Catalytic intramolecular hydroamination with a bifunctional iridium pyrazolato complex: Substrate scope and mechanistic elucidation

Article abstract of DOI:10.1021/om301063n

Catalytic intramolecular cyclization of nonactivated aminoalkene with functional group compatibility provides an atom-economical and concise route to valuable nitrogen-containing heterocycles yet remains a challenge. In this paper, we report the detailed

Full text of DOI:10.1021/om301063n

Article
pubs.acs.org/Organometallics
Catalytic Intramolecular Hydroamination with a Bifunctional Iridium
Pyrazolato Complex: Substrate Scope and Mechanistic Elucidation
Yohei Kashiwame, Shigeki Kuwata,* and Takao Ikariya*
Department of Applied Chemistry, Graduate School of Science and Engineering, Tokyo Institute of Technology, O-okayama,
Meguro-ku, Tokyo 152-8552, Japan
S
* Supporting Information
ABSTRACT: Catalytic intramolecular cyclization of non-
activated aminoalkene with functional group compatibility
provides an atom-economical and concise route to valuable
nitrogen-containing heterocycles yet remains a challenge. In
this paper, we report the detailed substrate scope and
mechanism of catalytic intramolecular hydroamination with a
half-sandwich-type iridium pyrazolato complex we have
recently developed. This metal−ligand bifunctional catalyst
promoted the hydroamination of various primary and
secondary aminoalkenes at mild temperatures (50−110 °C)
without side reactions such as oxidative amination. Cyclization of secondary aminoalkenes containing ester, cyano, bromo, and
hydroxy groups occurred with maintenance of these functional groups, while the reactions of aminoalkenes bearing allylic
substituents proceeded with a perfect diastereoselectivity. Catalyst optimization revealed that the proton-responsive functional
group at the position β to the metal is crucial to efficient catalytic turnover. Kinetic analysis indicated a highly ordered transition
state associated with N−H bond cleavage in the rate-determining step. On the basis of these data along with the stoichiometric
reactions and DFT calculations, we propose an unprecedented metal−ligand cooperating mechanism, in which cyclization occurs
through syn addition of the amino group to the coordinated olefin bond with the aid of the Brønsted basic pyrazolato ligand.
The reaction mechanisms of hydroamination of nonactivated
olefins with late-transition-metal catalysts are roughly divided
into two categories.1 One involves primary N−H bond cleavage
followed by alkene insertion into the resulting metal−amido
bond, and the other entails nucleophilic attack of the amine at
the π-coordinated olefin. In each case, either the amino or the
olefin group undergoes primary activation. We considered that
simultaneous activation of both functional groups by the
metal−ligand bifunctional catalysts, in which the Brønsted
acidic and basic ligands take part in the catalysis through
hydrogen bonding and proton transfer,14−16 would lead to the
development of novel hydroamination catalysts for a broader
range of substrates with higher efficiency.
As an extension of our continuing study of metal−ligand
bifunctional catalysis,14,15 we recently communicated that the
protic pyrazole complex 1 as well as its dehydrochlorinated
form 2 catalyzes cyclization of both primary and secondary
aminoalkenes at a fairly low temperature (50 °C), as shown in
eq 1.17 Importantly, a preliminary catalyst survey revealed that
the proton-responsive functional group placed at the position β
to the metal is crucial to the catalysis, suggesting that a
bifunctional mechanism based on the metal−ligand coopera-
tion is operative. We report here the broad substrate scope and
remarkable selectivity of this novel bifunctional pyrazole
INTRODUCTION
■
Intramolecular hydroamination of aminoalkenes is a powerful,
straightforward, and atom-economical methodology to access
cyclic amines, which are useful building blocks for a vast
number of bioactive natural alkaloids and other pharmaceutical
compounds. Intensive efforts have thus been devoted to the
development of efficient and practical hydroamination
catalysts.1 Currently the most active catalysts for the cyclization
of simple aminoalkenes, in which the olefin bond is not
activated by conjugation or electron-withdrawing substituents,
contain group 2−4 metals as a key component.2,3 These
catalysts are, however, scarcely compatible with polar functional
groups as well as air and moisture due to the highly Lewis acidic
nature of the metals. Late-transition-metal catalysts are more
promising in this regard, and actually, those with increased
substrate scope and functional group tolerance have been
reported during the past decade.4−11 Rational improvement of
the late-metal catalysts is still required in order to promote the
cyclization of relatively inert aminoalkenes, such as those with a
less nucleophilic primary amino group and those lacking gem
substituents on the chain that facilitate the cyclization by a
Thorpe−Ingold effect,12 under mild conditions. Judicious
catalyst design is also crucial to control the stereochemistry
of the cyclization product, which has rarely been explored in
late-metal catalysis,13 and to avoid undesired side reactions
exemplified by the formation of imines and olefin isomer-
ization.
Received: November 7, 2012
Published: November 19, 2012
© 2012 American Chemical Society
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Table 1. Intramolecular Hydroamination Catalyzed by C−N
a
Chelate Complexes
b
entry
cat.
base
solvent
toluene
t, h
yield,
%
1
1
KOBut
KOBut
none
6
15
6
75
98
29
80
96
8
2
1
toluene
3
1
toluene
4
2
none
toluene
6
5
2
none
toluene
15
6
6
5
KOBut
KOBut
none
toluene
7
6
toluene
15
15
6
20
0
8
7
toluene
catalyst as well as the mechanistic details elucidated by
stoichiometric reactions, kinetic experiments, and theoretical
calculations.
9
none
2
KOBut
toluene
0
10
11
12
13
14
none
THF
6
84
73
17
5
2
none
acetonitrile
methanol
tert-butyl alcohol
6
2
none
6
RESULTS AND DISCUSSION
■
2
none
6
Catalyst Screening and Solvent Dependence. To
corroborate the importance of the β-NH group in the
bifunctional pyrazole catalyst 1, we initially prepared a series
of related C−N chelate half-sandwich-type iridium complexes
5−7 and assessed the catalytic activity toward intramolecular
hydroamination of the ω-alkenic primary amine 3a. Masking of
the NH group in 1 was achieved by the reaction of the
pyrazolato-bridged dimer 2 with iodomethane, giving the N-
methylpyrazole complex 5 (eq 2). We additionally synthesized
2
none
ClCH2CH2Cl
6
0
a
b
1
Conditions: 3a:Ir = 20:1, [3a] = 0.2 M. Determined by H NMR
analyses.
composed of [Rh(cod)(CH3CN)2]BF4 and a bis-
(diethylamino) derivative of xantphos proceeds in tert-butyl
alcohol with high efficiency and selectivity, which may be
ascribed to facile proton transfer in the turnover-limiting step;
however, this solvent proved less effective in our catalyst system
(entry 13), possibly because of the low catalyst solubility. No
cyclization product was obtained from the reaction in 1,2-
dichloroethane under otherwise identical reaction conditions
(entry 14).
the C−N chelate imidazole complex 6, wherein the NH group
lies at the position γ to the metal,17,18 by acetate-promoted
cyclometalation of 2-phenylimidazole. These modified azole
complexes 5 and 6 exhibited only poor catalytic activity (Table
1, entries 6 and 7), unlike the β-protic complex 1 (entry 1). On
the other hand, the pyrazolato-bridged dimer 2 was almost as
efficient as the 1/KOBut binary catalyst even in the absence of
the base (entry 1 vs 4), indicating that the dehydrochlorinated
mononuclear bifunctional species is the catalytically active
intermediate. In contrast, the amido complex 719 obtained by
dehydrochlorination of an α-protic amine chlorido complex was
totally ineffective toward intramolecular hydroamination (entry
8). These observations imply that the proton-responsive group
built in a suitable position of the ligand is involved directly in
the catalysis.
A wide range of solvents can be employed in this catalytic
hydroamination. The high efficiency of the pyrazolato-bridged
dimer 2 was preserved in the coordinating solvents THF and
acetonitrile, as shown in entries 10 and 11, which promises
catalyst compatibility with Lewis basic functional groups in the
substrates. The reaction in methanol was much slower (entry
12), probably due to concomitant transfer hydrogenation of the
pyrazolato complex with the alcohol.17 Julian and Hartwig5
demonstrated that cyclization of aminoalkenes with a catalyst
Substrate Scope and Limitations. The scope of the
substrates for intramolecular hydroamination catalyzed by the
pyrazolato-bridged dimer 2 is summarized in Table 2.
Cyclization of the primary aminoalkene 3b with a sterically
crowded 1,1-disubstituted olefin bond was completed at a
higher temperature (entry 2) in comparison to the case for the
less substituted congener 3a (entry 1). The reactions of the
more nucleophilic secondary amines 3c−f were readily
accomplished with much lower catalyst loadings (1 mol %;
entries 3−6). It should be noted that side products due to β-
hydride elimination were not observed at all in these
hydroamination reactions. Notably, the allyl-branched amino-
alkene 3f yielded the cyclization product with a perfect trans/
cis diastereoselectivity (entry 6). The stereochemistry was
determined by an X-ray analysis of the HBF4 salt of the product
(Figure 1). Such successful control of the relative configuration
of two adjacent stereogenic centers through intramolecular
hydroamination is very rare.20 It is also remarkable that the N-
benzylaminoalkene 3g, unbiased toward cyclization by the
chain substituents, was converted to the hydroamination
product in excellent yield at 80 °C (entry 7). Indeed,
hydroamination of this class of substrates is rarely achieved
by late-transition-metal catalysts.5−7 Formation of a six-
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a
Table 2. Substrate Scope of the Hydroamination Catalyzed by 2
a
b
c
d
e
Reaction conditions: 3 (0.2 M in toluene), 2, 15 h. Ratio of 3 to iridium. Isolated yield. Determined by 1H NMR analyses. Determined by 1H
NMR analysis using durene as an internal standard.
membered ring (entry 8) as well as cyclization of an arylamine
3i (entry 9) proved to be sluggish and required higher
temperatures. In contrast, hydroamination of an internal alkene
3j did not proceed at all (entry 10).
secondary hydroxy group at the allylic position took place to
give the desired cyclic amine as a single diastereomer (entry
14), despite the fact that the catalyst 2 oxidizes 2-propanol17
and the catalysis is retarded in alcohols (vide supra). Only a
small amount of saturated ketones derived from substrate
isomerization and product oxidation were produced concom-
itantly in variable yields (8% and 3% at most, respectively).
Oxidation of the hydroxy group may be suppressed by steric
hindrance of the substrate 3n. The anti configuration of 4n,
similar to that of 4f (entry 6), was confirmed by 1D NOE
difference 1H NMR experiments, as summarized in Chart 1. An
NOE correlation between the methyl protons and the
neighboring vicinal methine proton was observed, while an
interaction between the two vicinal methine protons was not
detected (see the Supporting Information). Liu and Hartwig6
The bifunctional pyrazolato catalyst 2 was found to exhibit
wide functional group compatibility. Substrates bearing ester or
cyano groups underwent hydroamination with maintenance of
these functional groups to afford the corresponding cyclic
amines quantitatively (entries 11 and 12). An aryl bromide
moiety also remains intact (entry 13), implying that the
catalysis does not involve low-valent coordinatively unsaturated
intermediates that would suffer oxidative addition of the C−Br
bond. To our knowledge, hydroamination catalysts compatible
with the aryl bromide function are limited to only two catalyst
systems.8 Strikingly, cyclization of the substrate 3n bearing a
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possible key steps for the hydroamination with the pyrazolato
catalyst 2. The first two paths, A and B, include nucleophilic
attack of the amino group at the olefin bond activated by
coordination to the Lewis acidic iridium(III) center. Path A
features the anti addition of the amino group and metal across
the olefin bond, which is typically observed in Wacker-type
heterocyclization.22,23 Quite recently, Tobisch24 investigated
our present catalyst system computationally and proposed a
modified pathway assisted by an additional amine molecule
(path A2). Alternatively, nucleophilic attack of the amino group
with the aid of the Brønsted basic pyrazolato ligand may be
possible (path B), although that would lead to syn addition,
which is uncommon in coordinatively saturated complexes,
since such an addition is generally associated with the
precoordination of the nucleophile.25 In the last mechanism,
path C, initial cleavage of the N−H bond in the substrate
occurs by metal−pyrazolato cooperation and subsequent olefin
insertion into the resulting metal−amido bond completes the
cyclization.26
Figure 1. Structure of 4f·HBF4. One of the two crystallographically
independent molecules is shown. The anion and hydrogen atoms,
except for the NH proton and the methine protons, are omitted for
clarity.
Chart 1. The NOE Correlation in 4n
In order to gain further insights into the reaction
mechanisms, we first investigated stoichiometric reactions of
the pyrazolato-bridged dimer 2 with alkenes and amines.
Exposure of a dichloromethane solution of the pyrazolato-
bridged dimer 2 to ethylene (1 atm) resulted in the formation
of the pyrazolato−ethylene complex 8, as shown in Scheme 2.
reported that intramolecular hydroamination of 3n with a
rhodium−biarylphosphine catalyst affords the cyclization
product with an 11:1 diastereomer ratio. The major product
Scheme 2. Stoichiometric Reactions of 2
1
in their reaction is not identical with 4n in the H NMR
criteria,21 suggesting that different types of mechanisms operate
in the Rh-catalyzed hydroamination and the present bifunc-
tional catalysis with 2.
Stoichiometric Reactions of Pyrazolato Complex 2.
The remarkable efficiency, functional group tolerance, and
product selectivity without formation of potential diastereomers
and other byproducts in the intramolecular hydroamination
with the bifunctional pyrazolato catalyst prompted us to explore
more details of the reaction mechanism. Scheme 1 illustrates
Scheme 1. Possible Reaction Pathways for Hydroamination
a
Catalyzed by 2
The 13C{1H} NMR spectrum of 8 exhibited a signal ascribed to
the coordinated ethylene at δ 48.8, which is typical for Ir(III)
ethylene complexes.27 The CC bond length in 8 (1.389(10)
Å), measured by X-ray analysis (Figure 2), is only slightly
longer than that of free alkenes (1.335 Å),28 suggesting that π
back-donation to the ethylene is not dominant and the ligated
ethylene is potentially electrophilic. We also found that the
ethylene complex 8 serves as a catalyst precursor almost as
efficiently as the pyrazolato-bridged dimer 2, indicating that the
ethylene ligand is sufficiently labile. For example, intramolecular
hydroamination of the aminoalkene 3a with 8 instead of 2
under conditions otherwise identical with those in entry 1 of
Table 1 afforded the cyclization product 4a in 82% NMR yield.
On the other hand, when 2 was treated with aniline and
benzylamine, the corresponding amine complexes 9 were
a
1
[Ir] = Cp*Ir.
obtained (Scheme 2). In the H NMR spectra of 9, broad
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Figure 2. Structure of 8. One of the two crystallographically
independent molecules is shown. Hydrogen atoms, except for those
in the ethylene ligand, are omitted for clarity.
Figure 4. Structure of 10. One of the two crystallographically
independent molecules is shown. Hydrogen atoms, except for the NH
protons, are omitted for clarity.
resonances assignable to the amine protons appear in the range
δ 2−5. The crystal structures of these amine complexes are
depicted in Figure 3. In both crystals, a solvated water molecule
preparation of the N-methyl complex as shown in eq 2, the
reaction provides an example of bond cleavage by acid/base
bifunctional complexes, which has been established in the
reactions of bifunctional amido complexes with various
Brønsted acidic organic compounds, including nitromethane,
terminal alkynes, and malonates.26,29
We also monitored the reaction of the catalyst precursor 2
1
and the less reactive aminoalkene substrate 3b by H NMR
spectroscopy (Scheme 3). After 22 h at room temperature,
Scheme 3. Reaction of 2 with 3b
Figure 3. Structures of 9a (left) and 9b (right). For 9a, one of the two
crystallographically independent molecules is shown. Hydrogen atoms,
except for the amine protons, are omitted for clarity.
links two molecules of the amine complexes through
N(pyrazolato)···H2O and RNH2···OH2 hydrogen bonds with
four short N···O distances ranging from 2.804(5) to 2.984(5)
Å, indicating the Brønsted acidic/basic nature of the amine and
pyrazolato ligands.
Isolation of 9 demonstrated that the chelating pyrazole is
more acidic than the coordinated amines. The order of acidity
is, however, delicately affected by a subtle change of the
substituents. In fact, treatment of 2 with p-toluenesulfonamide
led to the formation of the sulfonamidato−pyrazole complex
signals assignable to the amine complex 9c appeared in the
spectrum, which illustrates the diastereotopic nature of the
amine protons as observed in the benzylamine complex 9b. A
prolonged reaction led to slow conversion of 9c into a 1:1
mixture of the pyrrolidine complexes 11, which was also
obtained more conveniently by the reaction of 2 and 3b in
toluene at 50 °C. An X-ray analysis revealed that the mixture
contains one of the two possible diastereomers (11a) with two
stereogenic centers, the iridium and amine nitrogen atoms
(Figure 5). Since the H NMR signals of the two products are
closely related to each other, we assigned the other product 11b
as the diastereomer of 11a.
Because the observation of 8−11 indicates that both olefin
and amine activation pathways are plausible, we next estimated
the stability of the intermediates assumed in Scheme 1 by DFT
1
10, as shown in Scheme 2. The H NMR spectrum of 10
displays a characteristic low-field resonance due to the pyrazole
NH group at δ 10.46 as well as the sulfonamidato NH singlet at
δ 2.17. The detailed structure of 10 has been determined by X-
ray analysis (Figure 4). The pyrazole ligand is engaged in
intermolecular hydrogen bonding with a sulfonyl oxygen atom
in a neighboring molecule, forming a one-dimensional infinite
chain. Protonation of the pyrazolato ligand is also deduced
from the larger N(α)−N(β)−C angle (109.7°, mean of the two
crystallographically independent molecules);15 the correspond-
ing angles in the pyrazolato complexes 9 are 105.9° (9a, mean)
and 105.4(4)° (9b). Formation of the pyrazole complex 10
manifests a facile proton shift between the amine substrate and
the cooperating pyrazolato ligand. In addition to the
1
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high-field methyl singlet at δ −0.27 as well as a β-NH
resonance at δ 9.56. Isolation of 12 was, however, hampered by
slow decomposition during recrystallization in toluene−hexane,
even at −30 °C. Although the decomposition product has
1
eluded full identification, the H NMR spectrum indicated loss
of the methyl ligand and retention of the pyrazole proton (δ
10.28). Importantly, the pyrazolato-bridged dimer 2 was not
observed. The result may imply that direct proton transfer from
the pyrazole to the alkyl ligand is unfeasible, although the
behavior of 12 does not necessarily represent the nature of the
(alkyl)iridium intermediate. The pyrrolidine moiety and the
metal center in the aminoalkyl intermediate as well as external
substrate/product amine molecules may be involved in the
proton relay in the catalytic hydroamination.9,24,31
Kinetic Experiments. We then carried out a series of
kinetic experiments to draw a clear picture of the reaction
mechanism. Since the insufficient solubility of the pyrazolato-
bridged dimer 2 prevented precise control of the catalyst
concentration, we used the ethylene complex 8, which also
produces the catalytically active mononuclear pyrazolato
species (vide supra), as the catalyst precursor. We first
monitored consumption of the aminoalkene 3d in the presence
of a catalytic amount of 8 by 1H NMR spectroscopy (Figure 6).
Figure 5. Structure of 11a. Hydrogen atoms, except for the amine
proton, are omitted for clarity.
calculations. Chart 2 shows the scrutinized species, which are
derived from the secondary aminoalkene 3d, with their
Chart 2. Calculated Relative Free Energies of Assumed
Intermediates
calculated relative free energies. The olefin complex A proved
to be more stable than the amine complex B, a congener of the
experimentally observed 9c, by 14.9 kcal mol−1, suggesting that
both species are likely to be present in the catalytic cycle as
resting states or intermediates. On the other hand, the much
higher energy of the pyrazole−amido complex C contradicts
path C, the N−H activation of the Brønsted basic alkylamine
substrates.
Figure 6. Profile for the decay of secondary aminoalkenes 3d and 3d-d
in the presence of 8. Reaction conditions: 3d:Ir = 20:1, [3d] = 0.20 M,
40 °C, in C6D6.
Synthesis and Properties of Pyrazole−Alkyl Complex.
The possible mechanisms shown in Scheme 1 all involve
(alkyl)iridium species arising from the C−N bond formation
step. To explore the nature of the metal−alkyl bond, we
synthesized an alkyl complex bearing a protic pyrazole ligand.
Treatment of the chlorido complex 1 with 0.5 equiv of
dimethylzinc resulted in the formation of the pyrazole−methyl
complex 12 along with a small amount of uncharacterized
The reaction obeyed zero-order kinetics with regard to the
concentration of the aminoalkene until about 65% conversion,
and consequently the substrate coordination step to the iridium
center should be relatively fast. The apparent rate constant kobs
at the early stage of the reaction with an [Ir]0 value of 0.010 M
at 40 °C was determined to be 7.54 × 10−5 M s−1. When the
deuterium-enriched aminoalkene 3d (ca. 60% D) was subjected
to the catalytic cyclization, the reaction rate significantly
decreased, as illustrated in Figure 6. The kobs value of the
deuteriated substrate (2.65 × 10−5 M s−1) is much smaller than
that of the nondeuteriated aminoalkene 3d, and the kH/kD ratio
is thus estimated to be more than 2.8.
byproduct (eq 3).30 The H NMR spectrum of 12 features a
1
On the other hand, the reaction rate exhibited approximate
first-order dependence on the initial concentration of the
catalyst [Ir]0, as shown in Figure 7. The deviation of the plot
from linearity may be explained by an equilibrium between the
catalytically active mononuclear pyrazolato species and the
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Ea = 15.9 kcal mol−1, an activation enthalpy of ΔH⧧ = 15.2 kcal
mol−1, and an activation entropy of ΔS⧧ = −30 cal mol−1 K−1.
This large negative ΔS⧧ value suggests a highly ordered
transition state in the rate-determining step.
Computational Study of Protonolysis Step. Given that
the cyclization step is rate-determining, the observed primary
KIE of the NH proton and the zero-order rate dependence of
the substrate concentration are best explained by path B in
Scheme 1. An alternative scenario that merits discussion is one
involving rate-determining protonolysis of the (alkyl)iridium
species which results from the cyclization. Stradiotto and co-
workers revealed similar primary KIE (3.4(3)) and ΔS⧧ values
(−23.1(8) cal mol−1 K−1) in [IrCl(cod)]2-catalyzed intra-
molecular hydroamination, and with the aid of DFT
calculations, they concluded that reductive elimination from
an (alkyl)(hydrido)iridium(III) intermediate, which is gener-
ated by cyclization and subsequent proton migration, is rate-
determining.9 The large negative activation entropy value was
ascribed to a highly ordered transition-state structure in the
reductive elimination, although the actual ΔS⧧ values for
reductive elimination reported in the literature fall in both the
positive and negative ranges.32 Tobisch24 also proposed that
protonolysis of the (alkyl)iridium species in our present
bifunctional catalysis involves turnover-limiting reductive
elimination from an (alkyl)(hydrido)iridium(V) intermediate
after proton migration assisted by external amine molecules.
We therefore estimated the thermodynamic parameters in the
reductive elimination from the (tert-aminoalkyl)(hydrido)-
iridium(V) intermediate by DFT calculations (Scheme 4).
The slightly positive ΔS⧧ value thus obtained is inconsistent
with the result of the kinetic experiments, indicating that the
reductive elimination stage is not rate-determining.
Figure 7. Plot of kobs versus [Ir]0 in hydroamination of 3d in the
presence of various amounts of 8. Reaction conditions: 3d:Ir = 20−
200, [3d] = 0.22 M, 40 °C, in C6D6.
dimerized resting state 2, which would shift to the latter as the
concentration of the iridium complexes increases.
The reaction rates of the cyclization of 3d were determined
at temperatures ranging from 30 to 60 °C. The Arrhenius and
Eyring plots shown in Figure 8 provided an activation energy of
Proposed Mechanism of Catalytic Hydroamination.
The accumulated data led to the following mechanistic
considerations. The DFT calculations exclude the primary
N−H cleavage (path C in Scheme 1) and rate-determining
protonolysis of the (alkyl)iridium species. The zero-order rate
dependence on substrate concentration indicates that the initial
olefin coordination as well as assistance of the external amine
(path A2) is not involved in the turnover-limiting step.
Therefore, the cyclization stage is most likely to be the rate-
determining step. Since path A1 is against the observed primary
KIE of the NH proton, we conclude that the path B is the most
probable mechanistic scenario. The syn addition therein may
further be implied by the stereochemical outcome in the
cyclization of 3n, which is different from the result in the
Figure 8. Arrhenius plot (above) and Eyring plot (below) for the
hydroamination of 3d catalyzed by 8. The reactions were conducted at
a temperature range of 30−60 °C. Reaction conditions: 3d:Ir = 50:1,
[3d] = 0.23 M, in C6D6.
Scheme 4. Calculated Activation Parameters for the Reductive Elimination Step
a
Values relative to that of the olefin complex A in Chart 2.
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rhodium−biarylphosphine catalyst (vide supra),6 for which an
anti addition mechanism has been proposed.10 Unfortunately,
conclusive experiments to distinguish the two stereochemical
courses using appropriately designed internal aminoalkenes10,33
were hampered by the low catalytic activity of 2 toward such
substrates.
The overall mechanism for the intramolecular hydro-
amination catalyzed by the bifunctional pyrazolato complex is
illustrated in Scheme 5. The coordinatively unsaturated
methyl−pyrazole complex 12, yielding no pyrazolato-bridged
dimer 2; apparently, more complicated proton migration
should take place. On the basis of comprehensive DFT
calculations, Tobisch23 recently proposed a distinct mechanism
featuring nucleophilic anti addition (path A2 in Scheme 1) and
rate-determining reductive elimination from a (hydrido)-
iridium(V) intermediate. However, this mechanism seems
inconsistent with the markedly negative ΔS⧧ value observed.
The discrepancy may be ascribed to the difference in the
aminoalkenes under consideration: our kinetic experiments
were carried out for the secondary aminoalkene 3d, while
Tobisch used a less hindered primary aminoalkene, wherein the
hydrogen-bonding stabilization with the external amine
substrate may be overestimated.
Scheme 5. Proposed Mechanism of the Intramolecular
Hydroamination Catalyzed by 2
CONCLUSION
■
We have demonstrated that the bifunctional iridium pyrazolato
complex 2 is an efficient, functional-group-tolerant intra-
molecular hydroamination catalyst for aminoalkenes. A series
of stoichiometric reactions and kinetic experiments of the
pyrazolato complexes as well as theoretical calculations are fully
consistent with the unprecedented metal−ligand bifunctional
mechanism,35 in which the Lewis acidic metal and the Brønsted
basic pyrazolato ligand cooperatively activate the olefin and
amino groups of the substrate in the rate-determining transition
state (Scheme 4). Owing to the multipoint binding of the
substrate delicately controlled by the cooperating ligand, the
bifunctional pyrazolato catalyst is applicable to less reactive
aminoalkenes bearing a primary amino group or without gem
substituents on the linker chain. The tight-fitting assembly of
the catalyst and substrate in the transition state also contribute
to the perfect diastereoselectivity in the hydroamination of
aminoalkenes bearing allylic substituents. In addition, inter-
mediacy of the coordinatively saturated alkyl species would
result in the excellent selectivity of hydroamination over
oxidative amination arising from β-elimination. Use of the
metal−ligand cooperating bifunctional catalyst thus provided a
novel strategy in hydroamination, which will guide the future
development of increasingly effective catalysts.
EXPERIMENTAL SECTION
■
General Procedures. All manipulations were performed under an
atmosphere of argon using standard Schlenk techniques unless
otherwise specified. Solvents were dried by refluxing over sodium
benzophenone ketyl (THF, toluene, C6D6, diethyl ether, and hexane)
or CaH2 (CH2Cl2) and distilled before use. Reagents were purchased
from Kanto Chemicals, Aldrich, and Tokyo Chemical Industry and
used as received. Silica gel column chromatography was performed
using Fuji Silysia silica gel FL100D. Automated silica gel column
chromatography was performed using a Yamazen YFLC AI-580
pyrazolato complex, which would be in equilibrium with the
dimer 2, first reacts with the substrate aminoalkene to form an
olefin-bound or amine-bound complex. The experimentally
observed latter complex is a resting state. The coordinated
olefin in the former then undergoes rate-determining
nucleophilic attack of the amino group from the same side as
the metal, which is assisted by the concurrent deprotonation of
the amino group with the pyrazolato ligand. The sterically
constrained transition state involving N−H bond cleavage
agrees with the observed negative activation entropy and
primary KIE. The multiple noncovalent interactions between
the bifunctional pyrazolato catalyst and the substrate in the
transition state may be responsible for the high stereoselectivity
in the catalysis. A subsequent proton shift in the resulting
alkyl−pyrazole complex affords the cyclization product and
regenerates the unsaturated pyrazolato complex. The coor-
dinative saturation of the alkyl intermediate would inhibit the
competing β-elimination that leads to undesired oxidative
amination.22,34 This final protonolysis step seems, however, not
so straightforward when considering the decomposition of the
1
instrument with a Yamazen Hi-Flash column. H (399.78 MHz) and
13C (100.53 MHz) NMR spectra were obtained on a JEOL JNM-
ECX400 spectrometer. 1H NMR shifts are relative to the signal of the
residual protiated solvent: CHCl3, δ 7.26; C6D5H, δ 7.15. 13C{1H}
NMR shifts are relative to the signal of the solvent: CDCl3, δ 77.0. IR
spectra were recorded on a JASCO FT/IR-610 spectrometer.
Elemental analyses were performed on a Perkin-Elmer 2400II CHN
analyzer. HRMS spectra were recorded on a Bruker Daltonics
micrOTOF II spectrometer. The pyrazole complex 117 and the
pyrazolato complex 217 as well as aminoalkenes 3a,36 3c,8b 3d,8b 3e,3a
3g,37 3h,6 3i,8a 3k,8b 3l,8b 3m,8b and 3n6 were prepared according to
the literature.
Synthetic Details. Synthesis of 4-Methyl-2,2-diphenylpent-4-en-
1-amine (3b). This compound was synthesized in a manner similar to
that for the synthesis of 3a35 using diphenylacetonitrile and 3-chloro-2-
8451
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Organometallics
Article
methylprop-1-ene as starting materials and identified according to the
reported spectroscopic data.6 1H NMR (δ, CDCl3): 1.07 (s, 3H, CH3),
2.92 (s, 2H, CH2C(CH3)CH2), 3.41 (s, 2H, CH2NH2), 4.59, 4.82
(m, 1H each, CH2C(CH3)), 7.16−7.20 (m, 6H, C6H5), 7.25−7.29
(m, 4H, C6H5).
(m, 1H, CHCHCH2), 7.15−7.30 (m, 10H, C6H5). 13C{1H} NMR
(δ, CDCl3): 18.0, 39.8, 48.5, 51.6, 125.9, 126.7, 128.0, 128.2, 146.4.
1
Data for the Z isomer are as follows. H NMR (δ, CDCl3): 1.51 (dd,
4
3
3JHH = 6.7 Hz, JHH = 1.5 Hz, 3H, CH3), 2.90 (d, JHH = 7.3 Hz, 2H,
CHCHCH2), 5.08 (m, 1H, CHCHCH2), 5.45 (m, 1H, CH
CHCH2), 7.15−7.30 (m, 10H, C6H5). 13C{1H} NMR (δ, CDCl3):
12.9, 33.9, 49.0, 51.9, 126.0, 126.4, 128.3, 146.3. The signals of olefin
and phenyl carbon atoms were not fully assigned due to the overlap.
Synthesis of 5. To a suspension of 2 (43.8 mg, 40.1 μmol) in THF
(4 mL) was added CH3I (5.00 μL, 80.3 μmol), and the mixture was
stirred for 16 h at room temperature. After removal of the solvent in
vacuo, the resulting solid was recrystallized from THF/hexane (1 mL/
20 mL) to give 5 as red crystals (23.8 mg, 34.6 μmol, 43%). 1H NMR
(δ, CDCl3): 1.81 (s, 15H, C5(CH3)5), 3.98 (s, 3H, NCH3), 6.56 (s,
1H, aryl), 6.96, 7.08 (m, 1H each, aryl), 7.42−7.52 (m, 6H, aryl), 7.72
(m, 1H, aryl). Anal. Calcd for C26H28IIrN2: C, 45.41; H, 4.10; N, 4.07.
Found: C, 45.71; H, 4.30; N, 3.95.
Synthesis of 3-Methyl-2,2-diphenylpent-4-en-1-amine (3f). This
compound was synthesized by a regioselective Tsuji−Trost reaction38
with some modifications. To a suspension of NaH (60 wt % in mineral
oil, 207.9 mg, 5.20 mmol) in THF (10 mL) was added
diphenylacetonitrile (869.9 mg, 4.502 mmol), and the mixture was
stirred for 1 h at 0 °C before diluted with THF (40 mL). Separately, a
39
solution of [PdCl(η3-crotyl)]2 (29.5 mg, 0.0749 mmol) and PBut3
(73 μL, 0.30 mmol) in THF (6 mL) was stirred for 30 min at room
temperature. After addition of but-3-en-2-yl acetate (0.38 mL, 3.0
mmol) to the catalyst solution, this mixture was added to the solution
prepared first. The resulting solution was stirred for 16 h, during which
time the temperature was gradually increased from 0 °C to room
temperature. Water (20 mL) was added to the solution, and the
mixture was extracted with ethyl acetate (20 mL). The organic phase
was washed with saturated aqueous NH4Cl solution and brine (20 mL,
respectively) and dried with MgSO4, and the solvents were removed in
vacuo. Purification by automatic silica gel column chromatography
with gradually increasing amounts of ethyl acetate in hexane (from 0%
to 13% v/v) as eluent gave 3-methyl-2,2-diphenylpent-4-enenitrile as a
Synthesis of 8. A solution of 2 (49.8 mg, 45.6 μmol) in
dichloromethane (4 mL) was degassed by three freeze−pump−thaw
cycles. C2H4 (1 atm) was introduced, and the mixture was stirred for
40 min at room temperature. After removal of the solvent in vacuo, the
resulting solid was dissolved in diethyl ether (1 mL). Addition of
hexane (20 mL) to the solution gave 8 as ocher solids (13.0 mg, 22.7
μmol, 25%). The mother liquid was concentrated to dryness, and the
resulting solid was dissolved in hexane (ca. 5 mL). Cooling of the
solution to −30 °C afforded additional 8; the combined yield was 25.6
mg (44.6 μmol, 74%). 1H NMR (δ, CDCl3): 1.70 (s, 15H, C5(CH3)5),
2.98, 3.04 (m, 2H each, C2H4), 6.53 (s, 1H, aryl), 6.91, 7.04, 7.17 (m,
1H each, aryl), 7.33−7.41 (m, 4H, aryl), 7.88 (m, 2H, aryl). 13C{1H}
NMR (δ, CDCl3): 8.2, 48.8, 95.0, 98.3, 120.3, 123.6, 125.0, 125.7,
128.2, 135.9, 136.3, 141.3, 147.9, 153.1, 157.7. Anal. Calcd for
C27H29IrN2: C, 56.52; H, 5.09; N, 4.88. Found: C, 56.77; H, 5.24; N,
4.87. Recrystallization of the solid from diethyl ether at −30 °C gave
the ether adduct 8·Et2O as yellow crystals suitable for X-ray analysis.
Synthesis of 9a·0.5H2O. To a suspension of 2 (40.0 mg, 36.7 μmol)
in THF (3 mL) was added aniline (6.70 μL, 73.4 μmol), and the
mixture was stirred for 12 h at room temperature. After removal of the
solvent in vacuo, the resulting solid was recrystallized from THF/
hexane (0.5 mL/20 mL) to give 9a·0.5H2O as yellow-green crystals
(20.3 mg, 31.8 μmol, 43%). 1H NMR (CDCl3): δ 1.52 (s, 15H,
C5(CH3)5), 4.30 (br, 2H, NH2), 6.66 (s, 1H, aryl), 6.88, 7.00 (m, 2H
each, aryl), 7.11 (m, 1H, aryl), 7.21 (m, 3H, aryl), 7.39 (m, 2H, aryl),
7.51 (m, 1H, aryl), 7.77 (m, 1H, aryl), 7.96 (m, 2H, aryl). Anal. Calcd
for C31H33IrN3O0.5: C, 57.47; H, 5.13; N, 6.49. Found: C, 57.34; H,
5.37; N, 6.41.
1
colorless oil (0.7441 g, 3.009 mmol, 100%). H NMR (δ, CDCl3):
3
1.19 (d, JHH = 6.7 Hz, 3H, CH3), 3.45 (pseudo quint, 1H, CH2
3
CHCH(CH3)), 5.05−5.13 (m, 2H, CH2CH), 5.83 (ddd, JHH
=
18.0, 10.4, 7.6 Hz, 1H, CH2CH), 7.21−7.40 (m, 6H, C6H5), 7.47−
7.52 (m, 4H, C6H5).
To a suspension of LiAlH4 (285.0 mg, 7.510 mmol) in dehydrated
diethyl ether (8 mL) was added 3-methyl-2,2-diphenylpent-4-
enenitrile (0.7441 g, 3.009 mmol) at 0 °C, and the mixture was
refluxed for 17 h at 50 °C. After dilution with diethyl ether (15 mL),
the reaction was quenched by slow addition of Na2SO4·10H2O at 0 °C
and the mixture was stirred at room temperature. The resulting white
precipitate was filtered off and extracted with diethyl ether (ca. 50
mL). Evaporation of the solvent in vacuo gave a colorless oil, which
was purified by bulb-to-bulb distillation to give 3-methyl-2,2-
1
diphenylpent-4-en-1-amine (657.1 mg, 2.614 mmol, 87%). H NMR
(δ, CDCl3): 0.93 (d, 3JHH = 6.7 Hz, 3H, CH3), 3.26 (AB pattern, 2H,
CH2NH2), 3.27 (m, 1H, CH2CHCH(CH3)), 4.98−5.01, 5.07−5.11
3
(m, 1H each, CH2CH), 5.43 (ddd, JHH = 18.6, 10.1, 8.6 Hz, 1H,
CH2CH), 7.17−7.34 (m, 10H, C6H5).
To a solution of 3-methyl-2,2-diphenylpent-4-en-1-amine (657.1
mg, 2.614 mmol) in methanol (7 mL) was added benzaldehyde (0.28
mL. 2.8 mmol), and the solution was stirred for 4 h at room
temperature in air. Then the solution was treated with NaBH4 (148
mg, 3.91 mmol) and stirred for 15 h at room temperature. The
resulting mixture was treated with water (20 mL) and 1 M NaOH
solution (7 mL) and extracted with CH2Cl2 (3 × 15 mL). The
combined organic layer was dried with MgSO4, and the solvents were
removed in vacuo. Purification by automated silica gel column
chromatography with gradually increasing amounts of ethyl acetate in
hexane (from 0% to 15% v/v) as eluent gave 3f as a colorless oil
Synthesis of 9b·0.5H2O. To a suspension of 2 (47.5 mg, 43.5 μmol)
in THF (4 mL) was added benzylamine (9.50 μL, 86.9 μmol), and the
mixture was stirred for 1 h at room temperature. After removal of the
solvent in vacuo, the resulting solid was recrystallized from
dichloromethane/hexane (1 mL/20 mL) with a drop of water to
1
give 9b·0.5H2O as yellow crystals (43.8 mg, 66.2 μmol, 76%). H
NMR (δ, CDCl3): 1.85 (s, 15H, C5(CH3)5), 2.41, 3.35 (br, 1H each,
NH2), 3.56 (m, 2H, CH2), 6.62 (s, 1H, aryl), 6.79 (m, 2H, aryl), 6.96,
7.08 (m, 1H each, aryl), 7.13−7.18 (m, 3H, aryl), 7.33 (m, 3H, aryl),
7.48, 7.69 (m, 1H each, aryl), 7.91 (m, 2H, aryl). Anal. Calcd for
C32H35IrN3O0.5: C, 58.07; H, 5.33; N, 6.35. Found: C, 58.20; H, 5.09;
N, 6.33.
1
3
(658.7 mg, 1.929 mmol, 74%). H NMR (δ, CDCl3): 0.90 (d, JHH
=
7.0 Hz, 3H, CH3), 3.15 (AB pattern, 2H, CPh2CH2NH), 3.53 (pseudo
quint, 1H, CH2CHCH(CH3)), 3.62 (AB pattern, 2H, NHCH2Ph),
3
4.92−4.95, 5.03−5.08 (m, 1H each, CH2CH), 5.44 (ddd, JHH
=
Synthesis of 10. To a suspension of 2 (39.8 mg, 36.5 μmol) in THF
(3 mL) was added TsNH2 (12.5 mg, 73.0 μmol), and the mixture was
stirred for 4 h at room temperature. After removal of the solvent in
vacuo, the resulting solid was recrystallized from dichloromethane/
hexane (1 mL/20 mL) to give 10 as orange crystals (33.3 mg, 46.4
18.6, 10.1, 8.6 Hz, 1H, CH2CH), 7.11−7.29 (m, 15H, C6H5).
13C{1H} NMR (δ, CDCl3):16.6, 40.5, 54.1, 54.7, 57.5, 115.1, 125.98,
126.04, 126.6, 127.1, 127.5, 127.8, 128.1, 129.7, 130.1, 140.7, 141.2,
143.1, 144.2. Anal. Calcd for C25H27N: C, 87.93; H, 7.97; N, 4.10.
Found: C, 88.00; H, 7.93; N, 4.11.
1
μmol, 64%). H NMR (δ, CDCl3): 1.78 (s, 15H, C5(CH3)5), 2.14 (s,
Synthesis of 2,2-Diphenylhex-4-en-1-amine (3j). This compound
was synthesized in a manner similar to that for the synthesis of 3a35
using diphenylacetonitrile and 1-chlorobut-2-ene (mixture of E and Z
isomers) as starting materials and identified according to the reported
spectroscopic data.40 Data for the E isomer are as follows. 1H NMR (δ,
3H, C6H4CH3), 2.17 (s, 1H, NHTs), 6.18 (s, 1H, aryl), 6.61, 6.81 (d,
3JHH = 8.1 Hz, 2H each, SO2C6H4), 7.07, 7.12 (m, 1H each, aryl),
7.34−7.47 (m, 6H, aryl), 7.72 (m, 1H, aryl), 10.46 (br, 1H, aryl-NH).
Anal. Calcd for C32H34IrN3O2S: C, 53.61; H, 4.78; N, 5.86. Found: C,
53.36; H, 4.90; N, 5.89.
Reaction of 2 with 4-Methyl-2,2-diphenylpent-4-en-1-amine
(3b). In an NMR tube equipped with a J. Young valve were added
3
4
CDCl3): 1.56 (dd, JHH = 6.4 Hz, JHH = 1.2 Hz, 3H, CH3), 2.83 (d,
3JHH = 7.0 Hz, 2H, CHCHCH2), 5.01 (m, 1H, CHCHCH2), 5.45
8452
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3b (3.8 mg, 15 μmol), 2 (8.1 mg, 7.4 μmol), and C6D6 (0.5 mL). The
mixture was maintained at room temperature and monitored by H
increasing amounts of ethyl acetate in hexane (from 10% to 100%
v/v) as eluent to afford 4a (88.6 mg, 373 μmol, 89%), which gave an
1H NMR spectrum in agreement with that reported in the literature.36
Cyclic amines 4b,6 4c,8b 4d,8b 4e,3a 4g,37 4h,6 4i,8a 4k,8b 4l,8b and
1
NMR. After 22 h, signals assigned to the amine complex 9c were
1
observed. H NMR (δ, C6D6): 0.77 (s, 3H, CH2C(CH3)), 1.46 (s,
4m8b were also identified by comparing their H NMR spectra with
1
15H, C5(CH3)5), 2.14 (AB pattern, 2H, CH2C(CH3)CH2), 2.28,
2.52 (br t, 1H each, NH2), 2.87, 3.00 (m, 1H each, CH2NH2), 4.08 (s,
those reported in the literature. Analytical data for the other
2
1H, CH2C(CH3)), 4.63 (d, JHH = 1.5 Hz, 1H, CH2C(CH3)),
hydroamination products are as follows.
trans-N-Benzyl-2,3-dimethyl-4,4-diphenylpyrrolidine (4f). 1H
6.61 (m, 4H, aryl), 6.90 (m, 6H, aryl), 6.96 (s, 1H, aryl), 7.16 (m, 2H,
aryl), 7.27 (m, 1H, aryl), 7.38 (m, 2H, aryl), 7.73, 7.79 (m, 1H each,
aryl), 8.36 (m, 2H, aryl). The connectivity of the protons was
3
3
NMR (δ, CDCl3): 0.71 (d, JHH = 6.4 Hz, 3H, CH3), 1.20 (d, JHH
= 5.6 Hz, 3H, CH3), 2.66 (m, 2H, CHCH3), 3.41, 3.46 (AB pattern,
1
confirmed by a H−1H COSY analysis.
3
1H each, NCH2CPh2), 3.76, 4.10 (d, JHH = 14.0 Hz, 1H each,
Synthesis of 11. To a solution of 3b (17.9 mg, 71.2 μmol) in
toluene (2 mL) was added 2 (38.7 mg, 35.5 μmol), and the mixture
was stirred for 14 h at 50 °C. After removal of the solvent under
reduced pressure, the resulting solid was recrystallized from diethyl
ether/hexane (2 mL/20 mL) to give yellow crystals of 11 as a 1:1
mixture of the diastereomers (22.7 mg, 28.5 μmol, 40%). 1H NMR (δ,
CDCl3): −0.32, −0.24 (s, 3H each, C(CH3)2), 1.20, 1.47 (s, 3H each,
C(CH3)2), 1.74, 1.75 (s, 15H each, C5(CH3)5), 2.34 (pseudo t, 2H,
PhCH2N), 6.94 (m, 2H, C6H5), 7.11−7.35 (m, 13H, C6H5). Colorless
crystals of 4f·HBF4·0.625Et2O suitable for X-ray analysis were
obtained by protonation with HBF4·Et2O and subsequent recrystal-
1
lization from methanol/diethyl ether (1.5 mL/15 mL). H NMR (δ,
3
3
CD3OD): 0.80 (d, JHH = 6.7 Hz, 3H, CH3), 1.59 (d, JHH = 6.4 Hz,
3H, CH3), 3.06, 3.50 (m, 1H each, CHCH3), 3.91, 4.42 (d, 3JHH = 13.1
Hz, 1H each, NCH2CPh2), 4.58, 4.76 (d, JHH = 13.1 Hz, 1H each,
3
NCH2Ph), 6.88 (m, 2H, C6H5), 7.29 (m, 5H, C6H5), 7.34 (m, 1H,
C6H5), 7.42 (m, 2H, C6H5), 7.58 (m, 3H, C6H5), 7.67 (m, 2H, C6H5).
The thoroughly dried sample was found to lose the solvating molecule,
2
C(CH3)2CH2CPh2), 2.52 (m, 2H, C(CH3)2CH2CPh2), 2.90 (d, JHH
2
= 12.5 Hz, 1H, NHCH2CPh2), 3.06 (d, JHH = 12.8 Hz, 1H,
1
NHCH2CPh2), 2.91, 3.05 (m, 1H each, NH), 4.09 (d, 2JHH = 12.5 Hz,
1H, NHCH2CPh2), 4.78 (2JHH = 12.8 Hz, 1H, NHCH2CPh2), 6.47 (s,
1H, aryl), 6.59 (m, 2H, aryl), 6.66 (s, 1H, aryl), 6.72 (m, 2H, aryl),
6.80−6.95 (m, 8H, aryl), 7.04−7.33 (m, 17H, aryl), 7.42 (m, 3H, aryl),
7.70 (m, 1H, aryl), 7.90 (m, 2H, aryl), 7.94 (m, 1H, aryl), 8.13 (m, 2H,
aryl). Anal. Calcd for C43H46IrN3: C, 64.80; H, 5.82; N, 5.27. Found:
C, 64.77; H, 6.00; N, 5.38.
on the basis of H NMR spectroscopy and combustion analysis. Anal.
Calcd for C25H28BF4N: C, 69.94; H, 6.57; N, 3.26. Found: C, 70.06;
H, 6.44; N, 3.18.
1
N-Benzyl-3-methyl-2-azaspiro[4.5]decan-4-ol (4n). H NMR (δ,
3
CDCl3): 1.20−1.60 (m, 10H, (CH2)5), 1.25 (d, JHH = 5.8 Hz, 3H,
2
CH3), 2.04, 2.83 (d, JHH = 9.6 Hz, 1H each, NCH2), 2.31 (m, 1H,
2
CH3CH), 3.16, 4.00 (d, JHH = 13.4 Hz, 1H each, PhCH2), 3.33 (d,
3JHH = 6.7 Hz, 1H, CHOH), 7.21−7.31 (m, 5H, C6H5). 13C{1H}
NMR (δ, CDCl3): 17.5, 22.9, 23.5, 26.1, 31.3, 36.7, 42.1, 57.6, 62.7,
66.3, 86.0, 126.7, 128.1, 128.6, 139.4. HRMS (ESI-TOF): m/z calcd
for C17H25NO + H+ 260.2009, found 260.2008.
Synthesis of 12. To a solution of 1 (50.0 mg, 85.9 μmol) in THF (4
mL) was added a solution of dimethylzinc (47 μL, 0.92 M in hexane)
at −78 °C, and the mixture was stirred for 1 h at −78 °C. After
removal of the solvent in vacuo, the resulting solid was extracted with
toluene (3 × 2 mL), and the extracts were evaporated to dryness. A 1H
NMR analysis of the product indicated the generation of 12 with a
small amount of uncharacterized byproduct(s). 1H NMR (δ, CD2Cl2):
−0.27 (s, 3H, IrCH3), 1.84 (s, 15H, C5(CH3)5), 6.83 (d, JHH = 2.1 Hz,
1 H, aryl), 6.95 (m, 2H, aryl), 7.60 (m, 2H, aryl), 9.56 (br, 1H, NH).
The signals of the aryl protons were masked by those of the
byproduct(s) and not fully assigned.
X-ray Diffraction Studies. Single crystals suitable for X-ray
analysis were mounted on a glass fiber or on a fiber loop followed by
data collection at 93 K. Diffraction experiments were performed on a
Rigaku Saturn CCD area detector with graphite-monochromated Mo
Kα radiation (λ = 0.710 70 Å) to a maximum 2θ value of 55°. Intensity
data were corrected for Lorentz−polarization effects and for
absorption. Details of crystal and data collection parameters are
summarized in Table S15 (Supporting Information). Structure
solution and refinements were performed with the CrystalStructure
program package.41 The heavy-atom positions were determined by a
direct methods program (SIR9242), and the remaining non-hydrogen
atoms were found by subsequent Fourier synthesis. The structures
were refined against F2 with anisotropic temperature factors for all
non-hydrogen atoms unless otherwise specified. One of the two
solvated diethyl ether molecules in 4f·HBF4·0.625Et2O was severely
disordered. The non-hydrogen atoms therein were located at two
disordered positions with a total occupancy of 0.5 and included in the
refinements with fixed parameters. The carbon atoms in the Cp*
ligand in 9b·0.5H2O were refined with isotropic thermal parameters.
The hydrogen atoms in the C2H4 ligand in 8 and solvating water
molecule in 9b·0.5H2O were located in the difference Fourier map and
refined isotropically, while the hydrogen atoms in the disordered
solvating diethyl ether molecule in 4f·HBF4·0.625Et2O and the
solvating water molecule in 9a·0.5H2O were not included in the
refinements. The rest of the hydrogen atoms were included in the final
stages of the refinements by using a riding model.
Computational Studies. All calculations were performed by
means of the density functional theory in the Gaussian 09 program43
using an exchange-correlation hybrid functional, denoted as
MPW1PW91. For this density functional method, the correlation
functional is from Perdew−Wang 1991 (PW91),44 while the exchange
functional is from Barone’s modified PW91 (MPW1).45 Geometry
optimizations were performed using SDD effective core potential
(ECP)46 along with its associated basis set for iridium and 6-31G(d,p)
basis set47 for the other typical atoms. This combination of the
functional and the basis sets reproduced the structure of the ethylene
complex 8 confirmed by X-ray analysis. Thermochemical values for
each optimized structure were obtained for 298.15 K and 1.0 atm by
frequency analyses using the same basis sets and ECP within the
harmonic approximation.
Representative Procedures for Kinetic Experiments. A
solution of 8 in C6D6 was prepared and , stored under an argon
atmosphere at 0 °C, and a requisite amount of the solution was taken
for each experiment. To an NMR tube equipped with a J. Young valve
was added 3d (39.6 mg, 121 μmol), 1,3,5-trimethoxybenzene (as an
internal standard, 11.2 mg, 66.6 μmol), and the C6D6 solution of 8
(12.0 mM, 0.50 mL, 6.0 μmol). The time course of the reaction was
monitored by the VT-NMR spectrum, and the concentration of the
substrate was calculated by comparing the peak intensity of the vinylic
protons at the 5-position to that of the methoxy protons of the internal
standard. The moment at which the probe temperature of the NMR
spectrometer reached the intended temperature was set as t = 0 s. For
the investigation of the effect of catalyst concentration, less than 0.5
mL of the catalyst solution was taken, and the mixture was diluted with
additional C6D6 to the intended concentration.
ASSOCIATED CONTENT
* Supporting Information
■
S
Tables, figures, and CIF files giving X-ray crystallographic data
for 4f·HBF4·0.625Et2O, 8·Et2O, 9a·0.5H2O, 9b·0.5H2O, 10,
and 11a and details of the NOE experiments, the computa-
tional studies, and the kinetic experiments. This material is
available free of charge via the Internet at http://pubs.acs.org.
Representative Procedure for Intramolecular Hydroamina-
tion Catalyzed by 2. To a solution of 3a (99.3 mg, 418 μmol) in
toluene (2.0 mL) was added 2 (11.4 mg, 10.4 μmol), and the mixture
was stirred for 15 h at 50 °C. After removal of the solvent in vacuo, the
resulting oil was chromatographed on silica gel with gradually
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Organometallics
Article
Can. J. Chem. 2010, 88, 700. (d) Lavery, C. B.; Ferguson, M. J.;
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AUTHOR INFORMATION
Corresponding Author
*E-mail: skuwata@apc.titech.ac.jp (S.K.); tikariya@apc.titech.
ac.jp (T.I.).
■
(12) Jung, M. E.; Piizzi, G. Chem. Rev. 2005, 105, 1735.
Notes
(13) Shen, X.; Buchwald, S. L. Angew. Chem., Int. Ed. 2010, 49, 564.
(14) (a) Ikariya, T. Bull. Chem. Soc. Jpn. 2011, 84, 1. (b) Ikariya, T.;
Kuwata, S.; Kayaki, Y. Pure Appl. Chem. 2010, 82, 1471. (c) Dub, P. A.;
Wang, H.; Watanabe, M.; Gridnev, I. D.; Ikariya, T. Tetrahedron Lett.
2012, 53, 3452. (d) Sato, Y.; Kayaki, Y.; Ikariya, T. Chem. Commun.
2012, 48, 3635. (e) Hasegawa, Y.; Gridnev, I. D.; Ikariya, T. Bull.
Chem. Soc. Jpn. 2012, 85, 316. (f) Watanabe, M.; Kashiwame, Y.;
Kuwata, S.; Ikariya, T. Eur. J. Inorg. Chem. 2012, 504. (g) Touge, T.;
Hakamata, T.; Nara, H.; Kobayashi, T.; Sayo, N.; Saito, T.; Kayaki, Y.;
Ikariya, T. J. Am. Chem. Soc. 2011, 133, 14960. (h) Ito, M.; Ootsuka,
T.; Watari, R.; Shiibashi, A.; Himizu, A.; Ikariya, T. J. Am. Chem. Soc.
2011, 133, 4240. (i) Ito, M.; Shiibashi, A.; Ikariya, T. Chem. Commun.
2011, 47, 2134.
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(b) Kashiwame, Y.; Watanabe, M.; Araki, K.; Kuwata, S.; Ikariya, T.
Bull. Chem. Soc. Jpn. 2011, 84, 251. (c) Yoshinari, A.; Tazawa, A.;
Kuwata, S.; Ikariya, T. Chem. Asian J. 2012, 7, 1417.
(16) (a) Praneeth, V. K. K.; Ringenberg, M. R.; Ward, T. R. Angew.
Chem., Int. Ed. 2012, 51, 10228. (b) van der Vlugt, J. I. Eur. J. Inorg.
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The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research (S) (22225004) from the Ministry of Education,
Culture, Sports, Science and Technology of Japan. Y.K.
acknowledges a Japan Society for the Promotion of Science
Research Fellowship for Young Scientists.
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NOTE ADDED AFTER ASAP PUBLICATION
■
In the version of this paper published on November 19, 2012, a
statement near the end of the paper regarding the mechanism
was incorrect. The version that appears as of December 10,
2012, is correct.
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