General and practical carboxyl-group-directed remote C-H oxygenation reactions of arenes

Article abstract of DOI:10.1002/chem.201303511

Two methods for remote aromatic C-H oxygenation reactions, have been developed. Method1, the Cu-catalyzed oxygenation reaction, is highly efficient for cyclization of electron-neutral and electron-rich biaryl carboxylic acids into 3,4-benzocoumarins. Method2, the K₂S₂O ₈-mediated oxygenation reaction, is more general and practical for cyclization of substrates with electron-donating and -withdrawing groups (see scheme). Copyright

Full text of DOI:10.1002/chem.201303511

COMMUNICATION
DOI: 10.1002/chem.201303511
À
General and Practical Carboxyl-Group-Directed Remote C H Oxygenation
Reactions of Arenes
Yang Wang, Anton V. Gulevich, and Vladimir Gevorgyan*[a]
Transition-metal-catalyzed ar-
À
omatic C H oxygenation reac-
tion[1] is a very powerful tool
for straightforward synthesis of
valuable
products
oxygen-containing
from abundant
arenes.[2] Of these reactions, in-
À
À
tramolecular C H/O H oxida-
tive coupling of carboxylic acid
2
À
with unactivated sp C H bond
is an important transformation,
because it gives an access to
a variety of valuable lactone-
containing molecules.[3] Thus,
3,4-benzocoumarin fragment 2,
containing six-membered lac-
tone moiety, is widely found in
natural and bioactive molecules,
as well as in useful materials.[4]
Expectedly, 2 can be accessed
through cyclization of nonpre-
À
Scheme 1. Carboxyl-group-directed C H oxygenation reactions.
functionalized
2-arylbenzoic
acids 1; however, the existing methods require either em-
ployment of stoichiometric amounts of toxic oxidants[5] or
UV irradiation,[6] which substantially limits applicability of
these methods (Scheme 1). We hypothesized that it should
be possible to develop a general, practical, and environmen-
tally benign dehydrogenative C H/O H lactonization reac-
tion of 2-arylbenzoic acids 1 into 3,4-benzocoumarins 2 en
route to oxygenated biaryls 3. We envisioned that C H oxy-
genation could potentially be performed by formation of
mation was disclosed by Gallardo-Donaire and Martin.[8]
Most importantly, we also developed a more general and
practical Method 2, the K2S2O8-mediated oxygenation reac-
tion, which is widely applicable for cyclization of electron-
neutral, electron-rich, as well as electron-deficient sub-
strates.
To develop mild and environmentally benign intramolecu-
lar lactonization reaction of 2-arylbenzoic acids, we per-
formed extensive screening of transition-metal catalysts and
oxidants.[9] It was found that this reaction can efficiently be
accomplished by using CuII catalyst. Thus, 2-phenylbenzoic
acid 1a was converted into the desired benzocoumarin prod-
À
À
À
carboxyl O-centered radical A, which would undergo a sub-
[7]
À
sequent C O bond formation.
Herein, we report two complimentary methods for this
transformation. Method 1, the Cu-catalyzed oxygenation re-
action of 2-arylbenzoic acids, which is efficient for electron-
neutral and electron-rich substrates. During preparation of
this manuscript, a similar to Method 1 Cu-catalyzed transfor-
uct 2a in 88% yield in the presence of CuACTHNUGRTNEUNG(OAc)2·H2O
(5 mol%) and tert-butyl peroxybenzoate (TBPB, Luperox P)
in dichloroethane (Method 1). We found that substrates
with electron-neutral and electron-donating substituents, as
well as aryl halide fragments (Hal=F, Cl, Br) and cyano-
group on the “guest” aryl ring, produced the desired prod-
ucts in good to excellent yield (Table 1, entries 2a–j). In
general, benzoic acids substituted with arene ring containing
meta-substituents (F, Cl, OMe, tBu) preferentially under-
went cyclization at the less hindered site (Table 1, en-
tries 2k–n). In contrast, meta-Me substituted substrate 1o
cyclized at the more hindered site producing 2o as a major
[a] Y. Wang, Dr. A. V. Gulevich, Prof. Dr. V. Gevorgyan
Department of Chemistry, University of Illinois at Chicago
845 W. Taylor St., Chicago, Illinois 60607 (USA)
Fax : (+1)312-355-0836
E-mail: vlad@uic.edu
Homepage: http://www.chem.uic.edu/vggroup/
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201303511.
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À
Table 1. Cu -catalyzed C H oxygenation reaction.
ment of a complementary method for cyclization of electron
deficient 2-arylbenzoic acids. Delightfully, we found that this
transformation can be performed in the presence of K2S2O8
oxidant in aqueous acetonitrile.[11] Thus, benzocoumarin 2a
was formed in 93% yield from 2-phenylbenzoic acid 1a in
gram-scale manner by using this convenient and environ-
mentally benign protocol (Table 2). We found that Method 2
works efficiently for electron-neutral and electron-deficient
substrates under these conditions (entries 2a,i,p,r,t,u). No-
tably, in the presence of K2S2O8, benzoic acids substituted
with arene ring containing meta-substituents produced the
corresponding products in higher selectivity compared to
that of Method 1 (Table 2, entries 2k–o’). Most importantly,
the developed protocol can be successfully applied to a vari-
ety of electron-deficient substrates. Accordingly, 2-arylben-
zoic acids with CF3 (2w, 2aa), COMe (2x), CONMe2 (2y),
and CHO (2z) groups underwent cyclization producing the
corresponding products in good to excellent yields. More-
over, previously incompetent substrates with highly elec-
tron-withdrawing NO2 group (2ac, 2ad, 2ae) and even two
CF3 groups (2ab) now were smoothly transformed into the
corresponding benzocoumarin products (Method 1, Table 1).
À
Table 2. K2S2O8-mediated C H oxygenation reaction.
regioisomer (4:1).[10] In addition, 2-naphthyl substituted ben-
zoic acid 1p gave the product of cyclization at the more
electron-rich 1-position, exclusively (2p). Likewise, sub-
strates containing 3,5-disubstituted arene ring also under-
went efficient cyclization into benzocoumarin products 2q
and r. 2-Phenylbenzoic acids containing substituents at 1-,
À
2-, and 3-positions also underwent smooth C H oxygenation
reaction producing products 2s–v. Although electron-neutral
and electron-rich substrates under these reaction conditions
(Method 1) gave the corresponding benzocoumarins in good
to excellent yields, cyclization reaction of electron-deficient
substrates was less efficient. Hence, 2-arylbenzoic acids with
important electron-withdrawing functional groups, such as
CF3 (1w), COMe (1x), and CONMe2 (1y) provided the cor-
responding products in diminished yields, whereas substrates
possessing CHO (1z), CF3 (1aa, ab), and NO2 groups (1ac–
ae) produced trace to no product at all (Table 1).
To overcome this limitation of the Cu-catalyzed oxygena-
tion reaction (Method 1, Table 1), we aimed at the develop-
[a] AgNO3 (10 mol%) additive was used.
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Remote C H Oxygenation Reactions of Arenes
COMMUNICATION
It should be mentioned that in
some cases, addition of a cata-
lytic
amount
of
AgNO3
(10 mol%) led to substantial in-
creases of reaction rates.[12,13]
Naturally, the developed
methods open access to a varie-
ty of densely functionalized
benzocoumarin molecules.[4] In
addition, considering the impor-
tance of aryl ether moiety, we
have shown that the obtained
3,4-benzocoumarins could be
nearly quantitatively converted
into the corresponding biaryl
ethers 3 (Scheme 2).
Scheme 2. Conversion of lactones into aryl ethers.
It is likely that the CuII-cata-
lyzed oxygenation reaction
(Method 1) proceeds through
an active CuIII intermediate A
(Scheme 3), which may abstract
the adjacent hydrogen atom to
form aryl radical B (Path A).
The latter, upon oxidative ring
closure, would produce B’, fol-
lowed by a reductive elimina-
tion to form 2.[14,15] Alternative-
Scheme 3. Proposed mechanism for Method 1.
ly,
(SET) process in A would give
radical–cation specie
a single-electron transfer
C
(Path B), which would be trans-
formed into 2 by a subsequent
[16]
À
C O bond-forming reaction.
The K2S2O8-mediated oxy-
genation reaction (Method 2)
most likely proceeds by oxida-
tion of benzoic acid 1 into an
O-centered carboxylic radical
D, which undergoes addition to
the arene ring to form an aryl
radical
intermediate
E
(Scheme 4, [Eq. (1)], Path A).
The latter converts into the
benzocoumarin product 2a
upon loss of a hydrogen radical.
This homolytic aromatic substi-
tution mechanism is supported
by our experiments on cycliza-
tion of substrates containing 2-
haloaryl substituents 4a–c (G=
F, Cl, Br). It was found that
these reactions exclusively pro-
duce substitution products 2a
Scheme 4. Proposed mechanism for Method 2.
À
instead of possible C H cou-
pling products 5 (Scheme 4, [Eq. (2)]).[17] Alternative mecha-
nism involving an abstraction of hydrogen radical from the
aromatic ring in the intermediate D to form the aromatic
radical F cannot be ruled out at this stage (Scheme 4,
[Eq. (1)], Path B).
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V. Gevorgyan et al.
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In conclusion, two complimentary methods for carboxyl-
À
group-directed remote C H oxygenation reaction of arenes
were developed. Method 1, the Cu-catalyzed reaction, pro-
duces a variety of 3,4-benzocoumarins containing electron-
neutral and electron-releasing substituents. In addition,
a more general Method 2, the K2S2O8-mediated transforma-
tion, which is widely applicable to various electron-rich and
electron-deficient 2-arylbenzoic acids, was developed. This
protocol features a broad scope, a good functional group tol-
erance, and good selectivity. It is also benign, operationally
simple, easily scalable, and proceeds under mild conditions.
À
À
[3] For recent selected examples on transition metal-catalyzed C H/O
Experimental Section
H oxidative coupling of carboxylic acid with unactivated sp2 C H
À
bond, see: a) Y. Li, Y.-J. Ding, J.-Y. Wang, Y.-M. Su, X.-S. Wang,
Org. Lett. 2013, 15, 2574; b) M. Yang, X. Jiang, W.-J. Shi, Q.-L. Zhu,
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Procedure for oxygenation of 2-phenylbenzoic acid: Under ambient at-
mosphere, 2-phenylbenzoic acid 1a (1.98 g, 10 mmol) and K2S2O8 (8.2 g,
30 mmol, 3 equiv) were added to
a round-bottom flask (250 mL)
equipped with stirring bar, followed by addition of H2O/MeCN (100 mL,
1:1) mixture. The resulting reaction mixture was heated for 18 h at 508C
by using oil bath (GC monitoring). After reaction was complete, an aque-
ous solution of NaOH (50 mL, 1m) was added to the reaction mixture at
RT. The product was extracted with ethyl acetate (3ꢁ30 mL), the com-
bined organic extract was dried (Na2SO4), filtered (short path of silica
gel), and the solvent was removed in vacuo. The product 2a was obtained
in 93% yield (1.82 g) as a white solid.
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Acknowledgements
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[6] For UV-promoted ArIACTHNUTRGNEUNG(OCOR)2-mediated cyclization, see: a) H.
À
Keywords: benzocoumarins
activation · oxygenation · radical reactions
·
carboxylic acids
·
C H
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À
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[10] The observed selectivity is similar to that in recently reported radi-
À
cal-mediated C O bond-formation reaction, see: C. Yuan, Y. Liang,
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À
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À
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Remote C H Oxygenation Reactions of Arenes
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Gian
3292.
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[15] For
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Received: September 6, 2013
Published online: && &&, 0000
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V. Gevorgyan et al.
Synthetic Methods
Y. Wang, A. V. Gulevich,
V. Gevorgyan* ................ &&&& — &&&&
General and Practical Carboxyl-
À
Group-Directed Remote C H
Oxygenation Reactions of Arenes
À
Two methods for remote aromatic C
into 3,4-benzocoumarins. Method 2,
the K2S2O8-mediated oxygenation
reaction, is more general and practical
for cyclization of substrates with elec-
tron-donating and -withdrawing groups
(see scheme).
H oxygenation reaction have been
developed. Method 1, the Cu-catalyzed
oxygenation reaction is highly efficient
for cyclization of electron-neutral and
electron-rich biaryl carboxylic acids
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ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
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These are not the final page numbers!