Facial strategy for radical species through Ag(I)-mediated oxidation of the alkyl trifluoroborates

Article abstract of DOI:10.1080/00397911.2018.1431280

A rapid and highly efficient method for the radical formation using potassium alkylfluoroborates as radical precursor is devised and developed which conducts under relatively mild condition using silver(I) oxide as the oxidant. The observed silver mirror

Full text of DOI:10.1080/00397911.2018.1431280

Synthetic Communications
An International Journal for Rapid Communication of Synthetic Organic
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Facial strategy for radical species through Ag(I)-
mediated oxidation of the alkyl trifluoroborates
Siyi Ding, Shaopeng Tian, Yuzhen Zhao, Qiang Ma, Min Zhu, Huaping Ren,
Kexuan Li & Zongcheng Miao
To cite this article: Siyi Ding, Shaopeng Tian, Yuzhen Zhao, Qiang Ma, Min Zhu, Huaping
Ren, Kexuan Li & Zongcheng Miao (2018): Facial strategy for radical species through
Ag(I)-mediated oxidation of the alkyl trifluoroborates, Synthetic Communications, DOI:
10.1080/00397911.2018.1431280
To link to this article: https://doi.org/10.1080/00397911.2018.1431280
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https://doi.org/10.1080/00397911.2018.1431280
Facial strategy for radical species through Ag(I)-mediated
oxidation of the alkyl trifluoroborates
Siyi Ding , Shaopeng Tian, Yuzhen Zhao, Qiang Ma, Min Zhu, Huaping Ren,
Kexuan Li, and Zongcheng Miao
Key Laboratory of Organic Polymer Photoelectric Materials, School of Science, Xijing University, Xi’an,
Shaanxi, China
ABSTRACT
ARTICLE HISTORY
Received 18 September 2017
A rapid and highly efficient method for the radical formation using
potassium alkylfluoroborates as radical precursor is devised and
developed which conducts under relatively mild condition using silver
KEYWORDS
Alkyl radical; alkyl
trifluoroborates;
(
I) oxide as the oxidant. The observed silver mirror phenomenon hints
at the fact that Ag O is the real oxidant. This approach effectively
2
silver(I)-mediated oxidation
overcomes the drawbacks-stringent reaction conditions and poor
tolerance of a variety of functional groups.
GRAPHICAL ABSTRACT
Introduction
Radical chemistry has attracted special research interest and has found widespread
applications in medicinal chemistry, agrochemicals, and material science.[1] Over the past
few years, radical reactions have gradually become versatile and useful synthetic methods
[
2]
for the construction of carbon–carbon bond. By virtue of the tandem radical reactions,
including radical addition or cyclization of functionalized alkenes,[ various heterocycles
can be obtained in convenient pathways.
3]
Organometallic compounds, such as organolithium reagents and Grignard reagents, can
[
4,5]
be oxidized to their relevant radicals.
Using organometallic compounds as the radical
precursors, however, we face several drawbacks because of their high reactivity and their
[
6]
sensitivity to air and moisture. Another critical defect for the wide application of such
organometallic compounds is poor tolerance of many functional groups. To overcome
these limitations, the top priority is to find another softer organometallic reagent. Organo-
trifluoroborates, because of their lack of the empty p-orbitals, are less sensitive to numerous
organic reagents than their boronic acid analogues. This important characteristic facilitates
their ease of handling, stability and robustness under harsh reaction conditions. Recently,
CONTACT Zongcheng Miao
miaozongcheng@xijing.edu.cn
Key Laboratory of Organic Polymer Photoelectric
Materials, School of Science, Xijing University, Xi’an, Shaanxi 710123, China.
1
13
Supplemental data (full experimental details and HNMR, CNMR, and HRMS for all compounds) can be accessed on the
publisher’s website.
©
2018 Taylor & Francis

2
S. DING ET AL.
Scheme 1. Approaches toward the radical formation using alkyl trifluoroborate as the precursors.
potassium organotrifluoroborates have been used widely in as nucleophiles transition-
metal-catalyzed reactions.[7] As is the case with boronic acids, potassium organotrifluoro-
borates also can serve as radical precursors. Thus far, the generation of carbon-centered
radicals from alkyl potassium organotrifluoroborates (alkyl BF K) has been performed
3
by stoichiometric or excess amount of oxidants (Scheme 1a). In 2010, Fensterbank and
colleagues reported that alkylBF K served as radical precursors under oxidative conditions
3
using copper(II) acetate (Cu(OAc) ) or copper(II) chloride (CuCl ) and 2,2,6,
2
2
[
8]
6
-tetramethylpiperidinooxy (TEMPO). This method was compatible with primary and
tertiary substrates. The following year, Molander’s group put forward another oxidative
[
9]
system using 2.5 equiv. of manganese (III) acetate in the presence of trifluoroacetic acid
in a 1:1 mixture of acetic acid and water. Two years later, Yu’s finding hinted at the fact
[
10]
that silver(I) carbonate played an essential role in the generation of free alkyl radicals.
Moreover, the formed alkyl radicals were successfully applied in the Palladium(II)
2
catalyzed ortho-C(sp )-H alkylation reactions. Baran reported that radical reactions could
be induced by a combination of a catalytic amount of silver(I) nitrate and an excess amount
[
11]
of potassium persulfate as co-oxidant (Scheme 1b).
Alternatively, a visible-light-driven single-electron tranmetalation photoredox catalysis
provides a facial and efficient access to carbon centered radicals through oxidation of
organotrifluoroborates (Scheme 1c). This strategy recently has attracted significant interest
of synthetic chemists and has been accepted widely as an effective way to generate radical
[
12]
[12d,12e,12g]
species. Molander and colleagues developed a dual catalytic system
containing
nickel salt along with photocatalyst, which allowed for the efficient use of alkyltrifluorobo-
rates in cross-coupling reactions under relatively mild conditions. The alkyl radicals, which
were generated through on oxidation process in the presence of visible-light photoredox
catalyst, easily underwent facial single-electron transmetalation onto a nickel catalyst
and then gave the target products through a reductive elimination process. The previously

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mentioned methods, however, still have some shortcomings, including, for example, the
formation of large amounts of metallic wastes, harsh reaction conditions, poor tolerance
of many different functional groups, the requirement of special equipments and expensive
photoredox catalysts. Therefore, it is essential to develop a more efficient method for the
generation of free radicals.
Results and discussion
Initially, to probe our design, we examined the reactivity of phenylpropyl trifluoroborate
1a, embedding in our memory that the phenylpropyl radical should be the classical alkyl
radical. The generated radials were then trapped by TEMPO, affording 2a and showing
crucial evidence for the existence of the radical intermediate. We first operated reactions
with Cu(OAc) as the oxidant, together with 1.0 equiv. of silver oxide (Ag O) as the
2
2
co-oxidant. The reactions were easily monitored by gas chromatography–mass spec-
trometry (GC-MS) and thin-layer chromatography (TLC). Notably, a good yield of 2a
was detected in toluene/water (50:1) mixture (Table 1, entry 2). Furthermore, adding a
small amount of water was highly beneficial to guarantee a good yield (Table 1, entry
1
3), suggesting the possible role of water in keeping the alkylboron species in the reactive
boronic acid form. Although the protic solvent, such as methanol, was not suitable for this
reaction (Table 1, entry 5), polar solvents together with trace distilled water provided worse
results (Table 1, entries 3–4, 6–7). In the toluene/water system, each kind of copper salts
together with Ag O gave a similar yield (for more details, see supplemental information).
2
Table 1. Oxidation of phenylpropyl trifluoroborate 1a.
d
Entry
Catalyst (0.2 equiv.)
Oxidant (1.0 equiv.)
Solvent
2a yield [%]
b
1
2
3
4
5
6
7
8
9
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
Cu(OAc)
–
2
2
2
2
2
2
2
2
2
2
Ag
Ag
Ag
Ag
Ag
Ag
Ag
2
O
2
O
2
O
2
O
2
O
2
O
2
O
Tol
Tol
ND
98
65
26
ND
30
42
c
c
DCM
c
EA
c
MeOH
c
DMF
c
MeCN
c
MnO
Mn(OAc)
AgNO
Cu(OAc)
Ag
2
Tol
ND
ND
ND
ND
c
2
Tol
c
1
1
0
1
3
Tol
c
2
Tolc
g
1
2
–
2
O
Tol
98(95)
b
13
14
15
–
–
Ag
Ag
Ag
2
O
O
O
Tol
ND
8
ND
c,e
2
2
Tol
c,f
–
Tol
a
b
c
Reaction conditions: RBF
3 2
K (0.1 mmol, 1.0 equiv.), TEMPO (0.1 mmol, 1.0 equiv.), Ag O (0.1 mmol, 1.0 equiv.).
The reaction was conducted without addition of distilled water.
The reaction was conducted with addition of distilled water(20 μL).
d
NMR yield, 1,3,5-trimethoxyl benzene as the internal standard reagent.
The reaction was run under air.
e
f
The reaction was conducted under oxygen atmosphere.
g
Yield of the isolated product, purified by column chromatography.
ND, not determined; DCM, dichloromethane; DMF, dimethylformamide; TEMPO, 2,2,6,6-tetramethyl-1-piperidinyloxy, free
radical.

4
S. DING ET AL.
Interestingly, a similar result could be obtained without copper salts (Table 1, entry 12).
Using other oxidants instead of Ag O, we could not observe any radical adduct by TLC
2
or GC-MS (Table 1, entries 8–10). These findings proved that Ag O was an effective
2
oxidant to produce the alkyl radicals in high yield. Cu(OAc) was totally unreactive under
2
the current conditions (Table 1, entries 11 and 12). This is remarkable because Cu(OAc)2
has been proved to be an effective oxidant of alkyl trifluoroborates in other different
[
8]
conditions. Attempts to run this reaction under an air or oxygen atmosphere resulted
in very low yield (Table 1, entries 14 and 15). Increasing or lowering the reaction
temperature was of no advantage to these reactions (for more details, see supplemental
information). Finally, we ran the model reaction at a 5.0 mmol scale using 1a as the starting
materials, and the isolated yield of the aim product was 86%, compared with 95% at
the 0.1 mmol scale and 93% at the 1.0 mmol scale, respectively (for more details, see
supplemental information).
Having defined an appropriate set of reaction conditions, we briefly investigated the
scope of alkyl trifluoroborates (Scheme 2). Notably, benzyl trifluoroborate (1e) could
be easily oxidized to generate the benzyl radical, which was trapped by TEMPO. Primary
alkyl trifluoroborates bearing functional groups, such as ester (1j, 1k, and 1l) and even
ketone (1i), were suitable substrates. In addition, alkyl trifluoroborates with heteroarene
moieties were compatible (1m and 1n). Note that the alkyl moiety with bromo- or
chloro-atoms (1c and 1d) remained intact under these conditions, demonstrating the
mild nature of the reaction condition. When we used branched alkyl trifluoroborates,
we obtained a moderate yield, which was not sensitive to steric hindrance (1g, 1h,
and 1l). Furthermore, secondary alkyl-trifluoroborates (1o and 1p), and tertiary alkyl-
trifluoroborate (1q) were also viable substrates under the current conditions, and they
could be quantitatively oxidized to form the relevant radicals. After the process was
completed, silver mirror formed on the surface of the reactor, which was so difficult
to remove that we had to use nitric acid to get rid of the silver(0). We ran all of these
reactions at a 1.0 mmol scale under the standard reaction conditions with excellent
isolated yield, which are showed in the brackets.
Following these theoretical knowledge,[ we think that a single-electron transfer from
7]
the copper-catalyst generates a transient radical and a low-valent copper species, which
can be oxidized by Ag O to re-participate in the process (Scheme 3a). On the basis of
2
our experimental results, however, we put forward a more reasonable mechanism
(
Scheme 3b). A single electron that is transferred from the oxidant Ag O can generate alkyl
2
radical, and is accompanied by the formation of boron trifluoride. Then, TEMPO can trap
the alkyl radical to get the adduct.
Thus far, we have successfully applied this new radical formation strategy in a
[
13]
boron-selective oxidative cross-coupling reaction
using arylboronic acids and alkyltri-
fluoroborates as the coupling partners (Scheme 4). The carbon-centered radical, generated
from the Ag O-mediated oxidative process, undergoes the single-electron transmetalation
2
onto the aryl-Cu(II)X species, which was formed through transmetalation of the aryl boro-
nic acids to the copper catalyst, and then reductive elimination occurs from the reactive
intermediate ArCu(III)RX to produce the desired cross-coupling product. This strategy
provides us a new way to construct C–C bond. Primary and secondary alkyltrifluoroborates
can successfully participate in the current reaction. Fortunately, the bromine group, which
may not be compatible under the reaction conditions containing the organometallic

SYNTHETIC COMMUNICATIONS®
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Scheme 2. Oxidation of potassium alkyl trifluoroborates. Note: TEMPO, 2,2,6,6-tetramethylpiperidinooxy.
compounds, is also viable substrate with moderate yield. Under the same condition,
the benzylic alkyltrifluoroborate 1e can be oxidized to form its corresponding benzyl
radical, which has special structure and high reactivity, and then lead to relatively low
yield.
Encouraged by these preliminary results, we explored more meaningful application from
the synthetic point. Aryl isonitriles are another well-established radical acceptor, which
are isoelectronic with carbon monoxide, and they can undergo insertion reaction to
provide N-containing heterocycles that are important substrate present in many natural
products with different biological activities.[14] In practice, using the model substrate
0
1
f under this reaction condition with the addition of 2-isocyano-1,1 -biphenyl, we found

6
S. DING ET AL.
Scheme 3. (a) Proposed mechanism and (b) revised mechanism.
the phenanthridine 4f was formed in a moderate yield. The result obtained with Ag O is
2
2
3
depicted in Scheme 5. This is another strategy for the new C(sp )–C(sp ) bond formation,
which might be compatible with various functionalized groups. These results suggest the
need for elaboration and will be reported in due course.
Scheme 4. Application in the copper-catalyzed boron-selective C(sp )–C(sp ) oxidative cross-coupling
2
3
reactions between arylboronic acids and alkyltrifluoroborates.

SYNTHETIC COMMUNICATIONS®
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Scheme 5. Application in the insertion reaction to construct the phenanthridine.
Conclusion
In summary, we discovered an Ag O-oxidized method to form alkyl radicals using potass-
2
ium alkyl-trifluoroborates as the precursors. This reaction is interesting and potentially
advantageous. For the radical precursors, in comparison with other organometallic
reagents, organoboronic acid derivatives are more readily available, stable to air and moist-
ure, and compatible with many functional groups. Moreover, this new strategy features
excellent product selectivity, a short reaction time, mild reaction conditions, simple oper-
ation, and broad functional group tolerance. In comparison with conventional strategies,
the current reaction requires an additional step to obtain an organoboron reactant using
the corresponding halide as the starting materials. Nevertheless, taking into consideration
that many shelf-stable alkyl-organoboron derivatives are already available in the market,
this reaction should be of great use in facilitating small-molecule array synthesis. Although
the complete mechanism remains unclear, this silver(I) oxidized method can be used in
many different kinds of organic reactions, including radical addition or cyclization of func-
tionalized alkenes. Its application prospect in organic chemistry and functional material
chemistry is very broad and quite optimistic. Research in this area is ongoing in our lab.
Experimental
General
Unless otherwise noted, all reactions were performed in a flame-dried, sealed Schlenk reac-
tion tube under nitrogen atmosphere.
Analytical thin-layer chromatography was performed on glass plates coated with
.25 mm 230–400 mesh silica gel containing a fluorescent indicator (Merck). Visualization
0
was accomplished by exposure to a UV lamp, and/or treatment with a solution of KMnO4
or a solution of phosphomolybdic acid followed by brief heating with a heating gun. Most
of the products in this article are compatible with standard silica gel chromatography. Col-
umn chromatography was performed on silica gel 60N (spherical and neutral, 140–325
mesh) using standard methods.
Structural analysis
NMR spectra were measured on a Bruker Avance-400 spectrometer and chemical shifts (δ)
1
are reported in parts per million (ppm). H NMR spectra were recorded at 400 MHz in
NMR solvents (CDCl , Acetone-d , DMSO-d ) and referenced internally to corresponding
3
6
6
1
3
solvent resonance, and C NMR spectra were recorded at 100 MHz and referenced to
corresponding solvent resonance, Carbons bearing boron substituents were generally not
observed due to quadrupolar relaxation. Coupling constants are reported in Hz with

8
S. DING ET AL.
multiplicities denoted as s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet),
and br (broad). Infrared spectra were collected on a Thermo Fisher Nicolet 6700 FI-IR
spectrometer using attenuated total reflectance method. Absorption maxima are reported
−
1
in wavenumbers (cm ). High resolution mass spectra (HRMS) were obtained on a Bruker
Apex IV FTMS spectrometer or an Agilent 6224 LC/MS TOF spectrometer.
Materials
Commercial reagents were purchased from J&K, Energy, Sigma-Aldrich, Alfa Aesar, Acros
Organics, Strem Chemicals, TCI and used as received unless otherwise stated. Solvents,
including hexane, THF, Et O, toluene, were purified by distillation over sodium, and stored
2
under N2.
General procedure
In air, the potassium alkyltrifluoroborate (1.0 equiv.), Ag O (1.0 equiv.), and TEMPO (1.0
2
equiv.) were sequentially weighed and added to a screw-capped Schenk tube containing
a magnetic stir bar. The vessel was evacuated and refilled with nitrogen for three times.
−
1
−1
Toluene (10.0 mL mmol ) and distilled water (200 μL mmol ) were added in turn under
2
N atmosphere using syringes through a septum which was temporarily used to replace the
screw cap. The reaction mixture was then vigorously stirred at room temperature for the
®
indicated time. The resulting mixture was filtered through a pad of Celite , and the filter
cake was washed with ethyl acetate (30 mL � 3). The combined filtrate was evaporated
under vacuum to dryness and the residue was purified by column chromatography to yield
the desired product.
Selected spectral data
2
-(4-((2,2,6,6-tetramethylpiperidin-1-yl)oxy)butyl)isoindoline-1,3-dione (2n)
The general procedure was followed using (1) 0.1 mmol gram scale: 2-(4-(trifluoro-l4-
boranyl)butyl)isoindoline-1,3-dione, potassium salt (1n) (30.9 mg, 0.1 mmol, 1.0 equiv.)
and 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO, 1.0 equiv.) as the starting materials,
alkyl-TEMPO 2n was obtained as colorless oil (34.4 mg, yield 96%).
(
2) 1.0 mmol gram scale: 2-(4-(trifluoro-l4-boranyl)butyl)isoindoline-1,3-dione, potass-
ium salt (1n) (309.1 mg, 1.0 mmol, 1.0 equiv.) and 2,2,6,6-tetramethylpiperidine-1-oxyl
(
TEMPO, 1.0 equiv.) as the starting materials, alkyl-TEMPO 2n was obtained as colorless
oil (333.1 mg, yield 93%).
IR (thin film): 3500, 3080, 2980, 2840, 1888, 1680, 1620, 1550, 1470, 1220, 1010, 900,
−1 1
7
(
70 cm ; H NMR (400 MHz, CDCl ) δ 7.83 (m, 2H), 7.69 (m, 2H), 3.72 (m, 2H), 1.76
3
13
m, 2H), 1.40 (m, 4H), 1.24 (m, 4H), 1.11 (s, 6H), 1.06 (s, 6H); C NMR (100 MHz,
CDCl ) δ 168.5, 133.9, 132.1, 123.1, 75.9, 59.8, 39.6, 37.8, 32.8, 29.4, 26.2, 20.1, 16.9; HRMS
3
þ
(
ESI ): Calcd for C H N O [MþH] 375.2279, found 375.2272.
2
1
30 2 3
Funding
We are grateful for financial support by the National Science Foundation of China (No. 51673157)
and Special Fund for Talent Research of Xijing University (Nos. XJ17B01 and XJ16T05). Thank Pro
Pengfei Li (Xi’an Jiaotong University) very much for his guidance and advices during this work.

SYNTHETIC COMMUNICATIONS®
9
ORCID
Siyi Ding
http://orcid.org/0000-0001-5446-0254
References
[
1] (a) Renaud, P.; Sibi, M. P. Radicals in Organic Synthesis; Wiley-VCHL: Weinheim, 2001;
(
(
b) Gansäuer, A. Radicals in Synthesis I & II; Springer: Berlin, 2006; Vols. 263, 264;
c) Rowlands, G. J. Tetrahedron 2009 65, 8603–8655; (d) Rowlands, G. J. Tetrahedron 2010,
66, 1593–1636.
[2] For selected examples for the formation of the C–C bond through radical process: (a) Ryu, I.;
Sonoda, N.; Curran, D. P. Chem. Rev. 1996, 96, 177–194; (b) Wang, K. K. Chem. Rev. 1996, 96,
2
07–222; (c) Malacria, M. Chem. Rev. 1996, 96, 289–306; (d) Snider, B. B. Chem. Rev. 1996, 96,
39–364; (e) Gansäuer, A.; Bluhm, H. Chem. Rev. 2000, 100, 2771–2788; (f) Bar, G.;
3
Parsons, A. F. Chem. Soc. Rev. 2003, 32, 251–283; (g) Sibi, M. P.; Manyem, S.; Zimmerman,
J. Chem. Rev. 2003, 103, 3263–3296; (h) Recupero, F.; Punta, C. Chem. Rev. 2007, 107,
3
800–3842; (i) Zard, S. Z. Chem. Soc. Rev. 2008, 37, 1603–1618; (j) Tang, S.; Liu, K.; Liu, C.;
Lei, A. W. Chem. Soc. Rev. 2015, 44, 1070–1082.
[3] For selected examples of the tandem radical cyclization reactions: (a) Chen, J. R.; Yu, X. Y.;
Xiao, W. J. Synthesis 2014, 47, 604–629; (b) Wu, T.; Zhang, H.; Liu, G. Tetrahedron 2012,
68, 5229–5233; (c) Wei, W. T.; Zhou, M. B.; Fan, J. H.; Liu, W.; Song, R. J.; Liu, Y.; Hu, M.;
Xie, P.; Li, J. H. Angew. Chem. Int. Ed. 2013, 52, 3638–3641; (d) Li, Y. M.; Sun, M.; Wang,
H. L.; Tian, Q. P.; Yang, S. D. Angew. Chem. Int. Ed. 2013, 52, 3972–3976; (e) Matcha, K.;
Narayan, R.; Antonchick, A. P. Angew. Chem. Int. Ed. 2013, 52, 7985–7989; (f) Shen, T.; Yuan,
Y.; Jiao, N. Chem. Commun. 2014, 50, 554–556; (g) Li, Z.; Zhang, Y.; Zhang, L.; Liu, Z. Q. Org.
Lett. 2014, 16, 382–385; (h) Mai, W. P.; Wang, J. T.; Yang, L. R.; Yuan, J. W.; Xiao, Y. M.; Mao,
P.; Qu, L. B. Org. Lett. 2014, 16, 204–207; (i) Han, G.; Wang, Q.; Liu, Y.; Wang, Q. Org. Lett.
2
014, 16, 5914–5917.
[
[
[
4] Maji, M. S.; Pfeifer, T.; Studer, A. Angew. Chem. Int. Ed. 2008, 47, 9547–9550.
5] Nagashima, T.; Curran, D. P. Synlett 1996, 1996, 330–332.
6] (a) Whitesides, G. M.; Newirth, T. L. J. Org. Chem. 1975, 40, 3448–3450; (b) Dalko, P. I.
Tetrahedron Lett. 1999, 40, 4035–4036.
7] For selected examples of organotrifluoroborates as the coupling partners in the metal-catalyzed
reactions: (a) Molander, G. A.; Figueroa, R. Aldrichim. Acta 2005, 38, 49; (b) Stefani, H. A.;
Cella, R.; Vieira, A. S. Tetrahedron 2007, 63, 3623–3658; (c) Molander, G. A.; Ellis, N. Acc.
Chem. Res. 2007, 40, 275–286; (d) Darses, S.; GenÞt, J. P. Chem. Rev. 2008, 108, 288–325;
[
(
e) Vogler, T.; Studer, A. Synthesis 2008, 2008, 1979–1993; (f) Rudolph, A.; Lautens, M. Angew.
Chem. Int. Ed. 2009, 48, 2656–2670; (g) Doucet, H. Eur. J. Org. Chem. 2010, 2008, 2013–2030;
(
h) Jana, R.; Pathak, T. P.; Sigman, M. S. Chem. Rev. 2011, 111, 1417–1492; (i) Kambe, N.;
Iwasaki, T.; Terao, J. Chem. Soc. Rev. 2011, 40, 4937–4947; (j) Han, C.; Buchwald, S. L.
J. Am. Chem. Soc. 2009, 131, 7532–7533; (k) Thaler, T.; Haag, B.; Gavryushin, A.; Schober,
K.; Hartmann, E.; Gschwind, R. M.; Zipse, H.; Mayer, P.; Knochel, P. Nat. Chem. 2010, 2,
1
2
2
25–130; (l) Pompeo, M.; Froese, R. D. J.; Hadei, N.; Organ, M. G. Angew. Chem. Int. Ed.
012, 51, 11354–11357; (m) Joshi-Pangu, A.; Wang, C. Y.; Biscoe, M. R. J. Am. Chem. Soc.
011, 133, 8478–8481; (n) Bartoccini, F.; Cabri, W.; Celona, D.; Minetti, P.; Piersanti, G.;
Tarzia, G. J. Org. Chem. 2010, 75, 5398–5401 (o) Molander, G. A.; Canturk, B. Angew. Chem.
Int. Ed. 2009, 48, 9240–9261.
[
8] Sorin, G.; Mallorquin, R. M.; Contie, Y.; Baralle, A.; Malacria, M.; Goddard, J. P.; Fensterbank,
L. Angew. Chem. Int. Ed. 2010, 49, 8721–8723.
[
9] Mn(III) complex as the oxidant for the radical formation: (a) Dickschat, A.; Studer, A. Org.
Chem. 2010, 12, 3972–3974; (b) Molander, G. A.; Colombel, V.; Braz, V. A. Org. Chem.
2
011, 13, 1852–1855.
[
10] Thuy-Boun, P. S.; Villa, G.; Dang, D.; Richardson, P.; Su, S.; Yu, J. Q. J. Am. Chem. Soc. 2013,
1
35, 17508–17513.

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0
S. DING ET AL.
[
11] Examples of silver nitrite as the oxidant for the radical formation: (a) Fujiwara, Y.; Domingo,
V.; Seiple, I. B.; Gianatassio, R.; Bel, M. D.; Baran, P. S. J. Am. Chem. Soc. 2011, 133, 3292–3295;
(
b) Lockner, J. W.; Dixon, D. D.; Risgaard, R.; Baran, P. S. Org. Lett. 2011, 13, 5628–5631;
c) Liwosz, T. W.; Chemler, S. R. Org. Lett. 2013, 15, 3034–3037; (d) Presset, M.;
(
Fleury-Brégeot, N.; Oehlrich, D.; Rombouts, F.; Molander, G. A. J. Org. Chem. 2013, 78,
4
615–4619.
[
12] Examples for the single-electron transfer (SET) oxidative process which was conducted under
photocatalytic conditions to form the radical: (a) Nishigaichi, Y.; Orimi, T.; Takuwa, A. J. Org.
Met. Chem. 2009, 694, 3837–3839; (b) Yasu, Y.; Koike, T.; Akita, M. Adv. Synth. Catal. 2012,
354, 3414–3420; (c) Huang, H.; Zhang, G.; Gong, L.; Zhang, S.; Chen, Y. J. Am. Chem. Soc.
2014, 136, 2280–2283; (d) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science 2014, 345,
433–436; (e) Gutierrez, O.; Tellis, J. C.; Primer, D. N.; Molander, G. A.; Kozlowski, M. C.
J. Am. Chem. Soc. 2015, 137, 4896–4899; (f) Oderinde, M. S.; Varela-Alvarez, A.; Aquila, B.;
Robbins, D. W.; Johannes, J. W. J. Org. Chem. 2015, 80, 7642–7651; (g) Primer, D. N.;
Karakaya, I.; Tellis, J. C.; Molander, G. A. J. Am. Chem. Soc. 2015, 137, 2195–2198; (h) Dai,
J.; Zhang, W.; Shu, Y.; Sun, Y.; Xu, J.; Feng, Y.; Xu, H. Chem. Commun. 2016, 52, 6793–6796;
(
i) Nishigaichi, Y.; Orimi, T.; Koyachi, K.; Ohmuro, Y.; Suzuki, M. Chem. Lett. 2016, 45,
1
7
382–1384; (j) Chen-Neberg, L.; Lévêque, C.; Corcé, V.; Fensterbank, L. Synlett 2016, 27,
31–735; (k) Zhang, W.; Dai, J.; Xu, J.; Xu, H. J. Org. Chem. 2017, 82, 2059–2066.
[
[
13] Ding, S. Y.; Xu, L.; Li, P. F. ACS Catal. 2016, 6, 1329–1333.
14] For selected examples for the radical cyclization reaction to form the substituted phenanthri-
dine derivatives: (a) Zhang, B.; Muck-Lichtenfeld, C.; Daniliuc, C. G.; Studer, A. Angew. Chem.
Int. Ed. 2013, 52, 10792–10795; (b) Jiang, H.; Cheng, Y.; Wang, R.; Zheng, M.; Zhang, Y.; Yu, S.
Angew. Chem. Int. Ed. 2013, 52, 13289–13292; (c) Liu, J.; Fan, C.; Yin, H.; Qin, C.; Zhang, G.;
Zhang, X.; Lei, A. W. Chem. Commun. 2014, 50, 2145–2147; (d) Xu, Z.; Yan, C.; Liu, Z. Org.
Lett. 2014, 16, 5670–5673; (e) Zhang, B.; Studer, A. Org. Lett. 2014, 16, 3990–3993; (f) Fang, H.;
Zhao, J.; Ni, S.; Mei, H.; Han, J.; Pan, Y. J. Org. Chem. 2015, 80, 3151–3158; (g) Zhou, Y.; Wu,
C.; Dong, X.; Qu, J. J. Org. Chem. 2016, 81, 5202–5208; (h) Yao, Q.; Zhou, X.; Zhang, X.; Wang,
C.; Wang, P.; Li, M. Org. Biomol. Chem. 2017, 15, 957–971.