−60
−181.4 (coord)
−96.2 (H-bond)
c
6-BA
−385.0
a
1
Measured except as otherwise noted for the benzylamine ligand of 4-BA using H−15N gHMBC data. See Supporting Information for assigned
b
cross-peaks. In the “N interacting” column, “coord” means coordinated, “H-bond” means engaged in a hydrogen bond. Data in entries 1 to 6 are
from ref 12 for ready comparison with new data. The 15N shifts for 2 given in the reference were found to be mistaken due to errors in calculation
c
and are here corrected. Data for compound made with 15N-labeled benzylamine, from the 1D 15N spectrum instead of H−15N gHMBC, probe
1
d
−
temperature 30 °C. Analogue of 1 with PF6 instead of chloride counterion.
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Scheme 3. 15N NMR Comparison between Products of
Reacting 2, 4, and 6 with Benzylamine
amine. Approximately 0.04 mmol of 6 was combined with an
equimolar amount of labeled benzylamine, with 0.6 mL of
CD2Cl2 as solvent, forming 6-BA (Scheme 3), which showed a
structure similar to that of previously published amine adducts
2-BA and 4-BA. 15N NMR data for the three benzylamine
adducts are summarized in Table 1.
a
When the chelate is opened by binding of benzylamine to the
iridium, in 6-BA the pyridine nitrogen signal shifts downfield to
−96.2 ppm, which is clear evidence for no more coordination
to the metal. However, as to the nature of hydrogen bonding,
the 15N chemical shift is less diagnostic than in other systems
previously examined (e.g., 4-BA12 or various heteoraryl
phosphines31,33): the value for 6-BA is about 3 ppm upfield
that in the closest model compound, 21, whereas for 4-BA,
which had two pyrimidyl nitrogens that would be equivalent
except for hydrogen bonding to one of them, the 15N chemical
shift of the hydrogen-bonding N was seen to be 17.4 ppm
upfield of the second, noninteracting nitrogen (Table 1, entry
6).
In order to gain more insight into the hydrogen bonding in
6-BA, the NMR data for the two protons of the bound amino
group were examined. In the spectrum of 6-BA distinctive
features include a four-spin system for the −CH2NH2 unit, with
the two NH protons resonating at 6.65 ppm (dddd, JHH = 4.7,
11.6, 11.7 and JHN = 73.1 Hz) and 4.01 ppm (dddd, JHH = 1.5,
10.9, 11.3, and JHN = 70.7 Hz). Because 15N-labeled
benzylamine was used, the two distinct one-bond N−H
coupling constants were seen, with that of the downfield
proton resonance being larger by 2.4 Hz, consistent with a
significant difference in chemical environment for the two N−
H bonds, one of which is proposed to be engaged in hydrogen
bonding.
a
Data for 2-BA and 4-BA are from ref 12.
mono tert-butyl analogue, as well as for the di-tert-
butylpyrimidyl system previously reported12) (entries 11 and
12; 8 and 9; and 3 and 4). Turning to the specific case of the di-
tert-butylpyridine substituent relevant to 6, the 15N shifts
showed that as an imidazolium salt with no coordination to the
pyridine ring the shift is −104.5 ppm (entry 11). Significantly,
the 15N pyridine peak for 6 (entry 13) shifts upfield by 76.9
ppm to −181.4 ppm, definitely indicating coordination to the
metal.31,33 The NMR evidence strongly implicates formulation of 6
as the chelate shown, in methylene chloride. Similarly, for
pyrimidyl system 4, with one coordinating N and one free N,
a chemical shift difference of 62.6 ppm was noted (Table 1,
entry 5).
Intramolecular Hydroamination and Cyclization of
Alkenylamines. Catalyzed cyclization of the primary amine
26a to give 27a in Scheme 4 was performed in order to
Scheme 4. Products from Reaction of Primary Amine 26a or
Secondary Amine 26b: Cyclization (27a,b), Alkene
isomerization (28a,b), and Subsequent Dehydrogenation of
27a (29)
1D 1H and 13C{1H} NMR spectra for 6 in methylene
chloride solution showed a single set of peaks, whether at +30
°C or at −40 °C, and although there was some slight
broadening of some of the resonances, the appearance of the
peaks did not change over the temperature range mentioned.
The estimated detection limit for any minor species may be
conservatively estimated as 5%. Given the identification of 6 as
the chelate in CD2Cl2 at −40 °C (by 15N chemical shift data,
with the −18 °C temperature used to sharpen signals and allow
for detection of cross-peaks) and the appearance of one set of
NMR peaks or 1H−13C cross-peaks over a temperature range of
70 °C, we conclude that if chloride-bridged dimer (6)2 is also
present, it must be in small amounts. However, our proposal is
that when the mixture is subjected to conditions where crystals
slowly form, the chloride-bridged dimer (6)2 can form because
the dicationic salt form is presumably less soluble under the
conditions of crystallization.
compare the (pyridyl)NHC-based catalysts to the previously
published pyrimidyl analogues. The reactions were performed
in sealed J. Young NMR tubes in order to eliminate any loss of
reactant material or accidental introduction of contamination
that might be introduced because of sampling, and THF-d8 was
used rather than toluene because it effectively dissolved the
catalyst. Table 2 shows that 4 and 6 are very similar in activity.
Looking at results from primary amine 26a, among
(pyridyl)NHC derivatives, an increase in conversion occurs
on going from 1, which is virtually inactive, to [Cp*Ir(μ-
Cl)Cl]2, and finally to 4 and 6, which are the most active, but
similar to each other in activity. It is interesting to note that the
isomerization of 26a to 28a occurred only in an appreciable
amount using [Cp*Ir(μ-Cl)Cl]2 and in a very small amount
using 1. Using 4 or 6, the cyclization reaction is essentially
In order to investigate the lability of the chelate in 6, the
complex was treated with a primary amine, 15N-labeled benzyl
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a
Table 2. Percent Yields for the Cyclization of Primary Amine 26a
1 h
24 h
72 h
catalyst
26a
27a
28a
29
26a
27a
28a
29
26a
27a
28a
29
[Cp*Ir(μ-Cl)Cl]2
69
96
0
0
17
0
0
61
92
65
0
1.6
0
26
5.6
0
0
0
51
78
36
0
3.6
0.5
55
31
5.6
3
0
0
1
2
6
4
2.1
27
78
78
0
0
68
60
22
31
1.1
4.1
7.8
9.1
2.0
17
72
0.5
26
0
3.3
21
0
64
0.4
33
a
26a (0.125 mmol) and catalyst (5 mol %; 2.5 mol % in the case of [Cp*Ir(μ-Cl)Cl]2 in THF-d8 (0.5 mL) at 100 °C). Yields shown are based on 1H
NMR spectroscopic analysis, averaging results from two separate runs, except for 4, using 1,3,5-trimethoxybenzene as an internal standard. Estimated
experimental uncertainties in yields are about 2% for larger values and as low as 0.5% for smaller values; hence yield totals may be as much as 105%
in some cases, within the uncertainties of the method.
a
Table 3. Percent Yields for the Cyclization of Secondary Amine 26b
1 h
24 h
72 h
catalyst
26b
27b
28b
26b
27b
28b
26b
27b
28b
1
6
4
2
99
16
2.9
37
0
83
89
62
0
95
0
1.3
84
1.0
0
85
0
2.6
79
1.0
0
0
2.0
3.9
3.0
3.8
89
2.0
4.4
86
a
26b (0.125 mmol) and catalyst in THF-d8 (0.5 mL) at 100 °C. Yields shown are based on 1H NMR spectroscopic analysis, averaging results from
two separate runs, except for 2 and 4, using 1,3,5-trimethoxybenzene as an internal standard.
complete within 24 h, but the yield of 27a (78%) was
diminished by a side reaction, dehydrogenation to give imine
29, the amount of which increased at the 72 h time point. We
cannot exclude the possibility that other minor products such as
the six-membered-ring cyclization product are present in some
samples, but if present there must be less than 5%.
Catalyzed cyclization of secondary amine 26b to give 27b
was also examined (Table 3). Catalysts 2, 4, and 6 all cyclized
the secondary amine much more quickly than was the case for
the primary amine, with pyrimidyl species 4 working slightly
faster than pyridyl analogue 6, which was in turn slightly faster
than imidazolyl analogue 2. The observed relative rate of
reactivity suggests that there may be an inverse correlation
between the basicity of the chelating nitrogen group and the
reactivity of the catalyst for interacting with incoming proton
donors; although given the significant differences in basicity
between imidazole, pyridine, and pyrimidine, it would appear
that hemilability rather than basicity is the dominant factor in
the reactions examined.35 Pyridyl catalyst 6 appears to give the
cleanest reaction mixture.
group next to the nitrogen, which enables hydroamination, the
rate differences are somewhat modest but increase in the order
imidazolyl < pyridyl < pyrimidyl, which may be an effect of
basicity but because of the similarity in rates is perhaps better
ascribed to hemilability or counterbalancing of more than one
factor. The current study highlights the need to weaken
chelation by steric hindrance, as well as use a variety of
techniques, particularly 15N NMR spectra, to determine catalyst
structure. Moreover, the new functionalized imidazolium salts
10 and 19 and NHC ligands in silver complexes 20 and 21 are
expected to be useful in creating other novel bifunctional
catalysts.
EXPERIMENTAL SECTION
■
General Methods. Reactions were performed under dry nitrogen,
using a combination of Schlenk line and glovebox techniques. CDCl3
was distilled from CaH2 prior to use. NMR tube reactions were
performed in resealable NMR tubes (J. Young). Unless otherwise
1
specified, H and 13C data were measured at 30 °C on a 400 MHz
1
spectrometer (399.8 MHz for H and 100.5 MHz for 13C) and 15N
data on a 600 MHz spectrometer. 1H and 13C NMR chemical shifts are
reported in ppm downfield from tetramethylsilane and referenced to
solvent resonances (1H NMR: δ 7.27 for CHCl3, δ 5.32 for CHDCl2;
CONCLUSIONS
■
Complex 1, lacking a hindered pyridyl substituent, was known
to form a chelate, which from our previous studies on
fluxionality of the similar pyrimidyl analogue 3 would be
tightly bound. Successful formation of a weakly N-coordinated
analogue (6) was achieved by synthesizing a ligand with not
only a tert-butyl group at C-6, next to the pyridyl nitrogen, but
also a second tert-butyl group at C-4, to avoid metalation by the
Cp*Ir fragment (seen in 22 and 23). In solution, 15N NMR
chemical shift information on di-tert-butylated species 6 was
consistent with the expected chelate structure, whereas slow
growth of a crystal suitable for X-ray diffraction led to chloride-
bridged dimer (6)2.
13C NMR: δ 77.23 for CDCl3, δ 54.00 for CD2Cl2). H NMR signals
1
are given followed by multiplicity, coupling constants J in hertz, and
integration in parentheses. For complex coupling patterns, the first
coupling constant listed corresponds to the first splitting listed; for
example, for (dt, J = 3.2, 7.9, 1 H) the doublet exhibits a 3.2 Hz
coupling constant. Raman spectra at ambient temperatures were
obtained on a Thermo Scientific DXR Raman microscope with an
excitation laser set at 532 nm. Samples were examined in CD2Cl2
solutions in quartz cells. Elemental analyses were performed at
NuMega Laboratories in San Diego, CA, USA.
Synthesis of 6. In a 20 mL screw cap vial, solid (Cp*Ir(μ-Cl)Cl)2
(0.3309 g, 0.4183 mmol) was added to 21 (0.3304 g, 0.4153 mmol)
and silver hexafluorophosphate (0.1077 g, 0.4260 mmol) in CH2Cl2 (1
mL) under nitrogen. The resulting mixture was stirred for 18 h. The
orange-red mixture was filtered through Celite in order to remove the
silver chloride; the filter cake was rinsed with CH2Cl2 (5 mL total) in
several portions. The orange-red solution was purified by column
Complex 6 catalyzes intramolecular hydroamination much
faster than its less substituted analogue 1, as well as faster than
carbene-free precursor [Cp*Ir(μ-Cl)Cl]2. Comparing
(heteroaryl)NHC species 2, 4, and 6, each with a tert-butyl
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chromatography on silica gel using ethyl acetate to elute product. The
red solvent was removed using a rotary evaporator, and then the solid
was placed under oil-pump vacuum for 1 day, leaving 6 as a red foam
(0.4956 g, 0.6360 mmol, 77% yield). Red crystals were grown using
vapor diffusion of ether into ethyl acetate for X-ray analysis, which
revealed that the crystals consisted of the dimer (6)2, whereas
1H), 4.10 (s, 3H), 1.41 ppm (s, 9H). 13C{1H} NMR (CD2Cl2, 150.8
MHz): δ 171.3, 145.2, 141.3, 134.2, 124.9, 121.8, 120.0, 110.8, 38.3,
37.7, 30.2 ppm.
Synthesis of 12. A heat-dried 200 mL flask, under nitrogen in the
glovebox, was charged with triethylamine (100 mL). Pivaloyl chloride
(8.606 g, 71.4 mmol) was then added to the flask, forming a white
solid. 3,3-Dimethylbut-1-yne (5.860 g, 71.3 mmol) was added,
followed by palladium dichloride bis-triphenylphosphine (0.050 g,
0.071 mmol) and copper iodide (0.198 g, 1.04 mmol). The yellow
solution was stirred at 23 °C for 1.5 h, at which point the solution
turned a green color. The reaction was then stirred for an additional
1
solution-phase 15N NMR data for the single species detected by H
and 13C NMR are consistent with formulation as monomeric 6. Anal.
Calcd for C27H40ClF6IrN3P (779.26 g/mol): C, 41.61; H, 5.17; N,
1
5.39. Found: C, 41.45; H, 5.30; N, 5.39. H NMR (CD2Cl2, 599.6
MHz): δ 7.73 (s, 1H), 7.64 (s, 1H), 7.47 (s, 1H), 7.33 (d, J = 2.1, 1H),
4.01 (s, 3H), 1.52 (s, 9H), 1.48 (s, 15H), 1.41 ppm (s, 9H). 13C{1H}
NMR (CD2Cl2, 150.8 MHz): δ 174.9, 168.0, 166.3, 154.4, 126.1,
120.0, 119.8, 108.8, 92.9, 41.1, 37.2, 36.3, 32.4, 30.6, 9.7 ppm.
Synthesis of 8. In a glovebox, a 250 mL Schlenk flask with a stir bar
was charged with NaH (1.658 g, 61.1 wt % in oil, 42.2 mmol) and
NMP (30 mL). Outside the glovebox, the flask was placed in an ice
bath. Under positive nitrogen flow imidazole (2.93 g, 43.0 mmol) was
added in portions over 5 min, producing foaming, and the flask was
capped with a septum once more. After 5 min, the ice bath was
removed. After 50 min, under positive nitrogen flow was added 6-tert-
butyl-2-chloropyridine (7, 5.71 g, 33.7 mmol; see ref 36 for synthesis
of 15N-labeled analogue). The flask was capped with a septum once
more, and the flask was placed in a 140 °C oil bath for 44 h. To the
cooled mixture was added water (150 mL), and the resulting mixture
was extracted with CH2Cl2 (5 × 50 mL). Analysis by TLC showed that
most product was in extracts 1 and 2, with a trace in 4. Extracts 1 and 2
were combined, as were 3 and 4, and each portion was washed with
water (3 × 125 mL). The combined aqueous washes were back-
extracted with CH2Cl2 extract 5. After drying, filtration, and
concentration, crude product (14.5 g) was purified by flash
chromatography over silica, eluting with ethyl acetate/petroleum
ether (1:4) containing some aqueous ammonia. Product-containing
fractions were concentrated, and the residue (6.66 g) was recrystallized
from CH2Cl2, hexane, and pentane. 8 was afforded as colorless crystals
(5.81 g, 86%). Anal. Calcd for C12H15N3 (201.27 g/mol): C, 71.61; H,
7.51; N, 20.88. Found: C, 71.71; H, 7.17; N, 21.00. 1H NMR (CDCl3,
499.94 MHz): δ 8.40 (narrow m, 1H), 7.73 (t, J = 7.7, 1H), 7.67
(narrow m, 1H), 7.26 (d, J = 8, 1H), 7.19 (narrow m, 1H), 7.14 ppm
(d, J = 8, 1H).
1
18.5 h, and an aliquot for H NMR was taken to check the reaction.
Starting material was still observed, so an additional portion of
palladium dichloride bis-triphenylphosphine (0.050 g, 0.071 mmol)
was added to the reaction. After 4 h the starting material was no longer
1
observed by H NMR, and the reaction was worked up using water
(200 mL) and diethyl ether (500 mL). The resulting heterogeneous
mixture was extracted with diethyl ether (3 × 200 mL) in a 1000 mL
separatory funnel. The first three organic extracts were combined and
washed with 1 M HCl (200 mL). The diethyl ether layer was then
washed with a saturated solution of sodium bicarbonate (50 mL)
followed by a saturated solution of ammonium chloride (50 mL).
Organic extracts were dried over MgSO4 and filtered, and the filtrate
was concentrated. The sample was then purified through partial
vacuum distillation. Using a distillation setup with a fractionating
column and an oil bath, the oil bath was heated to 110 °C and the
pressure was slowly reduced to 25 mmHg. Pure product was collected
at 82−86 °C, resulting in 12 as a slightly yellow oil (9.6278 g, 57.9
mmol, 81%). NMR data matched literature values.21
Synthesis of 13. Compound 13 was made following the procedure
as reported in the literature.21 NMR data matched literature values for
the product. 1H NMR (CDCl3, 399.76 MHz): δ 6.11 (s, 1H), 3.89 (s,
3H), 1.29 (s, 9H), 1.28 (s, 9H). However, an impurity was also
1
observed every time the reaction was run. H NMR (may be partial)
(CDCl3, 399.76 MHz): δ 5.71 (s, 1H), 3.78 (s, 3H), 3.62 (s, 1H), 1.17
(s, 9H), 1.14 ppm (s, 9H).
Synthesis of 14 and 15. Two thick-walled pressure reaction tubes
(48 mL volume each) were charged with half of a sample of 13
(containing ca. 15% of unknown impurity from its reported synthesis)
(2.833 g, 10.6 mmol assuming 100% purity). To each tube was added
1,4-dioxane (6 mL) followed by concentrated ammonium hydroxide
(12 mL to each). Each tube was sealed with a threaded Teflon stopper,
and the tubes were heated for 2.8 h in an oil bath held at 80 °C, behind
a safety shield, as the contents were stirred. Initially, within about 20
min the solids mostly dissolved, giving a cloudy mixture. After an
additional 15 min and thereafter, reappearance of solids was noted.
After a total of 2.8 h, the tubes were allowed to cool before the
contents were transferred to a round-bottom flask. Methanol was used
in portions for quantitative transfer. The mixture was concentrated to
dryness by rotary evaporation, followed by storage under oil pump
vacuum overnight, leaving a white solid (2.23 g). Analysis by 1H,
13C{1H}, HSQC, and HMBC NMR spectroscopy was consistent with
the presence of 14 and 15, in a molar ratio of 1 to 10. For 15 in the
mixture: 1H NMR (CDCl3, 499.94 MHz): δ 10.94 (br s, 1H), 6.36 (d,
J = 1.5, 1H), 6.13 (d, J = 1.5, 1H), 1.36 (s, 9H), 1.25 ppm (s, 9H).
13C{1H} NMR (CDCl3, 125.72 MHz): δ 165.53, 165.37, 112.8, 100.5,
35.50, 35.09, 30.2, 29.3 ppm.
Synthesis of 9. Compound 8 (0.9105 g, 4.52 mmol) and
iodomethane (6.940 g, 48.9 mmol) were added to a round-bottom
flask with a magnetic stir bar under nitrogen. The reaction was then
left to stir under nitrogen for 24 h. Excess iodomethane was then
removed under vacuum. The 9 appeared as an off-white solid (1.5026
g, 4.38 mmol, 97% yield). Anal. Calcd for C13H18N3I (343.21 g/mol):
1
C, 45.49; H, 5.29; N, 12.24. Found: C, 45.12; H, 5.01; N, 12.06. H
NMR (CDCl3, 599.6 MHz): δ 10.99 (s, 1H), 8.26 (t, J = 1.8, 1.8, 1H),
8.07 (d, J = 7.9, 1H), 7.92 (dd, J = 8.2, 7.9, 1H), 7.71 (t, J = 1.8, 1.8,
1H), 7.46 (d, J = 7.9, 1H), 4.31 (s, 3H), 1.36 ppm (s, 9H). 13C{1H}
NMR (CDCl3, 150.8 MHz): δ 170.2, 144.5, 140.7, 135.0, 124.1, 120.8,
118.8, 111.4, 37.73, 37.68, 29.9 ppm.
Synthesis of 10 (ref 37). Solid 9 (0.3004 g, 0.875 mmol) was added
to a 20 mL vial, followed by acetone (10 mL) as the solvent. To the
resulting suspension was added while stirring potassium hexafluor-
ophosphate (0.1620 g, 0.880 mmol) dissolved in acetone (5 mL). The
reaction turned a pale yellow color and was then left to stir for 2 h at
room temperature. The mixture was filtered through Celite, the filter
cake was rinsed with acetone (5 mL), and the combined filtrates were
concentrated by rotary evaporation. In order to ensure that the ion
exchange fully took place, more potassium hexafluorophosphate
(0.1674 g, 0.909 mmol) dissolved in methanol (5 mL) was added
while stirring. After 2 h water was added to precipitate the product as a
solid, the mixture was filtered, and the solid was dried. Product 10
appeared as a pale yellow solid (0.1496 g, 0.414 mmol, 47% yield).
Anal. Calcd for C13H18F6N3P (361.27 g/mol): C, 43.22; H, 5.02; N,
11.63. Found: C, 43.60; H, 4.66; N, 11.90. 1H NMR (CD2Cl2, 499.94
MHz, 20 s acquisition time giving digital resolution of 0.05 Hz per
point): δ 9.28 (narrow m, 1H), 8.13 (t, J = 1.9, 1H), 7.97 (t, J = 8.0,
1H), 7.56 (dd, J = 0.5, 8.0, 1H), 7.54 (d, J = 8.0, 1H), 7.48 (t, J = 1.8,
1
For the intermediate 14 (tentatively identified) in the mixture: H
(CDCl3, 499.94 MHz): δ 12.00 (br s, 1H), 6.18 (s, 1H), 3.87 (s, 3H),
1.32 (s, 9H); second t-Bu singlet obscured by large singlet for
carbocyclic group at 1.36 ppm. 13C{1H} NMR (CDCl3, 125.72 MHz):
δ 169.6, 163.5, 160.2, 156.0, 100.8, 52.3, 36.8, 35.3, 30.5, 29.2 ppm.
To the solid was added concentrated sulfuric acid (12 mL), and the
resulting syrup was stirred as the flask was held in a 100 °C oil bath for
2 h. The flask was cooled in ice, and ice chips (ca. 50 cm3) were added,
followed by portions of KOH (20.0 g) in water (15 mL). The mixture
was still acidic (pH = 1), but by adding portionwise most of a mixture
of K2CO3 (20.3 g) and water (20 mL) until no more foaming was
evident, the pH was raised to 9. The resulting heterogeneous mixture
was diluted with water (200 mL) and extracted with CH2Cl2 (1 × 100
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mL, 3 × 50 mL) in a 250 mL separatory funnel. The first three organic
extracts were combined and washed with water (2 × 100 mL). The
two water washes were combined and back-extracted with the fourth
CH2Cl2 extract. Organic extracts were dried over MgSO4 and filtered,
and the filtrate was concentrated. The white solid was stored under an
oil pump vacuum for 1 d, leaving 15 (1.94 g, 9.35 mmol, 88% overall
yield from 13). Anal. Calcd for C13H21NO (207.32 g/mol): C, 75.32;
showed about 10% unreacted 17. Thus, iodomethane (0.90 g, 6.3
mmol) was added, and the mixture was stirred for 1 h. A third
treatment with iodomethane (0.61 g, 4.3 mmol) for 21 h afforded
product 18 as white solid (0.4366 g, 1.09 mmol, 101% yield), suitable
for the next step. A sample from another smaller reaction was isolated
in 94% yield and gave correct analytical data. Anal. Calcd for
C17H26IN3 (399.31 g/mol): C, 51.13; H, 6.56; N, 10.52. Found: C,
50.90; H, 6.39; N, 10.66. 1H NMR (CDCl3, 499.94 MHz): δ 11.62 (s,
1H), 8.23 (dd, J = 2.0, 1.7, 1H), 8.12 (d, J = 1.2, 1H), 7.47 (d, J = 1.2,
1H), 7.32 (dd, J = 1.7, 1.7, 1H), 4.30 (s, 3H), 1.46 (s, 9H), 1.40 ppm
(s, 9H).
1
H, 10.21; N, 6.76. Found: C, 76.31; H, 10.91; N, 7.14. H NMR
(CDCl3, 599.6 MHz): δ 10.94 (s, 1H), 6.36 (s, 1H), 6.13 (s, 1H), 1.36
(s, 9H), 1.25 ppm (s, 9H). 13C{1H} NMR (CDCl3, 150.8 MHz): δ
165.5, 165.4, 155.3, 112.8, 100.5, 35.5, 35.1, 30.2, 29.3 ppm.
Synthesis of 16. Compound 15 (2.47 g, 11.9 mmol) was added to a
dry 100 mL Schlenk flask containing phosphorus oxychloride (2.1 mL)
as the solvent. The solution was then bubbled with nitrogen gas for 5
min, and the flask was placed in a 100 °C oil bath. Phosphorus
pentachloride (2.853 g, 13.7 mmol) was then added to the reaction
slowly, with fizzing seen while stirring, while kept under a nitrogen
atmosphere. A condenser was then attached to the flask, and the oil
bath was heated to 165 °C. After 1 h the reflux was stopped, and the
volatiles were removed under reduced pressure (20 mmHg) at 120 °C.
The residue was a white solid with a yellow-colored oil. To this was
added water (24 mL), and the reaction was set in an ice bath.
Potassium hydroxide (3.8966 g, 68.5 mmol) was slowly added to the
flask to adjust the pH. The yellow-colored solution was then worked
up using water (5 mL) and diethyl ether (50 mL) in a 250 mL
separatory funnel. The aqueous layer was then extracted four times
with diethyl ether (4 × 25 mL). The organic layers were then
combined and washed with two portions of saturated potassium
carbonate solution (2 × 40 mL) and once with water (40 mL). The
organic layer was dried over magnesium sulfate, and most of the yellow
colorant was removed on a plug of silica, using diethyl ether as the
solvent. The solvent was removed under vacuum to give 16 as a pale
yellow oil (2.3458 g, 10.4 mmol, 89% yield). Anal. Calcd for
C13H20ClN (225.76 g/mol): C, 69.16; H, 8.93; N, 6.20. Found: C,
Synthesis of 19. Compound 18 (0.1266 g, 0.317 mmol) was added
to a 20 mL vial with acetone (2 mL) as the solvent. To this was added,
while stirring, potassium hexafluorophosphate (0.0613 g, 0.333 mmol)
dissolved in water (2 mL). The reaction turned a pale yellow color and
was then left to stir for 1 h at room temperature. The acetone was then
removed under vacuum, and a white solid precipitated out of the
solution. An aqueous workup was done using 5 mL of water and 5 mL
of CH2Cl2 in a 60 mL separatory funnel. The aqueous phase was then
extracted with three portions of CH2Cl2 (3 × 5 mL). The organic
layers were then combined, and the CH2Cl2 was removed under
vacuum. Product 19 appeared as a white solid (0.114 g, 0.273 mmol,
86% yield). Anal. Calcd for C17H26F6N3P (417.37 g/mol): C, 48.92;
1
H, 6.28; N, 10.07. Found: C, 49.20; H, 6.06; N, 10.33. H NMR
(CDCl3, 599.6 MHz): δ 9.35 (s, 1H), 8.17 (d, J = 1.8, 1H), 7.57 (s,
1H), 7.50 (d, J = 1.8, 1H), 7.45 (s, 1H), 4.10 (s, 1H), 1.37 (s, 9H),
1.36 ppm (s, 9H). 13C{1H} NMR (CDCl3, 150.8 MHz): δ 170.0,
166.0, 145.0, 133.8, 124.1, 119.4, 117.6, 108.0, 37.8, 36.8, 35.7, 30.4,
30.0 ppm.
Synthesis of 20. In the glovebox, a scintillation vial was charged
with solid 10 (0.1014 g, 0.281 mmol) and silver oxide (0.0281 g, 0.121
mmol). To the solids were added a stir bar, CH2Cl2 (4 mL), followed
by aqueous NaOH (0.28 mL, 1 M). The resulting mixture was stirred.
Analysis of an aliquot (ca. 0.5 mL) with CD2Cl2 added for NMR lock
showed clean conversion. Outside the glovebox, the vial and aliquot
NMR tube contents were transferred quantitatively to a separatory
funnel using CH2Cl2 (5 mL in portions) and water (5 mL). The
aqueous phase was extracted with two portions of CH2Cl2 (2 × 5 mL).
The combined organic phases were washed with water (5 mL), and
the methylene chloride was removed under vacuum (no drying agent
used). The residue was taken up in CH2Cl2 (ca. 2 mL) and filtered
through a 0.2 μm syringe filter into a tared vial, and the solution
concentrated. The solids were taken up in CH2Cl2 (1 mL), and
pentane was added in portions to precipitate the product. After a few
minutes, the pale yellow supernatant was pipetted off carefully, leaving
a white solid, which was dried in air in the dark, then under oil pump
vacuum for 1 h. Yield of 20 as a white powder: 0.0965 g, 100.6%. Some
of this sample was used for an experiment, leaving 55.7 mg, which was
stored under oil pump vacuum for an additional 35 h, affording 53.8
mg, part of which was used to obtain combustion analysis; thus the
yield of 20 was 97%. Anal. Calcd for C26H34AgF6N6P (683.42 g/mol):
1
68.90; H, 9.32; N, 6.47. H NMR (CDCl3, 599.6 MHz): δ 7.21 (s,
1H), 7.10 (s, 1H), 1.36 (s, 9H), 1.31 ppm (s, 9H). 13C{1H} NMR
(CDCl3, 150.8 MHz): δ 170.2, 163.4, 150.5, 108.2, 114.5, 37.6, 35.1,
30.6, 30.1 ppm.
Synthesis of 17. On the balance, 16 (0.148 g, 0.656 mmol) was
added to a dry 25 mL flask; then dimethyl sulfoxide (1.3 mL) was
added as the solvent. Imidazole (0.0672 g, 0.984 mmol), copper(I)
iodide (0.0272 g, 0.0656 mmol), and potassium hydroxide (0.0789 g,
1.41 mmol) were then added to the reaction flask in that order. The
solution, green in color, was then bubbled with nitrogen gas for 5 min,
and the flask placed in a 150 °C oil bath for 48 h. After 1 h of heating
the reaction solution turned a dark red color. The reaction was
1
checked periodically by analyzing aliquots by H NMR spectroscopy
until all of the peaks for the starting material were gone. The red liquid
was then worked up with 10 mL of 10% ammonium hydroxide and 30
mL of methylene chloride in a 150 mL separatory funnel. The brown-
colored aqueous phase was then extracted with three portions of
CH2Cl2 (3 × 20 mL). The organic layers were then combined and
washed with 10 mL of saturated ammonium chloride solution. The
organic layer, a brown color, was dried over sodium sulfate, and most
of the brown colorant was removed by passing the mixture through a
plug of silica, using CH2Cl2 as the eluant. After concentration, the
residue was further purified through recrystallization using the
diffusion of pentane into a diethyl ether solution while the sample
was kept in the freezer. Product 17 appeared as a white crystalline solid
(0.797 g, 0.380 mmol, 47% yield). Anal. Calcd for C16H23N3 (257.37
g/mol): C, 74.67; H, 9.01; N, 16.33. Found: C, 74.47; H, 8.95; N,
1
C, 45.69; H, 5.01; N, 12.30. Found: C, 45.68; H, 4.84; N, 12.43. H
NMR (CD2Cl2, 599.6 MHz): δ 7.78 (d, J = 2.0, 1H), 7.76 (t, J = 7.9,
1H), 7.54 (dd, J = 0.7, 7.9, 1H), 7.40 (dd, J = 0.5, 7.9, 1H), 7.29 (d, J =
2.0, 1H), 3.98 (s, 3H), 1.26 ppm (s, 9H). 13C{1H} NMR (CD2Cl2,
150.8 MHz): δ 181.2 (looks like br d, J ≈ 195), 170.4, 150.3, 140.1,
123.8 (d, J = 5.1), 121.0 (d, J = 4), 119.8, 112.6, 40.2, 38.0, 30.3 ppm.
Synthesis of 21. Solid 19 (0.0474 g, 0.114 mmol) was added to a 20
mL vial, wrapped in foil to keep light out, followed by CH2Cl2 (2 mL)
as the solvent. To the resulting solution was added sodium hydroxide
(0.1 mL, 1 M) followed by silver oxide (0.0096 g, 0.041 mmol). The
mixture was set to stir under nitrogen for 22 h. The resulting mixture
was a tan color solution. An aqueous workup was done using 5 mL of
water and 5 mL of CH2Cl2 in a 60 mL separatory funnel. The aqueous
phase was then extracted with three portions of CH2Cl2 (2 × 5 mL).
The organic layers were then combined, and the CH2Cl2 was removed
under vacuum. Product 21 appeared as a tan foam (0.0440 g, 0.0553
mmol, 97% yield). Anal. Calcd for C34H50AgF6N6P (795.63 g/mol): C,
51.33; H, 6.33; N, 10.56. Found: C, 51.60; H, 6.23; N, 10.66. 1H NMR
(CD2Cl2, 599.6 MHz): δ 7.80 (t, J = 1.6, 2H), 7.52 (d, J = 1.3, 2H),
1
16.09. H NMR (CDCl3, 599.6 MHz): δ 8.38 (s, 1H), 7.68 (s, 1H),
7.26 (d, J = 1.6, 1H), 7.19 (s, 1H), 7.11 (d, J = 1.6, 1H), 1.39 (s, 9H),
1.37 ppm (s, 9H). 13C{1H} NMR (CDCl3, 150.8 MHz): δ 169.2,
163.7, 148.1, 135.1, 130.3, 116.2, 114.2, 106.0, 37.7, 35.3, 30.7, 30.1
ppm.
Synthesis of 18. To solid 17 (0.2780 g, 1.08 mmol) in a vial was
added iodomethane (1.940 g, 13.7 mmol), and the resulting mixture
was stirred for 0.5 h. The mixture was concentrated on the rotary
evaporator. Analysis of the crude product by NMR spectroscopy
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7.35 (d, J = 1.3, 2H), 7.30 (t, J = 1.6, 2H), 4.00 (s, 6H), 1.25 (s, 18H),
1.20 ppm (s, 18H). 13C{1H} NMR (CD2Cl2, 150.8 MHz): δ 181.2
(two d, JC−Ag‑109 = 214.9, JC−Ag‑107 = 185.7), 170.0, 164.8, 150.6,
123.7 (d, J = 5.6), 121.0 (d, J = 5.0), 116.7, 109.7, 40.2, 38.1, 35.8,
30.8, 30.4 ppm.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: grotjahn@chemistry.sdsu.edu. Fax: (+1) 619-594-
4634. Tel: (+1) 619-594-0231.
1
1
Attempted Synthesis of 5, Forming 22 and Then 23. In a 20 mL
screw cap vial, solid (Cp*Ir(μ-Cl)Cl)2 (0.0547 g, 0.0676 mmol) was
added to 20 (0.0462 g, 0.0676 mmol) and silver hexafluorophosphate
(0.0170 g, 0.0676 mmol) in CH2Cl2 (1 mL) under nitrogen. The
resulting mixture was stirred for 12 h. The orange-red mixture was
filtered through Celite in order to remove the silver chloride; the filter
cake was rinsed with CH2Cl2 (5 mL total) in several portions. An
aliquot of the orange-yellow-colored solution was checked by 1H
NMR spectroscopy in CD2Cl2, and a spectrum consistent with
compound 22 was observed, indicated by a broad peak at 12.63 ppm,
ascribed to a protonated pyridine nitrogen NH, and only two sharp
doublets for pyridine ring protons at 8.54 and 7.26 ppm (J = 7.6 Hz);
this pattern was nothing like the three separate signals (two doublets
and a triplet) expected around 7 to 8 ppm for the three-spin system of
the pyridine ring protons shown in 5. The proton was then removed
from the pyridine nitrogen by dissolving the solid in CH2Cl2 and
adding Amberjet 4400 OH resin (0.092 g), then swirling the solution
for approximately 5 min. The solution turned a deep red color. The
Amberjet was then removed by passing the sample through a Celite
filter using 5 mL of CH2Cl2 in small portions. The CH2Cl2 was then
removed using a rotary evaporator, and then the solid was set to
recrystallize by dissolving the sample in toluene and slowly diffusing
hexanes while in the freezer. The crystals were then set to dry under
vacuum for 1 day, leaving 23 as a red solid (0.0388 g, 0.0537 mmol,
40% yield). Red crystals were then grown using vapor diffusion of
ether into ethyl acetate for X-ray analysis. The X-ray analysis and
elemental analysis were done using samples made in previous
experiments that had lower yields. Anal. Calcd for C23H31ClIrN3
(577.18 g/mol): C, 47.86; H, 5.41; N, 7.28. Found: C, 48.22; H, 5.80;
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the San Diego Foundation, SDSU, and NSF for
partial support of this work, including SDSU NMR facilities
(MRI CHE-0521698).
REFERENCES
■
(1) Kantchev, E. A. B.; O’Brien, C. J.; Organ, M. G. Angew. Chem., Int.
Ed. 2007, 46, 2768−2813.
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1
N, 7.05. H NMR (CDCl3, 599.5 MHz): δ 7.93 (d, J = 7.7, 1H), 7.64
(s, 1H), 6.97 (s, 1H), 6.93 (d, J = 7.7, 1H), 3.98 (s, 3H), 1.81 (s, 15H),
1.35 ppm (s, 9H). 13C{1H} NMR (CDCl3, 150.76 MHz): δ 162.8,
161.1, 159.2, 143.7, 130.3, 121.1, 116.6, 115.7, 90.6, 36.56, 36.40, 30.4,
9.7 ppm.
X-ray Crystallography. All crystallographic data were collected on
Bruker diffractometers equipped with APEX CCD detectors. All
structures were solved by direct methods and refined with anisotropic
thermal parameters and idealized hydrogen atoms. All software is
contained in the SMART, SAINT, and SHEXTL libraries distributed
by Bruker-AXS (Madison, WI, USA). Complete disclosures about the
crystallographic work may be found in the deposited CIF file.
Hydroamination. For the cyclization studies, using either primary
or secondary amine compounds the methodology for testing was
similar. Either 2,2-dimethylpent-4-en-1-amine as the primary amine or
N,2,2-trimethylpent-4-en-1-amine as the secondary amine (0.25
mmol) and catalyst (5 mol %; 2.5 mol % in the case of [Cp*Ir(μ-
Cl)Cl]2 in THF-d8 (1.0 mL) were used at 100 °C. Yields shown are
1
based on H NMR spectroscopy, averaging results from two separate
runs, except for [Cp*Ir(μ-Cl)Cl]2, using 1,3,5-trimethoxybenzene as
an internal standard.
ASSOCIATED CONTENT
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S
* Supporting Information
Additional figures including graphical summaries of 2D NMR
data and assignments of all proton and carbon resonances for
compounds 6, 9, 10, 14−17, 19−21, and 23, Raman spectra
and analysis, and CIF files for complexes 6 and 23. This
material is available free of charge via the Internet at http://
pubs.acs.org.
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Organometallics
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(35) Many mechanistic studies of hydroamination and in particular,
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(37) We thank Dr. Sara Cortes-Llamas for performing this particular
experiment.
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