Photoredox-Coupled F-Nucleophilic Addition: Allylation of gem-Difluoroalkenes

Article abstract of DOI:10.1002/anie.201814308

A novel strategy for the expedient construction of CF₃-embeded tertiary/quarternary carbon centers was developed by taking advantage of photoredox catalysis. Thanks to a key step of single-electron oxidation, electron-rich gem-difluoroalkenes, which otherwise are essentially reluctant towards F-nucleoplilic addition, now readily participate in this fluoroallylation reaction. Furthermore, this strategy provides an elegant example for the generation, as well as functionalization, of α-CF₃-substituted benzylic radical intermediates using cheap and readily available starting materials.

Full text of DOI:10.1002/anie.201814308

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Accepted Article
Title: Photoredox-Coupled F-Nucleophilic-Addition-Induced Allylation of
gem-Difluoroalkenes
Authors: Haidong Liu, Liang Ge, Ding-Xing Wang, Nan Chen, and
Chao Feng
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201814308
Angew. Chem. 10.1002/ange.201814308
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Photoredox-Coupled F-Nucleophilic Addition: Allylation of gem-
Difluoroalkenes
Haidong Liu, Liang Ge, Ding-Xing Wang, Nan Chen, and Chao Feng*
Abstract: A novel strategy for the expedient construction of CF3-
embeded tertiary/quarternary carbon centers is developed by taking
advantage of photoredox catalysis. Thanks to a key step of single
electron oxidation, electron-rich gem-difluoroalkenes, which
otherwise are essentially reluctant towards F-nucleoplilic addition,
now readily participate in this fluoroallylation reaction. Furthermore,
this strategy provides an elegant example for the generation as well
as functionalization of α-CF3-substituted benzylic radical
intermediates using cheap and readily available starting materials.
The fluorine-containing compounds find extensive applications in
many disciplines, which bring forth far-reaching influence in the
research areas of pharmaceuticals, agrochemicals and materials
science.[1] Specifically, the development of strategies for the
construction of trifluoromethyl-containing molecules especially
aroused considerable attention from chemists during the past
two decades.[2] In this respect, while the exploration of new
synthetic methods for the assembly of CF3-substituted aromatic
framework constituted a flourishing direction,[2a-2d] progress in
the development of strategies for the construction of benzylic
CF3-embeded tertiary/quarternary carbon centers lagged far
more behind.[3] Aside from a handful of CF3-radical based
functionalization of structurally elaborated styrene derivatives,[4]
Scheme 1. Construction of CF3-substituted tertiary carbon centers. FG,
functional group. EWG, electron-withdrawing group. EDG, electron-donating
group.
these molecules could virtually be created either by direct
trifluoromethylation of aliphatic skeletons[5] or through cross-
coupling using α-CF3-derived precursors, from a retrosynthetic
point of view (Scheme 1a).[6,12-16] With Li’s pioneering work on
trifluoromethylation of alkyl radical using Grushin’s reagent,[7] the
groups of MacMillan,[8] Cook[9] and Liu,[10] respectively,
developed decarboxylative and benzylic C-H trifluoromethylation
protocols, although the employment of expensive CF3-reagents
as well as restricted substrate scope are still of big concerns.
Making use of trifluoroethylarene derivatives as building
blocks also allows a smooth construction of the target molecules.
In this regard, the manipulation of α-CF3-substituted benzylic
cation[11], anion[12] and radical[13] intermediates were extensively
explored with elegant works from the groups of Moran, Tredwell,
Molander, Hu and Fu constituting a major breakthrough in this
territory. Despite these advances, reactions proceeding via α-
CF3-substituted benzylic cation or anion intermediates in
themselves possess innate limitations because of stability
problems.[14] By contrast, α-CF3-substituted benzylic radical
intermediates, albeit nontrivial in their generation, is
comparatively more tractable and devoid of substrate
deactivation or degradation via β-F elimination,[15] which leaves
ample room for potential elaborations.
In 2016, our group have coined a strategy of “F-nucleophilic-
addition-induced functionalization of gem-difluoroalkenes”.[16] By
making use of CsF as fluoride donor for the in situ generation α-
CF3-substituted carbanion intermediates and resorting to
palladium-catalyzed allylation as the quenching step, providing a
straightforward
avenue
for
the
construction
(Scheme
of
homoallyltrifluoromethane
derivatives
1b).[16a]
Notwithstanding the merits of reaction efficacy and reagent
economy, its heavy reliance on electron-deficient gem-
difluorostyrene substrates, for stabilizing thus generated
carbanion intermediates, however, poses a great limitation
toward more wide applications. To ameliorate such conspicuous
deficiency while offering a nice complement to the previous
reaction protocol, the exploration of new working modes which
could readily accommodate electron-rich gem-difluoroalkene
substrates is still highly desirable. Based on our experience on
gem-difluoroalkene functionalization[16,17] as well as the inspiring
report from Hu’s group,[13b] we envisioned the potential possibility
of merging photoredox catalysis[18] with F-nucleophilc-addition-
induced functionalization. We posit that a single electron
oxidation of the aryl system of gem-difluoroalkene substrate
would provide a radical cationic intermediate,[19] which is primed
for ensuing nucleophilic addition by the external fluoride donor
(Scheme 1c). The distinguishing feature of engaging photoredox
catalysis is twofold: i) one electron removal from the neutral aryl
substituent enables substrate activation, thereby favoring the
subsequent nucleophilic addition process because of the strong
[a]
H. Liu, L. Ge, D.-X. Wang, N. Chen, Prof. C. Feng
Institute of Advanced Synthesis, College of Chemistry and
Molecular Engineering,
Nanjing Tech University
Nanjing, Jiangsu 210009, (P. R. China)
E-mail: iamcfeng@njtech.edu.cn
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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10.1002/anie.201814308
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electron-withdrawing property of aryl radical cation part; ii) upon
a sequence of fluoride nucleophilic addition and intramolecular
experiments indicated the vital importance of photocatalyst and
light irradiation in this protocol (Table1, entries 7-8).
electron-regulation,
α-CF3-substituted
benzylic
radical
With the optimized reaction conditions in hand, the reaction
scope of gem-difluoroalkene was subsequently investigated
using allyl sulfone 2a. As presented in Table 2, aromatic
substrates decorated at the para position with electron donating
group such as ether (3b-3d, 3u), thioether (3e), pyrazole (3y),
morpholine (3z) afforded the desired products in moderate to
excellent yields. In the cases of using substrates with relatively
high oxidation potentials, for example those with alkyl (3f, 3ah),
halogen (3h), trifluoromethoxy (3g), or even the ester (3i)
substituents, reactions proceed smoothly with PC-I as the
catalyst. However, substrates with electron withdrawing groups
such as ester, cyano, nitro and ketone in para-position of the
phenyl ring are not suitable. Poly-functionalized substrates were
also applicable and the presence of one activating substituent
enables a decent tolerance of remaining electron-withdrawing
ones, even CF3 and carbonyl groups (3l-3o, 3ad). The
compatibility of halogen substituents provides a potential handle
for further synthetic transformation through cross-coupling
techniques. Furthermore, gem-difluoroalkenes derived from
extended aromatic systems took part in this reaction
uneventfully as showcased by 3q and 3r. The nice tolerance of
ortho-substitution was somewhat beyond our expectation taking
into account of both steric congestion and potential impeding
pathways such as geometry-allowed 1,5-hydrogen shift manifold
(3p, 3r, 3v, 3w). It is also of note, gem-difluoroalkene substrate,
which has an ortho-allyl substituent, engaged in this reaction to
selectively afford product 3aj. The devoid of constitution isomer
formation could be rationalized from both thermodynamic and
kinetic considerations. With the anticipation that more electron-
rich aryl motif is more inclined to undergo one electron oxidation,
the comparatively low reaction efficiencies of 3z, 3ab are
ostensibly counterintuitive. These outcomes, however, could be
interpreted in this way that the radical cationic intermediates
generated from those strongly activating substrates are
thermodynamically too stable, which, on the contrary, offer a
poor magnitude of driving force for triggering nucleophilic
addition by fluoride ion. On the other hand, substrates derived
from heterocycles including indole (3ac), pyridine (3aa) and
dibenzofuran (3t) were all well tolerated and showed good
performances in this transformation. Interestingly, in the case of
1,4-bis(2,2-difluorovinyl)benzene, selective functionalization on
one side was observed, which leaves room for further synthetic
manipulation of the remaining gem-difluoroalkene segment if
needed (3x). It is worth notifying that the present reaction was
able to effectively discriminate between gem-difluoroalkenyl and
normal alkenyl substituents as represented by the example of
3ai. This result is ascribed to higher electrophilicity of gem-
difluoroalkenyl part, which guarantees the selective nucleophilic
intermediate (in stark contrast to the formation of intermediate in
the case of nucleophilic addition to neutral molecules) would be
smoothly generated. The contrasting chemical properties of
carbanion and radical species would therefore provide
discrepant but complementary possibilities for the following
transformations.
Table 1. Reaction conditions optimization.[a]
Entry
1
Catalyst
PC-I
Conversion (%)
76
Yield 3a/4a (%)
33/4
2
3
PC-II
PC-III
PC-IV
PC-V
PC-VI
-
51
79
8
13/11
31/8
4
trace
5
60
100
0
34/4
6
39/19
0
7
8
PC-V
PC-V
PC-V
PC-V
3
trace[b]
48/14[c]
47/3[c,d]
79/2[d,e]
9
72
67
91
10
11
[a] Reaction conditions: 1a (0.1 mmol), 2a (0.3 mmol), Et3N·3HF (0.2 mmol),
PC (2.0 mol%), irradiating with 8 W blue LEDs under N2 atmosphere at room
temperature for 12 h. Yields were determinated by 19F NMR with 1-iodo-4-
(trifluoromethyl)benzene as the internal standard. [b] Without light irradiation.
[c] 0.2 M MeCN and reaction for 24 h. [d] With 0.2 mol% catalyst. [e] 0.5 M
MeCN and reaction for 48 h. PC, photocatalyst. DCE, 1,2-dichloroethane.
To translate our hypothesis into reality, cyclic voltammetry
measurement of gem-difluoroalkene substrate 1a was initially
conducted, which showed the oxidative potential being around
1.65 V (VS SCE in MeCN). The model reaction between 1a and
ethyl 2-((phenylsulfonyl)methyl)acrylate 2a[20] was attempted
using a series of external fluoride donors while intentionally
choosing photocatalysts with relatively high oxidative
potentials.[21] After the optimization of extensive reaction
parameters, we were pleased to find that when using Et3N·3HF,
Acr+-Mes (PC-I, E01/2= +2.06 V vs. SCE in MeCN)[22] as the
fluoride donor and photocatalyst, respectively, the model
reaction irradiated with blue LEDs in DCE gave rise to the
desired product 3a in 33% yield, accompanied by the formation
of hydrofluorination byproduct 4a in 4% yield (Table1, entry 1).
Examination of different photocatalysts came to a conclusion
that the employment of [Ir(dF(CF3)ppy)2(5,5’-dCF3bpy)](PF6)
addition
process.
Gratifyingly,
ketone-derived
gem-
difluoroalkenes also adapted to this multi-component reaction,
by which an easy construction of CF3-embeded quarternary
carbon center-containing architectures is made possible, albeit
with relative attenuated reaction efficiencies because of steric
effects (3ae, 3af). To further challenge the applicability of the
present reaction, tocopherol derived gem-difluoroalkene was
examined and product 3ag was obtained in superb yield, thus
(PC-V, E0 III*/II= +1.69 V vs. SCE in MeCN)[23] enabled the best
1/2
balance between reaction yield and selectivity, albeit with
moderate conversion (Table1, entries 1-6). Further fine tuning
the reaction conditions eventually led to the formation of product
3a in 79% yield (Table1, entries 9-11). Notably, control
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10.1002/anie.201814308
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Table 2. Substrate scope of the photoredox-coupled fluoroallylation of gem-dinfluoroalkenes.[a]
[a] Reaction conditions: 1 (0.2 mmol), 2 (0.6 mmol), Et3N·3HF (0.4 mmol), PC-V (0.2 mol%) in MeCN (0.4 mL), irradiated with 8 W blue LEDs under N2
atmosphere at room temperature with indicated time course. Isolated yields were provided. [b] PC-I was emplyeed as photocatalyst. [c] CH2Cl2 was used as the
reaction solvent.
indicating the potential of this method in the elaboration of
complex molecules.
respective fluoroallylation products in good yields (3ak-3am,
3ar). In addition to ester, a variety of electron-withdrawing
substituents, for example halogens, CN, sulfonyl, benzoyl and
even phenyl, were turned out to be viable as the activating
groups (3an-3aq, 3as, 3at). Notably, allyl sulfones derived from
naturally occurring molecules such as menthol (3au),
epiandrosterone (3av) also well engaged in this transformation
The scope with respect to allyl sulfone coupling partner was
subsequently investigated.[24]
substituents, such as those derived from Me, Bu and Bn, were
all found to participated in this reaction smoothly to deliver
A
series of 2-alkoxycarbonyl
t
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10.1002/anie.201814308
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without any problem. It is also worth mentioning that the present
reaction protocol could be readily extended to fluoroallylation of
monofluoroalkene derivatives without modification of the
optimized reaction conditions, which in turn offers a convenient
avenue for the construction of homoallylic difluoromethane
analogues (3aw-3az).
subsequent interaction of intermediate II and allyl sulfone 2
through a sequence of free radical addition and β-fragmentation
delivers the desired product 3 while producing benzenesulfonyl
radical, which is integral to the IrIII regeneration process through
single electron transfer with IrII.
In summary, we have developed a photoredox-coupled F-
In order to shed more light on the nature of the present
reaction, some control experiments were further launched.
When substrate 1ba was subjected to the standard conditions,
product 3ba, which was formed through a sequence of β-
cleavage of cyclopropyl substituent and primary carbon radical
functionalization, was isolated in 15% yield (Scheme 2a).
Furthermore, the inhibition of 3a formation in the presence of
stoichiometric amount of 2,2,6,6-Tetramethylpiperidinooxy
(TEMPO) or 2,6-di-tert-butyl-4-methylphenol (BHT) is also in well
accordance with the involvement of radical intermediate in this
transformation (Scheme 2b). Stern–Volmer fluorescence
quenching studies indicated that the excited state of PC* was
only positively quenched by gem-difluoroalkene substrate.
Besides, the oxidation potential of gem-difluoroalkene substrate
examined by cyclic voltammetry laying within the window of that
of photocatalyst implicated reaction initiation via a reductive
quenching process. In addition, the light-on/off experiment
revealed a heavy reliance of reaction progress on the continuing
light irradiation.
nucleophilic-addition-induced allylic
difluoroalkenes. This protocol allows a straightforward synthetic
access to large collection of functionalized homoallylic
trifluoromethane derivatives, which in the meantime opens up a
new dimension in the area of nucleophilic-addition-induced
alkylation
of
gem-
a
functionalizations. Furthermore, the present case offers
a
conceptually novel tactic for the convenient production and
further elaboration of α-CF3-substituted benzylic radical
intermediates from readily accessible and cheap starting
materials.
Acknowledgements ((optional))
We gratefully acknowledge the financial support of the
“Thousand Talents Plan” Youth Program, the “Jiangsu Specially-
Appointed Professor Plan”, the National Natural Science
Foundation of China (21871138), and the Natural Science
Foundation of Jiangsu Province (BK20170984).
Based on the experimental results, a tentatively proposed
reaction mechanism for this reaction is put forward (Scheme 2,
bottom). Upon irradiation by the visible light, photocatalyst IrIII is
Keywords: trifluoromethyl • photoredox • benzylic radical • gem-
difluoroalkene • allylation
*
sensitized to its excited state IrIII, which undergoes reductive
quenching by gem-difluoroalkene 1 to generate IrII accompanied
by the production of radical cationic intermediate I. Because of
the electronic activation, intermediate I then readily participates
in nucleophilic addition by fluoride ion to afford benzylic radical
II[25] upon further intramolecular electron regulation. The
[1]
a) K. Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881−1886; b)
S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev.
2008, 37, 320−330; c) J. Wang, M. Sánchez-Roselló, J. L. Aceña, C.
del Pozo, A. E. Sorochinsky, S. Fustero, V. A. Soloshonok, H. Liu,
Chem. Rev. 2014, 114, 2432−2506.
[2]
a) J. Charpentier, N. Fruh, A. Togni, Chem. Rev. 2015, 115, 650−682;
b) C. Alonso, E. M. de Marigorta, G. Rubiales, F. Palacios, Chem. Rev.
2015, 115, 1847−1935; c) X. Liu, C. Xu, M. Wang, Q. Liu, Chem. Rev.
2015, 115, 683−730; d) T. Furuya, A. S. Kamlet, T. Ritter, Nature 2011,
473, 470−477; e) P. A. Champagne, J. Desroches, J.-D. Hamel, M.
Vandamme, J.-F. Paquin, Chem. Rev, 2015, 115, 9073−9174; f) M. G.
Campbell, T. Ritter, Chem. Rev. 2015, 115, 612−633.
[3]
a) J. P. Phelan, S. B. Lang, J. S. Compton, C. B. Kelly, R. Dykstra, O.
Gutierrez, G. A. Molander, J. Am. Chem. Soc. 2018, 140, 8037−8047;
b) M. Hu, C. Ni, J. Hu, J. Am. Chem. Soc. 2012, 134, 15257−15260; c)
W. Yang, D. Ma, X. Zhou, X. Dong, Z. Lin, J. Sun, Angew. Chem. Int.
Ed. 2018, 57, 12097–12101; d) J. E. M. N. Klein, S. Rommel, B.
Plietker, Organometallics 2014, 33, 5802−5810; e) H. Kawai, K. Tachi,
E. Tokunaga, M. Shiro, N. Shibata, Angew. Chem. Int. Ed. 2011, 50,
7803–7806; f) M. Holmes, K. D. Nguyen, L. A. Schwartz, T. Luong, M. J.
Krische, J. Am. Chem. Soc. 2017, 139, 8114–8117.
[4]
[5]
a) Q.-Y Wu, G.-Z. Ao, F. Liu, Org. Chem. Front. 2018, 5, 2061−2064;
b) Y. Yasu, T. Koike, M. Akita, Angew. Chem. Int. Ed. 2012, 51, 9567–
9571; c) Y. Itoh, K. Mikami, Org. Lett. 2005, 7, 4883−4885; d) A. Prieto,
E. Jeamet, N. Monteiro, D. Bouyssi, O. Baudoin, Org. Lett. 2014, 16,
4770−4773; e) Q. Wang, P. Shi, R. Zeng, RSC Adv. 2018, 8, 25961–
25965.
a) Y. Kuninobu, M. Nagase, M. Kanai, Angew. Chem. Int. Ed. 2015, 54,
10263–10266; b) L. Zhu, S. Liu, J. T. Douglas, R. A. Altman, Chem. -
Eur. J. 2013, 19, 12800–12805; c) Y. Miyake, S. Ota, M. Shibata, K.
Nakajima, Y. Nishibayashi, Org. Biomol. Chem. 2014, 12, 5594–5596.
Scheme 2. Control experiments and proposed mechanism.
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[6]
[7]
G. Hughe, P. O’Shea, J. Goll, D. Gauvreau, J. Steele, Tetrahedron
2009, 65, 3189–3196.
[18] For selected reviews, see: a) C. K. Prier, D. A. Rankic, D. W. C.
MacMillan, Chem. Rev. 2013, 113, 5322−5363; b) K. L. Skubi, T. R.
Blum, T. P. Yoon, Chem. Rev. 2016, 116, 10035−10074; c) J. M. R.
Narayanam, Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102−113;
d) J. Xuan, W.-J. Xiao, Angew. Chem., Int. Ed. 2012, 51, 6828−6838.
[19] For the generation of arene radical cation intermediates by
photoinduced single electron oxidation, see: a) N. A. Romero, K. A.
Margrey, N. E. Tay, D. A. Nicewicz, Science 2015, 349, 1326−1330; b)
J. B. McManus, D. A. Nicewicz, J. Am. Chem. Soc. 2017, 139,
2880−2883; c) L. Niu, J. Liu, H. Yi, S. Wang, X.-A. Liang, A. K. Singh,
C.-W. Chiang, A. Lei, ACS Catal. 2017, 7, 7412−7416; d) S. Bloom, M.
McCann, T. Lectka, Org. Lett. 2014, 16, 6338−6341; e) G. Pandey, S.
Pal, R. Laha, Angew. Chem. Int. Ed. 2013, 52, 5146–5149; f) Y.-W.
Zheng, B. Chen, P. Ye, K. Feng, W. Wang, Q.-Y. Meng, L.-Z. Wu, C.-H.
Tung, J. Am. Chem. Soc. 2016, 138, 10080−10083; g) T. R. Blum, Y.
Zhu, S. A. Nordeen, T. P. Yoon, Angew. Chem. Int. Ed. 2014, 53,
11056–11059; h) R. Zhou, H. Liu, H. Tao, X. Yua, J. Wu, Chem. Sci.
2017, 8, 4654–4659; i) H. Liu, L. Ma, R. Zhou, X. Chen, W. Fang, J. Wu,
ACS Catal. 2018, 8, 6224−6229; j) K. Ohkubo, K. Mizushima, R. Iwataa,
S. Fukuzumi, Chem. Sci. 2011, 2, 715−722.
a) X. Tan, Z. Liu, H. Shen, P. Zhang, Z. Zhang, C. Li, J. Am. Chem. Soc.
2017, 139, 12430−12433; b) H. Shen, Z. Liu, P. Zhang, X. Tan, Z.
Zhang, C. Li, J. Am. Chem. Soc. 2017, 139, 9843−9846.
J. A. Kautzky, T. Wang, R. W. Evans, MacMillan, D. W. C. J. Am. Chem.
Soc. 2018, 140, 6522−6526.
[8]
[9]
S. Guo, D. I. AbuSalim, S. P. Cook, J. Am. Chem. Soc. 2018, 140,
12378−12382.
[10] M. Peath, W. Carson, J.-H. Luo, D. Tierney, Z. Cao, M.-J. Cheng, W.
Liu, Chem. - Eur. J. 2018, 24, 11559−11563.
[11] a) V. D. Vuković, E. Richmond, E. Wolf, J. Moran, Angew. Chem. Int.
Ed. 2017, 56, 3085–3089; b) L. Yang, W. X. Fan, E. Lin, D. H. Tan, Q.
Li, H. Wang, Chem. Commun. 2018, 54, 5907−5910; c) G. S. Prakash,
F. Paknia, T. Mathew, G.Mlostoꢀ, J. P. Joschek, G. A. Olah, Org. Lett.
2011, 13, 4128−4131.
[12] M. Brambilla, M. Tredwell, Angew. Chem. Int. Ed. 2017, 56,
11981−11985.
[13] a) D. Ryu, D. N. Primer, J. C. Tellis, G. A. Molander, Chem. - Eur. J.
2016, 22, 120−123; b) B. Gao, Y. Zhao, J. Hu, Angew. Chem. Int. Ed.
2015, 54, 638−642; c) B. Gao, Y. Zhao, C. Ni, J. Hu, Org. Lett. 2013, 16,
102−105; d) Y. Liang, G. C. Fu, J. Am. Chem. Soc. 2015, 137,
9523−9526; e) Y. Liang, G. C. Fu, Angew. Chem. Int. Ed. 2015, 54,
9047−9051.
[20] a) W. Shu, A. Genoux, Z. Li, C. Nevado, Angew. Chem. Int. Ed. 2017,
56, 10521−10524; b) J. Zhang, Y. Li, F. Zhang, C, Hu, Y. Chen, Angew.
Chem. Int. Ed. 2016, 55, 1872−1875; c) X. Huang, S. Luo, O. Burghaus,
R. D. Webster, K. Harms, E. Meggers, Chem. Sci. 2017, 8, 7126−7131;
d) L. Qi, Y. Chen, Angew. Chem. Int. Ed. 2016, 55, 13312−13315; e)
Q.-Q. Zhao, J. Chen, D.-M. Yan, J.-R. Chen, W.-J. Xiao, Org. Lett.
2017, 19, 3620−3623; f) K. Wu, Y. Du, T. Wang, Org. Lett. 2017, 19,
5669−5672.
[14] a) K. Uneyama, T. Katagiri, H. Amii, Acc. Chem. Res. 2008, 41,
817−829; b) D. Bonnet-Delpon, C. Cambillau, M. Charpentier-Morize, R.
Jacquot, D. Mesureur, M. Ourevitch, J. Org. Chem. 1988, 53, 754−759.
[15] a) K. Fuchibe, H. Hatta, K. Oh, R. Oki, J. Ichikawa, Angew. Chem. Int.
Ed. 2017, 56, 5890−5893; b) S. B. Lang, R. J. Wiles, C. B. Kelly, G. A.
Molander, Angew. Chem. Int. Ed. 2017, 56, 15073−15077.
[16] a) P. Tian, C.-Q. Wang, S.-H. Cai, S. Song, L. Ye, C. Feng, T.-P. Loh, J.
Am. Chem. Soc. 2016, 138, 15869−15872; b) H.-J. Tang, L.-Z. Lin, C.
Feng, T.-P. Loh, Angew. Chem. Int. Ed. 2017, 56, 9872−9876; c) H.-J.
Tang, Y.-F. Zhang, Y.-W. Jiang,; C. Feng, Org. Lett. 2018, 20,
5190−5193.
[21] See supporting information for details.
[22] K. Ohkubo, K. Mizushima, R. Iwata, K. Souma, N. Suzuki, S. Fukuzumi,
Chem. Commun. 2010, 46, 601−603.
[23] G. J. Choi, Q. Zhu, D. C. Miller, C. J. Gu, R. R. Knowles, Nature 2016,
539, 268−271.
[24] Other radical trapping reagents were also tested. See SI for more
details.
[17] a) P. Tian, C. Feng, T.-P. Loh, Nat. Commun. 2015, 6, 7472-7478; b) L.
Zhou, C. Zhu, T.-P. Loh, C. Feng, Chem. Commun. 2018, 54,
5618−5621; c) S.-H. Cai, L. Ye, D.-X. Wang, Y.-Q. Wang, L.-J. Lai, C.
Zhu, C. Feng, T.-P. Loh, Chem. Commun. 2017, 53, 8731−8734; d) C.
Zhu, S. Song, L. Zhou, D.-X. Wang, C. Feng, T.-P. Loh, Chem.
Commun. 2017, 53, 9482−9485; e) L. Zhou, C. Zhu, P. Bi, C. Feng,
Chem. Sci. 2019, 10, 1144−1149.
[25] We appreciate one of the referees for the suggestion of generation
intermediate II by single electron oxidation of in situ generated α-CF3
benzylic anion. For more discussion, see SI.
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10.1002/anie.201814308
Angewandte Chemie International Edition
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COMMUNICATION
Haidong Liu, Liang Ge, Ding-Xing Wang,
Nan Chen, and Chao Feng*
Page No. – Page No.
Photoredox-Coupled F-Nucleophilic
Addition: Allylation of gem-
Difluoroalkenes
A fluoro-allylation of gem-difluoroalkenes with inexpensive Et3N·3HF and readily
available allylsulfone has been developed. The photoredox-coupled fluoride
nucleophilic addition process, combined with the radical allylation allows an
expedient access to a large collection of functionalized homoallylic trifluoromethane
derivatives under mild visible-light-induced conditions at room temperature.
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