Synthesis of 2-aryloxy butenoates by copper-catalysed allylic C-H carboxylation of allyl aryl ethers with carbon dioxide

Article abstract of DOI:10.1039/c7ob00341b

Efficient synthesis of 2-aryloxy-3-butenoic acid esters by allylic C-H bond carboxylation of allyl aryl ethers with CO₂ has been achieved through deprotonative alumination with an aluminium ate compound (iBu₃Al(TMP)Li) followed by NHC-copper-catalysed carboxylation of the resulting aryloxy allylaluminum species. Functional groups such as halogens (F, Cl, Br, I), CF₃, amino, methylthio, silyloxy and hetero aromatic groups survived the reaction conditions. The regio- and stereoselective transformation (isomerization) of 2-aryloxy-3-butenoate products to (Z)-2-aryloxy-2-butenate isomers has also been achieved in the presence of a catalytic amount of DBU. These transformations thus constitute an efficient protocol for the divergent synthesis of both 2-aryloxy-3- and 2-butenonates from a single allyl aryl ether substrate using CO₂ as a C1 building block.

Full text of DOI:10.1039/c7ob00341b

View Article Online
View Journal
Organic &
Biomolecular
Chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: A. Ueno, M.
Takimoto and Z. Hou, Org. Biomol. Chem., 2017, DOI: 10.1039/C7OB00341B.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Volume 14 Number
1 7 January 2016 Pages 1–372
Organic &
Biomolecular
Chemistry
www.rsc.org/obc
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
author guidelines.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the ethical guidelines, outlined
in our author and reviewer resource centre, still apply. In no
event shall the Royal Society of Chemistry be held responsible
for any errors or omissions in this Accepted Manuscript or any
consequences arising from the use of any information it contains.
ISSN 1477-0520
COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 1 of 6
View Article Online
DOI: 10.1039/C7OB00341B
Org. Biomol. Chem.
ARTICLE
Synthesis of 2-Aryloxy Butenoates by Copper-Catalysed Allylic
C−H Carboxylation of Allyl Aryl Ethers with Carbon Dioxide
Atsushi Ueno,a Masanori Takimotoa,b and Zhaomin Hou*a,b
Received 00th January 20xx,
Accepted 00th January 20xx
The efficient synthesis of 2-aryloxy-3-butenoic acid esters by the allylic C−H bond carboxylation of allyl aryl ethers with CO2
has been achieved through the deprotonative alumination with an aluminium ate compound (iBu3Al(TMP)Li) followed by
the NHC-copper-catalysed carboxylation of the resulting aryloxy allylaluminum species. Functional groups such as halogens
(F, Cl, Br, I), CF3 , amino, methylthio, silyloxy and hetero aromatic groups survived the reaction conditions. The regio- and
stereoselective transformation (isomerization) of the 2-aryloxy-3-butenoate products to the (Z)-2-aryloxy-2-butenate
isomers has also been achieved in the presence of a catalytic amount of DBU. These transformations thus constitute an
efficient protocol for the divergent synthesis of both 2-aryloxy-3- and 2-butenonates from a single allyl aryl ether substrate
using CO2 as a C1 building block.
DOI: 10.1039/x0xx00000x
www.rsc.org/
allylaluminum species towards CO2 remained unexplored.
Recently, the use of CO2 for carboxylation reactions has
received intensive attention.3,8-10 In this context, we have
reported the carboxylation of various substrates,10 including
aryl10f and alkenyl10e aluminum species, with CO2 catalysed by
Introduction
The development of efficient and selective methods for
the synthesis of 2-aryloxy butenoic acid derivatives is of much
interest and importance, because these compounds could
NHC-copper complexes. These studies encouraged us to
examine the allylic C–H carboxylation of aryl allyl ethers with
CO2. Herein, we report the efficient synthesis of 2-aryloxy
butenoates through the copper-catalysed carboxylation of
aryloxy allylaluminum species generated by the deprotonative
serve as useful building blocks for the synthesis of α-aryloxy
carboxylic acid derivatives, which are important structural
motifs in medicinal and bioorganic chemistry.1 Among possible
approaches for the synthesis of 2-aryloxy butenoic acids,2 the
deprotonative allylic C–H carboxylation of allyl aryl ethers with
carbon dioxide (CO2) could, in principle, be the most efficient
and straightforward route. However, such transformation has
not been reported previously.3 A general problem in this
approach is the intrinsic instability of an aryloxy allyl metal
species generated by the deprotonation of an allyl aryl ether
for the carboxylation with CO2. It was previously shown that
the deprotonation of an allylic C–H bond of allyl phenyl ethers
by strong bases such as alkyllithium, lithium amide, and tBuOK
could easily cause undesired side reactions, such as Wittig
rearrangement,4 isomerization5 and deallylation.6 Uchiyama
and co-workers reported the use of an aluminum ate
C−H alumination of allyl aryl ethers with iBu3Al(TMP)Li using
CO2 as a C1 building block. Both 2-aryloxy-3-butenoates and
(Z)-2-aryloxy-2-butenates have been easily obtained in a regio-
and stereoselective fashion from the same allyl aryl ether
substrates under appropriate reaction conditions (see Scheme
1).
cat. [Cu]
ArO
CO2
Bu Al(TMP)Li
i
ArO
ArO
3
COOH
H
"Al"
1) cat. [Cu]
CO2
ArO
2) cat. DBU
COOH
compound such as iBu3Al(TMP)Li (TMP
=
2,2,6,6-
tetramethylpiperidide) as a base for the selective allylic C
−
H
Scheme 1 Regio- and stereodivergent synthesis of α-aryloxy butenoic
deprotonation of allyl aryl ethers without causing apparent
side reactions.7 However, the reactivity of the resulting aryloxy
acids through formal allylic C–H carboxylation of allyl aryl ethers with
CO2
Results and Discussion
Synthesis of methyl 2-aryloxy-3-butenoates
At first, the carboxylation of the allylaluminum species 2a
generated in situ by the deprotonative alumination of allyl
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 2 of 6
View Article Online
DOI: 10.1039/C7OB00341B
ARTICLE
Journal Name
phenyl ether 1a with iBu3Al(TMP)Li in THF was examined
under various conditions. The allylaluminum 2a alone was
relatively unreactive towards CO2 (1 atm) in THF at room
temperature, giving the expected carboxylation product
methyl 2-phenyloxy-3-butenoate 3a only in 10% yield in 2 h
after hydrolytic workup and treatment of the resulting crude
material with TMSCHN2 (Table 1, entry 1). By the initial
catalyst screening, we found that (IMes)CuOtBu (IMes = 1,3-
bis(2,4,6-trimethylphenyl)imidazol-2-ylidene) showed high
catalytic activity for the carboxylation of 2a. In the presence of
(IMes)CuOtBu (10 mol%), the reaction of 2a with CO2
smoothly completed at room temperature in 2 h to afford an
inseparable mixture of 3a and methyl 2-phenyloxy-2-
butenoate 4a (ratio of 85:5) in 90% yield (Table 1, entry 2).
The ratio of 4a increased as the extension of the reaction
period without decrease of the total yield of 3a and 4a (Table
1, entries 2-4). These results suggested that 2-butenoate 4a
was formed through an isomerization of the initial product in
basic condition, which originally lead to 3-butenoate 3a. Also
the reaction temperature had a significant effect on the
10
CuCl/tBuOK e
0
2
35
-
a
The reactions were carried out using iBu3Al(TMP)Li (2.0 equiv.),
substrate (0.5 mmol), catalyst (10 mol%), and CO2 (1 atm) in THF unless
otherwise noted. Isolated yield. The product was obtained as an
inseparable mixture of 3a and 4a. d The yields were calculated by 1H NMR.
e The ratio of Cu salt to tBuOK was 1:1.
b
c
With this optimized condition (Table 1, entry 6) in hand,
we examined the carboxylation of various aryl allyl ethers to
synthesize
2-aryloxy-3-butenoates. The
results
are
summarized in Table 2. Similar to the carboxylation of 1a
,
substituted-phenyl allyl ethers bearing a slightly electron-
donating alkyl group, such as 4-tBu- and 4-Bn- groups, on their
phenyl moiety were good substrate to provide the
corresponding methyl 2-aryloxy-3-butenoates 3b and 3c in
88% and 85% yields, respectively. Also an allyl ether bearing
2,3-dihydro-1H-indenyl group as the aryl moiety also gave the
desired product 3d in high yield. In the same way, methyl 2-(2-
naphtoxy)-3-butenoate 3e (80%) could be prepared from the
corresponding naphthyl allyl ether. Substituted-phenyl allyl
ethers bearing an electron-rich substituent, such as m-NMe2-,
p-SMe-, p-TBDMSO-, and p-MeO groups, on their phenyl
group were also suitable substrate giving the corresponding
selectivity. The reaction at higher temperature (50 ̊C for 48 h)
gave 4a as a major product in 70% yield along with a small
amount of 3a (9%) (Table 1, entry 5). In contrast, 3-butenoate
3a was selectively obtained in 91% yield as a sole product
when the carboxylation of 2a was carried out at 0 °C for 2 h
(Table 1, entry 6). The catalyst prepared in situ from
(IMes)CuCl (10 mol%) and tBuOK (10 mol%) showed almost
same catalytic activity with (IMes)CuOtBu (Table 1, entry 7).
methyl 2-aryloxy-3-butenoate 3f
, 3g, 3h, and 3i in high yields,
selectively. Although these substituents might act as
a
directing group on potential ortho-metallation on the phenyl
ring,11 there was no evidence of such unwanted reaction
under the present reaction conditions. Also electron-
withdrawing property of p-CF3 group on the phenyl ring did
not cause any negative effect, both on reactivity and
regioselectivity; the reaction of allyl p-trifluoromethylphenyl
ether provided methyl 2-aryloxy-3-butenoate 3j in 89% yield.
It is also noteworthy that the carboxylation of p-fluoro-,12 p-
chloro-, p/o-bromo-, and p-iodo-substituted-phenyl allyl
The copper catalysts bearing IPr (IPr
=
1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene) and SIPr (SIPr = 1,3-
bis(2,6-diisopropylphenyl)imidazolidin-2-ylidene) were slightly
less effective (Table 1, entries 8 and 9). In the absence of these
NHC ligands, the yield of 3a was much lower (Table 1, entry
10).
ethers selectively occurred at allylic C
present catalyst conditions, affording the desired
carboxylation products (3k 3l 3m 3n, and 3o) in high yields,
while the C X (X = F, Cl, Br, I) bonds remained unchanged.
−H bond under the
Table 1 Optimization of reaction conditions for the synthesis of
methyl 3-butenoatea
,
,
,
−
Hetero-aromatic units were also acceptable substituents on
the aryl moiety; for instance, 3p was obtained in 75% yield
from the corresponding aryl allyl ether bearing a 2H-1,2,3-
benzotriazol-2-yl group. The carboxylation of aryl allyl ethers
bearing a disubstituted allyl group such as 1q and 1r could also
proceed under the present conditions, though the yields were
slightly lower (3q, 70% and 3r, 65%) than that of the parent
mono-substituted aryl ether (3m). The aryl allyl ether bearing
yield, % b
temp.
(°C)
time
(h)
entry
[cat]
3a
4a
a
γ
-alkyl group gave a mixture of
products. Moreover, the present method could be applicable
to the propargylic C H carboxylation of a phenyl propargyl
α- and γ-carboxylation
1
2
3
4
5
6
7
8
9
-
r.t.
r.t.
r.t.
r.t.
50
0
2
2
10
85
66
45
9
-
5
(IMes)CuOtBu c,d
(IMes)CuOtBu c,d
(IMes)CuOtBu c,d
(IMes)CuOtBu c,d
(IMes)CuOtBu
−
12
24
48
2
20
44
70
-
ether; 2-phenyloxy-3-nonynoate 3s was obtained in in 79%
yield from the corresponding substituted-propargyl ether.
Moreover, this method could be applied to the carboxylation
91
90
70
69
of carbamic acid allyl esters. The allyic C−H carboxylation of
allyl diisopropylcarbamate smoothly proceeded to give the
(IMes)CuCl/tBuOK e
(IPr)CuCl/tBuOK e
(SIPr)CuCl/tBuOK e
0
2
-
corresponding methyl 3-butenoate derivative 3t in 91% yield.
0
2
-
Remarkably, α
underwent the allylic C
-methylallyl diisopropylcarbamate smoothly
H carboxylation at the more sterically
0
2
-
−
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 3 of 6
View Article Online
DOI: 10.1039/C7OB00341B
Journal Name
ARTICLE
hindered position selectively to give carboxylic acid ester 3u allylaluminum species
bearing a quaternary carbon center in 89% yield. Alkyl allyl
ethers were not suitable for the present protocol; the reaction would afford a free 3-butenoic acid which was isolated as
A
would give the aluminum carboxylate
D
regenerating allylcopper species B. The hydrolysis of D
of tert-buyl allyl ether or benzyl allyl ether produced a mixture methyl 3-butenoate 3 after treatment with TMSCHN2.
of uncharacterizable products.
Table 2 Substrate scope on the synthesis of methyl 3-butenoatea
3b, 88%
3d, 90%
3g, 79%
3c, 85%
3f, 75%
3e, 80%
3h, 87%
3i, 86%
3l, 73%
3j, 89%
Scheme 2 A possible reaction pathway for the allylic C−H bond
carboxylation.
3k, 54%
3n, 82%
3q, 70%
3m, 84%
Regio- and stereoselective synthesis of methyl 2-aryloxy-(Z)-
2-butenoates
In addition to 2-aryloxy-3-butenoic acids, 2-aryloxy-2-butenoic
acid derivatives have been recognized as an attractive building
block in organic synthesis,2h,2i,14 therefore, we next examined
the selective synthesis of methyl 2-aryloxy-2-butenoates by
3o, 80%
3r, 65%
3p, 75%
3s, 79%
modifying the present method for the formal allylic C−H
carboxylation. As previously mentioned, in the carboxylation
of 1a, the amount of methyl 2-phenoxy-2-butenoate 4a
increased accompanied by the extended reaction period and
elevated reaction temperature (Table 1, entries 1-6). From
these results, we speculated that isomerization from the initial
product such as
D in Scheme 2 to the secondary product
leading to 4a might take place, possibly through a base-
promoted deprotonation/protonation mechanism because
excess amounts of basic components such as iBu3Al(TMP)Li
3t, 91%
3u, 89%
a
The reactions were carried out using iBu3Al(TMP)Li (2.0 equiv.),
substrate (0.5 mmol), catalyst (10 mol%), and CO2 (1 atm) in THF unless
otherwise noted. b Isolated yield.
exist in the present reaction system and the initial product
D
has an acidic proton placed at
group.
α-position to the carbonyl
Upon this hypothesis, we initially attempted the
isomerization reaction of the isolated methyl 2-phenoxy-3-
butenoate 3a by using a stoichiometric amount of KOtBu and
DBU as the base. Interestingly, the results were quite different
depending on the base used. When 3a was treated with KOtBu
(1.0 equiv.) in THF at room temperature for 24 h, phenol was
obtained as a major product in 80% via deallylation reaction,6
and the yield of the desired isomerization product 4a was only
12%. In contrast, 2-butenoic acid ester 4a was quantitatively
obtained when 3a was treated with DBU (1.0 equiv.) at room
temperature for 24 h. In addition, a catalytic amount of DBU
A
possible reaction mechanism for the present
deprotonative allylic C H carboxylation is shown in Scheme 2.
Deprotonation of an allylic compound by the aluminum ate
base iBu3Al(TMP)Li would generate allylaluminum species
Then, transmetalation between and (IMes)CuOtBu would
proceed to give the allylcopper species along with the
release of Al(OtBu)(iBu)3Li. Carboxylation would take place on
allylcopper species by insertion of CO2 into copper-carbon
bond in
to afford copper carboxylate species C 13
Transmetalation reaction between and another molecule of
−
A
.
A
B
B
B
.
C
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 3
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 4 of 6
View Article Online
DOI: 10.1039/C7OB00341B
ARTICLE
Journal Name
(10 mol%) was effective to complete the isomerization to give
4a in
quantitative yield (Scheme 3). 1H NMR NOE
a
experiments on 4a confirmed that the double bond has a (Z)-
configuration. Moreover, we could achieve the one-pot
synthesis of 4a without isolation of 3a (Table 3); by simply
treating the reaction mixture after the carboxylation of 1a by a
catalytic amount of DBU (10 mol%) at room temperature for
24 h, 4a was obtained in 91% yield in a completely regio- and
stereoselective manner.
4f, 77%
4i, 78%
4e, 82%
4h, 82%
4d, 86%
4g, 79%
4j, 76%
4l, 72%
4k, 52%
Scheme 3 Isomerization of 3a to 4a by using catalytic amount of DBU.
4m, 80%
4n, 78%
This newly developed protocol for the synthesis of 4a was
applicable to various substrates (Table 3). The present method
worked efficiently with the substrates bearing alkyl
substituents (4-tBu, 4-Bn and dihydroindenyl) on the aryl
moieties to give the corresponding 2-aryloxy-(Z)-2-butenoic
4o, 78%
acid ester 4b, 4c and 4d in 87%, 83% and 86% yields,
4p, 80%
respectively. Naphtyl allyl ether was also suitable substrate for
this method involving the DBU-catalysed isomerization and 4e
was selectively obtained in 82% yield. The electron donating
substituents (4-SMe, 3-NMe2 and 4-OMe, 4-OSiMe2tBu) on the
aryl moiety of the substrates did not disturb the DBU-
catalysed isomerization and 2-aryl-(Z)-2-butenoates 4f-i were
obtained in high yields in a regio- and stereoselective manner.
Moreover, the aryl allyl ethers bearing a trifluoromethyl
group, halogen substituent, or benzotriazolyl group on the aryl
moiety could selectively give the desired 2-aryl-(Z)-2-
butenoates 4j-p in moderate to high yields under the similar
conditions. In all cases demonstrated in Table 3, the yields of
a The reactions were carried out using iBu3Al(TMP)Li (2.0 equiv.), substrate
(0.5 mmol), catalyst (10 mol%), DBU (10 mol%), and CO2 (1 atm) in THF
unless otherwise noted. b Isolated yield.
The DBU-catalysed isomerization process could be
explained as illustrated in Scheme 4. In our reaction,
aluminum carboxylate
after carboxylation process. The isomerization would start
with deprotonation of an acidic proton attached to the
carbon of the carbonyl group of by DBU. On this occasion,
the stereo-electronic effect would require the subtracted
proton to be perpendicular to the -face of the allyl group
shown as and E’. Among these two conformers, would be
more favourable due to the lower allylic 1,3-strain,15 thus the
deprotonation would take place preferentially from to afford
[DBU-H]+ and an allyl anion
bearing an anti-configuration.
Then, protonation of would proceed at the sterically less
hindered terminal sp2 carbon by [DBU-H]+ to give aluminum
D was formed as the initial product
α
-
D
π
2-aryl-2-butenoates
the 2-aryl-3-butenoates
mentioned in Table 2. However, the present DBU catalyzed
isomerization was unsuccessful on aryl ally ethers 1q 1r and
4
were almost comparable with those of
E
E
3
obtained in the reactions above-
E
,
F
allyl carbamate 1t. In the reaction of 1q, the isomerization did
not proceed due to the thermodynamic stability of conjugated
styrene moiety even in the presence of an excess amount of
DBU. The reactions of 1q and 1r under the same conditions
gave complicated product mixtures.
F
carboxylate
G
bearing a (Z)-configuration regenerating DBU.
Table 3 Substrate scope on the synthesis of methyl 2-butenoatea
O
COOMe
Bn
4b, 87%
4c, 83%
4a, 91%
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 5 of 6
View Article Online
DOI: 10.1039/C7OB00341B
Journal Name
ARTICLE
Conclusion
I
n summary, we have achieved efficient and regioselective
synthesis of 2-aryloxy-3-butenoic acid esters by formal C
carboxylation of allyl aryl ethers. The reaction consists of the
deprotonative allylic C H bond alumination of the allyl aryl
−
H
−
ethers by an aluminum ate base (iBu3Al(TMP)Li) and the
subsequent carboxylation of the resulting allylaluminum
species with CO2 catalysed by an NHC-copper complex. The
carboxylation proceeds in highly regioselective manner in high
yield and the present protocol features relatively broad
substrate scope, certain functional group tolerance, simple
one-pot reaction operation. Moreover, regioselective
synthesis of (Z)-2-aryloxy-2-butenoic acid esters has also been
realized by DBU-catalysed one-pot double bond isomerization
of the initially formed 2-aryloxy-3-butenoates. Thus, the
divergent synthesis of 2-aryoxy-3- and 2-butenoates from the
single staring materials using CO2 as the C1 building block has
been achieved. These methods could be applied also to
benzylic carboxylation of allylbenzenes or a toluene derivative,
which demonstrated the potential of the present sequential
deprotonative alumination-carboxylation strategy.
Scheme 4 A possible reaction pathway for the isomerization by DBU
Allylic C−H carboxylation of allylbenzenes with CO2
Finally, carboxylations of less acidic substrates such as
allylbenzenes by the present methods were examined. As
shown in Scheme 5, the deprotonative alumination of benzylic
C−H bonds of allylbenzenes 5a and 5b smoothly proceeded by
iBu3Al(TMP)Li and the subsequent Cu-catalysed carboxylation
of the resulting benzylaluminum took place under the similar
conditions to give corresponding methyl 2-aryl-3-butenoate 6a
(85%) and 6b (84%), respectively. When the reaction mixtures
of the carboxylation reactions were treated with DBU (1.0
equiv) at room temperature, isomerization of the generated
aluminum 2-aryl-3-butenoate took place smoothly to afford
methyl (E)-2-aryl-2-butenoates 7a and 7b in high yields.
Moreover, the present protocol could also applicable to the
Acknowledgements
This work was partly supported by a Grant-in-Aid for Scientific
Research (S) (No. 26220802 to Z.H.) and (C) (No. 26460029 to
M.T.) from JSPS.
Notes and references
formal benzylic carboxyation of p-methylbenzamide
provide
potentially reactive aromatic ortho-C
8
to
1
(a) F. Gualtieri, C. Bottalico, A. Calandrella, S. Dei, M. P.
Giovannoni, S. Mealli, M. N. Romanelli, S. Scapecchi, E.
Teodori, N. Galeotti, C. Ghelardini, A. Giotti and A. Bartolini,
J. Med. Chem., 1994, 37, 1712; (b) S. K. Gorla, M. Kavitha, M.
Zhang, J. E. W. Chin, X. Liu, B. Striepen, M. Grzyska, Y. Kim, A.
Joachimiak, L. Hedstrom and G. D. Cuny, J. Med. Chem.,
2013, 56, 4028; (c) K. Mandapati, S. K. Gorla, A. L. House, E.
S. McKenney, M. Zhang, S. N. Rao, D. R. Gollapalli, B. J.
Mann, J. B. Goldberg, G. D. Cuny, I. J. Glomski and L.
9
selectively in 52% yield despite the presence of
−
H bonds.
R
3) H3O+
work up
4) TMSCHN2
COOMe
1) iBu3Al(TMP)Li
(2.0 equiv.)
6a (R = H): 85%
6b (R = OMe): 84%
R
Hedstrom, ACS Med. Chem. Lett., 2014,
5, 846; (d) R. S.
Ferreira, M. A. Dessoy, I. Pauli, M. L. Souza, R. Krogh, A. I. L.
Sales, G. Oliva, L. C. Dias and A. D. Andricopulo, J. Med.
Chem., 2014, 57, 2380; (e) Y. Xu, C. J. Rito, G. J. Etgen, R. J.
Ardecky, J. S. Bean, W. R. Bensch, J. R. Bosley, C. L.
Broderick, D. A. Brooks, S. J. Dominianni, P. J. Hahn, S. Liu, D.
E. Mais, C. M. Rafizadeh, K. M. Ogilvie, B. A. Oldham, M.
Peters, D. K. Rungta, A. J. Shuker, G. A. Stephenson, A. E.
Tripp, S. B. Wilson, L. L. Winneroski, R. Zink, R. F. Kauffman
and J. R. McCarthy, J. Med. Chem., 2004, 47, 2422.
For the synthesis of 2-aryloxy-3-butenoates, see: (a) Y.
Nishimoto, H. Ueda, M. Yasuda, and A. Baba, Angew. Chem.,
Int. Ed., 2012, 51, 8073; (b) Y. Nishimoto, Y. Kita, H. Ueda, H.
Imaoka, K. Chiba, M. Yasuda and A. Baba. Chem. Eur. J., 2016,
22, 11837; (c) Y. Landis and D. Planchenault, Synlett, 1995,
1191. For the synthesis of 2-aryloxy-2-butenoates, see: (d) T.
Padmanathan and M. U. S. Sultanbawa, J. Chem. Soc., 1963,
4210. (e) K. Tanaka, T. Nakai and N. Ishikawa, Chem. Lett.,
1977, 1379; (f) V. Rosnati, A. Saba and A. Salibeni,
2) (IMes)CuOtBu
(10 mol%)
CO2 (1 atm)
3) DBU
(1.0 equiv.)
THF, r.t. 24 h
R
H
5a(R = H)
5b(R = OMe)
4) H3O+
work up
5) TMSCHN2
COOMe
7a (R = H): 82%
7b (R = OMe): 79%
NiPr2
H3O+
work up
N Pr
i
2
1) iBu3Al(TMP)Li
(2.0 equiv.)
2
O
O
2) (IMes)CuOtBu
(10 mol%)
CO2 (1 atm)
H
H
COOH
9: 52%
8
H
Scheme 5. Carboxylation of several allylic and benzylic compounds.
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 5
Please do not adjust margins

Please do not adjust margins
Organic & Biomolecular Chemistry
Page 6 of 6
View Article Online
DOI: 10.1039/C7OB00341B
ARTICLE
Tetrahedron. Lett., 1981, 22, 167; (g) P. Seneci, I. Leger, M.
Journal Name
Chem. Eur. J., 2015, 21, 15218; (h) S. S. Gholap, M. Takimoto,
and Z. Hou, Chem. Eur. J., 2016, 22, 8547; (i) B. Carry, L.
Zhang, M. Nishiura and Z. Hou, Angew. Chem., Int. Ed., 2016,
55, 6257.
Souchet and G. Nadler, Tetrahedron, 1991, 53, 17097; (h) P.
E. Maligres, S. W. Krska, and G. R. Humphrey, Org. Lett.,
2004, 6, 3147; (i) S. Li, S. Zhu, J. Xie, S. Song, C. Zhang, and Q.
Zhou, J. Am. Chem. Soc., 2010, 132, 1172.
For examples of carboxylation reactions via allyl metal
11 (a) W. Bauer, P. A. A. Klusener, S. Harder, J. A. Kanters, A. J.
M. Duisenberg, L. Brandsma and P. V. R. Schleyer,
3
Organometallics, 1988,
T. Hirao, J. Am. Chem. Soc., 1998, 120, 5124; (c) Y. Kim, M.
Kim and F. P. Gabbaı, Org. Lett., 2010, 12, 600; (d) Y. Kim, H.
Zhao and F. P. Gabbaı, Angew. Chem., Int. Ed., 2009, 48
4957; (e) D. W. Slocum, T. K. Reinscheld, C. B. White, M. D.
Timmons, P. A. Shelton, M. G. Slocum, R. D. Sandlin, E. G.
Holland, D. Kusmic, J. A. Jennings, K. C. Tekin, Q. Nguyen, S.
J. Bush, J. M. Keller and P. E. Whitley, Organometallics, 2013,
32, 1674.
7, 552; (b) T.Ishikawa, A. Ogawa and
species without
Nicholas, J. Am. Chem. Soc., 1997, 119
α
-aryloxy group, see: (a) M. Shi and K. M.
5057; (b) R.
,
̈
Johansson and O. F. Wendt, Dalton Trans., 2007, 488; (c)
D.P.Hruszkewycz, J. Wu, N. Hazari and C. D. Incarvito, J. Am.
Chem. Soc., 2011, 133, 3280; (d) J .Wu, N. Hazari, Chem.
Commun., 2011, 47, 1069; (e) H. A. Duong, P. B. Huleatt, Q.
Tan, and E. L. Shuying, Org. Lett., 2013, 15, 4034; (f) B. Miao
and S. Ma, Chem. Commun., 2014, 50, 3285; (g) T. Moragas,
̈
,
J. Cornella and R. Martin, J. Am. Chem. Soc., 2014, 136
,
12 In case of fluoro substituted starting material 1k
,
17702; (i) T. Mita, Y. Higuchi and Y. Sato, Chem. Eur. J., 2015,
21, 16391.
(a) D. R. Dimmel and S. B. Gharpure, J. Am. Chem. Soc., 1971,
93, 3991; (b) W. F. Bailey, M. D. England, M. J. Mealy, C.
deallylation occurred prior to deprotonation and
carboxylation.
13 There might be another pathway for the carboxylation
4
5
process. The resulting allyl copper species
equilibrium with a more sterically accessible
species, in which the copper atom is placed at the terminal
carbon (copper species B’). Then, carboxylation at the
carbon in this copper species B’ by the SE’ mechanism would
take place to give the carboxylate . For related examples,
B
would be in
Thongsornkleeb and L. Teng, Org. Lett., 2000,
Barluenga, F. J. Fañanás, R. Sanz, C. Marcos and M. Trabada,
Org. Lett., 2002, , 1587; (d) S. Strunk and M. Schlosser, Eur.
2, 489; (c) J.
σ
-allyl copper
4
J. Org. Chem., 2006, 4393.
γ
-
(a) D. A. Evans, G. C. Andrews and B. Buckwalter, J. Am.
Chem. Soc., 1974, 96, 5560; (b) W. C. Still and T. L.
Macdonald, J. Am. Chem. Soc., 1974, 96, 5561; (c) C. Su and
P. G. Williard, Org. Lett., 2010, 12, 5378.
C
see: M. Kanai, R. Wada, T. Shibuguchi and M. Shibasaki, Pure
Appl. Chem., 2008, 80, 1055. See also ref 3e.
6
7
8
(a) C. D. Broaddus, J. Org. Chem., 1965, 30, 4131; (b) W. F.
Bailey, M. D. England, M. J. Mealy, C. Thongsornkleeb and L.
Teng, Org. Lett., 2000, 2, 489.
H. Naka, M. Uchiyama, Y. Matsumoto, A. E. Wheatley, M.
McPartin, J. V. Morey and Y. Kondo, J. Am. Chem. Soc., 2007,
129, 1921.
14 For recent examples, see: (a) X. Cheng, J. Xie, S. Li and L.
Zhou, Adv. Synth. Catal., 2006, 348, 1271; (b) P. E. Maligres,
G. R. Humphrey, J. Marcoux, M. C. Hillier, D. Zhao, S. Krska
and E. J. J. Grabowski, Org. Process Res. Dev., 2009, 13, 525;
(c) A. Monos-Turvey, E. M. M. Bulloch, P. J. Rutledge, E. N.
Baker, J. S. Lott and R. J. Payne, ChemMedChem, 2010, 5,
1067.
15 For the example of similar 1,3-allylic strain, see (a) K. N.
Houk, S. R. Moses, Y. Wu, N. G. Rondan, V. Jäger, R. Schohe
and F. R. Fronczek, J. Am. Chem. Soc., 1984, 106, 3880; (b) E.
Recent reviews: (a) T. Sakakura, J.-C. Choi and H. Yasuda,
Chem. Rev., 2007, 107, 2365; (b) R. Martin, A. W. Kleij,
ChemSusChem 2011,
Chem. Commun., 2012, 48, 9956; (d) L. Zhang, Z. Hou, Chem.
Sci., 2013, , 3395 (e) Q. Liu, L. Wu, R. Jackstell and M. Beller,
Nat. Commun., 2015, , 5933. (f) L. Zhang and Z. Hou,
4, 1259; (c) Y. Tsuji and T. Fujihara,
Vedejs and C. K. McClure, J. Am. Chem. Soc., 1986, 108
,
4
1094; (c) K. N. Houk, H. Duh, Y. Wu and S. R. Moses, J. Am.
Chem. Soc., 1986, 108, 2754; (d) M. T. Reetz, F. Kayser and K.
Harms, Tetrahedron Lett., 1992, 33, 3453.
6
Current Opin. Green Sus. Chem, 2017, 3, 17.
Selected recent examples: (a) T. Moragas, M. Gaydou, and R.
Martin, Angew. Chem., Int. Ed. 2016, 55, 5053; (b) K. Nogi, T.
9
Fujihara, J. Terao and Y. Tsuji, J. Am. Chem. Soc., 2016, 138
,
5547; (c) S. S. Bhojgude, T. Roy, R. G. Gonnade, and A. T.
Biju, Org. Lett., 2016, 18, 5424; (d) Z. Zhang, L. Liao, S. Yan, L.
Wang, Y. He, J. Ye, J. Li, Y. Zhi and D. Yu, Angew. Chem. Int.
Ed., 2016, 55, 7068; (e) T. W. Butcher, E. J. McClain, T. G.
Hamilton, T. M. Perrone, K. M. Kroner, G. C. Donohoe, N. G.
Akhmedov, J. L. Petersen and B. V. Popp, Org. Lett., 2016,
18, 6428; (f) M. Juhl, S. L. R. Laursen, Y. Huang, D. U. Nielsen,
K. Daasbjerg and T. Skrystrup, ACS Catl. 2017,
Suga, T. Saitou, J. Takaya, and N. Iwasawa, Chem. Sci. 2017,
, 1454.
7, 1392; (g) T.
8
10 (a) T. Ohishi, M. Nishiura and Z. Hou, Angew. Chem. Int. Ed.,
2008, 47, 5792; (b) L. Zhang, J. Cheng, T. Ohishi and Z. Hou,
Angew. Chem., Int. Ed., 2010, 49, 8670; (c) T. Ohishi, L.
Zhang, M. Nishiura and Z. Hou, Angew. Chem., Int. Ed., 2011,
50, 8114; (d) L. Zhang, J. Cheng, B. Carry and Z. Hou, J. Am.
Chem. Soc., 2012, 134, 14314; (e) M. Takimoto and Z. Hou,
Chem. Eur. J., 2013, 19, 11439; (f) A. Ueno, M. Takimoto, W.
N. O. Wylie, M. Nishiura, T. Ikariya and Z. Hou, Chem. Asian
J., 2015, 10, 1010; (g) M. Takimoto, S. S. Gholap and Z. Hou,
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
Please do not adjust margins