Mechanochemical Oxidative Heck Coupling of Activated and Unactivated Alkenes: A Chemo-, Regio- and Stereo-Controlled Synthesis of Alkenylbenzenes

Article abstract of DOI:10.1002/adsc.201900965

In this work, we present an efficient mechanochemical strategy for chemo-, regio- and stereo-selective oxidative Heck coupling of readily accessible arylboron reagents/heteroaromatics with cyclic and acyclic olefins. Mono- and bis-arylation were achieved without the need of ligands, directing groups or prefunctionalized alkenes, and the reaction chemo-selectivity could be controlled by tuning of the oxidative system. This protocol offers the synthesis of alkenylbenzenes in broad substrate scope, satisfactory yields and excellent selectivity even in the gram scale. (Figure presented.).

Full text of DOI:10.1002/adsc.201900965

COMMUNICATIONS
DOI: 10.1002/adsc.201900965
Mechanochemical Oxidative Heck Coupling of Activated and
Unactivated Alkenes: A Chemo-, Regio- and Stereo-Controlled
Synthesis of Alkenylbenzenes
Jingbo Yu,a Haowen Shou,a Wangyang Yu,a Haodong Chen,a and Weike Sua,*
a
National Engineering Research Center for Process Development of Active Pharmaceutical Ingredients, Collaborative Innovation
Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, People’s
Republic of China
Tel: +86 57188320899
E-mail: pharmlab@zjut.edu.cn
Manuscript received: August 1, 2019; Revised manuscript received: September 16, 2019;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201900965
promote/accelerate reactions and control selectivity
Abstract: In this work, we present an efficient
(Scheme 1a, b);[5] 2) installing a functional group to
mechanochemical strategy for chemo-, regio- and
unactivated olefin (such as OH, NHR, etc.) to form
stereo-selective oxidative Heck coupling of readily
chelation with metal catalysts, thereby induces the
accessible arylboron reagents/heteroaromatics with
reactivity and facilitates selectivity[6] (Scheme 1c).
cyclic and acyclic olefins. Mono- and bis-arylation
Representative examples are Duan’s[5d] and Lee’s[5h]
were achieved without the need of ligands, directing
works of bidentate ligands enabled oxidative arylations
groups or prefunctionalized alkenes, and the reac-
of coumarins and cyclopentene-1,3-diones. And also,
tion chemo-selectivity could be controlled by tuning
independent studies by Maiti[5g] and Yu[5i] using amino-
of the oxidative system. This protocol offers the
synthesis of alkenylbenzenes in broad substrate
scope, satisfactory yields and excellent selectivity
even in the gram scale.
Keywords: unactivated alkenes; cross-coupling; oxi-
dative arylation; mechanochemistry; solvent-free re-
actions
Palladium-catalyzed oxidative coupling reactions as a
synthetic strategy for CÀ C and CÀ heteroatom bonds
formation received much attention in the past years.[1]
Among them, approaches employing oxidative Heck
couplings have emerged as one of the most powerful
tools for modern organic syntheses in virtue of their
high efficiency and widespread applications[2] in the
preparation of pharmaceutical drugs, natural products,
and functional materials. However, these reactions
have been largely restricted to electronically activated
alkenes such as acrylates and styrenes. In the absence
of suitable electronic bias, the oxidative Heck cou-
plings with unactivated olefins often suffer from severe
reactivity,[3] and regioselectivity issues.[4] Two strat-
egies are usually employed to relieve these problems:
Scheme 1. Oxidative Heck coupling reactions with unactivated
olefins.
1) utilizing ligands and/or directing groups to adjust
the steric and electronic property of metal catalysts to
Adv. Synth. Catal. 2019, 361, 1–8
1
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Table 1. Optimization of reaction conditions.[a]
quinoline directing group and amide auxiliary in
synergy with racemic 1,1’-binaphthyl-2,2’-diamine
ligand or amino acid-based ligand to induce aryl CÀ H
olefination with unactivated aliphatic alkenes. More-
over, Zhu[6a], Xu[6d] and Jiang[6e] et al. reported
hydroxyl and amino groups assisted oxidative aryla-
tions of the allylic alcohols and the protected-allyl-
amines, respectively. Despite significant advances for
acyclic aliphatic alkenes and cycloenones, multi-
substituted cyclic olefins involved oxidative Heck
coupling continues to be particularly challenging, the
unsatisfactory efficiency as well as scarcity of exam-
ples substantially hampered the utility of this
reaction.[7] Additionally, chemo-selectivity was another
commonly faced problem even within directing-group-
assisted CÀ H olefination.[8] Hence, it is of great
synthetic worth to develop a practical methodology to
address these long-standing issues.
In the past decade, a resurgence in mechanochemis-
try by ball-milling has led to remarkable advances in
organic synthesis.[9] Such mechanochemical techniques
often provide ameliorative sustainability metrics
through solvent-free conditions,[10] allow the improve-
ment of traditional transformations,[9a,11] and most
importantly alter chemical reactivity as well as
selectivity.[9d–e,12] In light of our successful studies in
mechanosynthesis[13] and oxidative cross couplings,[14]
herein we report an efficient mechanochemical strategy
for chemo-, regio- and stereo-selective arylation of
unactivated cyclic and acyclic olefins under Pd-
catalyzed oxidative conditions. The reactions were
totally ligand-free and pre-functionalization-free, and
the chemo-selectivity could be easily controlled by
tuning of the oxidative system. To the best of our
knowledge, this was the first method where the
mechanochemical technique was used for activating
Entry Oxidant/eq
Additive/ Yield/%[b] (3/
eq
4)
1
2
Cu(OAc)2·H2O (1.0)
–
20 (100/0)
30 (>99/1)
Cu(OAc)2·H2O (1.0)
K2S2O8 (1.0)
BQ (1.0)
AcOH
(2.0)
AcOH
(2.0)
AcOH
(2.0)
AcOH
(2.0)
3
4
5
6
7
8
28 (100/0)
<10 (100/0)
58 (50/50)
70 (100/0)
DDQ (1.0)
Cu(OAc)2·H2O/DDQ (0.5/ AcOH
0.5) (2.0)
Cu(OAc)2·H2O/DDQ (0.5/ TCA (2.0) 72 (70/30)
0.5)
Cu(OAc)2·H2O/DDQ (0.5/ TCA (2.0) 69 (99/1)
0.1)
9
10
11
DDQ (0.2)
DDQ (0.5)
DDQ (1.0)
TCA (2.0) 70 (100/0)
TCA (2.0) 72 (70/30)
TCA (2.0) 72 (50/50)
TCA (2.0) 76 (40/60)
TCA (3.0) 78 (2/98)
TCA (4.0) 75 (2/98)
12[c] DDQ (1.0)
13[c] DDQ (1.5)
14[c] DDQ (2.0)
[a] Reaction conditions: 1a (0.5 mmol), 2a (0.5 mmol), Pd
(OAc)2 (10 mol%), oxidants, additives and silica gel (0.4 g)
were placed in a stainless-steel vessel with two stainless-steel
balls (ø=1.2 cm) milling at 20 Hz for 30 min.
[b] Isolated yields.
[c] 1a (1 mmol), 2a (0.5 mmol).
unbiased olefins and helping regio- and stereo-selectiv- This assumption was confirmed, and the utilization of
ity control. Cu(OAc)2·H2O (0.5 equiv.)/DDQ (0.5 equiv.) offered
We began our initial investigation by screening the 70% yield of 3aa as an exclusive product (entry 6).
oxidative systems that can facilitate the cross-coupling We further investigated the effects of additives and
of phenylboronic acid 1a and methyl cyclopent-1-ene- noted that trichloroacetic acid (TCA) exerted a signifi-
1-carboxylate 2a under solvent-free ball-milling (Ta- cant positive effect, in which catalytic amount of DDQ
ble 1). Cu(OAc)2·H2O (1.0 equiv.) afforded only 20% (0.2 equiv.) was sufficient to give comparable yield
yield of methyl 5-phenylcyclopent-1-ene-1-carboxylate (70%) and complete selectivity (3aa/4aa=100:0) in
3aa accompanied with plenty of biphenyl by-products the absence of Cu(OAc)2·H2O (entry 9). Surprisingly,
(entry 1). The addition of acetic acid gave a slight an increasement of DDQ and phenylboronic acid 1a
increase of the yield (entry 2), which probably due to allowed alteration of the coupling product portfolio to
the beneficial effects of acid to migratory insertion of give a gradual elevation of bis-arylation product 4aa
olefins.[15] Alternative K2S2O8 and benzoquinone (BQ) (entries 10–12). Subsequent rising of DDQ and TCA
were detrimental to the product yields (entries 3–4). in equal proportion led to the produce of 4aa as the
Interestingly,
4,5-dichloro-3,6-dioxocyclohexa-1,4- absolute major product, and the optimal result (78%
diene-1,2-dicarbonitrile (DDQ) gave a mixture of yield, 3aa/4aa=2:98) was obtained by the use of 1.5
monoarylation product 3aa and diarylation product equivalent of DDQ and 3.0 equivalent of TCA
4aa in 58% yield with a molar ratio of 3aa to 4aa of (entry 13).
50:50, and the biphenyl formation was fully suppressed
With the optimized conditions in hand, the substrate
(entry 5). Thus, a positive effect was anticipated by scope for the mono-arylation of methyl cyclopent-1-
using combined oxidants of Cu(OAc)2·H2O and DDQ. ene-1-carboxylate 2a via oxidative boron-Heck cou-
Adv. Synth. Catal. 2019, 361, 1–8
2
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
Table 2. Substrate scope study for mono-arylation.[a]
Table 3. Substrate scope study for activated and unactivated
alkenes.[a]
[a] Reaction conditions: 1a (0.5 mmol), 2 (0.5 mmol), Pd(OAc)2
(10 mol%), DDQ (0.2 equiv.), TCA (2.0 equiv.) and silica gel
(0.4 g) were placed in a stainless-steel vessel with two
stainless-steel balls (ø=1.2 cm) milling at 20 Hz for 30 min.
[b] Isolated yields. All products were E-isomers and were
[a] Reaction conditions: 1 (0.5 mmol), 2a (0.5 mmol), Pd(OAc)2
(10 mol%), DDQ (0.2 equiv.), TCA (2.0 equiv.), and silica
gel (0.4 g) were placed in a stainless-steel vessel with two
stainless-steel balls (ø=1.2 cm) milling at 20 Hz for 30 min.
[b] Isolated yields.
1
determined by H NMR analysis.
[c] Comparative experiment: 1a (0.5 mmol), 2a (0.5 mmol), Pd
(OAc)2 (10 mol%), DDQ (0.2 equiv.), TCA (2.0 equiv.) and
°
DMF (5 mL), 50 C, 24 h.
[d] 1a (0.5 mmol), 2 (1.0 mmol).
[e] 1 (0.5 mmol), 2f (0.5 mmol), Pd(OAc)2 (10 mol%), Cu
(OAc)2·H2O (1.0 equiv.), DMSO (2.0 equiv.) and silica gel
(0.4 g), 30 Hz, 30 min.
pling was explored. As shown in Table 2, reactions
with electron-donating group (Me, Et, i-Pr, t-Bu, OMe,
or dioxol) and electron-withdrawing group (Cl, F, CF3,
or MeOOC) substituted phenylboronic acids at ortho-,
meta- or para-positions were well tolerated and
exhibited excellent mono-arylation selectivity. Among (3aa–3ac) were obtained by the reaction of multi-
which, electron-rich phenylboronic acids were pre- substituted cyclic olefins, while cyclohexene exclu-
ferred, offering the corresponding products in satisfac- sively gave styrenyl olefin (3ad). Gratifyingly, a wide
tory yields (up to 85%). Of note, the steric hindrance range of acyclic olefins underwent the coupling
properties of arylboronic acids did not show significant smoothly: either unbiased aliphatic, multi-substituted,
influences on the reactions (3ba–3ca vs 3ea), high- non-terminal or functionalized alkenes were tolerated
lighted by the use of disubstituted phenylboronic acids (3ae–3al). In all cases, only the E-isomers were
that gave very beneficial yields (3ma–3pa).
selectively obtained, and the mono-arylations were
In view of the forementioned results, we turned our also regioselective, no branched[4a,c] or allylic
attention to the scope of activated and unactivated products[4b,5j–l] were observed. However, other inacti-
olefins (Table 3). Inert cyclic olefins as important vated alkenes with “α-methyl” such as prop-1-en-2-
starting materials for the synthesis of natural products, ylbenzene, 1-methyl-4-(prop-1-en-2-yl)cyclohex-1-ene
lubricants and functional materials[2d,5h] were initially and (2-methylprop-1-en-1-yl)benzene (see Table S2 in
surveyed. It was interesting to find that allylic products Supporting Information) showed extremely poor reac-
Adv. Synth. Catal. 2019, 361, 1–8
3
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
tivity which gave no desired products or other side- arylation conditions (4aj and 4ak). The advantage of
products. In addition, pharmacological important heter- mechanochemical protocol on reaction selectivity was
oaromatics like furan, thiophene and indole were also demonstrated by a comparative experiment carried
amenable to the mono-arylation reactions via direct C– out under solvent-based conditions that gave only 19%
H activation with a slight variation of the oxidative yield with mono-arylation product 3aa as the major
conditions (3qf–3sf). This mechanochemical protocol one.
was highlighted by a comparative experiment carried
out under solvent-based conditions that gave only 20% and bis-arylations of unactive olefins was demon-
product (3aa) after 24 h heating. strated by the scale-up reactions in relative low catalyst
The remarkable advantage of the selective mono-
Efficacy of the present reaction protocol was further and oxidant loadings, short reaction times and absence
established with bis-arylation of olefins in a DDQ/ of toxic solvent (Scheme 2).
TCA-controlled strategy (Table 4). Electron-rich, elec-
Table 4. Substrate scope study for bis-arylation.[a]
Scheme 2. Scale up reaction of mono- and bis-arylations.
Control experiments were further performed to get
insight into the reaction mechanism (Scheme 3).
Intermolecular competition experiments between dif-
ferent para-substituted phenylboric acid (1e and 1k)
revealed that 1e conspicuously outcompeted 1k for
both mono-, and bis-arylation reactions (Scheme 3a).
Specifically, electron-donating substrates are more
[a] Reaction conditions: 1a (1.0 mmol), 2a (0.5 mmol), Pd
(OAc)2 (10 mol%), DDQ (1.5 equiv.), TCA (3.0 equiv.) and
silica gel (0.4 g) were placed in a stainless-steel vessel with
two stainless-steel balls (ø=1.2 cm) milling at 20 Hz for
reactive than electron-withdrawing substrates during
transmetalation.[16] A sequential arylation of 3aa
carried out under standard bis-arylation conditions
gave 4aa in 63% yield, implying that the bis-arylation
goes by a stepwise coupling process (Scheme 3b).
Further reaction kinetics of bis-arylation demonstrated
that mono-arylation is initially faster than bis-arylation.
With an increasing of 4aa concertation, bis-arylation
rapidly overrode mono-arylation, and the amounts of
3aa continuously decreased after 5 min (Scheme 3c).
On the basis of the experimental results and
30 min.
[b] Isolated yields. The yield of mono-/bis-arylation ratio is
shown within parentheses.
[c] Comparative experiment: 1a (1.0 mmol), 2a (0.5 mmol), Pd
(OAc)2 (10 mol%), DDQ (1.5 equiv.), TCA (3.0 equiv.) and
DMF (5 mL), 50 C, 24 h.
°
tron-neutral and electron-poor phenylboronic acids
were generally well tolerated in the reaction of cyclic literature reports,[17] a plausible reaction mechanism
and acyclic olefins, giving bis-coupling products in was proposed and is shown in Scheme 4. Phenyl-
moderate to good yields (53% to 78%) and excellent palladium (II) species A was first formed by trans-
selectivity (> 2:98). Expectedly, the electronic effects metallation of phenylboronic acid, followed by migra-
and substitution patterns of the phenylboronic acids tory insertion of the olefin to produce the intermediate
were mostly in accordance with those of mono- B. Then, β-hydride elimination of B gave product 3aa
arylations (4aa–4ca, 4ea, 4fa and 4ka), while ortho- and palladium hydride (HPdX). A second migratory
and meta-substituted phenylboronic acids showed insertion of 3aa with A resulted in intermediate C,
inferior yields (4ba and 4ca). Distinctively, the bis- which underwent another β-hydride elimination to
arylation reactions of methyl methacrylate 2j and butyl furnish bis-arylation product 4aa. Finally, the Pd(0)
methacrylate 2k underwent a second arylation of species obtained in the reductive elimination of HPdX
allylic products that were not formed under mono-
Adv. Synth. Catal. 2019, 361, 1–8
4
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
simple conversion of accessible starting materials to
valuable alkenylbenzenes.
Experimental Section
Typical procedure for the synthesis of methyl 5-phenyl-
cyclopent-1-ene-1-carboxylate 3aa: A mixture of phenyl-
boronic acid 1a (0.5 mmol, 1.0 equiv.), methyl cyclopent-1-
ene-1-carboxylate 2a (0.5 mmol, 1.0 equiv.), Pd(OAc)2
(0.05 mmol, 10 mol%), DDQ (0.1 mmol, 20 mol%), TCA
(1.0 mmol, 2.0 equiv.) and silica gel (0.4 g) was placed in a
50 mL screw-capped stainless-steel vessel, along with two
stainless-steel balls (ø=1.2 cm, ΦMB =0.036). Then, the vessel
was placed in the mixer mill, and the contents were milled at
20 Hz for 30 min. At the end of the experiment, the mixture
was scratched from the vessel and purified by column
chromatography (Alumina-N; petroleum ether/ethyl acetate,
100:1–50:1) to give the desired product.
Typical procedure for the synthesis of methyl 2,5-diphenyl-
cyclopent-1-ene-1-carboxylate 4aa: A mixture of phenyl-
boronic acid 1a (1.0 mmol, 2.0 equiv.), methyl cyclopent-1-
ene-1-carboxylate 2a (0.5 mmol, 1.0 equiv.), Pd(OAc)2
(0.05 mmol, 10 mol%), DDQ (0.75 mmol, 1.5 equiv.), TCA
(1.5 mmol, 3.0 equiv.) and silica gel (0.4 g) was placed in a
50 mL screw-capped stainless-steel vessel, along with two
stainless-steel balls (ø=1.2 cm, ΦMB =0.036). Then, the vessel
was placed in the mixer mill, and the contents were milled at
20 Hz for 30 min. At the end of the experiment, the mixture
was scratched from the vessel and purified by column
chromatography (Alumina-N; petroleum ether/ethyl acetate,
100:1–50:1) to give the desired product.
Scheme 3. Control experiments.
Typical procedure for the synthesis of methyl (E)-3,3-
dimethyl-5-(5-methylthiophen-2-yl)pent-4-enoate 3qf:
A
mixture of 2-methylthiophene 1q (0.5 mmol, 1.0 equiv.), meth-
yl 3,3-dimethylpent-4-enoate 2f (0.5 mmol, 1.0 equiv.), Pd
(OAc)2 (0.05 mmol, 10 mol%), Cu(OAc)2·H2O (0.5 mmol,
1.0 equiv.), DMSO (1.0 mmol, 2.0 equiv.) and silica gel (0.4 g)
was placed in a 50 mL screw-capped stainless-steel vessel,
along with two stainless-steel balls (ø=1.2 cm, ΦMB =0.036).
Then, the vessel was placed in the mixer mill, and the contents
were milled at 30 Hz for 30 min. At the end of the experiment,
the mixture was scratched from the vessel and purified by
column chromatography (Alumina-N; petroleum ether/ethyl
acetate, 100:1–50:1) to give the desired product.
Scheme 4. Plausible mechanism.
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (No. 21978270 and 21406201) for
financial support.
from two β-hydride elimination process was oxidized
by DDQ to regenerate the Pd(II) species.
In summary, we have elaborated the Pd(II)-cata-
lyzed ligand- and solvent-free oxidative arylation of
cyclic and acyclic olefins. The mono- and bis-arylation
were achieved through a DDQ/TCA-controlled mecha-
nochemical strategy. Both arylboronic acids and heter-
oaromatics were tolerated in the reaction with a wide
range of unactivated olefins, and provided the desired
products in satisfactory yields with excellent selectivity
even in the gram scale. The present reaction allowed
References
[1] a) S. H. Cho, J. Y. Kim, J. Kwak, S. Chang, Chem. Soc.
Rev. 2011, 40, 5068–5083; b) C. Liu, H. Zhang, W. Shi,
A. Lei, Chem. Rev. 2011, 111, 1780–1824; c) N. Gulzar,
Adv. Synth. Catal. 2019, 361, 1–8
5
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
B. Schweitzer-Chaput, M. Klussmann, Catal. Sci. Tech-
nol. 2014, 4, 2778–2796.
Huang, C. Huang, W. Wu, H. Jiang, J. Org. Chem. 2015,
80, 1235–1242.
[2] a) J. L. Bras, J. Muzart, Chem. Rev. 2011, 111, 1170–
1214; b) J. Yamaguchi, A. D. Yamaguchi, K. Itami,
Angew. Chem. Int. Ed. 2012, 51, 8960–9009; c) H. P. L.
Gemoets, V. Hessel, T. Noël, Org. Lett. 2014, 16, 5800–
5803; d) C. J. C. Lamb, B. G. Nderitu, G. McMurdo,
J. M. Tobin, F. Vilela, A. L. Lee, Chem. Eur. J. 2017, 23,
18282–18288; e) W. Li, Y. Zhao, S. Mai, Q. Song, Org.
Lett. 2018, 20, 1162–1166; f) A. Crusco, H. Whiteland,
R. Baptista, J. E. F. Thomas, M. Beckmann, L. A. J. Mur,
R. J. Nash, A. D. Westwell, K. F. Hoffmann, ACS Infect.
Dis. 2019, 5, 1188–1199.
[3] a) G. G. Pawar, G. Singh, V. K. Tiwari, M. Kapur, Adv.
Synth. Catal. 2013, 355, 2185–2190; b) K. Seth, M.
Bera, M. Brochetta, S. Agasti, A. Das, A. Gandini, A.
Porta, G. Zanoni, D. Maiti, ACS Catal. 2017, 7, 7732–
7736; c) S. Maity, P. Dolui, R. Kancherla, D. Maiti,
Chem. Sci. 2017, 8, 5181–5185; d) M.-Z. Lu, X.-R.
Chen, H. Xu, H.-X. Dai, J.-Q. Yu, Chem. Sci. 2018, 9,
1311–1316; e) T. K. Achar, X. Zhang, R. Mondal, M. S.
Shanavas, S. Maiti, S. Maity, N. Pal, R. S. Paton, D.
Maiti, Angew. Chem. Int. Ed. 2019, 58, 2–10.
[7] a) U. Pindur, R. Adam, Helv. Chim. Acta. 1990, 73, 827–
838; b) K. Mikami, M. Hatano, M. Terada, Chem. Lett.
1999, 28, 55–56; c) K. Akiyama, K. Wakabayashi, K.
Mikami, Adv. Synth. Catal. 2005, 347, 1569–1575;
d) K. S. Yoo, J. O’Neill, S. Sakaguchi, R. Giles, J. H.
Lee, K. W. Jung, J. Org. Chem. 2010, 75, 95–101; e) H.
Lia, A. Gao, X.-Y. Liu, C.-H. Ding, B. Xu, X.-L. Hou,
Synthesis 2017, 49, 159–166.
[8] a) N. Gigant, F. Quintin, J.-E. Bäckvall, J. Org. Chem.
2015, 80, 2796–2803; b) P. Annamalai, K.-C. Hsu, S.
Raju, H.-C. Hsiao, C.-W. Chou, G.-Y. Lin, C.-M. Hsieh,
P.-L. Chen, Y.-H. Liu, S.-C. Chuang, J. Org. Chem.
2018, 83, 3840–3856.
[9] For selected reviews, see: a) G.-W. Wang, Chem. Soc.
Rev. 2013, 42, 7668–7700; b) J. G. Hernández, T. Friščić,
Tetrahedron Lett. 2015, 56, 4253–4265; c) J. G. Hernán-
dez, Chem. Eur. J. 2017, 23, 17157–17165; d) J. G.
Hernández, C. Bolm, J. Org. Chem. 2017, 82, 4007–
4019; e) J. L. Howard, Q. Cao, D. L. Browne, Chem. Sci.
2018, 9, 3080–3094; f) D. Tan, T. Friščić, Eur. J. Org.
Chem. 2018, 1, 18–33; g) C. Bolm, J. G. Hernández,
Angew. Chem. Int. Ed. 2019, 58, 3285–3299.
[4] a) C. Zheng, D. Wang, S. S. Stahl, J. Am. Chem. Soc.
2012, 134, 16496–16499; b) N. Gigant, J.-E. Bäckvall, [10] a) G. N. Hermann, P. Becker, C. Bolm, Angew. Chem.
Org. Lett. 2014, 16, 4432–4435; c) A. Deb, D. Maiti,
Eur. J. Org. Chem. 2017, 1239–1252.
Int. Ed. 2016, 55, 3781–3784; b) T. Raj, H. Sharma,
Mayank, A. Singh, T. Aree, N. Kaur, N. Singh, D. O.
Jang, ACS Sustainable Chem. Eng. 2017, 5, 1468–1475;
c) A. Y. Li, A. Segalla, C.-J. Li, A. Moores, ACS
Sustainable Chem. Eng. 2017, 5, 11752–11760; d) Z.-Z.
Gu, F.-C. Guo, P. Zhang, Y.-J. Qin, Z.-X. Guo,
Tetrahedron Lett. 2019, 60, 1687–1690.
[5] For studies of utilizing ligands to promote/accelerate
reactions, see: a) D. J. Berrisford, C. Bolm, K. B.
Sharpless, Angew. Chem. Int. Ed., 1995, 34, 1057–1070;
b) Y.-H. Zhang, B.-F. Shi, J.-Q. Yu, J. Am. Chem. Soc.
2009, 131, 5072–5074; c) A. Kubota, M. H. Emmert,
M. S. Sanford, Org. Lett. 2012, 14, 1760–1763; d) Y. Li, [11] Y. Pang, T. Ishiyama, K. Kubota, H. Ito, Chem. Eur. J.
Z. Qi, H. Wang, X. Fu, C. Duan, J. Org. Chem., 2012, 2019, 25, 4654–4659.
77, 2053–2057; e) J. H. Delcamp, P. E. Gormisky, M. C. [12] a) J. L. Howard, M. C. Brand, D. L. Browne, Angew.
White, J. Am. Chem. Soc. 2013, 135, 8460–8463; f) X.
Cong, H. Tang, C. Wu, X. Zeng, Organometallics 2013,
32, 6565–6575; g) A. Deb, S. Bag, R. Kancherla, D.
Chem. Int. Ed. 2018, 57, 16104–16108; b) M. Bilke, P.
Losch, O. Vozniuk, A. Bodach, F. Schüth, J. Am. Chem.
Soc. 2019, 141, 11212–11218.
Maiti, J. Am. Chem. Soc., 2014, 136, 13602–13605; [13] a) K. Jia, J.-B. Yu, Z.-J. Jiang, W.-K. Su, J. Org. Chem.
h) S. E. Walker, C. J. C. Lamb, N. A. Beattie, P. Nikode-
miak, A.-L. Lee, Chem. Commun. 2015, 51, 4089–4092;
i) P. Wang, P. Verma, G. Xia, J. Shi, J. X. Qiao, S. Tao,
P. T. W. Cheng, M. A. Poss, M. E. Farmer, K.-S. Yeung,
J.-Q. Yu, Nature 2017, 551, 489–454. For studies of
utilizing directing groups to accelerate reactions and
2016, 81, 6049–6055; b) J.-B. Yu, Y. Zhang, Z.-J. Jiang,
W.-K. Su, J. Org. Chem. 2016, 81, 11514–11520; c) J.
Yu, Z. Hong, X. Yang, Y. Jiang, Z. Jiang, W. Su,
Beilstein J. Org. Chem. 2018, 14, 786–795; d) J. Yu, C.
Zhang, X. Yang, W. Su, Org. Biomol. Chem. 2019, 17,
4446–4451.
control selectivity, see: j) S. Maity, R. Kancherla, U. [14] a) J. Zhou, C. Jin, X. Lia, W. Su, RSC Adv. 2015, 5,
Dhawa, E. Hoque, S. Pimparkar, D. Maiti, ACS Catal.
2016, 6, 5493–5499; k) X. Xue, J. Xu, L. Zhang, C. Xu,
Y. Pan, L. Xu, H. Li, W. Zhang, Adv. Synth. Catal. 2016,
358, 573–583; l) R. Manoharan, G. Sivakumar, M.
Jeganmohan, Chem. Commun. 2016, 52, 10533–10536.
7232–7236; b) Z. Guo, C. Jin, J. Zhou. W. Su, RSC Adv.
2016, 6, 79016–79019; c) Z. Guo, X. Jiang, C. Jin, J.
Zhou, B. Sun, W. Su, Synlett 2017, 28, 1321–1326; d) B.
Sun, Y. Wang, D. Li, C. Jin, W. Su, Org. Biomol. Chem.
2018, 16, 2902–2909.
[6] a) C. Zhu, J. R. Falck, Angew. Chem. Int. Ed. 2011, 50, [15] a) Y. Fujiwara, I. Moritani, S. Danno, R. Asano, S.
6626–6629; b) M. Chen, J. Wang, Z. Chai, C. You, A.
Lei, Adv. Synth. Catal. 2012, 354, 341–346; c) T.-S. Mei,
E. W. Werner, A. J. Burckle, M. S. Sigman, J. Am. Chem.
Soc. 2013, 135, 6830–6833; d) L. Zhang, C. Dong, C.
Ding, J. Chen, W. Tang, H. Li, L. Xu, J. Xiao, Adv.
Synth. Catal. 2013, 355, 1570–1578; e) J. Zheng, L.
Teranishi, J. Am. Chem. Soc. 1969, 91, 7166–7169; b) C.
Jia, W. Lu, T. Kitamura, Y. Fujiwara, Org. Lett. 1999, 1,
2097–2100; c) W.-L. Chen, Y.-R. Gao, S. Mao, Y.-L.
Zhang, Y.-F. Wang, Y.-Q. Wang, Org. Lett. 2012, 14,
5920–5923.
Adv. Synth. Catal. 2019, 361, 1–8
6
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
asc.wiley-vch.de
[16] a) W. Jin, W.-T. Wong, G.-L. Law, ChemCatChem 2014,
6, 1599–1603; b) A. Vasseur, C. Laugel, D. Harakat, J.
Muzart, J. L. Bras, Eur. J. Org. Chem. 2015, 5, 944–948;
c) H. Zhang, Z. Yang, Q. Ma, J. Liu, Y. Zheng, M. Guan,
Y. Wu, Green Chem. 2018, 20, 3140–3146.
S. Roy, M. S. Subhas, M. L. Kantam, B. Sreedhar, Adv.
Synth. Catal. 2008, 350, 1968–1974; c) A.-L. Lee, Org.
Biomol. Chem. 2016, 14, 5357–5366; d) D. S. Lee, E. J.
Cho, Org. Biomol. Chem. 2019, 17, 4317–4325.
[17] a) Y. C. Jung, R. K. Mishra, C. H. Yoon, K. W. Jung,
Org. Lett., 2003, 5, 2231–2234; b) P. R. Likhar, M. Roy,
Adv. Synth. Catal. 2019, 361, 1–8
7
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
These are not the final page numbers!

COMMUNICATIONS
Mechanochemical Oxidative Heck Coupling of Activated and
Unactivated Alkenes: A Chemo-, Regio- and Stereo-Con-
trolled Synthesis of Alkenylbenzenes
Adv. Synth. Catal. 2019, 361, 1–8
J. Yu, H. Shou, W. Yu, H. Chen, W. Su*