Free-Radical-Promoted Site-Selective C-H Silylation of Arenes by Using Hydrosilanes

Article abstract of DOI:10.1021/acs.orglett.7b02717

A free-radical-promoted aryl/heteroaryl C-H silylation using hydrosilane was developed. This cross-dehydrogenative silylation enables both electron-rich and electron-poor aromatics to afford the desired arylsilanes in unique selectivity. A "para-selectivity" was observed by examination of over 54 examples. This exceptional orientation is quite different from that in Friedel-Crafts C-H silylation or transition-metal-catalyzed dehydrogenative silylation.

Full text of DOI:10.1021/acs.orglett.7b02717

Letter
pubs.acs.org/OrgLett
Free-Radical-Promoted Site-Selective C−H Silylation of Arenes by
Using Hydrosilanes
Zhengbao Xu,† Li Chai,† and Zhong-Quan Liu*,†,‡
†State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China
‡State Key Laboratory Cultivation Base for TCM Quality and Efficacy, College of Pharmacy, Nanjing University of Chinese Medicine,
Nanjing 210023, China
S
* Supporting Information
ABSTRACT: A free-radical-promoted aryl/heteroaryl C−H silylation
using hydrosilane was developed. This cross-dehydrogenative silylation
enables both electron-rich and electron-poor aromatics to afford the
desired arylsilanes in unique selectivity. A “para-selectivity” was observed
by examination of over 54 examples. This exceptional orientation is quite
different from that in Friedel−Crafts C−H silylation or transition-metal-
catalyzed dehydrogenative silylation.
rganosilicon compounds find wide applications in
It is well-known that the site-selectivity in radical reactions is
unique, which is quite different from that in polar reactions.11 For
example, C2 silylation happened in radical-initiated reaction of
indole with hydrosilane as reported by Grubbs.10 Sila Friedel−
Crafts reactions afford C3-silylated products.4 Previous studies
on radical-initiated homolytic aromatic alkylation showed special
regioselectivity, which was called “para-selectivity”.12 It is
believed that the resonance stabilization of the σ-complex
might be responsible for this exceptional selectivity. As part of
our continuous studies on free-radical-promoted C−Si bond
formation,13 we began to envision whether a similar “para-
selectivity” could be observed in radical silylation of arenes.
Fortunately, we successfully accomplished a direct C−Si bond
formation via free-radical reaction of arenes/heteroarenes with
hydrosilanes. Furthermore, a unique and predictable selectivity
was observed in this homolytic aromatic silylation by
examination of over 54 examples. To the best of our knowledge,
it is the first time the “para-selectivity” in radical-promoted
silylation of aryl C−H bond has been revealed.
O
synthetic chemistry, material, and polymer science.1 Direct
silylation of inert C−H bonds using hydrosilanes represents the
most atom-economic and waste-minimizing access to organo-
silanes.2 As depicted in Scheme 1, two main pathways through
Scheme 1. Accesses to Aryl and Heteroaromatic Silanes via
C−H Silylation Using Hydrosilane
cross-dehydrogenative coupling (CDC)3 reactions of arenes/
heteroarenes with hydrosilanes have been explored to afford
arylsilanes in recent years. One is the Friedel−Crafts C−H
silylation via electrophilic aromatic substitution (SEAr).4,5
Usually, only electron-rich aromatics could be smoothly silylated
through this method. The other is the transition-metal-catalyzed
dehydrogenative silylation.6,7 Generally, ortho- and meta-
silylation of aryl C−H bonds could be selectively achieved by
this strategy. A directing group and noble metal catalysts as well
as hydrogen acceptor are often required in these systems. There
is, in fact, a third pathway to aryl C−H silylation. That is free-
radical-promoted homolytic aromatic silylation.8,9 It was
considered unpractical because of very low yields and poor
selectivities. Recently, Grubbs and Stoltz et al.10 realized a series
of highly efficient radical heteroaryl C−H silylations initiated by
alkali metal oxides, which made a significant breakthrough in this
area. Although this system is sensitive to oxygen and moisture
and aromatics with electron-withdrawing groups were generally
not tolerated in this chemistry, the features of unique selectivity,
transition-metal-free, and mild conditions enable this radical
silylation service to be an elegant alternative to path I and II.
Initially, we chose N-phenylacetamide and triethylsilane as the
model compounds to evaluate the regioselectivity in aryl C−H
silylation under free-radical initiation (Table 1). It was found that
the Cu2O was more efficient than Cu powder, CuBr, and
Fe(OAc)2, etc. (entries 1−5). In the case of the solvent, it seemed
that only t-BuOH was effective (entries 6−8). Additionally, the
peroxide DTBP (di-tert-butyl peroxide), used as the radical
initiator, is more efficient than DCP (dicumyl peroxide) and
BPO (benzoyl peroxide), etc. (entries 9 and 10). Finally, a good
isolated yield of N-(4-(triethylsilyl)phenyl)acetamide was
obtained as the unique product by using a catalytic amount of
1
Cu2O (entries 11 and 12). The H and 13C nuclear magnetic
resonance (NMR) spectra indicated that the para-silylation is
dominant (>20:1).
Received: August 31, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b02717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
nally, we examined several para-substituted arenes (15−17). N-
(4-Methoxyphenyl)acetamide and N-(2,4-dimethoxyphenyl)-
acetamide yielded meta-silylation products 15 and 16,
respectively. A 52% yield of (3,6-dimethoxy-1,2-phenylene)bis-
(triethylsilane) (17) was isolated by using 1,4-dimethoxyben-
zene. Surprisingly, 1,3-dimethoxybenzene gave 18 as the major
product. Silylation occurred at a more hindered position in this
case.
Table 1. Optimization of the Reaction Conditions
b
entry
initiator (mol %)
peroxide
solvent
yield (%)
1
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DCP
t-BuOH
t-BuOH
t-BuOH
t-BuOH
t-BuOH
DMF
trace
42
2
Cu (10)
3
Cu2O (10)
CuBr (10)
Fe(OAc)2 (10)
Cu2O (10)
Cu2O (10)
Cu2O (10)
Cu2O (10)
Cu2O (10)
Cu2O (5)
56
To further study the site-selectivity of this radical silylation of
aryl C−H, a wide range of electron-deficient aromatics were
tested. As demonstrated in Scheme 3, para-silylated arenes were
4
14
5
trace
NR
NR
NR
trace
trace
62
6
7
DMSO
TFE
a
Scheme 3. Silylation of Electron-Poor Arenes with HSiEt3
8
9
t-BuOH
t-BuOH
t-BuOH
t-BuOH
10
11
12
BPO
DTBP
DTBP
Cu2O (2)
51
a
Reaction conditions: N-phenylacetamide (1 equiv, 0.1 mmol), HSiEt3
(12 equiv, 1.2 mmol), peroxide (18 equiv, 1.8 mmol), solvent (0.5
mL), sealed tube, 120 °C (measured temperature of the oil bath), 12 h
later, additional portions of HSiEt3 (1.2 mmol) and peroxide (1.8
b
mmol) were added, refluxing for a further 12 h. Isolated yield.
With the above optimized conditions in hand, we set out to
investigate the substrate scope and the site selectivity of this
system (Scheme 2). First a set of N-phenylalkylamides including
a
Scheme 2. Silylation of Electron-Rich Arenes with HSiEt3
a
b
c
Typical reaction conditions. Isolated yield. The ratio of
1
regioisomers were determined by H NMR.
also isolated as the major products. Benzamide gave regioisomers
in 35% yield with the ratio of p/m = 2/1 (19). while a 71% yield
of isomers with p/m = 3/1 ratio was obtained with N-
methylbenzamide (20). Gratifyingly, an array of benzoates
afforded the products in high yields with p/m = 4/1 ratio (21−
26). Variation of the structure of alcohol in esters could not affect
the site-selective ratio. To our delight, meta-substituted
benzamides and benzoates all generated the desired products
in 38−86% yields, and the ratios of para/meta were up to 20/1
(27−35). Interestingly, dimethyl phthalate led to a unique silane
in 70% yield (36). Similarly, meta-silylation occurred when the
para-position of benzamide and benzoate was occupied (37 and
38).
In addition, various heterocycles were examined. As depicted
in Scheme 4, heteroaromatics such as benzofuran, benzo[b]-
thiophene, thiophene, indole, pyridine, and pyrrole were
amenable to this system. The C2-silylation products were
isolated in high yields with C3-substituted benzofurans,
benzo[b]thiophenes, and thiophenes (39−43). In contrast, N-
heterocycles afforded C3-silylated products (44−47). The
possible reason for this C3-selectivity is unclear now, where
silyl cation might be involved in these cases.
a
Typical reaction conditions: arene (1 equiv, 0.1 mmol), HSiEt3 (1.2
mmol), DTBP (1.8 mmol), Cu2O (5 mol %), t-BuOH (0.5 mL),
sealed tube, 120 °C (measured temperature of the oil bath), 12 h later,
additional portions of HSiEt3 (1.2 mmol) and DTBP (1.8 mmol) were
added, refluxing for further 12 h. Isolated yield. 4,4′-Bis-
(triethylsilyl)-1,1′-biphenyl.
b
c
1-phenylpyrrolidin-2-one were examined to be effective
substrates, and all gave the desired para-silylated products in
moderate to good yields (1−5). In these cases, no regioisomers
were observed by NMR spectra. Next, a series of substituted N-
phenylacetamides were screened (6−11). As a result, both ortho-
and meta-substituted N-phenylacetamides afforded the corre-
sponding para-silylation products. Then 1,1-biphenyl and its
derivatives also reacted smoothly with triethylsilane to produce
the expected [1,1′-biphenyl]-4-yltriethylsilanes (12−14). Fi-
Finally, a series of hydrosilanes has been screened. It can be
seen from Scheme 5 that both alkyl and aryl hydrosilanes are
compatible with this system (48−54). Once again, para-silylated
B
DOI: 10.1021/acs.orglett.7b02717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
demonstrated here (Figure 1). Diverse transformations from
arylsilanes to aryl halides, phenols, and biaryls were achieved by
halogenation reactions, oxidation reactions, and cross-coupling
reactions.
Scheme 4. Silylation of Heteroaromatics with HSiEt3
a
Reaction conditions: heteroaromatics (1 equiv, 0.2 mmol), HSiEt3
(2.0 mmol), CuF2 (5 mol %), DTBP (0.8 mmol), t-BuOH (3 mL),
b
c
130 °C, 12 h. Isolated yield. (3-Phenylthiophene-2,5-diyl) bis-
(triethylsilane).
Figure 1. Transformation of the arylsilane products. Reaction
conditions: (i) 1 (1 equiv), NCS (5 equiv), N2, CH3CN, 40 °C; (ii) 1
(1 equiv), NBS (5 equiv), N2, CH3CN, rt; (iii) 1 (1 equiv), NIS (5
equiv), N2, CH3CN, rt; (iv) 21 (1 equiv), 5 mol % Pd(OAc)2,
PhI(OCOCF3)2 (1.5 equiv), AcOH, 100 °C; H2O, 100 °C; (v)
Benzo[b]thiophene (1 equiv), 1 (2 equiv), 5 mol % of PdCl2(CH3CN)2,
CuCl2 (2 equiv), N2, toluene, 100 °C; (vi) naphthalene (1 equiv), 13 (2
equiv), 5 mol % PdCl2, CuCl2 (4 equiv), DCE, 120 °C
a
Scheme 5. Silylation of Aromatics with Hydrosilanes
On the basis of the above results and previous reports, a
plausible mechanism for the present process is proposed and
shown in Scheme 7. Initially, heterolysis of the O−O bond in
a
b
Scheme 7. Proposed Mechanism
Typical reaction conditions. Isolated yield.
N-phenylacetamides and benzoates were isolated in moderate to
high yields.
With these data in hand, we began to discuss the site-selectivity
of this chemistry. Pioneering studies by Russell,14 Giese,15 and
Tedder and Walton16 et al. suggested that factors such as bond
strength, polarity, stereoelectronic effects, and steric effects are
critically important to govern the reactivity and orientation of
free-radical addition reactions. As mentioned above, previous
investigations on homolytic aromatic alkylation indicated a
“para-selectivity” was found in these reactions.12 The site-
selectivity largely depends on the resonance stabilization of the σ-
complex. Clearly a similar “para-selectivity” was observed in this
radical-promoted aryl C−H silylation. It can be seen from
Scheme 6 that the σ-complex intermediates would be formed by
peroxide by Cu(I) would afford tert-butoxyl radical and Cu(II)
species. Hydrogen abstraction from the hydrosilane by t-BuO
radical gives t-BuOH and a silyl radical, which then adds to arene
leading to the σ-complex intermediate A. Finally, direct
hydrogen-atom transfer from A to tert-butoxyl radical forms
the product, or single-electron oxidation of A by Cu(II) would
generate a radical anion, which then deprotonates by tert-butoxyl
anion performs to produce t-BuOH and arylsilane. Meanwhile,
the Cu(I) is regenerated to enter the next reaction cycle.
In summary, a Cu/peroxide-promoted free-radical aryl/
heteroaryl C−H silylation is developed. It allows a site-selective
and predictable access to various arylsilanes. Additionally, the
experimental results indicated that a “para-selectivity” was found
in this homolytic aromatic silylation. The exceptional selectivity
enables this radical silylation to be an attractive strategy for C−Si
formation.
Scheme 6. Para-Selectivity in Radical-Promoted Aryl C−H
Silylation
ASSOCIATED CONTENT
* Supporting Information
■
S
addition of the silyl radical to arenes. Although both the para- and
ortho-addition could lead to efficient delocalization that thus
stabilize the radical intermediates, para-addition would occur
prior to ortho-addition due to the steric effect. When there is
para-substituent on the aromatic core, meta-addition would
occur due to the collective effects of hindrance and polarity.17
The silyl-substituted arenes generated from this radical process
are known to undergo a variety of powerful synthetic
transformations. A number of representative examples are
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.7b02717.
Experimental procedures, characterization, and spectral
data (PDF)
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: liuzhq@lzu.edu.cn.
C
DOI: 10.1021/acs.orglett.7b02717
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
ORCID
Letter
2015, 518, 80. (j) Komiyama, T.; Minami, Y.; Hiyama, T. Angew. Chem.,
Int. Ed. 2016, 55, 15787. (k) Elsby, M. R.; Johnson, S. A. J. Am. Chem.
Soc. 2017, 139, 9401. (l) Bahr, S.; Oestreich, M. Angew. Chem., Int. Ed.
Zhong-Quan Liu: 0000-0001-6961-0585
Notes
̈
2017, 56, 52.
(7) For selected recent intramolecular transition-metal-catalyzed
dehydrogenative silylation, see: (a) Furukawa, S.; Kobayashi, J.;
Kawashima, T. J. Am. Chem. Soc. 2009, 131, 14192. (b) Ureshino, T.;
Yoshida, T.; Kuninobu, Y.; Takai, K. J. Am. Chem. Soc. 2010, 132, 14324.
(c) Kuninobu, Y.; Yamauchi, K.; Tamura, N.; Seiki, T.; Takai, K. Angew.
Chem., Int. Ed. 2013, 52, 1520.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This project is supported by the National Natural Science
Foundation of China (Nos. 21472080 and 21672089).
(8) For reviews on silyl radicals, see: (a) Chatgilialoglu, C. Acc. Chem.
Res. 1992, 25, 188. (b) Chatgilialoglu, C. Chem. Rev. 1995, 95, 1229.
(c) Chatgilialoglu, C.; Schiesser, C. H. In The Chemistry of Organic
Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; Wiley: Chichester,
2001; Vol. 3, Chapter 4. (d) Chatgilialoglu, C.; Timokhin, V. I. Adv.
Organomet. Chem. 2008, 57, 117. (e) Chatgilialoglu, C. Chem. - Eur. J.
2008, 14, 2310. (f) Oestreich, M. Angew. Chem., Int. Ed. 2016, 55, 494.
(9) For a very recent review on radical-mediated C−H silylation, see:
(a) Shang, X.; Liu, Z.-Q. Org. Biomol. Chem. 2016, 14, 7829. For
selected examples of radical C−H silylation, see: (b) Sakurai, H.;
Hosomi, A.; Kumada, M. Tetrahedron Lett. 1969, 10, 1755. (c) Sakurai,
H.; Hosomi, A. J. Am. Chem. Soc. 1971, 93, 1709. (d) Du, W.; Kaskar, B.;
Blumbergs, P.; Subramanian, P.-K.; Curran, D. P. Bioorg. Med. Chem.
2003, 11, 451. (e) Wang, L.; Zhu, H.; Guo, S.; Cheng, J.; Yu, J.-T. Chem.
Commun. 2014, 50, 10864. (f) Romain, E.; Fopp, C.; Chemla, F.;
Ferreira, F.; Jackowski, O.; Oestreich, M.; Perez-Luna, A. Angew. Chem.,
Int. Ed. 2014, 53, 11333. (g) Xu, L.; Zhang, S.; Li, P. Org. Chem. Front.
2015, 2, 459. (h) Leifert, D.; Studer, A. Org. Lett. 2015, 17, 386. (i) Gao,
P.; Zhang, W.; Zhang, Z. Org. Lett. 2016, 18, 5820. (j) Gu, J.; Cai, C.
Chem. Commun. 2016, 52, 10779. (k) Yang, Y.; Song, R.-J.; Ouyang, X.-
H.; Wang, C.-Y.; Li, J.-H.; Luo, S. Angew. Chem., Int. Ed. 2017, 56, 7916.
(10) (a) Fedorov, A.; Toutov, A. A.; Swisher, N. A.; Grubbs, R. H.
Chem. Sci. 2013, 4, 1640.
(11) (a) Tedder, J. M. Angew. Chem., Int. Ed. Engl. 1982, 21, 401.
(b) Viehe, H. G., Janousek, Z., Merenyi, R., Eds. Substituent Effects in
Radical Chemistry; Reidel: Dordrecht, 1986. (c) Giese, B. Angew. Chem.,
Int. Ed. Engl. 1989, 28, 969. (d) Curran, D. P.; Porter, N. A.; Giese, B.
Stereochemistry of Radical Reactions; VCH: Weinheim, 1996.
(12) (a) Minisci, F. Synthesis 1973, 1973, 1. (b) Minisci, F.; Mondelli,
R.; Gardini, G. P.; Porta, O. Tetrahedron 1972, 28, 2403. (c) Tiecco, M.;
Testaferri, L. Homolytic Aromatic Substitution by Alkyl Radicals. In
Reactive Intermediates; Abramovitch, R. A., Ed.; Plenum Press: New
York, 1983.
DEDICATION
■
In memory of Prof. You-Cheng Liu.
REFERENCES
■
(1) For reviews on silicon chemistry, see: (a) The Chemistry of Organic
Silicon Compounds; Patai, S., Rappoport, Z., Eds.; Wiley Interscience:
New York, 1989. (b) Brook, M. Silicon in Organic, Organometallic and
Polymer Chemistry; Wiley: New York, 2000. (c) The Chemistry of
Organic Silicon Compounds; Rappoport, Z., Apeloig, Y., Eds.; Wiley:
Chichester, 2003. (d) Birot, M.; Pillot, J.-P.; Dunogues, J. Chem. Rev.
1995, 95, 1443. (e) Buriak, J. M. Chem. Mater. 2014, 26, 763. (f) Silicon-
Containing Polymers; Jones, R. G., Ando, W., Chojnowski, J., Eds;
Kluwer: Dordrecht, 2000. (g) Zelisko, P. M. Bio-Inspired Silicon-Based
Materials; Springer: Dordrecht, 2014. (h) Langkopf, E.; Schinzer, D.
Chem. Rev. 1995, 95, 1375. (i) Sore, H. F.; Galloway, W. R. J. D.; Spring,
D. R. Chem. Soc. Rev. 2012, 41, 1845. (j) Denmark, S. E.; Sweis, R. F. Acc.
Chem. Res. 2002, 35, 835. (k) Hiyama, T.; Shirakawa, E. Top. Curr. Chem.
2002, 219, 61. (l) Marciniec, B. Coord. Chem. Rev. 2005, 249, 2374.
(m) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188. (n) Fleming, I.;
Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063.
(2) For recent reviews, see: (a) Cheng, C.; Hartwig, J. F. Chem. Rev.
2015, 115, 8946. (b) Yang, Y.; Wang, C. Sci. China: Chem. 2015, 58,
1266. (c) Xu, Z.; Huang, W.-S.; Zhang, J.; Xu, L.-W. Synthesis 2015, 47,
3645. (d) Sharma, R.; Kumar, R.; Kumar, I.; Singh, B.; Sharma, U.
Synthesis 2015, 47, 2347.
(3) For selected recent reviews on CDC reactions, see: (a) Li, C.-J. Acc.
Chem. Res. 2009, 42, 335. (b) Yeung, C. S.; Dong, V. M. Chem. Rev.
2011, 111, 1215. (c) Girard, S.; Knauber, T.; Li, C.-J. Angew. Chem., Int.
Ed. 2014, 53, 74. (d) Jia, F.; Li, Z. Org. Chem. Front. 2014, 1, 194.
(4) For selected intermolecular Friedel−Crafts-type C−H silylations,
see: (a) Furukawa, S.; Kobayashi, J.; Kawashima, T. Dalton Trans. 2010,
39, 9329. (b) Klare, H. T.; Oestreich, M.; Ito, J.; Nishiyama, H.; Ohki, Y.;
Tatsumi, K. J. Am. Chem. Soc. 2011, 133, 3312. (c) Curless, L. D.; Clark,
E. R.; Dunsford, J. J.; Ingleson, M. J. Chem. Commun. 2014, 50, 5270.
(d) Yin, Q.; Klare, H. F. T.; Oestreich, M. Angew. Chem., Int. Ed. 2016,
55, 3204. (e) Ma, Y.; Wang, B.; Zhang, L.; Hou, Z. J. Am. Chem. Soc.
2016, 138, 3663. (f) Chen, Q.; Klare, H. T.; Oestreich, M. J. Am. Chem.
Soc. 2016, 138, 7868. (g) Sollott, G. P.; Peterson, W. R. J. Am. Chem. Soc.
1967, 89, 5054. (h) Olah, G. A.; Bach, T.; Prakash, G. K. S. J. Org. Chem.
1989, 54, 3770. (i) Han, Y.; Zhang, S.; He, J.; Zhang, Y. J. Am. Chem. Soc.
2017, 139, 7399.
(5) For selected intramolecular Friedel−Crafts-type C−H silylations,
see: (a) Furukawa, S.; Kobayashi, J.; Kawashima, T. J. Am. Chem. Soc.
2009, 131, 14192. (b) Curless, L. D.; Ingleson, M. J. Organometallics
2014, 33, 7241. (c) Omann, L.; Oestreich, M. Angew. Chem., Int. Ed.
2015, 54, 10276.
(6) For selected recent intermolecular transition-metal-catalyzed
dehydrogenative silylation, see: (a) Lu, B.; Falck, J. R. Angew. Chem.,
Int. Ed. 2008, 47, 7508. (b) Ihara, H.; Suginome, M. J. Am. Chem. Soc.
2009, 131, 7502. (c) Simmons, E. M.; Hartwig, J. F. J. Am. Chem. Soc.
2010, 132, 17092. (d) Klare, H. F.; Oestreich, M.; Ito, J.-i.; Nishiyama,
H.; Ohki, Y.; Tatsumi, K. J. Am. Chem. Soc. 2011, 133, 3312.
(e) Oyamada, J.; Nishiura, M.; Hou, Z. Angew. Chem., Int. Ed. 2011,
50, 10720. (f) Zarate, C.; Martin, R. J. Am. Chem. Soc. 2014, 136, 2236.
(g) Cheng, C.; Hartwig, J. F. Science 2014, 343, 853. (h) Cheng, C.;
Hartwig, J. F. J. Am. Chem. Soc. 2015, 137, 592. (i) Toutov, A. A.; Liu,
W.-B.; Betz, K. N.; Fedorov, A.; Stoltz, B. M.; Grubbs, R. H. Nature
(13) (a) Zhang, L.; Liu, D.; Liu, Z.-Q. Org. Lett. 2015, 17, 2534.
(b) Zhang, L.; Hang, Z.; Liu, Z.-Q. Angew. Chem., Int. Ed. 2016, 55, 236.
(14) Russell, G. In Free Radicals; Kochi, J. K., Ed.; Wiley: New York,
1973; Vol. I, p 275.
(15) (a) Giese, B. Angew. Chem., Int. Ed. Engl. 1977, 16, 125. (b) Giese,
B. Acc. Chem. Res. 1984, 17, 438.
(16) (a) Tedder, J. M.; Walton, J. C. Acc. Chem. Res. 1976, 9, 183.
(b) Tedder, J. M.; Walton, J. C. Adv. Free Radical Chem. 1980, 6, 155.
(17) (a) Ruchardt, C. Angew. Chem., Int. Ed. Engl. 1970, 9, 830.
̈
(b) Pryor, W. A.; Lin, T. H.; Stanley, J. P.; Henderson, R. W. J. Am.
Chem. Soc. 1973, 95, 6993. For discussions on scale of electrophilicity
and nucleophilicity for radicals, see: (c) Fleming, I. Frontier Orbitals and
Organic Chemical Reactions; Wiley: New York, 1976. (d) Heberger, K.;
Lopata, A. J. Org. Chem. 1998, 63, 8646. (e) Fischer, H.; Radom, L.
Angew. Chem., Int. Ed. 2001, 40, 1340. (f) Arthur, N. L.; Potzinger, P.
Organometallics 2002, 21, 2874. (g) De Vleeschouwer, F.; Van
Speybroeck, V.; Waroquier, M.; Geerlings, P.; De Proft, F. Org. Lett.
2007, 9, 2721.
D
DOI: 10.1021/acs.orglett.7b02717
Org. Lett. XXXX, XXX, XXX−XXX