Nickel-Catalyzed Monofluoroalkylation of Arylsilanes via Hiyama Cross-Coupling

Article abstract of DOI:10.1021/acs.orglett.6b02803

The first example of nickel-catalyzed monofluoroalkylation of arylsilanes has been developed with readily available fluoroalkyl halides. This novel transformation has demonstrated high reactivity, broad substrate scope, excellent functional group tolerance, and mild reaction conditions. The selective activation of a relatively inert C-Si bond for slow release of aryl carbanion is the key reason for reducing the amount of arylmetal species, which makes this method more promising for fluorine-containing modification of complex bioactive molecules. Mechanistic investigations indicate that a free fluoroalkyl radical is involved in this catalytic cycle.

Full text of DOI:10.1021/acs.orglett.6b02803

Letter
pubs.acs.org/OrgLett
Nickel-Catalyzed Monofluoroalkylation of Arylsilanes via Hiyama
Cross-Coupling
Yun Wu,† Hao-Ran Zhang,† Yi-Xuan Cao,† Quan Lan,† and Xi-Sheng Wang*,†,‡
†Department of Chemistry, University of Science and Technology of China, Hefei 230026, China
‡Key Laboratory of Synthetic and Self-Assembly Chemistry for Organic Functional Molecules, Chinese Academy of Sciences,
Shanghai Institute of Organic Chemistry, Shanghai 200032, China
S
* Supporting Information
ABSTRACT: The first example of nickel-catalyzed monofluoroalkyla-
tion of arylsilanes has been developed with readily available fluoroalkyl
halides. This novel transformation has demonstrated high reactivity,
broad substrate scope, excellent functional group tolerance, and mild reaction conditions. The selective activation of a relatively
inert C−Si bond for slow release of aryl carbanion is the key reason for reducing the amount of arylmetal species, which makes
this method more promising for fluorine-containing modification of complex bioactive molecules. Mechanistic investigations
indicate that a free fluoroalkyl radical is involved in this catalytic cycle.
high as 1.5−2.0 equiv, probably because of the simultaneous
he selective incorporation of fluorine or fluorine-containing
Tgroups into organic molecules has emerged as a general and aryl−aryl homocoupling side reactions. Thus, it hampered their
practical use in organic synthesis, especially for the fluoroalky-
lation of complex molecules. Meanwhile, nickel-11 palladium-12
or copper-catalyzed13 cross coupling of arylsilanes with organic
halides, known as Hiyama coupling, has already been well
developed as a highly efficient method to build C−C bonds
selectively. As one part of our continuous efforts to develop
transition-metal-catalyzed fluoroalkylations,14 we envisioned
that the selective activation of the much less polarized and
relatively inert C−Si bond in arylsilanes will greatly inhibit the
Ar−Ar homocoupling, thus allowing a reduction in the amount
of arylmetal species that can broaden its potential applications on
modification of complex bioactive molecules. Herein, we report
the first example of nickel-catalyzed monofluoroalkylation of
arylsilanes with readily available fluoroalkyl halides, in which high
reactivity and broad substrate scope have been demonstrated.
Meanwhile, to the best of our knowledge, there was still no report
on fluoroalkylation via transition-metal-catalyzed Hiyama
coupling.
Inspired by our previous research on nickel-catalyzed
monofluoromethylation of arylboronic acids with activated
fluoroalkylating reagents,9g we commenced our study with
phenylsilyl ether 1a as the pilot substrate and EtO2CFHBr 2 as
the fluoroalkyl coupling partner in the presence of a catalytic
amount of Ni(dme)Cl2 (10 mol %) and 1,10-phenanthroline
(L1, 12 mol %) in dioxane at 80 °C. Considering the key role of
fluoride ion for activation of the inert C−Si bond, several
fluorides have been used to start this coupling reaction via the
attack on organosilicon compounds to form pentacoordinate
species.12 The desired monofluoroalkylated product 3a was
obtained smoothly in 22% yield when 2.0 equiv of CsF was used
as the activator, while other fluorides gave almost none of the
effective strategy in drug design and screening because the
fluorinated compounds can often drastically enhance the
metabolic stability, lipophilicity, and bioavailability of their
parent molecules.1 Among all intriguing fluoroalkylated moieties,
the monofluoromethyl group (CH2F) and its functionalized
derivatives are widely found in many biologically active
molecules as the essential motif2 because the exchange of
hydrogen by fluorine prevents the metabolic oxidation owing to
the electron-withdrawing effect of fluorine and the strength of
the C−F bond.3 While a great number of methods for
trifluoromethylation4 and difluoroalkylation5 of arenes have
been well developed in recent decades, there are still few
examples of transition-metal-promoted monofluoroalkylation.6
As recent research on catalysis in organic synthesis tends to
move away from precious-metal catalysts, nickel has attracted
increasing attention very recently as a more abundant and lower
cost metal.7 Accordingly, nickel-catalyzed fluoroalkylation of
aryl- or alkylmetal species has recently been developed as a
powerful tool to synthesize fluorine-containing compounds
(Scheme 1). The coupling nucleophiles to construct fluorinated
arenes were limited to arylmagnesium,8 -boron,9 or -zinc10
species. However, the amount of such metal species needed as
Scheme 1. Nickel-Catalyzed Fluoroalkylation of Arylmetal
Species
Received: September 18, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.6b02803
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
product (entry 1, Table 1). To improve the yield further, a variety
of phosphine and diamine ligands were next examined. In
of arylsilane 1a was decreased to 1.2 equiv (entry 23). Lastly, a
control experiment indicated that none of the monofluoroalky-
lated product was obtained without the addition of nickel catalyst
(entry 24).
a,b
Table 1. Optimization of Conditions
With the optimized reaction conditions in hand, we next
investigated the substrate scope of this nickel-catalyzed
monofluoroalkylation of arylsilanes to provide a practical method
for modification of complex bioactive molecules. As shown in
Scheme 2, aryl silyl ethers with para-, meta-, and ortho-
substituents are all compatible coupling partners, affording the
corresponding monofluoroalkylated arenes in good to excellent
yields. Arylsilanes installed with electron-donating groups were
monofluoroalkylated smoothly to give the desired products with
good yields (3b−i). A range of halogenated silyl ethers were also
entry
ligand
L1
base
CsF
yield (%)
1
22
26
37
45
22
30
0
2
L2
CsF
a,b
Scheme 2. Scope of Arylsilane Substrates
3
L3
CsF
4
L4
CsF
5
L5
CsF
6
TMEDA
L6
CsF
7
CsF
8
PPh3
dppp
L4
CsF
0
9
CsF
0
10
11
12
13
14
KF
0
L4
TBAF
K2CO3
Cs2CO3
NaOH
CsF
0
L4
0
L4
0
L4
0
c
15
L4
37
41
30
87
90
90
d
16
L4
CsF
e
17
L4
CsF
f
18
L4
CsF
g
19
L4
CsF
h
20
L4
CsF
i
j
21
L4
CsF
96 (93)
k
22
L4
CsF
96
l
j
23
L4
CsF
96 (93)
m
24
L4
CsF
0
0
0
n
25
L4
o
26
CsF
a
Unless otherwise noted, the reaction conditions were as follows:
EtO2CCFHBr (0.2 mmol, 1.0 equiv), 1 (1.5 equiv), Ni(dme)Cl2 (10
mol %), ligands (12 mol %), CsF (2.0 equiv), 1,4-dioxane, 80 °C, 24 h.
b
Yields determined by 19F NMR using CF3Ph as an internal standard.
c
d
e
DCM was used as solvent. THF was used as solvent. DMF was
f
g
h
used as solvent. CsF (4.0 equiv). CsF (5.0 equiv). CsF (6.0 equiv).
i
j
k
l
1,4-Dioxane (2.5 mL). Isolated yield. 1,4-Dioxane (3.0 mL). 1a (1.2
m
n
equiv) and 1,4-dioxane (2.5 mL). Without Ni(dme)Cl2. Without
CsF. Without ligand. TMEDA = N,N,N′,N′-tetramethylethylenedi-
amine.
o
contrast to our previous report on nickel-catalyzed fluoroalky-
lation of arylboronic acids, in which phosphine ligands are the
most effective,9g diamine ligands, including 1,10-phenanthroline,
bipyridine and their derivatives, and TMEDA, afforded 3a in up
to 45% yield (entries 2−6), while di- and monophosphines and
tpy (L6) showed no catalytic activity at all (entries 7−9).
Unfortunately, the replacement of CsF with other bases
quenched the reaction completely. Furthermore, a careful survey
of solvents (Table S3) was then performed, which showed
dioxane was still the best choice. Notably, an increase of the
amount of CsF to 5.0 equiv improved the yield greatly, and up to
93% yield was finally obtained when the reaction concentration
was adjusted, and no reduction was observed even if the amount
a
Unless otherwise noted, the reaction conditions were as follows: BrRf
(0.2 mmol, 1.0 equiv), 1 (1.2 equiv), Ni(dme)Cl2 (10 mol %), L4 (12
mol %), CsF (5.0 equiv), 1,4-dioxane (2.5 mL), 80 °C, 24 h. Isolated
yield. 2.0 equiv of 1t was used, and the temperature was 100 °C. 2.0
equiv of 1u was used.
b
c
d
B
DOI: 10.1021/acs.orglett.6b02803
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
well-tolerated by this method (3j−n). The presence of halogen
substituents in the products offered the synthetic potential for
further elaboration via transition-metal-catalyzed coupling
reactions. In particular, aryl silyl ethers containing electron-
withdrawing groups, such as trifluoromethyl (3o−q), aldehyde
(3u), sulfone (3w), and ester (3x), were fluoroalkylated
successfully with pretty good yields in this catalytic system. In
contrast, our previously reported nickel-catalyzed monofluor-
oalkylations using arylboronic acids as the coupling partners
required higher catalyst and ligand loadings and batch addition of
catalyst and substrates.9g Additionally, aryl silyl ethers derived
from heteroarenes, including thiophene, indole, and even
quinoline, were also monofluoroalkylated successfully, leading
to 3y, 3z, 3aa, and 3ab, respectively, all in satisfactory yields
under the standard reaction conditions. Notably, a styryl silane
was also well tolerated in this transformation, giving the
fluoroalkyl alkene 3ac in moderate yield and excellent E/Z
selectivity (>20/1). Most remarkably, some other available
fluoroalkyl halides, such as α-bromo-α-fluoroacetophenone and
bromodifluoroacetate, were also applicable to the reaction (3ad−
ae).
Scheme 4. Plausible Mechanism
To demonstrate both the functional group tolerance and the
application prospect of this method, this novel transformation
has also been attempted in the late-stage fluoroalkylation of a
complex bioactive molecule. As shown in Scheme 5, the
To gain some insight into the mechanism of this trans-
formation, a series of control experiments were then performed.
First, the reaction was completely quenched when 1.0 equiv of
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO), a well-known
free radical inhibitor, was added into the standard conditions (eq
1, Scheme 3). This observation is consistent with the reports that
Scheme 5. Monofluoroalkylation of Ezetimibe Derivative
Scheme 3. Radical-Trapping Experiments
arylsilane 5 derived from ezetimibe, a drug known to inhibit
cholesterol absorption,18 underwent fluoroalkylation to yield the
monofluoroalkylated ezetimibe 6 smoothly in excellent yield
(91%). This type of fluorine-containing modification shows great
promise for drug discovery and development as a powerful tactic
for fluorinated analogue synthesis.
In summary, we have developed the first example of
monofluoroalkylation reaction of arylsilanes catalyzed by in
situ generated nickel/4,4′-ditBu-bpy complex. Both electron-rich
and electron-deficient arylsilanes are found to be compatible with
this new transformation under mild conditions. The reduction in
the amount of arylmetal reagent makes this method promising
for future applications in fluorine-containing modification of
complex bioactive molecules. Mechanistic investigations indicate
that a monofluoroalkyl radical is involved in the catalytic cycle.
Further exploration of the mechanistic details of this trans-
formation and the application of this novel tactic to the late-stage
modification of complex molecules are ongoing in our
laboratory.
the oxidative addition step in the catalytic cycle of nickel-
catalyzed cross-couplings proceeds via a radical pathway.15
Meanwhile, the EtCO2CHF• radical was trapped successfully
with β-pinene used as a radical scavenger under the standard
conditions, affording the ring-opened diene 4 as an isomeric
mixture (eq 2, Scheme 3) along with the desired fluoroalkylated
product 3g, which further implicated the generation of the
monofluoroalkyl radical in the catalytic cycle.
Although the definite mechanism of this transformation is still
unclear at this stage, on the basis of our preliminary results and
previous reports,16 a plausible mechanism involving a Ni(I)/
Ni(III) catalytic cycle is proposed as shown in Scheme 4. The
Ni(I)−Ar species B can be generated via transmetalation
between the initial Ni(I) species A with the arylsilane under
the activation of CsF. Subsequently, Ni(I) species B activates
EtO2CFHBr 2 via single-electron transfer (SET) to afford Ni(II)
intermediate C and the fluoroalkyl radical, and Ni(III) species D
is generated through the following oxidative radical addition of
monofluoroalkyl radical to intermediate C. The final mono-
fluoroalkylated product 3 is obtained after the reductive
elimination from Ni(III) species D, and Ni(I) catalyst A is
regenerated to complete the catalytic cycle.17
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.orglett.6b02803.
Experimental procedure and characterization of all new
compounds (PDF)
C
DOI: 10.1021/acs.orglett.6b02803
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Lett. 2015, 17, 3086. (i) Rong, J.; Deng, L.; Tan, P.; Ni, C.; Gu, Y.; Hu, J.
Angew. Chem., Int. Ed. 2016, 55, 2743.
(7) For recent reviews of Ni-catalyzed cross-coupling reactions, see:
AUTHOR INFORMATION
■
Corresponding Author
́
(a) Phapale, V. B.; Cardenas, D. J. Chem. Soc. Rev. 2009, 38, 1598.
*E-mail: xswang77@ustc.edu.cn.
Notes
(b) Rudolph, A.; Lautens, M. Angew. Chem., Int. Ed. 2009, 48, 2656.
(c) Rosen, B. M.; Quasdorf, K. W.; Wilson, D. A.; Zhang, N.; Resmerita,
A.-M.; Garg, N. K.; Percec, V. Chem. Rev. 2011, 111, 1346. (d) Han, F.-S.
Chem. Soc. Rev. 2013, 42, 5270. (e) Tellis, J. C.; Kelly, C. B.; Primer, D.
N.; Jouffroy, M.; Patel, N. R.; Molander, G. A. Acc. Chem. Res. 2016, 49,
1429.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(8) Tarui, A.; Kondo, S.; Sato, K.; Omote, M.; Minami, H.; Miwa, Y.;
Ando, A. Tetrahedron 2013, 69, 1559.
We gratefully acknowledge the Strategic Priority Research
Program of the Chinese Academy of Sciences (Grant No.
XDB20000000), the National Basic Research Program of China
(973 Program 2015CB856600), the National Science Founda-
tion of China (21522208, 21372209), the Chinese Academy of
Sciences, and the Excellent Young Scientist Foundation of Anhui
Province (2013SQRL003ZD) for financial support.
(9) (a) Xiao, Y.-L.; Guo, W.-H.; He, G.-Z.; Pan, Q.; Zhang, X. Angew.
Chem., Int. Ed. 2014, 53, 9909. (b) Jiang, X.; Sakthivel, S.; Kulbitski, K.;
Nisnevich, G.; Gandelman, M. J. Am. Chem. Soc. 2014, 136, 9548.
(c) Xiao, Y.-L.; Pan, Q.; Zhang, X. Huaxue Xuebao 2015, 73, 383. (d) An,
L.; Xiao, Y.-L.; Min, Q.-Q.; Zhang, X. Angew. Chem., Int. Ed. 2015, 54,
9079. (e) Jiang, X.; Gandelman, M. J. Am. Chem. Soc. 2015, 137, 2542.
(f) Tarui, A.; Miyata, E.; Tanaka, A.; Sato, K.; Omote, M.; Ando, A.
Synlett 2015, 26, 55. (g) Su, Y.-M.; Feng, G.-S.; Wang, Z.-Y.; Lan, Q.;
Wang, X.-S. Angew. Chem., Int. Ed. 2015, 54, 6003. (h) Xiao, Y.-L.; Min,
Q.-Q.; Xu, C.; Wang, R.-W.; Zhang, X. Angew. Chem., Int. Ed. 2016, 55,
5837.
(10) (a) Liang, Y.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 5520.
(b) Liang, Y.; Fu, G. C. J. Am. Chem. Soc. 2015, 137, 9523.
(11) For selected examples of Hiyama reaction catalyzed by nickel, see:
(a) Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788.
(b) Strotman, N. A.; Sommer, S.; Fu, G. C. Angew. Chem., Int. Ed. 2007,
46, 3556. (c) Dai, X.; Strotman, N. A.; Fu, G. C. J. Am. Chem. Soc. 2008,
130, 3302. (d) Saijo, H.; Sakaguchi, H.; Ohashi, M.; Ogoshi, S.
Organometallics 2014, 33, 3669.
REFERENCES
■
(1) Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881.
̈
(2) Selected examples: (a) Kollonitsch, J.; Patchett, A. A.; Marburg, S.;
Maycock, A. L.; Perkins, L. M.; Doldouras, G. A.; Duggan, D. E.; Aster, S.
D. Nature 1978, 274, 906. (b) Kuo, D.; Rando, R. R. Biochemistry 1981,
20, 506. (c) Grunewald, G. L.; Caldwell, T. M.; Li, Q.; Slavica, M.;
Criscione, K. R.; Borchardt, R. T.; Wang, W. J. Med. Chem. 1999, 42,
3588. (d) Grunewald, G. L.; Seim, M. R.; Regier, R. C.; Martin, J. L.;
Gee, C. L.; Drinkwater, N.; Criscione, K. R. J. Med. Chem. 2006, 49,
5424. (e) Mckeage, K.; Keam, S. J. Drugs 2009, 69, 1799.
(3) Fujiwara, Y.; Dixon, J. A.; O’Hara, F.; Funder, E. D.; Dixon, D. D.;
Rodriguez, R. A.; Baxter, R. D.; Herle, B.; Sach, N.; Collins, M. R.;
́
Ishihara, Y.; Baran, P. S. Nature 2012, 492, 95.
(4) For selected reviews of trifluoromethylation, see: (a) Ma, J.-A.;
Cahard, D. J. Fluorine Chem. 2007, 128, 975. (b) Furuya, T.; Kamlet, A.
S.; Ritter, T. Nature 2011, 473, 470. (c) Zhang, C. Org. Biomol. Chem.
2014, 12, 6580. (d) Chu, L.; Qing, F.-L. Acc. Chem. Res. 2014, 47, 1513.
(12) For selected reviews of Hiyama reaction catalyzed by palladium,
see: (a) Hiyama, T.; Hatanaka, Y. Pure Appl. Chem. 1994, 66, 1471.
(b) Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions; Diederich,
F., Stang, P. J., Eds.; Wiley-VCH: New York, 1998; Chapter 10.
(c) Hiyama, T. J. Organomet. Chem. 2002, 653, 58. (d) Denmark, S. E.;
Sweis, R. F. Acc. Chem. Res. 2002, 35, 835. (e) Denmark, S. E.; Regens, C.
S. Acc. Chem. Res. 2008, 41, 1486.
(e) Charpentier, J.; Fruh, N.; Togni, A. Chem. Rev. 2015, 115, 650.
̈
(f) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683. (g) Ni,
C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765. (h) Yang, X.; Wu, T.;
Phipps, R. J.; Toste, F. D. Chem. Rev. 2015, 115, 826. (i) Alonso, C.;
Marigorta, E. M.; Rubiales, G.; Palacios, F. Chem. Rev. 2015, 115, 1847.
(5) For recent reviews of difluoroalkylation, see: (a) Reference 4g. For
selected examples of difluoroalkylations of arenes, see:. (b) Fujikawa, K.;
Fujioka, Y.; Kobayashi, A.; Amii, H. Org. Lett. 2011, 13, 5560.
(c) Fujiwara, Y.; Dixon, J. A.; Rodriguez, R. A.; Baxter, R. D.; Dixon,
D. D.; Collins, M. R.; Blackmond, D. G.; Baran, P. S. J. Am. Chem. Soc.
2012, 134, 1494. (d) Fier, P. S.; Hartwig, J. F. J. Am. Chem. Soc. 2012,
134, 5524. (e) Lin, Q.; Chu, L.; Qing, F.-L. Chin. J. Chem. 2013, 31, 885.
(f) Xia, J.-B.; Zhu, C.; Chen, C. J. Am. Chem. Soc. 2013, 135, 17494.
(g) Mizuta, S.; Stenhagen, I. S. R.; O’Duill, M.; Wolstenhulme, J.;
Kirjavainen, A. K.; Forsback, S. J.; Tredwell, M.; Sandford, G.; Moore, P.
R.; Huiban, M.; Luthra, S. K.; Passchier, J.; Solin, O.; Gouverneur, V.
Org. Lett. 2013, 15, 2648. (h) Jiang, X.-L.; Chen, Z.-H.; Xu, X.-H.; Qing,
F.-L. Org. Chem. Front. 2014, 1, 774. (i) Ge, S.; Chaładaj, W.; Hartwig, J.
F. J. Am. Chem. Soc. 2014, 136, 4149. (j) Su, Y.-M.; Hou, Y.; Yin, F.; Xu,
Y.-M.; Li, Y.; Zheng, X.; Wang, X.-S. Org. Lett. 2014, 16, 2958. (k) Sun,
X.; Yu, S. Org. Lett. 2014, 16, 2938. (l) Xu, P.; Guo, S.; Wang, L.; Tang, P.
Angew. Chem., Int. Ed. 2014, 53, 5955. (m) Belhomme, M.-C.; Poisson,
T.; Pannecoucke, X. J. Org. Chem. 2014, 79, 7205. (n) Jung, J.; Kim, E.;
You, Y.; Cho, E. J. Adv. Synth. Catal. 2014, 356, 2741. (o) Shao, C.; Shi,
G.; Zhang, Y.; Pan, S.; Guan, X. Org. Lett. 2015, 17, 2652.
(13) For recent selected examples on copper-catalyzed Hiyama
coupling reactions, see: (a) Gurung, S. K.; Thapa, S.; Vangala, A. S.; Giri,
R. Org. Lett. 2013, 15, 5378. (b) Cornelissen, L.; Lefrancq, M.; Riant, O.
Org. Lett. 2014, 16, 3024.
(14) Li, G.; Wang, T.; Fei, F.; Su, Y.-M.; Li, Y.; Lan, Q.; Wang, X.-S.
Angew. Chem., Int. Ed. 2016, 55, 3491 See also ref 9g..
(15) (a) Powell, D. A.; Maki, T.; Fu, G. C. J. Am. Chem. Soc. 2005, 127,
510. (b) Gonzalez-Bobes, F.; Fu, G. C. J. Am. Chem. Soc. 2006, 128,
́
5360. (c) Smith, S. W.; Fu, G. C. J. Am. Chem. Soc. 2008, 130, 12645.
(16) (a) Jones, G. D.; Martin, J. L.; McFarland, C.; Allen, O. R.; Hall, R.
E.; Haley, A. D.; Brandon, R. J.; Konovalova, T.; Desrochers, P. J.; Pulay,
P.; Vicic, D. A. J. Am. Chem. Soc. 2006, 128, 13175. (b) Phapale, V. B.;
́
́
Bunuel, E.; Garcla-Iglesias, M.; Cardenas, D. J. Angew. Chem., Int. Ed.
̃
2007, 46, 8790. (c) Hu, X. Chem. Sci. 2011, 2, 1867. (d) Wilsily, A.;
Tramutola, F.; Owston, N. A.; Fu, G. C. J. Am. Chem. Soc. 2012, 134,
5794. (e) Zultanski, S. L.; Fu, G. C. J. Am. Chem. Soc. 2013, 135, 624.
(f) Schley, N. D.; Fu, G. C. J. Am. Chem. Soc. 2014, 136, 16588.
(g) Cornella, J.; Edwards, J. T.; Qin, T.; Kawamura, S.; Wang, J.; Pan, C.-
M.; Gianatassio, R.; Schmidt, M.; Eastgate, M. D.; Baran, P. S. J. Am.
Chem. Soc. 2016, 138, 2174. (h) Wang, J.; Qin, T.; Chen, T.-G.;
Wimmer, L.; Edwards, J. T.; Cornella, J.; Vokits, B.; Shaw, S. A.; Baran, P.
S. Angew. Chem., Int. Ed. 2016, 55, 9676 See also ref 9a,d,g..
(17) While a Ni(I)/Ni(III) catalytic cycle involving a fluoroalkyl
radical was proposed for this reaction, the other possible mechanisms
can’t be completely excluded at this stage. For a discussion of the use of
(6) For selected examples of monofluoroalkylations, see: (a) Zhang,
X.; Qiu, W.; Burton, D. J. J. Fluorine Chem. 1998, 89, 39. (b) Zhang, X.;
Qiu, W.; Burton, D. J. Tetrahedron Lett. 1999, 40, 2681. (c) Guo, C.;
Yue, X.; Qing, F.-L. Synthesis 2010, 2010, 1837. (d) Zhao, Y.; Gao, B.;
Ni, C.; Hu, J. Org. Lett. 2012, 14, 6080. (e) Guo, C.; Wang, R.-W.; Guo,
Y.; Qing, F.-L. J. Fluorine Chem. 2012, 133, 86. (f) Zhao, Y.; Ni, C.; Jiang,
F.; Gao, B.; Shen, X.; Hu, J. ACS Catal. 2013, 3, 631. (g) Sun, X.; Yu, S.
Org. Lett. 2014, 16, 2938. (h) Hu, J.; Gao, B.; Li, L.; Ni, C.; Hu, J. Org.
radical traps as a test for radical mechanism, see: Alben
́
iz, A. C.; Espinet,
P.; Lopez-Fernandez, R.; Sen, A. J. Am. Chem. Soc. 2002, 124, 11278.
́
́
(18) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc.
Rev. 2008, 37, 320.
D
DOI: 10.1021/acs.orglett.6b02803
Org. Lett. XXXX, XXX, XXX−XXX