RhIII-Catalyzed C-H Olefination of Benzoic Acids under Mild Conditions using Oxygen as the Sole Oxidant

Article abstract of DOI:10.1002/asia.201500601

Phthalide skeletons have been synthesized for the first time through a Rh^III-catalyzed C-H olefination of benzoic acids under mild conditions using oxygen as the sole oxidant. Aromatic acids bearing a variety of functional groups could react wi

Full text of DOI:10.1002/asia.201500601

DOI: 10.1002/asia.201500601
Communication
CÀH activation
|Very Important Paper|
III
Rh -Catalyzed CÀH Olefination of Benzoic Acids under Mild
Conditions using Oxygen as the Sole Oxidant
[
a]
Quandi Jiang, Changlei Zhu, Huaiqing Zhao,* and Weiping Su*
require high temperature or have poor functional group toler-
Abstract: Phthalide skeletons have been synthesized for
[
8]
III
ance.
the first time through a Rh -catalyzed CÀH olefination of
The phthalide skeleton is present in a large number of natu-
ral products and pharmaceuticals and showed biological prop-
benzoic acids under mild conditions using oxygen as the
sole oxidant. Aromatic acids bearing a variety of functional
groups could react with diverse alkenes to afford the de-
sired cyclized lactones or uncyclized alkenylarenes in mod-
erate-to-excellent yields.
[
9]
erties (Figure 1). As part of our research project that aims at
[
10]
the reactivity of benzoic acids, we attempted to synthesize
III
the phthalide skeleton via the Rh -catalyzed aerobic oxidative
ortho-CÀH olefination of benzoic acids. Herein, we report the
results from this investigation and present a very mild, efficient
III
Rh -catalyzed method for the construction of phthalide skele-
Transition metal catalyzed CÀH functionalization has become
a very powerful tool for chemists to synthesize useful organic
[
1]
molecules. One of the most intensively explored reactions is
the direct coupling of unactivated aromatic substrates with al-
[
2]
kenes to construct different alkenylarene frameworks. Al-
though a variety of transition metal and transition metal com-
III
plexes have been explored to catalyze such reactions, Rh
Figure 1. Antiplatelet for ischemia-cerebralapoplexy (I) and softening agent
and plant growth regulator (II).
complexes are considered to be a valuable catalyst for the ole-
fination of an inert aryl CÀH bond because of its high catalytic
[3]
III
activity and excellent functional group tolerance. Rh com-
plexes have catalyzed the ortho-selective CÀH olefination of
arenes with diverse directing groups such as N-oxides, N-
Table 1. Optimization of the Rh-catalyzed olefination.
[3a,4]
alkoxy-amides, oxime ester, carbonyl and carboxyl.
Howev-
er, most of these reactions used peroxides, hypervalent iodoni-
um salts or metal oxidants as terminal oxidants to maintain
[
5]
the catalytic cycle, in which unpleasant byproducts and
waste materials were produced. A greener method that uses
oxygen as the terminal oxidant will be highly attractive be-
[a]
[6]
Entry
Base [equiv]
Additives [equiv]
Solvent
1 2
3a /3a Yield[%]
cause it only generates water as the byproduct. So far, some
research groups have successfully achieved the goal of using
molecular oxygen as the terminal oxidant in CÀH olefination
b
1
CsOAc (0.5)
CsOAc (0.5)
CsOAc (0.5)
CsOAc (0.6)
CsOAc (0.2)
CsOAc (0.5)
CsOAc (0.5)
NaOAc(0.5)
–
–
–
–
–
–
–
–
DCE
DCE
DCE
DCE
DCE
DMF
DMSO
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
–(40/trace)
–(45/trace)
–(36/trace)
39/trace
trace
0
0
10
23
–(50/trace)
–(30/trace)
88(70/12)
67(58/4)
18
2
3
c
[7]
reactions with some metal complexes. Very recently, the rare
4
5
6
7
8
9
III
examples of Rh -catalyzed aerobic oxidative CÀH functionaliza-
tion have appeared, however, these reported reactions usually
KHCO
KHCO
KHCO
3
(0.5)
3
(0.5)
3
(0.5)
–
[
a] Q. Jiang, C. Zhu, H. Zhao, Prof. Dr. W. Su
State Key Laboratory of Structural Chemistry
Fujian Institute of Research on the Structure of Matter
Chinese Academy of Sciences
10
HOAc(0.5)
HOAc(0.2)
HOAc(0.7)
HOAc(0.8)
HOAc(0.6)
HOAc(0.7)
PivOH(0.7)
1
1
12
KHCO
KHCO
CO
NaHCO
KHCO (0.5)
3
(0.5)
(0.5)
(0.5)
1
1
1
1
3
4
5
6
3
Yangqiao West Road 155, Fuzhou, Fujian 350002 (China)
E-mail: wpsu@fjirsm.ac.cn
K
2
3
3
(0.5)
52(35/trace)
44/trace
hqzhao@fjirsm.ac.cn
3
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.201500601.
2 2
Reaction conditions: 1a (0.2 mmol), 2a (0.5 mmol), [Cp*RhCl ] (2.5 mol%),
solvent (1.5 mL), 608C, 24 h, Schlenk tube (35 mL) with an oxygen balloon
was used. [a] GC yield; yield of isolated product in parentheses. [b] The ratio
of 1a to 2a is 1:2. [c] The ratio of 1a to 2a is 1:3.
This manuscript is part of a special issue on catalysis and transformation
of complex molecules. Click here to see the Table of Contents of the special
issue.
Chem. Asian J. 2016, 11, 356 – 359
356
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
tons through ortho-alkenylation
of benzoic acids under an
oxygen atmosphere without any
other external oxidants.
We started our study by ex-
amining the model reaction of
benzoic acid (1a) and methyl ac-
rylate (2a) in the presence of
[
(
Cp*RhCl2]2 as the catalyst
Table 1). Initially, the model re-
action was conducted at 608C in
dichloroethane (DCE) using
CsOAc as a base with an oxygen
balloon and this generated the
desired product in 40% yield
(
Table 1, entry 1). Increasing the
amount of 2a to 2.5 equiv from
.0 equiv improved the yield of
the desired product slightly
Table 1, entry 2). However, fur-
ther increasing the ratio of 2a to
a up to 3:1 led to a decrease in
2
(
1
yield (Table 1, entry 3), presuma-
bly because an excess of 2a
might influence the interaction
III
of 1a with the Rh catalyst. No
desired products were detected
when the reactions were carried
out in other solvents such as
N,N-dimethylformamide (DMF)
and dimethyl sulfoxide (DMSO)
(
Table 1, entries 6 and 7). Gratify-
ingly, a 50% yield was obtained
in the presence of KHCO as the
3
base and CH COOH (0.5 equiv)
3
[
a]
Scheme 1. Rh-catalyzed olefination of different benzoic acids.
[
(
as an additive (Table 1, entry 10).
The best result (82%) was ob-
tained when the amount of
a] reaction conditions: 1a (0.2 mmol), 2a (0.5 mmol), [Cp*RhCl
0.14 mmol), DCE (1.5 mL), in a Schlenk tube (35 mL) with an oxygen balloon. All yields are yields of isolated prod-
2
]
2
(2.5 mol%), KHCO
3
, (0.1 mmol), HOAc
ucts, the value in parentheses is 3a
1
:3a
2
. [b] 1.5 mL CH
2
Cl
2
was used as the solvent in a 55 mL Schlenk tube.
CH COOH was increased to
3
0
.7 equiv (Table 1, entry 12), and
further increasing the amount of
additive caused a drop in yield, thereby suggesting that the
concentration of acid additive had an effect on the transforma-
tion (Table 1, entry 13). Other acids, such as pivalic acid
a slightly lower yield, perhaps this is due to the strong elec-
tron-donating effect (3i, 3k). Substrates with an electron-with-
drawing group afforded the products in moderate yield (3e). It
is worth noting that when para-chlorinated or brominated sub-
strates were used the products were furnished in good yields;
these products possess versatile handles for further chemical
transformations (3 f, 3g). Methyl, chloro, phenoxyl, 4-chloro-
benzoyl substituents at the 2-position of substrates afforded
the desired products 3p, 3q, 3s, 3t in 64%, 64%, 60%, 91%
yield, respectively. Interestingly, the benzoic acid with an ortho-
acetyl substituent gave a mixture of lactone product and un-
cyclized product in 1:1 ratio, probably because the hydrogen
bond between the carboxyl and acetyl (3ab) had an impact on
the cyclization. We further examined some disubstituted or tri-
substituted benzoic acids, and to our delight, the optimal con-
ditions were applicable to both disubstituted and trisubstitut-
(
Table 1, entry 16) and propionic acid (see the Supporting In-
formation) were inferior to acetic acid, thus indicating that the
reaction outcome depended on the nature of acid additives.
With the optimized conditions in hand (Table 1, entry 12),
we evaluated the substrate scope of the reaction with respect
to benzoic acids. As shown in Scheme 1, the benzoic acids
containing electron-donating groups such as a methyl, tert-
butyl, phenoxyl, acetoxyl, trifluoromethoxyl or trifluorome-
thylthio substituent at the para or meta positions of the aryl
moiety were efficiently coupled with the methyl acrylate, pro-
ducing the desired products with good to excellent yields (3b,
3
d, 3j, 3l–3o). However, the substrates with a methoxy or
benzyloxy at the para position of the aromatic ring resulted in
Chem. Asian J. 2016, 11, 356 – 359
www.chemasianj.org
357
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
the alkenylation product. At this point, the above steps are re-
I
peated to give disubstituted product. The Rh species is re-
leased from b-hydride elimination and reacts with dioxygen to
III
regenerate the Rh catalyst. The ortho-alkenylated product fur-
ther undergoes an intramolecular Michael addition to afford
the lactone product.
III
In summary, an operationally simple, mild Rh -catalyzed
method for the directed ortho CÀH bond olefination of benzo-
ic acids has been developed. This protocol featured the use of
oxygen as the sole oxidant, tolerance to a broad range of func-
tional groups, and gave the desired products in high yields,
thus providing a useful method for the synthesis of phthalide
skeletons.
Experimental Section
General Experimental Procedures
In a glove box, the Schlenk tube was equipped with a stirrer bar
and was charged with [Cp*RhCl ] (2.5 mol%), KHCO (0.5 equiv),
and benzoic acid (0.2 mmol). The tube was fitted with a rubber
2
2
3
[
a]
Scheme 2. Rh-Catalyzed olefination of different alkenes.
a] reaction conditions: 1v (0.2 mmol), 2 (0.5 mmol), [Cp*RhCl
KHCO , (0.1 mmol), HOAc (0.14 mmol), DCE (1.5 mL), in a Schlenk tube
35 mL) with an oxygen balloon. All yields are yields of isolated products.
[
2 2
] (2.5 mol%),
plug and removed out of the glove box. DCE (1.5 mL), CH COOH
3
3
(
7.9 mL), and 2 (2.5 equiv) were added to the Schlenk tube using
(
syringes and then the tube was subjected to a vacuum and refilled
with an O flow, the procedure was repeated three times, and then
2
an oxygen balloon was used. The reaction was slowly heated to
ed benzoic acids to afford the desired products in good-to-ex-
cellent yields (3v, 3y, 3z, 3aa). Notably, benzoic acids with
two halide substituents were also tolerated and afforded 3r,
6
08C and stirred for 24 h. Upon completion, the reaction mixture
was diluted with ethyl acetate (10 mL), filtered through a pad of
silica gel, followed by washing the pad of the silica gel with the
ethyl acetate (20 mL). The filtrate was concentrated under reduced
3
u, 3w, 3x in 66%, 62%, 83%, 93% yields, respectively.
Subsequently, we utilized a representative set of
substituted alkenes to explore the versatility of the
standard conditions. As shown in Scheme 2, electron-
deficient olefins, such as ethyl acrylate, tert-butyl ac-
rylate, benzyl acrylate, isobutyl acrylate, and phenyl
acrylate, afforded the lactone products 4a–4d and
4
g in good-to-excellent yields. Surprisingly, (vinylsul-
fonyl)benzene and diethyl vinylphosphonate reacted
smoothly with 4-chloro-2-methoxybenzoic acid to Scheme 3. Hydrogen–deuterium exchange experiments.
form the corresponding products 4e and 4 f in 77%
and 79% yields, respectively. Unfortunately, when the
unactivated 1-nitro-3-vinylbenzene was used, the de-
sired product (5a) was afforded in only 23% yield,
this could be due to the homo-coupling of styrene
derivatives under acidic conditions.
An intermolecular competition reaction between
1
a and [D ]-1a for CÀH alkenylation was performed
5
and it found that the kH/D value was 4.7 (Scheme 3);
this suggests that the ortho-CÀH bond cleavage is
likely the rate-limiting step in this transformation.
On the basis of our experiments and previous re-
[
5a,7f,8a,d]
lated research
we proposed a plausible mech-
anism for this transformation (Scheme 4). The coordi-
III
nation of 1a to the [Rh ] catalyst facilitates CÀH
cleavage to form a cyclometalation intermediate A,
then coordination of the olefin substrate to the Rh
center forms complex B, which then undergoes mi-
gration/insertion and b-hydride elimination to yield Scheme 4. The proposed mechanism of this transformation.
Chem. Asian J. 2016, 11, 356 – 359
www.chemasianj.org
358
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communication
pressure. The residue was then purified by preparative TLC to pro-
vide the corresponding product 3 (eluent: 25% EtOAc/hexane).
9412; Angew. Chem. 2011, 123, 9581–9584; d) N. D. Ball, J. W. Kampf,
M. S. Sanford, J. Am. Chem. Soc. 2010, 132, 2878–2879; e) A. John, K. M.
Nicholas, J. Org. Chem. 2012, 77, 5600–5605; f) S. R. Whitfield, M. S. San-
ford, J. Am. Chem. Soc. 2007, 129, 15142–15143; g) M. Miura, C. G.
Feng, S. Ma, J. Q. Yu, Org. Lett. 2013, 15, 5258–5261.
Acknowledgements
[
[
6] a) S. S. Stahl, Angew. Chem. Int. Ed. 2004, 43, 3400–3420; Angew. Chem.
2004, 116, 3480–3501; b) S. S. Stahl, Science 2005, 309, 1824–1826;
Financial support from NSFC (21431008, 21332001 and
c) W. Wu, H. Jiang, Acc. Chem. Res. 2012, 45, 1736–1748; d) Z. Shi, C.
Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41, 3381–3430; e) K. M.
Gligorich, M. S. Sigman, Chem. Commun. 2009, 3854–3867.
7] a) G. Wu, W. Su, Org. Lett. 2013, 15, 5278–5281; b) K. M. Engle, D. H.
Wang, J. Q. Yu, Angew. Chem. Int. Ed. 2010, 49, 6169–6173; Angew.
Chem. 2010, 122, 6305–6309; c) A. N. Campbell, S. S. Stahl, Acc. Chem.
Res. 2012, 45, 851–863; d) T. Punniyamurthy, S. Velusamy, J. Iqbal,
Chem. Rev. 2005, 105, 2329–2363; e) A. E. Wendlandt, A. M. Suess, S. S.
Stahl, Angew. Chem. Int. Ed. 2011, 50, 11062–11087; Angew. Chem.
2
1302184), the 973 Program (2011CB932404, 2011CBA00501) is
greatly appreciated.
Keywords: CÀH activation · dioxygen · Heck reaction · Michael
addition · rhodium
[
[
1] a) M. Zhang, Y. Zhang, X. Jie, H. Zhao, G. Li, W. Su, Org. Chem. Front.
2
011, 123, 11256–11283; f) S. Warratz, C. Kornhaass, A. Cajaraville, B.
Niepotter, D. Stalke, L. Ackermann, Angew. Chem. Int. Ed. 2015, 54,
513—5517; Angew. Chem. 2015, 127, 5604–5608.
8] a) G. Zhang, L. Yang, Y. Wang, Y. Xie, H. Huang, J. Am. Chem. Soc. 2013,
35, 8850–8853; b) G. Zhang, H. Yu, G. Qin, H. Huang, Chem. Commun.
014, 50, 4331–4334; c) L. Yang, G. Y. Zhang, H. M. Huang, Adv. Synth.
2
2
014, 1, 843–895; b) C. Jia, T. Kitamura, Y. Fujiwara, Acc. Chem. Res.
001, 34, 633–639; c) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc.
5
Rev. 2011, 40, 5068–5083; d) K. M. Engle, T. S. Mei, M. Wasa, J. Q. Yu,
Acc. Chem. Res. 2012, 45, 788–802; e) D. A. Colby, A. S. Tsai, R. G. Berg-
man, J. A. Ellman, Acc. Chem. Res. 2012, 45, 814–825; f) L. Yang, H.
Huang, Chem. Rev. 2015, 115, 3468–3517.
[
1
2
Catal. 2014, 356, 1509–1515; d) Y. Lu, H.-W. Wang, J. E. Spangler, K.
Chen, P.-P. Cui, Y. Zhao, W.-Y. Sun, J.-Q. Yu, Chem. Sci. 2015, 6, 1923–
2] a) X. F. Wu, P. Anbarasan, H. Neumann, M. Beller, Angew. Chem. Int. Ed.
2
010, 49, 9047–9050; Angew. Chem. 2010, 122, 9231–9234; b) H. X.
Dai, G. Li, X. G. Zhang, A. F. Stepan, J. Q. Yu, J. Am. Chem. Soc. 2013, 135,
567–7571; c) B. Liu, Y. Fan, Y. Gao, C. Sun, C. Xu, J. Zhu, J. Am. Chem.
Soc. 2013, 135, 468–473; d) C. Zhu, R. Wang, J. R. Falck, Chem. Asian J.
012, 7, 1502–1514; e) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111,
1
3
927; e) W. Han, G. Zhang, G. Li, H. Huang, Org. Lett. 2014, 16, 3532–
535.
7
[
9] a) H. Yang, G. Y. Hu, J. Chen, Y. Wang, Z. H. Wang, Bioorg. Med. Chem.
Lett. 2007, 17, 5210–5213; b) J. J. Beck, S. C. Chou, J. Nat. Prod. 2007,
2
7
0, 891–900; c) R. A. Limaye, V. B. Kumbhar, A. D. Natu, M. V. Paradkar,
1
4
215–1292; f) L. Ackermann, J. Pospech, Org. Lett. 2011, 13, 4153–
155.
V. S. Honmore, R. R. Chauhan, S. P. Gample, D. Sarkar, Bioorg. Med. Chem.
Lett. 2013, 23, 711 –714.
[
3] a) D. A. Colby, R. G. Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624–
[
[
10] a) P. Forgione, M. C. Brochu, M. St-Onge, K. H. Thesen, M. D. Bailey, F. Bi-
lodeau, J. Am. Chem. Soc. 2006, 128, 11350–11351; b) V. Ritleng, C.
Sirlin, M. Pfeffer, Chem. Rev. 2002, 102, 1731–1770; c) L. J. Goossen, G.
Deng, L. M. Levy, Science 2006, 313, 662–664; d) X. Qin, D. Sun, Q. You,
Y. Cheng, J. Lan, J. You, Org. Lett. 2015, 17, 1762–1765.
11] a) H. Zhao, Y. Shang, W. Su, Org. Lett. 2013, 15, 5106–5109; b) Y. Shang,
X. Jie, H. Zhao, P. Hu, W. Su, Org. Lett. 2014, 16, 416–419; c) Y. Zhang, H.
Zhao, M. Zhang, W. Su, Angew. Chem. Int. Ed. 2015, 54, 3817–3821.
6
55; b) B. Li, J. Ma, W. Xie, H. Song, S. Xu, B. Wang, Chem. Eur. J. 2013,
1
9, 11863–11868; c) X. S. Zhang, Q. L. Zhu, Y. F. Zhang, Y. B. Li, Z. J. Shi,
Chem. Eur. J. 2013, 19, 11898–11903; d) F. W. Patureau, F. Glorius, J. Am.
Chem. Soc. 2010, 132, 9982–9983; e) G. Song, F. Wang, X. Li, Chem. Soc.
Rev. 2012, 41, 3651–3678; f) F. W. Patureau, J. Wencel-Delord, F. Glorius,
Aldrichimica Acta 2012, 45, 31–41.
[
[
4] a) B. Ye, N. Cramer, Science 2012, 338, 504–506; b) M. Presset, D. Oehl-
rich, F. Rombouts, G. A. Molander, Org. Lett. 2013, 15, 1528–1531;
c) S. H. Park, J. Y. Kim, S. Chang, Org. Lett. 2011, 13, 2372–2375; d) C.
Feng, D. Feng, T. P. Loh, Org. Lett. 2013, 15, 3670–3673; e) M. Zhang,
H. J. Zhang, T. Han, W. Ruan, T. B. Wen, J. Org. Chem. 2015, 80, 620–627.
5] a) K. Ueura, T. Satoh, M. Miura, Org. Lett. 2007, 9, 1407–1409; b) H. X.
Dai, J. Q. Yu, J. Am. Chem. Soc. 2012, 134, 134–137; c) M. H. Emmert,
A. K. Cook, Y. J. Xie, M. S. Sanford, Angew. Chem. Int. Ed. 2011, 50, 9409–
Manuscript received: June 10, 2015
Accepted Article published: July 14, 2015
Final Article published: July 28, 2015
Chem. Asian J. 2016, 11, 356 – 359
www.chemasianj.org
359
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim