C-H Activation Relay (CHAR): An Efficient Construction of Isatin Skeleton by Aerobic Oxidation of Glycine Esters

Article abstract of DOI:10.1021/acscatal.6b01781

Directed by the strategy of C-H activation relay (CHAR), an efficient construction of isatin skeleton was developed through catalytic oxidation of glycine esters. The mechanistic study reveals that the oxidation of the relatively active C-H bonds initiated the followed activation of remote and inert C-H bonds, and an intramolecular 1,6-hydrogen shift was involved as a key step.

Full text of DOI:10.1021/acscatal.6b01781

Subscriber access provided by Northern Illinois University
Letter
C-H Activation Relay (CHAR): an Efficient Construction
of Isatin Skeleton by Aerobic Oxidation of Glycine Esters
Xiaodong Jia, Yingzu Zhu, Yu Yuan, Xuewen Zhang, Shiwei Lü, Liang Zhang, and Liangliang Luo
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.6b01781 • Publication Date (Web): 08 Aug 2016
Downloaded from http://pubs.acs.org on August 8, 2016
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
ACS Catalysis is published by the American Chemical Society. 1155 Sixteenth Street
N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 5
ACS Catalysis
1
2
3
4
5
6
7
8
C-H Activation Relay (CHAR): an Efficient Construction of Isatin
Skeleton by Aerobic Oxidation of Glycine Esters
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Xiaodong Jia*, †, ‡, Yingzu Zhu, ‡ Yu Yuan, † Xuewen Zhang, † Shiwei Lü, ‡ Liang Zhang, ‡ and Liangli-
ang Luo ‡
† College of Chemistry and Chemical Engineering, Yangzhou University, Yangzhou, Jiangsu 225002, China
‡ College of Chemistry and Chemical Engineering, Northwest Normal University, Lanzhou, Gansu 730070, China
KEYWORDS C-H activation, Aerobic oxidation, Glycine ester, Isatin, 1,6-Hydrogen shift
ABSTRACT: Directed by the strategy of C-H activation relay (CHAR), an efficient construction of isatin skeleton was developed
through catalytic oxidation of glycine esters. The mechanistic study reveals that the oxidation of the relatively active C-H bonds
initiated the followed activation of remote and inert C-H bonds, and an intramolecular 1,6-hydrogen shift was involved as a key
step.
The ubiquitous and diverse nature of C-H bonds in complex
organic compounds makes C-H bond activation an attractive
approach to C-C and C-X bonds, providing some novel syn-
thetic disconnections for constructions of organic molecules.[1-
3]
However, due to their relatively inert nature, the selective
activation and functionalization of C-H bonds is still a chal-
lenge in organic synthesis. Beside sp2 C-H activation, [2] which
was mainly conducted through the use of transition-metal me-
diated reactions, activation of sp3 C-H bonds is a tougher task.
[3,4]
Generally, by transition-metal promoted transformations,
the existence of an appropriate directing group is crucial to
achieve activity and selectivity control, and great improve-
ments have been achieved in the past decade. [3]
Another method to sp3 C-H activation is by free radical me-
diated process. The high bond energy of sp3 C-H bonds makes
it hard to be broken, and activating groups are needed, such as
nitrogen, oxygen and so on, for the generated radical can be
stabilized by the adjacent heteroatoms through the lone pair
Figure 1. Design of C-H Activation Relay (CHAR)
electrons. Second, the selectivity of C-H functionalization
In recent years, our group has developed several related
mediated by radical processes is problematic. Due to the reac-
methodologies using N-arylglycine derivatives, building a
series of heterocyclic structures. In these investigations, we
found that the C-H bonds adjacent to nitrogen in N-glycine are
tivity and selectivity, the functionalization of the C-H bonds
adjacent to nitrogen, oxygen and phenyl group attracted exten-
[6]
sive attention, and a variety of applicable transformations were
[4]
reactive and easy to be oxidized to the corresponding radicals
or iminiums. So we speculate whether this active position
could act as the first runner in a relay-race, launching further
C-H oxidation. Then, phenethyl N-methyl-N-phenylglycinate
was designed to test the possibility of CHAR (Figure 1, eq 2,
up). Different from our initial design, an isatin product was
detected, which means that not only the C-H bonds adjacent to
nitrogen but also the C-H and C-O bonds in ester were activat-
ed. After evaluation of the reaction mechanism, we found that
after oxidation of N-arylglycine ester, a radical intermediate is
generated, which is trapped by dioxygen. Then an intramolec-
ular 1,6-H shift occurs via 7-membered transition state
(CHAR). This process is preferred, for the driving force of
this H-shift from the inert sp3 C-H bonds is the formation of a
stronger O–H bond (about 103 kcal/mol) than C–H bond
developed.
However, activation of the inert C-H bonds is
still a great problem.
It is well-known that the intramolecular 1,5- or 1,6-
hydrogen atom shift, which undergoes six- and seven-
membered ring respectively, is a common process in radical
chemistry, and in some cases, was used in functionalization of
[5]
remote and inert C-H bonds. So we wondered whether we
can initially generate a radical on an active position and then
trigger the remote and inactive C-H functionalization through
intramolecular hydrogen atom abstraction, which was named
C-H Activation Relay (CHAR, Figure 1, eq 1). It will be a
new way to achieve C-H activation and selectivity control.
ACS Paragon Plus Environment

ACS Catalysis
Page 2 of 5
[7]
(about 96 kcal/mol) in alkyl groups.
Encouraged by this solvents, such as DCM, DCE, THF, were then examined (en-
1
2
3
4
5
6
7
8
promising result, we tried the more accessible substrate, ethyl
N-arylglycinate (1a), and to our delight, the isatin was isolated
in 57% yield (Table 1, entry 1).
tries 9-11), and MeCN is still the best solvent. Interestingly,
we found that anisole is an excellent solvent in this transfor-
mation, which is superior in yield, catalyst loading and reac-
tion time (compare entry 12 with entry 1). Although the exact
reason remains unknown, the electron-rich nature of anisole
might be beneficial of stabilizing the electron-deficient inter-
mediate. In the absence of dioxygen, no desired product was
detected, and the starting material was recovered in 95% yield,
implying that O2 is crucial to oxidation of the sp3 C-H bonds
(entry 13). More oxidizing tris(2,4-dibromophenyl)amine rad-
ical cation (TDBPA+., entry 14) was also tested, and the de-
sired product 2a was isolated in lower yield (65%) together
with some unidentified by-products. It is attributed that the
stronger radical cation would result in some undesired side
reactions. So we chose TBPA+. (10 mol %) and O2 in anisole
as the optimized conditions.
Although the first synthesis of isatin could be traced back to
1840, [8] the construction of isatin motif still attracted extensive
attentions and some newly improved protocols have been de-
[9-12]
veloped.
However, some limitations also exist in these
efficient approaches, such as inaccessible starting materials,
harsh reaction conditions, expensive reagents and narrow sub-
strate scope. Therefore, the synthesis of structurally diverse
isatins through more simple and applicable methods is still
highly desirable. Herein, we demonstrate a radical cation salt
initiated CHAR to give isatins in good yields.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of Reaction Conditions a
Scheme 1. Reaction of Alkyl N-Arylglycinates a
Initiator
(mol %)
10
En-
try
Additive
(mol %)
Time
(h)
Yield
(%) b
Solvent
1
No
No
No
No
No
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
78
52
28
24
48
52
120
20
79
29
29
50
60
50
57
2
20
73
3
30
82
4
CAN c
TBHP c
30
13
5
n. d.
90
6
InCl3 (10) CH3CN
FeCl3 (10) CH3CN
7
30
trace
75
8
30
TFA (10)
CH3CN
9
30
InCl3 (10) DCM
InCl3 (10) DCE
InCl3 (10) THF
87
10
11
12
13
14
30
58
30
14
10
No
No
No
MeOPh
95
trace d
10
TDBPA+.
MeOPh
MeOPh
65
a Unless otherwise specified, the reaction was carried out with
1a (0.1mmol) in the presence of TBPA+., and anhydrous solvent
b
(1.0 mL).
Yield of crude product 1HNMR using 1,3,5-
trimethoxylbenzene as internal standard; c One equivalent of the
oxidant was used; d The reaction was performed under argon.
Our efforts toward this CHAR to isatins initially focused on
intramolecular cyclization of N-aryl-N-methylglycinate (Table
1). Under TBPA+. (tris(4-bromophenyl)aminium hexachloro-
anti-monate) induced conditions, the desired isatin was ob-
tained in 57% yield after 78 hours (Table 1, entry 1). This
encouraging result prompted us to optimize the reaction condi-
tions further. It was found that the loading of the initiator ex-
erts an important impact on the outcome of this transformation.
Higher catalyst loading led to better yields and shorter reaction
time (entries 2-3). Evaluation of other initiators show that
TBPA+. is more efficient to promote the aerobic oxidation (en-
trie 4-5). To further increase the reaction efficiency, some
additives were tested. Addition of InCl3 exerts positive effect
on the reaction, and the yield of the desired isatin increased to
90% at the cost of elongated reaction time (entry 6). Various
a Reaction conditions: 1 (1 mmol), TBPA+. (10 mol %), anisole
b
(5 mL), 60 °C under O2, isolated yield; The corresponding
benzyl ester was used.
With the best conditions established, the scope of substitut-
ed glycine esters was investigated. Firstly, the substituent ef-
ACS Paragon Plus Environment

Page 3 of 5
ACS Catalysis
fect on anilines was examined, and the results were compiled only 19% yield together with a variety of unidentified com-
1
2
3
4
5
6
7
8
in Scheme 1. Electron-donating groups enhanced the reaction
efficiency, giving the desired products in good to excellent
yields (2a to 2c). Slightly lower yields were obtained, when
electron-withdrawing groups were connected (2d to 2f). How-
ever if strong EWGs (NO2, CF3 and CO2Me) were introduced,
the reaction efficiency was reduced dramatically, and only
trace amount of products were detected (not shown in Scheme
1). The reason was attributed to the fact that the conjugation
between the lone pair electrons of nitrogen and the generated
radical is weakened. These results supported our hypothesis
that the oxidation of the active C-H bond enabled the subse-
quent C-H bond activation. Then we investigated the substrate
scope with respect to the N-groups. Straight N-groups do not
affect the reaction, giving isatin in high yields (2g to 2l).
Bulky groups such as the iso-butyl, cyclohexylmethyl and
neopentyl analogs performed as well in good to excellent
yields under the optimized conditions, and the isatin products
were isolated in 90% (2m), 80% (2n) and 86% (2o) yields,
respectively. The efficiency of this reaction was not decreased,
when the diethyl diacetate was employed, providing the de-
sired products in 71% yields (2p). In accord with the reported
results, the absence of para-groups would reduce the yields of
the desired products significantly (2q and 2r). [6, 13]
pounds. When benzyl ester was employed, the expected pro-
cess was enhanced, providing 2u in 81% yield. The reasons
lied in that the introduction of phenyl group could increase the
activity of the C-H bonds adjacent to oxygen, and further sta-
bilized the generated radical intermediate.
To understand the mechanism, a series of control reactions
were conducted, as shown in Scheme 3. It was found that the
addition of TEMPO (1 eq) inhibits the reaction, suggesting a
single electron transfer (SET) pathway might be involved in
this reaction (eq 1, up). To further confirm the involvement of
radical intermediate, TEMPO (2 eq) was added 10 hours after
the reaction was conducted, and then we performed HRMS
experiments to detect the capture product (eq 1, down). We are
delighted to observe the signal at m/z 333.2180 (Calc’d for
C19H28N2O3 + H+, 333.2178); this signal is related to the mass
of an acyl radical trapped by TEMPO, implying that the C-O
bond in ester was activated. When the corresponding benzyl
ester was used, the eliminated benzaldehyde and its oxidative
product, benzoic acid, were detected by chromatography-mass
spectrometry. Then the standard oxidative condition was ap-
plied to 3 (eq 2), and no reaction occurred, which completely
excluded the possibility of direct intramolecular Friedel-Crafts
reaction of glycine ester. Glycine amide shows no reactivity
(eq 3), while the corresponding N-benzylamide gave 2a in
13% yield (eq 4). The relative rate of different esters was then
measured (eq 5), and in accordance with the above observa-
tions, the benzyl esters gave the fastest rate (for details, see
Electronic Supplementary Information), while the tert-butyl
ester gave only trace of the expected product (not shown in
Scheme 3). These results show that the α-H adjacent to ester
or amide is crucial to formation of isatin, which supports the
existence of 1,6-H shift in this CHAR.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Competition Reactions of Glycine esters a
Scheme 3. Control Experiments
a Reaction conditions: 1 (1 mmol), TBPA+. (10 mol %), anisole
(5 mL), 60 °C under O2, isolated yield.
To test the selectivity of CHAR, phenethyl group was in-
stalled on nitrogen, which has another active benzyl position
that might disturb the expected 1,6-H shift process (Scheme 2,
up). The reaction became complicated, and only trace of the
desired product 2t was detected. It is attributed to that the 1,6-
H shift on the benzylic C-H bonds might compete with the
desired process. To enhance the desired 1,6-H shift, benzyl
ester was subjected to standard oxidation conditions, and the
reaction occurred smoothly, yielding the desired products in
67% yields (2t). Similar result was obtained in the synthesis of
N-cyclopropyl isatin (Scheme 1, 2s). As we know, 1,5-H shift,
which mediated by six-membered ring, is faster than 1,6-H
shift. [8] So we designed an ethyl N-benzylglycinate (1u) to test
the competition of 1,5- and 1,6-H shift (Scheme 2, down). As
expected, the former process was totally disturbed, and the
reaction became complicated, yielding the desired isatin in
Scheme 4. Proposed Mechanism
ACS Paragon Plus Environment

ACS Catalysis
Page 4 of 5
2. For recent examples of sp2 C-H activation, see: (a) Zhang, G.;
Liu, C.; Yi, H.; Meng, Q.; Bian, C.; Chen, H.; Jian, J.-X.; Wu, L.-Z.;
Lei, A. J. Am. Chem. Soc. 2015, 137, 9273-9280; (b) Lee, T.; Wilson,
T. W.; Berg, R.; Ryberg, P.; Hartwig, J. F. J. Am. Chem.
Soc., 2015, 137, 6742-6745; (c) Kong, W.-J.; Liu, Y.-J.; Xu, H.; Chen,
Y.-Q.; Dai, H.-X.; Yu, J.-Q. J. Am. Chem. Soc., 2016, 138, 2146-2149;
(d) Liu, B.; Huang, Y.; Lan, J.; Song, F.; You, J. Chem. Sci. 2013, 4,
2163-2167; (r) Liang, Y.-F.; Wang, X.; Yuan, Y.; Liang, Y.; Li, X.;
Jiao, N. ACS Catal., 2015, 5, 6148-6152. (f) Ye, J.; Lautens,
M. Nature Chem. 2015, 7, 863-870.
1
2
3
4
5
6
7
8
3. For sp3 C-H activation, see: (a) Jiang, H.; He, J.; Liu, T.; Yu, J.-
Q. J. Am. Chem. Soc., 2016, 138, 2055-2059; (b) Wang, B.; Nack, W.
A.; He, G.; Zhang, S.-Y.; Chen, G. Chem. Sci.2014, 5, 3952-3957; (c)
Cho, S. H.; Hartwig, J. F. Chem. Sci. 2014, 5, 694-698. (d) Richter, H.;
Mancheño, O. G. Angew. Chem. Int. Ed. 2012, 51, 8656-8660. (e)
Zhang, W.; Ren, S.; Zhang, J.; Liu, Y. J. Org. Chem., 2015, 80, 5973-
5978; (f) Peng, J.; Chen, C.; Chen, J.; Su, X.; Xi, C.; Chen, H. Org.
Lett., 2014, 16, 3776-3779; (g) Fan, Z.; Shu, S.; Ni, J.; Yao, Q.;
Zhang, A. ACS Catal., 2016, 6, 769-774.
4. For selected radical mediated C-H activation, see: (a) Zhang, L.;
Hang, Z.; Liu, Z.-Q. Angew. Chem. Int. Ed. 2016, 55, 236-239. (b)
Qin, G.; Chen, X.; Yang, L.; Huang, H. ACS Catal., 2015, 5, 2882-
2885. (c) Ke, J.; Tang, Y.; Yi, H.; Li, Y.; Cheng, Y.; Liu, C.; Lei, A.
Angew. Chem. Int. Ed. 2015, 54, 6604-6607; (d) Zhang, J.; Li, Y.;
Zhang, F.; Hu, C.; Chen, Y. Angew. Chem. Int. Ed. 2016, 55, 1872-
1875; (e) Wang, Y.; Liu, G.-X.; Yang, G.; He, G.; Chen, G. Chem. Sci.
2016, 7, 2679-2683; (f) Huang, H.; Cai, J.; Ji, X.; Xiao, F.; Chen, Y.;
Deng, G.-J. Angew. Chem. Int. Ed. 2016, 55, 307-311. (g) Liu, C.; Liu,
D.; Lei, A. Acc. Chem. Res. 2014, 47, 3459-3470.
5. (a) Huang, L.; Lin, J.-S.; Tan, B.; Liu, X.-Y. ACS
Catal. 2015, 5, 2826-2831. (b) Qin, Q.; Yu, S. Org. Lett. 2015, 17,
1894-1897. (c) Kundu, R.; Ball, Z. T. Org. Lett., 2010, 12, 2460-2463.
(d) Hashimoto, T.; Hirose, D.; Taniguchi, T. Angew. Chem. Int. Ed.
2014, 53, 2730-2734. (e) Yu, P.; Lin, J.-S.; Zheng, S.-C.; Xiong, Y.-P.;
Zhao, L.-J.; Tan, B.; Liu, X.-Y. Angew. Chem. Int. Ed. 2014, 53,
11890-11894.
6. (a) Jia, X.-D.; Peng, F.-F.; Qing, C.; Huo, C.-D.; Wang, X.-C.
Org. Lett. 2012, 14, 4030-4033. (b) Jia, X.-D.; Wang, Y.-X.; Peng, F.-
F.; Huo, C -D.; Yu, L.-L.; Wang, X.-C. J. Org. Chem. 2013, 78, 9450-
9456. (c) Wang, Y.-X.; Peng, F.-F.; Liu, J.; Huo, C.-D.; Wang, X.-C.;
Jia, X.-D. J. Org. Chem. 2015, 80, 609-614. (d) Liu, J.; Liu, F.; Zhu,
Y.-Z.; Ma, X.-G.; Jia, X.-D. Org. Lett. 2015, 17, 1409-1412.
7. Togo, H. Advanced Free Radical Reactions for Organic Synthe-
sis; Elsevier, 2004.
8. (a) Erdmann, O. L. Journal für Praktische Chemie 1840, 19, 321;
(b) Laurent, A. Annales de Chimie et de Physique 1840, 3, 393.
9. (a) Ilangovan, A.; Satish, G. Org. Lett. 2013, 15, 5726-5729; (b)
Liu, Y.; Chen, H.; Hu, X.; Zhou, W.; Deng, G.-J. Eur. J. Org. Chem.
2013, 4229-4232; (c) Ilangovan, A.; Satish, G. J. Org. Chem. 2014,
79, 4984-4991; (d) Reddy, M. R.; Rao, N. N.; Ramakrishna, K.; Me-
shram, H. M. Tetrahedron Lett. 2014, 55, 4758-4762; (e) Gao, F.-F.;
Xue, W.-J.; Wang, J.-G.; Wu, A.-X. Tetrahedron 2014, 70, 4331-
4335.
10. Tang, B.-X.; Song, R.-J.; Wu, C.-Y.; Liu, Y.; Zhou, M.-B.; Wei,
W.-T.; Deng, G.-B.; Yin, D.-L.; Li, J.-H. J. Am. Chem. Soc. 2010, 132,
8900-8902.
11. Li, W.; Duan, Z.; Zhang, X.; Zhang, H.; Wang, M.; Jiang, R.;
Zeng, H.; Liu, C.; Lei, A. Angew. Chem. Int. Ed. 2015, 54, 1893-1896.
12. (a) Rogness, D. C.; Larock, R. C. J. Org. Chem. 2011, 76,
4980-4986; (b) Satish, G.; Polu, A.; Ramara, T.; Ilangovan, A. J. Org.
Chem. 2015, 80, 5167-5175; (c) Zi, Y.; Cai, Z.-J.; Wang, S.-Y.; Ji, S.-
J. Org. Lett. 2014, 16, 3094-3097.
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Based on above results, a possible mechanism was proposed
(Scheme 4). In the presence of dioxygen, the relatively active
C-H of glycine ester is oxidized by radical cation salt,
[14]
yielding a radical intermediate A. Second, A is trapped by
dioxygen to produce a peroxide radical B. After the intramo-
lecular 1,6-H shift, the C-H bond adjacent to oxycarbonyl
group is activated, followed by β-cleavage and elimination of
water, providing an acyl radical C. This species is further oxi-
dized to a carbonyl cation, and then an intramolecular Friedel-
Crafts type cyclization occurs. After a proton loss and re-
aromatizaion, the isatin product is afforded.
In conclusion, designed by CHAR, an efficient construction
of isatin skeleton was developed from accessible glycine es-
ters. The scope examination shows good substrate generality
and functional group tolerance. The mechanistic studies re-
vealed that the oxidation of the relatively active C-H bonds
initiates the subsequent activation of remote and inert C-H
bonds. So this reaction provides a new way to achieve C-H
activation and the corresponding selectivity control. Further
applications of this reaction and more designs of CHAR are
still underway in our laboratory.
ASSOCIATED CONTENT
Experimental details and spectroscopic data. This material is
available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* E-mail: jiaxd1975@163.com
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was financially supported by National Natural Science
Foundation of China (NNSFC, No. 21362030 and 21562038) for
supporting our research.
REFERENCES
1. For review of C-H activation, see: (a) Alberico, D.; Scott, M. E.;
Lautens, M. Chem. Rev. 2007, 107, 174-238; (b) Lyons, T. W.; San-
ford, M. S. Chem. Rev. 2010, 110, 1147-1169; (c) Cheng, C.; Hartwig,
J. F. Chem. Rev., 2015, 115, 8946-8975; (d) Liu, C.; Yuan, J.;
Gao, M.; Tang, S.; Li, W.; Shi, R.; Lei, A. Chem.
Rev., 2015, 115, 12138-12204.
13. In the absence of a para group, the reaction became complicat-
ed. For details, see: (a) Richter, H.; Mancheño, O. G. Org. Lett. 2011,
13, 6066-6069; (b) Rohlmann, R.; Stopka, T.; Richter, H.; Mancheño,
O. G. J. Org. Chem. 2013, 78, 6050-6064.
14. For mechanistic details of TBPA+. and dioxygen initiated C-H
bond
oxidation,
see
ref
6a.
ACS Paragon Plus Environment

Page 5 of 5
ACS Catalysis
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
ACS Paragon Plus Environment