Dual Photoredox/Nickel-Catalyzed Three-Component Carbofunctionalization of Alkenes

Article abstract of DOI:10.1002/anie.201906692

The potential of merging photoredox and nickel catalysis to perform multicomponent alkene difunctionalizations under visible-light irradiation is demonstrated here. Secondary and tertiary alkyl groups, as well as sulfonyl moieties can be added to the terminal position of the double bond with simultaneous arylation of the internal carbon atom in a single step under mild reaction conditions. The process, devoid of stoichiometric additives, benefits from the use of bench-stable and easy-to-handle reagents, is operationally simple, and tolerates a wide variety of functional groups.

Full text of DOI:10.1002/anie.201906692

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Accepted Article
Title: Dual Photoredox/Nickel-Catalyzed Three-Component
Carbofunctionalization of Alkenes
Authors: Andrés García-Domínguez, Rahul Mondal, and Cristina
Nevado
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201906692
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10.1002/anie.201906692
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Dual Photoredox/Nickel-Catalyzed Three-Component
Carbofunctionalization of Alkenes
Andrés García-Domínguez, Rahul Mondal, Cristina Nevado*[a]
Abstract: The potential of merging photoredox and nickel catalysis to
perform multicomponent alkene difunctionalizations under visible light
irradiation is demonstrated here. Secondary and tertiary alkyl groups
as well as sulfonyl moieties can be added to the terminal position of
the double bond with simultaneous arylation of the internal carbon
atom in a single step under mild conditions. The process, devoid of
stoichiometric additives, benefits from the use of bench-stable and
easy-to-handle reagents, is operationally simple and tolerates a wide
variety of functional groups.
enable the addition of several groups (both, carbon- and
heteroatom-based) across the olefin under analogous reaction
conditions. Herein, we report the first examples of photoredox
alkene carbosulfonylations and alkylarylations by combination of
aromatic halides with both, secondary and tertiary alkyl silicates
and sulfonyl derivatives, respectively (Scheme 1, bottom). These
reactions proceed with complete chemo- and regiocontrol
employing bench-stable starting materials under mild conditions.
In addition to its operational simplicity, this method significantly
broadens the scope of existing strategies[3-5] both in terms of the
compatible olefins (acrylates, acrylonitriles, vinylboronic esters,
allylic acetates) and addition partners (secondary and tertiary
alkyl as well as alkyl and arylsulfonyl groups), which highlights the
synergistic potential of dual photoredox/Ni catalysis beyond the
cross-coupling realm.
The intermolecular difunctionalization of alkenes represents a
powerful strategy to construct complex aliphatic structures by
concomitant formation of C-C and/or C-X bonds across the π-
system.[1] The use of radicals in this context has become
particularly attractive due to their ability to rapidly add onto
unsaturated moieties under mild conditions.[2] Because of their
synthetic utility, alkene dicarbofunctionalization reactions, i.e.
transformations involving the simultaneous formation of two new
C-C bonds have been thoroughly studied in this context.[3-5]
Typically, these strategies utilize tertiary or perfluoroalkyl radical
precursors that are combined either with electron-rich styrenes
and arenes[3] or, alternatively, with activated olefins and
functionalized aromatics (arylmetal Ar-M or haloarenes Ar-X) in
the presence of a metal catalyst (Scheme 1, top).[4] The need for
activated tertiary or perfluoroalkyl derivatives and for
electronically biased substrates together with the use of sensitive
organometallic reagents under harsh conditions, still limits the
synthetic potential of these methods.
Photoredox catalysis has emerged as a powerful tool to enable
single electron transfer (SET) reactions under mild conditions.[5]
On the other hand, the ability of nickel catalysts to forge C-C and
C-X bonds involving Csp3 partners is also well established.[6] The
combination of these two strategies has bared fruit, and thus
novel alkyl-alkyl and alkyl-aryl cross coupling reactions have been
developed under such paradigm.[7] However, and despite its
potential, three-component dicarbofunctionalizations of alkenes
Scheme 1. Three-component carbofunctionalizations of alkenes. FG
Functional Group.
=
First, we focused our efforts on the activation of secondary alkyl
silicates (Eox= 0.3 - 0.9 V vs SCE in DMF)[9a-c] by the photoexcited
ruthenium (II) tris(bypiridine) complex (Ered= 0.77 V vs SCE in
MeCN)[9d] in order to address one of the main limitations in current
methods. Alkyl silicates are produced in three steps from the
corresponding trichlorosilanes according to previously described
procedures.[9] Further, aryl iodides were selected as Csp2
partners given their facile reaction with nickel catalysts.[10] The
reaction of tert-butylacrylate with diisopropylammonium
cyclohexylbis-(catecholato)silicate and 4-tert-butyliodobenzene
in the presence of a nickel precatalyst, bipyridine type ligands and
Ru(bpy)3Cl2·6H2O under blue light irradiation was investigated
first (Table 1).[11] The molar ratio between the reaction partners
was found to be crucial for a successful outcome. A slight excess
of alkene and alkyl silicate significantly favored the
difunctionalization product minimizing the direct alkyl-arene
cross-coupling. After initial optimization, the use of
NiCl2·6H2O/dtbbpy (10 mol%) in DMF (0.1 M) provided 1 in 68%
exploiting the synergy between photoredox and Ni catalysis are
7l]
still scarce.[4c,
Given our ongoing interest in the radical
difunctionalization of -systems,[8] we set out to explore a
photoredox/nickel dual catalysis towards flexible three-
a
component difunctionalization of alkenes. We envisioned that an
off-cycle radical generation by the excited photocatalyst would
[*]
A. García-Domíguez, R. Mondal and Prof. Dr. Cristina Nevado
Department of Chemistry
University of Zurich
Winterthurerstrasse 190, CH-8057, Zurich (Switzerland)
E-mail: cristina.nevado@chem.uzh.ch
Supporting information for this article is given via a link at the end of
the document.
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10.1002/anie.201906692
Angewandte Chemie International Edition
COMMUNICATION
isolated yield (Table 1, entry 1). Other bipyridine ligands led to
lower yields (Table 1, entries 2-3), whereas the use of a
preformed nickel catalyst did not improve the reaction outcome
(Table 1, entry 4). An hexafluorophosphate ruthenium salt gave
the incorporation of cycloalkyl groups but also isopropyl and
tertiary linear alkyl silicates could be engaged with similar
efficiencies under the standard reaction conditions (16-19). To our
delight, the use of tertiary alkyl silicates completely avoided the
formation of Hiyama-type coupling products allowing the
dicarbofunctionalization of a wider range of olefins. In this manner,
electron rich olefins, vinyl boranes and even unactivated alkenes
similar
results
(Table
1,
entry
5)
while
tris(phenathroline)ruthenium(II) dichloride monohydrate as
photocatalyst gave lower yields (Table 1, entry 6). The presence
of oxygen was detrimental for the reaction as demonstrated by
the results shown in entries 7 and 8. Further, control experiments
confirmed the need for nickel, photocatalyst and light irradiation
to produce the desired difunctionalized product 1 (entry 9).
could
be
successfully
transformed
into
desired
dicarbofunctionalization products 20-22.
Table 1. Optimization of the reaction conditions for the alkene
dicarbofunctionalization reaction.
Entry
Deviations from Above
NMR Yield of 1
(%)[a]
1
2
3
4
5
6
7
8
9
none
69 (68)
58
diMeObpy (10 mol%)
bpy (10 mol%)
55
Using Ni(dtbbpy)(H2O)4Cl2 (10 mol%)
Using Ru(bpy)3(PF6)2 (1 mol%)
Using Ru(phen)3Cl2·H2O (1 mol%)
Under air
64
68
50
34
Not degassed DMF
43
Scheme 2. Scope of the dual photoredox/nickel catalyzed dicarbofunctionali-
No nickel / No photocatalyst / No light
0
zation.
[a] NMR yields using 4-nitroacetophenone as internal standard. In
brackets: Isolated yield after column chromatography on silica gel. DMF:
Difunctionalizations incorporating simultaneously both, sulfonyl
and aryl groups across simple olefins have been mainly explored
on intramolecular settings.[12] Thus, encouraged by the above-
mentioned results and the feasibility of oxidizing sodium
arenesulfinates (Eox = 0.3-0.6 vs SCE in MeCN)[13] by the Ru-
photocatalyst,[14] we set out to expand the utility of our protocol in
this context. When the previous standard conditions (Table 1,
entry 1) were applied to the reaction of tert-butylacrylate with 4-
tert-butyliodobenzene and sodium benzenesulfinate, an
encouraging 41% yield of compound 23 was obtained together
with 28% of the undesired biarylsulfone 23´ (Table 2, entry 1).
Increasing the amount of aryl iodide led to a slight improvement
of the yield (48%) on the desired product (Table 2, entry 2). The
use of 10 mol% NiCl2Py4 led to the formation of 23 in 44% yield
(Table 2, entry 3). Further improvement was observed when DMF
was replaced by DMSO, as 23 and 23´could be obtained in 53
and 18% yield, respectively (Table 2, entry 4). Finally, the use of
a more electron-rich bipyridine ligand (diMeObipy) furnished 23 in
72% yield together with 13% of 23´ (Table 2, entry 5). Reducing
the catalyst loading proved to be beneficial so that, under the
newly optimized reaction conditions, compound 23 could be
isolated in 69% yield and less than 10% of 23´ was detected in
N,N-dimethylformamide;
dttbpy:
4,4'-di-tert-butyl-2,2'-bipyridine;
diMeObpy: 4,4'-dimethoxy-2,2'-bipyridine; bpy: 2,2'-bipyridine; phen:
1,10-phenantroline.
With the optimized conditions in hand, we set out to explore the
scope of this transformation (Scheme 2). Both, electron-rich as
well as electron-deficient substituted aryl iodides delivered the
desired products 1-6 in moderate to good yields. The reaction is
orthogonal with respect to classical cross-coupling procedures as
the C-Boron bond remained intact in product 6, which could be
isolated in 66% yield. A 5-cyanofurane derivative 7 could only be
isolated in 22% yield. However, other acrylates containing benzyl
or ketone groups in their structures as well as acrylonitriles and
vinylsulfones could be successfully engaged in the reaction (8-11),
highlighting the functional group compatibility of this method. In
addition, an internal olefin (E:Z = 4:1) delivered the highly
congested product 12 with exquisite diastereoselectivity (dr >
20:1).
Different alkyl silicates were evaluated next. Cyclic derivatives as
well as species containing double bonds in their structures were
well tolerated as demonstrated by the efficient isolation of
products 13-15. Additionally, the method is not only restricted to
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10.1002/anie.201906692
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the reaction media (Table 2, entry 6. For additional optimization
experiments, see SI).[11]
To further showcase the synthetic potential of these
transformations, the reactions to produce adducts 2, 28 and 30
were carried out in 1 mmol scale. Under the standard reaction
conditions, these products could be isolated in 58, 65 and 59%
yield, respectively.
The reaction scope was investigated next (Scheme 3). Under the
optimized conditions, different substitutions and functionalities in
the ester moiety were tolerated, furnishing the desired
arylsulfonylated products 24-39 in good yields. Remarkably the
reaction proved not only suitable for the use of aryl iodides, but
also for aryl bromides thus expanding the synthetic utility of the
method (30-35).
After the successful development of both transformations, several
control experiments were designed to interrogate the reaction
pathway. First, the use of radical scavengers such as TEMPO or
1,1-diphenylethylene decreased reaction efficiencies, which
suggests a radical based mechanism (for details, see SI).[11]
Further, competitive intermolecular experiments were carried out
combining two different olefins at an equimolar ratio in the
presence of the tert-butyl silicate derivative and 4-tert-butyl
iodobenzene (Scheme 4A, top). A mixture of difunctionalization
products from both olefins was obtained, favoring, in all cases, the
adducts stemming from the most reactive olefinic acceptor
towards the tert-butyl radical (19 vs. 1; 1 vs. 20; 20 vs. 22).[15]
Besides, when both olefins were located within the same
substrate, the addition of the alkyl or the sulfonyl group took place
exclusively onto the more activated one to give 1,2-
carbofunctionalization products 41-42 (Scheme 4A, bottom).
These competition experiments suggest the formation of radicals
from the ‘nucleophilic’ reaction partner and its subsequent
addition to the olefin on the outset of the reaction. These
conclusions were further supported by radical clock experiments
using a diallyl ether probe, which revealed the sole formation of
the tetrahydrofuran derivative 44 in 61% yield as a 4:1 mixture of
diastereoisomers (Scheme 4B). As the rate of the cyclization of
similar substrates has been reported (k ~ 4-6·106 s-1),[16] these
results indicate that the reaction of secondary radicals with the
intermediates responsible to deliver the C-Ar bond at last may be
a much slower process.[17] Further, the fact that cyclized product
43 is not observed reflects the preference of the secondary C-
centered radical in α position to the ester group to recombine with
the corresponding ArNi(II) complex. In contrast, upon addition of
the tBu radical to the double bond on the diallylether radical clock,
the secondary radical undergoes cyclization with the vicinal
double bond rather than recombination with the Ni(II) species to
give cyclized product 44. These results showcase the effect that
the different stabilization of the secondary C-centered radical
intermediates can have on the reaction outcome.
Table 2. Optimization of the reaction conditions for the alkene
carbosulfonylation reaction.
Entry
Reaction conditions
As in Scheme 2
NMR yield of 23
(%)[a]
1
2
41[b]
48[c]
NiCl2·6H2O (10 mol%),
dtbbpy (10 mol%) in DMF (0.1 M)
3
4
5
6
NiCl2Py4 (10 mol%),
dtbbpy (10 mol%) in DMF (0.1 M)
44
53[d]
NiCl2Py4 (10 mol%),
dtbbpy (10 mol%) in DMSO (0.1 M)
NiCl2Py4 (10 mol%),
diMeObpy (10 mol%) in DMSO (0.1 M)
72[e]
NiCl2Py4 (10 mol%),
76 (69)[f]
diMeObpy (4 mol%) in DMSO (0.1 M)
[a] NMR yields using 4-nitroacetophenone as internal standard. In brackets:
Isolated yield after column chromatography on silica gel. [b] 28% of
diarylsulfone tBuC6H4SO2Ph 23´ was obtained. [c] 20% 23´ [d] 18% of 23´
[e] 13% of 23´ [f] 8% of 23´
In addition, sulfinates with different electronic features were nicely
engaged in the reaction giving products 37-39 in moderate to high
efficiencies. Vinyl amides could also be incorporated in the
reaction scope, as demonstrated by the successful isolation of
difunctionalized product 40.
Scheme 3. Scope of the dual photoredox/nickel catalyzed carbosulfonylation.
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10.1002/anie.201906692
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generation of radicals is independ from the nickel complex, the
use of an affordable photocatalyst has allowed the utilization of
sulfinates and alkylsilicates to generate sulfonyl and both,
secondary and tertiary alkyl radicals, respectively, with minor
changes in the reaction conditions. In addition, the stability and
ease of handling of all precursors confers excellent functional
group compatibility and operational simplicity to this approach,
while significantly expanding the scope of existing alkene
carbofunctionalization methods.
Acknowledgements
We thank the European Research Council (ERC Starting-grant
agreement no. 307948) and the Swiss National Science
Foundation (200020_146853) for financial support.
Keywords: photoredox catalysis
•
nickel catalysis
•
carbosulfonylation • dicarbofunctionalization • three-component
reaction
Scheme 4. Control experiments.
[1]
[2]
For recent reviews, see: a) E. Merino, C. Nevado Chem. Soc. Rev. 2014,
43, 6598; b) D. A. Petrone, J. Ye, M. Lautens, Chem. Rev. 2016, 116,
8003; c) R. K. Dhungana, S. KC, P. Basnet, R. Giri, Chem. Rec. 2018,
18, 1314;d) T. Fujihara, Y. Tsuji, Synthesis 2018, 50, 1737; e) J.-S.
Zhang, L. Liu, T. Chem, L.-B. Han, Chem. Asian J. 2018, 13, 2277.
For selected publications, see: a) M. Hartmann, Y. Li, A. Studer, J. Am.
Chem. Soc. 2012, 134, 16516; b) B. Ovadia, F. Robert, Y. Landais,
CHIMIA 2016, 70, 34; c) X.-W. Lan, N.-X. Wang, Y. Xing, Eur. J. Org.
Chem. 2017, 5821; d) S. N. Gockel, T. L. Buchanan, K. L. Hull, J. Am.
Chem. Soc. 2018, 140, 58; e) Y. Cheng, C. Mꢀck-Lichtenfeld, A. Studer,
J. Am. Chem. Soc. 2018, 140, 6221.
Based on these control experiments and existing evidence
gathered in the literature,[6,7] the following mechanism is proposed
(Scheme 5). The excited photocatalyst oxidizes the nucleophile
delivering the corresponding radical which, in an off-cycle process,
adds to the terminal carbon of the olefin to give secondary C-
centered radical A. The reaction of A with Ni(0) generates a
transient alkyl-Ni(I) complex B, that upon oxidative addition with
the aromatic halide produces the key Ar-Ni(III)-alkyl intermediate
C (Scheme 5, path I). Alternatively, the same species can be
formed as a result of the oxidative addition of the aromatic halide
onto Ni(0) followed by radical recombination with A (path II).[15] In
both cases, a C-C reductive elimination from C delivers the
product D together with a Ni(I) complex. Both catalytic cycles are
closed by oxidation of Ru(I) species by Ni(I), which regenerates
both, the Ru(II) photocatalyst and the Ni(0) catalyst,
respectively.[19]
[3]
For selected examples, see: a) A. Carboni, G. Dagousset, E. Magnier, G.
Masson, Chem. Commun. 2014, 50, 14197; b) Y. Ma, D. Zhang, Z. Yan,
M. Wang, C. Bian, X. Gao, E. E. Bunel, A. Lei, Org. Lett. 2015, 17, 2174;
c) X.-H. Ouyang, R.-J. Song, M. Hu, Y. Yang, J.-H. Li, Angew. Chem. Int.
Ed. 2016, 55, 3187; d) M. Li, J. Yang, X.-H. Ouyang, Y. Yang, M. Hu, R.-
J. Song, J.-H. Li, J. Org. Chem. 2016, 81, 7148; e) Y. Duan, W. Li, P. Xu,
M. Zhang, Y. Chenga, C. Zhu, Org. Chem. Front. 2016, 3, 1443; f) G.
Dagousset, C. Simon, E. Anselmi, B. Tuccio, T. Billard, E. Magnier,
Chem. Eur. J. 2017, 23, 4282; g) X. Yong, Y-F. Han, Y. Li, R.-J. Song,
J.-H. Li, Chem. Commun. 2018, 54, 12816; h) J.-S. Lin, T.-T. Li, J.-R. Liu,
G.-Y. Jiao, Q.-S. Gu, J.-T. Cheng, Y.-L. Guo, X. Hong, X.-Y. Liu, J. Am.
Chem. Soc. 2019, 141, 1074; i) F. J. R. Klauck, H. Yoon, M. J. James,
M. Lautens, F. Glorious, ACS Catal. 2019, 9, 236.
[4]
a) F. Wang, D. Wang, X. Mu, P. Chen, G.Liu, J. Am. Chem. Soc. 2014,
136, 10202; b) L. Wu, F. Wang, Xi. Wan, D.Wang, P. Chen, G. Liu, J.
Am. Chem. Soc. 2017, 139, 2904; For
a dual Cu/Ir photoredox
dicarbofunctionalization see, c) X.-L. Lv, C. Wang, Q.-L. Wang, W. Shu,
Org. Lett. 2019, 21, 56; d) J. Terao, F. Bando, N. Kambe, Chem Commun.
2009, 7336; e) T. Qin, J. Cornella, C. Li, L. R. Malins, J. T. Edwards, S.
Kawamura, B. D. Maxwell, M. D. Eastgate, P. S. Baran, Science 2016,
352, 801; f) J.-W. Gu, Q.-Q. Min, L.-C. Yu, X. Zhang, Angew. Chem. Int.
Ed. 2016, 55, 12270; g) A. García-Domínguez, Z. Li, C. Nevado, J. Am.
Chem. Soc. 2017, 139, 6835; h) A. García-Domínguez, C. Nevado,
CHIMIA 2018, 4, 212; i) L. Guo, F. Song, S. Zhu, H. Li, L. Chu, Nature
Commun. 2018, 9, 45.
[5]
For selected reviews, see: a) J. M. R. Narayanam, C. Stephenson, Chem.
Soc. Rev. 2011, 40, 102; b) C. K. Prier, D. A. Rankic, D. W. C. Macmillan,
Chem. Rev. 2013, 113, 5322; c) T. P. Yoon, C. R. J. Stephenson, Adv.
Synth. Catal. 2014, 356, 2739; d) J.-R. Chen, X.-Q. Hu, L.-Q. Lu, W.-
J.Xiao, Chem. Soc. Rev. 2016, 45, 2044.
Scheme 5. Proposed catalytic pathways towards product formation.
In summary, we showcase here the potential of merging
photoredox and nickel catalysis under visible light to perform
three-component carbofunctionalizations of alkenes. As the
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10.1002/anie.201906692
Angewandte Chemie International Edition
COMMUNICATION
[6]
For reviews, see: a) T. Moragas, A. Correa, R. Martin, R. Chem. Eur. J.
2014, 20, 8242; b) C. E. I Knappke,.S. Grupe, D. Gärtner, M. Corpet, C.
Gosmini, J. von Wangelin, Chem. Eur. J. 2014, 20, 6828; c) J. Gu, X.
Wang, W. Xue, H. Gong, Org. Chem. Front. 2015, 2, 1411; d) D. J. Weix,
Acc. Chem. Res. 2015, 48, 1767.
G. H. M. Davies, G. A. Molander, ACS Catal. 2017, 7, 5129; d) B. A. Vara,
M. Jouffroy, G. A. Molander, Chem. Sci. 2017, 8, 530.
[11] See Supporting Information for further details.
[12] For selected examples, see: a) X. Li, X. Xu, P. Hu, X. Xiao, C. Zhou, J.
Org. Chem. 2013, 78, 7343; b) D. Xia, T. Miao, P. Li, L. Wang, Chem.
Asian. J. 2015, 10, 1919; c) H. Wang, S. Sun, J. Cheng, Org. Lett. 2017,
19, 5844; d) X.-Q. Chu, H. Meng, X.-P. Xu, S.-J. Ji, Shun-Jun, Chem.
Eur. J. 2015, 21, 11359; e) S.-F. Wang, C.-P. Chuang, J.-H. Lee, S.-T.
Liu, Tetrahedron 1999, 55, 2273. For three-component vicinal
carbosulfonylations involving C-Ar bond formation on allenes: f) N. Vicart,
B. Gazes, J. Gore, Tetrahedron 1996, 52, 9101; g) Y. Hou, Q. Shen, Z.
Li, S. Chen, Y. Zhao, M. Qin, P. Gon Adv. Synth. Catal. 2018, 360, 631.
[13] a) A. U. Meyer, K. Straková, T. Slanina, B. König, Chem. Eur. J. 2016,
22, 8694. For a review on the use of sulfinates in organic synthesis, see:
b) J. Aziz, S. Messaoudi, M. Alami, A. Hamze, Org. Biomol. Chem. 2014,
12, 9743 and references therein.
[7]
For selected reviews, see: a) J. Twilton, C. C. Le, P. Zhang, M. H. Shaw,
R. W. Evans, D. W. C. MacMillan, Nature Rev. Chem. 2017, 1, 0052; b)
J. K. Matsui, S. B. Lang, D. R. Heitz, G. A. Molander, ACS Catal. 2017,
7, 2563; c) Y.-Y. Gui, L. Sun, Z.-P. Lu, D.-G. Yu, Org. Chem. Front. 2016,
3, 522. d) J. C. Tellis, C. B. Kelly, D. N. Primer, M. Jouffroy, N. R. Pattel,
G. A. Molander, Acc. Chem. Res. 2016, 49, 1429; e) J. A. Milligan, J. P.
Phelan, S. O. Badir, G.A. Molander, Angew. Chem. Int. Ed. 2019, DOI:
10.1002/anie.201809431.For selected examples, see: f) Z. Zuo, D. T.
Ahneman, L. Chu, J. A. Terrett, A. G. Doyle, D. W. C. MacMillan, Science
2014, 345, 437; g) J. Twilton, M. Christensen, D. A. DiRocco, R. T. Ruck,
I. W. Davies, D. W. C. MacMillan, Angew. Chem. Int. Ed. 2018, 57, 5369;
h) R. Alam, G. A. Molander, J. Org. Chem. 2017, 82, 13728; i) B. A. Vara,
N. R. Patel, G. A. Molander, ACS Catal. 2017, 7, 3955; j) Z. Zuo, H. Cong,
W. Li, J. Choi, G. C. Fu, D. W. C. MacMillan, J. Am. Chem. Soc. 2016,
138, 1832; k) Z. Duan, W. Li, A. Lei, Org. Lett. 2016, 18, 4012; For an
indoline synthesis under Nickel/Photoredox Dual Catalysis: l) S. Z.
Tasker, T. F. Jamison, J. Am. Chem. Soc. 2015, 137, 9531.
[14] For recent examples of coupling reactions using haloarenes with
sulfinates under photoredox catalysis, see: a) M. J. Cabrera-Alfonso, Z.-
P. Lu, C. B. Kelly, S. B. Lang, R. Dykstra, O. Gutierrez, G. A. Molander,
Chem. Sci. 2018, 9, 3186; b) N.-W. Liu, K. Hofman, A. Herbert, G.
Manolikakes, Org. Lett. 2018, 20, 760; c) H. Yue, C. Zhu, A. Rueping,
Angew. Chem. Int. Ed. 2018, 57, 1371; d) T. Knauber, R.
Chandrasekaran, J. W. Tucker, J. M. Chen, M. Reese, D. A. Rankic, N.
Sach, C. Helal, Org. Lett. 2017, 19, 6566.
[8]
a) N. Fuentes, W. Kong, L. Fernández-Sánchez, E. Merino, C. Nevado,
J. Am. Chem. Soc. 2015, 137, 964; b) Z. Li, A. García-Domínguez, C.
Nevado, J. Am. Chem. Soc. 2015, 137, 11610; c) Z. Li, A. García-
Domínguez, C. Nevado, Angew. Chem Int. Ed. 2016, 55, 6938; d) W.
Shu, A. Lorente, E. Gómez-Bengoa, C. Nevado, Nature Commun. 2017,
8, 13832; e) A. García-Domínguez, S. Müller, C. Nevado, Angew. Chem.
Int. Ed. 2017, 56, 9949; f) W. Shu, E. Merino, C. Nevado, ACS Catal.
2018, 8 6401.
[15] H. Fischer, L. Radom, Angew. Chem. Int. Ed. 2001, 40, 1340.
[16] M. Newcomb, Tetrahedron 1993, 49, 1151.
[17] A previous study on Csp3-Csp3 Negishi cross-coupling suggests that the
key C-C bond formation process may happen at a higher rate: V. B.
Phapale, E. Buñuel, M. García-Iglesias, D. J. Cárdenas, Angew. Chem.
Int. Ed. 2007, 46, 8790.
[9]
a) V. Corcé, L.-M. Chamoreau, E. Derat, J.-P. Goddard, C. Ollivier, L.
Fensterbank, Angew. Chem. Int. Ed. 2015, 54, 11414; b) Y. Nishigaichi,
A. Suzuki, A. Takuwa, Tetrahedron Lett. 2007, 48, 211; c) D. Matsuoka,
Y. Nishigaichi, Chem. Lett. 2014, 43, 559. For redox potential of common
photocatalysts, see: d) C. K. Prier, D. A. Rankic, D. W. C. Macmillan,
Chem. Rev. 2013, 113, 5322.
[18] For studies showing the favourable addition of benzyl radicals to Ni(0),
see: O. Gutierrez, J. C. Tellis, D. N. Primer, G. A. Molander, M. C.
Kozlowski, J. Am. Chem. Soc. 2015, 137, 4896.
[19] Based on photophysical characterization experiments, an alternative
mechanism involving a photoredox induced radical-chain mechanism in
which, after an initiation cycle by the Ru-catalyst, Ni species serve as
oxidant for the formation of the Nu-type radicals cannot be ruled out. See
ref. 11.
[10] For selected examples on alkyl-aryl cross-couplings using dual
ruthenium/nickel catalysis, see: a) M. Jouffroy, D. N. Primer, G. A.
Molander, J. Am. Chem. Soc. 2016, 138, 475; b) N. R. Patel, G. A.
Molander, J. Org. Chem. 2016, 81, 7271; c) K. Lin, R. J Wiles, C. B. Kelly,
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10.1002/anie.201906692
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Andrés García-Domínguez, Rahul
Mondal, Cristina Nevado*
Page No. – Page No.
Dual Photoredox/Nickel-Catalyzed
Three-Component
Carbofunctionalization of Alkenes
Herein, we demonstrate the use of a dual Ru/Ni catalytic system in a three-
component carbofunctionalization of alkenes under visible light irradiation. The
method allows the simultaneous and regiocontrolled addition of aromatic groups
together with sulfonyl or alkyl groups across the π-system with readily available,
bench-top stable sulfinates and alkylsilicates partners.
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