Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by Combining Visible Light and Nickel Catalysis

Article abstract of DOI:10.1021/jacs.7b13448

The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of styrenes with atmospheric pressure of CO₂ at room temperature using dual visible-light-nickel catalysis has been developed. In the presence of neocuproine as ligand, the Markovnikov product is obtained exclusively, while employing 1,4-bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the anti-Markovnikov product. A range of functional groups and electron-poor, -neutral, as well as electron-rich styrene derivatives are tolerated by the reaction, providing the desired products in moderate to good yields. Preliminary mechanistic investigations indicate the generation of a nickel hydride (H-Ni^II) intermediate, which subsequently adds irreversibly to styrenes.

Full text of DOI:10.1021/jacs.7b13448

Subscriber access provided by UNIV OF DURHAM
Communication
Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes
2
with CO by Combining Visible Light and Nickel Catalysis
Qing-yuan Meng, Shun Wang, Gregory Huff, and Burkhard König
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b13448 • Publication Date (Web): 15 Feb 2018
Downloaded from http://pubs.acs.org on February 15, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
Journal of the American Chemical Society is published by the American Chemical
Society. 1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the
course of their duties.

Page 1 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Ligand-Controlled Regioselective Hydrocarboxylation of Sty-
renes with CO2 by Combining Visible Light and Nickel Catalysis
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
̈
Qing-Yuan Meng, Shun Wang, Gregory Huff and Burkhard Konig*
Institute of Organic Chemistry, Faculty of Chemistry and Pharmacy, University of Regensburg, D-93040 Regensburg, Ger-
many
Supporting Information Placeholder
sequently added to the -position of styrenes to produce the
ABSTRACT: The ligand-controlled Markovnikov and anti-
more stable benzylic radical species, thus ensuring anti-
Markovnikov hydrocarboxylation of styrenes with atmospher-
Markovnikov selectivity (Scheme 1b).7 Herein, we describe a
ic pressure of CO2 at room temperature using dual visible-
ligand-controlled, regiodivergent hydrocarboxylation of sty-
light-nickel catalysis has been developed. In the presence of
renes by combining visible light and Ni catalysis. Both Mar-
neocuproine as ligand, the Markovnikov product is obtained
kovnikov and anti-Markovnikov products can be selectively
exclusively, while employing 1,4-bis(diphenylphosphino)-
obtained by the proper choice of ligands, i.e. employing neo-
butane (dppb) as the ligand favors the formation of the anti-
cuproine as the ligand yields the Markovnikov product
Markovnikov product. A range of functional groups and elec-
(b:l=100:0, b:branched, l: linear), whereas utilizing 1,4-
tron-poor, -neutral, as well as electron-rich styrene derivatives
are tolerated by the reaction, providing the desired products in
moderate to good yields. Preliminary mechanistic investiga-
tions indicate the generation of a nickel hydride (H-NiII) in-
termediate, which subsequently adds irreversibly to styrenes.
bis(diphenylphosphino)butane (dppb) as the ligand promotes
the formation of the anti-Markovnikov product (l:b≧97:3)
(Scheme 1c).
Scheme 1. Hydrocarboxylation of Styrenes with CO2
Previous works:
a
(
) Markovnikov hydrocarboxylation of styrenes
M
Carboxylation with CO2 as an abundant one-carbon (C1)
building block would provide an extremely appealing way to
synthetically access valuable carboxylic acids.1 Among these
reactions, the carboxylation of styrenes with CO2 has been
regarded as a simple and atom-economic approach to -
methyl phenylacetic acid derivatives, which are frequent struc-
tural motifs in synthetic pharmaceuticals, such as Ibuprofen,
Naproxen and Fenoprofen.2 Rovis and co-workers pioneered
Ni-mediated catalytic hydrocarboxylation of electron-deficient
and -neutral styrene analogues with excellent regioselectivity.3
Thomas and Greenhalgh used FeCl2 as catalyst to synthesize
α-methyl phenylacetic acids from electron-rich and -neutral
styrene derivatives with CO2.4 After that, catalysts based on Ti
or Rh have also been employed to realize the transformation of
electron-rich or electron-deficient styrene derivatives into the
corresponding products.5 Strong reductants, including Et2Zn
and EtMgBr are necessary, to enable these transformations,
thus typically leading to lower functional group tolerance.
Martin and co-workers reported an excellent strategy to ac-
complish the Ni-catalyzed site-selective carboxylation of un-
saturated hydrocarbons with tolerance to a wider variety of
functional groups by using Mn as the stoichiometric reduct-
ant.6 Notably, all these protocols afford highly selective the
Markovnikov hydrocarboxylation of styrenes due to the for-
mation of the more stable η3 benzylic metal species (Scheme
1a). Therefore, selective anti-Markovnikov hydrocarboxyla-
tion of styrenes by metal catalysis is challenging and much
more difficult to realize. Very recently, Jamison and co-
workers developed a photoredox catalytic anti-Markovnikov
hydrocarboxylation of styrenes under UV light irradiation of
p-terphenyl as photosensitizer (PS) in continuous flow. CO2
was initially reduced into its anion radical CO2, which sub-
COOH
CO2
H+
Ni, Ti, Fe or Rh (Cat.)
Ar
Ar
Et2Zn, EtMgBr or Mn
Ar
(b) Anti-Markovnikov hydrocarboxylation of styrenes under UV light irradiation
e-
2H+
p-terphenyl (PS)
COOH
COO
+
CO2
Ar
Ar
Ar
NR3, UV light
This work:
(
c) Ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of
styrenes by visible light catalysis
Ni (Cat.)
dppb (L)
LNiBr2 (Cat.)
L: Neocuproine
Ar
COOH
COOH
+
Ar
4CzIPN (PS)
visible light
4CzIPN (PS)
visible light
Ar
CO2
l:b > 97:3;
b:l = 100:0;
42-83% yields
=
40-62% yields
Building on our recent experience with the direct carboxyla-
tion of (pseudo)halides with CO2 by dual visible-light-Ni ca-
talysis,8 we commenced our investigation on hydrocarboxyla-
tion of styrene with the developed system. Initially, various
solvents and nitrogen ligands were screened; only Markovni-
kov hydrocarboxylation of styrene was observed and the best
result was obtained when using DMF as the solvent and neo-
cuproine as the ligand (Table S1, entries 1-4 and Table S2,
entries 1-5). Interestingly, the addition of K2CO3 was not es-
sential for the reaction to proceed, and a similar reactivity was
observed when CsF was added as the additive to replace
K2CO3 (Table S1, entry 5).9 Screening of other photosensitiz-
ers including dyes and metal complexes demonstrated that
only [Ir(ppy)2(dtbbpy)]PF6 and [Ir(dF(Me)ppy)2(dtbbpy)]PF6
gave comparable results (Table S2, entries 6-13). It is notable
that using LNiBr2 (L = neocuproine) instead of NiBr2·glyme
and neocuproine provides a slightly better yield (Table S1,
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 2 of 5
1
2
3
4
5
6
7
8
Table 1. Scope of styrene derivatives for the Markovnikov
hydrocarboxylation with CO2
4Å MS as drying agent or by adding 1 equiv. of H2O, the effi-
ciency of the reaction decreased (Table S3, entries 19 and 20).
Finally, a 62% yield of the anti-Markovnikov hydrocarboxyla-
tion of styrene was obtained when 4-Me-HEH was used as the
reductant, whereas other reductants gave lower efficiencies
(Table S1, entry 17 and Table S3, entries 15-18).
a
4CzIPN (1 mol%)
LNiBr2 (10 mol%)
2M HCl
COOH
+
CO2
o
Ar
HEH (1.5 equiv.), 4 A MS (50 mg)
K2CO3 (1 equiv.), DMF
blue LEDs, 24h, r.t.
Ar
(balloon)
2
1
9
COOH
Table 2. Scope of styrene derivatives for anti-Markovnikov
hydrocarboxylation with CO2
COOH
COOH
COOH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
a
F
O
2b, yield: 55%
COOH
2d
2c, yield: 42%
, yield: 58%
2a, yield: 72%
COOH
COOH
COOH
HO
MeCOO
HO
t-Bu
2e,yield: 64%
COOH
2f, yield: 56%
COOH
2h, yield: 72%
COOH
2g, yield: 67%
COOH
N
MeO2C
Ph
2i, yield: 62%
COOH
O
O
2j, yield: 47%
2k, yield: 83%
2l, yield: 81%
COOH
COOH
COOH
F
O
NC
F3C
2m, yield: 76%
2o, yield: 66%
2n, yield: 69%
2p, yield: 60%
O
COOH
COOH
COOH
H
H
H
HOOC
2s, Ibuprofen, yield: 62%
CF3
COOMe
2r, yield: 43%
2q, yield: 55%
2t, yield: 71%
a
a
All reactions were carried out with styrene derivatives (0.2
All reactions were carried out with styrene derivatives (0.2
mmol), 4CzIPN (0.002 mmol), NiBr2·glyme (0.02 mmol), dppb
(0.04 mmol), LiOOCCH3 (0.2mmol), 4-Me-HEH (0.2 mmol) and
50 mg 4Å MS in anhydrous DMF (2 mL), irradiation with blue
LEDs at room temperature with a CO2 balloon for 24 h (l: linear,
b: branched). 4-Me-HEH: 4-Me-Hantzsch ester.
mmol), K2CO3 (0.2 mmol), 4CzIPN (0.002 mmol), LNiBr2 (0.02
mmol, L = neocuproine), HEH (0.3 mmol) and 50 mg 4Å MS in
anhydrous DMF (2 mL), irradiation with blue LEDs at room tem-
perature with a CO2 balloon for 24 h. HEH: Hantzsch ester.
entry 6). Control experiments confirmed the dual catalytic
nature of the Markovnikov hydrocarboxylation of styrene, as
no reaction was observed in the absence of reaction compo-
nents (Table S2, entries 14-18). Particularly, only 11% yield of
the desired product is obtained in the absence of 4Å MS,
which is explained by the fact that 4Å MS absorbs the water
produced in situ from the reaction of K2CO3 and the proton
released from Hantzsch ester (HEH; Table S2, entry 19). After
that, we attempted to selectively realize an anti-Markovnikov
hydrocarboxylation of styrene. As ligands can control the re-
giodivergent functionalization,10 a variety of phosphine lig-
ands were tried instead of neocuproine (Table S1, entries 7-14).
To our delight, the desired linear product is observed when
bis(diphenylphosphino)methane (dppm) was used as the lig-
and, albeit the yield and regioselectivity are low (Table S1,
entry 12). Linear products were obtained exclusively and with
increased efficiencies when 1,3-bis(diphenylphosphino)-
propane (dppp) and 1,4-bis(diphenylphosphino)butane (dppb)
were used as ligand, respectively (Table S1, entries 13 and 14).
Further optimizations including solvents and additives demon-
strated that the use of lithium acetate promoted the efficiency
and 41% yield of the desired product was formed (Table S1,
entry 15 and Table S3, entries 1-14). Gratifyingly, decreasing
the amount of the reductant enhanced the formation of the
linear product, which was ascribed to a less efficient styrene
hydrogenation; ethyl benzene was confirmed as the main by-
product in the reaction (Table S1, entry 16). In the absence of
Having identified the optimal reaction conditions for the
hydrocarboxylation of styrene by this dual visible-light-Ni
catalysis, we then aimed to explore the generality of our meth-
odology. Firstly, it was found that Markovnikov hydrocarbox-
ylation of several different styrene derivatives bearing elec-
tron-neutral (2a, 2b and 2e-2h), -donating (2c, 2i and 2o) or -
withdrawing substituents (2d, 2i-2n and 2p-2r) at para-, meta-
or ortho- positions proceeds well under our protocol, giving
the desired products in moderate to good yields (shown in
Table 1). A range of functional groups including fluoro (2d
and 2p), aliphatic and aromatic carboxylic esters (2h, 2l and
2q), amide (2j), ketone (2k), cyano (2m) and trifluoromethyl
(2n and 2r) are tolerated. Particularly, unprotected primary
and secondary alkyl hydroxyl groups were also applicable
affording the corresponding products in 56% and 67% yields,
respectively (2f and 2g). To demonstrate the application of our
newly developed method further, Ibuprofen was synthesized
and Estrone was derivatized. First, 4-isobutyl styrene was syn-
thesized as the starting material by Ni-catalyzed Kumada cou-
pling reaction.11 Then a 62% yield of Ibuprofen was obtained
under our standard conditions (2s). Moreover, a vinyl group
was introduced efficiently into the Estrone scaffold by triflate
activation of its hydroxyl group and subsequent Pd-catalyzed
Heck coupling reaction.12 The vinyl compound was trans-
formed into the desired -carboxylic acid in 71% yield (2t). It
is important that all reactions herein provided only the Mar-
ACS Paragon Plus Environment

Page 3 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
kovnikov hydrocarboxylation products, which confirms an
excellent regioselectivity.
normal secondary kinetic isotope effect (KIE) is observed
when a 1:1 ratio of styrene and d3-styrene were used as start-
ing materials for the Markovnikov hydrocarboxylation. A
larger secondary KIE is observed for the anti-Markovnikov
hydrocarboxylation of styrene, indicating that the addition of
the H-NiII species to styrene or the subsequent CO2 inserting
into the Ni-R bond are rate limiting (Scheme 2, equation 3 and
Scheme 3, equation 3). Finally, radical inhibitors, such as bu-
tylated hydroxytoluene (BHT) and 9,10-dihydroanthracene
(DHA) were added and all reactions proceeded well, thus sup-
porting that radical intermediates are not essential for the pro-
cess (Scheme S2, equation 1 and 2; Scheme S3, equation 1
and 2). However, the use of TEMPO reduced the reactivity
presumably due to the oxidation of HEH (Scheme S2, equa-
tion 3 and Scheme S3, equation 3).14
After that, we turned our attention to explore the generality
of styrene derivatives for anti-Markovnikov hydrocarboxyla-
tion with CO2. As shown in Table 2, ortho-substituted styrene
is compatible with this protocol, leading to the desired product
with high regioselectivity (3b). In the case of meta-substituted
styrenes, reactions also proceeded well to give the correspond-
ing products in moderate yields (3c-3f). Notably, para-
substituted styrenes including fluoro, ester and un-protected
hydroxy groups were tolerated under our conditions, affording
anti-Markovnikov hydrocarboxylation products with excellent
regioselectivity (3g-3i). However, none of the desired anti-
Markovnikov products and only small yields of the Markovni-
kov products were obtained with electron-withdrawing sub-
stituents, such as nitrile or ester, present in the styrene core.13
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 4. Plausible Reaction Mechanism
4CzIPN
Scheme 2. Deuterium-Labelling Experiments for Markov-
nikov Hydrocarboxylation of Styrene with CO2
h
*4CzIPN
HEH
COO
COO
Ph
Ph
HEH
COONiIL122
COONiIL2
E
Ph
e
4CzIPN
e
4CzIPN
Ph
E'
e
CO2
4CzIPN
O
Ni0Ln
A
NiII
NiIL2
L122
C
O
Ph
Ph
CO2
O
H+
G
D
H-NiIILn
B
e
NiIIL2
C
4CzIPN
C
O
Ni0L122
Ph
4CzIPN Ph
F
Ph
Based on the above results and in combination with our
previous work,8 a preliminary mechanism is proposed in
Scheme 4. Irradiation of 4CzIPN with visible light yields a
long-lived photoexcited state *4CzIPN ( = 5.1±0.5 s), which
oxidizes HEH affording 4CzIPN•- (E1/2red = -1.21 V vs SCE).15
The active Ni0Ln species A is generated in situ via two single
electron transfer (SET) steps [E1/2red (NiII/Ni0) = –1.2 V vs SCE]
under the photocatalytic reduction conditions.16 Subsequent
regioselective hydrometalation of styrene is supported by DFT
calculations (see discussion in the supporting information).
When L2 (neocuproine) was used as the ligand, protonation by
HEH•+ produces a Ni hydride complex B, i.e. H-NiIILn. Then
L2-ligated H-NiIILn creates a transient two-coordinated geom-
etry with less steric hindrance, thus leading to the formation of
a more stable organonickel complex C. After accepting one
electron from the reduced form of 4CzIPN,17 the insertion of
CO2 into D proceeds smoothly,18 leading to the generation of a
nickel carboxylate intermediate E, followed by further reduc-
tion to give the desired product and regenerate A for the next
cycle. When L12 (dppb) was employed as the ligand, a transi-
ent Ni0 species A combined with two ligands were generated,
which can be supported by the observation that a 1:1 ratio of
NiBr2·glyme and L12 gave none or much lower yield of the
desired product (Table S3, entries 21 and 22), while a 1:2 ratio
of NiBr2·glyme and L12 still catalyzes the transformation with
varying effectivity (Table S3, entries 23-26). This Ni0 species
A may coordinate with CO2 first,19 giving rise to intermediate
F, which subsequently inserts into styrene to generate a 5-
membered cyclic intermediate G. Upon accepting one electron
from the reduced form of 4CzIPN, a nickel carboxylate inter-
mediate E′ was produced. Finally, the desired product is re-
leased by further reduction. As experimentally supported by
Scheme 3. Deuterium-Labelling Experiments for Anti-
Markovnikov Hydrocarboxylation of Styrene with CO2
To gain information on the reaction mechanism, we initially
carried out dihydrogen generation experiments. We detect
trace amount of dihydrogen under our reaction conditions,
while no dihydrogen was generated in the absence of the Ni
catalyst or 4CzIPN, confirming that the combination of the Ni
catalyst and 4CzIPN can produce dihydrogen, likely via a H-
NiII intermediate (Scheme S1). Combined with facts that the
main by-product of the reaction was ethyl benzene, it is likely
that the H-NiII species adds to styrene, giving rise to an inter-
mediate Ni species for subsequent carboxylation. Furthermore,
deuterium experiments demonstrated that there was no H/D
scrambling when d7-DMF or d3-styrene was used, which
shows that the hydrogen atom for the hydrocarboxylation
comes from the reductant HEH or 4-Me-HEH, and the addi-
tion of the H-NiII species on styrene is irreversible (Scheme 2,
equation 1 and 2; Scheme 3, equation 1 and 2). Additionally, a
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 5
1
2
3
4
5
6
7
8
9
(5) (a) Shao, P.; Wang, S.; Chen, C.; Xi, C. Org. Lett. 2016, 18,
deuterium experiments, both hydrometalation of styrene and
insertion of F into styrene are irreversible.
2050; (b) Kawashima, S.; Aikawa, K.; Mikami, K. Eur. J. Org.
Chem. 2016, 2016, 3166.
(6) Gaydou, M.; Moragas, T.; Juliá-Hernández, F.; Martin, R. J.
Am. Chem. Soc. 2017, 139, 12161.
(7) Seo, H.; Liu, A.; Jamison, T. F. J. Am. Chem. Soc. 2017, 139,
13969.
(8) Meng, Q.-Y.; Wang, S.; König, B. Angew. Chem. Int. Ed.
2017, 56, 13426.
(9) (a) Li, S.; Yuan, W.; Ma, S. Angew. Chem. Int. Ed. 2011, 50,
2578; (b) Cao, T.; Yang, Z.; Ma, S. ACS Catal. 2017, 7, 4504.
(10) (a) Moragas, T.; Cornella, J.; Martin, R. J. Am. Chem. Soc.
2014, 136, 17702; (b) Su, W.; Gong, T.-J.; Lu, X.; Xu, M.-Y.;
Yu, C.-G.; Xu, Z.-Y.; Yu, H.-Z.; Xiao, B.; Fu, Y. Angew.
Chem. Int. Ed. 2015, 54, 12957; (c) Sakae, R.; Hirano, K.;
Miura, M. J. Am. Chem. Soc. 2015, 137, 6460; (d) Xu, T.; Sha,
F.; Alper, H. J. Am. Chem. Soc. 2016, 138, 6629.
(11) Alper, H.; Hamel, N. J. Am. Chem. Soc. 1990, 112, 2803.
(12) (a) Molander, G. A.; Rivero, M. R. Org. Lett. 2002, 4, 107; (b)
Straathof, N. J. W.; Cramer, S. E.; Hessel, V.; Noël, T. Angew.
Chem. Int. Ed. 2016, 55, 15549.
(13) (a) When using 4-vinylbenzonitrile or methyl 4-vinylbenzoate
as the starting material, only the Markovnikov product was ob-
tained (26% yield for 4-vinylbenzonitrile and 34% yield for
methyl 4-vinylbenzoate).
(14) (a) Semproni, S. P.; Milsmann, C.; Chirik, P. J. J. Am. Chem.
Soc. 2014, 136, 9211; (b) Kim, D. K.; Riedel, J.; Kim, R. S.;
Dong, V. M. J. Am. Chem. Soc. 2017, 139, 10208.
(15) (a) Uoyama, H.; Goushi, K.; Shizu, K.; Nomura, H.; Adachi, C.
Nature 2012, 492, 234; (b) Luo, J.; Zhang, J. ACS Catal. 2016,
6, 873.
(16) (a) Tellis, J. C.; Primer, D. N.; Molander, G. A. Science 2014,
345, 433; (b) Zuo, Z.; Ahneman, D. T.; Chu, L.; Terrett, J. A.;
Doyle, A. G.; MacMillan, D. W. C. Science 2014, 345, 437; (c)
Johnston, C. P.; Smith, R. T.; Allmendinger, S.; MacMillan, D.
W. C. Nature 2016, 536, 322.
(17) Attempts to synthesize intermediate C were unsuccessful.
However, the reduction potentials of its analogues are known
and locate around -1.20 V (vs SCE), see (a) Klein, A.; Kaiser,
A.; Sarkar, B.; Wanner, M.; Fiedler, J. Eur. J. Inorg. Chem.
2007, 2007, 965; (b) Klein, A.; Budnikova, Y. H.; Sinyashin,
O. G. J. Organomet. Chem. 2007, 692, 3156; (c) Yakhvarov,
D. G.; Petr, A.; Kataev, V.; Büchner, B.; Gómez-Ruiz, S.; Hey-
Hawkins, E.; Kvashennikova, S. V.; Ganushevich, Y. S.; Mo-
rozov, V. I.; Sinyashin, O. G. J. Organomet. Chem. 2014, 750,
59. Thus, C or C′ should be easily reduced.
(18) (a) Fujihara, T.; Nogi, K.; Xu, T.; Terao, J.; Tsuji, Y. J. Am.
Chem. Soc. 2012, 134, 9106; (b) León, T.; Correa, A.; Martin,
R. J. Am. Chem. Soc. 2013, 135, 1221; (c) Liu, Y.; Cornella, J.;
Martin, R. J. Am. Chem. Soc. 2014, 136, 11212; (d) Menges, F.
S.; Craig, S. M.; Tötsch, N.; Bloomfield, A.; Ghosh, S.;
Krüger, H.-J.; Johnson, M. A. Angew. Chem. Int. Ed. 2016, 55,
1282.
In conclusion, we have developed a dual visible-light-Ni ca-
talysis accomplishing an operationally simple, mild and highly
regioselective hydrocarboxylation of aryl alkenes using CO2 as
the C1-feedstock. Particularly, employing different ligands can
promote selective Markovnikov and anti-Markovnikov hydro-
carboxylation of styrenes with tolerance of many functional
groups. Mechanistic investigations indicated that a H-NiLn
species is generated during the process and adds irreversible to
styrene. Further investigations on the reaction mechanism and
the development of an efficient version to realize anti-
Markovnikov hydrocarboxylation of electron-deficient sty-
renes are in progress.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ASSOCIATED CONTENT
Supporting Information
Experimental procedures, methods and product characterization.
This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
̈
burkhard.konig@ur.de
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
Financial support from the German Science Foundation (DFG)
(GRK 1626, Chemical Photocatalysis) is acknowledged. We
thank Prof. Ruben Martin (Institute of Chemical Research of Cat-
alonia) and Prof. Tomislav Rovis (Columbia University) for valu-
able discussions and suggestions. We thank Dr. Rudolf Vasold
(University of Regensburg) for his assistance in GC-MS meas-
urements and Sebastian Sandl (University of Regensburg) for his
assistance in glovebox experiments.
REFERENCES
(1) (a) Braunstein, P.; Matt, D.; Nobel, D. Chem. Rev. 1988, 88,
747; (b) Sakakura, T.; Choi, J.-C.; Yasuda, H. Chem. Rev.
2007, 107, 2365; (c) Correa, A.; Martín, R. Angew. Chem. Int.
Ed. 2009, 48, 6201; (d) Huang, K.; Sun, C.-L.; Shi, Z.-J. Chem.
Soc. Rev. 2011, 40, 2435; (e) Martín, R.; Kleij, A. W.
ChemSusChem 2011, 4, 1259; (f) Tsuji, Y.; Fujihara, T. Chem.
Commun. 2012, 48, 9956; (g) Sakakura, T.; Kohno, K. Chem.
Commun. 2009, 1312; (h) Liu, Q.; Wu, L.; Jackstell, R.; Beller,
M. Nat. Commun. 2015, 6, 5933. (i) Börjesson, M.; Moragas,
T.; Gallego, D.; Martin, R. ACS Catal. 2016, 6, 6739; (j) Gui,
Y.-Y.; Zhou, W.-J.; Ye, J.-H.; Yu, D.-G. ChemSusChem 2017,
10, 1337.
(2) (a) Weggen, S.; Eriksen, J. L.; Das, P.; Sagi, S. A.; Wang, R.;
Pietrzik, C. U.; Findlay, K. A.; Smith, T. E.; Murphy, M. P.;
Bulter, T.; Kang, D. E.; Marquez-Sterling, N.; Golde, T. E.;
Koo, E. H. Nature 2001, 414, 212; (b) Lolli, M. L.; Cena, C.;
Medana, C.; Lazzarato, L.; Morini, G.; Coruzzi, G.; Manarini,
S.; Fruttero, R.; Gasco, A. J. Med. Chem. 2001, 44, 3463; (c)
Takeda, T.; Kumar, R.; Raman, E. P.; Klimov, D. K. J. Phys.
Chem. B 2010, 114, 15394; (d) Rosario-Meléndez, R.; Yu, W.;
Uhrich, K. E. Biomacromolecules 2013, 14, 3542; (e) Lynagh,
T.; Romero-Rojo, J. L.; Lund, C.; Pless, S. A. J. Med. Chem.
2017, 60, 8192.
(19) (a) Aresta, M.; Nobile, C. F.; Albano, V. G.; Forni, E.; Manas-
sero, M. J. Chem. Soc., Chem. Commun. 1975, 636; (b) Ama-
tore, C.; Jutand, A. J. Am. Chem. Soc. 1991, 113, 2819.
(3)
Williams, C. M.; Johnson, J. B.; Rovis, T. J. Am. Chem. Soc.
2008, 130, 14936.
(4) Greenhalgh, M. D.; Thomas, S. P. J. Am. Chem. Soc. 2012,
134, 11900.
ACS Paragon Plus Environment

Page 5 of 5
Journal of the American Chemical Society
1
2
3
4
5
6
TOC:
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
ACS Paragon Plus Environment