Nickel-catalyzed intermolecular carboiodination of alkynes with aryl iodides

Article abstract of DOI:10.1039/c8cc07560c

Nickel-catalyzed intermolecular carboiodination of alkynes with aryl iodides to form highly substituted and functionalized alkenyl iodides has been developed. The reaction involves radical-mediated formal alkyne insertion into the carbon-nickel bond and c

Full text of DOI:10.1039/c8cc07560c

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Nickel-catalyzed intermolecular carboiodination
of alkynes with aryl iodides†
Cite this: Chem. Commun., 2018,
54, 12750
Toshifumi Takahashi,‡ Daiki Kuroda,‡ Toru Kuwano,‡ Yuji Yoshida,‡
Received 18th September 2018,
Accepted 16th October 2018
Takuya Kurahashi * and Seijiro Matsubara*
DOI: 10.1039/c8cc07560c
rsc.li/chemcomm
Nickel-catalyzed intermolecular carboiodination of alkynes with
aryl iodides to form highly substituted and functionalized alkenyl
iodides has been developed. The reaction involves radical-mediated
formal alkyne insertion into the carbon–nickel bond and carbon–
iodine reductive elimination facilitated by Ni(III) species.
Organohalogen compounds such as alkenyl iodides are versatile
and essential building blocks in organic synthesis.1,2 Many estab-
lished reactions (e.g. transition-metal-catalyzed cross-coupling
reactions) require organohalogen compounds as coupling
partners, and halogen atoms are easily replaced with other
organic structures or heteroatoms to construct new chemical
bonds.3 Although the carbometallation of an alkyne followed by
reaction with a halogen source such as N-iodosuccinimide or I2
is well known as a conventional synthetic method, the develop-
ment of a direct, facile method to afford tetrasubstituted alkenyl
Fig. 1 Transition-metal-catalyzed carboiodination.
halides remains a research topic of great interest. In the last However, the steric bulkiness of both ligands and alkyne
decade, the transition-metal-catalyzed insertion of an alkyne into substituents retards alkyne insertion, and therefore, the reac-
the carbon–halogen bond of an organohalogen compound, i.e. tion was designed as an intramolecular process to overcome the
carbohalogenation, has been identified as a significant reaction steric hindrance. Thus, under this circumstance, there is a
which enables straightforward access to highly substituted trade-off between the promotion of reductive elimination and
alkenyl halides without by-product formation.4 However, based alkyne insertion. Herein, we report the intermolecular carbo-
on Hartwig’s study of the chemistry of ArPd(II)X complexes, the iodination of alkynes with aryl iodides to form highly substituted
reductive elimination of a carbon–halogen bond from a transi- and functionalized alkenyl iodides enabled by nickel catalysis
tion metal is disfavored and largely promoted by sterically bulky and radical-involving reaction mechanism (Fig. 1(c)).
ligands (Fig. 1(a)).5 Thus, Lautens’ group succeeded in develop-
We initially hypothesized that the aryl radical species
ing intramolecular carbohalogenation reactions of alkynes by generated by homolysis of the carbon–nickel bond could react
using bulky Q-Phos, tri-tert-butylphosphine, or aryl phosphaada- with alkynes, and recombination of the obtained alkenyl radical
mantanes as ligands for the palladium catalysts, and sterically and Ni(II)I2 forms an alkenylNi(III)I2 complex, followed by facile
demanding mesityl or TIPS groups as substituents of the alkynes reductive elimination to form the carbon–iodine bond from
to facilitate the key reductive elimination step (Fig. 1(b)).6 this high-valent complex would generate the desired alkenyl
iodide. Accordingly, intermolecular formal alkyne insertion
Department of Material Chemistry, Graduate School of Engineering,
Kyoto University, Kyoto 615-8510, Japan. E-mail: kurahashi.takuya.2c@kyoto-u.ac.jp,
matsubara.seijiro.2e@kyoto-u.ac.jp
into carbon–halogen bonds would be achieved. To prove our
hypothesis, we examined the nickel-catalyzed carboiodina-
tion of 4-octyne (2a) with iodobenzene (1a) in toluene at 50 1C
(Table S1, ESI†), and we found that alkenyl iodide 3aa was
obtained in 92% yield when dtbpy was employed as the ligand
(Scheme 1) (Fig. 2).
† Electronic supplementary information (ESI) available. CCDC 1847370 and
1847371. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c8cc07560c
‡ These authors contributed equally.
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Scheme 1 Nickel-catalyzed carboiodination of 2a with 1a.
Fig. 2 Working hypothesis for intermolecular carboiodination.
To determine the scope of the reaction, we next performed
the nickel-catalyzed carboiodination of alkynes with substi-
tuted iodobenzenes to obtain the corresponding tetrasubsti-
tuted alkenyl iodides (Scheme 2). The reaction of 4-tolyl iodide
with 4-octyne 2a gave 3ba in 81% isolated yield. Even though a
longer reaction time was required, m- or o-methyl-substituted
phenyl iodides also afforded alkenyl iodides in high yields (3ca:
48 h, 71%; 3da: 96 h, 91%). Naphthyl iodides also participated in
the reaction to give the corresponding alkenyl iodides (3ea, 3fa).
Furthermore, various functional groups were tolerated under the
reaction conditions; aryl iodides possessing alkoxy (3ga), trifluoro-
methyl (3ha), nitrile (3ia), ketone (3ja), or ester (3ka) substituents
participated in the reaction to provide the corresponding
alkenyl iodides in moderate to high yields. Of note, aryl iodides
possessing bromine or chlorine substituents also participated
in the reaction to give alkenyl iodides 3la and 3ma in 83% and
60% yields, respectively; clearly, bromine and chlorine atoms
were tolerated under the reaction conditions, and the carbo-
iodination proceeded in a chemoselective manner. Further-
more, boryl-substituted aryl iodides reacted with alkyne 2a to
afford the desired products in moderate-to-high yields (3na,
3oa, and 3pa) and the structure of 3pa was confirmed with X-ray
single crystal analysis (Fig. 3). Alkynes possessing alkoxy or
ester groups successfully participated to provide alkenyl iodides
3jb, 3jc, and 3jd in 53%, 99%, and 90% yield, respectively. The
reaction of phenyl bromide with 2a resulted in low yield (o5%).
The use of alkyl iodides in place of aryl iodide did not afford the
products. The reaction using non-symmetrical alkynes afforded
mixture of isomers and the reaction with terminal alkynes
resulted in low yield.
Scheme 2 Substrate scope in the carboiodination of alkynes with aryl
iodides. All reactions were carried out using Ni(cod)2 (5 mol%), ligand
(5 mol%), 1 (0.5 mmol), and 2 (0.75 mmol) in 1 mL of toluene at 50 1C for
12 h, unless otherwise noted. Isolated yields are given. Z/E ratio were
determined by 1H NMR analysis and given in parentheses. a 24 h. b 48 h.
c 72 h. d 96 h.
Fig. 3 ORTEP drawing of 3pa.
We next analyzed the catalytic reaction spectroscopically to
gain insight into the reaction mechanism. The reaction mixture
was subjected to electron paramagnetic resonance (EPR) measure- iodobenzene (1a) and 4-octyne (2a) in toluene (25 mM) displays
ments (Fig. 4). The mixture of catalytic amount of Ni(0)/dtbpy, a signal at g = 2.124, which is significantly deviated from that of
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Fig. 4 X-Band EPR merged-spectrum of the reaction mixture (red solid
line) and simulated spectrum based on DFT calculations of Ni(I)I/dtbpy
complex 4 (black dashed line). Spin density plot of computed Ni(I)I/dtbpy
complex 4. Mulliken spin density: Ni, 0.93; N, 0.05; N, 0.03; I, 0.02.
Fig. 6 Plausible reductive elimination mechanisms. These calculations
were performed with M06/SDD(2f)(Ni),SDD(I),6-311+G(2d,p)(C,H,N)//M06/
Lanl2dz(f)(Ni),Lanl2dz(I),6-31G(d)(C,H,N) with CPCM(toluene) solvation. Further
details are given in the ESI.†
complexes reported by Hillhouse, MacMillan, Doyle, and their
co-workers.8a,11,14
In summary, we have developed the nickel-catalyzed inter-
molecular carboiodination of alkynes with simple aryl iodides
to afford tetrasubstituted alkenyl iodides. The nickel-catalyzed
radical-involving reaction mechanism affords a new way to
access direct carbohalogenation in an intermolecular fashion
with atom- and redox-economy. The mechanism is based on the
unique properties of nickel catalysts with redox-active ligands
such as bipyridine that allow Ni(I) and Ni(III) oxidation states.15
Further investigations on the reaction mechanism are under-
way, both experimentally and theoretically, and will be reported
in due course.
We are grateful to Prof. Tatsuhisa Kato for valuable support
in the EPR analysis. This work was supported by the Advanced
Catalytic Transformation Program for Carbon Utilization (ACT-C,
JPMJCR12YE) from the Japan Science and Technology Agency
(JST), and Grants-in-Aid for Scientific Research (No. 18H04253,
17KT0006, and 15H03809) from the Ministry of Education,
Culture, Sports, Science and Technology (Japan). T. K. also
acknowledges the Uehara Memorial Foundation, and the Asahi
Glass Foundation. T. T. acknowledges the Council of Human
Resources Fostering Program in Chemistry and Japan Chemical
Industry Association for fellowship support.
Fig. 5 Plausible catalytic cycle.
a free electron (g = 2.002). This result indicates the presence
of paramagnetic nickel complex in the reaction mixture and
unpaired electron is mostly nickel based.7–10 Further computa-
tional studies revealed that Ni(I)I/dtbpy 4 simulates the experi-
mentally observed EPR spectrum in good agreement.
Based on these experiments, we propose a catalytic cycle
involving odd-valent nickel complexes and radical species, e.g.
Ni(I)I/dtbpy 4 which is generated via comproportionation in situ
(Fig. 5).12,13 The proposed mechanism is as follows: (1) oxida-
tive addition of iodobenzene 1a to Ni(I)I 4 gives unstable
PhNi(III)I2 5, which (2) forms phenyl radical 6 via carbon–nickel
bond homolysis. (3) The alkenyl radical 8 formed from phenyl
radical 6 and alkyne 2a, so that (4) recombination with the Ni(II)
7 complex gives alkenylNi(III)I2 9. Finally, (5) alkenyl iodides 3aa
are obtained as final products via facile reductive elimination
from the unstable high-valent Ni(III) complexes 9. This is con-
sistent with preliminary computational studies (Fig. 6, see
also ESI†); carbon–iodine reductive elimination from Ni(III) is
exergonic with a sufficiently low activation barrier, in contrast
to the endergonic reductive elimination from a Ni(II) complex
with a high energy barrier. The observed reactivities of Ni(III)
and Ni(II) in the reductive elimination are in good agreement with
studies of the carbon–oxygen reductive elimination of nickel
Conflicts of interest
There are no conflicts to declare.
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