Visible light-driven cross-coupling reactions of alkyl halides with phenylacetylene derivatives for C(sp3)-C(sp) bond formation catalyzed by a B12 complex

Article abstract of DOI:10.1039/c9cc06185a

Visible light-driven cross-coupling reactions of alkyl halides with phenylacetylene and its derivatives catalyzed by the cobalamin derivative (B₁₂) with the [Ir(dtbbpy)(ppy)₂]PF₆ photocatalyst at room temperature are reported. The robust B₁₂ catalyst and Ir photocatalyst provided high turnover numbers of over 33?000 for the reactions.

Full text of DOI:10.1039/c9cc06185a

Showcasing research from Professor Hisashi Shimakoshi and
Professor Yoshio Hisaeda’s laboratory, Graduate School of
Engineering, Kyushu University, Fukuoka, Japan.
As featured in:
Volume 55 Number 87 11 November 2019 Pages 13019–13186
Visible light-driven cross-coupling reactions of alkyl halides
with phenylacetylene derivatives for C(sp3)–C(sp) bond
formation catalyzed by a B12 complex
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Chemical Communications
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The efficient coupling reaction of alkyl halides with alkynes
by the dual catalysis system of the B12 complex and Ir complex
under visible light irradiation at room temperature is reported.
The useful substituted alkynes were obtained by a mild method.
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Visible light-driven cross-coupling reactions of
alkyl halides with phenylacetylene derivatives for
C(sp3)–C(sp) bond formation catalyzed by a B12
complex†
Cite this: Chem. Commun., 2019,
55, 13070
Received 9th August 2019,
Accepted 20th September 2019
Li Chen, Yohei Kametani, Kenji Imamura, Tsukasa Abe, Yoshihito Shiota,
DOI: 10.1039/c9cc06185a
Kazunari Yoshizawa,
Yoshio Hisaeda * and Hisashi Shimakoshi
*
rsc.li/chemcomm
Visible light-driven cross-coupling reactions of alkyl halides with (C1) (Fig. 1), combined with the use of a photocatalyst at room
phenylacetylene and its derivatives catalyzed by the cobalamin temperature.6 In this reaction, the supernucleophilic Co(I) species of
derivative (B12) with the [Ir(dtbbpy)(ppy)2]PF6 photocatalyst at room the B12 complex is formed by photoinduced electron transfer from
temperature are reported. The robust B12 catalyst and Ir photocata- the photocatalyst, and the Co(I) complex reacted with the alkyl halide
lyst provided high turnover numbers of over 33000 for the reactions. to form an alkylated cobalt complex. Subsequent photolysis of the
Co–C bond produces an alkyl radical, which was utilized in the
Substituted alkynes are important structural motifs in various areas substituted alkene syntheses. As an expansion to these studies, we
such as medicinal chemistry, agrochemistry, and materials chem- now disclose a visible light-driven catalytic alkynylation reaction of
istry. Cross-coupling reactions of organic halides with terminal alkyl halides (R–X, X = Cl, Br, I) to form substituted alkynes at room
alkynes are useful methods of C(sp3)–C(sp) or C(sp2)–C(sp) bond temperature or 45 1C. As photoredox catalysts are utilized for various
formation for substituted alkynes in many relevant academic and molecular transformations,7 great attention has been paid to the
industrial applications.1 The most powerful and famous alkynylation light-driven molecular transformation in recent synthetic organic
of organic halides is the transition-metal, Pd and Cu, catalyzed chemistry. The advantage of the combined use of a photoredox
Sonogashira reaction.2 For the development of this useful reaction, catalyst and the B12 catalyst for the alkynylation reaction is shown in
various advanced protocols have been investigated such as the use of this study. Detailed mechanistic studies were also conducted.
non-expensive metals, transition-metal free, room temperature, non-
additive, expansion of the substrate scope, etc.3 Among them, the
coupling of terminal alkynes with unactivated alkyl halides which
promote the undesired b-hydride elimination is still a challenging
work.4 Furthermore, efficient, economical, and eco-friendly green
molecular transformation is a contentious requirement in industrial
synthetic organic chemistry. Light-driven molecular transformations
are one of the prominent protocols in organic synthesis including
the coupling reaction, and the alkynylation of aliphatic halides for
the C(sp3)–C(sp) bond formation by UV or VIS light irradiation is also
reported (Scheme 1).5 As some methods were reported in recent
years, the visible light-driven, room temperature coupling reactions
of non-activated aliphatic organic halides with terminal alkynes are
still being explored.
Recently, we reported a visible light-driven catalytic coupling
reaction of alkyl halides with styrene and its derivatives to form
substituted alkenes by the cobalamin derivative, the B12 complex
Department of Chemistry and Biochemistry, Graduate School of Engineering,
Kyushu University, Nishi-ku, Motooka, Fukuoka 744, 819-0395, Japan.
E-mail: yhisatcm@mail.cstm.kyushu-u.ac.jp, shimakoshi@mail.cstm.kyushu-u.ac.jp
† Electronic supplementary information (ESI) available: Experimental procedure,
Scheme 1 Methods of alkynylation of alkyl halides for C(sp3)–C(sp) bond
including synthesis and spectroscopic data of compounds. See DOI: 10.1039/
formation.
c9cc06185a
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Table 1 Photocatalytic alkynylation of phenethyl bromide (B1) under
visible light irradiation at room temperaturea
Conversion
(%)
Yield of
1a (%)
Entry
Reaction conditions
1
2
3
4
5
6
7
8
9b
As shown
No B12 complex
No PC
No i-Pr2NEt
No light
PC is [Ru(bpy)3]Cl2 (P2)
PC is Ir(ppy)3 (P3)
C2 catalyst
[A1] = 0.4 M, [B1] = 0.4 M, reaction
time was 48 h
Solar simulator
Adding 300 equiv. mole of DMPO
499
0
89
0
0
0
0
0
0
0
29
57
69
499
9
40
37
83
10c
11d
499
499
88
0
Light irradiation (LED, lmax = 448 nm). Conditions: [C1] = 1.0 Â 10À4 M,
[PC] = 1 Â 10À5 M, [A1] = 1.5 Â 10À1 M, [B1] = 2.0 Â 10À2 M, [i-Pr2NEt] = 1.0 Â
10À1 M, solvent: 10 mL of CH3OH under N2 at room temperature. Reaction
time: 6 h. Conversions of the substrate and the product yield were based on
the initial concentration of B1. b [C1] = 1 Â 10À5 M, [i-Pr2NEt] = 2 M. c Solar
simulator was used as the light source. d [DMPO] = 6.0 Â 10À1 M.
a
Fig. 1 Structure of the B12 complex (C1), Co(III){(C2C3)(DO)(DOH)pn}Br2
(C2), [Ir(dtbbpy)(ppy)2]PF6 (P1), [Ru(bpy)3]Cl2 (P2), and Ir(ppy)3 (P3).
We first studied the reaction of phenethyl bromide (B1) with
phenylacetylene (A1) under LED (lmax = 448 nm) irradiation using
the B12 complex (C1) as the catalyst and [Ir(dtbbpy)(ppy)2]PF6 (P1) as
the photocatalyst (PC) at room temperature (Fig. 1). The coupling
product, 1,4-diphenyl-1-butyne (1a), was obtained in 89% yield
without any by-products (entry 1 in Table 1). Optimization of the
reaction conditions is summarized in Table S1 (ESI†). Controlled
reactions showed that both the B12 catalyst and PS are essential for
the reaction (entries 2 and 3 in Table 1). Without light irradiation or
a sacrificial reagent (i-Pr2NEt), the reaction did not proceed (entries 4
and 5 in Table 1). When [Ru(bpy)3]Cl2 (P2) or Ir(ppy)3 (P3) was used
as the PC, the yield of 1a decreased to 9% and 40%, respectively
(entries 6 and 7 in Table 1). The cobalt complex (C2) having a similar
Co(II)/Co(I) redox couple (E1/2 = À0.65 V vs. SCE in CH3CN) to C1
(E1/2 = À0.64 V vs. SCE in CH3CN)8 decreased the product yield to
37% (entry 8 in Table 1). Catalyst C2 decomposed due to light
irradiation while the C1 catalyst survived during the reaction that
was confirmed by UV-vis absorption spectroscopy and MS analysis
(Fig. S25 and S26, ESI†). This result suggested that a higher turnover
number (TON) based on the catalyst might be achieved in the
present catalytic system. Actually, a high TON of 33 200 based on
C1 was obtained by increasing the concentration of the substrates
and reaction time (entry 9 in Table 1). The catalytic reaction was
Table 2 Scope of alkyl halidesa
a
Light irradiation (LED, lmax = 448 nm). Conditions: [C1] = 1.0 Â 10À4 M,
also carried out using a solar simulator to show the application [P1] = 1 Â 10À5 M, [A1] = 1.5 Â 10À1 M, [B1–B15] = 2.0 Â 10À2 M, [i-Pr2NEt] =
1.0 Â 10À1 M, solvent: 10 mL of CH3OH in N2 at room temperature.
of sunlight for the reaction and 1a was produced in 88% yield
(entry 10 in Table 1). It should be noted that the dual catalysis
Reaction time: 6 h. Product yields were based on the initial concentration
of the alkyl halide. Reaction was carried out at 45 1C, [A1] = 3.0 Â 10À1 M,
b
strategy combined use of an efficient nonphotochemical catalyst [R–X] = 3.0 Â 10À2 M. Reaction time: 8 h. (2-Cyclohexylvinyl)benzene
c
d
(E form) was formed in 52% yield. (2-Cyclohexylvinyl)benzene (E form)
and a suitable photocatalyst provided a useful protocol for the
was formed in 45% yield.
photochemical organic synthesis.9 Therefore, the present photo-
catalytic system should be applicable for the practical synthesis
temperature. Upon increasing the reaction temperature to 45 1C,
the yield of 1a increased to 91% for phenethyl chloride. Electron
withdrawing substitution on the phenyl ring of phenethyl bro-
mide decreased the yields of the products (1e and 1f) which is
of the product in an eco-friendly manner.
The alkynylation reaction was applied to other alkyl halides as
shown in Table 2. The yield of 1a was 92% for phenethyl iodide
while only 18% of 1a was obtained for phenethyl chloride at room
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Table 3 Scope of phenylacetylene derivativesa
a
Light irradiation (LED, lmax = 448 nm). Conditions: [C1] = 1.0 Â 10À4
M, [P1] = 1 Â 10À5 M, [A2–A11] = 1.5 Â 10À1 M, [B1] = 2.0 Â 10À2 M,
[i-Pr2NEt] = 1.0 Â 10À1 M, solvent: 10 mL of CH3OH in N2 at room
temperature. Reaction time: 6 h. Product yields were based on the
initial concentration of B1.
Scheme 3 Proposed mechanism.
species initiates the reaction.6,11 We hypothesized that the B12
complex catalyzes the alkynylation reaction via a radical pathway
during the initial part of the reaction. To support this mechanism,
some mechanistic experiments were performed. First, a radical-
clock experiment with 6-bromo-1-hexene (B16)6 verified the for-
mation of the initial phenethyl radical G from the alkylated cobalt
complex to form the cyclic coupling product 1j with 61% yield via
radical H followed by radical I in the reaction with the alkyne
(Scheme 4a). Next, an ESR spin-trapping experiment was conducted
probably due to the decreasing electron density of the phenethyl
radical to lower their nucleophilicities, while the yields of 1e and 1f
increased to 87% and 79%, respectively, by increasing the reaction
temperature to 45 1C. Benzyl halides (X = Br, Cl), (bromomethyl)-
cyclohexane, and bromo- or iodocyclohexane also afforded the
corresponding coupling products, 1g, 1h, and 1i, respectively.‡
The scope of the alkynylation of phenethyl bromide with various
substitution patterns of phenylacetylene is also shown in Table 3.
No large substituent effects on the phenyl ring of the alkynes
(A2–A11) were seen in the product yield, and moderate to good yields
of the coupling products were obtained.§ Finally, the advantage of
the present photo-catalytic system being superior to conventional
radical forming reagents, n-Bu3SnH/azobisisobutyronitrile (AIBN),
was investigated. Low yields of the products (1a, 1g, and 1h) were
obtained as shown in Scheme 2. Undesired homo-coupling products
from organic halides were also formed by this method.
The proposed reaction mechanism is shown in Scheme 3.
The UV-vis spectral change indicated the formation of the Co(I)
species of the B12 complex by visible light irradiation (Fig. S2,
ESI†). As the E(L/LÀ) value of [Ir(dtbbpy)(ppy)2]PF6 (E = À1.43 V
vs. SCE in CH3CN) is negative compared to that of [Ru(bpy)3]Cl2
(E = À1.30 V vs. SCE in CH3CN),10 the use of [Ir(dtbbpy)(ppy)2]PF6
showed a superior yield of the product as the efficient reductive
formation of Co(I) species by PS (entry 6 in Table 1). We already
clarified the reductive quenching of P1 by i-Pr2NEt followed
by the electron transfer to C1 by transient photoluminescence
measurements.8a ¶ The nucleophilic attack of the formed Co(I)
Scheme 4 Mechanistic investigations of the photocatalytic alkynylation
Scheme 2 Reactions by an n-Bu3SnH/AIBN system.
13072 | Chem. Commun., 2019, 55, 13070--13073
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using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as the radical trap- Scaffolding, and by a Grant from the Nippon Sheet Glass
ping reagent. The ESR signal for the carbon-centered radical Foundation (HAKF541800).
trapped by DMPO (g = 2.006, AN = 14.7 G, AH = 21.2 G) was
observed during the photocatalytic reaction (Fig. S3, ESI†). Under
this condition, DMPO fully inhibited the product formation (entry
Conflicts of interest
11 in Table 1), which implied a radical pathway for the coupling
reaction. Substituent effects on the phenyl ring of the phenethyl
There are no conflicts to declare.
radical for products 1e and 1f in Table 2 could be explained by the
Notes and references
decreasing electron density of the substrate radical, which under-
‡ Bulky t-butyl bromide and (1-bromoethyl)benzene provided no
went a nucleophilic attack on the alkyne. To elucidate the final step
desired cross-coupling product with A1.
for the alkyne formation from radical E in Scheme 3 or I in
Scheme 4a, the formation of hydrogen gas was analyzed by GC,
and no hydrogen gas was detected by GC after the reaction (Fig. S4,
ESI†), which excludes the b-elimination of radical E. Also no
deuterium isotopic effect was observed for the deuterated phenyl-
acetylene (A1–d), and 1a was formed in 85% yield (Scheme 4b),
which is similar to the standard conditions.8 Therefore, C–H bond
cleavage on A1 is not the rate-determining step in the reaction.
Finally, on–off light experiments were conducted to explore the
radical propagation mechanism. A clear light dependence was
observed for the reaction and radical propagation was unlikely.
Based on these experiments, the B12 catalyzed coupling reaction
should proceed by the mechanism as shown in Scheme 3. Radical E
should be oxidized to form carbocation F by the excited state of PS
(E(L*/LÀ) = 0.70 V vs. SCE in CH3CN for P1)8 and the energetically
preferred deprotonation of F to form the final product. To help
understand the deprotonation of the carbocation by i-Pr2NEt, we
performed DFT calculations using the B3LYP functional combined
with the 6-31G** basis. All the calculated energies and optimized
structures are summarized in the ESI,† and the DFT calculations
support the proposed mechanism of the energetically preferred
deprotonation step (Fig. S28, ESI†).
§ A nitro-substituent on the phenyl ring of A1 provided no desired
cross-coupling product with B1.
¶ The rate constant for the electron transfer between the photoexcited
P1 (P1*) and i-Pr2NEt is 7.0 Â 108 MÀ1
s
À1, while the electron transfer
from P1* to C1 is not observed. See ref. 8a.
8 Time courses of reactions are shown in Fig. S27 (ESI†).
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In summary, we have developed a visible light-driven cou-
pling reaction of alkyl halides with phenylacetylene derivatives
for C(sp3)–C(sp) bond formation. An efficient reaction system
by the dual catalyst under mild conditions was conducted. The
B12 complex worked as an excellent catalyst with a high turn-
over under light irradiation. On-going work in our laboratory is
focused on the application of the dual catalyst to develop
various organic synthesis methods with a green procedure.
This study was partially supported by a Grant-in-Aid for 10 D. M. Arias-Rotondo and J. K. McCusker, Chem. Soc. Rev., 2016, 45,
5803–5820.
Scientific Research (B) (JP19H02735) from the Japan Society
for the Promotion of Science (JSPS), KAKENHI Grant Number
11 See reviews: (a) M. Giedyk, K. Goliszewska and D. Gryko, Chem. Soc.
¨
Rev., 2015, 44, 3391–3404; (b) K. Gruber, B. Puffer and B. Krautler,
JP18H04265 in Precisely Designed Catalysts with Customized
Chem. Soc. Rev., 2011, 40, 4346–4363.
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