Visible-Light-Mediated Oxidative Decarboxylative Coupling of Cinnamic Acid Derivatives with Tetrahydrofuran

Article abstract of DOI:10.1055/s-0035-1560661

A visible-light-mediated protocol for direct oxidative decarboxylative coupling of various cinnamic acid derivatives with tetrahydrofuran was developed, leading to simple preparations of a range of vinyltetrahydrofurans under operationally mild and conven

Full text of DOI:10.1055/s-0035-1560661

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 2849–2852
letter
2849
Z. Liu et al.
Letter
Synlett
Visible-Light-Mediated Oxidative Decarboxylative Coupling of
Cinnamic Acid Derivatives with Tetrahydrofuran
Zheng Liu*
Leifeng Wang
Dong Liu
Zhigang Wang
School of Chemical Biology and Biotechnology,
Shenzhen Graduate School of Peking University,
Lishui Road, Shenzhen 518055, P. R. of China
pkuliuzheng@gmail.com
Received: 18.07.2015
Accepted after revision: 13.09.2015
Published online: 20.10.2015
that are widely present in various natural products of
demonstrated biological activities.7 Selective direct C(sp3)–
H functionalization of ethers provides a straightforward ap-
proach to the synthesis of diverse analogues from a com-
mon structural motif.8 On this topic, Li et al. have recently
DOI: 10.1055/s-0035-1560661; Art ID: st-2015-w0561-l
Abstract A visible-light-mediated protocol for direct oxidative decar-
boxylative coupling of various cinnamic acid derivatives with tetrahy-
drofuran was developed, leading to simple preparations of a range of
vinyltetrahydrofurans under operationally mild and convenient condi-
tions.
disclosed
visible
light-promoted
vinylations
of
tetrahydrofuran by a combination of a suitable alkyne sub-
strate, the photosensitizer eosin Y, and tert-butyl hydroper-
oxide as an external oxidant.9 Our design hypothesis in-
stead employs readily available cinnamic acid derivatives
with tetrahydrofuran (THF) as coupling precursors under
visible-light stimulation.10 The method, if realized, would
appear to have advantages, in terms of the reaction condi-
tions and reagents employed, over another recently report-
ed protocol for decarboxylative cross-coupling of carboxylic
acids with vinyl halides by synergistic photoredox and
nickel catalysis.5a
Key words alkenes, coupling, oxidations, carboxylic acids, photo-
chemistry, radical reactions, decarboxylations
Decarboxylative cross-coupling reactions have emerged
in recent years as a powerful synthetic technology that per-
mits the use of readily available and cost-competitive car-
boxylic acids as green replacements for conventional or-
ganometallic reagents,1 which are typically expensive and
difficult to handle because of their sensitivities to air and
moisture. To the best of our knowledge, the earliest exam-
ple of a decarboxylative arylation reaction was documented
in 1939 by Meerwein and co-workers, who used diazonium
salts and copper(II) chloride under acid conditions at a low
temperature to prepare certain aryl alkenes.2 Whereas re-
ported studies have focused on transition-metal-catalyzed
decarboxylative protocols, usually at high temperatures,3
there is clearly a need and interest in developing compli-
mentary mild and operationally simple reactions,4–6 which
are currently scarce. From this perspective, the develop-
ment of sustainable and mild (near room temperature) de-
carboxylative cross-coupling reactions that are capable of
constructing certain privileged molecular skeletons invites
investigations from the synthetic community and has
emerged as a major challenge.
visible light
COOH
photoredox catalyst
O
+
H
oxidant
O
R
R
Scheme 1 A decarboxylative coupling strategy to vinyl furans
With cinnamic acid (1a) and tetrahydrofuran (2a) as the
two representative coupling partners, we began our inves-
tigations by screening a range of photocatalysts, oxidants,
solvents, and bases (Table 1). We found that the use of light
from a 46 W household compact fluorescent lamp (CFL) in
the presence of the photocatalyst tris(bipyridyl)dichloro-
ruthenium(II) ([Ru(bpy)3]Cl2, 2 mol%) and benzoyl peroxide
(3 equivalents) in 1:1 tetrahydrofuran–acetonitrile at room
temperature for six hours gave the desired decarboxylative
coupling product 3a in 65% yield (Table 1, entry 1). Other
oxidants examined (potassium persulfate, tetrabromo-
As illustrated in Scheme 1, our interest has centered on
uncovering potential decarboxylative strategies for the syn-
thesis of vinylfurans, an important class of chemical motifs
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2849–2852

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Z. Liu et al.
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methane, and tert-butyl peroxybenzoate) were found to be
practically ineffective (entries 2–4), and the use of 2.8
equivalents of benzoyl peroxide turned out to be optimal
(entries 5–7). Other photoredox catalysts, such as tris(bi-
pyridyl)iridium, eosin Y, and rose bengal did not give the
desired product (entries 8–10). As might be expected from
the inhibitory effect of oxygen on radical pathways, the use
of argon as a protecting atmosphere slightly improved the
yield (entry 11). Other solvents or bases all gave lower
yields (entries 12–16). Careful control experiments con-
ducted in the absence of a photoredox catalyst or light gave
no coupling product (entries 17 and 18).
3-arylacrylic acids 1 reacted smoothly with tetrahydrofu-
ran (2a) to afford the corresponding (2-arylvinyl)tetrahy-
drofurans 3 in moderate to good yields (40–73%). The reac-
tion was not significantly affected by the electronic nature
or position of para- or meta-substituents on the aryl ring
(products 3a–i). However, when substituents were present
in the ortho-position, the yields of the corresponding prod-
ucts fell to 40–44% (products 3j–l). We next evaluated the
effect of the nature of the ether coupling partner in the
photoredox-mediated decarboxylative coupling. Three
common ethers were used instead of tetrahydrofuran in
this operationally simple coupling reaction. The six mem-
bered cyclic ethers tetrahydropyran and 1,4-dioxane react-
ed with lower efficiencies than tetrahydrofuran (products
3m,n, 22 and 35% yield, respectively). Remarkably, volatile
diethyl ether gave the corresponding coupling product 3o
in 26% yield under the mild conditions.
Table 1 Visible-Light-Mediated Oxidative Decarboxylative Coupling of
Cinnamic Acid with Tetrahydrofurana
46 W CFL
COOH
photoredox catalyst
+
O
H
46 W CFL
[Ru(bpy)3]Cl2 (2 mol%)
BPO (2.8 equiv)
oxidant
solvent
O
R2
COOH
1a
2a
3a
R1
R1
ether 2–MeCN (1:1)
Entry
Photoredox catalyst
Oxidant (equiv)
Solvent
Yieldb (%)
argon, r.t.
3
1
1
2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
Ir(bpy)3
BPOc (3.0)
K2S2O8 (3.0)
CBr4 (3.0)
TBPBd (3.0)
BPO (1.5)
BPO (4.5)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
BPO (2.8)
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
DMF
55
0
3
0
O
O
4
0
O
F
5
39
49
65
0
Me
3a, 73% yield
3d, 60% yield
3b, 67% yield
3e, 64% yield
3c, 60% yield
3f, 65% yield
6
7
O
O
O
O
8
F3C
Cl
Br
9
eosin Y
0
10
11e
12e
13e
14e
15e,f
16e,g
17h
18
rose bengal
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
[Ru(bpy)3]Cl2
none
0
75
52
44
22
49
46
0
MeO
O
O
NC
PhO
THF
3g, 67% yield
3h, 55% yield
3i, 63% yield
toluene
MeCN
MeCN
MeCN
MeCN
Cl
Br
O
O
O
O
Br
F
Cl
3j, 40% yield
3k, 44% yield
3l, 43% yield
0
O
O
a Reaction conditions: cinnamic acid (1a; 0.5 mmol), photoredox catalyst (2
mol%), oxidant, THF (2a; 3 mL), solvent (3 mL), 46 W CFL irradiation, r.t.
b Corrected NMR yield of the E-isomer, with mesitylene as internal stan-
dard.
O
c Benzoyl peroxide.
3m, 22% yield
3n, 35% yield
3o, 26% yield
d tert-Butyl peroxybenzoate.
e Under argon.
Scheme 2 Examination of the scope of the reaction scope; isolated
f K2CO3 (6 equiv) was added to the reaction mixture.
g Et3N (6 equiv) was added to the reaction mixture.
h In darkness.
yields are given, based on the cinnamic acid
Our experimental observations, in conjunction with rel-
evant literature reports, led us to propose a mechanistic
network for these novel oxidative decarboxylative coupling
reactions. As shown in Scheme 3, upon irradiation by the 46
Having determined the optimal reaction conditions,11
we investigated the substrate scope of this reaction with a
series of cinnamic acids (Scheme 2). Various substituted
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2849–2852

2851
Z. Liu et al.
Letter
Synlett
H
(PhCOO)2
O
PhCOOH
PhCOO–
+
SET
[Ru(bpy)3]2+*
PhCOO
O
A
oxidative
quenching
cycle
[Ru(bpy)3]3+
O
COOH
[Ru(bpy)3]2+
COOH
SET
B
+
O
O
COOH
– CO2
– H+
E-alkene
C
Scheme 3 A mechanistic proposal
W CFL, the photocatalyst undergoes a metal-to-ligand
charge transfer and subsequent intersystem crossing to
generate a relatively long-lived ruthenium(II) species in an
excited state.12 This reductant readily undergoes single-
electron transfer with benzoyl peroxide to give a benzoyl-
oxyl radical and a benzoate ion. The radical abstracts a hy-
drogen atom from tetrahydrofuran to give the new α-oxo
radical A, which undergoes addition to the C=C double bond
of the cinnamic acid to give the benzyl radical B. Oxidation
of intermediate B with the ruthenium(III) species gives the
β-cationic carboxylic acid C, which eventually undergoes
decarboxylation and deprotonation at room temperature to
give the (E)-(2-arylvinyl)tetrahydrofuran.13
(2) (a) Meerwein, H.; Bückner, E.; van Emster, K. J. Prakt. Chem.
1939, 152, 237. (b) Brunner, W. H.; Kustatscher, J. Monatsh.
Chem. 1951, 82, 100. (c) Rondestvedt, C. S. Jr. Org. React. (N. Y.)
1976, 24, 225.
(3) (a) Zhao, J.; Zhou, W.; Han, J.; Li, G.; Pan, Y. Tetrahedron Lett.
2013, 54, 6507. (b) Zhang, F.; Greaney, M. F. Angew. Chem. Int.
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Catal. 2009, 351, 2827. (e) Bhunia, S.; Ghorpade, S.; Huple, D. B.;
Liu, R.-S. Angew. Chem. Int. Ed. 2012, 51, 2939. (f) Bloom, S.;
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In summary, we have conceived and demonstrated an
efficient, visible-light-mediated, oxidative, decarboxylative
coupling of cinnamic acid derivatives with tetrahydrofuran
or other ethers. The methodology is experimentally simple
and characterized by good yields, low catalyst loadings,
mild conditions, and a broad substrate scope. These merits
should permit our protocol to be used by practitioners to
prepare vinylfuran motifs present in natural and synthetic
substances.
(5) (a) Noble, A.; McCarver, S. J.; MacMillan, D. W. C. J. Am. Chem.
Soc. 2015, 137, 624. (b) Ventre, S.; Petronijevic, F. R.; MacMillan,
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J. M.; MacMillan, D. W. C. Angew. Chem. Int. Ed. 2015, 54, 7929.
(d) Zuo, Z.; MacMillan, D. W. C. J. Am. Chem. Soc. 2014, 136,
5257. (e) Chu, L.; Ohta, C.; Zuo, Z.; MacMillan, D. W. C. J. Am.
Chem. Soc. 2014, 136, 10886.
(6) Xie, J.; Xu, P.; Li, H.; Xue, Q.; Jin, H.; Cheng, Y.; Zhu, C. Chem.
Commun. 2013, 49, 5672.
(7) (a) Rye, C. E.; Barker, D. Synlett 2009, 3315. (b) Miles, S. M.;
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Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0035-1560661.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
ortioInfgrmoaitn
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K.; Rankic, D. A.; MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322.
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(11) 2-Arylvinyl Ethers 3; General Procedure
= 7.40–7.29 (m, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 6.54 (d, J = 15.8 Hz,
1 H), 6.12 (dd, J = 15.8, 6.6 Hz, 1 H), 4.45 (dd, J = 13.4, 6.7 Hz, 1
H), 3.97 (dd, J = 14.5, 7.4 Hz, 1 H), 3.84 (dd, J = 14.2, 7.8 Hz, 1 H),
2.17–2.07 (m, 1 H), 2.04–1.91 (m, 2 H), 1.70 (ddd, J = 15.8, 12.0,
7.5 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 132.99, 130.24,
129.31, 127.93, 115.49, 115.28, 79.57, 68.17, 32.37, 25.91.
HRMS: m/z [M + H]+ calcd for C12H14FO: 193.1023; found:
193.1024.
Ru(bpy)3Cl2·6H2O (2 mol%, 6 mg), cinnamic acid derivative 1 (1
equiv, 0.5 mmol), benzoyl peroxide (2.8 equiv, 1.4 mmol), anhyd
ether 2 (3 mL), and anhyd MeCN (3 mL) were added to a 10 mL
reaction vessel equipped with a magnetic stirrer bar. The
mixture was irradiated with a 46 W CFL at r.t. for 4–6 h. The
yield was determined by isolation of the product using flash
chromatography.
2-[(E)-2-(5-Bromo-2-fluorophenyl)vinyl]tetrahydrofuran (3l)
Colorless oil; yield: 58.4 mg (43%). 1H NMR (400 MHz, CDCl3): δ
= 7.48 (dd, J = 8.8, 5.4 Hz, 1 H), 7.22 (dd, J = 9.8, 3.0 Hz, 1 H), 6.87
(d, J = 15.7 Hz, 1 H), 6.85–6.79 (m, 1 H), 6.16 (dd, J = 15.7, 6.4 Hz,
1 H), 4.53 (dd, J = 12.8, 6.4 Hz, 1 H), 3.99 (dd, J = 14.6, 7.3 Hz, 1
H), 3.86 (dd, J = 14.2, 7.8 Hz, 1 H), 2.19–2.10 (m, 1 H), 2.05–1.92
(m, 2 H), 1.73 (ddd, J = 15.5, 12.1, 7.3 Hz, 1 H). 13C NMR (100
MHz, CDCl3): δ = 160.79, 138.54 (d, J = 7.7 Hz), 134.88, 134.03
(d, J = 8.2 Hz), 128.32, 117.69 (d, J = 3.0 Hz), 115.94 (d, J = 22.7
Hz), 113.74 (d, J = 23.3 Hz), 79.12, 68.32, 32.29, 25.82. HRMS:
m/z [M + H]+ calcd for C12H13BrFO: 271.0128; found: 271.0131.
(12) Campagna, S.; Puntoriero, F.; Nastasi, F.; Bergamini, G.; Balzani,
V. Top. Curr. Chem. 2007, 280, 117.
2-[(E)-2-Phenylvinyl]tetrahydrofuran (3a)
Colorless oil; yield: 63.4 mg (73%). 1H NMR (400 MHz, CDCl3): δ
= 7.38 (d, J = 7.3 Hz, 2 H), 7.34–7.27 (m, 2 H), 7.25–7.17 (m, 1 H),
6.59 (d, J = 15.9 Hz, 1 H), 6.21 (dd, J = 15.9, 6.6 Hz, 1 H), 4.48 (dd,
J = 6.9 Hz, 1 H), 3.98 (dd, J = 14.5, 7.4 Hz, 1 H), 3.85 (dd, J = 14.2,
7.8 Hz, 1 H), 2.13 (ddd, J = 14.5, 9.6, 6.1 Hz, 1 H), 2.07–1.87 (m, 2
H), 1.79–1.68 (m, 1 H). 13C NMR (100 MHz, CDCl3): δ = 136.83,
130.49, 130.41, 128.47, 127.45, 126.42, 79.63, 68.14, 32.36,
25.88. HRMS: m/z [M + H]+ calcd for C12H15O: 175.1117; found:
175.1120.
2-[(E)-2-(4-Fluorophenyl)vinyl]tetrahydrofuran (3c)
(13) Johnson, W. S.; Hein, W. E. J. Am. Chem. Soc. 1949, 71, 2913.
Colorless oil; yield: 57.6 mg (60%). 1H NMR (400 MHz, CDCl3): δ
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2849–2852