Steric and electronic effects influencing β-aryl elimination in the Pd-catalyzed carbon-carbon single bond activation of triarylmethanols

Article abstract of DOI:10.1021/jo302592g

An analysis of the palladium-catalyzed activation of carbon-carbon single bonds within triarylmethanols has led to a greater understanding of factors influencing the β-aryl elimination process responsible for C-C bond cleavage. A series of competition reactions were utilized to determine that β-aryl elimination of aryl substituents containing ortho-substitution proceeds with significant preference to unsubstituted phenyl rings. Further experiments indicate that substrates containing either strongly donating or withdrawing substituents are cleaved from triarylmethanols more readily than relatively neutral species.

Full text of DOI:10.1021/jo302592g

Note
pubs.acs.org/joc
Steric and Electronic Effects Influencing β‑Aryl Elimination in the Pd-
catalyzed Carbon−Carbon Single Bond Activation of
Triarylmethanols
James R. Bour, Jacob C. Green, Valerie J. Winton, and Jeffrey B. Johnson*
Department of Chemistry, Hope College, Holland, Michigan 49423, United States
S
* Supporting Information
ABSTRACT: An analysis of the palladium-catalyzed activation of carbon−
carbon single bonds within triarylmethanols has led to a greater understanding
of factors influencing the β-aryl elimination process responsible for C−C bond
cleavage. A series of competition reactions were utilized to determine that β-aryl
elimination of aryl substituents containing ortho-substitution proceeds with
significant preference to unsubstituted phenyl rings. Further experiments
indicate that substrates containing either strongly donating or withdrawing
substituents are cleaved from triarylmethanols more readily than relatively
neutral species.
Scheme 1
espite the ubiquity of carbon−carbon single bonds in
virtually every aspect of organic chemistry, methods for
D
their controlled activation and functionalization remain largely
unrealized.1−3 Efforts to date rely upon the use of privileged
substrates, such as those containing strained rings4−6 or with
structures that enforce proximity of the metal to the targeted
C−C bond.7−9 Although the challenges are significant, limited
successes have been achieved,10−14 and the promise of general
and synthetically meaningful carbon−carbon bond activation
has the potential to greatly influence the means through which
complex molecules are synthesized.15−20
It is our belief that an increased understanding of the process
of carbon−carbon bond activation will assist in the rational
extension of known reactivity as well as the development of
new methodologies. Just as reactions utilizing carbon−carbon
single bond activation remain quite scarce, there have been very
few examples of mechanistic investigations of these trans-
formations within the context of a transition metal-catalyzed
process.21−23 As it is currently understood, single bond
activation occurs via one of two general methods: oxidative
addition or β-elimination. Our group has previously inves-
tigated a rhodium-catalyzed system shown to proceed via
oxidative addition,24,25 and for comparative purposes, we
initiated an investigation of the palladium-catalyzed β-aryl
elimination of triarylmethanols, first reported by Miura and co-
workers (Scheme 1).26−29 Herein we describe our efforts to
provide insight into the process of β-aryl elimination and the
factors that influence the course of this transformation.
oxidative addition, β-aryl elimination from a palladium alkoxide,
and reductive elimination to form biphenyl are all clearly
involved in this process. Due to complications arising from the
standard reaction conditions, particularly the heterogeneous
nature of the reaction mixture, a traditional kinetic study
proved intractable. Instead, a series of alternative mechanistic
investigations, primarily via competition reactions, were utilized
to develop a greater understanding of the nature of the
carbon−carbon bond activation step while simultaneously
providing insight into the overall catalytic cycle.
Our investigations began with an examination of the
influence of aryl halide on the reaction. Two aryl halides,
each present in a 1.2:1 excess to triphenylmethanol, were
reacted under otherwise standard conditions: Pd(OAc)2 (5 mol
%), PPh3 (20 mol %) and Cs2CO3 (3 equiv) in refluxing o-
xylene. After 16 h, the reaction mixture was analyzed by GC/
MS to determine the relative ratio of the two possible biaryl
species. The reaction of 3,5-bis(trifluoromethyl)-1-bromoben-
zene occurred in greater than 5:1 selectivity versus 4-
trifluoromethylbromobenzene, which in turn reacted with
greater than 50:1 selectivity over unsubstituted bromobenzene.
The series of aryl bromides and their respective reactivity is
provided in Scheme 2. These results illustrate that electron
deficient aryl halides undergo reaction with preference to their
electron rich counterparts. This trend is similar to the behavior
Congruent with our focus on the nature of the carbon−
carbon activation process was an interest in the reaction in the
context of catalysis. At the onset of this study, several reaction
sequences were envisioned as potential catalytic cycles for this
palladium-catalyzed process. Although the oxidation states and
the order of the elementary transformations are not
immediately obvious, the fundamental steps of aryl bromide
Received: November 28, 2012
Published: January 24, 2013
© 2013 American Chemical Society
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Note
Scheme 2
Scheme 4. Proposed Catalytic Cycle
of these species in oxidative addition,30,31 suggesting that this
fundamental transformation either limits the catalyst turnover
or reaches equilibrium prior to the turnover limiting step of
catalysis.32
A similar experiment was performed with an equimolar ratio
of p-trianisylmethanol (1.0 equiv) and triphenylmethanol (1.0
equiv) in the presence of 1.2 equiv of bromobenzene under
otherwise standard reaction conditions. Analysis of the product
mixture at approximately 50% conversion revealed a 2.7:1 ratio
of methoxybiphenyl to biphenyl. The differentiation between
the two species, which was also observed with other similar
competition reactions (vide infra), suggests that the cleavage of
the carbon−carbon bond occurs during, or prior to, the
turnover limiting step of catalysis.
In order to probe the reversibility of carbon−carbon bond
activation, a reaction was performed under standard reaction
conditions with the addition of exogenous 4,4′-dimethoxyben-
zophenone. The observation of methoxy-containing triarylme-
thanol or biphenyl species would provide evidence for
reversibility of the β-aryl elimination. After 16 h under
otherwise standard reaction conditions, benzophenone and
biphenyl were observed, but no sign of mixed methoxy-
containing species were observed (Scheme 3). These results
the determination of factors that influence the process of
carbon−carbon bond activation. To gain further insight on the
β-aryl elimination, a series of aryldiphenylmethanols were
prepared and subjected to palladium catalysis under standard
conditions.38 Upon reaction, several products can be formed:
activation of the carbon-aryl bond ultimately leads to
benzophenone (2) and a substituted biphenyl (5), whereas
activation of the carbon-phenyl bond leads to biphenyl (3) and
substituted benzophenone (6) (Scheme 5). These reactions
Scheme 5. Intramolecular Competition Reactions for
Examining Process of β-Aryl Elimination
Scheme 3. Probe of β-Aryl Elimination Reversibility
were quenched after 16 h and the relative propensity of aryl
cleavage versus phenyl cleavage was determined via GC/MS
analysis of the resulting product mixtures. The influence of
sterics upon β-aryl elimination was immediately apparent, as
aryl groups with ortho-substitution of any kind demonstrate a
dramatic propensity to cleave preferentially to the unsubstituted
phenyl ring (Table 1, entries 1−3). The extent of this
significant selectivity ranges from 29:1 for methyl substitution
to 114:1 for chloride substitution.39,40 While this effect is most
pronounced for species with Lewis basic ortho-substitution, the
significant selectivity observed with methyl substitution
suggests a purely steric contribution. X-ray structural data
from a bis(triethylphosphine)rhodium-triarylalkoxide complex,
an analogue of proposed intermediate B in Scheme 4, illustrates
a strong interaction between the metal center and a β-aryl
group prior to β-elimination.40 This coordination event serves
to orient the aryl ring in a parallel fashion to the phosphine
ligands while slightly lengthening the carbon−carbon bond
destined for cleavage. In the presence of aryldiphenylmethanols,
coordination of the β-aryl group with ortho-substitution may
effectively minimize interaction of the ortho-group with the
phosphine ligands as well as the other phenyl rings, thus
promoting selective cleavage.
suggest that β-aryl elimination is either an irreversible process
or that the resulting diaryl palladium complex is not sufficiently
stable to allow ketone exchange and insertion prior to further
reductive elimination. In a similar fashion, the exposure of a
substituted biphenyl to standard reaction conditions leads to no
evidence of carbon−carbon bond cleavage, suggesting that
reductive elimination is irreversible.
The results from the above experiments are most consistent
with a reaction sequence that begins with reversible oxidative
addition of the palladium(0) species with the aryl bromide to
form intermediate A (Scheme 4). Following ligand exchange,
irreversible β-aryl elimination generates benzophenone and
palladium diaryl species C, which in turn undergoes reductive
elimination to generate biphenyl. Because reductive elimination
to form sp2−sp2 carbon−carbon bonds typically occurs rapidly,
particularly under the high temperatures utilized in this study, it
is assumed that this step occurs rapidly relative to β-aryl
elimination.33−37
In contrast to the steric effects, variation of the electronic
nature of the aryl rings resulted in only a subtle influence on
selectivity of β-aryl elimination (Table 1). A series of
substituents, varying from electron deficient 3,5-bis-
(trifluoromethyl)phenyl to electron rich 4-dimethylaminophen-
yl were prepared and subjected to the reaction conditions.41
The observed selectivity was significantly attenuated relative to
With a schematic representation of the catalytic cycle in
hand, we turned our attention to the primary goal of this study,
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Table 1. Intramolecular Competition Reactions Utilizing
Aryldiphenylmethanol Substrates
Table 2. Intramolecular Competition Reactions Utilizing
Fluorinated Aryldiphenylmethanol Substrates
starting
material
product
ketone
starting
material
product
ketone
transfer ratio
cd
transfer ratio
cd
a
b
a
b
,
,
entry
Ar
4
6
Ar:Ph
entry
Ar
4
6
Ar:Ph
e
1
2-Cl−C6H4
4a
4b
4c
4d
4e
4f
6a
6b
6c
6d
6e
6f
114 13:1
50 5:1
1
2
3
4
5
6
7
8
9
2-F−C6H4
3-F−C6H4
4-F−C6H4
2,5-F2−C6H3
3,4-F2−C6H3
2,6-F2−C6H3
3,5-F2−C6H3
3,4,5-F3−C6H2
C6F5
4m
4n
4o
4p
4q
4r
6m
6n
6o
6p
6q
6r
76 2:1
4.0 1.1:1
3.5 1.1:1
190 33:1
8.1 1.4:1
240 30:1
11 1:1
2
2-OMe−C6H4
2-Me−C6H4
3-Me−C6H4
3-OMe−C6H4
4-Me−C6H4
4-NMe2−C6H4
4-CF3−C6H4
4-Cl−C6H4
3
29 2:1
4
0.9 0.1:1
1.0 0.1:1
1.2 0.3:1
2.9 0.2:1
3.0 0.5:1
2.6 0.1:1
3.0 0.3:1
6.0 0.4:1
3.0 0.2:1
5
6
7
4g
4h
4i
6g
6h
6i
4s
6s
8
4t
6t
>500 10:1
>500 10:1
9
4u
6u
a
10
11
12
4-OMe−C6H4
3,5-(CF3)2−C6H3
4j
6j
Reactions performed in refluxing o-xylene with [4] = 0.167 M, [Ph-
Br] = 0.40 M, [Pd(OAc)2] = 8.3 mM, [PPh3] = 0.043 M, [Cs2CO3] =
0.22 M for 16 h. Formed in addition to unsubstituted benzophenone.
Determined by GC/MS analysis of three trials. The error represents
the standard deviation. Values account for 2:1 ratio of Ph:Ar
substituents in 4.
4k
4l
6k
6l
b
3,4,5-(OMe)3−
c
C6H2
d
a
Reactions performed in refluxing o-xylene with [4] = 0.167 M, [Ph-
Br] = 0.40 M, [Pd(OAc)2] = 8.3 mM, [PPh3] = 0.043 M, [Cs2CO3] =
0.22 M for 16 h. Formed in addition to unsubstituted benzophenone.
Determined by GC/MS analysis of three trials. The error represents
b
c
bromobenzene (Scheme 6). As shown in Table 2, entry 2, 3-
fluoro-substituted substrate 4n undergoes reaction and
d
the standard deviation. Values account for 2:1 ratio of Ph:Ar
e
substituents in 4. Determined by analysis of two trials.
Scheme 6. Effects of Aryl Bromide Electronics on Selectivity
that observed for compounds containing ortho substitution,
peaking with the bis(trifluoromethyl)-substituted substrate 4k
in which the aryl group is transferred with 6:1 selectivity over
the phenyl ring. Compounds with electronically neutral
substitutions (entries 4−6) result in nearly statistical aryl
transfer. While there is a general selectivity for cleavage of the
more electron deficient aryl ring relative to more neutral
species, electron rich aryl rings are also cleaved more readily
than neutral substituents, up to 3:1 with the para-methoxy
substituted aryl (entry 10), with no clear correlation between
the electronic character of the aryl substituents and
corresponding migratory aptitude.42 This deviation from
linearity suggests that selectivity is not purely governed by
electronic factors and may be affected by Lewis acid−Lewis
base interactions between these triarylmethanol substrates and
other reaction components or variations in C−C bond length
of the substrates.
To minimize the effect of coordination events and other
unforeseen variables upon the selectivity of aryl group transfer,
a similar set of competition reactions was performed using a
series of fluorine substituted aryldiphenylmethanol substrates.
Results from these experiments are provided in Table 2. As
with previous examples, the significant influence of the ortho
substitution is readily apparent, with the further observation
that this effect appears to be cumulative with the incorporation
of a second fluorine substitution (entries 1 and 6). Specifically,
the selectivity of the C−C activation of ortho-fluorinated
compounds is attributed to stabilization of the intermediate Pd-
aryl species in analogy to that observed for related rhodium-aryl
species. Calculations have quantified this stabilization to be
approximately 5.5 kcal/mol for each ortho C−F bond versus the
unsubstituted phenyl ring.43,44 Beyond ortho-substitution, the
results contained in the remainder of Table 2 clearly
demonstrate that more electronic deficient aryl rings more
readily undergo β-aryl elimination and subsequent coupling
than do relatively more electron rich species.
coupling with bromobenzene with cleavage of the fluorinated
aryl ring favored by a 4:1 ratio. The use of 4-trifluoromethyl-1-
bromobenzene, however, resulted in a 1.2:1 product distribu-
tion of 6n and 2, indicating a reversal of selectivity as this ratio
of aryl to phenyl cleavage drops to 0.6:1. This ratio further
decreases to 0.2:1 with 3,5-bis(trifluoromethyl)-1-bromoben-
zene. These results clearly indicate that the aryl bromide
interacts with the palladium catalyst prior to β-aryl elimination
with the triarylmethanol substrate, lending further support for
the proposed catalytic cycle, and also demonstrates that the
electronic character of the metal center and its ligands
significantly influence the selectivity of the carbon−carbon
bond activation.45
This work has provided insight into the catalytic cycle of this
palladium-catalyzed transformation, suggesting that the turn-
over limiting β-aryl elimination process follows reversible aryl
bromide oxidative addition. Results from these intramolecular
competition reactions indicate that ortho-substituted triarylme-
thanol substrates have a significant propensity to undergo β-aryl
elimination and significantly electron deficient or electron rich
species undergo C−C cleavage more readily than neutral
substituents. These results present a potential strategy for the
generation of palladium-aryl species with sterically hindered
ortho-substitution and promise a means of utilizing these
difficult substituents in coupling processes.
EXPERIMENTAL SECTION
General Methods. Unless otherwise indicated, all reactions were
carried out under an atmosphere of nitrogen or argon in oven-dried
■
The selectivity of β-aryl elimination from aryldiphenylme-
thanols was also examined with aryl halides other than
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Note
glassware with magnetic stirring. Solvents, including toluene,
tetrahydrofuran, and diethyl ether were purged with argon and passed
through two columns of neutral alumina or molecular sieves. Starting
materials are commercially available and used with further purification.
Substituted aryldiphenylmethanol substrates (4) were commercially
available or prepared via Grignard reaction of the corresponding
benzophenone (vide infra). Those that are not previously reported are
fully characterized. Pd(OAc)2 was obtained commercially and utilized
mg, 0.025 mmol) were combined in a 250 mL round-bottom flask. A
condenser was attached to the flask and a rubber septum added to the
top of the condenser. The condenser/round-bottom flask system was
evacuated and refilled with argon (4×). To this flask, 3 mL of
anhydrous o-xylene and bromobenzene (2.5 equiv, 130 μL, 1.2 mmol)
were added via syringe. The flask was heated in an oil bath with a
temperature of 150 °C. After 16 h the reaction was removed from the
oil bath, cooled to room temperature and quenched with 10 mL of 2
M HCl (aq). Following extraction with Et2O (2× 10 mL), the organic
layers were combined, dried over MgSO4 and concentrated under
reduced pressure. Analysis was carried out via GC/MS and
assignments were made by comparison to commercially available
standards.
1
without further purification. H and 13C spectra were obtained using
standard acquisition parameters and referenced to TMS. 19F NMR
spectra were obtained using standard acquisition parameters and
referenced to an external standard of fluorobenzene. All HRMS
measurements were made using ESI with TOF detection.
General Procedure for Formation of Aryldiphenylmetha-
nols. This procedure will be illustrated with a specific example. 2,5-
Difluorobenzophenone (0.90 g, 4.1 mmol) was added to an oven-dried
50 mL round-bottom flask containing a stir bar, sealed with a septum
and evacuated and refilled with N2 (3×). Via syringe, 15 mL of
anhydrous THF was added. Phenylmagnesium bromide (3 M solution
in THF, 1.7 mL, 5.1 mmol) was added dropwise via syringe over ∼15
min. The reaction was allowed to stir overnight, at which point it was
quenched with 30 mL of 1H HCl (aq). The mixture was extracted
with Et2O (3× 20 mL) and the combined organic layers were washed
with sat. NaHCO3 (aq), H2O, and brine, then dried over MgSO4 and
concentrated. The resulting crude solid was recrystallized from
hexanes to form the product as a white crystalline solid in 68% yield
(0.83 g, 2.8 mmol).
Procedure for Intermolecular Competition Experiments
Using Two Aryl Bromides. This procedure will be illustrated with
a specific example. Prior to reaction setup, Cs2CO3 was dried for at
least 3 h under high vacuum at 125 °C. Dried Cs2CO3 (1.3 equiv, 220
mg, 0.67 mmol), triphenylmethanol (1 equiv, 130 mg, 0.5 mmol),
PPh3(25 mol %, 34.5 mg, 0.13 mmol), and Pd(OAc)2(5 mol %, 6.0
mg, 0.025 mmol) were combined in a 250 mL round-bottom flask. A
condenser was attached to the flask and a rubber septum added to the
top of the condenser. The condenser/round-bottom flask system was
evacuated and refilled with argon (4×). To this flask, 3 mL of
anhydrous o-xylene and bromobenzene (1.2 equiv, 65 μL, 0.6 mmol)
and 4-trifluoromethyl-1-bromobenzene (1.2 equiv, 84 μL, 0.6 mmol)
were added via syringe. The flask was heated in an oil bath with a
temperature of 150 °C. After 16 h the reaction was removed from the
oil bath, cooled to room temperature and quenched with 10 mL of 2
M HCl (aq). Following extraction with Et2O (2× 10 mL), the organic
layers were combined, dried over MgSO4 and concentrated under
reduced pressure. Analysis was carried out via GC/MS.
Procedure for Intermolecular Competition Experiments
Using Two Triarylmethanols. This procedure will be illustrated
with a specific example. Prior to the reaction, Cs2CO3 was dried for at
least 3 h under high vacuum at 125 °C. Dried Cs2CO3 (1.3 equiv, 220
mg, 0.67 mmol), triphenylmethanol (1 equiv, 130 mg, 0.5 mmol),
tri(p-anisyl)methanol (1 equiv, 175 mg, 0.5 mmol), PPh3(25 mol %,
34.5 mg, 0.13 mmol), and Pd(OAc)2(5 mol %, 6.0 mg, 0.025 mmol)
were combined in a 250 mL round-bottom flask. A condenser was
attached to the flask and a rubber septum added to the top of the
condenser. The condenser/round-bottom flask system was evacuated
and refilled with argon (4×). To this flask, 3 mL of anhydrous o-xylene
and bromobenzene (1.2 equiv, 130 μL, 1.2 mmol) were added via
syringe. The flask was heated in an oil bath with a temperature of 150
°C. After 16 h (prior to complete consumption of either
triarylmethanol) the reaction was removed from the oil bath, cooled
to room temperature and quenched with 10 mL of 2 M HCl (aq).
Following extraction with Et2O (2× 10 mL), the organic layers were
combined, dried over MgSO4 and concentrated under reduced
pressure. Analysis was carried out via GC/MS.
(2,5-Difluorophenyl)diphenylmethanol (4p). Product is a white
crystalline solid (816 mg, 2.8 mmol, 68%): Recrystallized from hexane.
1
mp = 82−85 °C. H NMR (400 MHz, CDCl3) δ 7.39−7.33 (mult,
6H), 7.33−7.26 (mult, 4H), 7.09−6.97 (mult, 2H), 6.61(ddd, J = 10,
6, 3 Hz, 1H), 3.48 (d, J = 9 Hz, 1H). 13C {1H} NMR (100 MHz,
1
3
1
CDCl3) δ 158.1 (dd, JCF = 243, JCF = 2 Hz), 156.6 (dd, JCF = 243,
3JCF = 2 Hz), 144.8, 136.1 (dd, J = 12, 7 Hz), 128.2, 127.8, 127.4, 117.0
(dd, J = 26, 4 Hz), 116.6 (dd, J = 24, 10 Hz), 116.3 (dd, 24, 10 Hz),
80.6. 19F (363 MHz, CDCl3) δ −116.4 (d, J = 21 Hz), −118.5 (d, J =
21 Hz). IR (diamond atr) 3450, 1482, 1445, 1241, 755, 695 cm−1.
HRMS (ESI, TOF) for C19H15F2O+, calcd 297.1085. Found 297.1096.
(3,4-Difluorophenyl)diphenylmethanol (4q). Product is a white
crystalline solid (486 mg, 1.6 mmol, 40%): Crystallized from hexane.
1
mp = 82−85 °C. H NMR (400 MHz, CDCl3) δ 7.36−7.29 (multi,
5H), 7.28−7.21 (mult, 5H), 7.18 (ddd, J = 19, 8, 2 Hz, 1H), 7.08 (q, J
= 9 Hz, 1H); 7.03−6.97 (mult, 1H). 13C {1H} NMR (100 MHz,
CDCl3) δ 149.8 (dd, J = 248, 13 Hz), 149.3 (dd, J = 248, 13 Hz),
146.1, 143.9 (t, J = 4 Hz), 128.2, 127.7, 127.6, 124.0 (dd, J = 6, 3 Hz),
117.2 (d, J = 19 Hz). 116.4 (d, J = 19 Hz), 81.4 (d, J = 2 Hz). 19F (363
MHz, CDCl3) δ −138.0 (d, J = 21 Hz), −140.4 (d, J = 21 Hz). IR
(diamond atr) 3460, 3061, 3027, 1512, 1445, 1278, 1110, 752 cm−1.
HRMS (ESI, TOF) for C19H14F2ONa+, calcd 319.0885. Found
319.0905.
(2,6-Difluorophenyl)diphenylmethanol (4r). Product is a white
crystalline solid (814 mg, 2.7 mmol, 67%): Crystallized from hexane.
1
mp =124−126 °C. H NMR (400 MHz, CDCl3) δ 7.35−7.25 (mult,
11H), 6.84 (dd, J = 9.8, 8.5 Hz, 2H), 3.89 (t, J = 7.5 Hz, 1H). 13C
{1H} NMR (100 MHz, CDCl3) δ 160.7 (dd, J = 249, 7 Hz), 145.5,
129.5 (t, J = 12 Hz), 127.9, 127.7, 127.1, 123.2 (t, J = 12 Hz), 112.7
(mult), 80.4. 19F (363 MHz, CDCl3) δ −107.0. IR (diamond ATR)
3609, 3404, 1619, 1447, 1390, 764, 676 cm−1. HRMS (ESI, TOF) for
C19H14F2ONa+, calcd 319.0885. Found 319.0868.
(3,5-Difluorophenyl)diphenylmethanol (4s). Product is a white
crystalline solid (1032 mg, 3.5 mmol, 85%): Recrystallized from
1
hexane. mp = 82−85 °C. H NMR (400 MHz, CDCl3) δ 7.35−7.28
(mult, 6H), 7.25−7.21 (mult, 4H), 6.89−6.82 (mult, 2H), 6.69 (tt, J =
9, 2 Hz, 1H), 2.76 (s, 1H). 13C {1H} NMR (100 MHz, CDCl3) δ
162.58 (dd, J = 248, 13 Hz), 150.8 (t, J = 8 Hz), 145.7, 128.2, 127.8,
127.7, 111.0 (mult), 102.6 (t, J = 25 Hz), 81.6 (t, J = 2 Hz). 19F (363
MHz, CDCl3) δ −110.1. IR (NaCl) 3579, 3467, 3058, 3024, 1622,
1599, 1444, 1295, 1156 cm−1. HRMS (ESI, TOF) for C19H15F2O+,
calcd 297.1085. Found 297.1071.
(3,4,5-Trifluorophenyl)diphenylmethanol (4t). Product is a white
crystalline solid (515 mg, 1.6 mmol, 41%): Crystallized from hexane.
1
mp = 72−74 °C. H NMR (400 MHz, CDCl3) δ 7.36−7.27 (mult,
6H), 7.23−7.18 (mult, 4H), 6.96 (dd, J = 9, 7 Hz, 2H), 2.74 (s, 1H).
13C {1H} NMR (100 MHz, CDCl3) δ 150.5 (ddd, J = 249, 10, 4 Hz),
145.5, 143.1 (dt, J = 6, 6 Hz), 138.7 (dt, J = 254, 18 Hz), 128.3, 127.9,
127.7, 112.2 (mult), 81.3. 19F (363 MHz, CDCl3) δ −134.6 (d, J = 22
Hz), −162.6 (t, J = 22 Hz). IR (diamond ATR) 3450.0, 1620.2,
1520.8, 1433.2, 1340.1, 1000.4, 856.5, 696.4 cm−1. HRMS (ESI, TOF)
for C19H14F3O+, calcd 315.0991. Found 315.0982.
General Procedure for Intramolecular Competition Experi-
ments. This procedure will be illustrated with a specific example.
Prior to the reaction, Cs2CO3 was dried for at least 3 h under high
vacuum at 125 °C. Dried Cs2CO3 (1.3 equiv, 220 mg, 0.67 mmol),
(2,6-difluorophenyl)diphenylmethanol (1 equiv, 148 mg, 0.5 mmol),
PPh3(25 mol %, 34.5 mg, 0.13 mmol), and Pd(OAc)2(5 mol %, 6.0
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Note
(25) Lutz, J. P.; Rathbun, C. M.; Stevenson, S. M.; Powell, B. M.;
Boman, T. S.; Baxter, C. E.; Zona, J. M.; Johnson, J. B. J. Am. Chem.
Soc. 2012, 134, 715.
(26) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J. Am.
Chem. Soc. 2001, 123, 10407.
ASSOCIATED CONTENT
■
S
* Supporting Information
Complete results for aryl bromide competition reactions and
characterization material for all new compounds. This material
is available free of charge via the Internet at http://pubs.acs.org.
(27) Terao, Y.; Wakui, H.; Nomoto, M.; Satoh, T.; Miura, M.;
Nomura, M. J. Org. Chem. 2003, 68, 5236.
(28) Terao, Y.; Nomoto, M.; Satoh, T.; Miura, M.; Nomura, M. J.
Org. Chem. 2004, 69, 6942.
(29) Wakui, H.; Kawasaki, S.; Satoh, T.; Miura, M.; Nomura, M. J.
Am. Chem. Soc. 2004, 126, 8658.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: jjohnson@hope.edu.
Notes
(30) Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28, 287.
́
(31) Foa, M.; Cassar, L. J. Chem. Soc., Dalton Trans. 1975, 2572.
The authors declare no competing financial interest.
(32) This conclusion is consistent with the observation that PhBr and
PhCl give similar transfer ratios using aryldiphenylmethanol substrates.
See ref 27.
ACKNOWLEDGMENTS
■
(33) For leading references, see Brown, J. M.; Cooley, N. A. Chem.
Rev. 1988, 88, 1031 and refs 34 and 35.
(34) Espinet, P.; Echavarren, A. M. Angew. Chem., Int. Ed. 2004, 43,
Acknowledgment is made to the Donors of the American
Chemical Society Petroleum Research Fund for partial support
of this research. We also thank the Arnold and Mabel Beckman
Foundation Scholars Program (J.R.B.), the Towsley Founda-
tion (J.B.J.) and the NSF (CHE-1148719) for financial support.
A grant from the NSF (CHE-0922623) for the purchase of
NMR spectrometers is also gratefully acknowledged.
4704.
(35) Jones, G. D.; Martin, J. L.; McFarland, C.; Allen, O. R.; Hall, R.
E.; Haley, A. D.; Brandon, R. J.; Konovalova, T.; Desrochers, P. J.;
Pulay, P.; Vicic, D. A. J. Am. Chem. Soc. 2006, 128, 13175.
(36) It is noted that ortho-substitution can have a significant influence
upon the rate of reductive elimination. See: Maestri, G.; Motti, E.;
Della Ca, N.; Malacria, M.; Derat, E.; Catellani, M. J. Am. Chem. Soc.
2011, 133, 8574 and references therein.
(37) Mann, G.; Shelby, Q.; Roy, A. H.; Hartwig, J. F. Organometallics
2003, 22, 2775.
(38) For additional information into the process of β-aryl elimination
from Rh-complexes, see: Zhao, P.; Hartwig, J. F. Organometallics 2008,
27, 4749 and references therein.
(39) Similar results have been previously observed with o-Me, o-OMe
and o-CF3 substitution. See ref 27. For additional insight into the
effects of ortho substitution on β-aryl elimination, see Zhao, P.;
Hartwig, J. F. J. Am. Chem. Soc. 2005, 127, 11618 and ref 40.
(40) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem. Soc. 2006,
128, 3124.
(41) Miura and co-workers previously utilized substrates 4f, 4h, and
4j in a similar fashion and observed different levels of selectivities. This
difference can be attributed to the use of PPh3 in the current study
versus PCy3 in the previous work. See ref 27.
(42) See the Supporting Information for a Hammett plot.
(43) Evans, M. E.; Burke, C. L.; Yaibuathes, S.; Clot, E.; Eisenstein,
O.; Jones, W. D. J. Am. Chem. Soc. 2009, 131, 13464.
(44) Clot, E.; Eisenstein, O.; Jasim, N.; MacGregor, S. A.; McGrady,
J. E.; Perutz, R. N. Acc. Chem. Res. 2011, 44, 333.
(45) An experiment to probe reversibility of the carbon−carbon
bond cleavage, similar to that presented in Scheme 3, was performed
with 1 and 4-trifluromethyl-1-bromobenzene in the presence of 2-
fluorobenzophonene. No evidence of reversibility was observed.
REFERENCES
■
(1) Murakami. M.; Ito, Y. In Activation of Unreactive Bonds and
Organic Synthesis; Murai, S., Ed.; Springer: Berlin, 1999; p 97.
(2) Crabtree, R. H. Chem. Rev. 1985, 85, 245.
(3) Jones, W. D. Nature 1993, 364, 676.
(4) For leading references, see Muller, C.; Lachicotte, R. J.; Jones, W.
̈
D. Organometallics 2002, 21, 1975 and refs 5 and 6.
(5) Kondo, T.; Kaneko, Y.; Taguchi, Y.; Nakamura, A.; Okada, T.;
Shiotsuki, M.; Ura, Y.; Wada, K.; Misudo, T. J. Am. Chem. Soc. 2002,
124, 6824.
(6) Ashida, S.; Murakami, M. Bull. Chem. Soc. Jpn. 2008, 81, 885.
(7) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc. Chem. Res. 2008, 41, 222.
(8) Salem, H.; Ben-David, Y.; Shimon, L. J. W.; Milstein, D.
Organometallics 2006, 25, 2292.
(9) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870.
(10) For examples of general systems for activation and
functionalization, see: Uto, T.; Shimizu, M.; Ueura, K.; Tsurugi, H.;
Satoh, T.; Miura, M. J. Org. Chem. 2008, 73, 298.
(11) Dreis, A. M.; Douglas, C. J. J. Am. Chem. Soc. 2009, 131, 412.
(12) Seiser, T.; Roth, O. A.; Cramer, N. Angew. Chem., Int. Ed. 2009,
48, 6320.
(13) Shigeno, M.; Yamamoto, T.; Murakami, M. Chem.Eur. J.
2009, 15, 12929.
(14) Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.; Shi, Z.-J. J. Am.
Chem. Soc. 2011, 133, 15244.
(15) For leading references, see Murakami, M.; Matsuda, T. Chem
Commun. 2011, 47, 1100 and refs 16 and 17.
̌
(16) Necas, D.; Kotora, M. Curr. Org. Chem. 2007, 11, 1566.
(17) Jun, C.-H. Chem. Soc. Rev. 2004, 33, 610.
(18) Significant advances have been made in the activation of C−CN
bonds. See Hirata, Y.; Yada, A.; Morita, E.; Nakao, Y.; Hiyama, T.;
Ohashi, M.; Ogoshi, S. J. Am. Chem. Soc. 2010, 132, 10070 and refs 19
and 20.
́
(19) Najera, C.; Sansano, J. M. Angew. Chem., Int. Ed. 2009, 48, 2452.
(20) Watson, M. P.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130,
12594.
(21) Atesi̧ n, T. A.; Li, T.; Lachaize, S.; García, J. J.; Jones, W. D.
Organometallics 2008, 27, 3811.
(22) Li, T.; García, J. J.; Brennessel, W. W.; Jones, W. D.
Organometallics 2010, 29, 2430.
(23) Evans, M. E.; Li, T.; Jones, W. D. J. Am. Chem. Soc. 2010, 132,
16278.
(24) Rathbun, C. M.; Johnson, J. B. J. Am. Chem. Soc. 2011, 133,
2031.
1669
dx.doi.org/10.1021/jo302592g | J. Org. Chem. 2013, 78, 1665−1669