Facile diversification of simple benzo[b]thiophenes via thienobenzyne intermediates

Article abstract of DOI:10.1246/cl.160901

Thienobenzynes, which are thiophene-fused novel benzyne species, are efficiently generated via an iodine-magnesium exchange reaction of ortho-iodoaryl triflate-type precursors using a silylmethyl Grignard reagent as the activator. The method allows for facile preparation of a diverse range of multisubstituted benzothiophenes from readily available simple benzothiophenes.

Full text of DOI:10.1246/cl.160901

Advance Publication Cover Page
Facile Diversification of Simple Benzo[b]thiophenes
via Thienobenzyne Intermediates
Takamoto Morita, Suguru Yoshida,* Masakazu Kondo, Takeshi Matsushita, and Takamitsu Hosoya*
Advance Publication on the web October 22, 2016
doi:10.1246/cl.160901
©
2016 The Chemical Society of Japan
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Publication manuscripts.

Facile Diversification of Simple Benzo[b]thiophenes
via Thienobenzyne Intermediates
1
1
2
2
1
Takamoto Morita, Suguru Yoshida,* Masakazu Kondo, Takeshi Matsushita, and Takamitsu Hosoya*
1
Laboratory of Chemical Bioscience, Institute of Biomaterials and Bioengineering,
Tokyo Medical and Dental University, 2-3-10 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-0062
Ichihara Research Center, JNC Petrochemical Corporation, 5-1 Goikaigan, Ichihara, Chiba 290-8551
2
(
E-mail: s-yoshida.cb@tmd.ac.jp, thosoya.cb@tmd.ac.jp)
Thienobenzynes, which are thiophene-fused novel
benzyne species, are efficiently generated via an iodine–
magnesium exchange reaction of ortho-iodoaryl triflate-type
precursors using a silylmethyl Grignard reagent as the
activator. The method has allowed for facile preparation of a
diverse range of multisubstituted benzothiophenes from
readily available simple benzothiophenes.
2,3-disubstituted benzothiophenes could be prepared easily
from an anisole derivative by means of several established
methods. Moreover, we were interested in investigating the
regioselectivity in the reactions of thieno[4,5-c]benzynes I (6,7-
thienobenzynes) with unsymmetric arynophiles or nucleophiles,
and comparing the results with those reported for other ring-
1
1a
fused benzynes such as 3,4-cyclobutabenzyne,
6,7-
1
1b
9e
Keywords: Aryne | Benzo[b]thiophene | Grignard Reagent
indolyne,
and thiazolobenzynes. Herein, we report an
efficient method for the generation of thienobenzynes and their
application to the synthesis of multisubstituted benzothiophenes.
Benzo[b]thiophene
applications in various disciplines, including pharmaceutical,
agrochemical, and materials sciences (Figure 1).
derivatives
have
important
1
–3
Various
This work
R2
efficient synthetic methods for benzothiophenes have been
developed, such as electrophile- or radical-mediated cyclization
and transition metal-catalyzed annulation approaches.
Br
R1
4,5
HO
S
MeO
1
. iodination
However, these methods are not always applicable to the
synthesis of more complex multisubstituted benzothiophenes,
including those fused with another ring system, for which an
alternative approach is required.
2. triflylation
R2
R2
arynophile
TMSCH2MgCl
R1
R1
S
S
TfO
A
R2
I
B
multisubstituted
benzothiophene
1
HO
HO
HO
O
R1
O
N
6
S
HO
7
O
S
I
OH
6,7-thienobenzyne
O
S
S
OH
HO
Figure 2. Thienobenzynes: new entries as ring-fused benzynes.
OH
O
S
O
Echinothiophene
Raloxifene
DNTT
Toward a tetrasubstituted benzo[b]thiophene synthesis, we
prepared 2,3-dibutyl-6-hydroxybenzo[b]thiophene from 4-
bromoanisole, 5-decyne, and elemental sulfur in four steps
Figure 1. Various benzothiophene derivatives.
5e
based on the method reported by Wu and Yoshikai and
Recent advances in aryne chemistry have offered easy
6
–9
derived it to ortho-iodoaryl triflate 1a by regioselective
access to a wide range of complex aromatic compounds. We
assumed that a thienobenzyne, which is an unused benzyne
species fused with a thiophene ring, would be a convenient
intermediate for preparing diverse benzothiophene derivatives.
This idea was based on our recent achievements in aryne
1
2
iodination and subsequent triflylation. Using a mixture of 1a
and methyl 4-(azidomethyl)benzoate (2, 5.0 equiv) in THF, we
screened for the reaction conditions that allowed for the
efficient generation of thienobenzyne (Table 1). Although
1
0a
8
,9
treatment of the mixture with n-butyllithium
or
at
chemistry.
In particular, we recently demonstrated that
1
0b
isopropylmagnesium chloride–lithium chloride complex
multisubstituted benzothiazoles are readily available via
thiazolobenzyne intermediates, thiazole-fused benzyne
−
78 °C afforded the desired cycloadduct 3a only in low yields
9
e
(entries and 2), treatment with
1
species. Thiazolobenzynes were efficiently generated from
1
0
(trimethylsilyl)methylmagnesium chloride gave 3a in high yield
with high regioselectivity (entry 3). These results were in good
agreement with our previous studies regarding the generation of
easily synthesized ortho-iodoaryl triflate-type precursors by
treatment with a trimethylsilylmethyl Grignard reagent, which
was used to trigger an iodine–magnesium exchange reaction.
We envisioned that a similar strategy, using thienobenzynes
instead of thiazolobenzynes, would provide easy access to
multisubstituted benzothiophenes (Figure 2). We assumed that
9
9
thiazolobenzynes and 3-triflyoxyarynes, indicating the
advantage of the silylmethyl Grignard reagent with low
nucleophilicity for generating arynes from ortho-iodoaryl
triflates. The reaction using a small excess of azide 2 and the
activator also proceeded smoothly to afford 3a in sufficient
yield (entry 4). The reaction performed at a higher temperature
a
variety of ortho-iodoaryl triflate-type thienobenzyne
precursors such as 1 could be prepared easily from 2,3-
disubstituted 6-hydroxybenzo[b]thiophenes in two steps:
iodination and triflylation. We also assumed that these simple
such as
0 °C significantly decreased the yield and
regioselectivity (entry 5).

2
Table 2. Cycloadditions of 6,7-thienobenzyne
Table 1. Optimization of the reaction conditions
arynophile
(
5.0 equiv)
N3
n-Bu
n-Bu
TMSCH2MgCl
MeO
(2.0 equiv)
n-Bu
n-Bu
O
2
OMe
S
THF
–78 °C, 1 h
S
TfO
A
(
5.0 equiv)
O
n-Bu
n-Bu
I
B
R–Mtl
2.0 equiv)
1
a
(
n-Bu
n-Bu
a
THF
temp., 1 h
S
Entry Arynophile
Product
yYield (%)
S
TfO
N
+
minor isomer
I
N
N
n-Bu
1
a
3a
3a'
O
Me
Me
n-Bu
a
1
2
4
6
5
81
Entry
R–Mtl
Temp. (°C) Yield (%)
Me
S
O
1
2
3
n-BuLi
–78
–78
–78
–78
0
25 (98:2)
31 (98:2)
Me
n-Bu
i-PrMgCl·LiCl
b
TMSCH
TMSCH
TMSCH
2
2
2
MgCl
MgCl
MgCl
93 (97:3)
Ph
N
c
n-Bu
4
80 (97:3)
7
92
S
b
5
58 (87:13)
N
a
1
Ph
Combined yields of 3a and 3a’ based on H NMR analyses, unless
otherwise noted. The ratio of the regioisomers (3a:3a’) is shown in
n-Bu
b
c
parentheses. Combined yields of isolated 3a and 3a’. Azide 2 (1.2
equiv) and TMSCH MgCl (1.2 equiv) were used.
9
+
O
t-Bu
N
n-Bu
93
(84:16)
2
3
4
8
S
O
Ph
9
’
+
regioisomer
N
Under the best of conditions (Table 1, entry 3), a variety
of multisubstituted benzothiophenes were successfully prepared
via the thienobenzyne intermediate generated in situ from the
precursor 1a (Table 2). Diels–Alder reaction between the
thienobenzyne and 2,5-dimethylfuran (4) or N-phenylpyrrole
Ph
t-Bu
n-Bu
O
Me
N
n-Bu
11
+
11’
7
9
S
10
O
+ regioisomer
(
81:19)
N
(
(
6) afforded efficiently the cycloadducts 5 and 7, respectively
entries 1 and 2). Cycloaddition with nitrone 8 or 10 also
Cl
Me
Cl
proceeded smoothly to yield oxazole-fused benzothiophenes 9
and 11, respectively, in high yields with high regioselectivity
n-Bu
1
+
3
9
1
N2
n-Bu
5
6
Me3Si
12
14
(entries 3 and 4). Diazo compounds such as 12 and 14
S
(52:48)
1
3’
participated in this reaction to afford imidazole-fused
benzothiophenes 13 and 15, respectively, albeit with low
N
NH
+ regioisomer
n-Bu
1
+
15’
5
regioselectivity (entries
5
and 6). Cyclobutene-fused
O
O
71
(77:23)
n-Bu
benzothiophenes 17 and 19 were obtained as a single isomer via
N2
EtO
S
EtO
[2+2] cycloaddition with ketene acetal 16 or 18, respectively
+ regioisomer
N
NH
(entries 7 and 8). Nucleophilic addition of amines to the
n-Bu
thienobenzyne also took place; the reaction with morpholine
20) afforded a mixture of 6- and 7-morpholinobenzothiophenes
OMe
OMe
(
n-Bu
n-Bu
b
7
8
16
18
17
80
S
21 and 21’ with moderate selectivity (entry 9). Furthermore,
OMe
OMe
6,7-difunctionalized benzothiophene 23 was obtained via
addition of N-methylaniline (22) to the thienobenzyne followed
n-Bu
1
3
by formylation with N,N-dimethylformamide (DMF).
OMe
b
The method was also applicable for the generation of 6,7-
thienobenzynes bearing various substituents at their C2- and
C3-positions, significantly expanding the scope of available
benzothiophenes such as 3b–d (Scheme 1). The
corresponding precursors 1 could be easily derived from
simple benzothiophenes, which were prepared in short steps
19
8
6
S
OTBS
OMe
OTBS
n-Bu
2
1
NH
91
(70:30)
9
20
22
n-Bu
+
O
S
N
2
1’
by several 2methods depending on the C2- and C3-
O
+ regioisomer
1
substituents.
Cycloaddition of 3-methyl-2-phenyl-6,7-
n-Bu
thienobenzyne with azide 2 afforded 1,2,3-triazole-fused
benzothiophene 3b with a small amount of regioisomer 3b’ in
a high combined yield. Benzothiophene 3c bearing an amide,
an ester, and chloro moieties was also obtained from the
corresponding thienobenzyne precursor leaving these
functional groups untouched. Furthermore, 2-methylthio-3-
trifluoromethyl-6,7- thienobenzyne also participated in this
reaction to furnish benzothiophene 3d.
Me
NH
b
+
DMF
n-Bu
10
23
34
Me
Ph
N
S
Ph CHO
a
Isolated yields. When regioisomers were obtained, the combined yields
are shown. The ratio of the regioisomers based on H NMR analysis by
using 1,1,2,2-tetrachloroethane as an internal standard is shown in
1
b
parentheses. Regioisomer was not detected.

3
2
(5.0 equiv)
1
. TMSCH2N3
R2
R2
OH
TMSCH MgCl
2
TMSCH MgCl
2
(
2.0 equiv)
THF, rt
2. TBAF, THF, rt
NMe2 70% (91:9) in 2 stepsb,c
R1
Ar
R1
Cl
THF
78 °C, 1 h
S
S
TfO
N
N
N
–
+
regioisomer
3'
I
1
3
S
O
3. ArB(OH)2,
NMe2
TfO
cat. L2PdCl2, K2CO3
H2O, 1,4-dioxane
I
1
c
Me
S
O
N
Me
Cl
CF3
1
5
00 °C
6% (91:9)b
N
29d
N
NMe2
O
Ar
Ph
Ar
Ar
SMe
1. phthalimide
DMEAD, PPh3
THF, rt
3.
O
S
S
S
N
N
N
N
N
N
N
+ regioisomer
N
N
+ regioisomer
Cl
2
. H2NNH2·H2O
EtOH, 80 °C
3
b
3b'
3c
3c'
3d
43%c
OMe
NEt3, CH2Cl2, rt
57% (3 steps)
7
3%
97:3)
62%
(91:9)
O
b
b
(
HN
O
HN
Scheme 1. Cycloadditions of various 2,3-disubstituted 6,7-
MeO
a
a
thienobenzynes . Ar = p-(MeO C)C H -. Isolated yields are shown.
2 6 4
b
Me
NMe2
O
MeO
When regioisomers were obtained, the combined yields are shown. The
ratio of the regioisomers. Regioisomer was not detected.
c
S
NMe2
Me
28
EP4 antagonist
S
O
A
5,6-thienobenzyne was similarly generated as
Me
N
N
N
demonstrated using precursor 24 (Scheme 2). The reaction
with pyrrole 6 afforded the cycloadduct 25 in moderate yield.
The reaction with azide 2 afforded a regioisomeric mixture of
cycloadducts 27 and 27’ in moderate yield with moderate
selectivity. In these cases, a considerable amount of triflone
30
a
a
Scheme 3. Synthesis of an EP4 antagonist analog. Isolated yields are
shown. Ar = p-(HOCH
di(2-methoxyethyl) azodicarboxylate. The ratio of the regioisomers is shown
in parentheses. A mixture of regioisomers was used. 29 was obtained by
2 2 6 4 2 6 4 2
CH )C H ; L = p-(Me N)C H P(t-Bu) ; DMEAD =
b
c
d
recrystallization.
9
b,f,14
2
6, formed via the thia-Fries rearrangement,
was also
obtained. This side reaction must have facilitated by the
strong electron-withdrawing effect of the trifluoromethyl
group, which contributed to stabilize the anionic intermediate,
generated via the iodine–magnesium exchange reaction.
A
θ6 = 133.6°
θ7 = 119.8°
θ1 = 132.1°
θ2 = 122.8°
θ6
θ1
θ2
θ7
+
0.04
–0.18 Ia
S
+0.03
S–p-Tol
Δθ6-7 = 13.8°
–0.18 II
Δθ1-2 = 9.3°
B
ΔE1‡ = 1.5 kcal/mol
Ia + MeN3
S
S
Me
N
Me
N
6
(5.0 equiv)
N
N
N
N
TMSCH MgCl
2
CF
3
CF
3
HO
Tf
TS1
31
(
2.0 equiv)
Ph
N
SMe +
SMe
THF
78 °C, 1 h
S
S
–
S
2
5
26
28%
S
ΔE2‡ = 3.5 kcal/mol
N
N
4
2%
CF
3
N
N
N
N
O
Me
Me
TfO
I
OMe
SMe
TS2
31'
S
2
4
Figure 3. Computational studies using a DFT method (M11-L/6-31G(d)).
(A) Optimized structures of 6,7-thienobenzyne (Ia) and 3-(4-
tolylthio)benzyne (II). The numbers show the charge distribution. (B)
Analysis of the reaction pathway for cycloadditions of Ia with methyl
azide.
2
(5.0 equiv)
TMSCH
(
2
MgCl
CF
3
2.0 equiv)
N
N
SMe + regioisomer
7'
4
+
26
THF
78 °C, 1 h
N
S
2
32%
–
3%b
2
7
(72:28)
a
a
Scheme 2. Cycloadditions of 5,6-thienobenzyne. Isolated yields are
Theoretical studies based on density functional theory
DFT) provided insights into the regioselectivity observed in the
reactions of thienobenzynes (Figure 3). We optimized the
b
shown. Combined yield of isolated regioisomers. The ratio of the
(
regioisomers is shown in parentheses.
structure of 6,7-thienobenzyne (Ia) at the M11-L/6-31G(d)
By using a thienobenzyne intermediate, we prepared a
16
level of theory using the GAMESS-US program package. As
ring-fused analog of the potent prostaglandin E
2
subtype 4
9e
in our previous study on thiazolobenzynes, the optimized
15
receptor (EP4) antagonist 28 (Scheme 3). To demonstrate the
utility of our approach in diversifying the substituents on the
benzo-moiety of 28, we aimed to alter the core 5,7-
geometry structure of Ia agreed well with that previously
17
reported by Paton, Houk, Garg, and coworkers. The internal
angle at C6 in optimized Ia was larger than that of C7, showing
the highly distorted structure of thienobenzyne (Figure 3A).
Population analysis also indicated higher electrophilicity at C6
dimethylbenzothiophene structure to
a
triazole-fused
benzothiophene structure such as that of 30. Thus,
cycloaddition of a thienobenzyne generated from the precursor
18
than C7. The magnitude of the distortion in Ia was greater
1c
with
trimethylsilylmethyl
azide,
followed
by
than that of optimized 3-(4-tolylthio)benzyne (II), indicating
desilylprotonation and Suzuki–Miyaura cross-coupling with an
arylboronic acid afforded 29 containing a small amount of
regioisomer. After removal of the regioisomer by
recrystallization, the hydroxy group of 29 was converted to an
amino group by the Mitsunobu method. Finally, acylation
afforded the desired EP4 antagonist analog 30.
that increase of strain, induced by the fused ring, enhanced the
distortion of thienobenzyne as in the other ring-fused
7o,9e,11,17
arynes.
The difference between the internal angles of
distorted aryne triple bond (Δθ) in Ia was larger than that in II,
which was in good agreement with the higher regioselectivity
observed for the reaction of thienobenzyne generated from 1a
with azide 2 (distal:proximal = 97:3 at −78 °C; Table 1, entry 3)

4
than our previously reported reaction of 3-(4-tolylthio)benzyne
Dobrovolsky, M. Lautens, J. Am. Chem. Soc. 2012, 134, 15572. d) T.
Hamura, Y. Chuda, Y. Nakatsuji, K. Suzuki, Angew. Chem., Int. Ed.
2012, 51, 3368. e) T. R. Hoye, B. Baire, D. Niu, P. H. Willoughby, B. P.
Woods, Nature 2012, 490, 208. f) S. Y. Yun, K.-P. Wang, N.-K. Lee, P.
Mamidipalli, D. Lee, J. Am. Chem. Soc. 2013, 135, 4668. g) H. Yoshida,
R. Yoshida, K. Takaki, Angew. Chem., Int. Ed. 2013, 52, 8629. h) F.-L.
Liu, J.-R. Chen, Y.-Q. Zou, Q. Wei, W.-J. Xiao, Org. Lett. 2014, 16,
8c
with benzyl azide (distal:proximal = 83:17 at −78 °C). In both
9e
Ia and II, as in the case of thiazolobenzyne, the increased p
19
character of the C–S bond, which renders the distal carbon of
11a
aryne triple bond more electron deficient, should be also
entertained as a significant factor that distorts the aryne
structure. Further theoretical analysis at the same level of theory
provided transition state (TS) structures for the cycloadditions
between Ia and methyl azide (Figure 3B). The calculated
activation energy for the distal cycloaddition via TS1 was 2.0
kcal/mol smaller than that for the proximal cycloaddition via
TS2, which was in good agreement with the observed
regioselectivity (Table 1, entry 3).
3768. i) Y. Mizukoshi, K. Mikami, M. Uchiyama, J. Am. Chem. Soc.
2015, 137, 74. j) M. Pawliczek, L. K. B. Garve, D. B. Werz, Org. Lett.
2015, 17, 1716. k) S. S. Bhojgude, D. R. Baviskar, R. G. Gonnade, A. T.
Biju, Org. Lett. 2015, 17, 6270. l) E. Demory, K. Devaraj, A. Orthaber,
P. J. Gates, L. T. Pilarski, Angew. Chem., Int. Ed. 2015, 54, 11765. m)
C. M. Holden, S. M. A. Sohel, M. F. Greaney, Angew. Chem., Int. Ed.
2016, 55, 2450. n) R. A. Dhokale, S. B. Mhaske, Org. Lett. 2016, 18,
3010. o) T. Ikawa, S. Masuda, A. Takagi, S. Akai, Chem. Sci. 2016, 7,
5206. p) N. F. F. Nathel, L. A. Morrill, H. Mayr, N. K. Garg, J. Am.
In summary, we have added thienobenzynes as a new entry
into an aryne toolbox, demonstrating that they serve as useful
intermediates for diverse multisubstituted benzothiophenes.
Further studies to expand the scope of the method and application
to the synthesis of bioactive compounds are now in progress.
Chem. Soc. 2016, 138, 10402. q) Y. Li, D. Qiu, R. Gu, J. Wang, J. Shi,
Y. Li, J. Am. Chem. Soc. 2016, 138, 10814.
a) S. Yoshida, T. Hosoya, Chem. Lett. 2013, 42, 583. b) Y. Sumida, T.
Kato, T. Hosoya, Org. Lett. 2013, 15, 2806. c) S. Yoshida, K. Uchida,
T. Hosoya, Chem. Lett. 2014, 43, 116. d) Y. Sumida, R. Harada, T.
Kato-Sumida, K. Johmoto, H. Uekusa, T. Hosoya, Org. Lett. 2014,
8
1
6, 6240. e) S. Yoshida, F. Karaki, K. Uchida, T. Hosoya, Chem.
The authors thank Central Glass Co., Ltd. for providing
Tf O. This work was supported by CREST from AMED,
2
Commun. 2015, 51, 8745. f) S. Yoshida, Y. Hazama, Y. Sumida, T.
Yano, T. Hosoya, Molecules 2015, 20, 10131. g) S. Yoshida, K.
Shimomori, T. Nonaka, T. Hosoya, Chem. Lett. 2015, 44, 1324. h) S.
Yoshida, T. Yano, Y. Misawa, Y. Sugimura, K. Igawa, S. Shimizu, K.
Tomooka, T. Hosoya, J. Am. Chem. Soc. 2015, 137, 14071.
Japan; the Project for Cancer Research and Therapeutic
Evolution （P-CREATE）from AMED, Japan; the Platform
for Drug Discovery, Informatics, and Structural Life Science
of MEXT and AMED, Japan; JSPS KAKENHI Grant
Numbers 15H03118 (B; T.H.), 16H01133 (Middle Molecular
Strategy; T.H.), and 26350971 (C; S.Y.); and Suntory
Foundation for Life Sciences (S.Y.).
9
a) S. Yoshida, T. Nonaka, T. Morita, T. Hosoya, Org. Biomol. Chem.
2014, 12, 7489. b) S. Yoshida, K. Uchida, K. Igawa, K. Tomooka, T.
Hosoya, Chem. Commun. 2014, 50, 15059. c) S. Yoshida, K. Uchida,
T. Hosoya, Chem. Lett. 2015, 44, 691. d) S. Yoshida, T. Morita, T.
Hosoya, Chem. Lett. 2016, 45, 726. e) S. Yoshida, T. Yano, Y.
Nishiyama, Y. Misawa, M. Kondo, T. Matsushita, K. Igawa, K.
Tomooka, T. Hosoya, Chem. Commun. 2016, 52, 11199. f) K.
Uchida, S. Yoshida, T. Hosoya, Synthesis 2016, in press; doi:
10.1055/s-0035-1562532.
Supporting Information for characterization of new
compounds is available electronically on J-STAGE.
1
1
0
1
a) T. Matsumoto, T. Hosoya, M. Katsuki, K. Suzuki, Tetrahedron
Lett. 1991, 32, 6735. b) T. Ikawa, A. Takagi, Y. Kurita, K. Saito, K.
Azechi, M. Egi, K. Kakiguchi, Y. Kita, S. Akai, Angew. Chem., Int.
Ed. 2010, 49, 5563.
a) T. Hamura, Y. Ibusuki, K. Sato, T. Matsumoto, Y. Osamura, K.
Suzuki, Org. Lett. 2003, 5, 3551. b) G.-Y. J. Im, S. M. Bronner, A. E.
Goetz, R. S. Paton, P. H.-Y. Cheong, K. N. Houk, N. K. Garg, J. Am.
Chem. Soc. 2010, 132, 17933.
References and Notes
1
a) K. Koike, Z. Jia, T. Nikaido, Y. Liu, Y. Zhao, D. Guo, Org. Lett.
999, 1, 197. (b) A. Martinez, C. Gil, in Privileged Scaffolds in
1
Medicinal Chemistry: Design, Synthesis, Evaluation (Ed.: Bräse, S.),
Royal Society of Chemistry, Cambridge, 2015; pp. 245–248.
2
Our study on bioactive benzo[b]thiophenes, see: S. Shimizu, T.
Hosoya, M. Murohashi, S. Yoshida, WO 2013/118842.
1
1
2
3
See Supporting Information for details.
W. Lin, I. Sapountzis, P. Knochel, Angew. Chem., Int. Ed. 2005, 44,
3
4
5
T. Yamamoto, K. Takimiya, J. Am. Chem. Soc. 2007, 129, 2224.
B. Wu, N. Yoshikai, Org. Biomol. Chem. 2016, 14, 5402.
4258.
1
4
F. A. M. Dyke, D. M. Gill, J. N. Harvey, A. J. Hester, G. C. Lloyd-
Jones, M. P. Muñoz, I. R. Shepperson, Angew. Chem., Int. Ed. 2008,
For some recent approaches, see: a) I. Nakamura, T. Sato, Y.
Yamamoto, Angew. Chem., Int. Ed. 2006, 45, 4473. b) S. Yoshida, H.
Yorimitsu, K. Oshima, Org. Lett. 2007, 9, 5573. c) S. Mehta, R. C.
Larock, J. Org. Chem. 2010, 75, 1652. d) T. Inami, Y. Baba, T.
Kurahashi, S. Matsubara, Org. Lett. 2011, 13, 1912. e) B. Wu, N.
Yoshikai, Angew. Chem., Int. Ed. 2013, 52, 10496. f) Y. Masuya, M.
Tobisu, N. Chatani, Org. Lett. 2016, 18, 4312. g) H. Zang, J.-G. Sun,
X. Dong, P. Li, B. Zhang, Adv. Synth. Catal. 2016, 358, 1746.
For some recent reviews, see: a) A. Bhunia, S. R. Yetra, A. T. Biju,
Chem. Soc. Rev. 2012, 41, 3140. b) C. M. Gampe, E. M. Carreira,
Angew. Chem., Int. Ed. 2012, 51, 3766. c) P. M. Tadross, B. M.
Stoltz, Chem. Rev. 2012, 112, 3550. d) A. E. Goetz, T. K. Shah, N. K.
Garg, Chem. Commun. 2015, 51, 34. e) H. Miyabe, Molecules 2015,
47, 5067.
1
1
5
6
L. Li, M.-C. Mathieu, D. Denis, Al. G. Therien, Z. Wang, Bioorg.
Med. Chem. Lett. 2011, 21, 734.
M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert, M. S.
Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S. J.
Su, T. L. Windus, M. Dupuis, J. A. Montgomery J. Comput. Chem.
1993, 14, 1347.
6
7
1
1
1
7
8
9
A. E. Goetz, S. M. Bronner, J. D. Cisneros, J. M. Melamed, R. S. Paton, K.
N. Houk, N. K. Garg, Angew. Chem., Int. Ed. 2012, 51, 2758.
T. Ikawa, H. Kaneko, S. Masuda, E. Ishitsubo, H. Tokiwa, S. Akai,
Org. Biomol. Chem. 2015, 13, 520.
M. B. Smith, in March’s Advanced Organic Chemistry: Reactions,
Mechanisms, and Structure, 7th Ed.; John Wiley & Sons: New Jersey,
20, 12558. f) S. Yoshida, T. Hosoya, Chem. Lett. 2015, 44, 1450.
For some recent reports, see: a) A. B. Smith III, W.-S. Kim, Proc. Natl.
Acad. Sci. U.S.A. 2011, 108, 6787. b) K. M. Allan, C. D. Gilmore, B. M.
Stoltz, Angew. Chem., Int. Ed. 2011, 50, 4488. c) D. A. Candito, D.
2013; pp. 25–27.