Merging photoredox catalysis with Lewis acid catalysis: Activation of carbon-carbon triple bonds

Article abstract of DOI:10.1039/c6cc03725a

Here, we demonstrate that merging photoredox catalysis with Lewis acid catalysis provides a fundamentally new activation mode of C-C triple bonds, to achieve the bond-forming reaction of alkynes with weak nucleophiles. Using a synergistic merger of Eosin

Full text of DOI:10.1039/c6cc03725a

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DOI: 10.1039/C6CC03725A
Merging Photoredox Catalysis with Lewis Acid Catalysis: Activation of
Carbon-Carbon Triple Bond
Ruiwen Jin, Yiyong Chen, Wangsheng Liu, Dawen Xu, Yawei Li, Aishun Ding, Hao
Guo*
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433, P.
R.
China.
Tel:
+86-21-55664361,
Fax:
+86-21-55664361,
E-mail:
Hao_Guo@fudan.edu.cn
Photoredox catalysis can be merged with Lewis acid catalysis, providing
fundamentally new activation mode of C-C triple bond.

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DOI: 10.1039/C6CC03725A
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Merging Photoredox Catalysis with Lewis Acid Catalysis: Activation of
Carbon-Carbon Triple Bond
Ruiwen Jin, Yiyong Chen, Wangsheng Liu, Dawen Xu, Yawei Li, Aishun Ding, Hao Guo*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Here we demonstrate that merging photoredox catalysis with shows much fewer organometallic reactivities. Therefore, novel
Lewis acid catalysis provides fundamentally new activation mode reactions achieved by merging photoredox catalysis with Lewis
of C-C triple bond to achieve the bond-forming reaction of alkynes acid catalysis via currently unknown or inaccessible mechanistic
with weak nucleophiles. Using this synergistic merger of Eosin Y and pathways remained undeveloped.
Cu(OTf)2, a highly efficient cyclization reaction of arene-ynes was
developed.
Alkyne, a very important class of organic compounds, has
been extensively applied in organic synthesis as building blocks
and versatile synthons.3 Studies on its reactivity have received
Sunlight, an almost inexhaustible energy source, is the basis extensive attention, resulting in many important protocols for
of all lives on the earth. Huge amounts of biochemical reactions C-C bond formation.4 The direct cleavage of C-C triple bond is
are powered by solar energy every day in Nature. In such non-trivial due to its high bond energy. π-Philic Lewis acid
transformations, the bond cleavage and/or construction are activation of alkynes represents an important method for
very effective at ambient temperature. Utilization of solar functionalization of alkynes, which enables π-bond cleavage
energy to realize efficient organic chemistry transformations and simultaneous formation of two σ-bonds.5 Copper, an
has recently regained much research interest to replace inexpensive metal, is well known as an efficient Lewis acid
traditional processes that employs stoichiometric oxidants. As a catalyst to activate the C-C triple bond for nucleophilic attack
result, much attention have been paid to visible light-mediated from a strong nucleophile.6 However, for typical weak
photoredox catalysis over the past decades.1 Indeed, numerous nucleophiles, copper does not show enough Lewis acidity,
novel synthetic methods have been developed in this field. which is determined by its natural attribute. We questioned
Several reports2 demonstrated that photoredox catalysis could whether photoredox catalysis could be merged with Lewis acid
be merged with transition-metal catalysis, among which some copper salt to create a dual-catalytic system for the activation
examples uncovered fundamentally novel reactivities.2b-2f of alkyne to enable the nucleophilic attack from a weak
Compared with transition-metal catalyst, Lewis acid catalyst nucleophile.
Scheme 1 Merging photoredox catalysis and Lewis acid catalysis to turn on the new activation mode of C-C triple bond.
In the model of a Cu(II)-alkyne complex, the bond between
the copper center and alkyne unit can be described by the
standard Dewar-Chatt-Duncanson model.7 The filled π orbital
Department of Chemistry, Fudan University, 220 Handan Road, Shanghai, 200433,
P. R. China. Tel: +86-21-55664361, Fax: +86-21-55664361, E-mail:
from one of the triple bonds can form a σ-bonding interaction
Hao_Guo@fudan.edu.cn
with an empty orbital of the copper(II) atom, together with
synergistic π-back-donation from one of the filled d orbitals of
†
Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 1
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copper(II) to π* empty orbital of the alkyne. In such a complex,
the π electrons of the alkyne are redistributed between alkyne
and copper(II) atom, resulting in a three-center two-electron
(3c-2e) delocalized system. As a result, the electron density of
the π bond decreases, which weakens the bond order,
rendering it easier to be oxidized via single electron transfer
(SET) process. On the other hand, the electron density of the
copper(II) atom is increased, i.e., it becomes easier to be
oxidized. In view of the overall model, SET from the Cu(II)-alkyne
complex to an external oxidant should be easier (Scheme 1).
Based on the above consideration, the following question
was raised: is it possible to break the π bond of alkyne via single
electron oxidation catalyzed by Lewis acid and photoredox
catalysts? We believe such a desired reaction must run via two
key and independent SET steps: firstly, oxidation of Cu(II)-alkyne
complex into (Cu(II)-alkyne)+ complex, which results in the
cleavage of the π bond; secondly, reduction of Cu(III) into Cu(II),
which regenerates the Lewis acid and photoredox catalysts. If
this idea works, a novel activation mode of C-C triple bond will
be developed.
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DOI: 10.1039/C6CC03725A
A detailed description of our dual-catalytic arene-yne
cyclization is shown in Scheme 2. The coordination of Cu(II) with
the alkyne
1 generated complex 2. In a thermal reaction,
Scheme 2 Proposed mechanism of the dual-catalysis.
intramolecular attack of the weakly nucleophilic aryl moiety to
the alkyne does not occur (vide infra). However, as discussed
above, this complex should be easier to be oxidized. On the
other hand, in the photoredox catalytic circle, the photoexcited
Eosin Y* is highly oxidizing.8 We assumed that the copper and
photoredox catalysis cycles would merge via SET for the first
time. The photoexcited Eosin Y* would abstract one electron
from the copper-alkyne complex to yield cationic intermediate
Eosin Y and reduction of Cu(III) into Cu(II). Thus, both the copper
and photoredox catalytic cycles closes simultaneously.
Based on the above design, our attempts were carried out
using 2-((4-methoxyphenyl)ethynyl)-1,1'-biphenyl 1a as the
model substrate, along with a catalyst combination of Cu(OTf)2
and Eosin Y under the photo irradiation of a 23 W household
lamp. To our great delight, careful optimizations (see Table S1
in Supporting Information) proved that our dual-cycle design
worked quite well to yield the desired cyclized product 9-(4-
methoxyphenyl)phenanthrene 6a in quantitive yield (entry 10,
Table S1). After establishing the optimal conditions, we turned
to the examination of the scope of the arene-ynes.11 As listed in
Table 1, a wide range of mono-, di-, or tri-substituted arene-
ynes with various functional groups were amenable to this dual-
catalysis strategy. Electron-rich substrates showed very nice
reactivities, affording the desired products in excellent yields
3
and the corresponding Eosin Y-., after which the three-center
two-electron (3c-2e) delocalized system was transferred into a
new three-center one-electron (3c-1e) delocalizeared system.
At this moment, the original π bond of the alkyne had already
been broken. The alkyne moiety, (in fact, it should be the three-
center one-electron (3c-1e) delocalized system), became
electropositive. Its chemical behavior would be no longer to
accept nucleophilic attack to break the π bond and build two σ
bonds, just as what a normal Lewis acid shows. Alternatively, as
a positive intermediate, it tends to electrophilicly add to the
former “nucleophile” (the aryl ring) to build a new C-C σ bond,
after which the rest single electron of the highly unstable three-
center one-electron (3c-1e) delocalized system would certainly
fill into the empty orbital of the copper(II) atom to form a new
C-Cu bond and the valence of copper rose up to three. After this
step, the three-membered ring system disintegrated. In the
whole process the cleavage of the π bond and the formation of
(
6a-e
weak electron withdrawing group, temperature as high as 60 oC
was required, which should be due to its lower reactivity (6g 6i
and 6t). Further studies indicated that no reaction occurred
under the standard condition when strong electron
, 6h, 6k, 6m-n, 6p-s, and 6x-y). In case of reactants with a
,
,
a
withdrawing group was introduced to the arene-ynes. After
extensive optimizations, it was found that the photo reactions
o
of such substrates could proceed in MeCN at 90 C, affording
two
protonation of the C-Cu bond (in species
generated proton (from intermediate ) resulted in the final
product phenanthrene derivative and delivered the free Cu(III)
σ
bonds occurred at three different steps. Next,
the desired products in excellent yields (6j, 6l, 6o, 6u-w, and 6z-
5
) by the in situ
aa). The above results clearly indicated that the substrate scope
was broad. Numerous functional groups, such as alkoxy,
acetoxyl, alkyl, halogen atom, methoxycarbonyl, acetyl, nitro,
nitrile, and trifluoromethyl, were all well tolerated in this
reaction. There might be two possible reasons for the observed
electronic effect. For electron-deficient arene-ynes, the lower
4
6
species.9 Given that the Cu(III) species is highly oxidizing,10
meanwhile, the resulting Eosin Y-. is quite reducing,8 we
envisioned these two catalytic cycles merging for the second
time, enabling the single electron oxidization of Eosin Y-. into
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DOI: 10.1039/C6CC03725A
Table 1 The photo reaction under optimal conditionsa
Catalyst Combination
Photon Source
Cu(OTf)2
Photoredox catalyst
Lewis acid catalyst
23 W household lamp
6a, 72 h, 100%
6b, 72 h, 100%
6c, 72 h, 90%
6d, 72 h, 100%
6e, 47 h, 100%
6f, 72 h, 98%
6g,b 72 h, 100%
6h, 72 h, 100%
6i,b 72 h, 100%
6j,c 120 h, 83%
6k, 48 h, 100%
6l,c 120 h, 90%
6m, 47 h, 100%
6n, 72 h, 98%
6q, 48 h, 98%
1.164 g, 72 h,
91%
6s, 34.5 h,
100%
6o,c 72 h, 94%
6p, 48 h, 100%
6r, 72 h, 100%
6t,b 72 h, 100%
6u,c 72 h, 92%
6v,c 72 h, 93%
6w,c 72 h, 95%
6x, 48 h, 100%
6y, 48 h, 100%
6z,c 72 h, 95%
6aa,c 72 h, 97%
a All reactions were carried out using
1 (0.2 mmol), Cu(OTf)2 (5 mol%), and Eosin Y (3 mol%) in anhydrous DCM (5 mL) in a thick
sealed tube irradiated by a 23 W household lamp at rt under argon atmosphere. Isolated yields were reported. b Reactions were
carried out at 60 oC. c Reactions were carried out in anhydrous MeCN (5 mL) at 90 oC.
electron density of the π bond in the alkyne renders oxidation
of the copper-alkyne complex more difficult. Meanwhile, the
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1
2
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low electron density of the aryl ring also makes electrophilic
addition to the aryl ring more challenging. It was also worthy to
note that this reaction could easily proceed in a high yield on a
gram scale (6q).
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After the above explorations, a series of control experiments
were carried out in order to gain more informations of this
designed dual-cycle reaction mechanism. First of all, Cu(OTf)
and some other Lewis acids were surveyed as the catalyst in this
reaction (entries 11-16, Table S1). The fact that no reaction
occurred in the presence of such catalysts clearly demonstrated
that only Cu(OTf)2 could catalyze this reaction. To examine
whether this reaction was catalyzed by the in situ generated
proton, reaction of 1a in the presence of 5 mol% of HOAc was
carried out. The results indicated that no reaction took place
under the catalysis of HOAc, which ruled out the above
possibility (see Scheme S1 in Electronic Supplymentary
Information). Omission of either Cu(OTf)2 (entry 17, Table S1) or
Eosin Y (entry 18, Table S1) from the standard reaction
conditions led to no conversion, indicating that both catalysts
were key factors in this transformation. The fact that no
reaction took place under dark conditions (entry 19, Table S1)
clearly illustrated that light was necessary. Notably, under the
irradiation of 254 nm UV light, dramatically increased reaction
rate and higher yield were obtained in the absence of Eosin Y
(entry 20, Table S1), but no reaction occurred in the absence of
Cu(OTf)2 under UV irradiation (entry 21, Table S1). In such a UV
reaction, we assumed that the reaction proceeded via Cu-
catalyzed photolytic π bond cleavage process which is distinct
from catalytic SET procedure. Considering that the household
lamp operates with a wide spectral window (around 400 to 760
nm) and the Eosin Y absorbs green light (characteristic peak at
539 nm,8 the green LED lamp (520 to 530 nm, 2 W) was used
instead of the household lamp. As a result, the reaction was
greatly accelerated (entry 22, Table S1). Moreover, the reaction
under the same irradiation conditions in the absence of Eosin Y
showed no conversion (entry 23, Table S1). These results
strongly suggested that the excited state of Eosin Y was a key
intermediate in this dual-catalysis mechanism.
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In conclusion, the strategy reported herein represents a
novel activation mode of carbon-carbon triple bond. In contrast
to the traditional reaction pathway, wherein the metal-
coordinated alkyne “passively” accepts the nucleophilic attack
resulting in concomitant cleavage of the
π bond and
10 M. Orbán, React. Kinet. Catal. Lett., 1990, 42, 343.
11 Note please: All the optimization reactions were carried
out in a thin glass tube (Table S1). All the scope
exploration reactions were carried out in a thick sealed
tube (Table 1). The transmittance of the thin glass tube
is more excellent than the thick sealed tube. Thus, the
corresponding reaction time of the same substrate
under the same reaction condition was not the same.
Reactions in a thick sealed tube took longer time.
construction of two new σ bonds at the same step, this new
strategy proceeds via electrophilic addition with the former
“nucleophile” to an initially formed positive species by SET-
induced cleavage of the π bond. In such a new reaction
procedure, the cleavage of the π bond and the constructions of
two new σ bonds proceed step by step. This new activation
mode will probably find wide applications in the design of
organic reactions.
We greatly acknowledge the financial support from National
Basic Research Program of China (973 Program, 2012CB720300)
and International Science & Technology Cooperation Program
of China (2014DFE40130).
Notes and references
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