Tunable Aerobic Oxidative Hydroxylation/Dehydrogenative Homocoupling of Pyrazol-5-ones under Transition-Metal-Free Conditions

Article abstract of DOI:10.1021/acs.orglett.7b00951

A practical and tunable transition-metal-free aerobic oxidation of pyrazol-5-ones preparing either 4-hydroxypyrazoles (via C-H hydroxylation) or bispyrazoles (via dehydrogenative homocoupling) is described. The K₂CO₃/dioxane reagent system predominately promoted hydroxylation to deliver the α-hydroxylated pyrazoles. In contrast, the formation of bispyrazoles was overwhelmingly preferred with CH₃CN as the reaction medium without any additives.

Full text of DOI:10.1021/acs.orglett.7b00951

Letter
pubs.acs.org/OrgLett
Tunable Aerobic Oxidative Hydroxylation/Dehydrogenative
Homocoupling of Pyrazol-5-ones under Transition-Metal-Free
Conditions
Xuguang Sheng,†,‡ Jinlong Zhang,† Huameng Yang,† and Gaoxi Jiang*,†
†State Key Laboratory for Oxo Synthesis and Selective Oxidation, Suzhou Research Institute of LICP, Lanzhou Institute of Chemical
Physics (LICP), Chinese Academy of Sciences, Lanzhou 730000, China
‡University of Chinese Academy of Sciences, Beijing 100049, China
S
* Supporting Information
ABSTRACT: A practical and tunable transition-metal-free aerobic oxidation
of pyrazol-5-ones preparing either 4-hydroxypyrazoles (via C−H hydrox-
ylation) or bispyrazoles (via dehydrogenative homocoupling) is described.
The K2CO3/dioxane reagent system predominately promoted hydroxylation
to deliver the α-hydroxylated pyrazoles. In contrast, the formation of
bispyrazoles was overwhelmingly preferred with CH3CN as the reaction
medium without any additives.
olecular oxygen is an essential part of multicellular life on
excavation of aerobic homocoupling of carbonyl compounds
MEarth and plays a significant role in biological under mild conditions, particularly without additives, is in great
metabolism.1 Biological metalloenzymes that frequently contain
demand yet remains challenging.
Pyrazol-5-one skeletons represent privileged structural units
ubiquitously appearing in biologically active natural products and
synthetic drugs,14 such as the first synthetic antipyretic and
analgesic drug by Ludwig Knorr in 1883,14c,d antibacterial
agents,14e and p38 inhibitors.14f Concerning extensive applica-
tions of multifunctionalized pyrazol-5-ones15,16 and our
sustaining interest in the aerobic oxidative reactions,17 we
determined to devote our efforts on the exploration for efficient
derivatization of pyrazoles by an aerobic oxidative strategy.
Recently, Wang and co-workers reported an oxidative hydrox-
ylation at the C4-position of pyrazol-5-ones with cumene
hydroperoxide (CHP) as the oxidant (Scheme 1a).18 In 1993,
the homocoupling of pyrazol-5-ones was first demonstrated by
Meske’s group using phenoxy radicals as oxidants (Scheme
2b).19 To the best of our knowledge, the direct aerobic oxidation
of pyrazol-5-ones for both hydroxylation and homocoupling is
unprecedented and still remains a great challenge. Herein, we
present the first switchable aerobic oxidation of pyrazol-5-ones to
afford either 4-hydroxypyrazoles (via C−H hydroxylation) or
bispyrazoles (via C−C homocoupling). The K2CO3/dioxane
system predominately promoted the aerobic hydroxylation; by
contrast, the aerobic homocoupling was overwhelmingly
preferred when CH3CN was used as the solvent without any
additives (Scheme 1c). Moreover, these two kinds of reactions
proceeded smoothly in air, making this tunable aerobic oxidation
more attractive.
catalytic metal centers usually utilize molecular oxygen as an
oxidant to oxidize a variety of substrates, namely, oxygenase and
oxidase.2 The biomimetic approaches employing abundant,
nontoxic, and environmentally benign molecular oxygen as an
oxygen atom source or oxidant into various organic reactions
have potential in the development of green and sustainable
chemistry.3 As two important transformations in this field,
oxidative C−H hydroxylation4 and C−C coupling reaction3,5
have attracted considerable attention for the synthesis of
important biological and pharmaceutical molecules. A traditional
method for access to C−H hydroxylation is the direct use of
organic oxidants (i.e., DMD,6a−c oxaziridines,6d,e m-CPBA,6f
6i
ROOH,6g,h H2O2 ) or with O2 by transition-metal catalysis (i.e.,
Pd,7a,b Ce,7c−e Co,7f Mn7g,h). From an atom-economical and
ecological point of view, the requirement for stoichiometric
amounts of organic oxidants or heavy metals presents a host of
disadvantages. Afterward, transition-metal-free aerobic oxidative
C−H hydroxylation by organo-,8 phase transfer,9 or inorganic
salt10 catalysis was realized. Despite those remarkable advances,
the use of P(OEt)3 for reduction of superoxide intermediate to a
final alcohol product is necessary in most cases, which inevitably
produces waste.9d,f,g,10a,b On the other hand, the oxidative
homocoupling of α-tertiary carbon adjacent to a carbonyl
function group could be an efficient tool for C−C bond
formation. Accordingly, a wide range of catalytic processes have
been developed using metal oxidants (i.e., KMnO4, V2O5,
FeCl2)11 or organic oxidants (i.e., CAN and I2),12 and only a few
examples of aerobic oxidative homocoupling catalyzed by
CuCl13a and Cu2O13b were reported. Nevertheless, further
Received: March 30, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00951
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Oxidative Hydroxylation/Homocoupling of
Pyrazol-5-ones
Table 1. Optimization of the Reaction Conditions for Aerobic
Oxidation of Pyrazoles
a
b
entry
solvent
base (mol %)
temp (°C)
2a/3a yield (%)
1
CH2Cl2
toluene
THF
60
60
60
60
60
60
60
60
60
60
60
60
60
80
35
20
35
35
35
80
35
60
21/35
38/51
39/49
19/73
43/50
41/48
36/51
84/8
2
3
4
CH3CN
dioxane
DMSO
DMF
5
6
7
8
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
CH3CN
CH3CN
CH3CN
K2CO3 (20)
Na2CO3 (20)
NaOAc (20)
K2PO4 (20)
Et3N (20)
9
81/10
77/16
82/11
75/13
78/15
80/13
84/8
10
11
12
13
14
15
DBU (20)
Scheme 2. Scope of Aerobic Oxidative Hydroxylation*
K2CO3 (20)
K2CO3 (20)
K2CO3 (20)
K2CO3 (40)
K2CO3 (10)
K2CO3 (20)
c
16
85/9
17
18
83/8
79/15
78/9
de
,
19
20
21
22
23/69
12/71
17/65
e
d
a
Reaction conditions: 1a (0.2 mmol) was stirred in solvent (3.0 mL)
b
under O2 (1 atm) with or without base for 12 h. Yield of isolated
product. Reaction for 20 h. In air (1 atm). Reaction for 40 h.
c
d
e
and found that the oxidative homocoupling preferentially
occurred to produce bispyrazole 3a in a reasonable yield of
73% at 60 °C (entries 4, 20, and 21). Excitingly, products 2a and
3a were also synthesized in 78 and 65% yields in air, although a
prolonged reaction time is necessary (entries 19 and 22). It
should be noted that the mixture of 2a and 3a can be completely
separated by one flash column chromatography.
*
Reaction conditions: pyrazol-5-ones 1 (0.2 mmol), K2CO3 (20 mol
a
%), dioxane (3.0 mL), O2 (1 atm), 35 °C, 12 h. Yield of isolated
product. Yield of isolated corresponding homocoupling product is in
parentheses. Reaction was conducted in DMSO (3.0 mL) due to
b
c
Under the optimized reaction conditions shown in entry 15 of
Table 1, we first investigated the substrate scope of the aerobic
oxidative hydroxylation (Scheme 2). Substituents at the para- or
meta-position in 4-benzylpyrazoles were very compatible
regardless of electric characteristics, leading to the tertiary
alcohols 2b−j in good yields of 80−92%. For substrates bearing a
methyl group or bromine atom at the ortho-position, the reaction
gave rise to the corresponding products 2k or 2l in slightly lower
yields and selectivity. Significantly, substituents at the C4-
position of pyrazol-5-ones can be easily expanded to methyl,
ethyl, and allyl groups, and the desired compounds 2m−o were
produced concisely in 84−93% yields. Furthermore, other
methyl-substituted pyrazol-5-ones 1p and 1q were also
applicable reactants to furnish exclusively the hydroxylation
products 2p and 2q in excellent yields of 95 and 97%,
respectively. Remarkably, 3-phenylpyrazoles 1r and 1s were
successfully reacted to synthesize the corresponding compounds
2r and 2s in 89 and 87% yields, respectively.
insolubility of substrate in dioxane.
Initially, pyrazol-5-one 1a was chosen as the model substrate to
optimize reaction conditions of this unprecedented oxidation at
60 °C for 12 h. As shown in Table 1, the reaction occurred readily
to give a mixture of products, and relatively high yields of 43 and
73% were obtained for 2a and 3a in dioxane and CH3CN,
respectively (entries 1−7). Next, various organic and inorganic
bases were used in dioxane to only improve the selectivity of
product 2a, and the results showed that K2CO3 was superior to
provide 2a in a yield of 84% (entries 8−13). Screening of the
reaction temperature indicated that the best outcomes were
acquired at 35 °C in terms of reaction time and product yield
(entries 14−16). If the base loading was increased from 20 to 40
mol %, no obvious influence on the reaction results was detected,
whereas a lower yield of 79% was obtained with a decreased base
loading to 10 mol % (entries 17 and 18) (for solvent screening,
see Supporting Information). Complementarily and compet-
itively with the above hydroxylation process, we commenced
investigating the homocoupling of pyrazol-5-one 1a in CH3CN
Subsequently, the same substrates 1a−s were subjected to the
optimal reaction conditions of aerobic oxidative homocoupling
shown in entry 4 of Table 1. As depicted in Scheme 3, reactions of
B
DOI: 10.1021/acs.orglett.7b00951
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 3. Scope of Aerobic Oxidative Homocoupling*
Scheme 5. Proposed Reaction Mechanism
the presence of molecular oxygen with addition of base (Path I),
4-hydroxylation of pyrazole is preferential due to the fast
deprotonation by K2CO3, providing the corresponding carban-
ion A, which reacts with O2 to generate a superoxide anion B.
Then, a proton migration occurs to form the superoxide C and
immediately regenerates carbanion A that was directly oxidized
by O2 or superoxide C. After a failure to separately synthesize the
1
intermediate C, we utilized the H NMR spectrum of the
reaction mixture to detect the acidic H atom of the superoxide
part, and the desired peak was not found. Reasonably, the later
redox reaction between carbanion A and superoxide C occurred
faster than O2, providing the desired 4-hydroxylated product 2.9e
Additionally, in the absence of base (path II), the homocoupling
predominates. Pyrazole might be auto-oxidized to radical
intermediate D that undergoes a homocoupling process to
deliver bispyrazole products 3.13a,b,19
In conclusion, we have described a practical and tunable
aerobic oxidation of pyrazoles from hydroxylation to homocou-
pling by changing solvent and base under transition-metal-free
reaction conditions. The aerobic oxidative hydroxylation was
favored in the K2CO3/dioxane reagent system to produce a
variety of 4-hydroxypyrazoles in high to excellent yields.
Complementarily, the aerobic oxidative homocoupling reaction
predominately occurred when the reaction was performed in a
nitrile solvent without any additives, providing bispyrazoles in
good yields. Importantly, the concise synthesis of these two kinds
of desired products via automatic oxidation in air with acceptable
yields makes this switchable aerobic oxidation more attractive.
*
Reaction conditions: pyrazol-5-ones 1 (0.2 mmol), CH3CN (3 mL),
a
O2 (1 atm), 60 °C, 24 h. Yield of isolated product, the yield of
isolated corresponding hydroxylation product is in parentheses. The
dr value was determined by H NMR. Reaction for 4 days.
b
c
1
different 4-benzylpyrazoles 1a−k proceeded smoothly to furnish
the coupling products bispyrazoles 3a−k in 65−77% yields and
up to 5.1:1 dr with reasonable selectivity in the above competitive
hydroxylation process. Only trace transformation occurred with
1l, and 96% of substrate was recovered. Moreover, with
treatment of the starting materials 1m−o in this transformation,
compounds 3m−o were obtained in 46−66% yields. In the case
of 4-methylpyrazol-5-one 1m, only one diastereomer was
identified by 1H NMR spectroscopy. Also, other methyl-
substituted molecules 1p and 1q were tolerated to afford
products 3p and 3q in yields of 48 and 50%, respectively. When
3-phenylpyrazole 1r was used as reaction substrate, a 55% yield
and 4.4:1 dr were detected for product 3r. However, a poor yield
of 9% was obtained for 3s, likely because of the high steric
hindrance between two benzyl groups in product 3s.
For practicality of this transformation to be highlighted, both
hydroxylation and homocoupling reactions of substrate 1a were
conducted under the optimized reaction conditions in 1 mmol
scale (Scheme 4). Gratifyingly, the same high yields of 83 and
73% were acquired for the desired compounds 2a and 3a,
respectively.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b00951.
1H and 13C NMR spectra of all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
On the basis of these preliminary results and pioneering works
on aerobic oxidation of the α-position of C−H in carbonyl
compounds, a possible mechanism is proposed in Scheme 5. In
■
*E-mail: gxjiang@licp.cas.cn. Fax: (+86) 931-4968129.
ORCID
Scheme 4. Synthesis of Both Hydroxylation and
Homocoupling Products from 1 mmol Scale of 1a
Gaoxi Jiang: 0000-0003-1555-1107
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
Financial support from the Hundred Talent Program of Chinese
Academy of Sciences (CAS), the National Natural Science
■
C
DOI: 10.1021/acs.orglett.7b00951
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
126, 8914. (d) Sunden
A. Angew. Chem., Int. Ed. 2004, 43, 6532.
́ ́
, H.; Engqvist, M.; Casas, J.; Ibrahem, I.; Cordova,
Foundation of China (21602231), and the Natural Science
Foundation of Jiangsu Province (Grant Nos. BK20151235 and
BK20160396) is gratefully acknowledged.
(9) (a) Zhou, S.; Zhang, L.; Li, C.; Mao, Y.; Wang, J.; Zhao, P.; Tang,
L.; Yang, Y. Catal. Commun. 2016, 82, 29. (b) Wang, Y.; Yin, H.; Tang,
X.; Wu, Y.; Meng, Q.; Gao, Z. J. Org. Chem. 2016, 81, 7042. (c) Wang, Y.;
Zheng, Z.; Lian, M.; Yin, H.; Zhao, J.; Meng, Q.; Gao, Z. Green Chem.
2016, 18, 5493. (d) Sim, S.-B. D.; Wang, M.; Zhao, Y. ACS Catal. 2015,
5, 3609. (e) Yang, Y.; Moinodeen, F.; Chin, W.; Ma, T.; Jiang, Z.; Tan,
C.-H. Org. Lett. 2012, 14, 4762. (f) Lubin, H.; Tessier, A.; Chaume, G.;
Pytkowicz, J.; Brigaud, T. Org. Lett. 2010, 12, 1496. (g) Sano, D.; Nagata,
K.; Itoh, T. Org. Lett. 2008, 10, 1593.
REFERENCES
■
(1) (a) Holland, H. D. The Chemistry of the Atmosphere and Oceans;
Wiley: New York, 1978. (b) Levine, J. S.; Augustsson, T. R.; Natarajan,
M. Origins Life 1982, 12, 245.
(2) (a) Snyder, R. A.; Butch, S. E.; Reig, A. J.; DeGrado, W. F.;
Solomon, E. I. J. Am. Chem. Soc. 2015, 137, 9302. (b) Brown-Marshall,
C. D.; Diebold, A. R.; Solomon, E. I. Biochemistry 2010, 49, 1176.
(c) Hewgley, J. B.; Stahl, S. S.; Kozlowski, M. C. J. Am. Chem. Soc. 2008,
130, 12232.
(10) (a) Liang, Y.-F.; Jiao, N. Angew. Chem., Int. Ed. 2014, 53, 548.
(b) de Vries, E. F. J.; Ploeg, L.; Colao, M.; Brussee, J.; van der Gen, A.
Tetrahedron: Asymmetry 1995, 6, 1123.
(11) (a) DeMartino, M. P.; Chen, K.; Baran, P. S. J. Am. Chem. Soc.
2008, 130, 11546. (b) Rathke, M. W.; Lindert, A. J. Am. Chem. Soc. 1971,
93, 4605. (c) Frazier, R. H.; Harlow, R. L. J. Org. Chem. 1980, 45, 5408.
(d) Kise, N.; Tokioka, K.; Aoyama, Y.; Matsumura, Y. J. Org. Chem.
1995, 60, 1100. (e) Ito, Y.; Konoike, T.; Saegusa, T. J. Am. Chem. Soc.
1975, 97, 2912. (f) Tokuda, M.; Shigei, T.; Itoh, M. Chem. Lett. 1975, 4,
621. (g) Kato, H.; Tani, K.; Kurumisawa, H.; Tamura, Y. Heterocycles
1987, 26, 1313. (h) Andersen, K. K.; Bray, D. D.; Kjær, A.; Lin, Y.; Shoja,
M.; Dooryhee, E. Acta Chem. Scand. 1997, 51, 1000.
(3) For reviews, see: (a) Elwell, C. E.; Gagnon, N. L.; Neisen, B. D.;
Dhar, D.; Spaeth, A. D.; Yee, G. M.; Tolman, W. B. Chem. Rev. 2017,
117, 2059. (b) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.;
Kozlowski, M. C. Chem. Rev. 2013, 113, 6234. (c) Shi, Z.; Zhang, C.;
Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3381. (d) Wu, W.; Jiang, H.
Acc. Chem. Res. 2012, 45, 1736. (e) Campbell, A. N.; Stahl, S. S. Acc.
Chem. Res. 2012, 45, 851. (f) Wendlandt, A. E.; Suess, A. M.; Stahl, S. S.
Angew. Chem., Int. Ed. 2011, 50, 11062. (g) Zhang, C.; Xu, Z.; Zhang, L.;
Jiao, N. Angew. Chem., Int. Ed. 2011, 50, 11088. (h) Piera, J.; Backvall, J.-
̈
(12) (a) Ghosh, S.; Chaudhuri, S.; Bisai, A. Org. Lett. 2015, 17, 1373.
(b) Nicolaou, K. C.; Gray, D. J. J. Am. Chem. Soc. 2004, 126, 607.
(c) Nicolaou, K. C.; Gray, D. Angew. Chem., Int. Ed. 2001, 40, 761.
(13) (a) Kozlowski, M. C.; DiVirgilio, E. S.; Malolanarasimhan, K.;
Mulrooney, C. A. Tetrahedron: Asymmetry 2005, 16, 3599. (b) Fang, X.;
Zhang, K.; Yao, H.; Huang, Y. Org. Biomol. Chem. 2016, 14, 8030.
(14) (a) Varvounis, G. Pyrazol-3-ones. Part IV: Synthesis and
Applications. In Advances in Heterocyclic Chemistry, Katritzky, A. R., Ed.;
Academic Press: New York, 2009; Vol. 98, p 143. (b) Horton, D. A.;
Bourne, G. T.; Smythe, M. L. Chem. Rev. 2003, 103, 893. (c) Tainter, M.
L.; Ann, N. Y. Ann. N. Y. Acad. Sci. 1948, 51, 3. (d) Brune, K. Acute Pain
1997, 1, 33. (e) Dipyrone. Martindale: The Complete Drug Reference;
Brayfield, A., Ed.; Pharmaceutical Press: London, 2014. (f) Clark, M. P.;
Laughlin, S. K.; Laufersweiler, M. J.; Bookland, R. G.; Brugel, T. A.;
Golebiowski, A.; Sabat, M. P.; Townes, J. A.; VanRens, J. C.; Djung, J. F.;
Natchus, M. G.; De, B.; Hsieh, L. C.; Xu, S. C.; Walter, R. L.; Mekel, M.
J.; Heitmeyer, S. A.; Brown, K. K.; Juergens, K.; Taiwo, Y. O.; Janusz, M.
J. J. Med. Chem. 2004, 47, 2724.
E. Angew. Chem., Int. Ed. 2008, 47, 3506. (i) Punniyamurthy, T.;
Velusamy, S.; Iqbal, J. Chem. Rev. 2005, 105, 2329. (j) Stahl, S. S. Science
2005, 309, 1824. (k) Stahl, S. S. Angew. Chem., Int. Ed. 2004, 43, 3400.
(l) Schweitzer, C.; Schmidt, R. Chem. Rev. 2003, 103, 1685. (m) Anastas,
P. T.; Kirchhoff, M. M. Acc. Chem. Res. 2002, 35, 686.
(4) For a review, see: Smith, A. M. R.; Hii, K. K. Chem. Rev. 2011, 111,
1637.
(5) For reviews, see: (a) Varun, B. V.; Dhineshkumar, J.; Bettadapur, K.
R.; Siddaraju, Y.; Alagiri, K.; Prabhu, K. R. Tetrahedron Lett. 2017, 58,
803. (b) Girard, S. A.; Knauber, T.; Li, C. Angew. Chem., Int. Ed. 2014,
53, 74. (c) Liu, C.; Liu, D.; Lei, A. Acc. Chem. Res. 2014, 47, 3459.
(d) Zhang, C.; Tang, C.; Jiao, N. Chem. Soc. Rev. 2012, 41, 3464.
(6) For examples using DMD, see: (a) Adam, W.; Smerz, A. K.
Tetrahedron 1996, 52, 5799. (b) Smith, A. M.; Rzepa, H. S.; White, A. J.;
Billen, D.; Hii, K. K. J. Org. Chem. 2010, 75, 3085. (c) Smith, A. M.;
Billen, D.; Hii, K. K. M. Chem. Commun. 2009, 3925. Using oxaziridines:
(d) Davis, F. A.; Chen, B. C. Chem. Rev. 1992, 92, 919. (e) Davis, F. A.;
Liu, H.; Chen, B.-C.; Zhou, P. Tetrahedron 1998, 54, 10481. Using m-
CPBA: (f) Andriamialisoa, R.; Langlois, N.; Langlois, Y. Tetrahedron
(15) For a review of pyrazol-3-one derivatization, see: (a) Chauhan, P.;
Mahajan, S.; Enders, D. Chem. Commun. 2015, 51, 12890. For several
recent examples, see: (b) Zhu, Z.-Q.; Shen, Y.; Liu, J.-X.; Tao, J.-Y.; Shi,
F. Org. Lett. 2017, 19, 1542. (c) Lin, H.-C.; Wang, P.-S.; Tao, Z.-L.;
Chen, Y.-G.; Han, Z.-Y.; Gong, L.-Z. J. Am. Chem. Soc. 2016, 138, 14354.
Lett. 1985, 26, 3563. Using ROOH: (g) Acocella, M. R.; Mancheno, O.
̃
G.; Bella, M.; Jørgensen, K. A. J. Org. Chem. 2004, 69, 8165. (h) Lian, M.;
Li, Z.; Du, J.; Meng, Q.; Gao, Z. Eur. J. Org. Chem. 2010, 2010, 6525.
Using H2O2: (i) Li, D. M.; Schroder, K.; Bitterlich, B.; Tse, M. K.; Beller,
M. Tetrahedron Lett. 2008, 49, 5976. Using other oxidants: (j) Vedejs,
E.; Engler, D.; Telschow, J. J. Org. Chem. 1978, 43, 188. (k) Schultz, A.
G.; Holoboski, M. A. Tetrahedron Lett. 1993, 34, 3021. (l) Duschek, A.;
Kirsch, S. F. Chem. - Eur. J. 2009, 15, 10713. (m) Yu, J.; Cui, J. A.; Zhang,
C. Eur. J. Org. Chem. 2010, 2010, 7020. (n) Tsang, A. S.-K.; Kapat, A.;
Schoenebeck, F. J. Am. Chem. Soc. 2016, 138, 518.
(d) Amr, F. I.; Vila, C.; Blay, G.; Munoz, M. C.; Pedro, J. R. Adv. Synth.
̃
Catal. 2016, 358, 1583.
(16) For our recent work on derivatization of pyrazoles, see: Zhou, H.;
Wei, Z.; Zhang, J.; Yang, H.; Xia, C.; Jiang, G. Angew. Chem., Int. Ed.
2017, 56, 1077.
(17) (a) Li, J.; Zhang, J.; Yang, H.; Gao, Z.; Jiang, G. J. Org. Chem. 2017,
82, 765. (b) Li, J.; Zhang, J.; Yang, H.; Jiang, G. J. Org. Chem. 2017, 82,
3284.
(18) (a) Xue, F.; Bao, X.; Zou, L.; Qu, J.; Wang, B. Adv. Synth. Catal.
2016, 358, 3971. (b) Guthrie, D. A.; Ho, A.; Takahashi, C. G.; Collins,
A.; Morris, M.; Toscano, J. P. J. Org. Chem. 2015, 80, 1338.
(19) Schulz, M.; Meske, M. J. Prakt. Chem./Chem.-Ztg. 1993, 335, 607.
(7) For examples using Pd, see: (a) Monguchi, Y.; Takahashi, T.; Iida,
Y.; Fujiwara, Y.; Inagaki, Y.; Maegawa, T.; Sajiki, H. Synlett 2008, 2008,
2291. (b) Chuang, G. J.; Wang, W. K.; Lee, E.; Ritter, T. J. Am. Chem. Soc.
2011, 133, 1760. Using Ce: (c) Christoffers, J.; Werner, T. Synlett 2002,
2002, 119. (d) Christoffers, J.; Werner, T.; Unger, S.; Frey, W. Eur. J.
Org. Chem. 2003, 2003, 425. (e) Christoffers, J.; Kauf, T.; Werner, T.;
Rossle, M. Eur. J. Org. Chem. 2006, 2006, 2601. (f) Rossle, M.;
Christoffers, J. Tetrahedron 2009, 65, 10941. Using Co: (g) Baucherel,
X.; Levoirier, E.; Uziel, J.; Juge, S. Tetrahedron Lett. 2000, 41, 1385.
Using Mn: (h) Christoffers, J. J. Org. Chem. 1999, 64, 7668.
́
(i) Lamarque, L.; Meou, A.; Brun, P. Can. J. Chem. 2000, 78, 128.
Using other transition metals: (j) Watanabe, T.; Ishikawa, T.
Tetrahedron Lett. 1999, 40, 7795.
(8) (a) Miao, C.-B.; Wang, Y.-H.; Xing, M.-L.; Lu, X.-W.; Sun, X.-Q.;
Yang, H.-T. J. Org. Chem. 2013, 78, 11584. (b) Buckley, B. R.;
Fernan
́
dez, D.-R. B. Tetrahedron Lett. 2013, 54, 843. (c) Cor
, H.; Engqvist, M.; Ibrahem, I.; Casas, J. J. Am. Chem. Soc. 2004,
́
dova, A.;
Sunden
́
D
DOI: 10.1021/acs.orglett.7b00951
Org. Lett. XXXX, XXX, XXX−XXX