Palladium-catalyzed intermolecular decarboxylative coupling of 2-phenylbenzoic acids with alkynes via C-H and C-C bond activation

Article abstract of DOI:10.1021/ja106130r

A novel protocol for palladium-catalyzed intermolecular formal [4 + 2] annulation of 2-phenylbenzoic acids with alkynes is described. Acridine is shown to be essential for the high reaction efficiency. Phenanthrene derivatives are formed in moderate to good yields without coupling (pseudo)halides or organometallic species.

Full text of DOI:10.1021/ja106130r

Published on Web 09/10/2010
Palladium-Catalyzed Intermolecular Decarboxylative Coupling of
2-Phenylbenzoic Acids with Alkynes via C-H and C-C Bond Activation
Congyang Wang,* Souvik Rakshit, and Frank Glorius*
Westfa¨lische Wilhelms-UniVersita¨t Mu¨nster, NRW Graduate School of Chemistry, Organisch-Chemisches Institut,
Corrensstrasse 40, 48149 Mu¨nster, Germany
Received July 11, 2010; E-mail: wangcy@iccas.ac.cn; glorius@uni-muenster.de
Table 1. Substrate Variation of Alkynesa b
,
Abstract: A novel protocol for palladium-catalyzed intermolecular
formal [4 + 2] annulation of 2-phenylbenzoic acids with alkynes
is described. Acridine is shown to be essential for the high
reaction efficiency. Phenanthrene derivatives are formed in
moderate to good yields without coupling (pseudo)halides or
organometallic species.
Transition-metal catalyzed carbon-carbon bond formations have
become powerful tools to construct organic molecules. Prefunc-
tionalized substrates such as organohalides or pseudohalides and
organometallic compounds are coupled in these transformations.
Recently, the use of carbon-based leaving groups emerged as an
a Reaction conditions: 1a (0.5 mmol), 2 (1.0 mmol), Pd(OAc)2 (0.05
mmol), acridine (0.25 mmol), Ag2CO3 (1.5 mmol), DMF (5 mL), 140
°C, 14 h. b Isolated yield. c Side product 4ab isolated in 9% yield.
attractive alternative defying the high dissociation energies (BDEs)
of C-C bonds.1 Among them, pioneering work from the groups
of Myers, Goossen, Bilodeau, and others employing arene car-
boxylic acids as coupling partners represents a major breakthrough
in this field.2-4 A variety of benzoic acids could be coupled with
aryl halides, triflates, diaryliodonium triflates, or tosylates via
decarboxylative coupling affording biaryl compounds under prop-
erly tuned catalyst systems.3
Subsequently, Crabtree et al., we, and others further extended
the concept to the C-H activation field disclosing the direct
aryl-aryl bond formation through a decarboxylation/C-H activa-
tion sequence (Scheme 1A).5 The merging of two challenging areas
created new attractive strategies for C-C bond formations since
neither organohalides nor sensitive organometallics are required in
these processes. Herein we report the palladium-catalyzed inter-
molecular formal [4 + 2] annulation of 2-phenylbenzoic acids with
alkynes affording phenanthrenes (Scheme 1B).6
reactions has recently been demonstrated by Stoltz et al. and Yu et
al.8 After surveying a variety of pyridine derivatives, the best results
were obtained using acridine.7 Finally, using 10 mol % Pd(OAc)2,
AgCO3 as the oxidant in DMF, and 0.5 equiv of acridine provided
optimal results.7
These conditions are compatible with a broad range of alkyne
substrates (Table 1). Diphenylacetylene derivatives work well
leading to the corresponding phenanthrenes 3ab-3ag in good
yields. Specifically, alkynes bearing electron-withdrawing nitro or
ester groups or an electron-donating methoxy group are all
successfully engaged in this reaction. It is noteworthy that halogen
functionalities remain intact after reactions, thus offering handles
for other valuable manipulations. Protected (OMe, OTBS) prop-
argylic alcohols containing rather labile methylene groups are also
applicable in this oxidative protocol (3ah, 3ai). Only one C-C
triple bond of buta-1,3-diyne was involved in the reaction leading
to phenylethynyl substituted phenanthrene 3aj. It should be noted
that, in certain cases, very small amounts of coproducts 4 as
mixtures of several regioisomers (see also Table 2) were detected
but were not isolable (except for 4ab).
Scheme 1. Merging Decarboxylation and C-H Activation
Next, a variety of 2-phenylbenzoic acid derivatives were
examined (Table 2). Substrates bearing different substitution
patterns on the benzene ring undergoing C-H activation all led to
the expected products 3b, 3c with the formation of 4b, 4c as minor
products. Benzoic acids with a naphthyl moiety on the ortho
positions afforded benzo[c]phenanthrene 3d and benzo[a] an-
thracene 3e under the same reaction conditions. Despite the
enhanced steric hindrance, phenanthrene 3f was obtained from the
reaction of 2-phenyl-6-methyl benzoic acid 1f and diphenylacetylene
in high yield. Encouraged by these results, we sought to investigate
the regioselectivity derived from the insertion of unsymmetrical
alkynes. Gratifyingly, phenanthrenes 3g-3i were formed as major
isomers from the reactions of three different sets of substituted
To test our hypothesis, we first examined the reaction of
2-phenylbenzoic acid 1a with 1-phenyl-1-butyne 2a (Table 1). After
extensive screening of a large array of reaction parameters,7 we
found that the addition of 0.5 equiv of pyridine derivatives played
a pivotal role for the high efficiency of the desired reaction. This
kind of beneficial effect of pyridine ligands in palladium-catalyzed
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C O M M U N I C A T I O N S
Table 2. Substrate Variation of 2-Phenylbenzoic Acidsa b
,
precluded because of its pseudosymmetrical nature, which is not
in agreement with the obtained high levels of selectivity (7:1).
Alternatively, carboxylic acid directed C-D activation might occur,
providing VI. Whereas decarboxylation to III (path c) can be
excluded (see above), the carbopalladation/decarboxylation/reduc-
tive elimination sequence (path d) is in agreement with the
experimental observations.11 Finally, Pd0 is reoxidized to PdII by
the AgI oxidant, thus closing the catalytic cycle (not shown).
In conclusion, we have developed the first palladium-catalyzed
formal [4 + 2] annulation of 2-phenylbenzoic acids with alkynes
via successive cleavage of both C-H and C-C bonds, obviating
the need for organometallic and halide coupling partners. This
methodology might find application in the synthesis of polycyclic
aromatic hydrocarbons (PAHs) for material science.12
Acknowledgment. Generous financial support by the Alexander
von Humboldt Foundation (C.W.) and the International NRW
Graduate School of Chemistry (S.R.) is gratefully acknowledged.
The research of F.G. was supported by the Alfried Krupp Prize for
Young University Teachers of the Alfried Krupp von Bohlen und
Halbach Foundation.
a Reaction conditions: 1 (0.5 mmol), 2 (1.0 mmol), Pd(OAc)2 (0.05
mmol), acridine (0.25 mmol), Ag2CO3 (1.5 mmol), DMF (5 mL), 140
°C, 14 h. b Yield of the isolated, pure product. c The isolated yields of
minor products 4 are listed in brackets. d Combined yield of two
regioisomers 3c and 3f in the ratio of 2:1 (major isomer shown).
e Combined yield of two regioisomers 3e and 3e′ in the ratio of 1:1 (one
isomer shown). f The ratio of two regioisomers are listed in brackets.
Supporting Information Available: Experimental procedures and
full spectroscopic data for all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
References
Scheme 2. Plausible Mechanism
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