Visible-Light Photoredox-Catalyzed Remote Difunctionalizing Carboxylation of Unactivated Alkenes with CO2

Article abstract of DOI:10.1002/anie.202008630

Remote difunctionalization of unactivated alkenes is challenging but a highly attractive tactic to install two functional groups across long distances. Reported herein is the first remote difunctionalization of alkenes with CO₂. This visible-light photoredox catalysis strategy provides a facile method to synthesize a series of carboxylic acids bearing valuable fluorine- or phosphorus-containing functional groups. Moreover, this versatile protocol shows mild reaction conditions, broad substrate scope, and good functional-group tolerance. Based on DFT calculations, a radical adds to an unactivated alkene to smoothly form a new carbon radical, followed by a 1,5-hydrogen atom-transfer process, the rate-limiting step, generating a more stable benzylic radical. The reduction of the benzylic radicals by an Ir^II species generates the corresponding benzylic carbanions as the key intermediates, which further undergo nucleophilic attack with CO₂ to generate carboxylates.

Full text of DOI:10.1002/anie.202008630

A Journal of the Gesellschaft Deutscher Chemiker
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Accepted Article
Title: Visible-Light Photoredox-Catalyzed Remote Difunctionalizing
Carboxylation of Unactivated Alkenes with CO2
Authors: Lei Song, Dong-Min Fu, Liang Chen, Yuan-Xu Jiang, Jian-
Heng Ye, Lei Zhu, Yu Lan, Qiang Fu, and Da-Gang Yu
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10.1002/anie.202008630
Angewandte Chemie International Edition
RESEARCH ARTICLE
Visible-Light Photoredox-Catalyzed Remote Difunctionalizing
Carboxylation of Unactivated Alkenes with CO2
Lei Song,[a] Dong-Min Fu,[b] Liang Chen,[a] Yuan-Xu Jiang,[a] Jian-Heng Ye,[a] Lei Zhu,[c] Yu Lan,*[b][c]
Qiang Fu,[d] Da-Gang Yu*[a][e]
[a]
[b]
L. Song, L. Chen, Y.-X. Jiang, Dr. J.-H. Ye, Prof. Dr. D.-G. Yu
Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University
29 Wangjiang Road, Chengdu 610064 (P. R. China)
E-mail: dgyu@scu.edu.cn
D.-M. Fu, Prof. Dr. Y. Lan
College of Chemistry and Institute of Green Catalysis, Zhengzhou University
Zhengzhou 450001 (P. R. China)
E-mail: lanyu@cqu.edu.cn
[c]
[d]
[e]
L. Zhu, Prof. Dr. Y. Lan
School of Chemistry and Chemical Engineering, and Chongqing Key Laboratory of Theoretical and Computational Chemistry, Chongqing University
Chongqing 400030 (P. R. China)
Dr. Q. Fu
School of Pharmacy, Southwest Medical University
Luzhou 646000 (P. R. China)
Prof. Dr. D.-G. Yu
Beijing National Laboratory for Molecular Sciences
Beijing 100190 (P. R. China)
Supporting information for this article is given via a link at the end of the document.
Abstract: Catalytic difunctionalization of alkenes is a powerful and
efficient tool to synthesize complex molecules from simple starting
materials. Remote difunctionalization of unactivated alkenes is more
challenging but highly attractive tactic to install two functional groups
across long distances. Herein, we report the first remote
difunctionalization of alkenes with CO2. This visible-light photoredox
catalysis strategy provides a facile method to synthesize a series of
carboxylic acids, such as non-natural -amino acids, bearing
valuable fluorine- or phosphorus-containing functional groups.
Moreover, this versatile protocol shows mild reaction conditions,
broad substrate scope, and good functional group tolerance. Based
on DFT calculations, the observed reaction starts via radical addition
to an unactivated alkene to smoothly form a new carbon radical. The
following 1,5-hydrogen atom transfer process, which is considered to
be the rate-limiting step, generates a more stable benzylic radical. In
contrast to previous reports of direct coupling or single-electron
oxidation of such radical species, experimental and computational
studies suggest the reduction of the benzylic radicals by an Ir(II)
species generates the corresponding benzylic carbanions as the key
intermediates, which further undergo nucleophilic attack with CO2 to
generate carboxylates. Following this mechanistic study, diverse
electrophiles, including aldehydes, ketones and benzylic bromides,
are also applicable in such transformation, demonstrating a general
strategy for redox-neutral remote difunctionalization of unactivated
alkenes.
contributions to this field and have developed varied strategies
to generate functionalized carboxylic acids with CO2. The visible
light-driven carboxylation of alkenes with CO2, in particular, has
attracted great attention due to the wide availability of a diversity
of alkenes (Scheme 1A). For example, Iwasawa[5e,5s] and
König[5n] both realized regioselective hydrocarboxylations of
alkenes via visible-light photoredox and transition metal dual
catalysis. Martin,[5h] Wu,[5r] Li[5z] and our group[5j,5x] have
developed different visible light-driven difunctionalizing
carboxylations of alkenes. These previously reported methods,
however, are limited to activated alkenes, including styrenes and
acrylates. In contrast, visible light-driven carboxylation of
unactivated alkenes still remains an unresolved challenge in this
field.
Catalytic difunctionalization of alkenes is an important tool to
generate highly functionalized skeletons.[6] The 1,2-
difunctionalization of alkenes has been investigated extensively,
resulting in diverse tools to generate complex molecules with
functional groups added across double bonds. With increased
interest in remote C–H functionalization,[7] chemists have been
recently investigating different strategies for the migrating
difunctionalization of alkenes to generate valuable compounds
with functional groups added over long relative distances.[8,9]
Compared to chain-walking reactions of alkenes catalyzed by
metal hydride species,[8] the strategy of radical-mediated remote
functionalization of
advantages such as mild reaction conditions, good
regioselectivity, and applicability to broader scope of
alkenes[9]
demonstrates significant
a
Introduction
substrates, including those in which pathways for chain-walking
might be blocked. This process combines radical attack to
alkenes, hydrogen atom transfer (HAT) and remote C–H
functionalization. In this process, to the best of our knowledge,
the newly generated radicals via HAT undergo either single
electron oxidation to an electrophilic carbocation[9c,9d,9f,9h] or
directly couple with reaction partners.[9e,9g] Another possibility
involving the reduction of the radical intermediate to a carbanion
and subsequent nucleophilic attack on an expectant electrophile
Carbon dioxide (CO2) is a promising one-carbon (C1) source in
chemical synthesis because of its abundance, availability, low
toxicity, and recyclability.[1] Carboxylations with CO2 are
fascinating processes to construct important carboxylic acids
with high atom- and step-economy.[2] Recently, due to significant
developments in photochemistry,[3] light-driven carboxylations
using CO2,[4,5] especially those employing visible light,[5] have
attracted growing attention. Many groups have made great
1
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10.1002/anie.202008630
Angewandte Chemie International Edition
RESEARCH ARTICLE
has never been reported for the remote functionalization of
alkenes. Herein, we report the first remote difunctionalization of
unactivated alkenes with CO2 via visible-light photoredox
catalysis (Scheme 1B). In addition to CO2, diverse electrophiles,
including aldehydes, ketones and benzylic bromides, are also
applicable in this process.
obtained in the absence of either (entries 5-7). A lower yield also
was obtained when reducing the amount of PC or shortening the
reaction time (entries 8-9). Additionally, the employment of other
solvents and/or PCs resulted in lower yields (entries 10-11)
Table 1. Reaction conditions screening.[a]
Entry
Variations
2a (%)[b]
3a (%)[b]
1
2
none
no light
81 (77)
N.D.
N.D.
14
13
N.D.
N.D.
69
3
no Ir(ppy)2(dtbbpy)PF6
N2 instead of CO2
no KOPiv
4
5
71
18
6
no Cs2CO3
60
30
Scheme 1. Visible light-driven carboxylations of alkenes with CO2.
7
no KOPiv and Cs2CO3
Ir(ppy)2(dtbbpy)PF6 (1 mol %)
12 h
50
14
It is well known that -amino acids are valuable synthetic
building blocks for peptides and they are widely used as
components of active drug molecules.[10] Moreover, due to the
effects on the metabolic stability, lipophilicity, and biopotency
induced by fluorine atoms, the introduction of fluorine-containing
groups on amino acids has beneficial effects in drug design and
peptide modification.[11] Therefore, at the early stage of this
project, we hoped to synthesize fluorine-containing -amino
acids via remote difunctionalization of alkenes. We envisioned
that the addition of fluorine-containing carbon radicals to the
unactivated alkene would generate new carbon radicals, which
then might undergo selective 1,5-HAT to give benzylic radicals.
Reduction to the corresponding benzylic carbanions and
nucleophilic attack on CO2 was expected to lead to generation of
the desired fluorine-containing -amino acids. This hypothesis,
however, faced several challenges, including the low reactivity of
unactivated alkenes as well as chemo- and regio-selectivity
issues arising from competitive monofunctionalization and other
side reactions.
8
76
14
9
67
24
10
11
DMF instead of DMAc
4CzIPN as PC
65
23
64
14
[a] Reaction conditions: 1a (0.2 mmol), Ir(ppy)2(dtbbpy)PF6 (2 mol %),
CF3SO2Na (2.5 equiv), Cs2CO3 (1.3 equiv), KOPiv (1 equiv), DMAc (0.1 M),
irradiation with 30 W blue LEDs at room temperature (22 - 25 °C) under
CO2 (1 atm) for 24 h. [b] 1H NMR yields using CH2Br2 as an internal
standard and isolated yields in parentheses. Bz = Benzoyl. N.D. = Not
detected. DMAc = N,N-dimethylacetamide, DMF = N,N-dimethylformamide,
4CzIPN = 2,4,5,6-tetrakis(carbazol-9-yl)-1,3-dicyanobenzene.
Table 2. Substrates with different amide motifs.[a]
Results and Discussion
On the basis of our hypothesis, we began our investigations
on the remote difunctionalizing carboxylation with substrate 1a
with Langlois reagent (CF3SO2Na, Eox = +1.05 V vs SCE in
MeCN)[12] and CO2 (1 atm) under visible-light irradiation at room
temperature. After systematically screening the reaction
parameters, the desired product 2a was obtained in 77% yield in
the presence of Ir(ppy)2(dtbbpy)PF6 (Ered [IrIII/IrII] = -1.51 V vs
SCE in MeCN)[13] as photocatalyst (PC) as well as the mixture of
Cs2CO3 and KOPiv as base (Table 1, entry 1). The
hydrotrifluoromethylation byproduct 3a was detected, which
presumably arose via competing protonation. Control
experiments revealed that the light, PC and CO2 were all
essential for the transformation (entries 2-4). It should be noted
that the desired product 2a also could be obtained in 14% yield
under N2 atmosphere (1 atm), which might because Cs2CO3 acts
as the source of CO2 (entry 4).[5i] Both KOPiv and Cs2CO3 played
an important role in the reaction, as lower yields of 2a were
[a] Standard reaction conditions (Table 1, entry 1) with yields of isolated
products. [b]: 5.0 mmol scale. Cy = cyclohexyl, Cp = cyclopropyl.
With the optimal reaction conditions in hand (Table 1, entry 1),
we then investigated substrates with different amide motifs,
which provided CF3-containing non-natural -amino acids in
moderate-to-good isolated yields (57-77%, Table 2). Moreover,
both electron-donating groups (EDGs) and electron-withdrawing
groups (EWGs) were tolerated at the para-position of the aryl
amides moieties (1a-1g). In addition to aryl amides, amides
substrates bearing heteroarenes, such as thiophene (1h), alkyl
groups (1i-1l), and carbamates (1m-1o) also worked well under
the standard conditions. Importantly, a 5 mmol scale reaction of
1a was carried out to afford 2a in 60% yield.
2
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10.1002/anie.202008630
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RESEARCH ARTICLE
Table 3. Substrates with different allyl arene motifs.[a]
Scheme 2. The reaction of 1ak bearing challenging tri-substituted unactivated
alkene under standard reaction conditions (Table 1, entry 1).
It should be noted that our reaction conditions also were
suitable for other structures containing an unactivated alkene an
a benzylic hydrogen (Scheme 3). For example, substrates 5
underwent the reaction smoothly to give products 6 with
satisfactory yields (48%-52%, Scheme 3A). In addition to the
synthesis of non-natural -amino acids, the strategy was also
amenable to the remote carboxylation of 1-allyl-2-ethylbenzene
(7) and hex-5-ene-1,1-diyldibenzene (9) to afford the
corresponding carboxylic acids in relatively lower yields
(Scheme 3B and 3C).
Scheme 3. Other substrates bearing unactivated alkenes.[a] [a] Standard
reaction conditions (Table 1, entry 1) with yields of isolated products. [b]
KOPiv (1.5 equiv).
[a] Standard reaction conditions (Table 1, entry 1) with yields of isolated
products. [b] Cs2CO3 (2.3 equiv). Boc
diastereoselectivity ratio.
= tert-butoxycarbonyl. d.r. =
We further explored the substrates with different allyl arene
motifs (Table 3). As expected, a broad range of benzylic amides
bearing diverse functional groups on the central arene
component, including amides (1s), esters (1t, 1aa), halides (1v,
1ac-1af), alkynes (1z), and carbonates (1ab), delivered the
corresponding products in moderate-to-good yields (44-78%).
This reaction was not hampered by ortho (1af, 1ag) or meta
substitutions (1w-1ae) on the central benzene ring. The
substrates bearing disubstitution on the arene core (1af) or
naphthalene (1ah) also were suitable. It is noteworthy that the
geminal-disubstituted alkene 1ai was also reactive, providing the
expected difunctionalization product 2ai in 59% yield.
Furthermore, the reaction of substrate 1aj also was smooth and
generated the corresponding ,-diaryl amino acid 2aj. To our
surprise, the tri-substituted unactivated alkene motifs (1ak) also
was compatible to give 4 as the major product via 1,6-HAT
process, which might arise from easier radical attack of alkene
at the less steric hindrance and generation of more stable
tertiary carbon radical (Scheme 2).
Scheme 4. Different radical precursors. [a] 1a (0.2 mmol), Ir(ppy)2(dtbbpy)PF6
(4 mol %), CHF2SO2Na (2.5 equiv), Cs2CO3 (1.3 equiv), KOPiv (1 equiv),
DMAc (0.1 M), irradiation with 30 W blue LEDs at room temperature under
CO2 (1 atm) for 48 h. [b] 1a (0.2 mmol, 1 equiv), 4CzIPN (2 mol %), HP(O)Ph2
(1.5 equiv), Cs2CO3 (1.5 equiv), DMSO (0.1 M), irradiation with 30 W blue
LEDs at room temperature under CO2 (1 atm) for 24 h.
Encouraged by the high reactivity of this transformation, we
wondered whether other radical precursors could also be
applied in the remote difunctionalizing carboxylation. As shown
in Scheme 4, we found that related difluoromethyl-containing -
amino acids are easily accessible when using CHF2SO2Na as
the radical precursor under similar reaction conditions (Scheme
4A). In addition to carbon-centered radicals, heteroatom-based
radicals were also examined. Considering the high value of
widely existing phosphorus-containing compounds,[14] we tested
HP(O)Ph2 as a radical precursor and successfully synthesized
the corresponding phosphorus-containing -amino acids by
using 4CzIPN as the photocatalyst (Scheme 4B). Taken
together, the results demonstrate the potential of this
methodology to construct functionalized -amino acids.
3
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RESEARCH ARTICLE
To further explore the potential application of our
transformation, the derivatizations of product 1a were performed
(Please see the supporting information (SI) for more details).
Firstly, the protecting benzoyl group could be removed easily to
generate the uniquely functionalized phenylglycine 13 in
excellent yield (96%). Moreover, the trifluomethyl-containing
dipeptide 14 and the thio-oxazolidine derivative 16 were easily
obtained from 2a in good yields. The success of these
experiments indicates the great potential of the methodology to
rapidly construct unique peptides for biological and
pharmaceutical evaluation.
To gain more insight into this new transformation, we
conducted various control experiments (Please see SI for more
details). When we tested the effect of radical scavengers,
including 2,2,6,6-tetramethyl-1-piperdiny-l-oxy (TEMPO) and
diphenyldiselenide (PhSeSePh), to the standard reaction
conditions, we found that only a trace amount or even no
desired product was detected (Please see SI for more details),
suggesting that radical intermediates might be involved. We then
subjected the deuterated substrate [D2]-1a to the reaction
conditions and obtained the [D2]-2a with more than 95% of
deuteration at the position  to the CF3 group, suggesting that a
1,5-deuterium atom transfer process occurred (Scheme 5A).
Partial H/D exchange at the position  to the carboxylic acid in
[D2]-2a also was observed, which might arise from high acidity
of this C−D/H bond. Additional isotope-labeling studies under a
nitrogen atmosphere suggested that an -amino benzylic anion
was formed as an intermediate, which can be quenched with
D2O to afford [D1]-3a (Scheme 5B). Moreover, kinetic isotopic
effects (KIE, H vs. D) of 4.0 and 1.5 were obtained for the intra-
and inter-molecular competition experiments, respectively
(Scheme 5C and 5D), which indicated that the 1,5-HAT process
might be involved in the rate-determining step. Finally, we
performed an intermolecular competition experiment, which
revealed that the substrate 1a with an EWG was slightly more
reactive than 1r with an EDG (Please see SI for more details).
Scheme 6. Plausible mechanism.
Based on the control experiments and previous studies,[5]
a
plausible mechanism for the overall transformation is proposed
and outlined in Scheme 6. First, the photo-excited Ir(III)-
photocatalyst is reductively quenched by CF3SO2Na to deliver a
CF3 radical and an Ir(II) species. The CF3 radical then
undergoes radical addition to the C=C bond to produce a new
carbon-centered radical (I). A rate-determining 1,5-HAT process
in a remote and site-selective manner then occurs to afford the
more stable benzylic radical II, which can be reduced by the Ir(II)
species to both afford the -amino benzylic anionic species III
and regenerate the requisite Ir(III)-photocatalyst. The
subsequent nucleophilic attack to CO2 and following protonation
can provide the observed carboxylic acids. Meanwhile, the direct
protonation of III would lead to the formation of byproduct 3a.
Table 4. Difunctionalization with aryl aldehydes.[a]
[a] All reactions were carried out with 1a (0.2 mmol, 1 equiv), ArCHO (1.5
equiv), CF3SO2Na (2.5 equiv), Ir(ppy)2(dtbbpy)PF6 (2 mol %), Cs2CO3 (1.1
equiv), 1 atm of N2 in anhydrous DMAc (0.1 M), irradiation with 30 W blue
LEDs at room temperature (22 - 25 °C) for 24 h, yields of isolated products.
Scheme 5. Control experiments.
4
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10.1002/anie.202008630
Angewandte Chemie International Edition
RESEARCH ARTICLE
theory.[15] As shown in Figure 1, the trifluoromethylsulfinate
(CP1) can undergo single-electron transfer (SET) with the
excited Ir(III)-photocatalyst to deliver a CF3SO2 radical (CP2).
Cleavage of the C–S bond then would readily generate
trifluoromethyl radical (CP3) with release of a gaseous SO2
molecule. Three possible pathways were duly considered in the
reaction between CF3 radical (CP3) and substrate 1a, including
radical addition to the C=C bond (black line), hydrogen atom
abstraction of the benzylic C−H (blue line), and radical type
substitution with the arene (red line). DFT calculations
determined that the activation free energy of radical addition to
the C=C bond via transition state TS1 was only 8.6 kcal/mol,
which was much lower than that found for the other two
processes via transition state TS4 or TS5. This radical addition
will generate a new C–C covalent bond in alkyl radical species I,
which is an irreversible exergonic process (29.8 kcal/mol). The
alkyl radical I can undergo a 1,5-HAT process via transition state
TS2 with an energy barrier of 12.7 kcal/mol to generate a
stabilized benzylic radical II. Then the radical II can be reduced
by Ir(II) to the benzylic carbanion III in an event that was
calculated to be exergonic by 12.5 kcal/mol. Subsequently, an
intermolecular nucleophilic attack of III to CO2 will take place via
transition state TS3 and a free energy barrier of only 3.4
kcal/mol to form carboxylate species CP4. In this process, the
1,5-HAT is considered to be the rate-limiting step with an energy
barrier of only 12.7 kcal/mol. The computational predictions are
consistent with the experimentally observed KIE values of 4.0
and 1.5 (Scheme 5C and 5D).
Scheme 7. Difunctionalization with other electrophiles.[a] [a] 1a (0.2 mmol), 19
(3 equiv), CF3SO2Na (2.5 equiv), Ir(ppy)2(dtbbpy)PF6 (2 mol %), K2CO3 (2
equiv), DMAc (0.1 M), irradiation with 30 W blue LEDs at room temperature
under N2 (1 atm) for 24 h. [b] 21 (3 equiv), Cs2CO3 (2 equiv).
Based on our proposed formation of -amino benzylic
carbanion III as a key intermediate under our reaction conditions,
we considered whether this remote difunctionalization could be
suitable for other electrophiles beyond CO2. To our delight, after
slightly modifying the reaction conditions, we demonstrated that
aryl aldehydes could be employed as electrophiles in a three-
component coupling protocol (Table 4). As illustrated, substrates
bearing either EDGs or EWGs (17a-17f) took part in this
reaction to deliver the corresponding 1,2-amino alcohols in
moderate-to-good yields (55-68%) without any significant
diastereoselectivity. A diverse range of functional groups, such
as fluoro (17a), phenoxyl (17c), ester (17d), sulfonyl (17e), and
pyridyl (17f), were well tolerated. In addition to aryl aldehydes,
aromatic ketoesters (19) also were appropriate coupling partners
in this reaction, affording β-amino acids 20 in moderate yields
(52-55%, Scheme 7A) and trace diastereoselectivity. Moreover,
benzyl bromides 21 also delivered corresponding products 22 in
relatively lower yields under the modified reaction conditions
(37-40%, Scheme 7B). Successful implementation of these
reactions suggests that this strategy would be useful for
achieving various other remote difunctionalizations of alkenes.
In order to validate the proposed reaction mechanism, we
conducted density functional theory (DFT) calculations at the
To evaluate the influence of different substitutions on the
reactivity, we further examined the 1,5-HAT process of two other
substrates. As shown in Figure S1b and S1c, the calculated free
energy barriers of 1,5-HAT for ortho-allylethylbenzene 23 and
amide 24 were 15.1 and 24.3 kcal/mol, respectively. Both of
these values are higher than that calculated for alkyl radical
species I (12.7 kcal/mol). These results revealed that the
stabilization of the carbon-centered radical was contributed by
both amino group and the conjugative phenyl ring, the latter of
which is considered to be the dominant factor.
M06-2X/def2-TZVP/SMD(DMAc)/B3LYP/def2-SVP
level
of
5
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10.1002/anie.202008630
Angewandte Chemie International Edition
RESEARCH ARTICLE
Figure 1. Free-energy profiles for the remote difunctionalizing carboxylation of unactivated alkenes. The values have been given in the unit of kcal/mol and
represent the relative free energies calculated using the M06-2x method in DMAc solvent.
We also thank the comprehensive training platform of the
Specialized Laboratory in the College of Chemistry at Sichuan
University for compound testing.
Conclusion
In summary, we have developed the first visible-light
Conflict of interest
photoredox-catalyzed remote difunctionalization of unactivated
alkenes with CO2. In contrast to previous strategies via direct
coupling or single-electron oxidation of radical intermediates
generated from 1,5-HAT process, our experimental and
computational investigations strongly indicate that our
transformation involves the single electron reduction of the
benzylic radicals to the corresponding carbanions, which further
undergo nucleophilic attack on CO2 to generate carboxylates.
This strategy provides a facile method to synthesize a series of
carboxylic acids, such as non-natural -amino acids, bearing
valuable fluorine- or phosphorus-containing functional groups,
and it features mild reaction conditions, broad substrate scope,
and good functional group tolerance. Moreover, this tactic can
be extended to different electrophiles, including aldehydes,
ketones, and benzylic bromides, allowing for the construction of
multifunctional amino acids or alcohols. Further application of
this strategy and biological activity testing for the novel small
molecules that it generates are underway in our labs.
The authors declare the following competing financial interest(s):
A Chinese Patent on this work has been applied with the
number 202010751742.3.
Keywords: visible-light photoredox catalysis
·
remote
difunctionalization · unactivated alkene · carbon dioxide · α-
amino acid
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Acknowledgements
We thank Prof. Jason Chruma (Sichuan University) for valuable
help. Financial support provided by the National Natural Science
Foundation of China (21822108, 21822303, 21772129 and
21772020), the Fok Ying Tung Education Foundation (161013),
Sichuan Science and Technology Program (20CXTD0112), and
the Fundamental Research Funds for the Central Universities.
6
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RESEARCH ARTICLE
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RESEARCH ARTICLE
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10.1002/anie.202008630
Angewandte Chemie International Edition
RESEARCH ARTICLE
Visible-Light Photoredox-Catalyzed Remote Difunctionalizing Carboxylation of
Unactivated Alkenes with CO2
Herein, we report the first remote difunctionalization of unactivated alkenes with CO2 via visible-light photoredox catalysis.
Mechanistic studies indicate that 1,5-hydrogen atom transfer process is the rate-limiting step and reduction of radical intermediates
generates the corresponding carbanions. Other electrophiles, including aldehydes, ketones and benzylic bromides, are also
applicable in this process, demonstrating a general strategy for redox-neutral remote difunctionalization of unactivated alkenes.
9
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