Solvent-dependent copper-catalyzed synthesis of pyrazoles under aerobic conditions

Article abstract of DOI:10.1039/c6cc06935e

We present a copper-catalyzed oxidative cyclization of β,γ-unsaturated hydrazones, utilizing molecular oxygen as a stoichiometric oxidant. The methodology provides distinct classes of pyrazoles simply by changing the reaction solvent. Tris-substituted pyr

Full text of DOI:10.1039/c6cc06935e

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DOI: 10.1039/C6CC06935E
Journal Name
ARTICLE
Solvent-Dependent Copper-Catalyzed Synthesis of Pyrazoles
Under Aerobic Conditions†
Florian Pünner,a,b Yoshihiro Sohtomea,b and Mikiko Sodeokaa,b
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
We present a copper-catalyzed oxidative cyclization of
, -
b g
unsaturated hydrazones, utilizing molecular oxygen as a
stoichiometric oxidant. The methodology provides distinct
classes of pyrazoles simply by changing the reaction solvent.
Tris-substituted pyrazoles, having a ketone functionality at
the C-5 position, were obtained as the major product in
ethanol, while di-substituted pyrazoles were predominantly
formed in 1,1,1,3,3,3-hexafluoro-2-propanol.
The pyrazole moiety is present in various pharmacologically
active substances, agrochemicals, and synthetic ligands.1
Although several synthetic methods are available,2 cyclization3
of a hydrazonyl radical has recently received particular
attention as a potentially useful synthetic strategy for pyrazole
and pyrazoline derivatives. However, most of the approaches
reported to date rely on the use of stoichiometric amounts of
oxidants such as TEMPO or azodicarboxylates (Scheme 1, I),4,5
and catalyst-controlled radical cyclization of hydrazones has
only rarely been reported.6 Here, we present a catalytic,
Scheme 1 Radical cyclization approaches for the synthesis of pyrazole and
pyrazoline derivatives.
problems by employing a redox-active transition metal catalyst
with molecular oxygen as the stoichiometric oxidant. We
anticipated that the generated hydrazonyl radical might
undergo sequential cyclization/oxygen incorporation (C–N/C–
O bond-formation), eventually leading to 5-keto-pyrazoles.
This structural motif has been used in sildenafil as a mimic of
cyclic guanosine monophosphate (cGMP).9
We began by investigating the aerobic cyclization of
hydrazone 1a, focusing mainly on copper salts (Table 1 and
supplementary information).8f,10 After detailed investigation,
we found that the nature of the solvent drastically influences
the product selectivity. The initial reaction conditions (Table 1,
entry 1), utilizing Cu(OAc)2 in DCM under an atmosphere of
oxygen, afforded a mixture of product 2a and the
fragmentation product 3a in 18% and 57% yields, respectively.
In THF, only ~50% conversion was observed and the selectivity
aerobic, and reductant-free synthesis of pyrazoles from b,g
-
unsaturated hydrazones. This reaction also features solvent-
dependent product switching (Scheme 1, II).
Although molecular oxygen (O2) or air is considered as an
ideal and environmentally friendly oxidant,7 applications to
catalytic transformations are still limited for several reasons.8
Molecular oxygen is usually in a triplet state, making it less
reactive towards non-radical species. On the other hand,
molecular oxygen could trap radical intermediates. Another
problem is the formation of highly reactive oxygen species
(ROS), such as superoxide anion radicals (O2 •), peroxo-species
–
(RO2•), and hydroxyl radicals (HO•), which often cause
undesired side-reactions. We aimed to circumvent those
for 2a/3a was low (entry 2). Reaction in 2-propanol gave 2a as
the major product, but the conversion was still incomplete
(entry 3). We found that EtOH led to complete conversion,
providing 2a in 83% yield (entry 4). When the reaction was run
in the absence of copper in EtOH (entry 5) only less than 5% of
1a was consumed by autoxidation and selective product
formation was not observed.11 Various other metal acetates
(M = Mn, Fe, Co, Ni) also failed to promote the selective
formation of 2a (entry 6). Different copper salts (e.g.
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Table 1 Selected screening results.a)
Table 2 Synthesis of 2 and 3 .
with various hydrazones 1 a)
View Article Online
DOI: 10.1039/C6CC06935E
Entry
1
[M]
Cu(OAc)2
Solvent Time [h] 1a [%] 2a [%]
3a [%]
57
Entry
1
Solvent
EtOH
Time [h]
2 [%]
84
3 [%]
10
DCM
24
18
18
18
20
20
21
24
18
19
-
51
26
-
18
<20
64
83b)
trace
trace
79b)
84b)
-
24
1
2
3
4
5
6
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
-
THF
<25
9
2
3
HFIP
EtOH
HFIP
EtOH
HFIP
19
24
20
24
22
-
49
-
99
40
iPrOH
EtOH
EtOH
EtOH
EtOH
EtOH
HFIP
<10
4
99
≥95
≥95
-
trace
trace
<12
10b)
quant.b)
5
NH(4-OMeC6H4)
Ph
60
-
18
N
c)
M(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
-
6
Ph
quant.
1c
7d)
8d,e
9
EtOH
HFIP
20
20
73
-
24
91
7
8
-
-
EtOH
HFIP
EtOHb)
20
20
96
76
-
14
93
10
9
HFIP
-
-
70
10
10
11
a) Conditions: 0.06 mmol 1a, 5 mol% catalyst [M], solvent (0.1
(1 atm), rt (20-25 ºC); NMR yields based on internal standard; b)
isolated yields; c) M(OAc)2 Mn(OAc)2, Fe(OAc)2, Co(OAc)2 or
M), O2
63
=
HFIP
EtOH
HFIP
EtOH
HFIP
20
24
20
24
24
-
81
-
95
8
Ni(OAc)2·4H2O; d) 0.20 mmol scale; e) 2 mol% Cu(OAc)2.
12
13
14
15
16
Cu(NO3)2·3H2O and [Cu(MeCN)4]PF6) gave inferior yields and
poor product selectivity (see SI for details). These results
suggest a significant contribution of Cu(OAc)2 to the selective
formation of 2a in EtOH under aerobic conditions. The amount
of catalyst could be reduced to 2 mol% on 0.20 mmol scale,
with a comparable yield of 84% of 2a (entries 7 and 8). On the
other hand, when the more acidic 1,1,1,3,3,3-hexafluoro-2-
propanol (HFIP) was used as the solvent, product 3a was
quantitatively formed with concomitant generation of
benzaldehyde (entry 9). In contrast to the reaction in EtOH, the
conversion of 1a in HFIP was complete even in the absence of
Cu(OAc)2, although the yield (70%) was significantly lower than
in the presence of Cu(OAc)2 (entry 10). Thus, addition of a
catalytic amount of Cu(OAc)2 in HFIP may suppress undesired
reaction pathways, thereby selectively affording 3a. Thus,
selective access to 2a and 3a from the same substrate 1a has
been realized simply by changing the solvent. As discussed
later, this is an interesting example of controlling the reaction
pathways of complex aerobic oxidation reactions.12 Both
transformations can also be conducted under air instead of
oxygen, providing the products in only slightly lower yields (see
SI for details).
quant.
<25c)
93
63
-
EtOH
HFIP
18
22
20d)
-
66d)
95
17
18
EtOH
HFIP
23
23
38
21
68
19
20
n.i. (trace)
EtOH
HFIP
23
23
17
-
25
21
22
quant.
EtOH
27
80
18
23
HFIP
27
21
n.i. (trace) <62c) (70)
24
25
EtOH
56
21
HFIP
EtOH
HFIP
21
28
22
-
33
-
79
n.i. (<5)
72
26
27
28
To evaluate the scope for selective synthesis of
2 or 3, the
a) Conditions: 0.20 mmol 1a, 2 mol% Cu(OAc)2, solvent (0.1
M), O2
two distinct conditions were next applied to various
hydrazones (Table 2). When substrates with different aromatic
substituents (R2) on the hydrazone nitrogen were tested
(1 atm), rt (20-25 ºC); isolated yields; NMR yields in parenthesis; n.i.:
not isolated; b) addition of 1 mL Et2O after 48 h; c) could not be
obtained in pure form; d) yield was calculated from the isolated
(entries 1-6), 99%–quantitative yields of 3a-3c were obtained
inseparable mixture of 2 and 3.
in HFIP, whereas marked variations in yield (49–84%) and
product selectivity were observed in EtOH. No significant
differences in yield and product selectivity were observed
between the reactions of E-isomer 1d (entries 7 and 8) and Z-
isomer 1e (entries 9 and 10). As for R1, electron-rich and
electron-deficient aromatic as well as aliphatic groups are
applicable for both types of conversions (entries 1, 2, 7-16),
and the reactions proceeded in 63–84% yield (for
and 91%– quantitative yields (for ) in HFIP. Starting materials
containing a heterocyclic moiety were potentially applicable
under both reaction conditions, giving and (entries 17-22).
Although the conversion to in HFIP proceeded smoothly with
2) in EtOH
3
2
3
3
2 | J. Name., 2012, 00, 1-3
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Ph
Ph
N
NH
N
O2 (1 atm)
HFIP, rt
N
Ph
O
View Article Online
Ph
Ph
3a
DOI: 10.1039/C6CC06935E
1a
PhCHO
+
H2O
step vi
Ph
ORf Ph
Scheme 2 Formation of 4a and its uncatalyzed oxidation to 2a
.
Ph
N
N
H
N
O
N
H
O
Ph
Ph
68%–quantitative yields, we found that the conversion to
HO
H
Ph
step v
ORf
V
H
products
2 proceeded in only 17–38% yields in EtOH. Finally,
different substituents R3 on the double bond were evaluated
(entries 1, 2 and 23-28). Aryl-substituted substrates with
electron-donating or electron-withdrawing groups 1l and 1m
were readily applicable under both conditions, while alkyl
substitution (1n) led to a significantly lower yield in EtOH
step iv
1a
Ph
step i
ORf Ph
O2H(solv)
step ii
Ph
N
O2
step iii
Ph
O O
N
H
N
N
N
N
Ph
Ph
Ph
Ph
Ph
III
IV
II
(entry 23: 33%), but still a good yield in HFIP (entry 24: 72%). Scheme 4 A plausible mechanism for the formation of 3 in HFIP.
Although the yields and product selectivities are not always
satisfactory in EtOH, the result is a remarkable example of radical moiety should be converted into the ketone by Cu(I), to
catalytic aerobic cyclization, enabling selective access to give 4a (step iv)10,12c with concomitant regeneration
different classes of pyrazoles from
reaction solvent.
1
by simply tuning the of the Cu(II) catalyst, affording water as the sole by-product.
The result (Scheme 2) suggests that further oxidation of 4a
,
Optimization studies (Table 1 and SI), as well as the scope under aerobic conditions smoothly produces 2a (step v).
of the reaction (Table 2), suggest that distinct reaction In contrast to the Cu(OAc)2-catalyzed formation of 2a in
mechanisms are involved, depending on the solvent used. In EtOH, copper is not required in the HFIP-mediated formation
terms of the procedure for the formation of 2a using of 3a (see Table 1, entry 10). We assume that HFIP plays
Cu(OAc)2/EtOH, a key intermediate 4a was captured when CuI, multiple roles in the selective formation of 3a (Scheme 4).14 In
instead of Cu(OAc)2, was used as the catalyst in EtOH. We the initial step (step i), HFIP accelerates hydrogen abstraction
found that the pyrazoline 4a is unstable upon exposure to air; from 1a by molecular oxygen through stabilization of the
NMR measurement revealed that 4a is gradually converted resulting hydrazonyl radical IV as well as the hydroperoxo
into 2a in CDCl3 even in the absence of any metals (Scheme 2). radical, even in the absence of Cu(II) catalyst. The subsequent
Based on these results, a plausible mechanism for the Cu- C–N (step ii)/C–O bond-formation (step iii) would give the
catalyzed formation of 2a is illustrated in Scheme 3. peroxo radical III, which could also be generated via a Cu-
Considering that I) copper is mandatory for promoting the catalyzed process, as shown in Scheme 3. However, in the
formation of 2a (Table 1, entry 5 and SI) and II) decomposition proposed scenario, HFIP makes 1a susceptible to hydrogen
of 1a occurred when 1a was treated with Cu(OAc)2 under abstraction by peroxo radical III to generate the hydrogen
nitrogen (see SI for details), we speculate that Cu(II) may peroxide species
participate as a redox-active transition metal in the single formation of would be direct radical-radical combination of II
electron transfer process to generate hydrazonyl radical (step and a HFIP-coordinated hydroperoxo radical (step v). Finally,
i), not as a simple Lewis acid. The resulting radical undergoes the fragmentation of produces 3a, benzaldehyde and
V (step iv). Another possibility for the
V
I
I
V
intramolecular C–N bond formation to generate carbon radical water.15 Considering that addition of a catalytic amount of
II (step ii). This radical intermediate II can be trapped by Cu(OAc)2 in HFIP significantly increased the yield of 3a (Table 1,
oxygen to form the peroxo radical III (step iii).13 The peroxo entry 9 vs. entry 10), copper may contribute to quenching the
highly reactive hydroperoxy radical, reducing the product
yield.16,17
In conclusion, we have presented a catalytic and aerobic
methodology for the oxidative cyclization of readily available
b,g-unsaturated hydrazones, which provides two different
pyrazole derivatives simply changing by the reaction solvent.
Tris-substituted pyrazoles, with a ketone functionality at the C-
5 position, were obtained when Cu(OAc)2/EtOH was utilized.
The procedure is an unusual example of direct incorporation of
a ketone functionality into a substrate using molecular oxygen.
On the other hand, Cu(OAc)2/HFIP gave di-substituted
pyrazoles in very high yields. We believe these findings provide
important mechanistic insights into catalytic transformations
under aerobic conditions.
Acknowledgements
Scheme 3
A
plausible mechanism for the Cu(OAc)2-catalyzed
in EtOH.
formation of
2
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Punniyamurthy, S. Velusamy, J. Iqbal, Chem. Rev., 2005, 105, 2329; i)
This work was supported in part by Grant-in-Aid for Scientific
Research (C) from MEXT (24550128) and Project Funding from
RIKEN. F.P thanks JSPS Fellowship Programs for Overseas
Researchers.
View Article Online
A. N. Campbell, S. S. Stahl, Acc. Chem. Res., 2012, 45, 851.
DOI: 10.1039/C6CC06935E
8
Recent reviews on catalytic aerobic oxidation: a) L. Boisvert, K. I.
Goldberg, Acc. Chem. Res., 2012, 45, 899; b) M. L. Scheurmann, K. I.
Goldberg, Chem. Eur. J., 2014, 20, 14556; c) Y. Seki, K. Oisaki, M.
Kanai, Tetrahedron Lett., 2014, 55, 3738; d) A. E. Wendlandt, A. M.
Suess. S. S. Stahl, Angew. Chem. Int. Ed., 2011, 50, 11062; e) Z. Shi, C.
Zhang, C. Tang and N. Jiao, Chem. Soc. Rev., 2012, 41, 3381; f) S. E.
Allen, R. R. Walvoord, R. Padilla-Salinas, M. C. Kozlowski, Chem. Rev.,
2013, 113, 6234; g) Q. Cao, L. M. Dornan, L. Rogan, L. Hughes, M. J.
Muldoon, Chem. Commun., 2014, 50, 4524; h) C. Parmeggiani, F.
Cardona, Green Chem., 2012, 14, 547.
Selected syntheses of 5-keto substituted pyrazoles: a) A. Kamal, K. N.
V. Sastry, D. Chandrasekhar, G. S. Mani, P. R. Adiyala, J. B. Nanubolu,
K. K. Singarapu, R. A. Maurya, J. Org. Chem., 2015, 80, 4325; b) D. J.
Babinski, H. R. Aguilar, R. Still, D. E. Frantz, J. Org. Chem., 2011, 76,
5915; c) M. B. Supurgibekov, D. Cantillo, C. O. Kappe, G. K. S.
Prakashd, V. A. Nikolaev, Org. Biomol. Chem., 2014, 12, 682; d) N.
Jianga, C.-J. Li, Chem. Commun., 2004, 394; e) W.-M. Shu, K.-L. Zheng,
J.-R. Ma, H.-Y. Sun, M. Wang, A.-X. Wu, Org. Lett., 2015, 17, 1914; f)
P. K. Mykhailiuk, Eur. J. Org. Chem. 2015, 7235; g) K. Kobayashi, Y.
Igura, S. Imachi, Y. Masui, M. Onaka, Chem. Lett., 2007, 36, 60.
Notes and references
1
Selected examples of pharmacologically active substances: a) A.
Schmidt, A. Dreger, Curr. Org. Chem., 2011, 15, 1423; b) M. L. Isidro,
F. Cordido, Mini-Rev. Med. Chem., 2009, 9, 664; c) N. K. Terrett, A. S.
Bell, D. Brown and P. Ellis, Bioorg. Med. Chem. Lett., 1996, 6, 1819;
d) A. V. Dolzhenko, A. V. Dolzhenko, W. K. Chui, Heterocycles, 2008,
75, 1575; e) S. Fustero, R. Román, J. F. Sanz-Cervera, A. Simón-
Fuentes, A. C. Cuñat, S. Villanova, M. Murguía, J. Org. Chem., 2008,
73, 3523; f) H.-X. Dai, A. F. Stepan, M. S. Plummer, Y.-H. Zhang, J.-Q.
Yu, J. Am. Chem. Soc., 2011, 133, 7222; examples of agrochemicals:
g) A. S. Gunasekara, T. Truong, K. S. Goh, F. Spurlock and R. S.
Tjeerdema, J. Pestic. Sci., 2007, 32, 189; h) Y. Li, H. Zhang, J. Liu, X.
Yang and Z. J. Liu, J. Agric. Food Chem., 2006, 54, 3636; i) C.
Lamberth, Heterocycles 2007, 71, 1467; j) P. R. G. Terçariol, A. F.
Godinho, Pest. Biochem. Physiol., 2011, 99, 221; a recent review on
pyrazolyl borate ligands: k) M. Sallmann, C. Limberg, Acc. Chem. Res.
2015, 48, 2734.
9
10 Selected Cu-catalyzed oxidation reactions of carbonyl compounds
using O2: a) S. Chiba, L. Zhang, J.-Y. Lee, J. Am. Chem. Soc., 2010, 132,
7266; b) K. Cheng, L. Huang, Y. Zhang, Org. Lett., 2009, 11, 2908; c) H.
Wang, Y. Wang, D. Liang, L. Liu, J. Zhang, Q. Zhu, Angew. Chem. Int.
Ed., 2011, 50, 5678.
11 Selected examples of aerobic autoxidation of pyrazoles: a) M. Harej,
D. Dolenc, J. Org. Chem., 2007, 72, 7214; b) T. Tezuka, S. Ando, Chem.
Lett., 1985, 1621; c) A. L. Baumstark, M. Dotrong, P.C. Vasquez,
Tetrahedron Lett., 1987, 28, 1963; d) J. Yu, J. W. Lim, S. Y. Kim, J. Kim,
J. N. Kim, Tetrahedron Lett., 2015, 56, 1432.
2
Reviews of the synthesis of pyrazole derivatives: a) S. Fustero, M.
Sánches-Roselló, P. Barrio, A. Simón-Fuentes, Chem. Rev., 2011, 111,
6984; b) K. Makino, H. S. Kim, Y. J. Kurasawa, Heterocycl. Chem.,
1999, 36, 321; c) S. Dadiboyena, A. Nefzi, Eur. J. Med. Chem., 2011,
46, 5258; d) S. Fustero, A. Simón-Fuentes, J. F. Sanz-Cervera, Org.
Prep. Proced. Int., 2009, 41, 253; e) M. Li, B.-X. Zhao, Eur. J. Med.
Chem., 2014, 85, 311; f) S. Kumari, S. Paliwal, R. Chauhan, Synth.
Commun., 2014, 44, 1521.
12 a) H. Wang, Q. Lu, C. Qian, C. Liu, W. Liu, K. Chen, A. Lei, Angew.
Chem. Int. Ed., 2016, 55, 1094; b) Y. Su, X. Sun, G. Wu, N. Jiao,
Angew. Chem. Int. Ed., 2013 , 52, 9808; c) A. S.-K. Tsang, A. Kapat, F.
Schoenebeck, J. Am. Chem. Soc., 2016, 138, 518.
3
4
a) J.-T. Yu, C. Pan, Chem. Commun., 2016, 52 , 2220; b) B. Giese, B.
Kopping, T. Gobel, J. Dickhaut, G. Thoma, K. J. Kulicke, F. Trach,
Radical Cyclization Reactions; Organic Reactions, 2004, 48:2, 301-
856; c) A. J. McCarroll, J. C. Walton, Angew. Chem. Int. Ed., 2001, 40,
2224; d) G. J. Rowlands, Tetrahedron, 2010, 66, 1593.
Radical cyclizations of hydrazones utilizing TEMPO and/or DIAD: a)
X.-Y. Duan, N.-N. Zhou, R. Fang, X.-L. Yang, W. Yu, B. Han, Angew.
Chem. Int. Ed., 2014, 53, 3158; b) M.-K. Zhu, Y.-C. Chen, T.-P. Loh,
Chem. Eur. J., 2013, 19, 5250; c) X.-Y. Duan, X.-L. Yang, R. Fang, X.-X.
Peng, W. Yu, B. Han, J. Org. Chem., 2013, 78, 10692; d) X. Zhu, S.
Chiba, Org. Biomol. Chem., 2014, 12, 4567; e) X.-Q. Hu, G. Feng, J.-R.
Chen, D.-M. Yan, Q.-Q. Zhao, Q. Wei, W.-J. Xiao, Org. Biomol. Chem.,
2015, 13, 3457; cyclization of a hydrazone with an aliphatic side-
chain utilizing TEMPO: f) X. Zhu, Y.-F. Wang, W. Ren, F.-L. Zhang, S.
Chiba, Org. Lett., 2013, 15, 3214.
13 See also SI for control experiments and further information.
14 a) T. Dohi, N. Yamaoka, Y. Kita, Tetrahedron, 2010, 66, 5775; b) Z.
Yang, H. Li, L. Zhang, M.-T. Zhang, J.-P. Cheng, S. Luo, Chem. Eur. J.,
2015, 21, 14723; c) E. Gaster, Y. Vainer, A. Regev, S. Narute, K.
Sudheendran, A. Werbeloff, H. Shalit, D. Pappo, Angew. Chem. Int.
Ed., 2015, 54, 4198; d) R. A. McClelland, N. Mathivanan, S. Steenken,
J. Am. Chem. Soc., 1990, 112, 4857; e) A. Kirste, B. Elsler, G.
Schnakenburg, S. R. Waldvogel, J. Am. Chem. Soc., 2012, 134, 3571;
f) A. Berkessel, J. A. Adrio, J. Am. Chem. Soc., 2006, 128, 13412; g) F.
L. Cozens, M. O’Neill, R. Bogdanova, N. Schepp, J. Am. Chem. Soc.,
1997, 119, 10652; h) F. L. Cozens, S. F. Lancelot, N. P. Schepp, J. Org.
Chem., 2007, 72, 10022; i) C. Yuan, Y. Liang, T. Hernandez, A.
Berriochoa, K. N. Houk, D. Siegel; Nature, 2013, 499, 192.
15 a) R. D. Bach, P. Y. Ayala, H. B. Schlegel, J. Am. Chem. Soc., 1996, 118,
12758; b) S. W. Benson, J. Chem. Phys., 1964, 40, 1007; c) J. M.
Simmie, G. Black, H. J. Curran, J. P. Hinde, J. Phys. Chem. A, 2008, 112,
5010.
16 a) J. Mao, S. Fan, D. J. Jacob, K. R. Travis, Atmos. Chem. Phys., 2013,
13, 509; b) D. Chen, Q. Wang, H. Zhang, S. Mi, J. Wang, Q. Zeng, G.
Zhang, Int. J. Quant. Chem., 2010, 110, 1394; c) V. V. Smirnov, J. P.
Roth, J. Am. Chem. Soc., 2006, 128, 16424; d) D. L. Sedlak, J. Hoigné,
M. M. David, R. N. Colvile, E. Seyffer, K. Acker, W. Wiepercht, J. A.
Lind, S. Fuzzi, Atmos. Environ., 1997, 31, 2515; f) X. Zhang, H. Yi, Y.
Luo. A. Lei, Chem. Asian. J., 2016, 11, 2117..
5
6
Tandem C–N/C–C/C–C reaction using stoichiometric amount of
tBuOOBut: a) X.-Y. Duan, X.-L. Yang, P.-P. Jia, M. Zhang, B. Han, Org.
Lett., 2015, 17, 6022; radical cyclizations of hydrazones utilizing
MnO2: b) I. Bhatnagar, M. V. George, Tetrahedron, 1968, 24, 1293.
Photocatalytic radical cyclization with several oxidants: a) X.-Q. Hu,
J.-R. Chen, Q. Wei, F.-L. Liu, Q.-H. Deng, A. M. Beauchemin, W.-J.
Xiao, Angew. Chem. Int. Ed., 2014, 53, 12163; photocatalytic radical
trifluoromethylation/cyclization: b) Q. Wei, J.-R. Chen, X.-Q. Hu, X.-C.
Yang, B. Lu, W.-J. Xiao, Org. Lett., 2015, 17, 4464; photocatalytic
radical cascade: c) X.-Q. Hu, X. Qi, Q.-Q. Zhao, Q. Wei, Y. Lan, W.-J,
Xiao, Nature Commun., 2016, 7, 11188; photocatalytic aerobic
oxyamination and deoxygenation with reductant: d) X.-Q. Hu, J.
Chen, J.-R. Chen, D.-M. Yan, W.-J, Xiao, Chem. Eur. J., 2016, 22,
14141.
17 We think there are two possible explanations for why HFIP produces
4a even in the presence of Cu(OAc)2. One is the acceleration of the
proposed sigmatropic fragmentation (step vi, Scheme 4).
Suppressing the reduction of III by Cu(I) is another possibility (step iv,
Scheme 3).
7
a) S. S. Stahl, Science, 2005, 309, 1824; b) S. S. Stahl, Angew. Chem.
Int. Ed., 2004, 43, 3400; c) B. M. Stoltz, Chem. Lett., 2004, 33, 362; d)
J. Muzart, Chem. Asian J., 2006, 1, 508; e) M. S. Sigman, D. R. Jensen,
Acc. Chem. Res., 2006, 39, 221; f) E. M. Beccalli, G. Broggini, M.
Martinelli, S. Sottocornola, Chem. Rev., 2007, 107, 5318; g) J. Piera, J.
E. Bäckvall, Angew. Chem. Int. Ed., 2008, 47, 3506; h) T.
4 | J. Name., 2012, 00, 1-3
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