C(sp3)-H alkenylation catalyzed by cationic alkylhafnium complexes: Stereoselective synthesis of trisubstituted alkenes from 2,6-dimethylpyridines and internal alkynes

Article abstract of DOI:10.1021/acs.organomet.6b00655

Dibenzylhafnium complexes 3a-d, supported by dianionic bidentate or tridentate ligands, upon activation via abstraction by either [Ph₃C][B(C₆F₅)₄] or B(C₆F₅)₃ served as catalysts for the C(sp³)-H alkenylation of 2,6-dimethylpyridines with dialkylalkynes to give corresponding C(sp³)-H alkenylated products 6. Complex 3c, containing a pyridine arm in the ligand skeleton, exhibited the highest catalytic activity among 3a-d; initial addition of 2,6-dimethylpyridine (4a) to the C₆D₅Br solution of 3c followed by [Ph₃C][B(C₆F₅)₄] and 3-hexyne (5a) produced trisubstituted alkene 6aa in stereoselective manner in up to 50% yield without any byproducts, while the addition of 5a prior to 4a and [Ph₃C][B(C₆F₅)₄] to the C₆D₅Br solution of 3c generated 6aa, together with the formation of byproduct (E)-(2-ethylpent-2-en-1-yl)benzene (7). When an asymmetrical pyridine, 3-bromo-2,6-dimethylpyridine, was used as the coupling partner, the corresponding trisubstituted alkene was obtained selectively. Catalytically active cationic benzylhafnium complexes 8a-d, which were prepared by the reactions of 3a-d and B(C₆F₅)₃, respectively, were characterized by ¹H, ¹³C, and ¹⁹F NMR spectroscopy. Kinetic studies of the catalytic reaction between 4a and 4-octyne (5b) using 3c and [Ph₃C][B(C₆F₅)₄] in C₆D₅Br revealed that the catalytic reaction was zero-order for both 4a and 5b, indicating that the rate-determining step involved the C(sp³)-H bond activation of 4a by vinylhafnium intermediate 11c.

Full text of DOI:10.1021/acs.organomet.6b00655

Article
pubs.acs.org/Organometallics
C(sp3)−H Alkenylation Catalyzed by Cationic Alkylhafnium
Complexes: Stereoselective Synthesis of Trisubstituted Alkenes from
2,6-Dimethylpyridines and Internal Alkynes
Michael J. Lopez, Ai Kondo, Haruki Nagae, Koji Yamamoto, Hayato Tsurugi,* and Kazushi Mashima*
Department of Chemistry, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, 560-8531, Japan
S
* Supporting Information
ABSTRACT: Dibenzylhafnium complexes 3a−d, supported by
dianionic bidentate or tridentate ligands, upon activation via
abstraction by either [Ph3C][B(C6F5)4] or B(C6F5)3 served as
catalysts for the C(sp3)−H alkenylation of 2,6-dimethylpyridines
with dialkylalkynes to give corresponding C(sp3)−H alkenylated
products 6. Complex 3c, containing a pyridine arm in the ligand
skeleton, exhibited the highest catalytic activity among 3a−d; initial
addition of 2,6-dimethylpyridine (4a) to the C6D5Br solution of 3c
followed by [Ph3C][B(C6F5)4] and 3-hexyne (5a) produced
trisubstituted alkene 6aa in stereoselective manner in up to 50%
yield without any byproducts, while the addition of 5a prior to 4a and
[Ph3C][B(C6F5)4] to the C6D5Br solution of 3c generated 6aa,
together with the formation of byproduct (E)-(2-ethylpent-2-en-1-
yl)benzene (7). When an asymmetrical pyridine, 3-bromo-2,6-
dimethylpyridine, was used as the coupling partner, the corresponding trisubstituted alkene was obtained selectively.
Catalytically active cationic benzylhafnium complexes 8a−d, which were prepared by the reactions of 3a−d and B(C6F5)3,
respectively, were characterized by 1H, 13C, and 19F NMR spectroscopy. Kinetic studies of the catalytic reaction between 4a and
4-octyne (5b) using 3c and [Ph3C][B(C6F5)4] in C6D5Br revealed that the catalytic reaction was zero-order for both 4a and 5b,
indicating that the rate-determining step involved the C(sp3)−H bond activation of 4a by vinylhafnium intermediate 11c.
group adjacent to N-heterocycles through a σ-bond metathesis
pathway under neutral conditions, leading to the formation of
new organometallic species. Further insertion of alkenes and
alkynes into the newly generated metal−carbon bond afforded
the C(sp3)−H alkylated and alkenylated metallacyclic com-
plexes, as initially demonstrated stoichiometrically by Jordan et
al. for the reaction with 2,6-dimethylpyridine by a cationic
methylzirconocene complex (Scheme 1a).20b In a seminal work
for catalytic C(sp3)−H bond functionalization, Tilley et al.
reported the catalytic C(sp3)−H alkylation of methane via
C(sp3)−H activation of methane and subsequent insertion of
alkenes by Cp*2ScMe (Scheme 1b).20d,e Recently, Hou and co-
workers achieved catalytic C(sp3)−H alkylation of ortho-
methylated N-heterocycles via C(sp3)−H bond activation of
the methyl group and further insertion of alkenes by half-
metallocene group 3 metal alkyl complexes (Scheme 1c).20g,h
Although catalytic C(sp3)−H alkenylation was recently
achieved by late transition metal catalysts,22 the related
transformation of the C(sp3)−H bond in early transition
metal complexes has been considered difficult due to formation
of the stable metallacycle, as shown in Scheme 1a.20b,c In a
related report, our group has recently shown the catalytic
INTRODUCTION
■
Functionalization of C−H bonds has recently attracted great
interest in terms of its versatility as one of the most
straightforward and atom-economical synthetic protocols to
introduce various functional groups into the unreactive
hydrocarbon skeletons, in sharp contrast to the standard
strategies to use prefunctionalized organometallic reagents as
well as halogenated and pseudohalogenated substrates, which
inevitably form wasteful byproducts.1 In the last two decades,
various transition metal complexes, especially those of noble
transition metals such as Ru, Rh, Pd, Ir, and Pt as well as base
transition metals, were developed to efficiently catalyze direct
C−H bond functionalization reactions.2−14 Beyond the well-
developed direct C(sp2)−H bond functionalization of aromatic
and vinylic compounds, a recent research target was devoted to
achieving direct functionalization of C(sp3)−H bonds under
mild reaction conditions without any specific directing
groups.15,16
Notably, it has been reported that early transition metal
complexes such as metallocene and half-metallocene alkyl
complexes of group 3 and 4 metals serve as stoichiometric
reagents and catalysts for functionalizing not only C(sp2)−H
bonds but also C(sp3)−H bonds of simple organic com-
pounds.17−21 The highly Lewis acidic early transition metal
centers cleaved the C(sp3)−H bonds of methane and a methyl
Received: August 15, 2016
© XXXX American Chemical Society
A
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Scheme 1. C(sp3)−H Bond Alkylation and Alkenylation by
the corresponding aldehyde, in toluene at −78 °C, followed by
allowing the reaction mixture to warm to room temperature to
give the analytically pure complexes 3a−d as red-orange
microcrystalline solids upon recrystallization from a mixture of
toluene and hexane (4:1) (Scheme 2). One benzyl group
a
Group 3 and 4 Metal Alkyl Complexes
Scheme 2. Preparation of Dibenzylhafnium Complexes 3a−d
migrated from the hafnium center to the imine carbon of the
pro-ligands, and the other benzyl group was protonated by the
secondary amine moiety to eliminate toluene, resulting in the
formation of the corresponding dianionic ligands. The benzyl
group migration to the ligand backbone of imine-based ligands
was one of the methodology to introduce the supporting ligand
into the metal center.23,24 Consequently, the dibenzylhafnium
complexes 3a−d were supported by the dianionic N,N-
bidentate ligands.
1
Complexes 3a−d were characterized by H and 13C NMR
spectroscopies, elemental analyses, and X-ray crystallography
studies (vide infra). Representative of the dibenzylhafnium
1
series 3a−d, the H NMR spectrum of 3c in C6D6 displayed
nonequivalent benzyl groups as two ABq resonances at δ 1.14
and 1.94 (2J = 11.4 Hz) and δ 1.41 and 1.61 (2J = 10.3 Hz) due
to the C1 symmetry of 3c. In addition, the ABX signals at δ
a
(a) Cationic zirconocene-mediated stoichiometric C(sp3)−H alkyla-
tion and alkenylation.20b (b) Scandocene-catalyzed C(sp3)−H
alkylation of methane.20d,e (c) Half-metallocene yttrium-catalyzed
C(sp3)−H alkylation of ortho-methylated N-heterocycles.20g,h
3
2.66, 2.77, and 4.42 (2J = 13.7 Hz, J = 5.6 and 3.0 Hz)
corresponded to the methylene and methine protons in the
NCHCH2Ph fragment, and the ABXY signals at δ 3.59, 3.88,
3
4.02, and 4.25 (2J = 11.0, 10.4 Hz, J = 6.7, 6.4, 5.6, 4.7 Hz)
formation of carbocycles by a cationic alkylhafnium complex, in
which four-membered (pyridylmethyl)hafnium species was
formed via C(sp3)−H bond activation of 2,6-dimthylpyridine
followed by insertion of 2 equiv of internal alkynes into the
hafnium−carbon bond.23 Herein, we report the first catalytic
example of an early transition metal complex for C(sp3)−H
alkenylation of 2,6-dimethylpyridine via C(sp3)−H bond
activation of the methyl group by cationic alkylhafnium
complexes, giving 1 to 1 coupling products of internal alkynes
and 2,6-dimethylpyridine derivatives. Based on the character-
ization of the cationic intermediate together with reaction
kinetics, the rate-determining step was assigned to be a
C(sp3)−H bond activation of 2,6-dimethylpyridine bound to
the six-membered metallacycle complex in the catalytic cycle.
were assigned as the methylene protons in the NCH2CH2N
fragment. The 13C NMR spectrum of 3c in C6D6 showed the
methylene carbon of one benzyl group at δ 66.4 (1JC−H = 119
Hz) as an η1 coordination and the other at δ 69.4 (1JC−H = 129
Hz) as an η2 coordination based on its JC−H coupling constants.
The characteristic of η1 versus η2 benzyl group coordination
modes are commonly observed in coordinatively unsaturated
1
metal complexes, in which higher JC−H coupling constants are
ascribed to an increase in the sp2 character of the benzyl carbon
and thus typically assigned as η2-coordination.23−25 A similar
trend occurred across the series of hafnium complexes 3a−d, in
which the methylene carbon of one benzyl group has a higher
1JC−H coupling constant (1JC−H = 126−131 Hz) assigned to the
η2 coordination mode, while that of the second benzyl group
with the lower coupling constant (1JC−H = 117−121 Hz) is
assigned as the η1 coordination mode.
RESULTS AND DISCUSSION
■
Synthesis and Characterization of Dibenzylhafnium
Complexes with Bidentate and Tridentate Diamido
Ligands. Dibenzylhafnium complexes 3a−d were synthesized
by treating Hf(CH2Ph)4 with pro-ligands 2a−d, which were
prepared from 1-(2,6-dimethylphenyl)-2-aminoethane (1) and
The molecular structures of all dibenzylhafnium complexes
3a−d were clarified by X-ray analyses as shown in Figure 1, and
their respective selected bond distances and angles are
summarized in Table 1. The hafnium center in complex 3a
B
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2.384(4) Å, respectively) are comparable to those reported for
Hf−O and Hf−N(sp2) distances.23,24d,e The other notable
feature is that 3d has two η1-coordinated benzyl moieties
(Hf1−C12 = 2.979(6) Å and Hf1−C19 = 3.153(5) Å) due to
strong donation of the nitrogen atom of the quinoline moiety,
values that are sufficiently elongated relative to 3a−c thereby
supporting an η1 over η2 coordination in the solid-state (Table
1).
Catalytic Coupling Reaction of 2,6-Dimethylpyridine
and 3-Hexyne. In our initial trials, we used 2,6-dimethylpyr-
idine (4a) as a substrate for C(sp3)−H alkenylation with 3-
hexyne (5a) using a 3:1 ratio of 4a/5a. In a typical experiment,
we added 4a to a solution containing one of the complexes 3a−
d (10 mol %) in C6D5Br followed by sequentially adding
[Ph3C][B(C6F5)4] (10 mol %) and 5a at room temperature;
then, the reaction mixture was allowed to heat at 100 °C for 12
h (Table 2, entries 1−4). Gratifyingly, complex 3c was found to
serve as a precatalyst, exclusively giving C(sp3)−H alkenylated
product 6aa as a single stereoisomer in 50% yield (46% isolated
yield). The moderate yield of the product was due to the
moderate conversion of 3-hexyne: We did not observe any
other byproducts or insoluble materials in the reaction mixture.
Notably, when we added 5a first to the solution of 3c in
C6D5Br at room temperature followed by the addition of
[Ph3C][B(C6F5)4] (10 mol %) and 4a, the yield of 6aa was
essentially the same, while (E)-(2-ethylpent-2-en-1-yl)benzene
(7) was obtained in equimolar amounts to the catalyst 3c
(entry 5), indicating that the insertion of 3-hexyne into the
benzyl-hafnium bond proceeded before the C(sp3)−H
activation of 4a. We thus fixed the addition order of 4a first,
then [Ph3C][B(C6F5)4] second before adding 5a to the
reaction mixture to avoid the formation of byproduct 7. Next,
we conducted the reaction using other catalyst precursors, 3a,b
and 3d, under the same reaction conditions: The yields of 6aa
were very low in all cases. Accordingly, we selected 3c as the
best catalyst precursor, whose catalytic activity upon activation
by [Ph3C][B(C6F5)4] was attributed to the enhanced stability
of the N,N,N-tridentate manifold. In addition, the sterically less-
encumbered environment of the pyridyl moiety of 3c compared
to the quinolinyl group of 3d allowed for the coordination of 4a
to release the product 6aa. This is in contrast to our previous
report using a bidentate diamido-supported cationic alkylhaf-
nium complex; under similar reaction condition, the double
insertion of alkyne was allowed following C−H activation of
2,6-dimethylpyridine, giving the 2-to-1 coupled product.23 It
was disfavored a second alkyne insertion for 3c due to the
sterically congested tridentate ligand system, thus forming the
Figure 1. Molecular structures of neutral dibenzylhafnium complexes
3a−d. Thermal ellipsoids are set to 30% probability level. Hydrogen
atoms have been omitted for clarity.
adopts a distorted tetrahedral geometry, in which the small bite
angle of the diamido ligand (81.83(17)°) induced coordinative
unsaturation around the hafnium center, resulting in one benzyl
group as the η2 coordination based on the shorter Hf1−C12
distance (2.589(6) Å) and the acute Hf1−C11−C12 angle
(84.3(4)°) and the other benzyl group as the η1 coordination
depicted by the longer Hf1−C19 distance (3.185(6) Å) and the
obtuse Hf1−C18−C19 angle (113.6(3)°).23,24d,e Thus, the η2
benzyl coordination persists in both solid-state and solution
(vide supra). The Hf−N(amido) distances (2.013(5) and
2.022(4) Å) are slightly shorter than those (2.070(3)−
2.867(12) Å) found in our previous hafnium complexes,
consistent with a more electron-deficient hafnium center
relative to the hafnium-amido complexes reported by us and
Waele et al.23,24d,e
Complexes 3b−d largely share bond distances and angles
comparable to those of 3a, albeit pentacoordinate due to the
coordination of the extra heteroatom of the ligand. Thus, all
complexes 3b−d adopt a distorted trigonal bipyramidal
geometry where the two benzyl groups (C11 and C18) and
N2 occupy the equatorial positions, while the N1 and either O1
(complex 3b) or N3 (complexes 3c−d) define the axial
positions. The hafnium-heteroatom distances in 3b (Hf1−O1 =
2.372(5) Å) and in 3c and 3d (Hf1−N3 = 2.344(5) Å and
Table 1. Selected Bond Distances (Å) and Angles (deg) in Complexes 3a−d
3a
3b (X = O1)
3c (X = N3)
3d (X = N3)
Hf1−N1
Hf1−N2
Hf1−C11
Hf1−C12
Hf1−C19
Hf1−X
N1−Hf1−N2
C11−Hf1−C18
N2−Hf1−X
Hf1−C11−C12
Hf1−C18−C19
2.013(5)
2.022(4)
2.280(7)
2.589(6)
3.185(6)
n.a.
2.046(5)
2.045(6)
2.272(6)
2.655(7)
3.242(7)
2.372(5)
81.6(2)
2.063(5)
2.047(5)
2.287(5)
2.702(6)
3.261(6)
2.344(5)
79.06(18)
117.37(18)
70.12(16)
88.8(3)
2.066(4)
2.045(4)
2.277(6)
2.979(6)
3.153(5)
2.384(4)
78.39(17)
120.3(2)
71.26(16)
102.5(4)
111.4(3)
81.83(17)
123.1(2)
n.a.
117.2(2)
69.54(17)
87.9(4)
84.3(4)
113.6(3)
116.6(4)
118.2(3)
C
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Table 2. Optimization of C(sp3)−H Alkenylation of 2,6-
Dimethylpyridine with 3-Hexyne Catalyzed by Hafnium
Complexes 3a−d
Table 3. Substrate Scope for C(sp3)−H Alkenylation of 2,6-
Dimethylpyridines with Both Internal Symmetric and
Unsymmetric Dialkylalkynes Catalyzed by Hafnium
a
Complex 3c
b
entry
cat.
2,6-lutidine
3-hexyne
6aa
<10%
1
2
3
4
3a
3b
3c
3d
3c
3c
3c
3c
3c
3c
3c
3
3
3
3
3
3
2
1
1
1
3
1
1
1
1
1
1
1
1
2
3
1
14%
c
50% (46%)
<10%
47%
df
,
5
6
7
8
9
e
f
14%
33%
f
32%
f
27%
10
11
0%
g
42%
a
Reaction conditions: hafnium complex (15 μmol) and 4a was
dissolved in C6D5Br, followed by [Ph3C][B(C6F5)4] (15 μmol) and
b
5a. NMR yield reported using the phenanthrene as internal standard.
c
d
e
Isolated yield. 5a was added prior to 4a. Loading of calatyst and
f
g
[Ph3C][B(C6F5)4] was 5 mol %. Alkene 7 was formed. Used
a
Isolated yield.
B(C6F5)3 and increased reaction time to 27 h.
and 44% yield as a mixture of regioisomers, respectively,
suggesting that the small steric differences, n-butyl versus
methyl for 5d as well as ethyl groups for 5e, were difficult to
distinguish by this hafnium catalyst. We further examined the
coupling reaction with trisubstituted pyridine derivatives:
electron-rich pyridine, 2,4,6-trimethylpyridine (4b), was
operative for the coupling reaction with 4-octyne (5b) to
give the C(sp3)−H alkenylated product 6bb in 32% yield, while
the coupling reaction of 5b with electron-deficient pyridines
such as 4-bromo-2,6-dimethylpyridine (4c) resulted in the
formation of 6cb in 48% yield. An unsymmetrical pyridine, 3-
bromo-2,6-dimethylpyridine (4d), selectively formed the C-
(sp3)−H alkenylated product 6db in 27% yield upon reacting
with 5b, where the sterically less-hindered methyl group was
alkenylated.
1-to-1 coupled product. Lowering the catalytic loading of 3c
down to 5 mol % resulted in a reduced yield (14%) of 6aa
(entry 6). The ratio of 4a and 5a was also sensitive to the yield:
When the 3:1 ratio of 4a/5a was changed to 2:1, 1:1, and 1:2,
the yield of 6aa was reduced to ∼30% yield along with the
production of 7 (entries 7−9). Further decreasing the ratio of
4a over 5a (4a/5a = 1:3) completely suppressed the reaction
(entry 10). Thus, we rationalized that the cationic species from
3c first reacted with 3-hexyne under this reaction condition to
give an alkenylhafnium species that possessed stronger affinity
to 3-hexyne relative to 2,6-dimethylpyridine under the reaction
condition. Upon activation with B(C6F5)3, 6aa was obtained in
a yield comparable to that of the reaction using [Ph3C][B-
(C6F5)4], albeit only after 27 h (entry 11), suggesting that
benzylborate anion [PhCH2B(C6F5)3]− competed with the
substrate to coordinate with the cationic hafnium center (vide
infra). In this catalytic reaction, the maximum turnover number
(TON) reached 5: The low TON was probably due to the
product inhibition via coordination of 6aa to the metal center.
With the optimized reaction conditions in hand, we screened
substrates for the reactions between 4a and dialkylalkynes (5b−
e) together with other 2,6-dimethylpyridines (4b−d) (Table
3). When 4-octyne (5b, bp 131 °C) was used for the reaction
with 4a, the isolated yield of C(sp3)−H alkenylated product
6ab was 50%, while the reaction between 4a and 5-decyne (5c,
bp 177 °C) gave 6ac in 60% yield. In both cases, single
stereoisomers were obtained from the reaction mixture.
Although unsymmetrical alkynes, such as 2-heptyne (5d) and
3-octyne (5e), were applicable to the C(sp3)−H alkenylation
reaction, trisubstituted alkenes 6ad and 6ae were obtained in 24
Characterization and Reactions of Cationic Benzyl-
hafnium Complexes. To gain additional insight into the
reaction mechanism, we carried out benzyl abstraction reactions
of 3a−c with both of [Ph3C][B(C6F5)4] and B(C6F5)3.
Reactions of 3a−c with B(C6F5)3 quantitatively generated
thermally stable cationic hafnium species 8a−c (Scheme 3),
whereas treatment of 3a−c with [Ph3C][B(C6F5)4] resulted in
decomposition. Due to difficulties isolating the highly reactive
cationic species 8a−c, in situ generated cationic species 8a−c
1
were characterized by H, 13C, and 19F NMR spectroscopies.
The 1H NMR spectrum of 8c, as a representative of the cationic
species 8a−c, displayed only one set of ABq resonances for the
benzyl protons at δ 1.85 and 2.16 (2J = 11.7 Hz), indicating
successful benzyl-abstraction by B(C6F5)3. Signals for the
methylene and methine protons in the NCHCH2Ph fragment
were observed at δ 2.78 (3J = 3.4 Hz) and 4.49 as a broad
doublet and broad singlet, respectively. It was noteworthy that
four upfield-shifted signals due to the phenyl group of the
benzylborate anion were detected at δ 5.30, 6.00, 6.14, and
D
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with those found for the η2-coordination of the phenyl ring of
the borate anion to cationic metal species: Horton et al.
observed similar upfield- and downfield-shifted resonances for
one phenyl group of the tetraphenylborate anion bound in an
η2-fashion to a cationic bis(indenyl)zirconium center, while
Floriani et al. reported the structurally characterized cationic
copper complex with an η2-coordinated phenyl ring of the
tetraphenylborate anion (Figure 2).26
Scheme 3. Preparation of Cationic Monobenzylhafnium
Complexes 8a−c
Figure 2. Examples of η2-coordination of borate anion to the metal
center.
6.27, as typically observed for the η6-coordinated benzylborate
anion.25 In the 13C NMR spectrum, the methylene resonance of
the benzylhafnium moiety was observed as a triplet at δ 61.6
(1JC−H = 118 Hz), which was best represented as an η1-
coordination to the hafnium center. The difference between
meta- and para-fluorine resonances in the 19F NMR spectrum
of 8c (Δδ(m-,p-F) = 3.7) also suggested η6-benzylborate
coordination through the abstracted benzyl group,25 resulting
in the η1-fashion of the remaining benzylhafnium moiety. A
similar coordination mode of the benzylhafnium moiety was
observed for complexes 8a (δ 62.2, 1JC−H = 118 Hz) and 8b (δ
We tested the catalytic activity of 8c for the C(sp3)−H
alkenylation of 2,6-dimethylpyridine (4a) with 4-octyne (5b),
as 3c exhibited the best catalytic performance (Scheme 4).
Scheme 4. In Situ Generation of 8c Followed by Subsequent
Addition of 2,6-Dimethylpyridine and 3-Hexyne
1
61.7, JC−H = 119 Hz), and in all cases, the signals for the
phenyl protons of the benzylborate anion were shifted upfield.
Similar to the cationic hafnium species series 8a−c, we
generated the cationic hafnium species 8d quantitatively
through the benzyl abstraction reaction using B(C6F5)3, since
the reaction with [Ph3C][B(C6F5)4] resulted in decomposition.
Analogous to series 8a−c, we characterized the in situ generated
8d by 1H, 13C, and 19F NMR spectroscopies. In sharp contrast,
a triplet signal with a large coupling constant was observed at δ
62.3 (1JC−H = 134 Hz) for the methylene carbon of the
benzylhafnium moiety in 8d in the 13C NMR spectrum, which
was typical for the η2-fashion of the benzylhafnium moiety (eq
1).
Addition of large excess amounts (30 equiv) of 4a to the
solution of 8c in C6D5Br followed by the addition of 10 equiv
of 5b the reaction mixture and heating at 100 °C for 12 h led to
the formation of target compound 6ab in 58% yield (based on
the amount of 4-octyne) without any byproducts, suggesting
that the cationic benzylhafnium complex was an active species.
Reaction Kinetics. We monitored the progress of the
reaction by 1H NMR spectroscopy and calculated the
thermodynamic parameters for the formation of the C(sp3)−
H alkenylated product 6. According to the conditions used for
the C(sp3)−H alkenylation reaction of 2,6-dimethylpyridine
(4a) with 4-octyne (5b) (Table 3, entry for 6ab), we
monitored the overall reaction rates at four different temper-
atures. The yield of 6ab increased linearly in the temperature
range of 353−368 K,27 indicating that the reaction was zero-
order for both substrates 4a and 5b under the condition of
excess 4a (3 equiv). In fact, even in the presence of 4.5 equiv of
4a, the reaction rate was almost the same as that under the
standard conditions (3 equiv of 4a), in good accordance with
C(sp3)−H activation of 4a being the rate-determining step.28
Eyring analysis of the reaction rate provided a high free
Although the more sterically congested quinoline-tethered
ligand attached to the hafnium in 8d, the difference between
the meta- and para-fluorine resonances in the 19F NMR was 3.8
ppm, suggesting that the benzylborate anion interacted with the
hafnium center, similar to the zwitterionic species 8a−c. In the
1H NMR spectrum at −20 °C in C6D5Br, an unusually upfield-
shifted phenyl resonance was observed at δ 4.21 for the para-
proton together with four other signals at δ 5.26 and 5.89 for
the meta-protons and 5.41 and 7.28 for the ortho-protons. The
upfield-shifted resonance for the para-position and the
downfield-shifted signal for one ortho-position were consistent
activation energy of 27.1
1.2 kcal/mol (at 368 K) for the
C(sp3)−H activation step to release the product.27 In the
E
DOI: 10.1021/acs.organomet.6b00655
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
related system of a cationic zirconocene-catalyzed C(sp2)−H
alkylation, Jordan et al. reported density functional theory
calculations for the C(sp2)−H alkylation of 2-methylpyridine
with propene: after the formation of a five-memberd chelating
structure, Cp2Zr{η2-C,N−CH2CHMe-(2-Me-6-pyridyl)}+ (A),
the activation free energy for the C(sp2)−H activation of 2-
picoline was 41.67 kcal/mol to release the C(sp2)−H alkylated
product (Scheme 5).28 Because the barrier for this C(sp2)−H
Scheme 6. Proposed Reaction Mechanism for the C(sp3)−H
Alkenylation of 2,6-Dimethylpyridine (4a) with Alkynes (5)
Catalyzed by 3c/[Ph3C][B(C6F5)4]
Scheme 5. Activation Energy for the Transformation of 5-
Membered Metallacycle Cp2Zr{η2-C,N−CH2CHMe-(2-Me-
6-pyridyl)}+ Reported by Jordan et al.28a
bond activation process was inaccessibly high, H2 gas was
necessary to afford the C(sp2)−H alkylated product with a
small activation free energy (25.29 kcal/mol). The activation
energy for the C(sp3)−H activation in our system was low
enough to produce the C(sp3)−H alkenylated compound
without H2 gas. In addition, the negative entropic value of
−24.0 1.7 e.u. suggests an ordered transition state of the C−
H bond activation.
CONCLUSIONS
■
We demonstrated the catalytic and stereoselective C(sp3)−H
alkenylation of 2,6-dimethylpyridine derivatives with internal
dialkylalkynes by cationic hafnium complexes. After screening a
series of four neutral dibenzyl hafnium complexes 3a−d
supported by nitrogen-based dianionic multidentate ligands in
combination with [Ph3C][B(C6F5)4], 3c proved to be the only
catalytically active hafnium complex. Addition of 2,6-
dimethylpyridine to the reaction mixture prior to 3-hexyne
led to selective formation of the C(sp3)−H alkenylated product
6aa. In contrast, when the reagent addition order of 2,6-
dimethylpyridine and 3-hexyne was reversed, the C(sp3)−H
alkenylated product 6aa was obtained together with byproduct
7. Kinetic analysis of the reaction progress revealed zero-order
dependence on both 2,6-dimethylpyridine and alkyne, suggest-
ing that the C(sp3)−H activation of precoordinated 2,6-
dimethylpyridine accompanied by release of the product was
the rate-determining step in the overall catalytic cycle.
Proposed Reaction Mechanism. Scheme 6 describes a
plausible reaction mechanism of the C(sp3)−H alkenylation of
4a with 5 catalyzed by 3c. The activation step of 3c is a benzyl
abstraction to produce the cationic species 8c, which directly
activates the C(sp3)−H bond of 4a to form a four-membered
metallacycle 9c. Complex 9c selectively allows insertion of only
1 equiv of internal alkyne 5 to give a six-membered metallacycle
10c due to the steric congestion of the supporting ligand, which
is in sharp contrast to the double insertion of internal alkynes
into the four-membered metallacycle for the related hafnium
complex having a N,N′-dialkylethylenediamido ligand.23 In the
next step, we hypothesize that further coordination of one
equivalent of 4a to the hafnium center produces six-
coordinated species 11c, which is in an equilibrium with the
five-coordinated species 10c. In the above-mentioned zircono-
cene-catalyzed C(sp2)−H alkylation by Jordan et al., coordina-
tion of pyridine derivatives to the metallacycle intermediate
before C(sp2)−H bond activation is proposed for H2-free
system, based on the density functional theory calculation.28a
Zero-order dependence for 4a and 5b in the kinetic study in the
presence of excess 4a suggests that the rate-determining step is
a C(sp3)−H activation of the precoordinated substrate 4a along
with the release of the trisubstituted alkene 6 in a stereo-
selective manner.
By increasingly the steric congestion around the hafnium
center relative to our previous report of hafnium-catalyzed
carbocycle synthesis (tridentate versus bidentate ligand frame-
works),23 we can control the insertion of either 1 equiv of
alkyne (tridentate ligand) or 2 equiv of alkyne (bidentate
ligand). Furthermore, in our current system, selectivity of the
reaction was high for the 1:1 coupling product due to the
limited coordination environment around the metal center. We
are currently working on the further applications of early
F
DOI: 10.1021/acs.organomet.6b00655
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
(br t, 3J = 6.0 Hz, 2H, NHCH2), 6.00 (dd, 3J = 3.4 Hz, 3J = 1.4 Hz, 1H,
transition metal alkyl complexes for C−H activation and
coupling reactions by small modifications of the nitrogen-based
supporting ligand system.
3
3
4-franyl), 6.57 (d, J = 3.4 Hz, 1H, 3-franyl), 6.84 (t, J = 7.5 Hz, 1H,
p-H of 2,6-(CH3)2C6H3), 6.98 (d, 3J = 7.5 Hz, 2H, m-H of 2,6-
3
(CH3)2C6H3), 7.02 (d, J = 1.4 Hz, 1H, 5-franyl), 7.74 (s, 1H, N
CH). The amine proton (NHCH2) was not observed in the 1H NMR
spectrum due to the fast exchange. 13C NMR (100 MHz, C6D6, 30
°C): δ 18.3 (2,6-(CH3)2C6H3), 48.8 (NC2H4N), 61.1 (NC2H4N),
111.3, 112.0, 121.6, 128.8, 129.2, 144.0, 146.2, 150.4, 152.5. HRMS
(EI) m/z calcd for C15H18N2O 242.1419, found 242.1419.
EXPERIMENTAL SECTION
■
General Remarks. All manipulations involving air- and moisture-
sensitive organometallic compounds were carried out under argon
using the standard Schlenk technique or argon-filled glovebox.
Hf(CH2Ph)4 was prepared according to the literature.29 2,6-
Dimethylpyridines and dialkylacetylenes were purchased and purified
by distillation over CaH2. B(C6F5)3 and [Ph3C][B(C6F5)4] were
purchased and used as received. Hexane and toluene were dried and
deoxygenated by distillation over sodium benzophenone ketyl under
argon or by using Grubbs purification system. Chlorobenzene,
benzene-d6, and bromobenzene-d5 were distilled from CaH2 and
1
2c. 85% yield, H NMR (400 MHz, C6D6, 30 °C): δ 2.21 (s, 6H,
2,6-(CH3)2C6H3), 3.12 (t, 3J = 5.5 Hz, 2H, CH2NCH), 3.44 (t, 3J =
3
5.5 Hz, 2H, NHCH2), 3.54 (br s, 1H, NHCH2), 6.63 (br dd, J = 6.3
Hz, 1H, 5-py), 6.87 (t, 3J = 7.3 Hz, 1H, p-H of 2,6-(CH3)2C6H3), 6.97
(d, 3J = 7.3 Hz, 2H, m-H of 2,6-(CH3)2C6H3), 7.07 (br dd, 3J = 7.8 Hz,
3
4
1H, 4-py), 8.03 (dd, J = 7.8 Hz, J = 1.0 Hz, 1H, 3-py), 8.44 (s, 1H,
3
NCH), 8.46 (d, J = 6.3 Hz, 1H, 6-py). 13C NMR (100 MHz,
1
CDCl3, 30 °C): δ 18.7 (2,6-(CH3)2C6H3), 49.2 (NC2H4N), 61.2
(NC2H4N), 120.7 (3-py), 122.2 (p-C of 2,6-(CH3)2C6H3), 124.6 (5-
py), 129.3, 129.6, 136.1, 146.6, 149.7, 155.5, 163.8 (NCH). HRMS
(EI) m/z calcd for C16H19N3 253.1579, found 253.1579.
thoroughly degassed by trap-to-trap distillation before use. H NMR
(400 MHz), 13C NMR (100 MHz), and 19F NMR (376 MHz) spectra
were measured on BRUKER AVANCEIII-400 spectrometer. Assign-
1
ments for H and 13C NMR peaks for some of the complexes were
1
1
1
1
aided by 2D H−1H COSY, 2D H−13C HMQC, and 2D H−13C
HMBC spectra. GC-MS measurement was carried out using a DB-1
capillary column (0.25 mm × 30 m) on a Shimadzu GCMS-
QP2010Plus. All melting points were measured in sealed tubes under
argon atmosphere. Mass spectra were recorded on a JEOL JMS-700
spectrometer. The elemental analyses were recorded by using
PerkinElmer 2400 at the Faculty of Engineering Science, Osaka
University.
2d. 85% yield, H NMR (400 MHz, C6D6, 30 °C): δ 2.23 (s, 6H,
2,6-(CH3)2C6H3), 3.15 (t, 3J = 5.6 Hz, 2H, CH2NCH), 3.49 (t, 3J =
3
5.6 Hz, 2H, NHCH2), 3.56 (br s, 1H, NHCH2), 6.87 (t, J = 7.4 Hz,
3
1H, p-H of 2,6-(CH3)2C6H3), 6.98 (d, J = 7.4 Hz, 2H, m-H of 2,6-
(CH3)2C6H3), 7.13−7.16 (m, 1H, quinolinyl), 7.32−7.37 (m, 2H,
3
3
quinolinyl), 7.59 (d, J = 8.5 Hz, 1H, 4-quinolinyl), 8.21 (d, J = 8.5
Hz, 1H, 3-quinolinyl), 8.27 (d, 3J = 8.3 Hz, 1H, 8-quinolinyl), 8.59 (s,
1H, NCH). 13C NMR (100 MHz, C6D6, 30 °C): δ 18.3 (2,6-
(CH3)2C6H3), 48.8 (NC2H4N), 60.9 (NC2H4N), 118.0, 121.8, 127.0,
128.6, 128.8, 129.2, 129.3, 130.0, 135.9, 146.2, 148.2, 155.0, 163.7
(NCH). HRMS (EI) m/z calcd for C20H21N3 303.1735, found
303.1737.
Synthesis of 1. To a solution of bromoethylamine hydrobromide
(2.66 g, 13.0 mmol, 1.0 equiv) in water (8.0 mL) was added 2,6-
dimethylaniline (3.03 g, 25.0 mmol, 2.0 equiv). The reaction mixture
was allowed to warm to 95 °C and vigorously stirred for 12 h. After
cooling to room temperature, water (7 mL) was added, and the
solution was washed (3 × 15 mL) with EtOAc. The aqueous phase
was evaporated to dryness. The resulting solid was recrystallized from
a MeOH/hexane mixture. The crystals were quenched using 10%
aqueous KOH, extracted with CH2Cl2 (3 × 5 mL) and dried under
Synthesis and Characterization of Dibenzylhafnium Complex
Series (3a). To a solution of Hf(CH2Ph)4 (2.25 g, 4.15 mmol, 1 equiv)
in toluene (20 mL), a solution of amine-imine pro-ligand 2a (1.16 g,
4.15 mmol, 1 equiv) in toluene (20 mL) was added via a syringe at
−78 °C. The reaction mixture was allowed to warm to room
temperature and stirred overnight. After removing all the volatiles
under reduced pressure, the resulting residue was washed with hexanes
(3 × 5 mL) to give 3a as yellow powders in 75% yield, mp 82−83 °C
(dec). The analytically pure complexes were crystallized from a
toluene/hexanes (4:1) solution placed overnight at −20 °C. 1H NMR
(400 MHz, C6D6, 30 °C): δ 0.76 (d, 2J = 10.1 Hz, 1H, Hf(CHHPh)),
1
vacuum giving a pale yellow oil in 45% yield. H NMR (400 MHz,
3
CDCl3, 30 °C, δ) 2.32 (s, 6H, 2,6-(CH3)2C6H3), 2.91 (br t, J = 5.6
Hz, 2H, HNCH2CH2NH2), 3.03 (br t, 3J = 5.6 Hz, 2H,
HNCH2CH2NH2), 6.81 (t, 3J = 7.4 Hz, 1H, p-H of 2,6-
3
(CH3)2C6H3), 6.90 (d, J = 7.4 Hz, 2H, m-H of 2,6-(CH3)2C6H3).
The three amine protons (HNCH2CH2NH2) were not observed in the
1H NMR spectrum due to the fast exchange. 13C NMR (100 MHz,
CDCl3, 30 °C, δ) 18.5 (2,6-(CH3)2C6H3), 42.5, (NCH2CH2NH2),
50.9 (NCH2CH2NH2), 121.7 (p-C of 2,6-(CH3)2C6H3), 128.8 (m-C
of 2,6-(CH3)2C6H3), 129.4, 146.1. HRMS (EI) m/z calcd for
C10H16N2 164.1313, found 164.1313.
2
2
1.24 (d, J = 11.5 Hz, 1H, Hf(CHHPh)), 1.47 (d, J = 10.1 Hz, 1H,
2
Hf(CHHPh)), 1.78 (d, J = 11.5 Hz, 1H, Hf(CHHPh)), 2.06 (s, 6H,
3,5-(CH3)2C6H3), 2.32 (s, 6H, 2,6-(CH3)2C6H3), 2.68 (dd, J = 12.0
2
3
2
3
Hz, J = 8.5 Hz, 1H, NCH(CHHPh)Ar), 2.98 (dd, J = 12.0 Hz, J =
4.3 Hz, 1H, NCH(CHHPh)Ar), 3.34 (dd, 3J = 8.5, 4.3 Hz, 1H,
NCH(CH2Ph)Ar), 3.77−3.83 (m, 1H, NCH2CHHNH), 3.93−3.98
(m, 1H, NCH2CHHNH), 4.10 (br ddd, 2J = 10.8 Hz, 3J = 6.2 Hz, 1H,
NCHHCH2NH), 4.27 (br dd, 2J = 10.8 Hz, 3J = 4.5 Hz, 1H,
NCHHCH2NH), 6.27 (d, 3J = 7.1 Hz, 2H, Ar), 6.66 (s, 1H, Ar), 6.77
(t, 3J = 7.6 Hz, 1H, Ar), 6.88−7.30 (17H, aromatic protons overlapped
with a residual proton signal of C6D6). 13C NMR (100 MHz, C6D6, 30
°C): δ 19.4, 21.5, 41.4, 50.1, 54.3, 66.9 (1JC−H = 118 Hz, Hf(CH2Ph)),
71.1 (1JC−H = 131 Hz, Hf(CH2Ph)), 71.3, 121.7, 123.6, 124.0, 124.9,
126.1, 126.7, 127.2, 128.3, 128.7, 128.8, 130.8, 131.6, 134.6, 139.5,
141.1, 141.3, 143.3, 149.4, 152.3. Anal. Calcd for C40H44HfN2: C,
65.70; H, 6.06; N, 3.83. Found: C, 65.26; H, 6.37; N, 3.87. Small
deviation of found E.A. values is probably due to high sensitivity of 3a
to air. Dibenzylhafnium complexes 3b−d was prepared using a similar
procedure as 3a.
Synthesis of 2a. 3,5-Dimethylbenzaldehyde (2.00 g, 12.2 mmol, 1
equiv) and 1-(2,6-dimethylphenyl)-2-aminoethane (1) (1.29 g, 12.2
mmol, 1 equiv) were sequentially added at room temperature to a
stirred mixture of diethyl either (ca. 20 mL) and MgSO4 (18.0 g, 149
mmol, 8 equiv). The reaction mixture was vigorously stirred overnight.
The MgSO4 was filtered, and the solvent was removed under reduced
pressure to give amine-imine compound 2a as an off-white oil in 65%
yield. 1H NMR (400 MHz, CDCl3, 30 °C): δ 2.30 (s, 6H, 2,6-
(CH3)2C6H3), 2.36 (s, 6H, 3,5-(CH3)2C6H3), 3.34 (t, 3J = 5.7 Hz, 2H,
3
3
CH2NCH), 3.76 (br t, J = 5.7 Hz, 2H, NHCH2), 6.83 (t, J = 7.4
3
Hz, 1H, p-H of 2,6-(CH3)2C6H3), 6.98 (d, J = 7.4 Hz, 2H, m-H of
2,6-(CH3)2C6H3), 7.08 (s, 1H, p-H of 3,5-(CH3)2C6H3), 7.37 (s, 2H,
o-H of 3,5-(CH3)2C6H3), 8.24 (s, 1H, NCH). The amine proton
(NHCH2) was not observed in the 1H NMR spectrum due to the fast
exchange. 13C NMR (100 MHz, CDCl3, 30 °C): δ 18.8 (2,6-
(CH3)2C6H3), 21.2 (3,5-(CH3)2C6H3), 49.4 (NC2H4N), 61.5
(NC2H4N), 122.0, 126.6, 129.3, 129.6, 137.0, 128.2, 146.7, 162.3
(NCH). HRMS (EI) m/z calcd for C19H24N2 280.1939, found
280.1944. Amine-imine compounds 2b−d was prepared using a similar
procedure as 2a.
3b. 82% yield, mp 79−81 °C (dec). 1H NMR (400 MHz, C6D6, 30
°C): δ 1.07 (d, 2J = 11.3 Hz, 1H, Hf(CHHPh)), 1.33 (d, 2J = 11.3 Hz,
2
1H, Hf(CHHPh)), 1.68 (d, J = 11.2 Hz, 1H, Hf(CHHPh)), 1.79 (d,
2
3
2J = 11.2 Hz, 1H, Hf(CHHPh)), 2.40 (dd, J = 13.3 Hz, J = 6.2 Hz,
1H, NCH(CHHPh)Ar), 2.49 (s, 6H, 2,6-(CH3)2C6H3), 2.66 (dd, 2J =
13.3 Hz, 3J = 3.2 Hz, 1H, NCH(CHHPh)Ar), 3.38 (dt, 2J = 10.6 Hz, 3J
1
2
3
2b. 82% yield, H NMR (400 MHz, C6D6, 30 °C:) δ 2.24 (s, 6H,
= 6.4 Hz, 1H, NCHHCH2NH), 3.70 (dt, J = 11.1 Hz, J = 6.4 Hz,
3
2,6-(CH3)2C6H3), 3.15 (dd, J = 6.0, 4.7 Hz, 2H, CH2NCH), 3.37
2H, NCH2CHHN), 3.83 (dt, 2J = 10.6 Hz, 3J = 5.6 Hz, 1H,
G
DOI: 10.1021/acs.organomet.6b00655
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Article
NCHHCH2N), 3.98 (dt, 2J = 11.1 Hz, 3J = 5.6 Hz, 1H NCH2CHHN),
4.16 (dd, 3J = 6.2, 3.2 Hz, 1H, NCH(CH2Ph)Ar), 5.37 (d, 3J = 3.2 Hz,
1H, 3-franyl), 5.78 (dd, 3J = 3.2, 1.9 Hz, 1H, 4-franyl), 6.42 (d, 3J = 7.6
MHz, C6D5Br, 30 °C): δ 18.5, 19.7, 21.0, 40.5, 48.6, 55.3, 62.2 (1JC−H
= 118 Hz, Hf(CH2Ph)), 70.7, 123.1, 124.4, 125.1, 127.6, 128.3, 128.9,
129.1, 129.2, 130.6, 131.6, 133.0, 135.6, 137.5, 138.1, 139.7, 141.5,
142.2, 146.9, 149.3, 154.6, 160.9. 19F NMR (376 MHz, C6D5Br, 30
3
Hz, 2H, Ar), 6.53 (d, J = 7.6 Hz, 2H, Ar), 6.74 (br s, 1H, 5-franyl),
6.77−7.14 (14H, aromatic protons). 13C NMR (100 MHz, C6D6, 30
°C): δ 40.2, 55.1, 55.2, 55.9, 66.0 (1JC−H = 121 Hz, Hf(CH2Ph)), 69.1
(1JC−H = 127 Hz, Hf(CH2Ph)), 120.6, 121.3, 121.5, 122.1, 120.0,
126.6, 127.9, 128.0, 128.1, 128.4, 128.6, 128.7, 129.3, 130.3, 137.1,
142.7, 146.1, 146.2, 148.1, 169.0. Anal. Calcd for C36H38HfN2O: C,
62.38; H, 5.53; N, 4.04. Found: C, 61.94; H, 5.91; N, 4.11. Small
deviation of found E.A. values is probably due to high sensitivity of 3b
to air.
°C): δ −164.0 (t, 3JF−F = 20.1 Hz, 2F, m-F of ArF ), −160.1 (t, 3JF−F
=
3
21.1 Hz, 1F, p-F of ArF ), −129.9 (t, 3JF−F = 21.5 Hz, 2F, o-F of ArF ).
3
3
Cationic monobenzylhafnium complexes 8b−d were prepared using a
procedure similar to that for 8a.
1
2
8b. H NMR (400 MHz, C6D5Br, 30 °C): δ 1.75 (d, J = 12.1 Hz,
1H, Hf(CHHPh)), 2.08 (s, 3H, 2,6-(CH3)2C6H3), 2.15 (d, J = 12.1
2
Hz, 1H, Hf(CHHPh)), 2.20 (s, 3H, 2,6-(CH3)2C6H3), 2.52−2.53 (m,
2
2
1H, NCH(CHHPh)Ar), 2.58 (dd, J = 13.7 Hz, J = 4.3 Hz, 1H,
NCH(CHHPh)Ar), 2.68 (dd, 2J = 11.4 Hz, 3J = 5.9 Hz, 1H,
NCHHCH2N), 2.84 (dd, 3J = 11.4 Hz, 3J = 5.2 Hz, 1H,
3c. 72% yield, mp 67−68 °C (dec). 1H NMR (400 MHz, C6D6, 30
°C, δ) 1.14 (d, 2J = 11.4 Hz, 1H, Hf(CHHPh)), 1.41 (d, 2J = 10.3 Hz,
1H, Hf(CHHPh)), 1.61 (d, 2J = 10.3 Hz, 1H, Hf(CHHPh)), 1.94 (d,
2J = 11.4 Hz, 1H, Hf(CHHPh)), 2.60 (s, 6H, 2,6-(CH3)2C6H3), 2.66
(dd, 2J = 13.7 Hz, 3J = 3.0 Hz, 1H, NCH(CHHPh)Ar), 2.77 (dd, 2J =
13.7 Hz, 3J = 5.6 Hz, 1H, NCH(CHHPh)Ar), 3.59 (ddd, 2J = 10.4 Hz,
NCH2CHHN), 3.32−3.46 (br m, 2H, PhCH2BArF ), 4.21 (br s, 1H,
3
NCH(CH2Ph)Ar), 4.23−4.30 (m, 1H, NCH2CHHN), 4.34−4.41 (m,
3
1H, NCHHCH2N), 5.47 (t, J = 7.4 Hz, 1H, p-H of PhCH2BArF ),
3
5.88 (d, 3J = 3.4 Hz, 1H, m-H of Hf(CH2Ph)), 6.00−6.02 (m, 2H, o-H
of PhCH2BArF and p-H of Hf(CH2Ph)), 6.19 (m, 2H, m-H of
2
3
3J = 6.4, 4.7 Hz, 1H, NCHHCH2NH), 3.88 (ddd, J = 11.0 Hz, J =
3
PhCH2BArF and Ar), 6.48 (d, J = 7.5 Hz, 2H, Ar), 6.53 (d, J = 7.2
3
3
6.7, 4.7 Hz, 1H, NCH2CHHNH), 4.02 (ddd, 2J = 10.4 Hz, 3J = 6.7, 5.6
Hz, 1H, NCH2CHHNH), 4.25 (ddd, J = 11.0 Hz, J = 6.4, 5.6 Hz,
1H, NCHHCH2NH), 4.42 (dd, J = 5.6, 3.0 Hz, 1H, NCH(CH2Ph)-
3
Hz, 2H, Ar), 6.63 (d, 3J = 1.4 Hz, 1H, m-H of Hf(CH2Ph)), 6.69 (t, 3J
= 7.3 Hz, 1H, Ar), 6.93−7.15 (aromatic protons overlapped with
residual proton signals of C6D5Br). 13C NMR (100 MHz, C6D5Br, 30
°C): δ 18.6, 19.7, 40.7, 55.6, 59.2, 61.7 (1JC−H = 119 Hz, Hf(CH2Ph)),
63.2, 104.7, 114.3, 118.9, 121.9, 125.4, 125.6, 127.4, 127.8, 128.2,
128.9, 129.0, 129.9, 133.7, 134.1, 135.9, 139.4, 148.0, 155.9, 159.6,
162.2. 19F NMR (376 MHz, C6D5Br, 30 °C, δ) −164.0 (t, 3JF−F = 20.1
2
3
3
3
3
Ar), 6.20 (t, J = 6.5 Hz, 1H, Ar), 6.34 (d, J = 7.3 Hz, 2H, Ar), 6.38
(d, 3J = 7.3 Hz, 2H, Ar), 6.51 (d, 3J = 8.0 Hz, 1H, Ar), 6.60 (t, 3J = 7.3
Hz, 1H, Ar), 6.77−7.08 (12H, aromatic protons), 7.21 (d, 3J = 7.6 Hz,
2H, Ar), 7.57 (d, 3J = 5.5 Hz, 1H, Ar). 13C NMR (100 MHz, C6D6, 30
°C): δ 18.2, 38.5, 55.0, 55.1, 66.4 (1JC−H = 119 Hz, Hf(CH2Ph)), 69.4
(1JC−H = 129 Hz, Hf(CH2Ph)), 118.7, 120.1, 120.6, 120.7, 123.4,
124.2, 124.9, 125.1, 127.6, 128.8, 129.1, 135.3, 135.4, 143.2, 143.8,
148.6, 150.3. Anal. Calcd for C37H39HfN3: C, 63.11; H, 5.58; N, 5.97.
Found: C, 62.62; H, 5.33; N, 5.92. Small deviation of found E.A. values
is probably due to high sensitivity of 3c to air.
3
Hz, 2F, m-F of ArF ), −160.2 (t, JF−F = 21.1 Hz, 1F, p-F of ArF ),
3
3
−130.0 (t, JF−F = 21.4 Hz, 2F, o-F of ArF ).
8c. H NMR (400 MHz, C6D5Br, 30 °C): δ 1.85 (d, J = 11.7 Hz,
1H, Hf(CHHPh)), 2.16 (s, 3H, 2,6-(CH3)2C6H3), 2.17 (d, 1H,
Hf(CHHPh), partial overlap with 2,6-(CH3)2C6H3), 2.22 (s, 3H, 2,6-
3
3
1
2
3
1
(CH3)2C6H3), 2.78 (d, J = 3.4 Hz, 2H, NCH(CH2Ph)Ar), 2.87 (dd,
3d. 41% yield, mp 117−118 °C (dec). H NMR (400 MHz, C6D6,
2J = 11.4 Hz, 3J = 5.8 Hz, 1H, NCHHCH2N), 3.00 (dd, J = 11.4 Hz,
3
30 °C) δ: 1.57 (d, 2J = 12.3 Hz, 1H, Hf(CHHPh)), 1.61 (d, 2J = 12.2
5.5 Hz, 1H, NCH2CHHN), 3.34 (br s, 1H, PhCHHBArF ), 3.49 (br s,
Hz, 1H, Hf(CHHPh)), 1.76 (d, 2J = 12.2 Hz, 1H, Hf(CHHPh)), 2.19
3
1H, PhCHHBArF ), 4.27−4.32 (m, 1H, NCH2CHHN), 4.38−4.45
2
(d, J = 12.3 Hz, 1H, Hf(CHHPh)), 2.67 (s, 6H, 2,6-(CH3)2C6H3),
3
3
2
2
(m, 1H, NCHHCH2N), 4.49 (br t, 1H, NCH(CH2Ph)Ar), 5.30 (t, J
2.81 (br d, J = 4.4 Hz, 2H, NCH(CH2Ph)Ar), 3.48 (ddd, J = 10.2
Hz, 3J = 6.5, 4.5 Hz, 1H, NCHHCH2NH), 3.77 (ddd, 2J = 11.2 Hz, 3J
= 6.9, 3.7 Hz, 1H, NCH2CHHNH), 4.18 (ddd, 2J = 10.2 Hz, 3J = 6.9,
3.7 Hz, 1H, NCH2CHHNH), 4.42 (ddd, 2J = 11.2 Hz, 3J = 6.5, 4.5 Hz,
= 7.3 Hz, 1H, p-H of PhCH2BArF ), 6.00 (d, J = 7.3 Hz, 1H, o-H of
3
3
PhCH2BArF ), 6.14 (t, J = 7.3 Hz, 1H, m-H of PhCH2BArF ), 6.27−
3
3
3
6.32 (m, 4H, m-H of PhCH2BArF and Ar), 6.50−6.57 (m, 2H, Ar),
3
6.72 (t, 3J = 7.5 Hz, 2H, Ar), 6.92−7.35 (aromatic protons overlapped
with residual proton signals of C6D5Br), 7.62 (d, 3J = 5.5 Hz, 1H, Ar).
13C NMR (100 MHz, C6D5Br, 30 °C): δ 18.8, 20.1, 21.4, 39.7, 58.5,
60.0, 61.6 (1JC−H = 118 Hz, Hf(CH2Ph)), 73.4, 118.5, 121.1, 122.8,
125.0, 125.1, 125.3, 127.2, 127.5, 128.0, 128.2, 128.8, 129.9, 131.4,
132.1, 133.1, 134.9, 135.2, 138.0, 146.7, 150.2, 157.0, 161.3, 166.6. 19F
3
1H, NCHHCH2NH), 4.54 (dd, J = 4.7, 4.4 Hz, 1H, NCH(CH2Ph)-
Ar), 6.22 (d, 3J = 7.1 Hz, 2H, Ar), 6.48 (t, 3J = 7.3 Hz, 1H, Ar), 6.62−
7.26 (19H, aromatic protons overlapped with a residual proton signal
of C6D6), 7.35 (d, 3J = 8.5 Hz, 1H, Ar), 7.75 (d, 3J = 8.5 Hz, 1H, Ar).
13C NMR (100 MHz, C6D6, 30 °C): δ 19.5, 39.7, 55.8, 57.3, 69.8
(1JC−H = 117 Hz, Hf(CH2Ph)), 72.4 (1JC−H = 126 Hz, Hf(CH2Ph)),
74.2, 119.4, 119.9, 121.3, 124.4, 125.5, 126.3, 126.4, 126.5, 126.8,
126.9, 127.7, 128.8, 128.9, 129.3, 129.4, 135.2, 136.1, 137.5, 144.5,
145.3, 148.4, 152.4, 170.4. Anal. Calcd for C41H41HfN3: C, 65.29; H,
5.48; N, 5.57. Found: C, 65.61; H, 5.70; N, 5.57.
3
NMR (376 MHz, C6D5Br, 30 °C): δ −164.1 (t, JF−F = 20.2 Hz, 2F,
m-F of ArF ), −160.4 (t, JF−F = 21.1 Hz, 1F, p-F of ArF ), −130.0 (t,
3
3
3
3JF−F = 21.4 Hz, 2F, o-F of ArF ).
3
1
8d. H NMR (400 MHz, C6D5Br, 30 °C): δ 1.79−1.87 (m, 7H,
Hf(CHHPh) and 2,6-(CH3)2C6H3), 2.23 (d, 2J = 12.8 Hz, 1H,
Hf(CHHPh)), 2.60 (br m, 2H, NCH(CHHPh)Ar and NCHHCH2N),
2.80−2.83 (br m, 2H, NCH(CHHPh)Ar and NCHHCH2N), 4.15 (br
Synthesis and Characterization of Cationic Monobenzylhafnium
Complex Series (8a). A yellow solution of dibenzylhafnium complex
3a (15.0 mg, 0.02 mmol) in bromobenzene-d5 (0.5 mL) was added to
B(C6F5)3 (10.5 mg, 0.02 mmol) at room temperature to quantitatively
3
dd, J = 8.5 Hz, 2H, NCH2CH2N), 4.46 (s, 1H, NCH(CH2Ph)Ar),
1
generate the orange solution of monobenzylhafnium complex 8a. H
5.91−6.17 (aromatic protons overlapped with residual proton signals
NMR (400 MHz, C6D5Br, 30 °C): δ 1.99 (s, 6H, 3,5-(CH3)2C6H3),
of C6D5Br), 6.62 (br s, 2H, Ar), 6.55−6.96 (aromatic protons
2.03 (s, 3H, 2,6-(CH3)2C6H3), 2.16 (d, 2J = 11.4 Hz, 1H,
3
overlapped with residual proton signals of C6D5Br), 7.04 (d, J = 8.0
2
Hf(CHHPh)), 2.22 (s, 3H, 2,6-(CH3)2C6H3), 2.40 (d, J = 11.4 Hz,
Hz, 1H, Ar), 7.40−7.48 (aromatic protons overlapped with residual
1H, Hf(CHHPh)), 2.59 (dd, 2J = 10.7 Hz, 3J = 5.6 Hz, 1H,
NCH(CHHPh)Ar), 2.80 (dd, 3J = 8.0 Hz, 4.5 Hz, 1H, NCHHCH2N),
2.84 (dd, 3J = 10.7 Hz, 4.6 Hz, 1H, NCH(CHHPh)Ar), 3.01 (br, 1H,
1
proton signals of C6D5Br). H NMR (400 MHz, C6D5Br, −20 °C): δ
1.83 (br s, 4H, 2,6-(CH3)2C6H3 and Hf(CHHPh)), 1.93 (s, 3H, 2,6-
(CH3)2C6H3), 2.34 (d, 2J = 12.9 Hz, 1H, Hf(CHHPh)), 2.55 (br d, 3J
= 8.5 Hz, 2H, NCHHCH2N and NCH(CHHPh)Ar), 2.71 (br s, 1H,
PhCHHBArF ), 3.26 (br, 1H, PhCHHBArF ), 3.98 (br dd, 3J = 6.6 Hz,
3
4.5 Hz, 1H, NCH2CHHN), 4.02 (dd, 33J = 5.6 Hz, 4.6 Hz, 1H,
NCH(CH2Ph)Ar), 4.16 (dd, 2J = 10.7 Hz, 3J = 8.0 Hz, 1H,
NCH2CHHN), 4.36 (m, 1H, NCHHCH2N), 5.70 (t, 3J = 7.3 Hz, 1H,
m-H of PhCH2BArF ), 5.81 (d, 3J = 7.3 Hz, 1H, o-H of PhCH2BArF ),
PhCHHBArF ), 2.79 (br m, 2H, NCHHCH2N and NCH(CHHPh)-
3
Ar), 3.75 (br s, 1H, PhCHHBArF ), 4.16−4.21 (br m, 3H,
3
NCH2CH2N and p-H of PhCH2BArF ), 4.46 (s, 1H, (NCH(CH2Ph)-
3
Ar), 5.26 (br s, 1H, m-H of PhCH2BArF ), 5.41 (d, 3J = 5.4 Hz, 1H, o-
3
3
3
3
3
5.98 (d, J = 7.3 Hz, 1H, o-H of PhCH2BArF ), 6.26 (t, J = 7.3 Hz,
H of PhCH2BArF ), 5.89 (br t, 1H, m-H of PhCH2BArF ), 5.96−7.00
3
3
3
1H, m-H of PhCH2BArF ), 6.43 (t, 3J = 7.3 Hz, 1H, p-H of
(aromatic protons overlapped with residual proton signals of C6D5Br),
3
PhCH2BArF ), 6.52 (s, 2H, Ar), 6.64−7.30 (aromatic protons
7.30 (d, 1H, J = 5.4 Hz, o-H of PhCH2BArF ), 7.39 (d, J = 8.3 Hz,
3
3
3
3
overlapped with residual proton signals of C6D5Br). 13C NMR (100
1H, Ar), 7.50 (s, 2H, Ar). 13C NMR (100 MHz, C6D5Br, 30 °C): δ
H
DOI: 10.1021/acs.organomet.6b00655
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
21.4, 34.3, 38.4, 57.6, 62.3 (1JC−H = 134 Hz, Hf(CH2Ph)), 74.0, 119.4,
125.3, 125.4, 127.2, 127.4, 127.8, 128.2, 128.3, 129.0, 129.1, 129.9,
135.6, 136.9, 138.0, 139.4, 139.8, 143.7, 147.1, 149.4, 157.9, 168.7. 19F
CH2CH2CH2CH3), 3.58 (s, 1.6H, pyCH2CCH). Overlapping
1
3
(shared): H NMR (400 MHz, C6D6, 30 °C): δ 0.84 (t, J = 7.3
Hz, 3H, CH2CH2CH2CH3), 0.87 (t, 3J
= 7.3 Hz, 3H,
NMR (376 MHz, C6D5Br, 30 °C): δ −164.4 (br s, 2F, m-F of ArF ),
CH2CH2CH2CH3), 1.19−1.43 (m, 8H, CH2CH2CH2CH3), 2.43 (s,
6H, pyCH3), 5.32−5.37 (m, 2H, pyCH2CCH), 6.59 (d, 3J = 7.6 Hz,
2H, 3H of py), 6.82 (d, 3J = 7.6 Hz, 2H, 5H of py), 7.08 (t, 3J = 7.6 Hz,
2H, 4H of py). 13C NMR (100 MHz, C6D6, 30 °C): δ 13.1
(CH2CH2CH2CH3), 13.8 (CH2CH2CH2CH3), 15.7 (pyCH2C
CCH3), 22.3 (CH2), 22.4 (CH2), 22.6 (CH2), 24.2 (pyCH3), 27.7
(CH2), 29.2 (CH2), 29.3 (CH2), 30.1 (CH2), 30.2 (CH2), 31.9 (CH2),
32.0 (CH2), 46.4 (pyCH2CCH), 48.9 (pyCH2CCH), 119.1 (py),
119.4 (py), 119.8, 119.9, 120.0, 121.2, 133.3 (pyCH2CCH), 135.6
(4C of py), 135.7 (4C of py), 138.8 (pyCH2CCH), 157.6 (py),
160.4 (py). HRMS (FAB) m/z calcd for [C14H21N + H] 204.1752,
found 204.1752.
3
3
−160.6 (br s, 1F, p-F of ArF ), −130.1 (t, JF−F = 21.3 Hz, 2F, o-F of
3
ArF ). 19F NMR (376 MHz, C6D5Br, −20 °C): δ −164.2 (t, JF−F
=
3
3
20.5 Hz, 2F, m-F of ArF ), −160.3 (t, 3JF−F = 21.2 Hz, 1F, p-F of ArF ),
3
3
−130.5 (br s, 2F, o-F of ArF ).
3
Synthesis and Characterization of C(sp3)−H Alkenylated
Products (6aa). In the glovebox, a solution of dibenzylhafnium
complex 3c (21.1 mg, 0.03 mmol) in bromobenzene-d5 (1.0 mL) was
added sequentially to 2,6-dimethylpyridine (96.4 mg, 0.90 mmol),
[Ph3C][B(C6F5)4] (27.7 mg, 0.03 mmol), and 3-hexyne (24.6 mg,
0.30 mmol) at room temperature. The reaction mixture was removed
from the glovebox and heated to 100 °C in an oil bath for 12 h. The
reaction was quenched with a saturated aqueous solution of NaHCO3
(ca. 3 mL) and extracted with Et2O (5 × 7 mL). Removing volatiles
under reduced pressure gave an oily residue, which was grafted on
silica. The alkenylated product was purified using flash column
chromatography with 10% EtOAc in hexane as the eluent. Alkene 7
was detected by GC-MS measurement when the addition of 2,6-
6ae. Product was isolated as a mixture of regioisomers (ca. 1:1).
Integration of nonoverlapping (not shared) peaks are reported as
decimal values when setting the triplet at 0.85 (CH2CH2CH2CH3) to
3, while the integration of overlapping (shared) peaks are reported as
1
3
integrals. H NMR (400 MHz, C6D6, 30 °C): δ 0.83 (t, J = 7.1 Hz,
2.9H, CH2CH2CH2CH3), 0.85 (t, 3J = 7.3 Hz, 3H, CH2CH2CH2CH3),
0.92−0.99 (m, 6H, CH2CH3), 1.21−1.43 (m, 8H, CH2CH2CH2CH3),
2.01−2.09 (m, 8H, CH2CH2CH2CH3 and CH2CH3), 2.42 (s, 6H,
pyCH3), 3.61 (s, 4H, pyCH2CCH), 5.27−5.31 (m, 2H, pyCH2C
CH), 6.59 (d, 3J = 7.6 Hz, 2H, 3H of py), 6.85 (d, 3J = 7.6 Hz, 2H, 5H
1
dimethylpyridines and 3-hexyne was reversed. H NMR (400 MHz,
3
3
C6D6, 30 °C): δ 0.92 (t, J = 6.4 Hz, 3H, CH2CH3), 0.95 (t, J = 6.4
Hz, 3H, CH2CH3), 1.94−2.08 (m, 4H, CH2CH3), 2.42 (s, 3H,
pyCH3), 3.59 (s, 2H, pyCH2C = CH), 5.25 (t, 3J = 7.1 Hz, 1H,
pyCH2C = CH), 6.59 (d, 3J = 7.6 Hz, 1H, 3H of py), 6.83 (d, 3J = 7.6
Hz, 1H, 5H of py), 7.08 (t, 3J = 7.6 Hz, 1H, 4H of py). 13C NMR (100
MHz, C6D6, 30 °C): δ 12.9 (CH2CH3), 14.4 (CH2CH3), 20.9
(CH2CH3), 22.8 (CH2CH3), 24.1 (pyCH3), 46.0 (pyCH2CCH),
119.4 (py), 119.8 (py), 128.7 (pyCH2CCH), 135.7 (4C of py),
139.0 (pyCH2CCH), 157.5 (py), 160.0 (py). HRMS (FAB) m/z
calcd for [C13H19N + H] 190.1596, found 190.1602. A similar
procedure was conducted for the other C(sp3)−H alkenylation
reactions in Table 3.
3
of py), 7.09 (t, J = 7.6 Hz, 2H, 4H of py). 13C NMR (100 MHz,
C6D6, 30 °C): δ 12.9 (CH2CH2CH2CH3), 13.8 (CH2CH2CH2CH3),
14.3 (pyCH2CCCH3), 21.1 (CH2), 22.3 (CH2), 22.6 (CH2), 22.8
(CH2), 24.1 (pyCH3), 27.4 (CH2), 29.5 (CH2), 30.5 (CH2), 32.2
(CH2), 46.0 (pyCH2CCH), 46.4 (pyCH2CCH), 119.4 (py),
119.8 (py), 127.1 (pyCH2CCH), 129.3 (pyCH2CCH), 135.6 (4C
of py), 137.4 (4C of py), 139.4 (pyCH2CCH), 157.5 (py), 160.4
(py). HRMS (FAB) m/z calcd for [C15H23N + H] 218.1909, found
218.1901.
6ab. 1H NMR (400 MHz, C6D6, 30 °C): δ 0.84 (t, 3J = 7.4 Hz, 3H,
6bb. 1H NMR (400 MHz, C6D6, 30 °C): δ 0.86 (t, 3J = 7.3 Hz, 3H,
CH2CH2CH3), 0.89 (t, 3J = 7.4 Hz, 3H, CH2CH2CH3), 1.32 (br dq, 3J
= 14.7, 7.4 Hz, 2H, CH2CH2CH3), 1.44 (br dq, 3J = 15.1, 7.6 Hz, 2H,
CH2CH2CH3), 1.90 (s, 3H, 3-CH3 of py), 2.00 (dd, 3J = 14.7, 7.4 Hz,
2H, CH2CH2CH3), 2.09 (br dd, 3J = 7.3 Hz, 2H, CH2CH2CH3), 2.44
CH2CH2CH3), 0.88 (t, 3J = 7.4 Hz, 3H, CH2CH2CH3), 1.31−1.40 (m,
3
2H, CH2CH2CH3), 1.41−1.49 (m, 2H, CH2CH2CH3), 1.98 (dd, J =
14.6, 7.4 Hz, 2H, CH2CH2CH3), 2.05 (dd, 3J = 9.1, 7.3 Hz, 2H,
CH2CH2CH3), 2.42 (s, 3H, pyCH3), 3.61 (br s, 2H, pyCH2CCH),
5.32 (t, 3J = 7.3 Hz, 1H, pyCH2CCH), 6.59 (br d, 3J = 7.6 Hz, 1H,
3H of py), 6.85 (br d, 3J = 7.6 Hz, 1H, 5H of py), 7.09 (t, 3J = 7.6 Hz,
1H, 4H of py). 13C NMR (100 MHz, C6D6, 30 °C): δ 13.6
(CH2CH2CH3), 13.8 (CH2CH2CH3), 21.3 (CH2), 23.1 (CH2), 24.2
(pyCH3), 29.9 (CH2), 31.8 (CH2), 46.4 (pyCH2CCH), 119.3 (py),
119.8 (py), 127.6 (pyCH2CCH, overlap with solvent), 135.6 (4C of
py), 137.8 (pyCH2CCH), 157.5 (py), 160.5 (py). HRMS (FAB) m/
z calcd for [C15H23N + H] 218.1909, found 218.1909.
3
(s, 3H, 6-CH3 of py), 3.63 (s, 2H, pyCH2CCH), 5.37 (t, J = 7.3
Hz, 1H, pyCH2CCH), 6.46 (s, 1H, 3H of py), 6.76 (s, 1H, 5H of
py). 13C NMR (100 MHz, C6D6, 30 °C): δ 13.6 (CH2CH2CH3), 13.8
(CH2CH2CH3), 20.2 (3-CH3 of py), 21.4 (CH2), 23.1 (CH2), 24.0 (6-
CH3 of py), 29.9 (CH2), 31.9 (CH2), 46.3 (pyCH2CCH), 120.4
(py), 121.0 (py), 127.7 (pyCH2CCH), 138.0 (4C of py), 146.3
(pyCH2CCH), 157.3 (py), 160.2 (py). HRMS (FAB) m/z calcd for
[C16H25N + H] 232.2065, found 232.2067.
1
6cb. 1H NMR (400 MHz, C6D6, 30 °C): δ 0.79 (t, 3J = 7.3 Hz, 3H,
CH2CH2CH3), 0.86 (t, 3J = 7.4 Hz, 3H, CH2CH2CH3), 1.26−1.42 (m,
4H, CH2CH2CH3), 1.91−2.01 (m, 4H, CH2CH2CH3), 2.21 (s, 3H,
pyCH3), 3.45 (s, 2H, pyCH2CCH), 5.24 (t, 3J = 7.3 Hz, 1H,
pyCH2CCH), 6.78 (s, 1H, 3H of py), 7.16 (s, 1H, 5H of py). 13C
NMR (100 MHz, C6D6, 30 °C): δ 13.6 (CH2CH2CH3), 13.7
(CH2CH2CH3), 21.2 (CH2), 23.0 (CH2), 23.7 (pyCH3), 29.8 (CH2),
31.7 (CH2), 45.9 (pyCH2CCH), 122.7 (py), 123.3 (py), 128.6
(pyCH2CCH), 132.6 (4C of py), 137.0 (pyCH2CCH), 159.1
(py), 162.1 (py). HRMS (FAB) m/z calcd for [C15H22NBr + H]
296.1014, found 296.1017.
6ac. H NMR (400 MHz, C6D6, 30 °C): δ 0.83−0.89 (m, 6H,
CH2CH2CH2CH3), 1.21−1.45 (m, 8H, CH2CH2CH2CH3), 2.03−2.12
(m, 4H, CH2CH2CH2CH3), 2.42 (s, 3H, pyCH3), 3.62 (s, 2H,
3
pyCH2CCH), 5.32 (t, J = 7.1 Hz, 1H, pyCH2CCH), 6.60 (d, 3J
= 7.6 Hz, 1H, 3H of py), 6.87 (d, 3J = 7.6 Hz, 1H, 5H of py), 7.10 (t, 3J
= 7.6 Hz, 1H, 4H of py). 13C NMR (100 MHz, C6D6, 30 °C): δ 13.8
(CH2CH2CH2CH3), 22.3 (CH2), 22.6 (CH2), 24.1 (pyCH3), 27.6
(CH2), 29.6 (CH2), 30.4 (CH2), 32.2 (CH2), 46.4 (pyCH2CCH),
119.3 (py), 119.8 (py), 127.8 (pyCH2CCH), 135.6 (4C of py),
137.9 (pyCH2CCH), 157.5 (py), 160.5 (py). HRMS (FAB) m/z
calcd for [C17H27N + H] 246.2222, found 246.2224.
6ad. Product was isolated as a mixture of regioisomers (ca. 1:1). 1H
NMR assignment is separated into three catagories; major isomer,
minor isomer, and overlapping (shared) peaks. Integration of
nonoverlapping (not shared) peaks are reported as decimal values
when setting the doublet at δ 1.55 (pyCH2CCCH3) to 3H intensity,
while the integration of overlapping (shared) peaks are reported as
integrals.
6db. 1H NMR (400 MHz, C6D6, 30 °C): δ 0.87 (t, 3J = 7.4 Hz, 3H,
CH2CH2CH3), 0.92 (t, 3J = 7.4 Hz, 3H, CH2CH2CH3), 1.30−1.41 (m,
2H, CH2CH2CH3), 1.47−1.57 (m, 2H, CH2CH2CH3), 1.96−2.02 (m,
2H, CH2CH2CH3), 2.14−2.17 (m, 2H, CH2CH2CH3), 2.23 (s, 3H,
pyCH3), 3.78 (s, 2H, pyCH2CCH), 5.25 (t, 3J = 7.1 Hz, 1H,
pyCH2CCH), 6.20 (d, 3J = 8.1 Hz, 1H, 3H of py), 7.24 (d, 3J = 8.1
Hz, 1H, 4H of py). 13C NMR (100 MHz, C6D6, 30 °C): δ 13.6
(CH2CH2CH3), 13.9 (CH2CH2CH3), 21.4 (CH2), 23.0 (CH2), 23.4
(pyCH3), 29.9 (CH2), 32.5 (CH2), 44.8 (pyCH2CCH), 121.7 (py),
127.5 (pyCH2CCH), 136.1 (4C of py), 139.8 (pyCH2CCH),
156.4 (py), 158.0 (py). HRMS (FAB) m/z calcd for [C15H22NBr + H]
296.1014, found 296.1017.
1
3
6ad-A: H NMR (400 MHz, C6D6, 30 °C): δ 1.55 (d, J = 6.8 Hz,
3H, pyCH2CCCH3), 2.08 (br dd, 3J
CH2CH2CH2CH3), 3.60 (s, 2H, pyCH2CCH).
= 7.7 Hz, 2H,
6ad-B: 1H NMR (400 MHz, C6D6, 30 °C): δ 1.62 (s, 2.3H,
pyCH2CH3CCH), 1.98 (br dt, 3J = 14.3, 7.7 Hz, 2.3H,
I
DOI: 10.1021/acs.organomet.6b00655
Organometallics XXXX, XXX, XXX−XXX

Organometallics
Article
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00655.
■
S
NMR spectra, kinetics and Eyring graphs, plot of yield of
6ab as a function of 2,6-dimethylpyridine equivalents
(PDF)
Crystallographic details for 3a−d (CIF)
AUTHOR INFORMATION
Corresponding Authors
*E-mail: tsurugi@chem.es.osaka-u.ac.jp.
*E-mail: mashima@chem.es.osaka-u.ac.jp.
Notes
■
(5) Representative recent reviews for Rh-catalyzed C−H function-
alization: (a) Satoh, T.; Miura, M. Chem. - Eur. J. 2010, 16, 11212.
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Sokeirik, Y.; Ghanem, A. Eur. J. Org. Chem. 2016, 2016, 1459.
(6) Representative recent examples for Rh-catalyzed C−H
functionalization reactions: (a) Umeda, N.; Tsurugi, H.; Satoh, T.;
Miura, M. Angew. Chem., Int. Ed. 2008, 47, 4019. (b) Kurokawa, T.;
Kim, M.; Du Bois, J. Angew. Chem., Int. Ed. 2009, 48, 2777.
(c) Ureshino, T.; Yoshida, T.; Kuninobu, Y.; Takai, K. J. Am. Chem.
Soc. 2010, 132, 14324. (d) Patureau, F. W.; Besset, T.; Glorius, F.
Angew. Chem., Int. Ed. 2011, 50, 1064. (e) Patureau, F. W.; Besset, T.;
Kuhl, N.; Glorius, F. J. Am. Chem. Soc. 2011, 133, 2154. (f) Rakshit, S.;
Grohmann, C.; Besset, T.; Glorius, F. J. Am. Chem. Soc. 2011, 133,
2350. (g) Tauchert, M. E.; Incarvito, C. D.; Rheingold, A. L.; Bergman,
R. G.; Ellman, J. A. J. Am. Chem. Soc. 2012, 134, 1482. (h) Wang, H.;
Glorius, F. Angew. Chem., Int. Ed. 2012, 51, 7318. (i) Brasse, M.;
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6427. (j) Duttwyler, S.; Chen, S.; Takase, M. K.; Wiberg, K. B.;
Bergman, R. G.; Ellman, J. A. Science 2013, 339, 678. (k) Kuninobu, Y.;
Yamauchi, K.; Tamura, N.; Seiki, T.; Takai, K. Angew. Chem., Int. Ed.
2013, 52, 1520. (l) Lian, Y.; Bergman, R. G.; Lavis, L. D.; Ellman, J. A.
J. Am. Chem. Soc. 2013, 135, 7122. (m) Lian, Y.; Huber, T.; Hesp, K.
D.; Bergman, R. G.; Ellman, J. A. Angew. Chem., Int. Ed. 2013, 52, 629.
(n) Lian, Y.; Hummel, J. R.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2013, 135, 12548. (o) Shi, Z.; Suri, M.; Glorius, F. Angew. Chem.,
Int. Ed. 2013, 52, 4892. (p) Wang, H.; Schroder, N.; Glorius, F. Angew.
Chem., Int. Ed. 2013, 52, 5386. (q) Zhang, G.; Yang, L.; Wang, Y.; Xie,
Y.; Huang, H. J. Am. Chem. Soc. 2013, 135, 8850. (r) Zhao, D.; Shi, Z.;
Glorius, F. Angew. Chem., Int. Ed. 2013, 52, 12426. (s) Bess, E. N.;
DeLuca, R. J.; Tindall, D. J.; Oderinde, M. S.; Roizen, J. L.; Du Bois, J.;
Sigman, M. S. J. Am. Chem. Soc. 2014, 136, 5783. (t) Cheng, C.;
Hartwig, J. F. Science 2014, 343, 853. (u) Wangweerawong, A.;
Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2014, 136, 8520.
(v) Romanov-Michailidis, F.; Sedillo, K. F.; Neely, J. M.; Rovis, T. J.
Am. Chem. Soc. 2015, 137, 8892. (w) Unoh, Y.; Satoh, T.; Hirano, K.;
Miura, M. ACS Catal. 2015, 5, 6634. (x) Vaughan, B. A.; Webster-
Gardiner, M. S.; Cundari, T. R.; Gunnoe, T. B. Science 2015, 348, 421.
(y) Liao, K.; Negretti, S.; Musaev, D. G.; Bacsa, J.; Davies, H. M. L.
Nature 2016, 533, 230.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
M.J.L. acknowledges financial support by a scholarship from
Monbukagakusho. H.T. acknowledges a financial supported by
JSPS KAKENHI Grant Number JP15KT0064, a Grant-in-Aid
for Scientific Research (B) of The Ministry of Education,
Culture, Sports, Science, and Technology, Japan.
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J
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K
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DOI: 10.1021/acs.organomet.6b00655
Organometallics XXXX, XXX, XXX−XXX