Transition-metal-free Suzuki-Miyaura coupling reaction of arylpropargylic bromides with aryl- and alkenylboronic acids

Article abstract of DOI:10.1055/s-0033-1339199

In the absence of transition-metal catalyst, Suzuki-Miyaura coupling reaction between aryl- and alkenylboronic acids and arylpropargylic bromides proceeded to give the corresponding acetylenic products selectively. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0033-1339199

LETTER
▌1683
letter
Transition-Metal-Free Suzuki–Miyaura Coupling Reaction of Arylpropar-
gylic Bromides with Aryl- and Alkenylboronic Acids
Aryl Benzyl and Aryl Allyl Substituted Alkynes
Mitsuhiro Ueda,* Kota Nishimura, Ilhyong Ryu*
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
Fax +81(72)2549670; E-mail: ueda@c.s.osakafu-u.ac.jp; E-mail: ryu@c.s.osakafu-u.ac.jp
Received: 24.04.2013; Accepted after revision: 21.05.2013
for 18 hours. We were pleased to find that the reaction
Abstract: In the absence of transition-metal catalyst, Suzuki–Miy-
proceeded to give 1-methoxy-4-[3-(p-tolyl)prop-2-yn-1-
aura coupling reaction between aryl- and alkenylboronic acids and
yl]benzene (3aa), albeit in low yield, in which no allenyl-
arylpropargylic bromides proceeded to give the corresponding acet-
type product was formed (Table 1, entry 1). The addition
of H2O (7.8 equiv) improved the yield of 2a to 74% (Table
1, entry 2). We then surveyed the solvents and bases.
While the reaction using CHCl3 as a solvent afforded 3aa
in a 47% yield (Table 1, entry 3), significant improvement
of the yield was achieved by using CHBr3 as a solvent
(84% yield, Table 1, entry 4). Switching the solvent from
CHBr3 to BTF (benzotrifluoride) and t-BuOH at 90 °C
gave 3aa in 66% and 51% yields, respectively (Table 1,
entries 5 and 6). The reaction using K2CO3 and KF in
CHBr3 afforded 3aa in 69% and 42% yields, respectively
(Table 1, entries 7 and 8).
ylenic products selectively.
Key words: regioselective, propargylation, transition-metal-free,
C–C bond formation, aryl- and vinylboronic acids
The transition-metal-catalyzed cross-coupling reaction of
organo halides or alcohols with organoboronic acids is
among the most useful carbon–carbon bond-forming re-
actions.1 The palladium-catalyzed cross-coupling reaction
of propargylic halides or alcohols with organoboronic ac-
ids generally gives a mixture of allenic and propargylic
products (Scheme 1, eq. 1).2–4 To the best of our knowl-
edge, there is only one example of selective propar-
gylation of organoboronic acid, in which 2-
methylphenylboronic acid was coupled with 3-trimethyl-
silyl-2-propyn-1-ol to give [3-(2-methoxyphenyl)prop-1-
yn-1-yl]trimethylsilane.2
Table 1 Screening of Reaction Conditions for the Transition-Metal-
Free Suzuki–Miyaura Coupling Reaction of 1-(3-Bromoprop-1-yn-1-
yl)-4-methylbenzene (1a) with 4-Methoxyphenylboronic Acid (2a)a
Br
R1
•
previous work
Me
R2
base (1.5 equiv)
1a
+
(1)
X
H2O (7.8 equiv)
R1
Pd
+
R2
R1
OMe
CHBr3
(HO)2B
+
90 °C, 18 h
Me
3aa
R2B(OH)2
this work
R2
OMe
2a (1.3 equiv)
(2)
R1
metal-free
X = Cl, Br, I, or OH
Entry
Base
Solvent
Yield of 3aa (%)b
Scheme 1 Two types of the Suzuki–Miyaura coupling reaction of
propargylic halides or alcohols
1c
2
3
4
5
6
7
8
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
KF
CH2Cl2
CH2Cl2
CHCl3
CHBr3
BTF
32
Recently, we5 and the Scrivanti group6 independently re-
ported that a cross-coupling reaction between arylboronic
acids and allylic bromides proceeded well without the use
of a transition-metal catalyst to give the allylated prod-
ucts. Herein, we wish to report that a similar metal-cata-
lyst-free reaction of arylpropargylic bromides with aryl-
and alkenylboronic acids proceeded well to give propar-
gylic products selectively (Scheme 1, eq. 2).
74
47
84 (81)d
66
t-BuOH
CHBr3
CHBr3
51
69
In our first investigation for the metal-catalyst-free
propargylation, 1-(3-bromoprop-1-yn-1-yl)-4-methylben-
zene (1a) was treated with 4-methoxyphenylboronic acid
(2a, 1.3 equiv) and Cs2CO3 (1.5 equiv) in CH2Cl2 at 90 °C
42
a Reaction conditions: 1a (1.0 equiv), 2a (1.3 equiv), base (1.5 equiv),
H2O (7.8 equiv), solvent (1.5 M for 1a), 90 °C (bath temp), 18 h.
b NMR yield. Tetrachloroethane was used as an internal standard.
c The reaction was carried out without H2O.
d Isolated yield by silica gel chromatography.
SYNLETT 2013, 24, 1683–1686
Advanced online publication: 28.06.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339199; Art ID: ST-2013-U0381-L
© Georg Thieme Verlag Stuttgart · New York

1684
M. Ueda et al.
LETTER
With the optimized reaction conditions (Table 1, entry 4) 62% and 51%, respectively (Table 2, entries 2 and 3). On
in hand, the scope of the regioselective Suzuki–Miyaura the other hand, the reaction of 4-fluorophenylboronic acid
coupling reaction with respect to various organoboronic (2d) with 1a was very sluggish to give 3ad in 13% yield
acids and propargylic bromides was investigated (Table (Table 2, entry 4). The cross-coupling reaction of trans-2-
2).7 The reaction of 3,4-dimethoxyphenylboronic acid (4-methylphenyl)vinylboronic acid (2e) with 1a also pro-
(2b) and 4-benzyloxyphenylboronic acid (2c) with 1a ceeded to give the expected 1,4-enyne 3ae in a 43% yield
gave the corresponding internal acetylenes 3ab and 3ac in (Table 2, entry 5).
Table 2 Transition-Metal-Free Suzuki–Miyaura Coupling Reaction of Propargylic Bromides 1 with Organoboronic Acids 2a
Cs2CO3 (1.5 equiv)
H2O (7.8 equiv)
Br
Ar2
+
Ar2B(OH)2
Ar1
Ar1
CHBr3
90 °C, 18 h
1
3
2 (1.3 equiv)
Entry
Propargylic bromide 1
Organoboronic acid 2
Product 3
Yield (%)b
Br
(HO)2B
OMe
1
81
OMe
Me
Me
2a
1a
3aa
OMe
OMe
Br
Br
Br
Br
(HO)2B
OMe
OMe
2
3
4
5
62
51
13
43
Me
Me
2b
1a
3ab
(HO)2B
OBn
OBn
Me
Me
2c
1a
3ac
(HO)2B
F
F
Me
Me
2d
1a
3ad
(HO)2B
Me
Me
Me
Me
2e
1a
3ae
Br
(HO)2B
OMe
6
7
8
71
58
62
OMe
OMe
OMe
MeO
MeO
1b
2a
3ba
Br
(HO)2B
OMe
2a
1c
3ca
Br
(HO)2B
OMe
F
F
2a
1d
3da
Synlett 2013, 24, 1683–1686
© Georg Thieme Verlag Stuttgart · New York

LETTER
Aryl Benzyl and Aryl Allyl Substituted Alkynes
1685
Table 2 Transition-Metal-Free Suzuki–Miyaura Coupling Reaction of Propargylic Bromides 1 with Organoboronic Acids 2a (continued)
Cs2CO3 (1.5 equiv)
H2O (7.8 equiv)
Br
Ar2
+
Ar2B(OH)2
Ar1
Ar1
CHBr3
90 °C, 18 h
1
3
2 (1.3 equiv)
Entry
Propargylic bromide 1
Organoboronic acid 2
Product 3
Yield (%)b
(HO)2B
Br
9
64
OMe
OMe
2a
1e
1f
3ea
3fa
(HO)2B
Br
10
0
OMe
OMe
2a
a Reaction conditions: 1 (1.0 equiv), 2 (1.3 equiv), Cs2CO3 (1.5 equiv), H2O (7.8 equiv), CHBr3 (1.5 M for 1), 90 °C, 18 h.
b Isolated yield of 3.
While the transition-metal-free reaction of some other ar-
ylpropargylic bromides 1b–e with 2a proceeded well to
give 3ba–ea in good yields (Table 2, entries 6–9), aliphat-
ic propargylic bromide 1f did not react give the coupling
product (Table 2, entry 10).
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific Research
on Innovative Areas (No. 2105) from the MEXT. M.U. acknow-
ledges a Grant-in-Aid for Scientific Research on Innovative Areas
‘Advanced Molecular Transformations by Organocatalysts’ from
the MEXT for financial support.
Although the mechanistic details of this reaction remain to
be elucidated, an ionic substitution mechanism including
an ipso attack of organoboronic acid is proposed in
Scheme 2. As a first step, 2a was converted into a borate
anion A by H2O and Cs2CO3. The borate anion A could
then react with 1c through a six-membered transition state
B to give the cross-coupling product 3ca with the libera-
tion of boronic acid.8,9
References and Notes
(1) For recent reviews, see: (a) Suzuki, A. Angew. Chem. Int.
Ed. 2011, 50, 6722. (b) Jana, R.; Pathak, T. P.; Sigman, M.
S. Chem. Rev. 2011, 111, 1417. (c) Heravi, M. M.; Hashemi,
E. Tetrahedron 2012, 68, 9145. (d) Johansson Seechurn, C.
C. C.; Kitching, M. O.; Colacot, T. J.; Snieckus, V. Angew.
Chem. Int. Ed. 2012, 51, 5062.
(2) Yoshida, M.; Gotou, T.; Ihara, M. Tetrahedron Lett. 2004,
45, 5573.
Br
Cs2CO3
Cs+
–
+
Ph
(3) We tested the Suzuki–Miyaura cross-coupling reaction of
(3-bromoprop-1-yn-1-yl)benzene (1c) with phenylboronic
acid by using Pd(PPh3)4 (1 mol%) and Cs2CO3 in toluene at
90 °C for 3 h. As the result, propargylic compound (36%
yield) and allenic compound (14% yield) were obtained.
(4) (a) Moriya, T.; Miyaura, N.; Suzuki, A. Synlett 1994, 149.
(b) Yoshida, M.; Ueda, H.; Ihara, M. Tetrahedron Lett.
2005, 46, 6705. (c) Molander, G. A.; Sommers, E. M.;
Baker, S. R. J. Org. Chem. 2006, 71, 1563. (d) Miura, T.;
Shimada, M.; Mendoza, P.; Deutsch, C.; Krause, N.;
Murakami, M. J. Org. Chem. 2009, 74, 6050.
B(OH)2
B(OH)3
1c
H2O
MeO
MeO
2a
A
Cs+
OH
MeO
HO
B
–
O
H
Ph
Br
OMe
B(OH)3
+
CsBr
3ca
Ph
(5) Ueda, M.; Nishimura, K.; Kashima, R.; Ryu, I. Synlett 2012,
23, 1085.
(6) Scrivanti, A.; Beghetto, V.; Bertoldini, M.; Matteoli, U. Eur.
J. Org. Chem. 2012, 264.
B
Scheme 2 Plausible mechanism for the formation of 3ca
(7) Typical Procedure for a Metal-Catalyst-Free Suzuki–
Miyaura Cross-Coupling Reaction of Propargylic
Bromides with Aryl- and Alkenylboronic Acids
A mixture of 1-(3-bromoprop-1-yn-1-yl)naphthalene (1e,
0.5 mmol), 4-methoxyphenylboronic acid (2a, 0.65 mmol,
1.3 equiv), Cs2CO3 (0.75 mmol, 1.5 equiv), and H2O (7.8
equiv) in CHBr3 (0.33 mL, 1.5 M for 1e) was stirred at 90 °C.
After 18 h, the reaction mixture was treated with aq 1 N HCl,
extracted with CH2Cl2, and dried over MgSO4. The organic
layer was concentrated in vacuo, and the resulting residue
In summary, we have developed a regioselective Suzuki–
Miyaura coupling reaction of arylpropargylic bromides
with aryl- and alkenylboronic acids to give aryl benzyl
and aryl allyl substituted alkynes, which does not require
a transition-metal catalyst. This work achieved regio-
selective propargylation at the carbon attached to the
bromine of propargylic bromides, which is complementa-
ry to the palladium-catalyzed Suzuki–Miyaura reaction.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 1683–1686

1686
M. Ueda et al.
LETTER
HRMS (EI): m/z calcd for C20H16O: 272.1201; found:
was purified by column chromatography on silica gel
(hexane–EtOAc, 100:1) to give 1-[3-(4-methoxy)-
272.1200.
phenylprop-1-yn-1-yl]naphthalene (3ea) as a yellow liquid
(87.4 mg, 64%). 1H NMR (500 MHz, CDCl3): δ = 3.82 (s, 3
H), 3.94 (s, 2 H), 6.91 (d, J = 8.7 Hz, 2 H), 7.41 (m, 3 H),
7.53 (m, 2 H), 7.67 (d, J = 6.9 Hz, 1 H), 7.80 (d, J = 8.3 Hz,
(8) The reaction of isolated sodium trihydroxy(4-
methoxyphenyl)borate (1.3 equiv) with 1c gave the
corresponding product 3ca in 41% yield under the same
conditions as shown in Table 2 without base.
(9) Methyl ester of 2a did not work as a substrate. This result
clarifies the significance of a six-membered transition state
B to give the corresponding acetylenic products selectively.
1 H), 7.84 (d, J = 7.4 Hz, 1 H), 8.35 (d, J = 8.3 Hz, 1 H). 13
C
NMR (125 MHz, CDCl3): δ = 25.2, 55.2, 80.4, 93.0, 114.0,
121.4, 125.2, 126.2, 126.5, 128.2, 128.8, 128.9, 130.2,
133.1, 133.5, 158.4. IR (neat): 3058, 2223, 1248, 1034 cm–1.
Synlett 2013, 24, 1683–1686
© Georg Thieme Verlag Stuttgart · New York