Reversible Concerted Metalation-Deprotonation C-H Bond Activation by [Cp*RhCl2]2

Article abstract of DOI:10.1021/acs.joc.9b01716

The reversibility of the concerted metalation-deprotonation exchange of eight para-substituted phenylpyridines is examined with the parent Cp*RhCl(κ-C,N-NC₅H₄-C₆H₄). Equilibrium constants are determined, and the free energies are used to extract the most important parameters that control the thermodynamics. K_eq values are found to correlate best with heterolytic C-H bond strengths but in a way that is not obvious considering the electrophilic nature of these activations.

Full text of DOI:10.1021/acs.joc.9b01716

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Article
Reversible Concerted Metallation-
Deprotonation C–H Bond Activation by [Cp*RhCl]
2
2
Andrew I VanderWeide, William W. Brennessel, and William D. Jones
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01716 • Publication Date (Web): 10 Sep 2019
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The Journal of Organic Chemistry
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Reversible Concerted Metallation-Deprotonation C–H Bond
Activation by [Cp*RhCl2]2
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Andrew I. VanderWeide, William W. Brennessel, William D. Jones*
Department of Chemistry, University of Rochester, Rochester, NY 14627
Email: jones@chem.rochester.edu
Keq
N
N
Cl
Cl
Rh
Rh
+
H
+
N
N
H
R
R
Keq is controlled by C-H heterolytic bond strength
ABSTRACT: The reversibility of the concerted metallation-deprotonation exchange of eight para-substituted phenylpyridines is
examined with the parent Cp*RhCl(-C,N-NC5H4–C6H4). Equilibrium constants are determined, and the free energies are used to
extract the most important parameters that control the thermodynamics. Keq values are found to correlate best with heterolytic C–H
bond strengths, but in a way that is not obvious considering the electrophilic nature of these activations.
work by Fagnou with [Cp*RhCl2]2.6 Examination of 11
INTRODUCTION
different carboxylates showed that with some, cyclometallation
The electrophilic activation and functionalization of aromatic
of 4-(2-pyridinyl)anisole went to equilibrium, not completion.16
C–H bonds is rapidly being recognized as one of the most
In this report, we examine the reversibility of the concerted
important transformations in organic methodology.1 Heck
metallation-deprotonation of a variety of para-substituted
showed as early as 1975 that palladium(II) metallacycles
phenylpyridines, and use equilibration data to examine the
formed via directed cyclometallation could be carbonylated to
factors that control the thermodynamics of the C–H activation.
give heterocycles.2 Pfeffer also reported a number of examples
in which metallacycles of palladium(II) and ruthenium(II)
,
reacted with alkynes to give heterocycles.3 4 Our group
demonstrated the use of alkynes for conversion of metallacycles
to isoquinolines with [Cp*RhCl2]2. Importantly, Fagnou first
RESULTS AND DISCUSSION
5
showed that catalytic [Cp*RhCl2]2 could be used with
Metallacycle Synthesis. Syntheses of the C–H activated
complexes shown in Scheme 1 were adapted from known
procedures.15 These reactions are believed to follow the CMD
pathway, where in the presence of NaOAc, [Cp*RhCl2]2
generates a [Cp*Rh(2-OAc)L]+ species. Coordination of 2-
phenylpyridine leads to C–H activation via deprotonation by the
acetate ligand as the aryl group bonds to the rhodium.12 Each of
the C–H activated complexes were generated by reaction of
[Cp*RhCl2]2 with the substituted 2-phenylpyridines, 1a-i, in the
presence of sodium acetate (Scheme 1). All products were
thoroughly characterized by NMR spectroscopy, elemental
analysis, and single-crystal structural determination. For 2c, 2e,
and 2g-i X-ray quality crystals were obtained by cooling a
saturated solution in methanol. For 2f, X-ray quality crystals
were obtained by diffusion of pentane into benzene. The
remaining complexes (2a, 2b, 2d) have previously published
crystal structures.17 Structural parameters will be commented
on in conjunction with equilibration data (vide infra).
Cu(OAc)2 for the synthesis of indoles6 and isoquinolines.7
In the 1980’s, Ryabov used kinetics to examine the
mechanism of cyclometallation of dimethylbenzylamine by
palladium acetate and concluded that a coordinated acetate
deprotonated a ligated amine while forming the Pd-aryl bond.8
A Hammett rho value of +1.4 was seen for the rate of activation,
as electron-withdrawing substituents resulted in a higher rate of
reaction. This result is similar to the related directed
functionalizations using lower oxidation state metals that
operate via C–H oxidative addition.9 The electrophilic cleavage
of the aromatic C–H bond adjacent to a coordinating functional
group using acetate as base and Ru, Rh, and Ir was studied
-
extensively by Davies,10 13 and has come to be referred to as
‘concerted metallation-deprotonation’, or CMD.14
Our group has examined the kinetics of concerted
metallation-deprotonation of arylimines with electron-donating
and –withdrawing groups at Cp*Rh and Cp*Ir centers, and
found that C-H activation proceeds by a [Cp*M(OAc)L]+
fragment.15 It was found that the C–H activation was reversible,
slowly, with acetic acid but was much more rapid if
trifluoroacetic acid was added. This observation is consistent
with ortho-deuteration of unreacted substrate seen in catalytic
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When C–H activated complex 2a is exposed to 4-(2-
Page 2 of 6
Scheme 1.
1
2
3
4
5
6
7
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pyridinyl)anisole, 1b, two new peaks slowly appear: one
corresponding to phenylpyridine substrate 1a, and one
corresponding to the C–H activated complex 2b generated via
exchange. Over the next few days the reaction was heated to 40
°C and the equilibrium constant was calculated from the
integrations of these resonances (Figures 1a and S10 to S17).
To ensure this exchange had reached equilibrium, a similar
experiment was performed starting from the opposite side of the
equilibrium, in this case combining C–H activated complex 2b
with phenylpyridine 1a (Figure 1b). In this way the equilibrium
was approached from both the left and the right, and the reaction
is guaranteed to be at equilibrium if the same Keq is observed.
N
NaOAc
MeOH
Cl
Rh
+ [Cp*RhCl2]2
N
1a
1e
R=H,
R=Cl,
R=CN,
R=Me,
R
1b
1c
1f
1g
1h
R=OMe,
R=CF3,
i
2a-i
1d
R= Bu,
R=F,
R= Pr,
R
t
1i
Equilibration Experiments. As earlier studies indicated that
C–H activation by the CMD process is reversible, equilibrium
constants for exchange of one substrate for another should be
measurable (eq 1). In Figure 1, the iminyl region of the 1H NMR
spectrum is shown for the equilibration of parent complex 2a
and 4-(2-pyridinyl)anisole 1b. Here, 2a was prepared in situ
using [Cp*RhCl2]2 and 1 equiv phenylpyridine in the presence
of a 5-fold excess of sodium acetate. Once formation of 2a was
complete, 1 equiv of 1b was added. The iminyl signals are
distinct for all 4 species involved in this equilibrium and appear
as doublets. The iminyl signal for 2a appears at  8.77 and the
corresponding signal for unactivated substrate 1b appears at 
8.51. Similarly, 2b has an iminyl doublet at  8.69, and the
unactivated substrate 1a appears at  8.57.
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In many cases, for inconsistant and unknown reasons,
equilibration from both directions did not reach the same
equilibrium position. Moreover, in the rare cases that these
reactions did reach the same point of equilibration they took
weeks to months to reach equilibrium. The 5-fold excess of
NaOAc used to prepare 2a drives the C–H activation to
completion and produces only a small amount of acetic acid in
the process. It was hypothesized that the long equilibration time
was because this small amount of acetic acid produced is not
sufficient to catalyze the reverse C–H activation to completion.
Therefore, a 5-fold excess of acetic acid was added to the
reaction following the formation of 2a. This 1:1 sodium acetate
: acetic acid buffer allows for both the forward and reverse
reactions to go to completion more rapidly, typically 40-50 hrs.
While the mechanism of the exchange was not examined in
detail, the above observation is consistent with a pathway
involving the microscopic reverse of the way these compounds
were formed: exchange of chloride for acetic acid followed by
protonation of the Rh-aryl bond to liberate phenylpyridine and
product [Cp*Rh(OAc)]+, which then activates the added
substituted phenylpyridine via CMD. Under reaction conditions
(acetate buffer in methanol solvent), only the starting materials
and products are observed – the pyridines 1a-i are not
protonated, nor are the chloride ligands replaced in compounds
2 (See Supporting Information, Fig. S27).
Keq
N
N
Cl
Cl
Rh
Rh
(1)
+
+
N
N
OMe
1b
1a
2a
2b
OMe
Similar experiments were performed with the remaining
substrates. In some cases the iminyl NMR resonances of a
substrate or metallacycle overlap with one another. In these
cases, the equilibrium was measured relative to another
substrate where there was no overlap of the iminyl resonances,
and then this Keq was referred back to the parent phenylpyridine
Keq. These equilibrium constants are listed in Table 1. As can
be seen, the Keq values vary only slightly, with substrates with
electron-withdrawing groups being favored.
Equilibration experiments were attempted with additional
electron-rich substrates, however amines were not chemically
compatible with this equilibration experiment. For the
corresponding dimethylamino substrate, with the 1:1 sodium
acetate acetic acid buffer, both protonated and deprotonated
amines in both the substrate and the C–H activated complex
were observed to equilibrate. Due to the complexity of these
equilibria, it was not possible to collect meaningful Keq data.
The G values for these equilibria with 2a can be obtained
from the Keq values, and are also listed in Table 1. It was found
that there is a reasonably good correlation of log Keq with the
Hammett m-value for the para substituent on the
phenylpyridine (Fig. 2). The correlation with m indicates that
the electron-donating/withdrawing power of the substituent is
responsible for affecting the equilibrium. The  value of +1.34
(20) indicates that electron withdrawing groups favor a shift of
Figure 1. Equilibration of 2a + 1b with 2b + 1a (a) approaching
from the left and (b) approaching from the right.
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the equilibrium toward activation of that phenylpyridine
Information, Fig. S28), and no trend was seen between
homolytic Rh-C bond strengths and the homolytic DC-H (see
Fig. S32). . The polar nature of these C–H activations suggested
that the Rh–C bond strengths in the metallacycle products may
correlate better to the heterolytic C–H bond strengths, which
were also calculated B3LYP/6-311g* level of theory from the
anions 4a-i (see Supporting Information). A plot of the
homolytic Drel(Rh-C) vs. these heterolytic C–H bonds strengths
showed only a modest correlation (see Fig. S31) with a slope of
+0.11 (R2 = 0.88).
1
substrate.
2
3
4
5
6
7
8
9
Table 1. Measured Keq of 4-R-(2-pyridyl)arene substrates
relative to 2-phenylpyridine in methanol at 40 °C in the
presence of 0.05 M NaOAc/HOAc buffer (eq 1).a
ΔG0
kcal/mol
dRh–aryl
Å
dRh–N
Å
Substrate
Keq
R = H, 1ab
1.0
0.0
2.0361 (13) 2.0917 (12)
2.0209 (15) 2.1000 (15)
2.022 (2) 2.099 (2)
2.024 (2) 2.1038 (18)
1.994 (11) 2.172 (9)
2.025 (3) 2.094 (2)
The data are scattered, as the range of Drel(Rh-C) spans only
~2 kcal/mol range, and is comparable to the errors in the Keq
measurements. The fact that the slope is far less than 1.0
indicates that one pays a higher price for breaking a strong C–
H bond than one gains in the strength of the Rh–C bond that is
formed. Therefore, substrates with larger heterolytic C–H bond
strengths (i.e., less acidic) are less favorable to activate than
substrates with weaker heterolytic C–H bond strengths. Since
substrates with electron-withdrawing groups have weaker
heterolytic bond strengths, cyclometallation of these substrates
is preferred.
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R = OMe, 1bc 2.0 (8)
–0.44 (25)
R = CF3, 1c 6.3 (25) –1.14 (25)
R = F, 1dd
R = Cl, 1ee 10.3 (8)
7.3 (8)
–1.24 (7)
–1.45 (5)
R = CN, 1f 9.1 (36) –1.37 (30)
R = Me, 1g
R = iPr, 1h
R = tBu, 1i
1.5 (8)
1.7 (8)
1.8 (8)
–0.24 (34) 2.0208 (16) 2.0955 (13)
2.032 (6) 2.099 (5)
2.032 (3) 2.097 (2)
–0.35 (28)
–0.36 (28)
A recent report by Davies and Macgregor investigated
similar substituent effects on the CMD activation of 1-
phenylpyrazoles by [Cp*MCl2]2 (M = Rh, Ir) in the presence of
carboxylate.19 These studies showed that substrates with
electron-donating substituents were kinetically favored, but that
substrates with electron-withdrawing substituents were
thermodynamically favored, as also seen here. A plot of log Keq
vs. m,p showed a slope of 1.46 with R2 = 0.90, comparable to
what is seen in Figure 2.
aNumbers in parentheses are standard deviations. Bond distances
b
observed in X-ray structures of metallacycles 2a-2i. X-ray data
c
d
from ref. 5. X-ray data from ref. 16. X-ray data from ref. 18.
ecrystal is an inversion twin - distances not reliable.
It is also worth comparing these results to those found earlier
by Ryabov in his investigations of cyclometallation of N,N-
dimethylbenylamines by Pd(OAc)2.20 In these studies, a dimeric
acetate-bridged metallacycle underwent exchange with
deuterated N,N-dimethylbenzylamine (eq 3), and acetic acid
was necessary to carry out the protonation. Under these
conditions, the protonolysis was the rate determining step for
the exchange, and it was noted that Pd(II) will orthometallate
preferably a ligand with a stronger electron-withdrawing group,
as seen here.
1.2
y = 1.34x + 0.31
R² = 0.88
Cl
1.0
0.8
0.6
0.4
0.2
0.0
CN
F
CF3
tBu
OMe
iPr
NMe2
NMe2
Me2
N
Me2
N
Me
D2C
D2C
Cl
Cl
Pd
+
Pd
+
-0.15
0
0.15
0.3
0.45
0.6
σm
(3)
2
2
d5
R
Figure 2. Hammett plot of log Keq values for equilibria vs. m.
d5
R
Relative Rhodium-Carbon Bond Strengths. Homolytic bond
strengths for the corresponding ortho-aryl C–H bond that
undergoes activation were calculated at the B3LYP/6-311g*
level of theory by comparing energies of the substituted
phenylpyridines 1a-i vs. the corresponding radicals 3a-i. The
relative rhodium-carbon homolytic bond strengths, Drel, can be
estimated by eq 2, where G corresponds to the experimentally
measured equilibrium constant for exchanging one substrate for
unsubstituted 2-phenylpyridine as in eq 1, and D(CH)H and
D(CH)R represent the homolytic C–H bond strengths of 2-
phenylpyridine and the substituted 2-phenylpyridine
respectively. S for the equilibration is anticipated to be zero.
CONCLUSIONS
Here we present evidence for the equilibration of para-
substituted phenylpyridines in the concerted metallation-
deprotonation
reaction
with
pentamethylcyclopentadienylrhodium(III) in the presence of
NaOAc/HOAc buffer. The results show that substrates with
electron-withdrawing groups present in the para-position are
preferred thermodynamically, as seen with palladium
metallacycles.20 This result is somewhat unexpected, as it might
have been expected that the electrophilic CMD reactions would
prefer substrates with electron-donating substituents. These
results can be explained in that the heterolytic C–H bond
strengths are weaker for the substrates with electron-
withdrawing groups, and it is the breaking of this C–H bond that
dominates the thermodynamics.
Drel = G – [D(CH)H – D(CH)R]
(2)
However, calculation of the ortho C–H homolytic bond
strengths in 1a – 1i at the B3LYP/6-311g* level of theory
showed little variation at all (1 kcal/mol; see Supporting
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(25 mL). The product was purified via column chromatography
Page 4 of 6
EXPERIMENTAL SECTION
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2
3
4
5
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7
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(1:1 hex:EtOAc to 100% EtOAc) and was isolated as a red-
orange solid (98.2 mg 90.0%).1H NMR (400 MHz, CDCl3) δ
8.76 (d, J = 5.6 Hz, 1 H), 8.06 (s, 1 H), 7.82 (d, J = 8.0 Hz, 1
H), 7.75 (td, J = 7.8, 1.4 Hz, 1 H), 7.66 (d, J = 8.1 Hz, 1 H),
7.29 (d, J = 8.1 Hz, 1 H), 7.22 (td, J = 6.4, 5.6, 1.5 Hz, 1 H),
1.63 (s, 15 H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.5 (d, J
= 32.8 Hz, Rh-C), 168.8, 164.1, 151.6, 147.1, 137.6, 133.3,
133.3, 123.2, 123.1, 120.0, 96.4 (d, J = 6.1 Hz, Rh-C), 9.3. Anal.
Calcd for C22H22NF3ClRh: C, 53.30; H, 4.47; N, 2.83. Found:
C, 53.29; H, 4.16; N, 2.30.
General Information. RhCl3 was obtained from Pressure
Chemical Co. and [Cp*RhCl2]2 was synthesized using literature
methods.21
2-(4-trifluoromethylphenyl)pyridine,
fluorophenyl)pyridine, 2-(4-chlorophenyl)pyridine,
2-(4-
4-
(pyridine-2-yl)benzonitrile, 2-(4-methylphenyl)pyridine, 2-(4-
isopropylphenyl)pyridine, and 2-(4-tertbutylphenyl)pyridine
were synthesized according to literature procedures.22 2-
phenylpyridine and 4-(2-pyridinyl)anisole were obtained from
TCI America and used without further purification. Sodium
acetate was obtained from JT Baker and used without further
purification. Methanol was purchased from Fischer Chemical,
dried over 3 Å molecular sieves, and filtered through PTFE
syringe filters prior to use. Methanol-d3 was obtained from
Cambridge Isotope Labs Inc., dried over 3 Å molecular sieves,
and transferred by vacuum distillation directly into J-Young
NMR tubes for use. Chloroform-d was obtained from
Cambridge Isotope Labs Inc., dried over 3 Å sieves, and filtered
through a plug of Celite prior to use. All reactions were
performed under N2 atmosphere; however once the reactions
were complete, further isolation of compounds was performed
with no precaution to avoid atmosphere as the compounds are
stable. All NMR spectra were collected using an Avance 400
NMR Spectrometer. Elemental analyses were determined at the
CENTC Elemental Analysis Facility at the University of
Rochester using a PerkinElmer 2400 Series II analyzer
equipped with a PerkinElmer Model AD-6 autobalance by Dr.
William W. Brennessel.
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Preparation of 2d.18 The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
fluorophenyl)pyridine (0.22 mmol, 38 mg 1.1 equiv), and
sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25
mL). The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) and was isolated as a red-orange
solid (81.0 mg, 82.6%). 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 5.6 Hz, 1 H), 7.70 (dd, J = 6.6, 1.7 Hz, 2 H), 7.58 (dd, J =
8.5, 5.3 Hz, 1 H), 7.50 (dd, J = 8.8, 2.6 Hz, 1 H), 7.12 (td, J =
6.0, 2.4 Hz, 1H), 6.75 (td, J = 8.7, 2.6 Hz, 1 H), 1.62 (s, 15 H).
13C{1H} NMR (101 MHz, CDCl3) δ 181.4 (d, J = 29.1 Hz, Rh-
C), 164.5, 162.1, 151.3, 140.0, 137.3, 124.7 (d, J = 8.7 Hz, F-
C), 122.8 (d, J = 101.2 Hz, F-C), 121.9, 119.1, 110.1 (d, J =
96.3 Hz, F-C), 96.2 (d, J = 6.2 Hz, Rh-C), 9.2.
Preparation of 2e. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
chlorophenyl)pyridine (0.22 mmol, 41 mg 1.1 equiv), and
sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25
mL). The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) and was isolated as a red-orange
solid (85.0 mg, 83.6%). 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 5.6 Hz, 1 H), 7.75 (d, J = 2.0 Hz, 1 H), 7.70 (d, J = 4.1 Hz,
2 H), 7.50 (d, J = 8.1 Hz, 1 H), 7.17 – 7.11 (m, 1 H), 7.02 (dd,
J = 8.2, 2.0 Hz, 1 H), 1.62 (s, 15 H). 13C{1H} NMR (101 MHz,
CDCl3) δ 180.0 (d, J = 33.3 Hz Rh-C), 164.5, 151.4, 142.3,
137.4, 136.2, 135.8, 124.3, 123.2, 122.4, 119.3, 96.2 (d, J = 6.0
Hz, Rh-C), 9.3(C5Me5). Anal. Calcd for C21H22NCl2Rh: C,
54.57; H, 4.80; N, 3.03. Found: C, 52.94; H, 4.51; N, 2.94.
Synthesis. Preparation of 2a.5 A mixture of [Cp*RhCl2]2
(0.10 mmol, 61 mg, 0.50 equiv), 2-phenylpyridine (0.22 mmol,
34 mg, 1.1 equiv), and sodium acetate (0.40 mmol, 32 mg, 2.0
equiv) was stirred in (dry) methanol (25 mL), under a nitrogen
atmosphere for 4 h. The solvent was evaporated to dryness on a
rotovap. The crude material was purified via column
chromatography (1:1 hex:EtOAc to 100% EtOAc) to give an
orange -red solid (70.3 mg, 74.7%). 1H NMR (400 MHz,
CDCl3) δ 8.73 (d, J = 5.4 Hz, 1 H), 7.81 (d, J = 7.8 Hz, 1 H),
7.75 (d, J = 7.8 Hz, 1 H), 7.69 (ddd, J = 8.2, 7.2, 1.6 Hz, 1 H),
7.60 (dd, J = 7.7, 1.4 Hz, 1 H), 7.24 (td, J = 7.4, 1.5 Hz, 1 H),
7.12 (ddd, J = 7.2, 5.6, 1.5 Hz, 1 H), 7.05 (td, J = 7.4, 1.1 Hz, 1
H), 1.62 (s, 15 H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.6
(d, J = 32 Hz, Rh-C), 165.5, 151.4, 143.8, 137.1, 137.0, 130.5,
123.5, 122.8, 122.0, 119.1, 96.0 (d, J = 6.3 Hz, Rh-C), 9.3 (s,
C5Me5).
Preparation of 2b.16 The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.50 equiv), 4-(2-
pyridinyl)anisole (0.22 mmol, 41 mg 1.1 equiv), and sodium
acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25 mL).
The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) to give an orange-red solid (80.1
mg, 79.6%). 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 5.6 Hz,
1 H), 7.69 – 7.58 (m, 2 H), 7.54 (d, J = 8.5 Hz, 1 H), 7.36 (d, J
= 2.5 Hz, 1 H), 7.04 (td, J = 6.2, 2.3 Hz, 2 H), 6.61 (dd, J = 8.5,
2.5 Hz, 1 H), 3.90 (s, 3 H), 1.63 (s, 15 H). 13C{1H} NMR (101
MHz, CDCl3) δ 180.8 (d, J = 32 Hz, Rh-C), 165.3, 160.6, 151.2,
137.0, 137.0, 124.6, 121.3, 121.0, 118.5, 109.4, 96.0 (d, J = 6.3
Hz, Rh-C), 55.3, 9.3 (s, C5Me5). Anal. Calcd for
C22H25NOClRh; C, 57.20; H, 5.50; N, 3.06. Found: C, 57.38; H,
5.50; N, 2.84.
Preparation of 2f. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 4-(pyridine-
2-yl)benzonitrile (0.22 mmol, 40 mg 1.1 equiv), and sodium
acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25 mL).
The product was purified as an orange-red solid via column
chromatography (1:1 hex:EtOAc to 100% EtOAc) and was
isolated as a red orange solid (69.6 mg, 69.9% ).1H NMR (400
MHz, CDCl3 δ 8.71 (d, J = 5.6 Hz, 1 H), 7.92 – 7.63 (m, 3 H),
7.52 (d, J = 8.2 Hz, 1 H), 7.15 (q, J = 4.9 Hz, 1 H), 7.03 (d, J =
8.1 Hz, 1 H), 1.62 (s, 15 H).13C{1H} NMR (101 MHz, CDCl3)
δ 178.3 (d, J = 34.3 Hz), 163.6, 151.7, 148.0, 140.0, 137.7,
126.6, 123.7, 123.1, 120.4, 120.1, 112.9, 96.5 (d, J = 7.0 Hz Rh-
C), 9.3 (C5Me5). Anal. Calcd for C22H22N2ClRh: C, 58.36; H,
4.99; N, 6.19. Found: C, 58.04; H, 4.71 N, 6.06.
Preparation of 2g. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
methylphenyl)pyridine (0.22 mmol, 37 mg 1.1 equiv), and
sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25
mL). The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) and was isolated as an orange-red
solid (78.1 mg, 80.4%) . 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 5.5 Hz, 1 H), 7.81 – 7.57 (m, 2 H), 7.48 (d, J = 7.8 Hz, 1 H),
7.07 (t, J = 6.3 Hz, 1 H), 6.86 (d, J = 7.7 Hz, 1 H), 2.40 (s, 3 H),
1.62 (s, 15 H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.7 (d, J
Preparation of 2c. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
trifluoromethylphenyl)pyridine (0.22 mmol, 49 mg 1.1 equiv),
and sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol
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The Journal of Organic Chemistry
= 32 Hz, Rh-C), 165.6, 151.3, 141.2, 140.3, 137.6, 137.0, 124.0,
123.3, 121.5, 118.8, 95.9 (d, J = 6.0 Hz, Rh-C), 21.9, 9.3
(C5Me5). Anal. Calcd for C22H25NClRh: C, 59.81; H, 5.70; N,
3.17. Found: C, 59.96; H, 5.62; N, 2.96.
Computational Information. Geometry optimizations and
frequency calculations were performed on phenylpyridines 1a-
i, radicals 3a-i, and anions 4a-i using the Gaussian 09 software
package, at the B3LYP/6-311g* level of theory. Homolytic and
heterolytic C–H bond dissociation energies were calculated
with from these enthalpies.
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2
3
4
5
6
7
8
Preparation of 2h. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
isopropylphenyl)pyridine (0.22 mmol, 43 mg 1.1 equiv), and
sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25
mL). The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) and was isolated as an orange-red
solid (72.5 mg, 70.1%). 1H NMR (400 MHz, CDCl3) δ 8.67 (d,
J = 5.5 Hz, 1 H), 7.72 – 7.59 (m, 2 H), 7.50 (d, J = 7.9 Hz, 1 H),
7.05 (ddd, J = 7.2, 5.6, 1.7 Hz, 1 H), 6.90 (dd, J = 7.9, 1.7 Hz,
1 H), 2.95 (hept, J = 6.9 Hz, 1 H), 1.60 (s, 15 H), 1.30 (dd, J =
6.9, 2.9 Hz, 6 H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.7 (d,
J = 32.3 Hz Rh-C), 165.5, 151.3, 150.9, 141.6, 137.0, 135.2,
123.4, 121.5, 121.2, 118.8, 96.0, 95.9 (d, J = 7.0 Hz Rh-C),
34.6, 24.7, 23.7, 9.3 (C5Me5). Anal. Calcd for C24H29NClRh: C,
61.35; H, 6.22; N, 2.98. Found: C, 59.35; H, 6.37; N, 3.35.
ASSOCIATED CONTENT
Supporting Information.
The Supporting Information is available free of charge on the ACS
Publications website at DOI: 10.1021/acs.joc.xxxxxxxxx.
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Detailed information regarding NMR spectra, X-ray data,
computational analysis, (PDF)
X-ray data for compound 2c (CIF)
X-ray data for compound 2e (CIF)
X-ray data for compound 2f (CIF)
X-ray data for compound 2g (CIF)
X-ray data for compound 2h (CIF)
X-ray data for compound 2i (CIF)
Preparation of 2i. The reaction was carried out as with 2a,
using [Cp*RhCl2]2 (0.10 mmol, 61 mg, 0.5 equiv), 2-(4-
tertbutylphenyl)pyridine (0.22 mmol, 46 mg 1.1 equiv), and
sodium acetate (0.40 mmol, 32 mg, 2.0 equiv) in methanol (25
mL). The product was purified via column chromatography (1:1
hex:EtOAc to 100% EtOAc) and was isolated as an orange-red
solid (75.5 mg 70.6%). 1H NMR (400 MHz, CDCl3) δ 8.70 (d,
J = 5.4 Hz, 1 H), 7.86 (d, J = 1.7 Hz, 1 H), 7.68 (ddd, J = 13.7,
8.6, 6.9 Hz, 2 H), 7.58 – 7.48 (m, 1 H), 7.09 (tdd, J = 7.1, 4.3,
2.7 Hz, 2 H), 1.62 (s, 15 H), 1.40 (s, 9 H). 13C{1H} NMR (101
MHz, CDCl3) δ 178.5 (d, J = 31.8 Hz, Rh-C), 165.5, 152.8,
151.3, 141.2, 137.0, 133.7, 123.1, 121.5, 120.4, 118.8, 97.0 (d,
J = 6.4 Hz, Rh-C), 35.3, 31.6, 9.3 (C5Me5). Anal. Calcd for
C25H31NClRh: C, 62.05; H, 6.55; N, 2.90. Found: C, 61.54; H,
6.38; N, 2.93.
Full structural details are available from the Cambridge
Crystallographic Data Centre (CCDC #1936428-1936433).
AUTHOR INFORMATION
Corresponding Author
*E-mail: jones@chem.rochester.edu
ORCHID
William D. Jones: 0000-0003-1932-0963
Andrew VanderWeide: 0000-0001-9486-3170
William W. Brennessel: 0000-0001-5461-1825
Notes
The authors declare no competing financial interest.
Example Equilibration Experiment. C–H activated
complexes for equilibration experiments were generated in situ
from stock solutions to improve reproducibility. 1 mL of a 5
mM (0.5 equiv, 0.005 mmol) solution of [Cp*RhCl2]2 in
methanol, 0.5 mL of a 20 mM (1 equiv, 0.01mmol) solution of
2-phenylpyridine in methanol, and 0.5 mL of a 100 mM (5
equiv, 0.05 mmol) solution of sodium acetate in methanol, were
charged into a J-Young type NMR tube. Protonated methanol
was removed in vacuo, and approximately 0.5 ml of deuterated
methanol was transferred into the NMR tube on a vacuum line.
Once complete disappearance of the unactivated 2-
ACKNOWLEDGMENT
We thank the National Science Foundation, Chemistry-Physical
Sciences: F.02 (award #CHE-1762350) for support for this work.
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