Photoinduced C(sp2)-H/C(sp2)-H Cross-Coupling of Alkenes: Direct Synthesis of 1,3-Dienes

Article abstract of DOI:10.1021/acs.orglett.9b04201

A highly concise route to substituted 1,3-dienes from vinylarenes and ketene dithioacetals under photoinduced cross-coupling reaction is described. The reaction proceeded in a highly regio- A nd stereoselective manner and showed broad functional group tol

Full text of DOI:10.1021/acs.orglett.9b04201

pubs.acs.org/OrgLett
Letter
Photoinduced C(sp2)−H/C(sp2)−H Cross-Coupling of Alkenes: Direct
Synthesis of 1,3-Dienes
Qi Xu, Baihui Zheng, Xiaoxuan Zhou, Ling Pan, Qun Liu, and Yifei Li*
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ABSTRACT: A highly concise route to substituted 1,3-dienes
from vinylarenes and ketene dithioacetals under photoinduced
cross-coupling reaction is described. The reaction proceeded in a
highly regio- and stereoselective manner and showed broad
functional group tolerance. More than 35 substituted 1,3-dienes
were synthesized with good to excellent yields through the
construction of the Csp2−Csp2 bond without using noble metal
and external oxidants, and natural sunlight could also induce the reaction to afford gram-scale synthesis under ambient conditions.
he 1,3-diene scaffold, frequently found in natural
Therefore, the development of mild catalytic methodologies
1
2
Tproducts and biologically active molecules, is important for direct C(sp2)−H/C(sp2)−H cross-coupling between
and also acts as a versatile precursor for diverse molecules.3,4
alkenes remains a formidable challenge.
Visible-light photoredox catalysis has emerged recently as an
attractive research area in green synthetic chemistry and
offered an opportunity to overcome the shortcomings of using
transition-metal catalysts in C−H functionalization.9−11
Taking advantage of the visible light, various organic
transformations were realized; for instance, a photoredox/
cobaloxime dual catalytic system12 was applied to the bond-
forming reactions of vinylarenes13−17 with selected nucleo-
philes such as H2O,14 alcohols,15 and aliphatic acids16 without
the use of external oxidants (Scheme 1, eq 2-1). More recently,
the dehydrogenative Csp2−Csp2 bond formation reaction
between arenes and alkenes was reported by Lei and co-
workers (Scheme 1, eq 2-2).17,18 However, the visible-light
photoredox catalyzed direct C(sp2)−H/C(sp2)−H cross-
coupling between two alkenes under external oxidant-free
conditions has not been established.
Although numerous methods for the synthesis of 1,3-
dienes,5−8 especially the step- and atom-efficient direct cross-
coupling approach of two different alkenes catalyzed by
transition metals (Scheme 1, eq 1),6−8 the use of expensive
metal catalysts, harsh oxidative conditions, multiple prefunc-
tionalization steps of substrates, and the poor selectivity for
highly substituted alkene substrates limit their applicability.
Scheme 1. Cross-Coupling reactions of alkenes
Herein, we report the first example of photoinduced
C(sp2)−H/C(sp2)−H crossing-coupling between two alkenes
without the use of external oxidants, and the readily available
ketene dithioacetals8a,19−21 were selected as the internal
alkenes due to their high reactivity toward electrophiles
(Scheme 1).
We commenced the reaction of styrene 1a with α-acetyl
dithioacetal 2a as a probe to try the reaction and optimize the
reaction conditions in the presence of a photoredox catalyst
with a cobaloxime catalyst under blue LED irradiation (Table
1). Several selected acridinium photosensitizers and cobalox-
Received: November 23, 2019
https://dx.doi.org/10.1021/acs.orglett.9b04201
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

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a
2. A range of styrenes having electron-deficient group on the
aryl ring, such as halogens (1b−1h) or trifluoromethyl (1i),
Table 1. Optimization of the Reaction Conditions
Scheme 2. Scope of Vinylarenes 1 in the C(sp2)−H/
a,b
C(sp2)−H Cross-Coupling Reaction
a
Styrene 1a (1.5 mmol), α-acetyl dithioacetal 2a (0.5 mmol), Mes-
−
Acr+ClO4 (5 mol %), Co(dmgH)2PyCl (15 mol %), and DCE (2
mL) were stirred in a tube irradiated using 5 W blue LEDs at rt for 72
b
h. Isolated yields.
ime catalysts were investigated in 1,2-dichloroethane (DCE).
−
To our delight, the use of 5 mol % of Mes-Acr+ClO4 and 15
mol % of Co(dmgH)2PyCl resulted in the formation desired
1,3-dienes 3a in 87% (entry 1). Replacing Mes-Acr+ClO4− with
other photocatalysts, such as acridinium photosensitizers Mes-
Acr-Ph+BF4 or Mes-Acr-Ph+Cl−, caused clear decline of the
−
yields of 3a (entries 2 and 3). No 3a was detected with
Ir(ppy)2(dtb-bpy)PF6 as the sensitizer (entry 4). The yield of
3a was decreased to 61% when [Co(dmgH)2Py2]PF6 was used
as a proton-reduction catalyst (entry 5). No 3a was detected
when Cu(OAc)2 or PhSSPh was applied to replace Co-
(dmgH)2PyCl (entries 6 and 7). A decreased yield of 3a was
formed with MeCN as the solvent (entry 8). A slightly lower
yield was obtained when reducing either the amount of catalyst
a
Vinylarene 1 (1.5 mmol), α-acetyl dithioacetal 2a (0.5 mmol), Mes-
Acr+ClO4 (5 mol %), Co(dmgH)2PyCl (15 mol %), and DCE (2
mL) were stirred in a tube irradiated using 5 W blue LEDs at rt for 72
h. Isolated yields.
−
b
(3 mol % Mes-Acr+ClO4 and 8 mol % Co(dmgH)2PyCl
provided the desired 1,3-dienes (3b−3i) in good to excellent
yields. On the other hand, styrenes bearing electron-donating
groups on the aryl ring, such as methyl (1j−1l) and tert-butyl
(1n), also gave the desired products (3j−3l and 3n) in good
yields. In addition, 2-vinylnaphthalene (1o) was a suitable
vinylarene component for the desired 1,3-diene 3o. However,
it is surprising that 4-MeO-styrene (1m) failed to give the
desired cross-coupling product (for details, see the mechanism
studies). Obviously, ortho-, meta-, para-, and multisubstituted
vinylarenes 1 did not show a significant difference in reactivity
(1b−1g and 1j−1l). Gratifyingly, in the case of indene 1q and
1,2-dihydronaphthalene 1r as the cyclic internal alkenes, the
−
(entry 9) or substrate 1a (entry 10). In addition, it was proved
−
that no 3a was produced in the absence of Mes-Acr+ClO4 ,
Co(dmgH)2Cl2 or light (entries 11−13), respectively,
indicating these components were essential for the photo-
induced C(sp2)−H/C(sp2)−H cross-coupling reaction de-
scribed above.
With the optimized reaction conditions (Table 1, entry 1),
the scope of the visible-light-induced C(sp2)−H/C(sp2)−H
cross-coupling reaction was investigated in detail. At first, α-
acetyl dithioacetal 2a was selected as the model reactant to
react with vinylarenes 1, and the results are shown in Scheme
B
https://dx.doi.org/10.1021/acs.orglett.9b04201
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corresponding C(sp2)−H/C(sp2)−H cross-coupling products
3q and 3r were also obtained, although methylstyrene 1p as
the acyclic internal alkene did not react with 2a to form the
corresponding 3p, due to probably the steric hindrance of 1p.
When 1,1-diarylethylenes (1s−1u) were applied, the desired
3s−3u were produced, and functional groups such as fluoro
(1t) and methyl (1u) can be well tolerated.
regio- and stereospecific E isomers 3 and 4 are constructed.
These results indicate the reaction proceeds in a regio- and
stereospecific manner.
In our research, it was demonstrated that 3a can be prepared
on gram-scale in good yields (Scheme 4) under standard
conditions or even induced by natural sunlight under ambient
conditions, showing this C(sp2)−H/C(sp2)−H cross-coupling
reaction is practical.
Next, the scope of ketene dithioacetals 2 as the internal
alkenes was investigated (Scheme 3). It was proven that
Scheme 4. Gram Synthesis
Scheme 3. Scope of Internal Alkenes 2 in the C(sp2)−H/
a,b
C(sp2)−H Cross-Coupling Reaction
To gain further insight into the photocatalytic process of the
reaction, a series of mechanism studies were performed
including control experiments, cyclic voltammetry,22 UV−vis
monitoring and Stern−Volmer studies (Scheme 5). As shown
Scheme 5. Mechanistic Studies
a
Styrene 1a (1.5 mmol), ketene dithioacetal 2 (0.5 mmol), Mes-
Acr+ClO4 (5 mol %), Co(dmgH)2PyCl (15 mol %), and DCE (2
−
in Scheme 5 (a), the reaction of 1a, in the absence of 2a, under
the standard conditions (Table 1, entry 1) give the
cyclodimerization−oxygenation product 5a in 26% yield.23
As a comparison, 2a was not reacted under otherwise identical
conditions in the absence of 1a. These results suggested that in
the cross-coupling reaction styrene 1 should be oxidized by the
excited state of the photosensitizer to generate a styrene radical
cation intermediate. As described in Scheme 5 (b), the UV−vis
mL) were stirred in a tube irradiated using 5 W blue LEDs at rt for 72
h. Isolated yield.
b
styrene 1a can react with a wide variety of α-oxo ketene
dithioacetals, including those having phenyl (2a), electron-
deficient aryl (2a−2f), electron-rich aryl (2g−2j), naphthyl
(2k), and hetero aromatic groups (2l and 2m), to afford the
desired 1,3-dienes 4a−4m in good to excellent yields. Notably,
the reactions of α-ethoxycarbony ketene dithioacetal 2n and α-
cyano ketene dithioacetal 2o with 1a also gave the expected 4n
and 4o, respectively, in good yields. In addition, α-oxo ketene
dithioacetal 2p with the 1,3-dithiane moiety afforded the
corresponding 1,3-diene 4p in 70% yield.
−
absorption spectrum confirms that Mes-Acr+ClO4 is the only
visible-light photosensitizer in the reaction. According to the
linear Stern−Volmer behavior (Scheme 5, (c)), either styrene
1a, α-acetyl dithioacetal 2a, or Co(dmgH)2PyCl can quench
−
the excited photosensitizer Mes-Acr+ClO4 in the emission-
quenching experiments, meaning the electron transfer among
It is noteworthy that for the photoinduced C(sp2)−H/
C(sp2)−H cross-coupling reaction mentioned above, only the
Mes-Acr+ClO4 , 1a and Co(dmgH)2PyCl. It worth mention
−
that 4-MeO styrene has a larger quenching rate than both of 1a
C
https://dx.doi.org/10.1021/acs.orglett.9b04201
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Letter
Other Authors
and 2a (Scheme 5 (b)), exhibiting the excited state of the
photosensitizer is to be inactive in this case.
Qi Xu − Northeast Normal University, Changchun, China
Baihui Zheng − Northeast Normal University,
Changchun, China
Xiaoxuan Zhou − Northeast Normal University,
Changchun, China
Ling Pan − Northeast Normal University, Changchun,
China; orcid.org/0000-0003-0654-9216
Qun Liu − Northeast Normal University, Changchun,
China
In light of the experimental results and mechanistic
elucidations,12−15,18,22−26 a plausible mechanistic cycle for
the photoinduced direct C(sp2)−H/C(sp2)−H cross-coupling
reaction (with 1a and 2a as an example) is outlined in Scheme
6. The process starts from the generation of excited state of
Scheme 6. Plausible Mechanism
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.9b04201
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful for the financial support provided by the
Fundamental Research Funds for the Central Universities
(2412019FZ013, 2412019FZ016), the National Natural
Science Foundation of China (21572031), and the Natural
Sciences Foundation of Jilin Province (20170101181JC).
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ASSOCIATED CONTENT
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AUTHOR INFORMATION
Corresponding Author
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́
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Yifei Li − Northeast Normal University, Changchun,
China; orcid.org/0000-0002-3167-7175;
Email: liyf640@nenu.edu.cn
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