Photoinduced Palladium-Catalyzed Dicarbofunctionalization of Terminal Alkynes

Article abstract of DOI:10.1002/chem.202005391

Herein, a conceptually distinct approach was developed that allowed for the dicarbofunctionalization of alkynes at room temperature using simple, bench-stable alkyl iodides and a second molecule of alkyne as coupling partner. Specifically, the photochemical activation of palladium complexes enabled this strategic dicarbofunctionalization via addition of alkyl radicals from secondary and tertiary alkyl iodides and formation of an intermediate palladium vinyl complex that could undergo subsequent Sonogashira reaction with a second alkyne molecule. This alkylation–alkynylation sequence allowed the one-step synthesis of 1,3-enynes including heteroarenes and biologically active compounds with high efficiency without exogenous photosensitizers or oxidants and now opens up pathways towards cascade reactions via photochemical palladium catalysis.

Full text of DOI:10.1002/chem.202005391

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
&
Photocatalysis
Photoinduced Palladium-Catalyzed Dicarbofunctionalization of
Terminal Alkynes
[a]
Zhen Yang and Rene M. Koenigs*
[
10]
event.
Moreover, it has recently been demonstrated that
Abstract: Herein, a conceptually distinct approach was de-
veloped that allowed for the dicarbofunctionalization of
alkynes at room temperature using simple, bench-stable
alkyl iodides and a second molecule of alkyne as coupling
partner. Specifically, the photochemical activation of palla-
dium complexes enabled this strategic dicarbofunctionali-
zation via addition of alkyl radicals from secondary and
tertiary alkyl iodides and formation of an intermediate pal-
ladium vinyl complex that could undergo subsequent So-
nogashira reaction with a second alkyne molecule. This al-
kylation–alkynylation sequence allowed the one-step syn-
thesis of 1,3-enynes including heteroarenes and biological-
ly active compounds with high efficiency without exoge-
nous photosensitizers or oxidants and now opens up
pathways towards cascade reactions via photochemical
palladium catalysis.
photoexcitation of Pd-complexes facilitates the formation of an
I
intermediate radical and Pd complex, which does not proceed
[
5]
via single-electron transfer processes (Scheme 1).
Today, the application of photochemical Pd-catalysis is rapid-
ly advancing as an important strategy to unveil the reactivity
of alkyl halides in Pd-catalyzed cross-coupling reactions, which
are typically challenging substrates owing to the ease of b-hy-
dride elimination. In this context, the photochemical, palladi-
um-catalyzed Heck-reaction of unactivated alkyl halides wit-
[
6]
nessed significant advances as reported by the groups of Fu,
[
3,7]
[8]
[5]
Gevorgyan,
Glorius, and Rueping. Currently available ap-
proaches focus on a singular catalytic bond-forming event,
while difunctionalization reactions of hydrocarbon frameworks
remain rare. In this context, Glorius and co-workers and Ge-
vorgyan and co-workers recently reported on the reactivity of
buta-1,3-dienes under photochemical palladium catalyzed con-
ditions to allow for the 1,4-difunctionalization via a Heck–allylic
[
7f,8b]
substitution reaction cascade (Scheme 1).
Against this background and our interest in metal-catalyzed
Palladium-catalyzed cross-coupling reactions constitute one of
the pillars of chemistry and have significantly shaped modern
organic synthesis methodology and applications, for example,
[
11]
CÀC bond-forming reactions, we became intrigued in study-
ing difunctionalization reactions of alkynes via multiple Pd-cat-
[1]
in materials’ sciences or drug development. Since the discov-
[2]
ery of Pd-catalyzed cross-coupling reactions, advances in cat-
alyst and ligand design have opened up a broad array of syn-
thetic transformations to push the boundaries of the classic ox-
idative addition–transmetalation–reductive elimination mecha-
nism. Only recently, the discovery of photochemical Pd-cata-
[
3]
lyzed cross-coupling reactions opened up a new paradigm.
This strategy harnesses the photochemical properties of palla-
dium complexes that often feature a strong absorption in the
[
3,4–9]
visible light region.
Hence, palladium complexes can take
up a dual function as both photosensitizers and cross-coupling
catalysts and thus contrast the developments in dual photore-
dox/ transition metal-catalyzed transformations that require
two different catalysts for the sensitization and coupling
[
a] Z. Yang, Prof. Dr. R. M. Koenigs
Institute of Organic Chemistry, RWTH Aachen University
Landoltweg 1, 52074 Aachen (Germany)
E-mail: rene.koenigs@rwth-aachen.de
Supporting information and the ORCID identification number(s) for the
author(s) of this article can be found under:
https://doi.org/10.1002/chem.202005391.
ꢀ
2021 The Authors. Published by Wiley-VCH GmbH. This is an open access
article under the terms of the Creative Commons Attribution Non-Commer-
cial License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited and is not used for
commercial purposes.
Scheme 1. Photochemical Pd-catalyzed cross-coupling reactions.
Chem. Eur. J. 2021, 27, 3694 – 3699
3694
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
[
12]
alyzed bond forming events. Specifically, we hypothesized
that photochemical activation of a Pd-complex would allow
the formation of alkyl radicals that undergo addition reaction
with terminal alkynes to furnish an intermediate Pd-vinyl com-
plex, which in turn could be applied to subsequent Pd-cata-
lyzed cross-coupling reactions to realize photocatalytic dicar-
bofunctionalization reactions. In this context, Nevado and co-
homo-coupling product 4 was obtained exclusively. Bidentate
phosphine ligands gave the dicarbofunctionalization without
formation of the product of homo-coupling, albeit in lower
[
17]
yield (Table S1 in the Supporting Information). When using
10 mol% of the palladium catalyst, the product 3a was ob-
tained in 81% isolated yield (Table 1, entry 7). A control experi-
ment showed the necessity of the photochemical reaction con-
ditions as no reaction occurred in the dark (Table 1, entry 9).
Similarly, alkyl bromides proved incompatible and only trace
amounts of the 1,3-enyne product were observed (Table 1,
entry 8). To probe the potential of thermally induced process-
es, we examined the reaction under thermal conditions in the
dark, yet, no desired 1,3-enyne product was found.
[
13]
[14]
workers and Li et al. recently reported on their develop-
ments in dicarbofunctionalization reactions to allow for formal
alkylation–arylation or dialkylation reactions of alkynes, yet re-
[
13a]
quiring forcing thermal reaction conditions
or the use of re-
[14]
active organometallic reagents.
We initiated these studies by examining the reaction of phe-
nylacetylene 1a with cyclohexyl iodide 2a under photoin-
duced palladium-catalyzed reaction conditions. Indeed, we ob-
tained the 1,3-enyne product 3a in 55% yield and high stereo-
selectivity [diastereomeric ratio (d.r.) >20:1] without formation
With the optimized reaction condition in hand, we next ex-
amined the application of this enyne synthesis (Scheme 2).
Electron-donating substituents, such as methyl (3d, 3l), me-
thoxy (3e, 3m), and dimethylamino (3 f) were found compati-
ble, and the corresponding dicarbofunctionalization products
were obtained in moderate yield and excellent stereoselectiv-
ity.
[15]
of by-products from alkyne dimerization (4). This transforma-
tion now showcases one of the first examples of a catalytic al-
kylation-alkynylation reaction and now provides a one-step
[16]
access towards important 1,3-enynes. We thus examined dif-
ferent reaction parameters, such as stoichiometry, solvent,
base, palladium precursor, or ligand to further improve the
yield of 3a (for the full details of our optimization studies,
Electron-deficient alkynes gave an increased yield, which
might be related to a more facile radical addition, albeit with
lower stereoselectivity (3g, 3h, 3i, 3k). A notable limitation
was observed for halogen substituents. Fluorine-substituted ar-
ylalkynes gave the desired 1,3-enyne product (3b, 3j) in good
yield with excellent stereoselectivity. In the case of 4-chloro-
phenyl acetylene, the yield of the enyne 3c dropped signifi-
cantly due to background Sonogashira coupling reaction. 4-
Bromophenyl acetylene, however, gave only trace amounts of
the desired product. Further studies involved the use of heter-
ocyclic substrates. To our delight, heterocycle- or carbocycle-
substituted alkynes were also compatible under the present
conditions, and the heterocycle-substituted 1,3-enyne products
were isolated in excellent yield (3o–q). An Estrone-derived
alkyne was also found compatible in this transformation, and
the corresponding product 3r was obtained in 42% yield, thus
demonstrating the application in late-stage functionalization.
The limitations of the present methodology lie within the
use of aliphatic, or 1,2-disubstituted alkynes, which both did
not provide the enyne coupling product under the present re-
action conditions; instead, decomposition of cyclohexyl iodide
took place, and the formation of complex reaction mixtures
was observed. The missing reactivity of 1,2-disubstituted al-
kynes can be explained by the missing C(sp)ÀH proton that is
important for the final coupling step to access the enyne.
Next, we examined the compatibility of different alkyl io-
dides. Primary alkyl iodides gave only trace amounts of the
coupling product and decomposition of the alkyl iodide as ob-
[
17]
please see Tables S1–S7 in the Supporting Information). Of
all bases and solvents tested, the combination of Cs CO and
2
3
THF and an excess of phenylacetylene 1a gave the best yield
of the 1,3-enyne product (Table 1, entry 5). Monodentate phos-
phine ligands, such as RuPhos (Table 1, entry 6) failed to pro-
vide the desired alkylation-alkynylation product 3a, instead the
[
a]
Table 1. Reaction optimization.
[
b]
Entry Deviations from above
Yield (3a)
%]
[
1
2
3
4
5
6
–
55
40
1 equiv. 1a, 3 equiv. 2a
Pd source: PdCl
CO instead of Cs
THF instead of PhH solvent
10 mol% RuPhos instead of Xantphos
2
/Pd(TFA)
2
/Pd
2
(dba)
3
trace/24/16
trace
62
K
2
3
2
CO
3
3a: n.d.
4
: 63%
[c]
1
7
10 mol% Pd(OAc)
vent
2
, 20 mol% Xantphos, THF sol-
83 (81)
served by H NMR spectroscopy of the crude reaction mixture
(
for more details, please see the Supporting Information),
8
9
cyclohexyl bromide instead of 2a
reaction in the dark
trace
no reaction
which might be reasoned by the instability of primary radical.
Secondary, acyclic alkyl iodides gave the corresponding 1,3-
enyne products 5a and 5b in moderate yield and high stereo-
selectivity (Scheme 3). We then studied different ring sizes of
cyclic alkyl iodides, ranging from 5- to 8-membered ring size,
which gave the 1,3-enyne products 5c–e in good yield and ex-
cellent stereoselectivity for small ring sizes. The stereoselectiv-
[
0
a] Reaction conditions: 0.6 mmol 1a (3 equiv.), 0.2 mmol 2a (1 equiv.),
.4 mmol (2 equiv.) Cs CO , 5 mol% Pd(OAc) , 10 mol% Xantphos were
2
3
2
dissolved in 1 mL benzene under argon atmosphere, irradiated with 3 W
blue led (470 nm) at room temperature overnight. [b] The yield was de-
1
termined by H NMR spectroscopy of the crude reaction. The internal
3
standard was CHBr . [c] Isolated yield.
Chem. Eur. J. 2021, 27, 3694 – 3699
www.chemeurj.org
3695
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
Scheme 3. Evaluation of alkyl iodides.
To gain insight into the reaction mechanism, several control
experiments were studied. In a first experiment, we studied
the on/off experiment of the reaction of phenylacetylene with
cyclohexyl iodide (Figure 1). When the light was switched off,
the reaction did not proceed further; after turning the light
back on, the reaction resumed, which indicates that the reac-
tion only proceeds under constant irradiation.
In a second set of experiments, we probed the participation
of radical intermediates. When 0.5 equiv. of the radical quench-
er (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) was added to
the reaction mixture, the pathway towards 1,3-enyne forma-
tion was completely inhibited, and a 46% yield of Cy-TEMPO 6
1
was obtained as determined by H NMR spectroscopy of the
Scheme 2. Evaluation of different alkynes.
crude reaction mixture (Scheme 4a). We next probed the reac-
tion with (cyclopropyliodomethyl)-benzene 2l, which can read-
ily undergo ring-opening reactions via a radical clock mecha-
nism to give a primary alkyl radical (Scheme 4b). Consistently
with the above findings, no reaction product was formed due
to the missing reactivity of primary alkyl radicals, and decom-
position of iodo alkane 2l was observed. To further prove the
radical mechanism, a radical clock experiment was studied
with 5-iodohex-1-ene 2m. We could indeed observe an insepa-
rable mixture of the direct radical coupling product 5m and
product 5m’, which arises from radical formation, followed by
intramolecular radical cyclization with the pendant olefin
(Scheme 4b). This observation further supports the radical
mechanism and moreover demonstrates that the intramolecu-
lar radical cyclization is disfavored over the radical coupling
process. To further elucidate the role of radical intermediates
ity was slightly reduced in the case of cycloheptyl and cyclooc-
tyl iodide. Heterocyclic iodides, including tetrahydrofuran 2 f,
tetrahydropyran 2g, and piperidine 2h, reacted smoothly to
the heterocycle-substituted 1,3-enyne products 5 f–h in good
yield and stereoselectivity. In a scale-up experiment of 5g to
1
mmol, the desired 1,3-enyne product was obtained in slightly
reduced yield, which might be related to the low efficiency of
the 3 W blue LED lamps and thus missing penetration of the
light into the reaction mixture. Tertiary alkyl iodides, such as
tert-butyl-iodide 2i and adamantyl iodide 2j similarly gave the
1
,3-enyne product with 63 and 84% yield, respectively (5i,j).
The epiandosterone-derived iodide derivative 2k gave the de-
sired 1,3-enyne product 5k in moderate yield.
Chem. Eur. J. 2021, 27, 3694 – 3699
www.chemeurj.org
3696
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
in the reaction mechanism, different alkyl-substituted alkynes
were studied. When tert-butyl acetylene 1s was applied as
substrate, no desired 1,3-enyne was founded in the reaction
mixture. Contrarily, trimethylsilane (TMS)-acetylene 1t gave the
corresponding 1,3-enyne in moderate yield (Scheme 4c). For
this phenomenon, we rationalize that addition of alkyl radicals
to the terminal alkyne generates a highly reactive vinyl radical.
While a neighboring aromatic ring or TMS substitution can sta-
bilize this vinyl radical, alkyl groups only poorly stabilize this in-
termediate, resulting in missing reaction to the 1,3-enyne
product.
Next, we aimed at an understanding of the second CÀC
bond-forming step. We examined different viable intermedi-
ates that could rationalize the observed reactivity. First, we
proposed that a radical mechanism of alkyl iodide and phenyl-
acetylene could result in the formation of the corresponding
vinyl iodide. The latter could further react with another mole-
cule of phenylacetylene 1a via Sonogashira coupling reaction.
We thus studied the reaction of vinyl iodide 7 and phenylacet-
ylene 1a under the optimized conditions (Scheme 5a). The
corresponding 1,3-enyne 3a was obtained with moderate yield
under the irradiation of blue light. Interestingly, the 1,3-enyne
Figure 1. On/off experiment.
3
a was also observed in the dark, yet significantly higher reac-
tion temperatures are required to obtain a comparable yield,
which shows that the second CÀC bond forming reaction
occurs at room temperature only in the presence of visible
light with high efficiency. Moreover, NMR spectroscopy and
GC–MS analysis of the crude reaction mixture of cyclohexyl
iodide 2a with phenylacetylene 1a under optimized condi-
tions did not reveal the presence of vinyl iodide 7, which
shows that vinyl iodide 7 is either a short-lived intermediate or
Scheme 4. Control experiments on the participation of radical intermediates.
Scheme 5. Control experiments on the role of the alkyne reaction partner.
Chem. Eur. J. 2021, 27, 3694 – 3699
www.chemeurj.org
3697
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
might not even be formed at all. Next, we examined the po-
tential of a formal Sonogashira reaction–hydroalkynylation re-
action mechanism (Scheme 5b). Such a mechanism would in-
volve the formation of a 1,2-disubstitued alkyne 8, which could
undergo a hydroalkynylation reaction under the present reac-
tion conditions. Yet, a control experiment with 8 showed no
reaction and both reactants remained untouched under the
present reaction conditions, thus excluding a reaction mecha-
nism via a hydroalkynylation reaction. Finally, we examined the
potential of formation of higher homologues of 3a that stem
from multiple consecutive reactions with phenylacetylene
kynes this Sonogashira reaction is impossible and, resulting in
no formation of the 1,3-enyne product.
In the proposed mechanism, the photoinduced palladium
0
catalysis takes up different functions. First, the Pd complex
I
acts as a photosensitizer that is also key to access a Pd com-
plex and an alkyl radical and thus initiates this dicarbofunction-
alization reaction. Second, the palladium catalyst plays a key
role in enabling the subsequent Sonogashira coupling process
at room temperature via excitation with visible light to afford
the final 1,3-enyne product.
In summary, we have developed a visible-light-induced pal-
ladium-catalyzed alkylation-alkynylation reaction to construct
(
Scheme 5c). For this purpose, we studied the reaction of cy-
2
3
2
clohexyl iodide 2a under optimized conditions, yet with a
large excess of phenylacetylene 1a. However, no higher homo-
logues of 3a were identified via GC–MS or NMR spectroscopy,
which rules out a radical addition pathway in the second
bond-forming event and further supports the Sonogashira cou-
pling mechanism. At this point it is important to note that at-
tempts at the coupling of two different terminal alkynes did
not lead to the formation of any crossover reaction products
C(sp )ÀC(sp )/C(sp )ÀC(sp) bonds in one step from aromatic al-
kynes and alkyl iodides under mild reaction conditions without
the need of exogenous photosensitizers or oxidants. Various al-
kynes and iodide compounds including bioactive derivatives
are compatible to afford densely functionalized 1,3-enynes
with good yield and stereoselectivity. A possible reaction
mechanism was proposed and involves a palladium vinyl inter-
mediate, which now opens up new a pathway in photochemi-
cal palladium catalysis towards cascade reactions and multi-
functionalization reactions.
(
for details, please see the Supporting Information).
Based on the above control experiments and previous re-
[
5,17]
ports,
we hypothesize the following mechanism
0
(
Scheme 6): Photoexcitation of a Pd complex A provides a
Acknowledgements
photoexcited state A* that reacts with alkyl iodide compoun-
I
d 2a to give a Pd complex and alkyl radical B. Radical addition
R.M.K. thanks the German Science Foundation for financial sup-
port. Open access funding enabled and organized by Projekt
DEAL.
between B and one molecule of phenylacetylene 1a generates
vinyl radical Int-I, which is stabilized by the pendant aromatic
ring. Contrarily, a corresponding alkyl-substituted vinyl radical
would lack this stabilization and thus undergo decomposition.
The linear geometry of vinyl radical Int-I results in coordination
Conflict of interest
I
to Pd from the sterically less hindered face resulting in the cis
II
geometry of aryl and alkyl group. The vinyl Pd complex Int-II
The authors declare no conflict of interest.
can further undergo Sonogashira coupling reaction with an-
other molecule of phenylacetylene 1a by deprotonation of
Cs CO via Int-III to afford the 1,3-enyne product 3a and re-
Keywords: alkynes
palladium · radical coupling
· dicarbofunctionalization · enynes ·
2
3
0
generate the Pd catalyst. In the case of 1,2-disubstituted al-
[1] Selected reviews: a) A. Biffis, P. Centomo, A. Del Zotto, M. Zecca, Chem.
Rev. 2018, 118, 2249–2295; b) P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev.
2016, 116, 12564–12649; c) C. Zhu, J. Liu, M. B. Li, J.-E. Bäckvall, Chem.
Soc. Rev. 2020, 49, 341–353; d) C. Fricke, T. Sperger, M. Mendel, F.
Schoenebeck, Angew. Chem. Int. Ed. 2021, https://doi.org/10.1002/
anie.202011825; e) Q. Liu, X. Dong, J. Li, J. Xiao, Y. Dong, H. Liu, ACS
Catal. 2015, 5, 6111–6137; f) S. D. Roughley, A. M. Jordan, J. Med. Chem.
2011, 54, 3451–3479; g) D. G. Brown, J. Bostrçm, J. Med. Chem. 2016,
5
9, 4443–4458.
[
2] Selected review: C. C. C. Johansson Seechurn, M. O. Kitching, T. J. Cola-
cot, V. Snieckus, Angew. Chem. Int. Ed. 2012, 51, 5062–5085; Angew.
Chem. 2012, 124, 5150–5174.
[
[
3] M. Parasram, P. Chuentragool, D. Sarkar, V. Gevorgyan, J. Am. Chem. Soc.
2
016, 138, 6340–6343.
4] a) P. Chuentragool, D. Kurandina, V. Gevorgyan, Angew. Chem. Int. Ed.
019, 58, 11586–11598; Angew. Chem. 2019, 131, 11710–11722; b) S.
Sumino, A. Fasano, T. Fukuyama, I. Ryu, Acc. Chem. Res. 2014, 47, 1563–
574; c) R. Kancherla, K. Muralirajan, A. Sagadevan, M. Rueping, Trends
2
1
Chem. 2019, 1, 510–523; d) S. Ye, T. Xiang, X. Li, J. Wu, Org. Chem.
Front. 2019, 6, 2183–2199; e) W.-J. Zhou, G.-M. Cao, Z.-P. Zhang, D.-G.
Yu, Chem. Lett. 2019, 48, 181–191.
[
5] R. Kancherla, K. Muralirajan, B. Maity, C. Zhu, P. E. Krach, L. Cavallo, M.
Rueping, Angew. Chem. Int. Ed. 2019, 58, 3412–3416; Angew. Chem.
2019, 131, 3450–3454.
Scheme 6. Proposed reaction mechanism.
Chem. Eur. J. 2021, 27, 3694 – 3699
www.chemeurj.org
3698
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH

Communication
Chemistry—A European Journal
doi.org/10.1002/chem.202005391
[
[
6] a) G.-Z. Wang, R. Shang, W.-M. Cheng, Y. Fu, J. Am. Chem. Soc. 2017,
Tellis, C. B. Kelly, D. N. Primer, M. Jouffroy, N. R. Patel, G. A. Molander,
Acc. Chem. Res. 2016, 49, 1429–1439.
1
39, 18307–18312; b) G.-Z. Wang, R. Shang, Y. Fu, Synthesis 2018, 50,
908–2914; c) G.-Z. Wang, R. Shang, Y. Fu, Org. Lett. 2018, 20, 888–891;
2
[11] a) C. Empel, R. M. Koenigs, Synlett 2019, 30, 1929–1934; b) Z. Yang, M.
Mçller, R. M. Koenigs, Angew. Chem. Int. Ed. 2020, 59, 5572–5576;
Angew. Chem. 2020, 132, 5620–5624; c) Z. Yang, C. Pei, R. M. Koenigs,
Org. Lett. 2020, 22, 7234–7238; d) S. Jana, C. Empel, C. Pei, P. Aseeva,
T. V. Nguyen, R. M. Koenigs, ACS Catal. 2020, 10, 9925–9931; e) K. J.
Hock, A. Knorrscheidt, R. Hommelsheim, J. Ho, M. J. Weissenborn, R. M.
Koenigs, Angew. Chem. Int. Ed. 2019, 58, 3630–3634; Angew. Chem.
d) W.-M. Cheng, R. Shang, Y. Fu, Nat. Commun. 2018, 9, 5215.
7] a) P. Chuentragool, M. Parasram, Y. Shi, V. Gevorgyan, J. Am. Chem. Soc.
2
018, 140, 2465–2468; b) M. Ratushnyy, M. Parasram, Y. Wang, V. Ge-
vorgyan, Angew. Chem. Int. Ed. 2018, 57, 2712–2715; Angew. Chem.
018, 130, 2742–2745; c) D. Kurandina, M. Parasram, V. Gevorgyan,
Angew. Chem. Int. Ed. 2017, 56, 14212–14216; Angew. Chem. 2017, 129,
4400–14404; d) M. Parasram, P. Chuentragool, Y. Wang, Y. Shi, V. Ge-
2
2019, 131, 3669–3673.
1
[
12] For selected reviews: a) H. Yoshida, ACS Catal. 2016, 6, 1799–1811; b) R.
Chinchilla, C. Nµjera, Chem. Rev. 2014, 114, 1783–1826; c) Y. Shimizu, M.
Kanai, Tetrahedron Lett. 2014, 55, 3727–3737; d) T. Besset, T. Poisson, X.
Pannecoucke, Eur. J. Org. Chem. 2015, 2765–2789.
vorgyan, J. Am. Chem. Soc. 2017, 139, 14857–14860; e) P. Chuentragool,
D. Yadagiri, T. Morita, S. Sarkar, P. Chuentragool, Y. Wang, V. Gevorgyan,
Angew. Chem. Int. Ed. 2019, 58, 1794–1798; Angew. Chem. 2019, 131,
1
808–1812; f) K. P. S. Cheung, D. Kurandina, T. Yata, V. Gevorgyan, J.
[
13] a) Z. Li, A. Garcia-Dominguez, C. Nevado, Angew. Chem. Int. Ed. 2016, 55,
Am. Chem. Soc. 2020, 142, 9932–9937.
6938–6941; Angew. Chem. 2016, 128, 7052–7055; b) Z. Li, A. Garcia-
[
[
8] a) M. Koy, F. Sandfort, A. Tlahuext-Aca, L. Quach, C. G. Daniliuc, F. Glo-
rius, Chem. Eur. J. 2018, 24, 4552–4555; b) H.-M. Huang, P. Bellotti, P. M.
Pflueger, J. L. Schwarz, B. Heidrich, F. Glorius, J. Am. Chem. Soc. 2020,
Dominguez, C. Nevado, J. Am. Chem. Soc. 2015, 137, 11610–11613.
[
[
[
14] W. Li, S. Yu, J. Cai, Y. Zhao, Angew. Chem. Int. Ed. 2020, 59, 14404–
14408; Angew. Chem. 2020, 132, 14510–14514.
1
42, 10173–10183.
15] O. S. Morozov, A. F. Asachenko, D. V. Antonov, V. S. Kochurov, D. Y. Para-
schuk, M. S. Nechaev, Adv. Synth. Catal. 2014, 356, 2671–2678.
16] a) P. Nussbaumer, I. Leitner, K. Marz, A. Stuetz, J. Med. Chem. 1995, 38,
9] a) W.-J. Zhou, G.-M. Cao, G. Shen, X.-Y. Zhu, Y.-Y. Gui, J.-H. Ye, L. Sun, L.-L.
Liao, J. Li, D.-G. Yu, Angew. Chem. Int. Ed. 2017, 56, 15683–15687;
Angew. Chem. 2017, 129, 15889–15893; b) L. Sun, J.-H. Ye, W.-J. Zhou,
D.-G. Yu, Org. Lett. 2018, 20, 3049–3052; c) M. L. Czyz, G. K. Weragoda,
T. H. Horngren, T. U. Connell, D. Gomez, R. A. J. O’Hair, A. Polyzos, Chem.
Sci. 2020, 11, 2455–2463; d) R. Adamik, T. Fçldesi, Z. Novak, Org. Lett.
1831–1836; b) S. Saito, Y. Yamamoto, Chem. Rev. 2000, 100, 2901–
2916; c) Y. Liu, M. Nishiura, Y. Wang, Z. Hou, J. Am. Chem. Soc. 2006,
128, 5592–5593; d) G. Chen, L. Wang, D. W. Thompson, Y. Zhao, Org.
Lett. 2008, 10, 657–660.
2020, 22, 8091–8095; e) D. Kim, G. S. Lee, D. Kim, S. H. Hong, Nature
[
17] C. W. Cheung, F. E. Zhurkin, X. Hu, J. Am. Chem. Soc. 2015, 137, 4932–
Commun. 2020, 11, 5266; f) L. Chen, L.-N. Guo, S. Liu, L. Liu, X.-H. Duan,
Chem. Sci. 2021, https://doi.org/10.1039/D0SC04399K.
4935.
[
10] Selected articles: a) C. K. Prier, D. A. Rankic, D. W. C. MacMillan, Chem.
Rev. 2013, 113, 5322–5363; b) X. Huang, E. Meggers, Acc. Chem. Res.
Manuscript received: December 17, 2020
Accepted manuscript online: January 11, 2021
Version of record online: January 28, 2021
2019, 52, 833–847; c) D. C. Fabry, M. Rueping, Acc. Chem. Res. 2016, 49,
1
969–1979; d) O. Reiser, Acc. Chem. Res. 2016, 49, 1990–1996; e) J. C.
Chem. Eur. J. 2021, 27, 3694 – 3699
www.chemeurj.org
3699
ꢀ 2021 The Authors. Published by Wiley-VCH GmbH