Direct Decarboxylative Alkynylation of α,α-Difluoroarylacetic Acids under Transition Metal-Free Conditions

Article abstract of DOI:10.1002/adsc.201501028

An efficient and generally applicable protocol for decarboxylative coupling of α,α-difluoroarylacetic acids with ethynylbenziodoxolone (EBX) reagents has been developed, affording α,α-difluoromethylated alkynes bearing various functional groups in moderate to excellent yields. Remarkably, this potassium persulfate (K₂S₂O₈)-promoted reaction employs water as solvent under transition metal-free conditions, thus providing a green synthetic approach to α,α-difluoromethylated alkynes. (Figure presented.).

Full text of DOI:10.1002/adsc.201501028

UPDATES
DOI: 10.1002/adsc.201501028
Direct Decarboxylative Alkynylation of a,a-Difluoroarylacetic
Acids under Transition Metal-Free Conditions
Xiang Li,a Siyu Li,a Suyan Sun,a Fan Yang,a,* Weiguo Zhu,a Yu Zhu,a
Yusheng Wu,b,c,* and Yangjie Wua,*
a
The College of Chemistry and Molecular Engineering, Henan Key Laboratory of Chemical Biology and Organic
Chemistry Key Laboratory of Applied Chemistry of Henan Universities Zhengzhou University, Zhengzhou 450052,
Peopleꢀs Republic of China
E-mail: yangf@zzu.edu.cn or wyj@zzu.edu.cn
Tetranov Biopharm, LLC. 75 Daxue Road, Zhengzhou 450052, Peopleꢀs Republic of China
b
E-mail: yusheng.wu@tetranovglobal.com
Collaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Peopleꢀs Republic of
c
China
Received: November 8, 2015; Revised: February 23, 2016; Published online: April 15, 2016
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201501028.
Abstract: An efficient and generally applicable pro-
tocol for decarboxylative coupling of a,a-difluoro-
arylacetic acids with ethynylbenziodoxolone (EBX)
reagents has been developed, affording a,a-
difluoromethylated alkynes bearing various func-
tional groups in moderate to excellent yields. Re-
markably, this potassium persulfate (K2S2O8)-pro-
moted reaction employs water as solvent under
transition metal-free conditions, thus providing
a green synthetic approach to a,a-difluoromethylat-
ed alkynes.
Due to the their unique structure and properties,
developing a simple and facile route to a,a-difluoro-
methylated alkynes is highly desirable. Traditional
procedures for the preparation of a,a-difluoromethy-
lated alkynes mainly rely on two synthetic ap-
proaches.[5–7] One is the direct difluoropropargylation
of electrophiles (aldehydes or imines) with diverse
gem-difluoropropargyl synthons, such as gem-difluoro-
propargylmetal or difluoropropargylindium com-
plexes, but this approach is still suffering from the
harsh reaction conditions and narrow substrate
scope.[5] Another route to a,a-difluoromethylated al-
kynes is the direct transformation from gem-difluoro-
propargyl bromide or g-bromodifluoroallenes and nu-
cleophiles, affording the corresponding a,a-difluoro-
methylated alkynes in good yields. However, the mul-
tistep preparation and the unstable character of g-bro-
modifluoroallenes restrict the wide application of
these synthetic routes.[6] To resolve these limitations,
Keywords: alkynylation; decarboxylation; a,a-di-
fluoroarylacetic acids; a,a-difluoromethylated al-
kynes; transition metal-free conditions
Fluorine-containing compounds are of great impor- just recently, Zhang and co-workers developed a palla-
tance in pharmaceuticals, agrochemicals and material dium-catalyzed Suzuki-type reaction of gem-difluoro-
science.[1] Specifically, the difluoromethylene group propargyl bromide with organoboron compounds,
(CF2) plays an important role in medicinal chemistry generating a,a-difluoromethylated alkynes as the
because the incorporation of a difluoromethylene products in high yields (Scheme 1a).[8] However, this
group into an organic molecule not only leads to pro- pioneering work employed a water- and air-sensitive
found changes of the compoundꢀs physical, chemical, reagent, gem-difluoropropargyl bromide, as a difluoro-
and biological properties,[2] but also acts as a bioisos- methyl and alkyne source.
tere of an oxygen atom or carbonyl group.[3] In partic-
a,a-Difluoroarylacetic acids are easy to prepare,
ular, a,a-difluoromethylated alkynes have wide appli- usually stable, and insensitive to moisture or air, and
cations in organic synthesis, especially for the prepa- should serve as promising difluoromethylating re-
ration of CF2-containing compounds because the agents. Recently, Gouverneur and co-workers report-
alkyne moiety could be easily functionalized by oxida- ed the preparation of difluoromethylarenes via
tion, reduction, addition or click reactions,[4] thus pro- a silver-catalyzed decarboxylative fluorination of a-
viding potential opportunities for new discoveries in fluoroarylacetic acid under mild conditions.[9] On the
medicinal chemistry.
other hand, the reagent ethynylbenziodoxolone
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Xiang Li et al.
Table 1. Optimizing the reaction conditions.[a]
Scheme 1. Synthesis of a,a-difluoromethylated alkynes.
Entry Catalyst Oxidant
Solvent
Yield [%][b]
(EBX), which is prepared from commercially avail-
able 2-iodobenzoic acid and corresponding alkynylsi-
lane,[10] is a safe and air-stable alkyne source that has
1[c]
2
3
4
5
AgNO3 K2S2O8
AgNO3 K2S2O8
AgNO3 K2S2O8
AgNO3 K2S2O8
AgNO3 K2S2O8
CH3CN/H2O 47
CH3CN/H2O 91
CH2Cl2/H2O trace
acetone/H2O 65
À
found wide applications in decarboxylation, C H
bond activation and many other types of reactions in
recent years.[11–14] Inspired by these reports, we envi-
sioned a simple and facile construction of the
difluoropropargyl moiety under transition metal-free
conditions by using the above-mentioned a,a-
difluoroarylacetic acids and ethynylbenziodoxolone
(EBX) reagents as difluoromethyl and alkyne source,
respectively, which would establish a new synthetic
H2O
trace
6
AgNO3
–
CH3CN/H2O trace
CH3CN/H2O 93
CH3CN/H2O 55
7
8
9
10
11
12
13[d]
14[e]
–
–
–
–
–
–
–
–
K2S2O8
Na2S2O8
(NH4)2S2O8 CH3CN/H2O 28
PhI(OAc)2
TBHP
BQ
K2S2O8
K2S2O8
CH3CN/H2O trace
CH3CN/H2O trace
CH3CN/H2O trace
CH3CN/H2O 30
strategy
for
difluoropropargyl
derivatives
CH3CN/H2O trace
(Scheme 1b).
[a]
Initially, biphenyl-4-yl(difluoro)acetic acid (1a) and
1-[(triisopropylsilyl)-ethynyl]-1,2-benziodoxol-3(1H)-
one (TIPS-EBX, 2a) were used as model substrates to
optimize the reaction conditions. Using the typical
AgNO3/K2S2O8 catalytic decarboxylative system,[15]
the desired product 3a could be obtained in 47%
yield in aqueous media CH3CN/H2O (1 mL/1 mL) at
558C under air (Table 1, entry 1). To our delight,
Reaction conditions: 1a (0.2 mmol), 2a (0.22 mmol), cata-
lyst (20 mol), oxidant (2.0 equiv.), and solvent (2 mL) at
558C under a nitrogen atmosphere for 12 h.
Yield of isolated product.
Under air.
1.0 equiv. of oxidant was used.
[b]
[c]
[d]
[e]
At room temperature.
when the reaction was conducted under a nitrogen at- fluoroarylacetic acids was examined, and the sub-
mosphere, the yield was improved to 91% (Table 1, strates bearing either electron-donating groups[16] or
entry 2). Subsequently, other solvents such as CH2Cl2/ electron-withdrawing groups could be efficiently
H2O (1 mL/1 mL), acetone/H2O (1 mL/1 mL) or neat transformed into the corresponding gem-difluorome-
water were tested, and the CH3CN/H2O (1 mL/1 mL) thylated alkynes in good to high yields (Table 2, 3a–
was the best choice (Table 1, entries 3–5). Surprising- 3n). To our delight, the desired product 3f could be
ly, the reaction proceeded smoothly in the absence of obtained in 65% yield even if the reaction was per-
silver catalyst, affording the desired product in formed on a 2.0 mmol scale (Table 2, 3f). The gem-di-
a higher yield of 93%, while the reaction did not fluoroarylacetic acids with a halogen atom at the
occur without the oxidant, indicating that the oxidant para-position, which could be easily further function-
was essential for this reaction (Table 1, entries 6 and alized, were also well tolerated in this reaction afford-
7). Then, some other oxidants were checked, and ing the desired products in good yields (Table 2, 3h
among them, only Na2S2O8 and (NH4)2S2O8 gave and 3i). It was noteworthy that substrates bearing
lower yields (Table 1, entries 8–12). Finally, some con- a synthetically valuable alkyne moiety were also suc-
trol experiments were also performed (Table 1, en- cessfully converted into the corresponding products in
tries 13 and 14). For example, when the amount of ox- yields of 67% and 63%, respectively (Table 2, 3j and
idant was changed to 1.0 equiv., the yield decreased 3k). Moreover, the scope of electron-withdrawing
sharply to 30%, and the reaction did not occur at all groups
could be successfully extended to
at room temperature. NHCOCHC(CH3)3, COCH3 and CF3 (Table 2, 3l–3n).
With the optimized conditions in hand, we next ex- Furthermore, N-heteroaromatic gem-difluoroarylace-
plored the substrate scope and the result was summar- tic acids were also tolerated in this reaction, affording
ized in Table 2. First, the electronic effect of gem-di- the desired product in 49% yield (Table 2, 3o). Next,
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Direct Decarboxylative Alkynylation of a,a-Difluoroarylacetic Acids
Table 2. Decarboxylative coupling of gem-difluoroarylacetic acids with R-EBX.[a,b]
[a]
Reaction conditions: 1 (0.20 mmol), 2 (0.22 mmol), K2S2O8 (2.0 equiv.), CH3CN (1.0 mL), and H2O (1.0 mL) at 558C
under a nitrogen atmosphere.
Yield of isolated product.
Reaction was performed on a 2.0 mmol scale.
[b]
[c]
different hypervalent alkynyl iodine reagents were
also tested, and aryl-substituted EBXs worked well in
this process (Table 2, 3p–3x). For example, phenyl-
EBX could be coupled with various gem-difluoroaryl-
acetic acids efficiently, affording the products in good
yields (Table 2, 3p–3u). The reaction could be com-
patible with the reagents possessing a halogen atom
(Cl or Br), thus providing an opportunity for further
functionalization (Table 2, 3w–3x). In addition, an
alkyl-substituted EBX was also examined, and the de-
sired product could be obtained in 53% yield
(Table 2, 3y).
To further establish the scope of this reaction, we
next performed the reaction of 2,2’-([1,1’-biphenyl]-
4,4’-diyl)bis(2,2-difluoroacetic acid) (4a) with TIP-
EBX (2a) or Ph-EBX (2b) in the presence of
4.0 equiv. of K2S2O8, and the corresponding product
was obtained in 61% or 66% yields, respectively
(Scheme 2). Given the synthetic value of alkynes,
these products containing alkyne moieties might have 4,4’-diyl)bis(2,2-difluoroacetic acid).
Scheme 2. Decarboxylative reaction of 2,2’-([1,1’-biphenyl]-
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Xiang Li et al.
potential synthetic applications in the construction of
complicated complexes in medicinal chemistry.
To highlight the synthetic utility of this protocol,
a gram-scale experiment of biphenyl-4-yl(difluoro)-
acetic acid (1a) with TIPS-EBX (2a) was performed
under the standard conditions and the desired product
could be obtained in 75% yield. Subsequently, the
product 3a was treated with TBAF, affording a termi-
nal alkyne 6 as the product in 80% yield. Further
transformation of the terminal alkyne 6 with 4-iodo-
benzonitrile was also conducted, and the correspond-
ing product 3u was obtained in 70% yield (Scheme 3).
The mechanism was also preliminarily surveyed by
adding radical scavengers (TEMPO or BHT) to the
reaction system, and only a trace amount of desired
product was detected (Scheme 4a). Furthermore,
when the reaction of 1a with BHT was performed
under standard conditions, the product 7 could be de-
tected by HR-MS, these results indicated that the re-
Scheme 5. Proposed mechanism.
On the basis of these above-mentioned results and
action pathway probably involved a free radical pro- previous reports,[12,17] a plausible mechanism is out-
cess (Scheme 4b).
lined in Scheme 5. First, in the presence of K2S2O8, di-
fluoroacetic acid 1a underwent a decarboxylation pro-
cess to generate a radical intermediate I, releasing
a molecular carbon dioxide.[17] Then, the intermediate
I reacted with TIPS-EBX (2a) to produce an adduct
radical intermediate II, and b-elimination of the inter-
mediate II would occur to afford the desired product
3a, along with the formation of a benziodoxolonyl
radical III. Finally, the radical III may be reduced by
the remaining difluoroacetic acid to form 2-iodoben-
zoic acid through a reduction–protonation process.
In conclusion, we have developed an efficient and
facile synthetic protocol for a,a-difluoromethylated
alkynes through direct decarboxylative coupling of
a,a-difluoroarylacetic acids and ethynylbenziodoxo-
lone (EBX) reagents. Remarkably, this decarboxyla-
tive process could proceed smoothly in aqueous solu-
tion under transition metal-free conditions and was
compatible with various functional groups. Moreover,
this simple, mild and transition metal-free protocol
could represent a new gateway to difluoromethylated
alkynes, which should also belong to the green
chemistry process.
Scheme 3. Late-stage transformations.
Experimental Section
Typical Procedure
An oven-dried, 25-mL Schlenk tube was charged with the
biphenyl-4-yl(difluoro)acetic acid 1a (49.6 mg, 0.2 mmol),
TIPS-EBX 2a (94.0 mg, 0.22 mmol) and K2S2O8, then H2O/
CH3CN (1:1, 2.0 mL) was added under a nitrogen atmos-
phere. The reaction mixture was stirred at 558C for 12 h.
After the reaction was complete, the mixture was poured
into H2O (25 mL) and extracted with ethyl acetate three
times. The combined organic layer was dried with anhydrous
Na2SO4 and evaporated under vacuum. The crude product
Scheme 4. Mechanistic studies.
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Direct Decarboxylative Alkynylation of a,a-Difluoroarylacetic Acids
was purified by flash chromatography on silica gel using
hexane as the eluent to afford the pure product 3a; yield:
71.0 mg (93%).
g) G. Liu, S. Mori, X. Wang, S. Noritake, E. Tokunaga,
N. Shibata, New J. Chem. 2012, 36, 1769.
[6] B. Xu, G. B. Hammond, Angew. Chem. 2005, 117, 7570;
Angew. Chem. Int. Ed. 2005, 44, 7404.
[7] a) J. M. Baskin, J. A. Prescher, S. T. Laughlin, N. J.
Agard, P. V. Chang, I. A. Miller, A. Lo, J. A. Codelli,
C. R. Bertozzi, Proc. Natl. Acad. Sci. USA 2007, 104,
16793; b) E. M. Sletten, H. Nakamura, J. C. Jewett,
C. R. Bertozzi, J. Am. Chem. Soc. 2010, 132, 11799;
c) P. Bannwarth, D. GrØe, R. GrØe, Tetrahedron Lett.
2010, 51, 2413; d) A. Khalaf, D. GrØe, H. Abdallah, N.
Jaber, A. Hachem, R. GrØe, Tetrahedron 2011, 67,
3881; e) Y. Li, K. A. Wheeler, R. Dembinski, Org.
Biomol. Chem. 2012, 10, 2395.
Acknowledgements
We are grateful to the National Natural Science Foundation
of China (No. 21102134, 21172200) and the Excellent Doc-
toral Dissertation Engagement Fund of Zhengzhou Universi-
ty in 2014 for financial support of this research.
[8] Y.-B. Yu, G.-Z. He, X. Zhang, Angew. Chem. 2014, 126,
10625; Angew. Chem. Int. Ed. 2014, 53, 10457.
References
[9] S. Mizuta, I. S. R. Stenhagen, M. OꢀDuill, J. Wolsten-
hulme, A. K. Kirjavainen, S. J. Forsback, M. Tredwell,
G. Sandford, P. R. Moore, M. Huiban, S. K. Luthra, J.
Passchier, O. Solin, V. Gouverneur, Org. Lett. 2013, 15,
2648.
[10] a) M. Ochiai, Y. Masaki, M. Shiro, J. Org. Chem. 1991,
56, 5511; b) V. V. Zhdankin, C. J. Kuehl, A. P. Krasut-
sky, J. T. Bolz, A. J. Simonsen, J. Org. Chem. 1996, 61,
6547.
[1] For selected reviews, see: a) B. E. Smart, J. Fluorine
Chem. 2001, 109, 3; b) K. Muller, C. Faeh, F. Diederich,
Science 2007, 317, 1881; c) S. Purser, P. R. Moore, S.
Swallow, V. Gouverneur, Chem. Soc. Rev. 2008, 37,
320; d) O. A. Tomashenko, V. V. Grushin, Chem. Rev.
2011, 111, 4475; e) T. Furuya, A. S. Kamlet, T. Ritter,
Nature 2011, 473, 470; f) C. Hollingworth, V. Gouver-
neur, Chem. Commun. 2012, 48, 2929; g) J. Wang, M.
Sµnchez-Roselló, J. L. AceÇa, C. del Pozo, A. E. Soro-
chinsky, S. Fustero, V. A. Soloshonok, H. Liu, Chem.
Rev. 2014, 114, 2432; h) C. Ni, M. Hu, J. Hu, Chem.
Rev. 2015, 115, 765.
[2] a) L. W. Hertel, J. S. Kroin, J. W. Missner, J. M. Tustin,
J. Org. Chem. 1988, 53, 2406; b) F. Akahoshi, A. Ashi-
mori, H. Sakashita, T. Yoshimura, M. Eda, T. Imada,
M. Nakajima, N. Mitsutomi, S. Kuwahara, T. Ohtsuka,
C. Fukaya, M. Miyazaki, N. Nakamura, J. Med. Chem.
2001, 44, 1297; c) A. A. Makarov, P. O. Tsvetkov, C.
Villard, D. Esquieu, B. Pourroy, J. Fahy, D. Braguer, V.
Peyrot, D. Lafitte, Biochemistry 2007, 46, 14899; d) X.-
L. Qiu, X.-H. Xu, F.-L. Qing, Tetrahedron 2010, 66,
789; e) N. A. Meanwell, J. Med. Chem. 2011, 54, 2529.
[3] a) C. M. Blackburn, D. A. England, F. Kolkmann, J.
Chem. Soc. Chem. Commun. 1981, 930; b) G. M. Black-
burn, D. E. Kent, F. Kolkmann, J. Chem. Soc. Perkin
Trans. 1 1984, 1119; c) T. Kitazume, T. Kamazaki, Ex-
perimental Methods in Organic Fluorine Chemistry,
Gordon and Breach Science, Tokyo, 1998.
[4] a) H. C. Kolb, M. G. Finn, K. B. Sharpless, Angew.
Chem. 2001, 113, 2056; Angew. Chem. Int. Ed. 2001, 40,
2004; b) F. Diederich, P. J. Stang, R. R. Tykwinski,
Acetylene Chemistry: Chemistry, Biology and Material
Science, Wiley-VCH, Weinheim, 2005; c) F. Alonso,
I. P. Beletskaya, M. Yus, Chem. Rev. 2004, 104, 3079;
d) R. Chinchilla, C. Nµjera, Chem. Rev. 2007, 107, 874;
e) J. Liu, J. W. Y. Lam, B. Z. Tang, Chem. Rev. 2009,
109, 5799.
[5] a) P. -Y. Kwok, F. W. Muellner, C.-K. Chen, J. Fried, J.
Am. Chem. Soc. 1987, 109, 3684; b) M. Mae, J. A.
Hong, G. B. Hammond, K. Uneyama, Tetrahedron Lett.
2005, 46, 1787; c) B. Xu, M. S. Mashuta, G. B. Ham-
mond, Angew. Chem. 2006, 118, 7423; Angew. Chem.
Int. Ed. 2006, 45, 7265; d) B. Xu, G. B. Hammond,
Chem. Eur. J. 2008, 14, 10029; e) R. Surmont, G. Verni-
est, N. D. Kimpe, Org. Lett. 2009, 11, 2920; f) J. Lin, X.
Yue, P. Huang, D. Cui, F.-L. Qing, Synthesis 2010, 267;
[11] For selected examples, see: a) J. P. Brand, J. Charpenti-
er, J. Waser, Angew. Chem. 2009, 121, 9510; Angew.
Chem. Int. Ed. 2009, 48, 9346; b) S. Nicolai, S. Erard,
D. F. Gonzalez, J. Waser, Org. Lett. 2010, 12, 384; c) R.
Frei, J. Waser, J. Am. Chem. Soc. 2013, 135, 9620; d) Y.
Li, J. P. Brand, J. Waser, Angew. Chem. 2013, 125, 6875;
Angew. Chem. Int. Ed. 2013, 52, 6743; e) R. Frei, M. D.
Wodrich, D. P. Hari, P. A. Borin, C. Chauvier, J. Waser,
J. Am. Chem. Soc. 2014, 136, 16563; f) C. C. Chen, J.
Waser, Chem. Commun. 2014, 50, 12923; g) C. C. Chen,
J. Waser, Org. Lett. 2015, 17, 736; h) Y. Li, J. Waser,
Angew. Chem. 2015, 127, 5528; Angew. Chem. Int. Ed.
2015, 54, 5438.
[12] For selected examples, see: a) X. Liu, Z. Wang, X.
Cheng, C. Li, J. Am. Chem. Soc. 2012, 134, 14330;
b) H. Wang, L.-N. Guo, S. Wang, X.-H. Duan, Org.
Lett. 2015, 17, 3054; c) H. Huang, G. Zhang, Y. Chen,
Angew. Chem. 2015, 127, 7983; Angew. Chem. Int. Ed.
2015, 54, 7872; d) Q.-Q. Zhou, W. Guo, W. Ding, X.
Wu, X. Chen, L.-Q. Lu, W.-J. Xiao, Angew. Chem.
2015, 127, 11348; Angew. Chem. Int. Ed. 2015, 54,
11196; e) F. L. Vaillant, T. Courant, J. Waser, Angew.
Chem. 2015, 127, 11352; Angew. Chem. Int. Ed. 2015,
54, 11200.
[13] For selected examples, see: a) F. Xie, Z. Qi, S. Yu, X.
Li, J. Am. Chem. Soc. 2014, 136, 4780; b) K. D. Collins,
F. Lied, F. Glorius, Chem. Commun. 2014, 50, 4459;
c) C. Feng, T.-P. Loh, Angew. Chem. 2014, 126, 6219;
Angew. Chem. Int. Ed. 2014, 53, 2760; d) C. Feng, D.
Feng, T.-P. Loh, Chem. Commun. 2014, 50, 9865; e) C.
Feng, D. Feng, Y. Luo, T.-P. Loh, Org. Lett. 2014, 16,
5956; f) Y. Wu, Y. Yang, B. Zhou, Y. Li, J. Org. Chem.
2015, 80, 1946; g) D. Kang, S. Hong, Org. Lett. 2015,
17, 1938; h) H. Wang, F. Xie, Z. Qi, X. Li, Org. Lett.
2015, 17, 920.
[14] a) T. Aubineau, J. Cossy, Chem. Commun. 2013, 49,
3303; b) Z. Wang, X. Li, Y. Huang, Angew. Chem. An-
Adv. Synth. Catal. 2016, 358, 1699 – 1704
ꢁ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1703

UPDATES
Xiang Li et al.
gew.Chem. 2013, 125, 14469; Angew. Chem. Int. Ed.
2013, 52, 14219; c) A. Nierth, M. A. Marletta, Angew.
Chem. 2014, 126, 2649; Angew. Chem. Int. Ed. 2014, 53,
2611; d) L. F. Silva Jr, A. Utaka, L. Calvalcanti, Chem.
Commun. 2014, 50, 3810; e) R.-Y. Zhang, L.-Y. Xi, L.
Zhang, S. Liang, S.-Y. Chen, X.-Q. Yu, RSC Adv. 2014,
4, 54349; f) Z. Wang, L. Li, Y. Huang, J. Am. Chem.
Soc. 2014, 136, 12233; g) H. Huang, G. Zhang, L. Gong,
S. Zhang, Y. Chen, J. Am. Chem. Soc. 2014, 136, 2280.
[15] a) Z. Wang, L. Zhu, F. Yin, Z. Su, Z. Li, C. Li, J. Am.
Chem. Soc. 2012, 134, 4258; b) F. Yin, Z. Wang, Z. Li,
C. Li, J. Am. Chem. Soc. 2012, 134, 10401; c) C. Liu, X.
Wang, Z. Li, L. Cui, C. Li, J. Am. Chem. Soc. 2015,
137, 9820; d) P.-F. Wang, X.-Q. Wang, J.-J. Dai, Y.-S.
Feng, H.-J. Xu, Org. Lett. 2014, 16, 4586; e) F. Hu, X.
Shao, D. Zhu, L. Lu, Q. Shen, Angew. Chem. 2014, 126,
6219; Angew. Chem. Int. Ed. 2014, 53, 6105.
[16] When the substrate 2,2-difluoro-2-(4-methoxyphenyl)-
acetic acid was used, the corresponding ynones were
obtained as major products instead of the direct decar-
boxylative products.
[17] a) F. Gozzo, C. R. Patrick, Nature 1964, 202, 80;
b) L. D. Kispert, H. Liu, C. U. Pittman Jr, J. Am. Chem.
Soc. 1973, 95, 1657.
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