Palladium(0)-Catalyzed Dearomatization of 2-Nitrobenzofurans through Formal (3+2) Cycloadditions with Vinylcyclopropanes: A Straightforward Access to Cyclopenta[ b ]benzofurans

Article abstract of DOI:10.1055/s-0036-1591540

In the context of the palladium-catalyzed dearomatization of electron-poor arenes, we report herein that various 2-nitrobenzofurans efficiently undergo a dearomative (3+2) cycloaddition with vinylcyclopropanes. This new method gives access to a wide variety of cyclo-penta[ b ]benzofuran derivatives in a straightforward manner.

Full text of DOI:10.1055/s-0036-1591540

SYNLETT
0
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-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2018, 29, A–E
letter
A
en
Synlett
J. Ling et al.
Letter
Palladium(0)-Catalyzed Dearomatization of 2-Nitrobenzofurans
through Formal (3+2) Cycloadditions with Vinylcyclopropanes:
A Straightforward Access to Cyclopenta[b]benzofurans
Johanne Ling
0
0
0
0
0-
0
0
3
2-
1
3
4
8-
7
1
1
NO2
[Pd(0)]
O
Maxime Laugeois
O
NO2
+
Véronique Michelet
0
0
0
0
0-
0
0
2
2-
2
1
7
9-
1
1
5
R
R
18 examples
EWG up to 90% yield
up to 1:4.4 dr
EWG
H
EWG
Virginie Ratovelomanana-Vidal
EWG
Maxime R. Vitale*
0
0
0
0
0-
0
0
2
6-
7
4
0
2-
4
7
2
PSL Research University, Chimie ParisTech, CNRS, Institut de
Recherche de Chimie Paris, 11, rue Pierre et Marie Curie, Paris,
75005, France
maxime.vitale@chimie-paristech.fr
Dedicated to Professor Miguel Yus on the occasion of his 70th
birthday.
Received: 08.01.2018
Accepted after revision: 15.01.2018
Published online: 05.02.2017
2
014 - Trost et al.
NO2
DOI: 10.1055/s-0036-1591540; Art ID: st-2017-d0867-l
O2N
[Pd(0)]
+
(a)
cat.
H
Abstract In the context of the palladium-catalyzed dearomatization of
electron-poor arenes, we report herein that various 2-nitrobenzofurans
efficiently undergo a dearomative (3+2) cycloaddition with vinylcyclo-
propanes. This new method gives access to a wide variety of cyclo-
penta[b]benzofuran derivatives in a straightforward manner.
AcO
SiMe3
N
N
O2N
R
2
017
X = C(EWG')2
(
b)
EWG'
EWG'
our previous
work
N
Key words dearomatization, palladium(0) catalysis, (3+2) cycloaddi-
tion, nitrobenzofurans, vinylcyclopropanes, cyclopenta[b]benzofurans
NO2
H
R
EWG
[
Pd(0)]
+
cat.
N
X
O2N
EWG
R
Dearomatization reactions represent powerful methods
for building high molecular complexity and diversity start-
ing from readily available feedstock materials such as
X = NTs
(c)
NTs
Hyland et al.
N
H
EWG
1–4
arenes and heteroarenes. For this reason, much effort has
been devoted to their development, notably by means of ro-
This work
NO2
O
O
H
2
NO2
+
bust metal-based catalytic processes. In this particular
[Pd(0)]
(d)
area of research, palladium catalysis has undeniably shown
R
EWG
R
cat.
EWG
3,4
great potential. Interestingly though, the vast majority of
such catalytic transformations have so far capitalized on
EWG
EWG
OMe
Ph
the nucleophilic character of electron-rich aromatic rings
3
(
phenols, anilines, indoles, etc.), and the complementary
(–)-rocaglamide
(antileukemic activity)
O
palladium-catalyzed dearomatization of electron-deficient
MeO
4
systems remains comparatively scarce. In 2014, Trost et al.
CONMe2
HO
reached a significant milestone in this field by demonstrat-
ing that several nitroarenes, including 5-nitroquinoline,
could undergo a formal (3+2) dearomative cycloaddition
with a trimethylenemethane equivalent (Scheme 1, a).4
More recently, we and the group of Hyland demonstrated
that such an approach was not limited to the use of
trimethylenemethane equivalents and that, under palladi-
OH
MeO
Scheme 1 Palladium(0)-catalyzed dearomatizations of nitroarenes and
the aim of this work
a,5
As a continuation of our interest in the use of VCPs in
palladium-catalyzed dearomatization reactions, we ques-
tioned if such a cycloaddition strategy could be applied to
nitrobenzofurans. If successful, we anticipated that it would
enable an efficient and atom-economical access to the
cyclopenta[b]benzofuran core, a key scaffold prevalent in
4
b,6
um(0) catalysis, vinylcyclopropanes (VCPs) (Scheme 1, b)
and vinylaziridines (Scheme 1, c)4c were also 1,3-dipole
precursors capable of promoting the dearomatization of N-
protected 3-nitroindoles.
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Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Synlett
J. Ling et al.
Letter
several bioactive flavaglines, such as (–)-rocaglamide
Scheme 1, d).7,8 Although several synthetic methods to this
Table 1 Optimization of the Reaction Conditions
(
8,9
structural motif have been developed, such a straightfor-
ward palladium-catalyzed dearomative (3+2) cycloaddition
approach is, to the best of our knowledge, unprecedented.10
At the outset of this study, the feasibility of a palladium
catalyzed dearomative cycloaddition process between nitro-
benzofurans and VCPs was surveyed in a model reaction be-
O
NO2
NO2
O
Pd2(dba)3⋅CHCl3
+
(
2.5 mol%)
NC
ligand (x mol%)
CN
Br
H
Br
NC CN
1a (1 equiv)
2a (1 equiv) solvent, r.t., 2 h
3aa
11
Ph2P
PPh2
tween 5-bromo-2-nitrobenzofuran (1a)
vinylcyclopropane 2a. When using a catalytic system com-
posed of Pd (dba) ·CHCl (2.5 mol%) and 1,2-
and dicyano
dppe
PPh2
PPh2
O
Fe
Ph2P
PPh2
Ph2P
PPh2
Ph2P
PPh2
2
3
3
dppp
dppm
Xantphos
dppf
bis(diphenylphosphino)ethane (dppe) (5 mol%) in toluene
at room temperature, we were pleased to observe the for-
mation of the desired diastereoisomeric cyclopenta[b]benzo-
furan 3aa in 1:1.2 dr (Scheme 2).
Entry
Solvent
Ligand (mol%)
Conversion (%)a,b
drc
1
2
3
4
5
6
7
8
9
toluene
THF
dppe (5)
dppe (5)
dppe (5)
dppe (5)
dppe (5)
dppe (5)
dppe (5)
dppp (5)
dppm (5)
dppf (5)
77
1:1.2
1:1.1
1:1.1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
–
83
O
NO2
NO2
O
dioxane
MeCN
74
Pd2(dba)3⋅CHCl3
2.5 mol%)
dppe (5 mol%)
+
(
NC
>95 (68)
89
Br
CN
H
Br
CHCl
DCEd
3
NC CN
1
a (1 equiv)
2a (1 equiv)
toluene, r.t., 2 h
3aa
1:1.2 dr
7
7% conversion (1a)
>95 (73)
>95 (88)
87
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
Cl
Cl
Cl
Cl
Cl
Cl
Cl
2
2
2
2
2
2
2
Scheme 2 A preliminary study of the Pd(0)-catalyzed dearomatization
of 5-bromo-2-nitrobenzofuran (1a) with VCP 2a
27
Although the proof of concept had been rapidly
achieved, despite full consumption of 2a, we were not able
to reach full conversion of 1a as a probable result of the
known propensity of VCPs to undergo competitive oligom-
erization in the presence of a palladium(0) complex.12 In
this context, we decided to optimize the reaction condi-
tions to improve the efficiency of this new dearomative
process (Table 1).
10
11
12
72
Xantphos (5)
<5
PPh
3
(10)
(10)
<5
–
13
P(o-Tol)
3
27
1:1.2
a
1
Determined by H NMR analysis of the crude reaction mixture using 2-
bromo-1,3,5-trimethoxybenzene as an internal standard.
b
Yield of isolated product in parentheses.
c
1
Determined by H NMR analysis of the crude reaction mixture.
d
Employing the Pd (dba) ·CHCl /dppe catalytic system
DCE = 1,2-dichloroethane.
2
3
3
and fixing the reaction time at 2 hours, the influence of the
solvent was examined at room temperature. Switching
from toluene to THF or dioxane did not lead to any signifi-
cant improvement (Table 1, entries 2 and 3). In acetonitrile,
full conversion of 1a was obtained but the cyclopen-
ta[b]benzofuran 3aa (1:1 dr) was isolated in 68% yield (en-
try 4). Indeed, in this case, the concurrent formation of sev-
triphenyl- and tri-(ortho-tolyl)phosphine led to poor re-
sults (entries 10–13). For this reason, dppe was identified
as the optimum ligand for this transformation.
With this optimized catalytic system in hand, we then
studied the scope and limitations of this new dearomatiza-
tion reaction. Employing vinylcyclopropane 2a, the influ-
ence of the 2-nitrobenzofuran partner was first surveyed
(Scheme 3).
Using 2-nitrobenzofuran (1b), the corresponding dearo-
matized cycloadduct 3ba was obtained in 90% yield and 1:1
dr. The reactivity of various 5-substituted 2-nitrobenzofu-
rans was then evaluated. While, in all cases, no significant
increase in the diastereoselectivity was observed, the ste-
reoelectronic properties of the substituent present at posi-
tion 5 did not seem to have a key impact on the overall effi-
ciency of the dearomative cycloaddition process. Accord-
ingly, cycloadducts bearing methyl (3ca), tert-butyl (3da),
fluoro (3ea), chloro (3fa), methoxy (3ga) or trifluorome-
thoxy (3ha) groups were all obtained in satisfactory yields
(68–88%). This trend was confirmed when subjecting the 6-
1
eral by-products could be witnessed in the H NMR spec-
trum of the crude reaction mixture. Probing the use of
chlorinated solvents (entries 5–7), excellent conversions
were achieved in 1,2-dichloroethane and dichloromethane.
In the latter case, the cyclopentannelation product 3aa (1:1
dr) was obtained in 88% yield and, as such, dichlorometh-
ane was selected for the rest of our study (entry 7). Next, we
decided to evaluate whether other phosphorus-based li-
gands could improve the diastereoselectivity of this cyc-
loaddition reaction. Analogs of dppe such as 1,3-bis(di-
phenylphosphino)propane (dppp) and bis(diphenylphos-
phino)methane (dppm) induced a significant decrease of
reactivity without improving the stereoselectivity (entries
8
and 9). In the same way, bidentate 1,1′-bis(diphenylphos-
phino)ferrocene (dppf) and Xantphos, or monodentate
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J. Ling et al.
Letter
NO2
1
O
H
Pd2(dba)3⋅CHCl3 (2.5 mol%)
7
O
2
NO2
dppe (5 mol%)
6
+
R
R
3
NC
CH2Cl2, r.t., 2 h
5
EWG
EWG
4
CN
1b–n (1 equiv)
2a (1.1 equiv)
3ba–na
NO2
NO2
O
NO2
O
NO2
NO2
O
H
O
H
O
H
H
H
Me
tBu
F
Cl
NC CN
NC CN
NC CN
NC CN
NC CN
3
ba
3ca
68%
3da
72%
3ea
88%
3fa
82%
90%
1:1 dr
1:1.1 dr
1.1:1 dr
1:1 dr
1:1 dr
Me
Br
NO2
NO2
NO2
O
NO2
O
NO2
O
O
H
O
Me
H
H
H
H
MeO
F3CO
MeO
NC CN
NC CN
NC CN
NC CN
NC CN
3
7
ga
4%
.2:1 dr
3ha
77%
1:1 dr
3ia
72%
1.1:1 dr
3ja
3ka
83%
1:1.1 dr
59%
1:1 dr
1
Me
NO2
O
NO2
NO2
O
O
H
H
H
NC CN
NC CN
NC CN
Me
3
7
la
4%
:1.1 dr
3ma
51%
1:1.3 dr
3na
51%
1:2.3 dr
1
Scheme 3 Evaluation of various 2-nitrobenzofurans
and 7-substituted 2-nitrobenzofurans 1i–l to the reaction
conditions. Indeed, the corresponding methyl-, bromo- and
methoxy-substituted cyclopenta[b]benzofurans 3ia–la
were isolated in yields ranging from 59–83% and approxi-
mately 1:1 dr values. On the other hand, 2-nitrobenzo-
furans 1m,n bearing a substituent at position 4 proved to
be more sluggish in their reactions with 2a. The corre-
sponding cycloadducts 3ma and 3na were both obtained in
only 51% yield, suggesting that an increase of steric hin-
drance next to the electrophilic 3-position may, to some
extent, impede the desired cycloaddition process. Whereas
the diastereoselectivity was not significantly improved for
Pd2(dba)3⋅CHCl3
2.5 mol%)
dppe (5 mol%)
NO2
O
H
(
O
NO2
+
CH2Cl2, r.t., 2 h
EWG
Br
EWG EWG
Br
EWG
1a (1 equiv)
2b–f (1.1 equiv)
3ab–af
NO2
NO2
O
NO2
O
H
O
H
H
Br
MeO C CO Me Br
iPrO C CO2iPr Br F CH CO C CO CH CF
2
2
2
3
2
2
2
2
3
3ab
7%
:1.4 dr
3ac
87%
1:1.3 dr
3ad
89%
9
1
1:1.4 dr
3
ma (1:1.3 dr), the naphthyl-derived cyclopenta[b]benzo-
NO2
NO2
NO2
O
O
O
furan 3na was formed in a higher 1:2.3 dr.
Next, the influence of the vinylcyclopropane partner
was evaluated by submitting 5-bromo-2-nitrobenzofuran
H
O
H
O
O
O
H
N
O
O
O
Br
Br
Br
3
3
ae
3%
1:4.3 dr
O
N
(
(
1a) to Pd(0)-catalyzed reactions with VCPs 2b–f
Scheme 4).
Me
Me
3
af
no reaction
Me Me
3ag
O
degradation
Pleasingly, this novel palladium-catalyzed dearomatiza-
(81%, 1:4.4 dr
with 2 equiv of 1a)
tion reaction proved to be compatible with the use of VCP
diesters 2b–d. Accordingly, the corresponding cyclo-
penta[b]benzofurans 3ab–ad were obtained in good to
excellent yields (87–97%) and slightly better diastereoselec-
tivities than in the previous series. Switching to the indan-
Scheme 4 Evaluation of other vinylcyclopropanes
significant improvement of the cycloaddition stereo-
selectivity (1:4.3 dr), albeit with a low 33% yield under the
standard reaction conditions. When employing 2 equiva-
1,3-dione-derived vinylcyclopropane 2e resulted in a
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E

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Synlett
J. Ling et al.
Letter
lents of 5-bromo-2-nitrobenzofuran (1a) and a prolonged
reaction time of 72 hours, the dearomative cycloaddition
process could compete more efficiently with the polymer-
ization of 2e, such that the desired cyclopentannulated
product 3ae was obtained in a superior 81% yield (1:4.4
References and Notes
(
1) For reviews, see: (a) Roche, S. P.; Porco, J. A. Angew. Chem. Int.
Ed. 2011, 50, 4068. (b) Pigge, F. C. Dearomatization Reactions: An
Overview, In Arene Chemistry: Reaction Mechanisms and
Methods for Aromatic Compounds, 1st ed. Mortier, J., Ed.; Wiley-
VCH: New York, 2016.
13
dr). On the other hand, the use of Meldrum’s acid or bar-
bituric acid derived VCPs 2f and 2g did not result in the de-
sired dearomatization reaction. Whereas in the first case no
reaction occurred, the degradation of 2g was preferentially
observed over the formation of the desired cycloadduct 3ag.
Finally, we decided to test if this palladium-catalyzed
dearomative cycloaddition reaction would be compatible
with the use of isomeric 3-nitrobenzofurans. For this pur-
pose, the 5-acetoxy derivative 4 was prepared and reacted
(2) For reviews, see: (a) Zhuo, C. X.; Zhang, W.; You, S. L. Angew.
Chem. Int. Ed. 2012, 51, 12662. (b) Ding, Q.; Zhou, X.; Fan, R. Org.
Biomol. Chem. 2014, 12, 4807. (c) Wu, W.-T.; Zhang, L.; You, S.-L.
Chem. Soc. Rev. 2016, 45, 1570. (d) Zheng, C.; You, S. L. Chem
2016, 1, 830. (e) Asymmetric Dearomatization Reactions; You,
S.-L., Ed.; Wiley-VCH: Weinheim, 2016, For selected examples,
see. (f) Wu, Q. F.; He, H.; Liu, W. B.; You, S. L. J. Am. Chem. Soc.
2010, 132, 11418. (g) Wu, Q. F.; Liu, W. B.; Zhuo, C. X.; Rong, Z.
Q.; Ye, K. Y.; You, S. L. Angew. Chem. Int. Ed. 2011, 50, 4455.
(h) Shibuya, T.; Noguchi, K.; Tanaka, K. Angew. Chem. Int. Ed.
14
with VCP 2a. Satisfyingly, we obtained the desired cyclo-
addition product 5 in 94% yield (1.6:1 dr), suggesting that
this new dearomatization method is not limited to 2-nitro-
benzofurans (Scheme 5).
2
2
012, 51, 6219. (i) Zhu, S.; MacMillan, D. W. C. J. Am. Chem. Soc.
012, 134, 10815. (j) Nan, J.; Zuo, Z.; Luo, L.; Bai, L.; Zheng, H.;
Yuan, Y.; Liu, J.; Luan, X.; Wang, Y. J. Am. Chem. Soc. 2013, 135,
7306. (k) Xiong, H.; Xu, H.; Liao, S.; Xie, Z.; Tang, Y. J. Am. Chem.
1
Soc. 2013, 135, 7851. (l) Spangler, J. E.; Davies, H. M. L. J. Am.
Chem. Soc. 2013, 135, 6802. (m) Zhang, X.; Yang, Z.-P.; Liu, C.;
You, S.-L. Chem. Sci. 2013, 4, 3239. (n) Tong, M. C.; Chen, X.; Li, J.;
Huang, R.; Tao, H.; Wang, C. J. Angew. Chem. Int. Ed. 2014, 53,
4680. (o) Zi, W.; Wu, H.; Toste, F. D. J. Am. Chem. Soc. 2015, 137,
Pd2(dba)3⋅CHCl3
2.5 mol%)
dppe (5 mol%)
H CN
O
O
(
CN
+
NO2
NC
CH2Cl2, r.t.
94%
1.6:1 dr
O2N
AcO
AcO
CN
3
225. (p) Yang, D.; Wang, L.; Han, F.; Li, D.; Zhao, D.; Wang, R.
Angew. Chem. Int. Ed. 2015, 54, 2185. (q) Li, Z.; Shi, Y. Org. Lett.
015, 17, 5752.
4
(1 equiv)
2a (1.1 equiv)
5
Scheme 5 Evaluation of a 3-nitrobenzofuran derivative
2
(3) For representative examples, see: (a) Kimura, M.; Futamata, M.;
Mukai, R.; Tamaru, Y. J. Am. Chem. Soc. 2005, 127, 4592.
(
(
b) Trost, B. M.; Quancard, J. J. Am. Chem. Soc. 2006, 128, 6314.
c) García-Fortanet, J.; Kessler, F.; Buchwald, S. L. J. Am. Chem.
In summary, we have herein demonstrated that a vari-
ety of 2-nitrobenzofurans undergo a palladium-catalyzed
dearomative (3+2) cycloaddition with vinylcyclopropanes.
This novel methodology offers an efficient and atom-eco-
nomical access to a wide range of cyclopenta[b]benzofuran
derivatives with average to excellent yields and can also be
applied to the use of a 3-nitrobenzofuran. Further studies
concerning the development of an enantioselective variant
of this dearomatization reaction are currently underway
and will be reported in due course.
Soc. 2009, 131, 6676. (d) Rousseaux, S.; García-Fortanet, J.; Del
Aguila Sanchez, M. A.; Buchwald, S. L. J. Am. Chem. Soc. 2011,
1
33, 9282. (e) Wu, K. J.; Dai, L. X.; You, S. L. Org. Lett. 2012, 14,
772. (f) Nemoto, T.; Zhao, Z.; Yokosaka, T.; Suzuki, Y.; Wu, R.;
3
Hamada, Y. Angew. Chem. Int. Ed. 2013, 52, 2217. (g) Xiao, Q.;
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Sci. 2013, 4, 97.
15
(
4) (a) Trost, B. M.; Ehmke, V.; O’Keefe, B. M.; Bringley, D. A. J. Am.
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2
017, 19, 2266. (c) Rivinoja, D. J.; Gee, Y. S.; Gardiner, M. G.;
Funding Information
Ryan, J. H.; Hyland, C. J. T. ACS Catal. 2017, 7, 1053. (d) During
the preparation of this manuscript, other palladium-catalyzed
dearomative (3+2) cycloadditions of nitroaromatics have been
described. For 2-nitrobenzofurans, see: Cheng, Q.; Zhang, H.-J.;
Yue, W.-J.; You, S.-L. Chem 2017, 3, 428. (e) For 3-nitroindoles,
see: Gee, Y. S.; Rivinoja, D. J.; Wales, S. M.; Gardiner, M. G.; Ryan,
J. H.; Hyland, C. J. T. J. Org. Chem. 2017, 82, 13517.
This work was supported by the Ministère de l’Education Nationale,
de l’Enseignement Supérieur et de la Recherche and the Centre
National de la Recherche Scientifique.
)(
Acknowledgment
(
(
5) For seminal works on the dearomatization of nitroarenes, see:
(a) Roy, S.; Kishbaugh, T. L. S.; Jasinski, J. P.; Gribble, G. W. Tetra-
hedron Lett. 2007, 48, 1313. (b) Lee, S.; Chataigner, I.; Piettre, S.
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2013, 19, 7181.
6) For recent reviews on the reactivity of vinylcyclopropanes, see:
(a) Ganesh, V.; Chandrasekaran, S. Synthesis 2016, 48, 4347.
(b) Meazza, M.; Guo, H.; Rios, R. Org. Biomol. Chem. 2017, 15,
We warmly thank Sandra Segondy for her contribution to the synthe-
sis of several 2-nitrobenzofurans.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591540.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
2479.
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Letter
(
7) King, M. L.; Chiang, C.-C.; Ling, H.-C.; Fujita, E.; Ochiai, M.;
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zofurans with VCPs; General Procedure
McPhail, A. T. J. Chem. Soc., Chem. Commun. 1982, 1150.
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Med. Chem. 2006, 6, 319. (b) Ribeiro, N.; Thuaud, F.; Nebigil, C.;
Désaubry, L. Bioorg. Med. Chem. 2012, 20, 1857. (c) Zhao, Q.;
Abou-Hamdan, H.; Désaubry, L. Eur. J. Org. Chem. 2016, 5908.
(
In a screw-capped vial, vinylcyclopropane (0.44 mmol, 1.1
equiv), 2-nitrobenzofuran (0.40 mmol, 1.0 equiv) and CH Cl2
2
(800 μL) were successively added. The resulting mixture was
stirred at r.t. for 5 min before a solution of Pd (dba) ·CHCl (0.01
2
3
3
(
9) For selected examples, see: (a) Davey, A. E.; Taylor, R. J. K. J. Chem.
Soc., Chem. Commun. 1987, 25. (b) Trost, B. M.; Greenspan, P. D.;
Yang, B. V.; Saulnier, M. G. J. Am. Chem. Soc. 1990, 112, 9022.
mmol, 0.025 equiv) and dppe (0.02 mmol, 0.05 equiv) in CH Cl2
2
(800 μL), previously stirred at r.t. for 25 min, was transferred via
cannula. The cannula was washed with an additional aliquot of
CH Cl (400 μL) (total volume of solvent = 2.0 mL) and the final
(c) Gerard, B.; Cencic, R.; Pelletier, J.; Porco, J. A. Angew. Chem.
2
2
Int. Ed. 2007, 46, 7831. (d) El Sous, M.; Khoo, M. L.; Holloway, G.;
Owen, D.; Scammells, P. J.; Rizzacasa, M. A. Angew. Chem. Int. Ed.
reaction mixture was stirred at r.t. for 2 h. At this point, CH Cl2
2
(10 mL) was added, the mixture was loaded onto a small silica
plug, eluted with additional CH Cl (40 mL) and concentrated
2007, 46, 7835. (e) Malona, J. A.; Cariou, K.; Frontier, A. J. J. Am.
2
2
Chem. Soc. 2009, 131, 7560. (f) Magnus, P.; Freund, W. A.;
Moorhead, E. J.; Rainey, T. J. Am. Chem. Soc. 2012, 134, 6140.
under reduced pressure. After measurement of the diastereo-
meric ratio by H NMR spectroscopy, the resulting crude
1
(
g) Stone, S. D.; Lajkiewicz, N. J.; Whitesell, L.; Hilmy, A.; Porco, J.
mixture was purified by flash column chromatography to afford
the desired cycloadduct.
7-Bromo-3a-nitro-3-vinyl-2,3,3a,8b-tetrahydro-1H-cyclo-
penta[b]benzofuran-1,1-dicarbonitrile (3aa)
A. J. Am. Chem. Soc. 2015, 137, 525. (h) Zhou, Z.; Tius, M. A.
Angew. Chem. Int. Ed. 2015, 54, 6037. (i) Paz, B. M.; Li, Y.;
Thøgersen, M. K.; Jørgensen, K. A. Chem. Sci. 2017, 8, 8086.
(
10) For alternative dearomatization of benzofurans leading to cyclo-
penta[b]benzofurans, see: (a) Saito, K.; Ishihara, H.; Kagabu, S.
Bull. Chem. Soc. Jpn. 1987, 60, 4141. (b) Fujita, M.; Oshima, M.;
Okuno, S.; Sugimura, T.; Okuyama, T. Org. Lett. 2006, 8, 4113.
Following the typical procedure, starting from 5-bromo-2-
nitrobenzofuran (1a) (97 mg), compound 3aa was obtained as a
white solid (126 mg, 88% yield, 1:1 dr) after flash column chro-
matography (toluene/petroleum ether, 6:4). Mp 162–164 °C; IR
–1 1
(c) Qu, J.-P.; Liang, Y.; Xu, H.; Sun, X.-L.; Yu, Z.-X.; Tang, Y. Chem.
(film): 2359, 1560, 1509, 1365, 1313, 1243 cm . H NMR (300
Eur. J. 2012, 18, 2196. (d) Pérez-Vázquez, J.; Veiga, A. X.; Prado,
G.; Sardina, F. J.; Paleo, M. R. Eur. J. Org. Chem. 2012, 975.
11) Tromelin, A.; Demerseman, P.; Royer, R. Synthesis 1985, 1074.
12) (a) Lishanskii, I. S.; Semenova, L. S. Polym. Sci. U.S.S.R. 1971, 13,
MHz, CDCl ): δ = 7.73–7.45 (m, 4 H), 7.03 (dd, J = 9.0, 5.8 Hz, 2
3
H), 5.95–5.74 (m, 1 H), 5.74–5.56 (m, 1 H), 5.55–5.32 (m, 4 H),
4.96 (s, 1 H), 4.78 (s, 1 H), 4.10–3.90 (m, 1 H), 3.60–3.39 (m, 1
H), 3.05–2.91 (m, 2 H), 2.87 (ddd, J = 13.5, 5.8, 1.3 Hz, 1 H), 2.36
(
(
13
2657. (b) Suzuki, M.; Sawada, S.; Saegusa, T. Macromolecules
(t, J = 13.5 Hz, 1 H); C NMR (101 MHz, CDCl ): δ = 157.9, 157.6,
3
1
989, 22, 1505. (c) Suzuki, M.; Sawada, S.; Yoshida, S.;
135.7, 135.4, 130.1, 128.1, 128.0, 127.6, 124.0, 123.5, 123.4,
121.8, 121.7, 121.2, 116.9, 116.6, 114.4, 113.5, 113.4, 112.7,
111.9, 111.6, 63.0, 60.4, 52.4, 51.3, 43.3, 41.1, 39.7, 38.5; MS
Eberhardt, A.; Saegusa, T. Macromolecules 1993, 26, 4748.
(
13) The relative stereochemistry of the major diastereoisomer of
+
•
3ae could not be established unambiguously by NOESY NMR
(EI): m/z = 312 [M – HNO ] .
2
experiments (see the Supporting Information).
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2018, 29, A–E