Cyanoborohydride-promoted radical arylation of benzene

Article abstract of DOI:10.1021/ol500614q

Radical biaryl coupling of iodoarenes and benzene can be effectively promoted by tetrabutylammonium cyanoborohydride with air under photoirradiation conditions using a Xe lamp. The utility of this methodology is highlighted by its functional group tolerance and chemoselectivity.

Full text of DOI:10.1021/ol500614q

Letter
pubs.acs.org/OrgLett
Cyanoborohydride-Promoted Radical Arylation of Benzene
Takuji Kawamoto, Aoi Sato, and Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
S
* Supporting Information
ABSTRACT: Radical biaryl coupling of iodoarenes and benzene can be
effectively promoted by tetrabutylammonium cyanoborohydride with air
under photoirradiation conditions using a Xe lamp. The utility of this
methodology is highlighted by its functional group tolerance and
chemoselectivity.
omolytic aromatic substitution (HAS) reactions by an
aryl radical are one of the most straightforward methods
irradiated with a 500 W Xe lamp in a Pyrex tube for 24 h under
H
air, the desired 4-methoxy-1-phenylbenzene (2a) was obtained
in 38% yield together with 2% yield of anisole (3a) (Table 1,
entry 1). For comparison, we also examined radical arylation of
benzene under degassed conditions by freeze−pump−thaw
cycles, which gave the arylation product 2a (38%) and an
increased amount of reduced product 3a (16%) (Table 1, entry
2).16 Under aerobic conditions, the addition of 0.75 and 1 equiv
of Bu4NBH3CN increased the yield of 2a to 55 and 78%,
respectively (Table 1, entries 3 and 4). However, further
increases of the amount of Bu4NBH3CN, such as 2 equiv,
resulted in an increase in the formation of reduced product
anisole (3a), compared to the desired arylation product (Table
1, entry 5).17
With the optimized conditions of entry 4 in hand, we next
examined the substrate scope for aromatic arylation and the
results are given in Table 2. 4-Iodotoluene (1b), ethyl 4-
iodobenzoate (1c), ethyl 2-(4-iodophenyl)acetate (1d), 4-
iodoacetophenone (1e), 1-fluoro-4-iodobenzene (1f), and 4-
trifluoromethyl-1-iodobenzene (1g) were converted to the
corresponding biaryls 2b, 2c, 2d, 2e, 2f, and 2g in 70, 68%,
53%, 55%, 67%, and 48%, respectively (Table 2, entries 2−7).
The reactions of 3-iodoanisole (1h), ethyl 3-iodobenzoate (1i),
2-iodoanisole (1j), 2-iodotoluene (1k), and ethyl-2-iodoben-
zoate (1l) were also successful (Table 2, entries 8−12). Both 1-
and 2-iodonaphthalene (1m and 1n) worked well to give 1-
phenylnaphthalene (2m) and 2-phenylnaphthalene (2n) in 57
and 82% yields, respectively (Table 2, entries 13 and 14). We
performed the reactions by reacting aryl iodides 1a with
toluene. As expected, reactions of 1a with toluene afforded
regioisomeric mixtures favoring the ortho products (Table 2,
entry 15).18
for the construction of biaryl motifs.1−4 Recent research in this
area includes base-promoted HAS (BHAS) reactions; for
example, in 2008, Itami reported that biaryl coupling of
electron-deficient nitrogen heterocycles and haloarenes was
promoted by KO-t-Bu.5 Kwong and Lei,6 Shi,7 and Shirakawa
and Hayashi8 all independently expanded this benzene−
arylation chemistry by using a strong base and a bidentate
ligand.9,10 Curran and Studer have reported BHAS reactions
using PhNHNH2 as an initiator with KO-t-Bu.11 Rossi
demonstrated that BHAS reactions could proceed under
photoirradiation conditions at ambient temperature.12 More
recently, Zheng and Guo reported that TMEDA-catalyzed
radical arylation of benzene under photoirradiation conditions
with high tolerance of functional groups.13 Recently, we
reported radical C−C bond-forming reactions using borohy-
dride reagents as chain mediators.14,15 In this paper, we report
that cyanoborohydride promotes the synthesis of biaryl
compounds from iodoarenes and benzene under aerobic
photoirradiation conditions. This reaction proceeds in a
chemoselective fashion for bromo- and iodo- substituted
arenes.
4-Iodoanisole (1a) was chosen as a model substrate for the
initial study (Table 1). When a benzene solution of 1a was
Table 1. Optimization of Arylation Reaction Conditions
Shirakawa and Hayashi have reported that under controlled
conditions the HAS reaction of 1-bromo-4-iodobenzene (1p)
with NaO-t-Bu and catalytic amount of Ph-phen (4,7-diphenyl-
1,10-phenanthroline) takes place chemoselectively at the aryl−
iodine bond to give 4-bromobiphenyl (2p).8 In contrast, KO-t-
Bu-promoted HAS reaction of benzene with either 1-chloro-
(1o) or 1-bromo-4-iodobenzene (1p) afforded only 1,4-
a
a
entry
1
Bu4NBH3CN (equiv)
2a (%)
3a (%)
0
38
38
55
2
16
7
b
2
0
3
4
5
0.75
1
c
78
9
2
38
41
a
b
GC yield. Reaction was performed under degassed conditions by
freeze−pump−thaw cycles. Isolated yield after silica gel column
c
Received: February 26, 2014
Published: April 3, 2014
chromatography.
© 2014 American Chemical Society
2111
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Organic Letters
Letter
Table 2. Arylation of Benzene with Various Aryl Iodides
Scheme 1. Reaction of 1-Halo-4-iodobenzenes
bond. Since 8% of terphenyl (4) was formed in the reaction of
1-bromo-4-iodobenzene, we examined the experiment with 1o
and stopped the reaction at low conversion. After 3 h, 38%
conversion was achieved but at this stage no terphenyl was
obtained. This result suggests that the formation of terphenyl is
via the further reaction of the initially formed 2p but not via the
formation of the biaryl radical anion, which was suggested by
Kwong and Lei.6 Similarly, the reaction of methyl 5-bromo-2-
iodobenzoate (1q) gave the bromo biaryl 2q (Scheme 1, eq 2).
The carbon−bromine bonds present in the biaryl products can
be subsequently converted to carbon−carbon bonds by cross-
coupling reactions such as Suzuki−Miraura and Sonogashira
reactions.19
A potential mechanism, mediated by oxygen and cyanobor-
ohydride, is shown in Scheme 2. Photoirradiation of aryl iodide
Scheme 2. Possible Mechanism
leads to generation of an aryl radical.2,20 The aryl radical adds to
benzene to form cyclohexadienyl radical, which reacts with
oxygen to give biaryl product and hydroperoxy radical.2,3a,21
The resulting hydroperoxy radical could abstract hydrogen
from cyanoborohydride to give the cyanoborane radical anion.
Subsequent reaction with aryl iodide through single-electron
transfer would give the corresponding radical anion that
fragments to aryl radical and iodide ion, thus completing the
radical chain reaction.
In summary, we have found that cyanoborohydride can
promote arylation of benzene under aerobic conditions. Using
this protocol, both aryl iodides bearing an electron-donating or
-withdrawing group can be accommodated. The reaction takes
place chemoselectively at the aryl−iodine bond in preference to
either an aryl−bromine or aryl−chlorine bond. These mild
reaction conditions are unusual for base-promoted HAS
reactions and provide considerable synthetic flexibility, as
a
b
Isolated yield based on 1. 1d was recovered in 20% yield.
c
d
Borohydride was added in two portions (0.5 + 0.5 equiv). Toluene
e
was used instead of benzene. Regioisomeric mixture with an o:m:p
ratio 62:24:14 was isolated.
diphenylbenzene (4).6,7,11,12,10b,f,g To gain insight into the
chemoselectivity of the present method, we tested the arylation
of benzene with the bihaloarenes 1o and 1p using
cyanoborohydride (Scheme 1, eq 1). Under our standard
reaction conditions, a chemoselective reaction took place at the
aryl−iodine bond but not at the aryl−bromine or aryl−chlorine
2112
dx.doi.org/10.1021/ol500614q | Org. Lett. 2014, 16, 2111−2113

Organic Letters
Letter
(12) Buden
1174.
́
, M. E.; Guastavino, J. F.; Rossi, R. A. Org. Lett. 2013, 15,
illustrated by the subsequent conversion of C−Br bonds into
C−C bonds via cross-coupling reactions following the
cyanoborhydride-promoted arylation reaction.
(13) Zheng, X.; Yang, L.; Du, W.; Ding, A.; Guo, H. Chem.Asian J.
2014, 9, 439.
(14) (a) Ryu, I.; Uehara, S.; Hirao, H.; Fukuyama, T. Org. Lett. 2008,
10, 1005. (b) Kobayashi, S.; Kawamoto, T.; Uehara, S.; Fukuyama, T.;
Ryu, I. Org. Lett. 2010, 12, 1548. (c) Kawamoto, T.; Fukuyama, T.;
Ryu, I. J. Am. Chem. Soc. 2012, 134, 875. (d) Kawamoto, T.; Ryu, I.
Chimia 2012, 66, 372. (e) Kawamoto, T.; Okada, T.; Curran, D. P.;
Ryu, I. Org. Lett. 2013, 15, 2144. (f) Fukuyama, T.; Kawamoto, T.;
Kobayashi, M.; Ryu, I. Beilstein J. Org. Chem. 2013, 9, 1791.
(15) For a review on NHC-borane, see: Curran, D. P.; Solovyev, A.;
ASSOCIATED CONTENT
* Supporting Information
Detailed experimental procedures and spectroscopic data. This
material is available free of charge via the Internet at http://
pubs.acs.org.
■
S
AUTHOR INFORMATION
Corresponding Author
Makhlouf Brahmi, M.; Fensterbank, L.; Malacria, M.; Laco
Chem., Int. Ed. 2011, 50, 10294.
̂
te, E. Angew.
■
(16) Kharasch also observed that more reduction product was
obtained when degassed conditions were used. The role of HI is
suggested for the reduction. See ref 2c.
*E-mail: ryu@c.s.osakafu-u.ac.jp.
Notes
(17) The reaction of 1a and benzene with AIBN in the presence of
Bu4NBH3CN at 90 °C gave the arylation product (9%) together with
an increased amount of anisole (21%).
(18) (a) Davies, D. I.; Hey, D. H.; Summers, B. J. Chem. Soc., C 1970,
2653. (b) Davies, D. I.; Hey, D. H.; Summers, B. J. Chem. Soc., C 1971,
2681.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas from the MEXT and the JSPS.
T.K. acknowledges the Research Fellowship of the JSPS for
Young Scientists.
(19) See the Supporting Information.
(20) It should be noted that no further reaction was observed when
the light was turned off (Supporting Information), which suggested
that this arylation reaction has poor chain propagation.
(21) The rate constant for hydrogen abstraction by oxygen from
cyclohexadienyl radical is estimated to be 1.6 × 109 M−1 s−1 at 27 °C
in benzene; see: Maillard, B.; Ingold, K. U.; Scaiano, J. C. J. Am. Chem.
Soc. 1983, 105, 5095.
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