Group exchange between ketones and carboxylic acids through directing group assisted Rh-catalyzed reorganization of carbon skeletons

Article abstract of DOI:10.1021/ja512003d

The Rh(I)-catalyzed direct reorganization of organic frameworks and group exchanges between carboxylic acids and aryl ketones was developed with the assistance of directing group. Biaryls, alkenylarenes, and alkylarenes were produced in high efficiency from aryl ketones and the corresponding carboxylic acids by releasing the other molecule of carboxylic acids and carbon monoxide. A wide range of functional groups were well compatible. The exchanges between two partners were proposed to take place on the Rh-(III) center of key intermediates, supported by experimental mechanistic studies and computational calculations. The transformation unveiled the new catalytic pathway of the group transfer of two organic molecules.

Full text of DOI:10.1021/ja512003d

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Article
Group Exchange between Ketones and Carboxylic Acids through Directing
Group Assisted Rh-catalyzed Reorganization of Carbon Skeletons
Zhi-Quan Lei, Fei Pan, Hu Li, Yang Li, Xi-Sha Zhang, Kang
Chen, Xin Wang, Yu-xue Li, Jian Sun, and Zhang-Jie Shi
J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 06 Apr 2015
Downloaded from http://pubs.acs.org on April 6, 2015
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Group Exchange between Ketones and Carboxylic Acids
through Directing Group Assisted Rh-catalyzed
Reorganization of Carbon Skeletons
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¶
Zhi-Quan Lei,†,‡ Fei Pan,‡ Hu Li,‡ Yang Li,‡ Xi-Sha Zhang,‡ Kang Chen,‡ Xin Wang,‡ Yu-Xue Li*,
,
¶
Jian Sun*,† and Zhang-Jie Shi*‡,
†Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu, Sichuan 610041 and ‡ Beijing National Laboratory
of Molecular Sciences (BNLMS) and Key Laboratory of Bioorganic Chemistry and Molecular Engineering ofthe Ministry
¶
of Education, College of Chemistry and Green Chemistry Center, Peking University, Beijing 100871 and State Key
Laboratory of Organometallic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China.
ABSTRACT: The Rh(I)-catalyzed direct re-organization of organic frameworks and group exchanges between carboxylic acids
and aryl ketones was developed with the assistance of directing group. Biaryls, alkenylarenes, and alkylarenes were produced in
high efficiency from aryl ketones and the corresponding carboxylic acids by releasing the other molecule of carboxylic acids and
carbon monoxide. A wide range of functional groups were well compatible. The exchanges between two partners were proposed to
take place on the Rh-(III) centre of key intermediates, supported by experimental mechanistic studies and computational
calculations. Thetransformation unveiled the new catalyticpathway of the group transfer of two organic molecules.
4e,4h,4k,4p,4q,7b,9b,9c ,9f ,9j -l,12h. For example, with directing strategy
in the presence of Rh(I), either one of the acyl C-C bond was
Introduction
Traditional organic synthesis basically depends on the
transformations between different functional groups. The
scaffold re-organization of organic compounds through C-C
cleaved through oxidative addition (path a and path b in
Figure 1). Through path a, the carbonyl group was remained
and new C-C bonds were formed through the exchange with
another molecular of unsaturated species2e,10b,12c,12d,12g (i) or
the cross coupling with organometallic reagents12e (ii). With
the same strategy, we conducted the extrusion of carbon
monoxide of ketones to form the new C-C bond by cleaving
the other acyl C-C bond of ketones13 (path b, iii). Based on
this observation, the intermolecular decarbonylation
coupling between arenes and in-situ formed mixed
anhydrides was also achieved.14 In this article, we developed
a novel group exchange transformation between ketone and
carboxylic acids to form new C-C bond by releasing one
molecule of new carboxylic acid and carbon monoxide
through the same intermediate in our previous studies (iv).
bond cleavage could be
a
conceptually different,
straightforward and efficient strategy to build up new
skeletons from existing structural units.1 Transition-metal
catalyzed selective C-C bond activation (cleavage) is
currently of great interest to organometallic chemists, due to
not only its fundamental academic interest to carry out the
re-organization of organic molecule skeletons, but also its
potential application in organic synthesis.2 However, the
cleavage of C-C bonds faces several challenges from both
thermodynamic and kinetic issues, including high bond
dissociation energy (BDE) of C-C bonds while relatively
lower BDE of forming C-M bonds, steric hindrance of
attacked C-C bonds, and selectivity among various C-C
bonds in the same molecule.3 Over the past few decades,
significant progress has been made to cleave C-C bonds
through different strategies, for example, by relieving the
strain of small rings,4 forming small molecules,5 inducing
aromatic stabilization,6 forming stable metallacyclic
complexes,7 cleavage of C-CN bond8 and others.9 Another
successful strategy is to use directing group to assist the C-C
cleavage, as shown in pioneer works by Suggs,10 Jun2c ,2e ,11
and others.12 With this strategy, our group recently reported
the Rh-catalyzed selective cleavage of C-C bonds of
Figure 1. Directed C-C Cleavage of Ketones via Rh(I)
Catalysis
secondary
benzyl
alcohols
and
following
transformations.5f,5h,12e
Among many type of organic molecules, ketones were
seriously regarded as an objective due to their unique
reactivity in the field of C-C activation (Figure 1)
Results and Discussion
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Serendipity and Further Design on Group Exchange
might enhance the chemoselectivity, o-toluyl ketone 1b was
selected as a substrate. To our delight, the desired product 3a
was obtained in 76% yield with an excellent selectivity
between intramolecular and intermolecular arylation (ratio =
20/1). Owing to the steric effect to slow down the C-C
cleavage, a longer reaction time was required to reach the
complete conversion. Predictably, more hindered substrate
1c gave better selectivity with a comparable yield. We
concluded that the steric hindrance was the most critical
factor to control the chemoselectivity in this transformation.
Indeed, the yield was not significantly improved with further
optimization of reaction parameters, such as temperature,
solvent, catalyst set, or the amount of catalyst and thepartner
of other carboxylic acids.
In our previous studies on the CO extrusion of arylketone,
we found a credible amount of protonated 2-phenylpyridine
3aa as byproduct if the ketone substrate 1aa in the absence
of meta-substituent was submitted (Eq 1). To catch the
proposed intermediate of Rh(III)-acyl species in catalytic
cycle, PhOH was added to the system and indeed the
corresponding phenyl ester 2zz was observed in 46% NMR
yield (Eq 2). Thus, we envisaged that, if another molecule of
carboxylic acid was introduced into the reaction system, two
acyl groups might be exchanged on Rh centre by releasing
the other molecule of carboxylic acid if matched. New
acyl-Rh species may undergo the decarbonylation to form
new substituted arenes. If this chemistry applied, new
concept to realize the group exchanges between two
independent organic molecules can be proved.
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To further explore the diversity of the substrates, various
alkyl aryl ketones were also investigated (Table 1). Fromthe
results we can see, alkyl acyl groups are better for both
efficiency and selectivity to form the biaryls, although less
hindered acetyl and propionyl substrates were not ideal,
which may arise from easy reductive elimination to form
alkylarenes from C-Rh-C intermediates. With more hindered
alkyl ketones as substrates, the selectivity and yields also
increased to some extent and the best result was given by 1g.
With this idea in mind, we set out to test the proposed
group exchange between biaryl ketone 1b in the presence of
1.0 equiv of p-methoxylbenzoic acid 2a. As designed, both
intramolecular and intermolecular decarbonylative products
3a and 3b were detected, companying with the formation of
benzoic acid 2b and carbon monoxide (Eq 3). Since the
protonation of ketone was also observed, the possibility to
produce the group-exchanging product 3a through the
sequence of C-C cleavage/ protonation/ C-H activation/
decarboxylative coupling with carboxylic acid could not be
rooted out from this transformation. To clearly understand
the pathway to produce the cross coupling product, the
control experiment was conducted with the corresponding
arylpyridine 3z in the presence of acid 2a under the same
condition (Eq 4). The recovery of both starting materials (2a
and 3z) supported the group exchange pathway rather than
the sequence initiated from the protonation without other
additives.
Table 1. Substrate-controlled selectivitya
Note: a. reaction conditions: 0.1 mmol of 1, 2.0 equiv of 2a
o
in PhCl at 140 C for 12 h; isolated yield; ratio of 3a/3’
1
was determined by crude HNMR in parenthesis; b. reacted
for 24 h.
Based on the balance of reactivity, efficiency, selectivity
and availability of the substrates, we chose 1g as a standard
model. After the systematic condition screening (Table S1),
we found that the reaction reached the best efficiency and
selectivity with 4.0 equiv of 2b in the presence of 5.0 mol%
of Rh(CO)2(acac) as catalyst. The 90% isolated yield was
obtained at 140 oC for 24 h under N2 atmosphere with a trace
amount of both direct decarbonylative and protonated
byproducts.
Figure 2. The initial results and control experiments
Investigation on Substrates Compatibility
With the optimized reaction condition in hand, various
acids were investigated (Table 2). The results indicated that
the electron-donating groups are beneficial for this group
exchange (3a, 3h, 3i, 3m). In contrast, the electron deficient
groups, such as trifluoromethyl (3j), acetyl (3k), and nitrile
To further prove our concept of group exchange and
evaluate the proper substrates for this process, we first
investigate the reactivity of different aryl ketones with the
same acid 2a (Table 1). Considering that the steric effect
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(3l), decreased the yields, and more protonated byproducts
while for electron poor and short chain alkyl carboxylic
acids with low boiling points (3j, 3k, 3s, 3t, 3v, 3w), 1.5
equiv amount of acid 2 resulted in decreased yields.
were detected. Other disubstituted acid substrates, such as
3,5-dimethoxyl- (3q) and 3,5-difluoro- (3r), also gave good
yields. Various functionalities, including PhO- (3c), AcO-
(3d), and different halides (3e-g), survived well, providing
opportunities for further functionalization.15 The steric
hindrance obviously decreased the efficiency although
ortho-methoxylbenzoic acid (3p) showed the credible
efficiency. Notably, heteroaromatic carboxylic acids, such as
2-thienylcarboxylic acid (3t) and 2-furic acid (3u), showed
the acceptable reactivity and the desired products were
isolated in good yields. It was important to note that,
cinnamic acid (3v) and various aliphatic acids (3w-3y) were
also the proper partners for this transformation. The
corresponding alkenyl- and alkyl- arenes were produced in
moderate to good yields. To our interest, the isomerisation of
long chain aliphatic acids to branched product was not
observed, which partially ruled out cationic and radical
intermediates. Thus, this method can serve as a supplement
to Friedel-Crafts reaction. It should be noted that, in many
reactions, the amount of acid 2 could be reduced to 1.5 equiv
with comparable yields (3a, 3b, 3f, 3h, 3m, 3n, 3p, 3y);
To explore the effect of substituents on ketone, we
investigated a variety of 2-phenylpyridine derivatives (Table
3). We found that, electron-neutral and electron-rich groups
promoted the efficiency and the desired cross
decarbonylative coupling products were produced in good
yields (4a, 4c). In contrast, electron-poor groups reduced the
efficiency and more protonation byproducts were detected
(4d). It should be noted that, 2-methyl on pyridine (4e) and
ortho-methoxyl-(4g), ortho-methyl-(4h) groups on phenyl
did not show strongly steric or chelating effects and the
yields were retained, or slightly decreased. To our interest,
for 2-(3-fluorophenyl-)pyridine (4f), both ortho- isomers and
diphenylated products were observed, which might be
attributed to the fluoride effect.16 According to this result, the
phenyl group scrambling was proved.13,17 Such an aryl
scrambling was also observed on 2-phenylpyridine or
4-substituted substrates, which indicated that the potential
pathway through C-H activation was involved,
accompanying with the group exchange. Other than pyridyl
group, 2-phenylquinolinyl, benzo[h]quinoliyl, pyrazolyl and
oxazolyl gave desired products in credible yields, while with
starting material remaining when 4l-n served.
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Table
2.
Pyridinyl-directed
Rh(I)-catalyzed
decarbonylation-coupling of acida
Table
3.
N-containing
heterocycles-directed
Rh(I)-catalyzed decarbonylation-coupling of acida
Note: a. reaction condition: 0.2 mmol of 1g, 4.0 equiv of 2,
o
140 C for 24 h, isolated yield; b. in the atmosphere of O2,
trace starting material remained by TLC; c. 0.2 mmol of 1g,
o
1.5 equiv of 2, 140 C for 24 h, isolated yields in the
parenthesis.
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Note: a. reaction condition: 0.2 mmol of 1, 4.0 equiv of 2b,
o
140 C for 24 h; b. some started materials remained; c. ratio
of RH/RPh was detected by crude 1H NMR (400 MHz).
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Isotopic Tracing Studies and Control Experiments
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Further experiments have been conducted to unveil the
reaction pathway. To identify the source of CO, a
13C-labeled acid was submitted (Figure 3). The 13C-labelled
CO was detected by GC-MS in the presence of 13C-labeled
benzoic acid in both reactions with aryl ketone and alkyl
ketone as substrates (Eqs 5 and 6). To further prove that CO
came from the ketone, both remained acid 2b and newly
generated o-toluic acid were quenched by esterification with
4-phenylphenol.18 The results confirmed that the released
acid did not contain the 13C-labelled motif, which was
consistent with our conclusion.
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Figure 4. Control experiments under different
atmosphere
To clearly rationalize the mechanism, we must answer
how the intermediate ketone 1b is formed? Was it generated
from the mixed anhydride?14,19 To our delight, a trace
amount of mixed anhydride was detected by HRMS in the
reaction system, which indicated that the anhydride might be
a key intermediate to facilitate such a group exchange.18
Several control experiments related to the mixed anhydride
were investigated (Figure 5 and Figure 6). The efficiency of
desired group exchange process is higher than the direct
arylation through C-H activation starting from the
corresponding 2-arylpyridine, thus provide the proof to
support that the "intramolecular" group exchange was
preferred to the sequence of C-C cleavage/ protonation/
direct C-H arylation with mixed anhydride, which was
supposedly produced in-situ from substrates and additional
acid (Eqs 10 and 11). Comparing the results from the
crossover experiments with the same benzoic acids (Eqs 12
and 13), we observed that the exchange product 3b was
preferred, thus also indicating that the "intramolecular"
reaction is dominated (if it was produced, the mixed
anhydride was not dissociate from the catalytic Rh centre).
However, the "intermolecular" process by dissociation was
also supported from these control experiments albeit in the
relatively lower efficacy.
Figure 3. Isotope-tracing Studies
While investigating the steric effect of the acid partner, we
found that a trace amount of exchanged ketone 1b
companying with a small amount of protonated byproduct 3z
were observed when steric hindered o-toluic acid 2z was
subjected to the reaction with a very low conversion (Eq 7).
It is of great importance to imply that the decarbonylation
might take place after the group exchange on Rh centre since
in the cases a trace amount of exchanged ketone was
observed after the group exchange. We tried to inhibit the
decarbonylation in the atmosphere of CO (1 atm) from 1g
with 2z or 2a as starting materials. However, the similar
results were observed and only a trace amount of exchanged
ketone 1b was observed with a very poor conversion when a
steric aromatic acid 2z applied as above results (Eq 8), while
only the decarbonylative cross coupling product 3a was
observed in an excellent yield when high reactive aromatic
acid 2a was applied (Eq 9). These results indicated that the
presence of CO was not a key issue for this transformation.
Figure 5. Comparison with mixed anhydride
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Figure 7. Ligand exchange of catalyst and resting states
of catalyst
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Figure 6. Crossover experiment
Electronic Effect of Benzoic Acid
Detecting of Active CatalyticSpecies
Although this transformation is well controlled by steric
hindrance, we also intended to study the electronic effect of
substituted benzoic acids. Two competition reactions were
explored under the typical conditions as shown in Tables 2
(Eqs 17 and 18). A 1:1 molar ratio mixture of 2a and 2b, 2b
and 2j were reacted with 1g, affording the arylation products
3a and 3b in a 44: 40 molar ratio (Eq 17), 3b and 3j in a
50:20 molar ratio (Eq 18), which further demonstrates that
an electron-donating substituent in the benzoic acid favored
the arylation while electron-withdrawing substituent in the
benzoic acid was less reacted. This result is opposite of
reactivity to aromatic aldehydes in Rh-catalyzed
decarbonylation,20 which could be explained that strong
electron withdrawing group on the benzoic acid causes the
increase of protonation byproduct.
Next, we intended to explore the role of acid 2, which is
might not only play a role as a partner. As the acidity of
benzoic acid was stronger than that of acetylacetone (acac),
the rapid ligand exchange of Rh(CO)2(acac) to form the new
complex Rh(CO)2(PhCOO) was observed in-situ and
1
confirmed by H NMR, which was considered the real active
species in this transformation (Eq 14). Indeed, the preformed
complex Rh(CO)2(PhCOO) showed comparable efficiency
as Rh(CO)2(acac) (Eq 15). Stoichiometric experiment with
Rh(CO)2(PhCOO) as starting material in the absence of
additional benzoic acid could also afford the desired product
with 50% yield (Eq 16). The released acid was found as a
ligand to facilitate the group exchange. During this process,
the additional acid is not required, so-called "intramolecular"
process, which was consistent with the crossover
experiments (Figure 6). Indeed, the rapid equilibriums
between precatalyst I with species B and F as resting states
were observed by in-situ IR18 (Figure 7). Thus, we
confirmed that the carboxylic acid 2 also acted as the ligand
of Rh catalyst and took part in the group exchange at the
initiating stage. For [Rh(CO)2Cl]2 catalyst, the acidity of
hydrogen chloride is much stronger than that of benzoic acid.
Thus the ligand exchange is more slow, probably resulting in
the background decarbonylative coupling of the starting
material.18
Figure 8. Competition study for the decarbonylative
coupling of benzoic acid and substituted benzoic acid
Based on these experiments, the whole catalytic cycle was
proposed as Figure 9. After the ligand exchange with acid
partner, the Rh complex I coordinated to the substrate 1 to
afford B. The oxidative addition of alkyl ketone to Rh centre
occurred to form the Rh(III)-acyl species C. After forming a
tight coordinated anhydride complex D and ligand slipping
to form the other complex E, the oxidative addition took
place at the acyl C-O bond to form another Rh(III)-acyl
species F (path a). Followed by the decarbonylation, the
complex G was formed. Finally the reductive elimination on
Rh centre took place to afford the desired product 3,
regenerating the active catalyst by ligand exchange with
benzoic acid. On the other hand, the dissociation of
anhydride from the Rh centre could also take place.
Depending on the acidity of benzoic acid, this pathway
might become important through the protonation of the
Rh-complex, which was consistent with the observation of
the protonated byproducts21 (path b). Since electron
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withdrawing benzoic acid exhibited stronger acidity, the
portion of path b might become an unignorable pathway.
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Proposed Catalytic Cycle
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Figure 10. Observed 12C/13C kinetic isotope effects for select
carbons during the decarbonylative coupling of acid.
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Computational Studies
To further rationalize the reaction mechanism, density
functional theory (DFT)24 studies have been performed with
GAUSSIAN09 program25 using the M0626 method. For Rh
atom the SDD basis set with Effective Core Potential
(ECP)27 was used; for the rest atoms, the 6-31+G** basis set
was used. Except for the CO molecule, geometry
optimization was performed in chlorobenzene=5.697)
using the SMD28 method. Harmonic vibration frequency
calculations were carried out at 413.15K, the optimized
structures are all shown to be either minima (with no
imaginary frequency) or transition states (with one
imaginary frequency). The calculation starts from complex B
(Figure 7), and the typical substrates 1g and 2b were used in
the caculation.
Figure 9. Catalytic Cycle ofCross Decarboxylative Coupling
of Aryl Ketone with Carboxylic Acid
As shown in Figure 11, in the first step, the oxidative
addition of the reactant complex B via transition state
TS-OA-BC (10.9 kcal/mol) leads to Rh(III)-acyl species C.
Subsequently, the reductive elimination of the acyl group
and the benzoic acid anion in C over transition state TS-RE
(11.6 kcal/mol) yields the mixed anhydride-Rh complex
INT1. The dissociation/recoordination of INT1 forms INT2,
in which the carbonyl coming from substrate 1g coordinates
with the Rh centre, like communicating on the Rh centre.
Then, oxidative addition of the mixed anhydride at the C-O
bond coming from benzoic acid via transition state TS -OA
(9.3 kcal/mol) leads to a new Rh(III)-acyl species D, in
which the acyl groups has been exchanged compared with C.
12C/13C KineticStudies
To prove the proposed pathway of the reaction, we
followed Singleton method22 to measure the 12C/13C kinetic
isotopic effects. We hoped that such studies ascertained the
potential involvement of the oxidative addition, the exchange
of Rh(III)-acyl process, decarbonylative and reductive
elimination into the turnover-limiting step of catalysis.
Obviously, there were four carbons involved in the reaction,
and two of these four carbons participated in two different
processes. Thus, two independent experiments were
conducted for ketone 1g23 and acid 2y. Four gram scale
reactions were run to approximately 80% conversion, and
the recovered starting material was examined for 13C content
The reductive elimination of
D over transition state
TS-RE-DH (18.1 kcal/mol) leads to the slightly unstable
exchanged ketone H (2.0 kcal/mol). Based on the calculated
barriers, under the reaction condition of 140 oC, the
equilibrium of the intermediates shown in Figure 11 can be
easily set up, and the acyl group can be exchanged easily via
R.E./O.A. and dissociation/recoordination processes of the
mixed anhydride intermediate. This mechanism is strongly
supported by the experiments shown in Figure 5 and Figure
by
using quantitative 13C
NMR spectroscopy.
4-(tert-butyl)benzoic acid was converted to methyl
4-(tert-butyl)benzoate for easy isolation. The 12C/13C kinetic
isotope effects were determined for a number of carbons,
including the carbonyl and adjacent aromatic and alkyl
carbons, and carbonyl of aromatic acid and adjacent
aromatic carbons, with the results summarized in Figure 10.
Significant large isotopic effects were synchronously
observed at the carbonyl of aromatic acid (1.032 ± 0.003 and
1.031 ± 0.003) and adjacent aromatic carbons of (1.024 ±
0.003 and 1.027 ± 0.004), indicating the rate-limiting step of
decarbonylation; while negligible isotopic effects on the
carbonyl of ketone and adjacent aromatic carbons (more than
0.998 and less than 1.004 in all experiments) suggested the
lack of involvement in the rate limiting step of oxidative
addition. In conclusion, these results suggested that the
decarbonylation is the turnover-limiting step of the reaction.
Similarly, in Madsen's studies, they also observed that the
decarbonylation was the rate limiting step for the
decarbonylation of aromatic aldehyde.20
6. A concerted -bond metathesis transition state was
located. However, the barrier is as high as 86.8 kcal/mol.
Therefore, this mechanism can be safely excluded.
As shown in Figure 12, the decarbonylation of
intermediate D via transition state TS -DeCO-D (21.6
kcal/mol) forms E-2CO which has two coordinated CO
molecules. On the attacking of the 2-methylbutanoic acid
anion (TS-E-CO-D', 23.5 kcal/mol), one CO molecule is
driven out leading to intermediate E. Subsequently, the
reductive elimination of E over transition state TS-RE-EF-D
(23.4 kcal/mol) affords the desired product 3. The
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Figure 11. The equilibrium of intermediates B, C, INT1, INT2, D and H. The acyl group can be exchanged easily via R.E./O.A. and
Dissociation/Recoordination processes of the mixed anhydride intermediate. The selected bond lengths are in angstroms, and the
relative free energies in chlorobenzene Gsol (413.15 K, 1.0 atm) are in kcal/mol.Calculated at M06/6-31+G**/SDD level
Figure 12. The decarbonylation, CO emission and reductive elimination steps of intermediate D. The decarbonylation and
reductive elimination transition states for intermediate C were also shown (in italic). The selected bond lengths are in angstroms,
and the relative free energies in chlorobenzene Gsol (413.15 K, 1.0 atm) are in kcal/mol. Calculated at M06/6-31+G**/SDD level.
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Kotsuma, T.; Murai, S. J. Am. Chem. Soc. 2002, 124, 10294; (d)
decarbonylation is the rate-determining step. However, the
barrier of the reductive elimination of intermediate E is just
slightly lower. These results are consistent well with the
observed large 12C/13C kinetic isotope effects at both the
aromatic acid and adjacent aromatic carbons (Figure 10).
Goldman, A. S.; Roy, A. H.; Huang, Z.; Ahuja, R.; Schinski, W.;
Brookhart, M. Science 2006, 312, 257; (e) Matsuda, T.; Tsuboi, T.;
Murakami, M. J. Am. Chem. Soc. 2007, 129, 12596; (f) Lee, S. I.;
Chatani, N. Chem. Commun. 2009, 371; (g) Ota, K.; Lee, S. I.; Tang,
J.-M.; Takachi, M.; Nakai, H.; Morimoto, T.; Sakurai, H.; Kataoka,
K.; Chatani, N. J. Am. Chem. Soc. 2009, 131, 15203; (h) Nakai, K.;
Kurahashi, T.; Matsubara, S. J. Am. Chem. Soc. 2011, 133, 11066;
(i) Grenning, A. J.; Tunge, J. A. Angew. Chem. Int. Ed. 2011, 50,
1688; (j) Grenning, A. J.; Tunge, J. A. J. Am. Chem. Soc. 2011, 133,
14785.
(2) (a) Crabtree, R. H. Chem. Rev. 1985, 85, 245; (b) Murakami,
M.; Ito, Y. Top. Organomet. Chem. 1999, 3, 97; (c) Jun, C.-H.
Chem. Soc. Rev. 2004, 33, 610; (d) Necas, D.; Kotora, M. Curr. Org.
Chem. 2007, 11, 1566; (e) Park, Y. J.; Park, J.-W.; Jun, C.-H. Acc.
Chem. Res. 2008, 41, 222; (f) Dermenci, A.; Coe, J. W.; Dong, G.
Org. Chem. Front. 2014, 1, 567; (g) Chen, F.; Wang, T.; Jiao, N.
Chem. Rev. 2014, 114, 8613; (h) Marek, I.; Masarwa, A.; Delaye,
P.-O.; Leibeling, M. Angew. Chem., Int. Ed. 2015, 54, 414.
(3) (a) Rybtchinski, B.; Milstein, D. Angew. Chem. Int. Ed. 1999,
38, 870; (b) Murakami, M.; Matsuda, T. Chem. Commun. 2011, 47,
1100.
(4) (a) Periana, R. A.; Bergman, R. G. J. Am. Chem. Soc. 1984,
106, 7272; (b) Murakami, M.; Amii, H.; Ito, Y. Nature 1994, 370,
540; (c) Murakami, M.; Takahashi, K.; Amii, H.; Ito, Y. J. Am.
Chem. Soc. 1997, 119, 9307; (d) Murakami, M.; Itahashi, T.; Amii,
H.; Takahashi, K.; Ito, Y. J. Am. Chem. Soc. 1998, 120, 9949; (e)
Kondo, T.; Nakamura, A.; Okada, T.; Suzuki, N.; Wada, K.;
Mitsudo, T.-a. J. Am. Chem. Soc. 2000, 122, 6319; (f) Kim, S.;
Takeuchi, D.; Osakada, K. J. Am. Chem. Soc. 2002, 124, 762; (g)
Kondo, T.; Kaneko, Y.; Taguchi, Y.; Nakamura, A.; Okada, T.;
Shiotsuki, M.; Ura, Y.; Wada, K.; Mitsudo, T.-a. J. Am. Chem. Soc.
2002, 124, 6824; (h) Murakami, M.; Itahashi, T.; Ito, Y. J. Am.
Chem. Soc. 2002, 124, 13976; (i) Kondo, T.; Taguchi, Y.; Kaneko,
Y.; Niimi, M.; Mitsudo, T.-a. Angew. Chem. Int. Ed. 2004, 43, 5369;
(j) Murakami, M.; Ashida, S.; Matsuda, T. J. Am. Chem. Soc. 2005,
127, 6932; (k) Matsuda, T.; Shigeno, M.; Makino, M.; Murakami,
M. Org. Lett. 2006, 8, 3379; (l) Yamamoto, Y.; Kuwabara, S.;
Hayashi, H.; Nishiyama, H. Adv. Synth. Catal. 2006, 348, 2493; (m)
Matsuda, T.; Shigeno, M.; Murakami, M. J. Am. Chem. Soc. 2007,
129, 12086; (n) Masuda, Y.; Hasegawa, M.; Yamashita, M.; Nozaki,
K.; Ishida, N.; Murakami, M. J. Am. Chem. Soc. 2013, 135, 7142; (o)
Souillart, L.; Cramer, N. Angew. Chem., Int. Ed. 2014, 53, 9640; (p)
Xu, T.; Dong, G. Angew. Chem. Int. Ed. 2014, 53, 10733; (q) Chen,
P.-h.; Xu, T.; Dong, G. Angew. Chem. Int. Ed. 2014, 53, 1674.
(5) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J.
Am. Chem. Soc. 2001, 123, 10407; (b) Nishimura, T.; Araki, H.;
Maeda, Y.; Uemura, S. Org. Lett. 2003, 5, 2997; (c) Takada, Y.;
Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. Org. Lett. 2006,
8, 2515; (d) Zhao, P.; Incarvito, C. D.; Hartwig, J. F. J. Am. Chem.
Soc. 2006, 128, 3124; (e) Winter, C.; Krause, N. Angew. Chem. Int.
Ed. 2009, 48, 2460; (f) Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.;Wang,
X.; Shi, Z.-J. J. Am. Chem. Soc. 2011, 133, 15244; (g) Sai, M.;
Yorimitsu, H.; Oshima, K. Angew. Chem. Int. Ed. 2011, 50, 3294;
(h) Chen, K.; Li, H.; Li, Y.; Zhang, X.-S.; Lei, Z.-Q.; Shi, Z.-J.
Chem. Sci. 2012, 3, 1645.
The barrier of decarbonylation of intermediate
C
(TS -DeCO-C, 21.2 kcal/mol) is similar to that of
intermediate D. Whereas the barrier of the reductive
elimination of the decarbonylative intermediate form C is
much higher (TS-RE-EF-C, 29.5 kcal/mol). This may
account for the chemoselectivity. From the calculation, we
also confirmed the decarbonylation is involved in the rate
determining step, which consistent with the 12C/13C kinetic
studies.
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Conclusion
In conclusion, we have developed an unprecedented
process to carry out the group exchange of two separated
carbonyl compounds. Two parts have been well proved
shaking their hands on the Rh(III) centre through two
different acyl-Rh intermediates. Isotopic-tracing studies and
by-product identification strongly supported the hypothesis
of group exchange via Rh catalysis. Systematic kinetic
experiments were conducted to find that decarbonylative is
the rate determining step. The calculation ascertained the
proposed mechanism and kinetic results. This study
extensively opens an eye to reconsider the organic synthesis
through completely new channel based on the reorganization
of the structural skeletons and group exchange. Further
investigations to explore new chemistry with this strategy are
underway in our laboratory.
ASSOCIATED CONTENT
Supporting Information
Details for calculation and experimental procedures, including
spectroscopic, analytical data of the new compounds are
reported in supporting information. “This material is available
free of charge via the Internet at http://pubs.acs.org.”
AUTHOR INFORMATION
Corresponding Author
Professor Yu-Xue Li, liyuxue@mail.sioc.ac.cn
Professor Jian Sun, sunjian@cib.ac.cn
Professor Zhang-Jie Shi, zshi@pku.edu.cn
Notes
The authors declare no competing financial interests.
(6) Youn, S. W.; Kim, B. S.; Jagdale, A. R. J. Am. Chem. Soc.
2012, 134, 11308.
(7)(a) van der Boom, M. E.; Kraatz, H.-B.; Ben-David, Y.;
Milstein, D. Chem. Commun. 1996, 2167; (b) Dermenci, A.;
Whittaker, R. E.; Dong, G. Org. Lett. 2013, 15, 2242.
(8) (a) Tobisu, M.; Kita, Y.; Chatani, N. J. Am. Chem. Soc. 2006,
128, 8152; (b) Nakao, Y.; Kanyiva, K. S.; Oda, S.; Hiyama, T. J.
Am. Chem. Soc. 2006, 128, 8146; (c) Nakao, Y.; Yada, A.; Ebata, S.;
Hiyama, T. J. Am. Chem. Soc. 2007, 129, 2428; (d) Nakao, Y.;
Ebata, S.; Yada, A.; Hiyama,T.; Ikawa, M.; Ogoshi, S. J. Am. Chem.
Soc. 2008, 130, 12874; (e) Watson, M. P.; Jacobsen, E. N. J. Am.
Chem. Soc. 2008, 130, 12594; (f) Nakao, Y.; Yada, A.; Hiyama, T.
J. Am. Chem. Soc. 2010, 132, 10024; (g) Rondla, N. R.; Levi, S. M.;
ACKNOWLEDGMENT
The authors gratefully acknowledge support for this work the
“973” project from the MOST of China (2015CB856600) and
2012SZ0219 from SCST and NSFC (grant nos. 21431008 and
21332001).
References
(1) (a) Vidal, V.; Théolier, A.; Thivolle-Cazat, J.; Basset, J.-M.
Science 1997, 276, 99; (b) Oi, S.; Tsukamoto, I.; Miyano, S.; Inoue,
Y. Organometallics 2001, 20, 3704; (c) Chatani, N.; Inoue, H.;
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1
2
3
4
5
6
7
8
Ryss, J. M.; Vanden Berg, R. A.; Douglas, C. J. Org. Lett. 2011, 13,
1940.
(9) (a) Daugulis, O.; Brookhart, M. Organometallics 2004, 23,
(25) Gaussian 09, R. A., Frisch, M. J.; Trucks, G. W.; Schlegel,
H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Scalmani,
G..; Barone, V.; Mennucci, B.; Petersson, G.. A.; Nakatsuji, H.;
Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.;
Zheng, G..; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.;
Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.;
Kitao, O.; Nakai, H.; Vreven, T.;. Montgomery, A. Jr.;Peralta, J. E.;
Ogliaro, F.; Bearpark, M.; Heyd, J. J.; Brothers, E.; Kudin, K. N.;
Staroverov, V. N.; Kobayashi, R.; Normand, J.; Raghavachari, K.;
Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.;
Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.
E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J.
W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas,
O.; Foresman, J. B.; Ortiz, J. V.; Cioslowski J.; Fox, D. J. Gaussian,
Inc., Wallingford CT, 2009.
527; (b) Kawata, A.; Takata, K.; Kuninobu, Y.; Takai, K. Angew.
Chem., Int. Ed. 2007, 46, 7793; (c) He, C.; Guo, S.; Huang, L.; Lei,
A. J. Am. Chem. Soc. 2010, 132, 8273; (d) Huang, L.; Cheng, K.;
Yao, B.; Xie, Y.; Zhang, Y. J. Org. Chem. 2011, 76, 5732; (e) Li,
H.; Li, W.; Liu, W.; He, Z.; Li, Z. Angew. Chem., Int. Ed. 2011, 50,
2975; (f) Kuninobu, Y.; Uesugi, T.; Kawata, A.; Takai, K. Angew.
Chem., Int. Ed. 2011, 50, 10406; (g) Kuninobu, Y.; Matsuzaki, H.;
Nishi, M.; Takai, K. Org. Lett. 2011, 13, 2959; (h) Arisawa, M.;
Kuwajima, M.; Toriyama, F.; Li, G.; Yamaguchi, M. Org. Lett.
2012, 14, 3804; (i) Zhou, W.; Li, H.; Wang, L. Org. Lett. 2012, 14,
4594; (j) Yamamoto, S.-i.; Okamoto, K.; Murakoso, M.; Kuninobu,
Y.; Takai, K. Org. Lett. 2012, 14, 3182; (k) Zhang, C.; Feng, P.;
Jiao, N. J. Am. Chem. Soc. 2013, 135, 15257; (l) Huang, X.; Li, X.;
Zou, M.; Song, S.; Tang, C.; Yuan, Y.; Jiao, N. J. Am. Chem. Soc.
2014, 136, 14858; (m) Tang, C.; Jiao, N. Angew. Chem., Int. Ed.
2014, 53, 6528; (n) Xing, Q.; Li, P.; Lv, H.; Lang, R.; Xia, C.; Li, F.
Chem. Commun. 2014, 50, 12181.
(10) (a) Suggs, J. W.; Jun, C. H. J. Am. Chem. Soc. 1984, 106,
3054; (b) Suggs, J. W.; Jun, C. H. J. Chem. Soc., Chem. Commun.
1985, 92; (c) Suggs, J. W.; Jun, C. H. J. Am. Chem. Soc. 1986, 108,
4679.
(11) (a) Jun, C.-H.; Huh, C.-W.; Na, S.-J. Angew. Chem., Int. Ed.
1998, 37, 145; (b) Jun, C.-H.; Lee, H. J. Am. Chem. Soc. 1999, 121,
880; (c) Jun, C.-H.; Hong, J.-B.; Kim, Y.-H.; Chung, K.-Y. Angew.
Chem., Int. Ed. 2000, 39, 3440.
(12) (a) Niwa, T.; Yorimitsu, H.; Oshima, K. Angew. Chem. Int.
Ed. 2007, 46, 2643; (b) Gribkov, D. V.; Pastine, S. J.; Schnürch, M.;
Sames, D. J. Am. Chem. Soc. 2007, 129, 11750; (c) Dreis, A. M.;
Douglas, C. J. J. Am. Chem. Soc. 2008, 131, 412; (d) Wentzel, M.
T.; Reddy, V. J.; Hyster,T. K.; Douglas, C. J. Angew. Chem. Int. Ed.
2009, 48, 6121; (e)Wang, J.; Chen,W.; Zuo, S.; Liu, L.; Zhang, X.;
Wang, J. Angew. Chem. Int. Ed. 2012, 51, 12334; (f) Wang, J.; Liu,
B.; Zhao, H.; Wang, J. Organometallics 2012, 31, 8598; (g) Ko, H.
M.; Dong, G. Nat. Chem. 2014, 6, 739; (h) Zeng, R.; Dong, G. J.
Am. Chem. Soc. 2015, 137, 1408.
(13) Lei, Z.-Q.; Li, H.; Li, Y.; Zhang, X.-S.; Chen, K.; Wang, X.;
Sun, J.; Shi, Z.-J. Angew. Chem. Int. Ed. 2012, 51, 2690.
(14) Pan, F.; Lei, Z.-Q.; Wang, H.; Li, H.; Sun, J.; Shi, Z.-J.
Angew. Chem. Int. Ed. 2013, 52, 2063.
(15) Yu, D.-G.; Li, B.-J.; Shi, Z.-J. Acc. Chem. Res. 2010, 43,
1486.
(16) Campeau, L.-C.; Parisien, M.; Jean, A.; Fagnou, K. J. Am.
Chem. Soc. 2005, 128, 581.
(17) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Am. Chem.
Soc. 1999, 121, 8645.
(18) For details, see Supporting Information.
(19) (a) Jin, W.; Yu, Z.; He, W.; Ye, W.; Xiao, W.-J. Org. Lett.
2009, 11, 1317; (b) Miranda, M. O.; Pietrangelo, A.; Hillmyer, M.
A.; Tolman,W. B. Green Chem. 2012, 14, 490.
(20) Fristrup, P.; Kreis, M.; Palmelund, A.; Norrby, P.-O.;
Madsen, R. J. Am. Chem. Soc. 2008, 130, 5206.
(21) (a) Miyamura, S.; Tsurugi, H.; Satoh, T.; Miura, M. J.
Organomet. Chem. 2008, 693, 2438; (b) Shuai, Q.; Yang, L.; Guo,
X.; Baslé, O.; Li, C.-J. J. Am. Chem. Soc. 2010, 132, 12212; (c)
Wencel-Delord, J.; Nimphius, C.; Patureau, F. W.; Glorius, F.
Angew. Chem. Int. Ed. 2012, 51, 2247.
(22) (a) Singleton, D. A.;Thomas, A. A. J. Am. Chem. Soc. 1995,
117, 9357; (b) Frantz, D. E.; Singleton, D. A.; Snyder, J. P. J. Am.
Chem. Soc. 1997, 119, 3383.
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10
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23
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27
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40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(26) Zhao, Y.;Truhlar, D. Theor. Chem. Acc. 2008, 120, 215.
(27) Fuentealba, P.; Preuss, H.; Stoll, H.; Von Szentpály, L.
Chem. Phys. Lett. 1982, 89, 418.
(28) Marenich, A. V.; Cramer, C. J.; Truhlar, D. G. J. Phys.
Chem. B 2009, 113, 6378.
(23) The
byproducts (total <10%) of ketone 1g were
protonation and intramolecular decarbonylative coupling products,
which all involved the same C-C bond cleavage of alkyl ketone.
After correction for 80% conversion, the actual KIEs would be
10% further from 1.000 than the values in Figure 11. This
correction is small compared to the uncertainty in these values.
(24) (a) Hohenberg, P.; Kohn, W. Phys. Rev. 1964, 136, B864; (b)
Kohn, W.; Sham, L. J. Phys. Rev.1965, 140, A1133.
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