Cobalt-catalyzed regioselective [3+2] annulation of ortho-formyl and acetyl substituted phenylboronic acids with alkynes

Article abstract of DOI:10.1016/j.tetlet.2017.06.049

Treatment of alkynes with ortho-formyl and acetyl phenylboronic acids in the presence of a cobalt catalyst resulted in the formation of 2,3-disubstituted indenols in good yields. When aryl silyl alkynes were used, 2-aryl-3-silyl indenols were obtained reg

Full text of DOI:10.1016/j.tetlet.2017.06.049

Accepted Manuscript
Cobalt-catalyzed regioselective [3+2] annulation of ortho-formyl and acetyl
substituted phenylboronic acids with alkynes
Mitsuhiro Ueda, Tamami Ueno, Yuki Suyama, Ilhyong Ryu
PII:
S0040-4039(17)30780-3
DOI:
http://dx.doi.org/10.1016/j.tetlet.2017.06.049
TETL 49041
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
26 May 2017
13 June 2017
16 June 2017
Please cite this article as: Ueda, M., Ueno, T., Suyama, Y., Ryu, I., Cobalt-catalyzed regioselective [3+2] annulation
of ortho-formyl and acetyl substituted phenylboronic acids with alkynes, Tetrahedron Letters (2017), doi: http://
dx.doi.org/10.1016/j.tetlet.2017.06.049
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Cobalt-catalyzed regioselective [3+2]
annulation of ortho-formyl and acetyl
substituted phenylboronic acids with alkynes
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Mitsuhiro Ueda,* Tamami Ueno, Yuki Suyama, and Ilhyong Ryu

1
Tetrahedron Letters
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Cobalt-catalyzed regioselective [3+2] annulation of ortho-formyl and acetyl
substituted phenylboronic acids with alkynes
1
1
1
Mitsuhiro Ueda,∗ Tamami Ueno, Yuki Suyama, and Ilhyong Ryu
1,2
1
Department of Chemistry, Graduate School of Science, Osaka Prefecture University, Sakai, Osaka 599-8531, Japan
Department of Applied Chemistry, National Chiao Tung University, Hsinchu 30010, Taiwan, R.O.C.
2
ARTICLE INFO
ABSTRACT
Article history:
Received
Treatment of alkynes with ortho-formyl and acetyl phenylboronic acids in the presence of a
cobalt catalyst resulted in the formation of 2,3-disubstituted indenols in good yields. When aryl
silyl alkynes were used, 2-aryl-3-silyl indenols were obtained regioselectively in good yields.
Received in revised form
Accepted
2
009 Elsevier Ltd. All rights reserved.
Available online
2
,3-disubstituted indenol
silyl aryl alkyne
cobalt
[
3+2] annulation
Ortho-carbonylated phenylboronic acid
Introduction
2,3-Disubstituted indenols are an important class of organic
molecules, since they serve as synthetic intermediates of
biological active compounds useful in pharmaceutical and
1
,2,3
agricultural chemistry. In 2005, Rh-catalyzed [3+2] annulation
reactions of ortho-carbonylated phenylboronic acids with alkynes
were studied for the synthesis of 2,3-disubstituted indenols by
4
a,4b
Hayashi and Murakami, independently.
studies exhibited variable regioselectivities when unsymmetrical
alkynes, such as 1-phenyl-1-propyne and 1-
trimethylsilyl)propyne, were used. In 2007, Lu and co-workers
These previous
Scheme 1. Cobalt-catalyzed [3+2] annulation of ortho-
carbonylated phenylboronic acids with silyl aryl acetylenes
(
reported a Pd-catalyzed reaction of ortho-formylphenylboronic
acids with alkynoate esters, which gave the corresponding 2-
4c
methoxycarbonyl-3-substituted indenols regioselectively. We
recently reported the synthesis of 2,3-disubstituted indenones by a
Co-catalyzed regioselective [3+2] annulation of ortho-
methoxycarbonylphenylboronic acid with alkynes, which gave
7
Co(acac)
2
and
DPPE,
the
reaction
of
ortho-
formylphenylboronic acid (1a) with 1-phenyl-2-trimethylsilyl
acetylene (2a) in acetonitrile was carried out at 80 ºC for 12 h,
which gave 2-phenyl-3-silyl indenol 3a as a single regioisomer in
5
,6
the corresponding indenones in good yields. In this study we
extended the Co-catalyzed [3+2] annulation method to the
synthesis of 2,3-disubstituted indenols, in which ortho-formyl and
acetyl phenylboronic acids were reacted with alkynes.
8
4% yield (Table 1). The reaction of [4-(methoxyphenyl)-
ethynyl]trimethylsilane (2b) with 1a also proceeded
regioselectively to form the corresponding 3-silyl-substituted
indenol 3b in 95% yield. 4-[(Trimethylsilyl)ethynyl]phenol (2c)
was also applicable albeit in modest yield due to the desilylation
Results and discussion
of 2c. Methyl 4-[(trimethylsilyl)ethynyl]benzoate (2d) gave 3d in
7
the reaction conditions and formed the corresponding indenol 3e
in 53% yield as a single regioisomer. The modest yield of 3e was
mainly attributed to the slow reaction. When 1-
In our previous work, the Co-catalyzed [3+2] annulation of
ortho-methoxycarbonylphenylboronic acid with 1-phenyl-2-
trimethylsilylacetylene (2a) produced 2-phenyl-3-silyl indenone
as a single regioisomer (1st equation, Scheme 1). This led us to
investigate the reaction of ortho-formylphenylboronic acid with
8
2% yield. 3-(Trimethylsilylethynyl)benzonitrile (2e) tolerated
(
trimethylsilyl)propyne (2f) was reacted with 1a, 2-methyl-3-silyl
indenol 3f was obtained in 70% yield with a regioselectivity of
5:5. In a similar protocol, ortho-acetylphenylboronic acid (1b)
2
a (2nd equation, Scheme 1). In the presence of 10 mol % of
9
—
——
∗
Corresponding author. Tel.: +81-72-254-9670; fax: +81-72-254-9670; e-mail: ueda@c.s.osakafu-u.ac.jp (M. Ueda)

2
Tetrahedron
reacted with silyl alkynes 2a–2d to give the corresponding Table 2. Co-catalyzed [3+2] annulation of 1 with internal
a
indenols 3g–3j in good to excellent yields.
alkynes 2g–2j
Table 1. Co-catalyzed regioselective [3+2] annulation of 1
with silyl alkynes 2a–2f
a
a
Reaction conditions: 1 (1.5 equiv), 2 (0.5 mmol), Co(acac)
b
2
(10 mol %),
DPPE (10 mol %) in MeCN (2 mL) at 80 °C for 12 h. Determined by
NMR analysis.
a
2
Reaction conditions: 1 (1.5 equiv), 2 (0.5 mmol), Co(acac) (10 mol %),
b
DPPE (10 mol %) in MeCN (2 mL) at 80 °C for 12 h. Determined by
NMR analysis.
In contrast to the regioselective [3+2] annulation with
silyl-substituted alkynes, other unsymmetrical alkynes 2g–2i
gave regioisomeric mixtures of the corresponding 2,3-
disubstituted indenols (Table 2). For example, the reaction of
methyl phenyl acetylene 2g with 1a gave 3k in good yield
with 81:19 selectivity in favor of the 2-phenyl orientation. 1-
Phenylpentyne (2h) and ethyl 2-butynoate (2i) gave 3l and
3
m
in 68% and 71% yields, respectively, with similar Scheme 2. Synthesis of indenone 4 from indenol 3d
regioselectivities. Diphenylacetylene (2j) reacted with 1a to
give 2,3-diphenyl indenol 3n in 89% yield. Similarly, 4-
octyne (2k) gave the corresponding product 3o in 98% yield.
We also examined the reaction of 2-formyl-3-thienylboronic
acid with 2j. As a result, the corresponding product 3p was
obtained, albeit in moderate yield due to the slow reaction.
The reaction of ortho-acetylphenylboronic acid (1b) with 2j
also proceeded to form the corresponding 2,3-disubstituted
indenol 3q in 90% yield.
A proposed mechanism for the Co-catalyzed annulation
process is shown in Scheme 3. Arylcobalt complex I would be
generated via the transmetalation of [Co]–X (X = OH or acac)
with ortho-formylphenylboronic acid (1a). The regioselective
insertion of silyl alkyne 2a forms vinylcobalt complex II. The
9
[Co]–carbon bond of complex II undergoes migratory insertion
into the aldehyde to form alkoxycobalt complex III, which
undergoes protonation to give indenol 3a and regenerates the
[Co]–X catalyst.
In our previous work, the [3+2] annulation of ortho-
methoxycarbonylphenylboronic
acid
(trimethylsilyl)ethynyl]benzoate (2d) gave the desired indenone
with
4-
[
4
in very low yield due to the sluggish reaction (Scheme 2). In
contrast, 2-(4-methoxycarbonylphenyl)-3-silyl indenol 3d was
obtained in good yield by the reaction of 1a and 2d. Indenol
was successfully converted to 2-(4-
methoxycarbonylphenyl)-3-silyl indenone 4 by PCC oxidation
in 90% yield (Scheme 2).
3
d

3
Cambie, R. C.; Metzler, M. R.; Rutledge, P. S.; Woodgate, P. D.
J. Organomet. Chem. 1990, 398, C22-C24. (f) Cambie, R. C.;
Metzler, M. R.; Rutledge, P. S.; Woodgate, P. D. J. Organomet.
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4
.
1
2
2
416-1417. (b) Shintani, R.; Okamoto, K.; Hayashi, T. Chem. Lett.
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5
6
.
.
Ueda, M.; Ueno, T.; Suyama, Y.; Ryu, I. Chem. Commun. 2016, 52,
3237-13240.
1
For selected examples of Co-catalyzed [3+2] annulation based on
C-H activation, see: (a) Kong, L.; Yang, X.; Zhou, X.; Yu, S.; Li,
X. Org. Chem. Front. 2016, 3, 813-816. (b) Yu, W.; Zhang, W.;
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Scheme 3. Proposed reaction mechanism
2
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431.
A survey of cobalt catalysts, ligands, and solvents revealed that the
optimal reaction conditions were as follows: 10 mol % Co(acac)
10 mol % DPPE, MeCN, 80 °C, 12 h.
5
Conclusion
7.
8.
2
,
In summary, we have demonstrated that the Co-catalyzed
[
3+2] annulation of ortho-formyl and acyl-substituted
phenylboronic acids with alkynes led to 2,3-disubstituted
indenols When silyl alkynes were used, regioselective annulation
Typical Procedure for a Cobalt-Catalyzed [3+2] Regioselective
Annulation of Ortho-Formyl and Acetyl Phenylboronic Acids
with Alkynes: A 25 mL sealed tube equipped with a magnetic
.
stirring bar was charged with Co(acac)
DPPE (0.05 mmol, 10 mol %), ortho-formylphenylboronic acid 1a
0.75 mmol, 1.5 equiv), an alkyne 2d (0.50 mmol, 1.0 equiv), and
2
(0.05 mmol, 10 mol %),
took place to give 3-silyl-substituted indenols. Further studies
regarding the synthesis of biological active compounds are
currently underway in our laboratory.
(
MeCN (2 mL). The reaction mixture was stirred at 80 °C for 12 h.
The mixture was then filtered through silica gel pad. The filtrate
was concentrated, and the residue was purified by column
chromatography on silica gel to yield the desired product 3d as a
yellow solid in 72% yield (121.6 mg, 0.359 mmol);
1
d: H NMR (400 MHz, CDCl
Acknowledgments
3
Hz, 1H), 3.94 (s, 3H), 5.39 (d, J = 8.0 Hz, 1H), 7.24 (dt, J = 7.2
3
) δ 0.12 (s, 9H), 1.62 (d, J = 8.8
This work was supported by a Grant-in-Aid for Scientific
Research from the MEXT (25810024 for MU) and the JSPS
Hz, 0.8 Hz, 2H), 7.33 (dt, J = 7.2 Hz, 1.2 Hz, 1H), 7.39-7.45 (m,
2
13
H), 7.56 (d, J = 7.2 Hz, 1H), 8.07 (d, J = 8.0 Hz, 2H); C NMR
(
26248031 for IR)
3
(100 MHz, CDCl ) δ 0.42, 52.3, 80.9, 123.0, 123.8, 125.9, 128.8,
1
1
29.4, 129.5 (two peaks overlap), 140.9, 142.5, 144.9, 146.3,
-1
60.0, 167.1; IR (neat) 3466, 2952, 1724, 1608 cm ; EI-MS m/z
+
(relative intensity) 338 ([M ], 40), 279 (20), 235 (19), 12 (100),
Supplementary Material
2
22 3
06 (93), 178 (16), 73 (87); HRMS (EI) m/z calcd for C20H O Si
+
[M] ) 338.1338, found: 338.1346.
(
Supplementary data associated with this article can be found, in
the online version, at http://
1
3
(
j: H NMR (400 MHz, CDCl
s, 1H), 3.94 (s, 3H), 7.23 (dt, J = 7.6 Hz, 1.2 Hz, 1H), 7.30 (dt, J
7.2 Hz, 1.6 Hz, 1H), 7.35 (d, J = 6.8 Hz, 2H), 7.40 (d, J = 7.2 Hz,
3
) δ 0.04 (s, 9H), 1.42 (s, 3H), 1.86
=
13
1
H), 7.46 (d, J = 7.2 Hz, 1H), 8.01 (d, J = 8.0 Hz, 2H); C NMR
100 MHz, CDCl ) δ 0.2. 23.8, 52.3, 84.3, 122.3, 123.0, 126.1,
128.7, 129.2, 129.4, 129.7, 138.8, 142.5, 145.0, 149.0, 162.4,
(
3
References and notes
-
1
1
intensity) 352 (59), 337 (43), 279 (100), 277 (47), 248 (78), 220
67.2; IR (neat) 3466, 3066, 1776 cm ; EI-MS m/z (relative
1
.
(a) Clive, D. L. J.; Yu, M.; Sannigrah, M. J. Org. Chem. 2004, 69,
+
Si ([M] )
(
64), 73 (59); HRMS (EI) m/z calcd for
52.1495, found: 352.1489.
C
21
H
24
O
3
4
2
116-4125. (b) Clive, D. L. J.; Yu, M. Chem. Commun. 2002,
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3
1
p: H NMR (400 MHz, CDCl
3
3
) δ 1.78 (d, J = 8.4 Hz, 1H), 5.56
K.; Pridgen, L. M.; Olsen, M. A.; Mills, R. J.; Lantos, I.; Braine,
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(
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13
(dd, J = 7.8 Hz, 1.8 Hz, 2H); C NMR (100 MHz, CDCl
3
) δ 74.7,
22.6, 126.4, 127.5, 128.4, 128.5, 128.7, 128.9, 129.2, 134.4,
1
1
(
e) Myers, A. G.; Proteau, P. J.; Handel, T. M. J. Am. Chem. Soc.
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-
1
34.5, 135.1, 144.4, 147.3, 147.6; IR (neat) 3408, 3060 cm ; EI-
1
MS m/z (relative intensity) 290 (100), 288 (57), 212 (43), 189 (35),
49 (38), 105 (76), 77 (33); HRMS (EI) m/z calcd for C19
2
.
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H14OS
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(
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4
Tetrahedron

5
Highlights:
Co-catalyzed regioselective [3+2] annulation
The formation of 2,3-disubstituted indenols
Regioselective synthesis of 2-aryl-3-silyl indenols

6
Tetrahedron