Copper-catalysed bromoalkynylation of arynes

Article abstract of DOI:10.1039/b919301d

Arynes were found to be inserted into a C(sp)-Br σ-bond of bromoalkynes in the presence of a copper catalyst, giving (alkynyl)bromoarenes in a straightforward manner.

Full text of DOI:10.1039/b919301d

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Copper-catalysed bromoalkynylation of arynesw
Takami Morishita, Hiroto Yoshida* and Joji Ohshita
Received (in Cambridge, UK) 16th September 2009, Accepted 5th November 2009
First published as an Advance Article on the web 18th November 2009
DOI: 10.1039/b919301d
Arynes were found to be inserted into a C(sp)–Br r-bond of
bromoalkynes in the presence of a copper catalyst, giving
(alkynyl)bromoarenes in a straightforward manner.
were not formed at all when the reaction was conducted in the
absence of cupric bromide, demonstrating the indispensability
of the copper catalysis for the bromoalkynylation. Besides 2a,
bromoarylacetylenes bearing an electron-rich (2b or 2c),
sterically hindered (2d–2f) or electron-deficient (2g or 2h)
moiety were applicable to the reaction, giving the corresponding
bromoalkynylation products (3b–3h, 30b–30h) in good yield
(entries 2–8), and furthermore, a C(sp)–Br bond of thienyl-
(2i), alkyl- (2j–2l) or alkenyl-substituted (2m) bromoalkynes
was also added across benzyne (entries 9–13).
Addition reactions of a carbon–halogen s-bonds to unsaturated
carbon–carbon compounds have been of high synthetic
significance, because these transformations provide convenient
and direct method for simultaneous formation of a carbon–
carbon and a carbon–halogen bond, leading to production of
new organic halides of structural complexity, which are further
convertible through cross-coupling reaction etc. Although a
variety of compounds including acid chlorides,1 allyl halides,2
benzyl halides3 and polyhalogenated alkanes4 (Kharasch
addition) have been reported to be added across unsaturated
carbon linkages by use of a transition-metal or a Lewis-acid
catalyst, there has been no precedent on the reaction with
alkynyl halides, to the best of our knowledge. During the
course of our studies on addition reactions of an element–
element s-bond to arynes,5,6 we have found that a C(sp)–Br
s-bond of alkynyl bromides is smoothly added across arynes
with the aid of cupric bromide. Herein we report on copper-
catalysed bromoalkynylation of arynes, in which insertion of
two molar amounts of arynes takes place predominantly,7
offering a convenient way for preparing (alkynyl)bromoarenes
of synthetic utility (eqn (1)).
Versatility of the present reaction has been extended by the
use of substituted arynes (Scheme 1). Thus, 4,5-dimethyl-
benzyne (from 1b) cyclopentane- (from 1c) or cyclohexane-
condensed arynes (from 1d) underwent the addition of 2e to
produce the multisubstituted bromoalkynylation products
(3n–3p, 30n–30p) in 54–86% yield.
As depicted in eqn (2), treatment of benzyne with cupric
bromide was found to provide a 33% yield of 2-bromobiphenyl
(4), which should be formed through protonation of an
intermediary aryl copper species (6, Scheme 2) arising from
insertion of benzyne into
a copper–bromine bond of
CuBr2.11,12 Hence, formation of bromoalkynylation products
(3 or 30) would be ascribable to nucleophilic coupling of an
aryl copper species (5 or 6)13 with an alkynyl bromide, which
has been verified by a stoichiometric reaction of in situ-generated
Table 1 Copper-catalysed bromoalkynylation of benzynea
ð1Þ
First, we examined the reaction of benzyne, generated in situ
from 2-(trimethylsilyl)phenyl triflate8 (1a) and a fluoride ion
(KF/18-Crown-6), with 1-bromo-2-phenylacetylene (2a) in the
presence of a substoichiometric amount of cupric bromide,
and observed that benzyne was inserted into the C(sp)–Br
bond to produce a 61% yield of bromoalkynylation products,
2-bromo-20-(phenylethynyl)biphenyl 3a and 1-bromo-2-
(phenylethynyl)benzene 30a, where insertion of two mol
equivalents of benzyne predominantly occured (3a : 30a =
85 : 15) (Table 1, entry 1).9,10 The bromoalkynylation products
Entry R0
t/h Yieldb (%)
17 61
14.5 81
3 : 30 Product
1
2
Phenyl (2a)
p-Tolyl (2b)
85 : 15 3a, 30a
72 : 28 3b, 30b
75 : 25 3c, 30c
499 : 1 3d
3
4
4-MeOC6H4 (2c)
Mesityl (2d)
24
44
18
63
51
76
5
6
7
8
1-Naphthyl (2e)
9-Phenanthryl (2f)
4-F-3-MeC6H3 (2g)
4-NCC6H4 (2h)
2-Thienyl (2i)
n-Hexyl (2j)
Cyclopentyl (2k)
t-Butyl (2l)
Cyclohexen-1-yl (2m) 21.5 55
78 : 22 3e, 30e
87 : 13 3f, 30f
68 : 32 3g, 30g
68 : 32 3h, 30h
499 : 1 3i
27.5 64
17.5 66
18
17
66
19
40
63
38
46
60
41
9
10
11
12
13
499 : 1 3j
82 : 18 3k, 30k
499 : 1 3l
Department of Applied Chemistry, Graduate School of Engineering,
Hiroshima University, Higashi-Hiroshima 739-8527, Japan.
E-mail: yhiroto@hiroshima-u.ac.jp; Fax: +81-82-424-5494;
Tel: +81-82-424-7724
w Electronic supplementary information (ESI) available: Experimental
procedures including spectroscopic and analytical data. See DOI:
10.1039/b919301d
71 : 29 3m, 30m
a
The reaction was carried out in DME (5 ml) at 25 1C using 1a
(0.225 mmol), 2 (0.075 mmol), CuBr2 (0.015 mmol), KF (0.45 mmol)
b
and 18-Crown-6 (0.45 mmol). Isolated yield of 3 + 30 based on 2.
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Scheme 1 Copper-catalysed bromoalkynylation using substituted
Scheme 2 A plausible catalytic cycle.
arynes.
phenyl copper(II) species (from cupric acetate and phenylboronic
acid)13 and 2a (eqn (3)).
ð2Þ
ð3Þ
The intermediacy of the aryl copper species in the bromo-
alkynylation prompted us to investigate new insertion
reactions into another C–Br bond by employing organic
bromides, which have adequate electrophilicity toward the
coupling with the aryl copper species. Thus, when propargyl
bromide 7 was treated with benzyne under the similar
conditions to those above, dimerisative insertion products
(8a and 8b) were mainly produced in 56% yield (8a : 8b=
77 : 23) via SN20- and SN2-type substitution (Scheme 3).14 Similar
insertion reaction into a C–Br bond of (E)-cinnamyl bromide
readily took place with the aid of cupric bromide, in which
formation of SN2-type substitution product 10b prevailed.15
Finally, synthetic utility of the dimerisative bromoalkynyl-
ation products have been demonstrated by the Suzuki–Miyaura
coupling. As shown in Scheme 4, the palladium-catalysed
reaction of 3a with phenylboronic acid (11a) proceeded
smoothly with 5-exo-dig cyclisation,16 affording diphenyldi-
benzofulvene (12a) in 81% yield. In addition, naphthyl- (11b)
or 4-cyanophenylbronic acid (11c) could be also applied to the
coupling reaction, giving the respective dibenzofulvenes (12b
and 12c) in 89 or 52% yield.
Scheme 3 Copper-catalysed addition of propargyl or allyl bromide.
Scheme 4 Synthesis of dibenzofulvene derivatives using 3a.
resulting dimerisative bromoalkynylation products have been
demonstrated to be excellent molecular scaffolds for constructing
diverse diaryldibenzofulvenes, which have attracted consider-
able attention by their aggregation-induced emission (AIE)
properties.17
In conclusion, we have disclosed that insertion reaction of
arynes into a C(sp)–Br bond of alkynyl bromides smoothly
occurred by using cupric bromide, and that an aryl copper
species derived from insertion of an aryne into a Cu–Br
bond is a key intermediate in the reaction. Furthermore, the
We thank Central Glass Co. Ltd. for a generous gift of
trifluoromethanesulfonic anhydride. T. M. also acknowledges
the support of JSPS Research Fellowships for Young Scientists.
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642 | Chem. Commun., 2010, 46, 640–642