Remote Arylative Substitution of Alkenes Possessing an Acetoxy Group via β-Acetoxy Elimination

Article abstract of DOI:10.1002/anie.202111396

Palladium-catalyzed remote arylative substitution was achieved for the reaction of arylboronic acids with alkenes possessing a distant acetoxy group to provide arylation products having an alkene moiety at the remote position. The use of β-acetoxy elimination as a key step in the catalytic cycle allowed for regioselective formation of unstabilized alkenes after chain walking. This reaction was applicable to various arylboronic acids as well as alkene substrates.

Full text of DOI:10.1002/anie.202111396

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Accepted Article
Title: Remote Arylative Substitution of Alkenes Possessing an Acetoxy
Group via β-Acetoxy Elimination
Authors: Kazuma Muto, Takaaki Kumagai, Fumitoshi Kakiuchi, and
Takuya Kochi
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10.1002/anie.202111396
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COMMUNICATION
Remote Arylative Substitution of Alkenes Possessing an Acetoxy
Group via β-Acetoxy Elimination
Kazuma Muto, Takaaki Kumagai, Fumitoshi Kakiuchi, and Takuya Kochi*
Abstract: Palladium-catalyzed “remote arylative substitution” was
achieved for the reaction of arylboronic acids with alkenes possessing
a distant acetoxy group to provide arylation products having an alkene
moiety at the remote position. The use of β-acetoxy elimination as a
key step in the catalytic cycle allowed for regioselective formation of
unstabilized alkenes after chain walking. This reaction was applicable
to various arylboronic acids as well as alkene substrates.
Remote functionalization of organic compounds via alkene
isomerization (or chain walking) has been attracting growing
attention, because it would provide unique methods to efficiently
transform multiple positions of organic molecules in a designed
manner.[1] Various reactions in this category have been
developed using catalysts containing metals such as Pd,[2,3,4,5]
Ni,[6] and Zr,[7] but the types of reactions are still limited,
considering the number of classical transition-metal catalyzed
reactions. For example, catalytic allylic substitutions have been
well studied and used considerably in organic synthesis (Figure
1a), but the corresponding “remote” substitutions have been
scarcely explored (Figure 1b).
One of the reasons for the difficulty in expansion of the
reaction diversity is that only a limited number of strategies are
available for selective product formation by effectively controlling
the selectivity of the final step (termination) in the catalytic cycle.
Redox-relay Mizoroki-Heck-type reaction[3,4,5] is one of the most
extensively studied in this field, and three strategies have been
used to terminate the reaction: (i) conversion of alcohols to
carbonyl groups (Figure 1c),[3] (ii) formation of π-allyl (or benzylic)
intermediates, followed by nucleophilic attack (Figure 1d), [4] and
[5]
(iii) formation of α,β-unsaturated systems (Figure 1e).
Selectivity of all of these reactions essentially relies on the
formation of thermodynamically stable products or intermediates.
Other types of remote functionalizations involving alkene
isomerization mostly use similar termination strategies or
formation of bonds at positions where metal-carbon bonds are
relatively stabilized such as terminal or benzylic positions.[1b,c]
By taking consideration of the available termination strategies,
Figure 1. Functionalization of Alkenes via Chain Walking Using Various
Termination Strategies.
regioselective formation of a simple alkene, which is not
resonance stabilized, is challenging, because this type of alkene
can be easily isomerized to give a more thermodynamically stable
one or a complex mixture of isomers. In fact, we have reported
the chain-walking cycloisomerization of 1,n-dienes to form five
alkene left in the product after chain walking in most cases.[8] In
-membered ring products but could not control the position of the
order to form an alkene moiety regioselectively after chain walking,
we envisioned that β-acetoxy elimination can be used, because it
[*]
K. Muto, T. Kumagai, Prof. Dr. F. Kakiuchi, Dr. T. Kochi
Department of Chemistry, Faculty of Science and Technology,
Keio University
3-14-1 Hiyoshi, Kohoku-ku, Yokohama, 223-8522 (Japan)
E-mail: kochi@chem.keio.ac.jp
would irreversibly generate an alkene at the position of the
acetoxy group. The use of β-acetoxy elimination for selective
formation of alkene has been reported previously.[9,10] Particularly,
Sawamura and co-workers developed a palladium-catalyzed
regioselective allylic arylation via a carbometalation/β-acetoxy
elimination pathway,[9] and we speculated that incorporation of a
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10.1002/anie.202111396
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chain-walking mechanism to this reaction may lead to
development of an alkene arylation with formation of a new alkene
moiety at a remote position. The use of β-elimination of a leaving
group in reactions via chain walking has been limited to a few
examples such as Ma’s palladium-catalyzed reaction of allenoic
acids with alkenes with a remote bromo group, which is
considered to proceed via allenoic acid cyclization, chain walking,
and β-bromo elimination (Figure 1f),[11] and the chain walking/β-X
elimination strategy has not been used for simple alkene arylation
reactions.
Here we report that palladium-catalyzed “remote arylative
substitution” was achieved for the reaction of arylboronic acids
with alkenes possessing a distant acetoxy group to provide
arylation products having an alkene moiety at the remote position.
The use of β-acetoxy elimination as a key step in the catalytic
cycle allowed for regioselective formation of unstabilized alkenes
in redox-relay Mizoroki-Heck-type arylation. This reaction was
applicable to various arylboronic acids and alkene substrates.
When a reaction of phenylboronic acid (1a) with a terminal
alkene bearing a remote acetoxy group (2a) was performed in the
presence of 10 mol % of Pd(OAc)2, 12 mol % of 1,10-
methylphenylboronic acids (entries 2 and 3). The electronic effect
of the substituents were investigated using 4-substituted
arylboronic acids (entries 4-10), and it was shown that
introduction of electron-withdrawing groups generally provides
improved linear/branched ratios. Various reactive functional
groups including chloro (entry 7), bromo (entry 8), and cyano
(entry 9) groups tolerated the reaction conditions to offer the
corresponding products in high yields. A variety of arylboronic
acids can also be used for the alkenes possessing a longer chain
of methylene spacers. The reactions of 2a with phenylboronic acid
1a as well as 2- and 4-substituted arylboronic acids gave the
corresponding products in 32-91% yields (entries 11-15).
Terminal alkene 2c, possessing 7 methylene units, can also react
with 1a via chain walking over 7 carbons to give the corresponding
product in 64% yield (entry 16).
Table 1. Scope of Arylboronic Acids for the Remote Arylative Substitution
of Terminal Alkenes.[a]
phenanthroline (3a), and 10 mol
% of AgSbF6 in 1,2-
dichloroethane (DCE) at 60 ºC for 24 h, using similar reaction
conditions to Sawamura’s allylic arylation,[9] the remote arylative
substitution proceeded to form the alkene moiety regioselectively
and gave the desired arylation product 4aa in 79% GC yield
(Scheme 1). However, the product was obtained as a 2.2:1
mixture of linear and branched products. Ligand screening was
then conducted to improve the linear/branched ratio and pyridine-
isoxazole ligand 3b[12] was found to provide 4aa with 3.5:1
selectivity in a slightly lower yield. Optimization of the reaction
conditions further improved the selectivity to 4.0:1 and product
4aa was obtained in 80% GC yield (Tables S2 and S3).
entry
1
Ar
n
1
1
1
1
1
1
1
1
1
1
3
3
3
3
3
7
time (h)
48
isolated yield (%)
82 (4ab)
80 (4bb)
63 (4cb)
36 (4db)
75 (4eb)
59 (4fb)
l/b
8.9
Ph (1a)
2
2-MeC6H4 (1b)
3-MeC6H4 (1c)
4-MeOC6H4 (1d)
4-FC6H4 (1e)
4-MeC6H4 (1f)
4-ClC6H4 (1g)
4-BrC6H4 (1h)
4-NCC6H4 (1i)
4-F3CC6H4 (1j)
Ph (1a)
48
12
11
3
72
4
72
6.3
5
48
7.5
8.3
8.0
9.7
9.8
6
72
7
48
85 (4gb)
84 (4hb)
93 (4ib)
8
48
9
48
10
11
12
13
14
15
16
48
75 (4jb)
12
12
80 (4aa)
32 (4ba)
67 (4fa)
4.1
5.7
3.4
4.3
5.2
3.0
2-MeC6H4 (1b)
4-MeC6H4 (1f)
4-NCC6H4 (1i)
4-F3CC6H4 (1j)
Ph (1a)
48
12
24
84 (4ia)
24
91 (4ja)
12
64 (4ac)
[a] Reaction conditions: 1 (0.15 mmol), 2 (0.10 mmol), Pd(OAc)2 (0.010
mmol), 3b (0.012 mmol), AgSbF6 (0.008 mmol), DCE (60 mL), 60 ºC.
The reactions of terminal alkenes possessing substituents
other than a tert-butyl group at the α-position of an acetoxy group
are shown in Scheme 2. The substrate having an isopropyl group
(2d) gave the corresponding phenylation product 4ad in 62% yield
with a 9.7 linear/branched ratio, which was improved to 12 for the
reaction with 4-trifluoromethylphenylboronic acid (1j). Higher
linear/branched ratios were observed for the reaction of an alkene
possessing a phenyl group (2e) with 1a and 1j. Substrates derived
from tertiary alcohols were also applicable to this reaction. While
the reaction of cyclohexane derivative 2f with 1b gave product 4af
in 76% yield with a linear/branched ratio of 21, installation of a
homoprenyl group on an aromatic ring was achieved in the
reaction of 1j with α,α-dimethylhomoallyl acetate 2g to give
product 4jg in 63% yield with a 26 linear/branched ratio.
Scheme 1. Remote arylative substitution of terminal alkene 2a with 1a
With the optimized reaction conditions in hand, the scope of
arylboronic acids was examined using terminal alkenes with
various lengths of the methylene chain (Table 1). The reactions of
homoallyl acetate 2b mostly give the corresponding products in
good yields with high regioselectivity (entries 1-10). The reaction
of 2b with phenylboronic acid (1a) provided the product in 82%
isolated yield with a 8.9 linear/branched ratio (entry 1), which was
improved to 12:1 and 11:1 for the reaction using 2-methyl- and 3-
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10.1002/anie.202111396
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Scheme 3. Remote arylative substitution with benzoate 5 and phenyl ether 6
Next, we explored the reactivity of substrates having 1,1-
disubstituted alkenes. After optimization of the reaction conditions
(Table S4), it was found that the remote arylative substitution of
1,1-disubstituted alkene 2h with 1a provided phenylation product
4ah with exclusive regioselectivity in 77% isolated yield (82% GC
yield), when the reaction was conducted in acetone using 3a as a
ligand (Table 2, entry 1). Regioselective formation of C–C bonds
at the terminal position for insertion of 1,1-disubstituted alkenes
to Pd–Ar bonds in a redox-relay Mizoroki-Heck-type reaction was
reported by Sigman and coworkers.[3d] A variety of arylboronic
acids 1 bearing electron-donating and –withdrawing groups were
applicable to this reaction and provided the corresponding
products in high yields (entries 2-11). The reactions of 1,1-
disubstituted alkenes possessing an isopropyl group (2i) and two
methyl groups (2j) instead of a tert-butyl group gave products 4ai
and 4aj in 57 and 53% yields, respectively (entries 12 and 13).
Homoallyl acetate 2k and an alkene substrate possessing 8
methylenes (2l) also reacted with 1a to furnish phenylation
products 4ak and 4al in good yields (entries 14 and 15).
Scheme 2. Scope of terminal alkenes for the remote arylative substitution.
Reaction conditions: 1 (0.15 mmol), 2 (0.10 mmol), Pd(OAc)2 (0.010 mmol), 3b
(0.012 mmol), AgSbF6 (0.008 mmol), DCE (60 mL), 60 ºC.
The proposed catalytic cycle for this arylation is shown in
Figure 2. Transmetallation between acetoxypalladium species A
with arylboronic acid 1 generates arylpalladium species B.
Coordination of 2 and 2,1-insertion gives alkylpalladium species
D. After chain walking of the palladium center (D to E) , β-acetoxy
elimination provides
4 with regenerating acetoxypalladium
species A. A key for the success of this reaction is that chain
walking occurs by the nondissociative mechanism where alkene
exchange does not take place before β-acetoxy elimination,
because alkene exchange during the chain walking process
would provide a palladium hydride species with a substrate, which
leads to the formation of byproducts without an aryl group.
Table 2. Remote Arylative Substitution of 1,1-Disubstituted Alkenes.[a]
entry
1
Ar
2
m
2
R
R’
time
(h)
isolated
yield (%)
Ph (1a)
2h
tBu
H
4
77 (4ah,
82)[b]
2
2-MeC6H4 (1b)
3-MeC6H4 (1c)
4-MeOC6H4 (1d)
4-FC6H4 (1e)
4-MeC6H4 (1f)
4-ClC6H4 (1g)
4-BrC6H4 (1h)
4-NCC6H4 (1i)
4-F3CC6H4 (1j)
4-O2NC6H4 (1k)
Ph (1a)
2h
2h
2h
2h
2h
2h
2h
2h
2h
2h
2i
2
2
2
2
2
2
2
2
2
2
2
2
0
7
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
tBu
iPr
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
8
20
8
78 (4bh)
78 (4ch)
75 (4dh)
75 (4eh)
79 (4fh)
77 (4gh)
75 (4hh)
74 (4ih)
73 (4jh)
73 (4kh)
57 (4ai)
53 (4aj)
67 (4ak)
65 (4al)
3
4
5
20
4
6
7
8
Figure 2. A proposed catalytic cycle.
8
2
9
4
10
11
12
13
14
15[c]
8
Based on the proposed catalytic cycle, the reaction may be
applicable to alkene substrates possessing a leaving group other
than acetoxy group. Consequently, the reaction was examined
using substrates possessing various leaving groups (Scheme 3).
While the reaction of 1a with benzoate 5 and phenyl ether 6
provided arylation product 4ab in 67 and 50% yields, respectively,
trifluoroacetoxy, butoxy, and phthalimidyl groups were not
applicable as leaving groups to this reaction to give less than a
trace amount of 4ab.[13]
4
3
Ph (1a)
2j
Me
tBu
tBu
4
Ph (1a)
2k
2l
4
Ph (1a)
4
[a] Reaction conditions: 1 (0.75 mmol), 2 (0.5 mmol), Pd(OAc)2 (0.05 mmol),
1,10-phenanthroline (0.06 mmol), AgSbF6 (0.05 mmol), acetone (10 mL),
60 ºC. [b] GC yield is shown in parentheses. [c] 1 (0.15 mmol), 2 (0.1 mmol),
Pd(OAc)2 (0.01 mmol), 1,10-phenanthroline (0.012 mmol), AgSbF6 (0.01
mmol), acetone (10 mL), 60 ºC.
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10.1002/anie.202111396
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COMMUNICATION
The remote arylative substitution was applied to the synthesis
of MPAQ, an antifungal agent isolated from hairy roots of
Sesamum indicum (Scheme 4).[14] The reaction of boronic acid 1l
with 2g at 80 ºC for 4 days provided MPAQ (4lg) in 54% yield with
an excellent linear/branched ratio. This result demonstrates the
utility of the reaction for facile installation of an alkyl group
containing an alkenyl moiety, such as homoprenyl group, onto
aromatic rings.
well as the Asahi Glass Foundation. K.M. is also grateful for
support by the Keio University Doctorate Student Grant-in-Aid
Program from Ushioda Memorial Fund.
Conflict of interest
The authors declare no competing financial interest.
Keywords: palladium • chain walking • arylation • alkenes • β-
acetoxy elimination
[1]
a) I. Franzoni, C. Mazet, Org. Biomol. Chem. 2014, 12, 233-241. b) A.
Vasseur, J. Bruffaerts, I. Marek, Nat. Chem. 2016, 8, 209-219. c) H.
Sommer, F. Julia-Hernandez, R. Martin, I. Marek, ACS Cent. Sci. 2018,
4, 153-165. d) T. Kochi, S. Kanno, F. Kakiuchi, Tetrahedron Lett. 2019,
60, 150938.
[2]
a) P. Roesle, C. J. Dürr, H. M. Möller, L. Cavallo, L. Caporaso, S.
Mecking, J. Am. Chem. Soc. 2012, 134, 17696-17703. b) S. Aspin, A.-S.
Goutierre, P. Larini, R. Jazzar, O. Baudoin, Angew. Chem. 2012, 124,
10966-10969; Angew. Chem. Int. Ed. 2012, 51, 10808-10811. c) E.
Larionov, L. Lin, L. Guénée, C. Mazet, J. Am. Chem. Soc. 2014, 136,
16882-16894. d) L. Lin, C. Romano, C. Mazet., J. Am. Chem. Soc. 2016,
138, 10344-10350. e) D. G. Kohler, S. N. Gockel, J. L. Kennemur, P. J.
Waller, K. L. Hull, Nat. Chem. 2018, 10, 333-340.
Scheme 4. Synthesis of MPAQ by the remote arylative substitution
One of the features of the reactions proceeding via
nondissociative chain walking is that the configurations of the
stereocenters present on the alkyl chain where migration of metal
catalysts are maintained.[2d,3d,15] The reaction of 1a with chiral
alkene substrate (S)-2m (94% ee) provided the corresponding
product (R)-4am with 92% ee (Scheme 5). The high level of
retention of the stereochemitry supports the involvement of the
nondissociative chain walking process for the remote arylative
substitution.
[3]
a) R. C. Larock, W.-Y. Leung, S. Stolz-Dunn, Tetrahedron Lett. 1989, 30,
6629-6632. b) E. W. Werner, T.-S. Mei, A. J. Burckle, M. S. Sigman,
Science 2012, 338, 1455-1458. c) T.-S. Mei, E. W. Werner, A. J. Burckle,
M. S. Sigman, J. Am. Chem. Soc. 2013, 135, 6830-6833. d) T.-S. Mei, H.
H. Patel, M. S. Sigman, Nature 2014, 508, 340-344. e) L. Xu, M. J. Hilton,
X. Zhang, P.-O. Norrby, Y.-D. Wu, M. S. Sigman, O. Wiest, J. Am. Chem.
Soc. 2014, 136, 1960-1967. f) Z.-M. Chen, M. J. Hilton, M. S. Sigman, J.
Am. Chem. Soc. 2016, 138, 11461-11464. g) S. Singh, J. Bruffaerts, A.
Vasseur, I. Marek, Nat. Commun. 2017, 8, 14200. h) J. Liu, Q. Yuan, F.
D. Toste, M. S. Sigman, Nat. Chem. 2019, 11, 710-715.
[4]
a) R. C. Larock, Y. D. Lu, A. C. Bain, C. E. Russell, J. Org. Chem. 1991,
56, 4589-4590. b) R. C. Larock, Y. Wang, Y. Lu, C. E. Russell, J. Org.
Chem. 1994, 59, 8107-8114. c) Y. Wang, X. Dong, R. C. Larock, J. Org.
Chem. 2003, 68, 3090-3098. d) C. Han, Z. Fu, S. Guo, X. Fang, A. Lin,
H. Yao, ACS Catal. 2019, 9, 4196-4202.
[5]
[6]
a) C. Zhang, C. B. Santiago, L. Kou, M. S. Sigman, J. Am. Chem. Soc.
2015, 137, 7290-7293. b) Q. Yuan, M. S. Sigman, J. Am. Chem. Soc.
2018, 140, 6527-6530. c) Q. Yuan, M. B. Prater, M. S. Sigman, Adv.
Synth. Catal. 2020, 362, 326-330.
Scheme 5. Remote arylative substitution of chiral alkene substrate (S)-2m. The
enantiomeric excess of (R)-4am was determined by chiral HPLC analysis after
ozonolysis, reduction, and esterification with 3,5-dinitrobenzoyl chloride.
a) D. Janssen-Müller, B. Sahoo, S. Z. Sun, R. Martin, Isr. J. Chem. 2020,
60, 195-206. b) W.-C. Lee, C.-H. Wang, Y.-H. Lin, W.-H. Shih, T.-G. Ong,
Org. Lett. 2013, 15, 5358-5361. c) J. S. Bair, Y. Schramm, A. G. Sergeev,
E. Clot, O. Eisenstein, J. F. Hartwig, J. Am. Chem. Soc. 2014, 136,
13098-13101. d) I. Buslov, J. Becouse, S. Mazza, M. Montandon-Clerc,
X. Hu, Angew. Chem. 2015, 127, 14731-14734; Angew. Chem., Int. Ed.
2015, 54, 14523-14526. e) Y. He, Y. Cai, S. Zhu, J. Am. Chem. Soc.
2017, 139, 1061-1064. f) F. Julia-Hernandez, T. Moragas, J. Cornella, R.
Martin, Nature 2017, 545, 84-89. g) M. Gaydou, T. Moragas, F. Juliá-
Hernández, R. Martin, J. Am. Chem. Soc. 2017, 139, 12161-12164. h) F.
Chen, K. Chen, Y. Zhang, Y. He, Y.-M. Wang, S. Zhu, J. Am. Chem. Soc.
2017, 139, 13929-13935. i) L. Peng, Y. Li, Y. Li, W. Wang, H. Pang, G.
Yin, ACS Catal. 2018, 8, 310-313. j) W. Wang, C. Ding, Y. Li, Z. Li, Z. Li,
L. Peng, G. Yin, Angew. Chem. 2019, 131, 4660-4664; Angew. Chem.
Int. Ed. 2019, 58, 4612-4616. k) S.-Z. Sun, C. Romano, R. Martin, J. Am.
Chem. Soc. 2019, 141, 16197-16201. l) S. Guven, G. Kundu, A. Weßels,
J. S. Ward, K. Rissanen, F. Schoenebeck, J. Am. Chem. Soc. 2021, 143,
8375-8380.
In summary, we developed the palladium-catalyzed remote
arylative substitution of alkenes bearing an acetoxy group. The
reaction with various alkenes possessing a distant acetoxy group
provided arylation products having an alkene moiety at the remote
position. A variety of arylboronic acids were also applicable to this
reaction. Future studies utilizing this “addition/chain
walking/elimination” strategy to other reactions are in progress.
Acknowledgements
This work was supported, in part, by JSPS KAKENHI Grant
Numbers, JP18H01985 (Grant-in-Aid for Scientific Research (B)),
and JP15KT0069 (Grant-in-Aid for Scientific Research (B)) as
[7]
a) N. Chinkov, S. Majumbar, I. Marek, J. Am. Chem. Soc. 2003, 125,
13258-13264. b) N. Chinkov, A. Levin, I. Marek, Angew. Chem. 2006,
This article is protected by copyright. All rights reserved.

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COMMUNICATION
118, 479-482; Angew. Chem. Int. Ed. 2006, 45, 465-468. c) A. Masarwa,
D. Didier, T. Zabrodski, M. Schinkel, L. Ackermann, I. Marek, Nature,
2014, 505, 199-203. d) L. Mola, M. Sidera, S. P. Fletcher, Aust. J. Chem.
2015, 68, 401-403. e) A. Vasseur, L. Perrin, O. Eisenstein, I. Marek,
Chem. Sci. 2015, 6, 2770-2776. f) X. Wang, X. Cui, S. Li, Y. Wang, C.
Xia, H. Jiao, L. Wu, Angew. Chem. 2020, 132, 13710-13714; Angew.
Chem. Int. Ed. 2020, 59, 13608-13612.
Soc. 2005, 127, 72-73. i) K. Shen, X. Han, X. Lu, Z. Hu, Tetrahedron Lett.
2017, 58, 3768-3771.
[11] a) S. Ma, Z. Yu, Angew. Chem. 2003, 115, 1999-2001; Angew. Chem.
Int. Ed. 2003, 42, 1955-1957. b) J. Li, S. Yang, H. Jiang, W. Wu, J. Zhao,
J. Org. Chem. 2013, 78, 12477-12486. c) M. Hu, Z. Lin, J. Li, W. Wu, H.
Jiang, Green. Chem. 2020, 22, 5584-5588.
[12] M. Gutiérrez, M. F. Matus, T. Poblete, J. Amigo, G. Vallejos, L. Astudillo,
J. Pharm. Pharmacol. 2013, 65, 1796-1804.
[8]
[9]
a) T. Kochi, T. Hamasaki, Y. Aoyama, J. Kawasaki, F. Kakiuchi, J. Am.
Chem. Soc. 2012, 134, 16544-16547. b) T. Hamasaki, Y. Aoyama, J.
Kawasaki, F. Kakiuchi, T. Kochi, J. Am. Chem. Soc. 2015, 137, 16163-
16171. c) T. Hamasaki, F. Kakiuchi, T. Kochi, T. Chem. Lett. 2016, 45,
297-299.
[13] The reaction of 1a with an alkene without a leaving group, 8,8-
dimethylnon-1-ene, was also examined but resulted in formation of a
complex mixture of isomers of both the alkene substrate and the
phenylation product.
a) H. Ohmiya, Y. Makida, T. Tanaka, M. Sawamura, J. Am. Chem. Soc.
2008, 130, 17276-17277. b) H. Ohmiya, Y. Makida, D. Li, M. Tanabe, M.
Sawamura, J. Am. Chem. Soc. 2010, 132, 879-889.
[14] a) T. Ogasawara, K. Chiba, M. Tada, Phytochemistry 1993, 33, 1095-
1098. b) R. N. Syed, H. Laurentin, R. Splivallo, P. Karlovsky, Int. J. Agric.
Biol. 2015, 15, 575-581. c) F. Lavaee, M. Moshaverinia, S. A.
MalekHosseini, A. Jamshidzade, M. Zarei, H. Jafarian, P. Haddadi, P.
Badiee, Braz. J. Parm. Sci. 2019, 55, e17479.
[10] a) X. Lu, Top. Catal. 2005, 35, 73-86. b) D. Pan, N. Jiao, Synlett 2010,
11, 1577-1588. c) J. L. Bras, J. Muzart, Tetrahedron 2012, 68, 10065-
10113. d) A. G. Steinig, A. de Meijere, Eur. J. Org. Chem. 1999, 1999,
1333-1344. e) Q. Zhang, X. Lu, J. Am. Chem. Soc. 2000, 122, 7604-
7605. f) J. Rammauth, O. Poulin, S.; Rakhit, S. P. Maddaford, Org. Lett.
2001, 3, 2013-2015. g) B. Mariampillai, C. Herse, M. Lautens, Org. Lett.
2005, 7, 4745-4747. h) M. Lautens, E. Tayama, C. Herse, J. Am. Chem.
[15] Y. Yamasaki, T. Kumagai, S. Kanno, F. Kakiuchi, T. Kochi, J. Org. Chem.
2018, 83, 9322-9333.
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10.1002/anie.202111396
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents
COMMUNICATION
Palladium-catalyzed “remote
arylative substitution” was achieved
for the reaction of arylboronic acids
with alkenes possessing a distant
acetoxy group via nondissociative
chain walking and β-acetoxy
elimination.
K. Muto, T. Kumagai, F. Kakiuchi, T.
Kochi*
Page No. – Page No.
Remote Arylative Substitution of
Alkenes Possessing an Acetoxy
Group via β-Acetoxy Elimination
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