Arene Trifunctionalization with Highly Fused Ring Systems through a Domino Aryne Nucleophilic and Diels–Alder Cascade

Article abstract of DOI:10.1002/anie.201911730

A convenient and efficient domino aryne process was developed under transition-metal-free conditions to generate a range of tetra- and pentacyclic ring systems. This transformation was realized via a 1,2-benzdiyne through a nucleophilic and Diels–Alder reaction cascade using styrene as the diene moiety. Three new chemical bonds, namely one C?N and two C?C bonds, and two benzofused rings could be constructed concomitantly, which was made possible by distinct chemoselective control at both the 1,2-aryne and 2,3-aryne stages. Moreover, in-depth studies were carried out on the domino aryne precursors and controlling the diastereoselectivity.

Full text of DOI:10.1002/anie.201911730

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Arene Trifunctionalization with Highly Fused Ring Systems
through Domino Aryne Nucleophilic, Diels-Alder Cascade
Authors: Jia He, Zizi Jia, Hongcheng Tan, Xiaohua Luo, Dachuan Qiu,
Jiarong Shi, Hai Xu, and Yang Li
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201911730
Angew. Chem. 10.1002/ange.201911730
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10.1002/anie.201911730
Angewandte Chemie International Edition
COMMUNICATION
Arene Trifunctionalization with Highly Fused Ring Systems
through Domino Aryne Nucleophilic, Diels-Alder Cascade
Jia He,[a] Zizi Jia,[a] Hongcheng Tan,[a] Xiaohua Luo,[a] Dachuan Qiu,[a] Jiarong Shi,[a] Hai Xu,[a] and
Yang Li*[a]
Abstract: A convenient and efficient domino aryne process was
developed under transition metal-free conditions, featuring a group of
tetra- and pentacyclic ring systems. This transformation was realized
were then chosen, and 1,2,3-trisubstituted arenes with [6,n,6]-
tricyclic system could be conceived through cascade
a
nucleophilic, [4+2]-cycloaddition process with our domino aryne
precursors (Scheme 1b). A challenge for the success of this
proposal, however, remains on how to tune the chemoselectivity
between two types of arynophiles, namely a nucleophile and a
diene arynophile. Therefore, a proper diene arynophile with
suitably low reactivity in intermolecular 1,2-aryne i step, but
sufficiently high reactivity in intramolecular 2,3-aryne ii stage, is
obligatory (Scheme 1b). Herein, we wish to present our study on
a domino aryne process by successfully tethering a N-nucleophile
by
a 1,2-benzdiyne-involved nucleophilic, Diels-Alder reaction
cascade using styrene as diene moiety. Three new chemical bonds,
namely one C-N and two C-C bonds, and two benzofused rings could
be concomitantly constructed, which was made possible by distinct
chemoselective control on both 1,2-aryne and 2,3-aryne stages.
Moreover, in-depth studies were carried out on domino aryne
precursors and diastereoselective control.
and
a
styrene moiety, affording [6,n,6,6]-tetracyclic and
Arynes are among the most reactive organic species, which
could readily prepare various vicinal difunctionalized arenes.[1]
Along with the extensive applications of mild aryne generation
methods developed by Kobayashi[2] and Hoye,[3] aryne chemistry
steps into a blooming era in recent years. In order to reach
polysubstituted arenes, equivalents of benzdiynes and
benztriynes have been employed.[4] Among these poly-benzyne
species, 1,2-benzdiyne is unique by utilizing a common C2-
position in both its 1,2-aryne and 2,3-aryne stages, which could
regulate a strict generation sequence with distinct regioselective
control.[4b-j] Recently, our group employed Kobayashi’s method in
1,2-benzdiyne processes and disclosed double nucleophilic
[6,5,6,6,6]-pentacyclic systems with a potential for the preparation
of biologically active molecular frameworks.
a. previous domino aryne strategies:
ene end
E
Nu2
H
3
LG
i
Nu
double Nu
Nu2
Nu1
E
and
E = H or R
Nu1
Nu
strategy I
strategy II
drawback:
1,2-difunctionalized arenes
b. proposal:
LG
LG
3
2
[4+2]
Nu
2
-LG
TMS
OTf
reactions with both substituted thiobenzamides[4b] and
sulfonamide nucleophiles[4c,
(strategy I, Scheme 1a).
1
4d]
Nu
Nu
domino aryne
precursors 1
Furthermore, a breakthrough was realized by combining two
different types of arynophiles into the same cascade process. To
1,2-aryne i
2,3-aryne ii
1,2,3-trifunctionalization
one C-Nu, two C-C bonds
two new benzofused rings
this end,
a domino aryne nucleophilic-ene reaction was
successfully accomplished (strategy II, Scheme 1a).[4h] Despite
the fact that this methodology is amenable to the preparation of
natural related indoline scaffolds, its drawback resides in only 1,2-
difunctionalization with the formation of a C-H bond on the C3-
position of benzene ring. In view of the prevailing presence of
polysubstituted arenes, especially those with highly fused ting
systems, more efficient and practical aryne multifunctionalization
maneuvers remain highly desired.
Scheme 1. Background and proposal.
Our study commenced with searching for suitable diene moiety.
Reactions of arynes with both N-nucleophiles and dienes,
however, normally take place facilely,[1] which would likely
disobey our demand on “nucleophile priority” in 1,2-aryne stage
and vice versa in 2,3-aryne stage. Indeed, when substrate 2 with
a furan tethered sulfonamide was utilized, a complex mixture was
observed, presumably attributed by the competing reaction of
highly reactive furan species (Scheme 2a).[6] In addition, substrate
3 with a linear 1,3-diene moiety only afforded 4 in 25% yield, the
formation of which underwent through an intramolecular ene
pathway (Scheme 2a).[7] Therefore, linear 1,3-diene is not
suitable for this cascade process as well. Both examples
demonstrate that dienes with mismatched reactivity would lead to
undesired reaction pathways. Gratifyingly, cinnamyl sulfonamide
5a with tethered styrene as diene moiety was found to produce
the desired product 6a (Scheme 2a).[8] Notably, the [6,5,6,6]-
tetracyclic framework assembled through this protocol can be
converted to naphthoxindoles,[8a, 9] which are structurally related
to a family of aristolactams with antitumor, antibacterial, and
antimalarial properties (Scheme 2b).[10] In addition, when
Along with our study on aryne chemistry and in line with our
goal on preparing biologically active as well as medicinally
4f, 4h, 4i, 5]
important molecules using these protocols,[4b-d,
we
envisioned that by switching 2,3-aryne ii reaction partner from ene
arynophile to the one that could incorporate two substituents other
than hydrogen would reach aryne trifunctionalization. 1,3-Dienes
[a]
J. He, Z. Jia, H. Tan, X. Luo, D. Qiu, J. Shi, H. Xu, and Prof. Dr. Y.
Li
School of Chemistry and Chemical Engineering
Chongqing University
174 Shazheng St., Chongqing, P. R. China, 400030
E-mail: y.li@cqu.edu.cn
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/anie.201911730
Angewandte Chemie International Edition
COMMUNICATION
nitrogen-imbedded analogues were utilized, ergot alkaloid
framework,[11] such as lysergic acid and lysergine, could be
conceived (Scheme 2b). Along with our study, Hoye and co-
workers recently applied their aryne-initiated hexadehydro-Diels-
Alder (HDDA) reaction concept[3e] in a distinct 1,2-benzdiyne-
HDDA cascade to access naphthynes.[12] In their study, they
LG
Cs2CO3
18-c-6
conditionsa
3
1
TMS
OTf
H
+
Ph
NHTs
5a
NTs
NTs
1
iii
6a
entry
temp(oC)
yield(%)
1
alternative conditions
solvent
1
2
3
4
5
6
7
130
130
100
150
130
130
130
74
60
25
40
26
38
42
1a
1a
1a
1a
no
addition of 1a over 2 h
PhCl
PhCl
dioxane
accomplished
a
sequential generation of three aryne
no
no
intermediates, namely domino 1,2-benzdiyne (1,2-aryne i and
2,3-aryne ii) and HDDA naphthyne, which could be then trapped
by arynophiles for the preparation of naphthalene products.[12] In
contrast, the employment of styrene arynophiles with lower
degree of unsaturation than 1,3-diyne would provide versatile
means toward either synthetically challenging molecular scaffolds,
particularly those possessing multiple stereocenters, or the
skeletons of natural products as well as biologically active
molecules.
o-dichlorobenzene
1a K2CO3 instead of Cs2CO3
PhCl
PhCl
PhCl
1a
1b
CsF instead of Cs2CO3
no
a conditions A: slow addition of a solution of 1a (0.6 mmol) in PhCl (10 mL) to
a suspension of 5a (0.3 mmol), Cs2CO3 (1.8 mmol), and 18-c-6 (0.6 mmol) in
PhCl (20 mL) at 130oC over 1 h.
Modification with different LGs:
conditions B: slow addition of a solution of 1 (0.6 mmol) in toluene (10 mL) to
a suspension of 5a (0.3 mmol), Cs2CO3 (1.8 mmol), and 18-c-6 (0.6 mmol) in
toluene (20 mL) at 100oC over 1 h.
O
O
O
O
S
S
O
O
=
LG
OTs
OTf
H
F
OMe
a. our initial study:
1a, 38%
1b, 30%
1c, 40%
1d, 38%
NHTs
O
F
CF3
O
O
S
O
O
O
O
O
O
O
S
F
S
S
O
O
2
O
complex
mixture
PhCl, 130oC
[4+2] vs Nu
this work:
Ph
1e, 65%
1f, 43%
1g, 53%
1h, 59%
OTs
i
NHTs
F
F
O
O
5a
O
O
mismatched
reactivity
O
O
O
O
Ph
S
S
CF3
S
S
PhCl, 130oC
56%
O
O
O
O
H
.
CF3
CF3
NTs
F
F
NO2
Cl
Ph
NHTs
3
6a
1i, 46%
1j, 55%
1k, 68%
1l, 52%
PhCl, 130oC, 25%
F
O
O
O
S
O
O
O
N
Ts
S
F
O
O
[4+2] vs ene
S
F
F
O
O
O
S
O
4
b. related structures:
R’
F
CF3
F
F
1o, 23%
HOOC
Me
R2
R1
1m, 42%
1n, 14%
1p, 22%
NMe
H
NMe
H
Cl
O
O
Cl
Cl
O
O
S
O
O
O
O
S
S
S
O
NR
O
O
O
O
O
R
NH
NH
NH
Cl
Cl
1r, 44%
Cl
1s, 31%
Cl
Cl
1t, 38%
naphthoxindoles
aristolactams
lysergic acid
lysergine
1q, 44%
Scheme 2. Our initial study.
Table 1. Optimization of the reaction.
this reaction under suitably low temperature, i.e., 100oC. When 1a
and 1b were utilized in toluene at 100oC, unfortunately, both
reactions produced 6a in low yields (Table 1). The mismatched
reactivity with respect to both 1a and 1b prompted us to examine
their analogues with different second leaving groups (LGs) that
could fill the leaving-ability gap between highly active OTf group
and comparatively inert OTs group. Consequently, a series of 1,2-
benzdiyne equivalents 1c-1t were prepared with substituted aryl
sulfonates as the second LGs (Table 1). Indeed, different
reactivity was observed with those domino aryne precursors. In
general, aryl sulfonates with electron-withdrawing groups depart
faster than those with electron-donating groups (i.e. 1d).
Moreover, ortho-substituted aryl sulfonates gave higher yields
than both meta- and para-substituted analogues (1e-1g, 1h-1j).
1k with two ortho-fluoro substituents obtained 6a in higher yield
than those of 1l with one ortho-fluoro and 1m with no ortho-fluoro
group. However, domino aryne precursors 1n-1p with strong
electron-withdrawing groups produced 6a in low yields. In
contrast to fluoro-substituents, those containing chloro-
Upon optimization of the reaction conditions, the yield of
compound 6a could reach to 74% at 130oC using chlorobenzene
as the solvent (conditions A, please see Table S1 in supporting
information for detailed information), the formation of which
experienced a rearomatization of intermediate iii via [1,3]-hydride
migration (entry 1, Table 1). Changing addition time of 1a to two
hours gave rise to 5a in 60% yield (entry 2), which could be
reasoned by the instability of 5a at 130oC. Altering the conditions
to both dioxane at 100oC and o-dichlorobenzene at 150oC only
resulted in low yields of 6a (entries 3 and 4). When Cs2CO3 was
replaced by either K2CO3 or CsF, 6a was afforded in only 26%
and 38% yields, respectively (entries 5 and 6). Employing TPBT
reagent 1b gave rise to 6a in 42% yield (entry 7).
Our previous study revealed that the OTs group on 1a only
departs facilely at ~130oC,[4h] whereas certain amount of cinnamyl
sulfonamide will decompose under this temperature. Meanwhile,
we noticed that elevated temperature is necessary in order to
propel the intramolecular Diels-Alder reaction with relatively less
active styrene moiety on 2,3-aryne ii stage (Table S1), while
preventing side reactions. Therefore, it is desirable to carry out
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substituents (1q-1t) could only generate 6a in low yields. Notably,
our study can not only be applied in this cascade transformation,
but also could set up a platform for future work on domino aryne
processes. Among these domino aryne precursors, 1k with 2,6-
difluorophenylsulfonate as the second LG could afford 6a in 68%
yield in toluene at 100oC, which was chosen as conditions B for
the following study.
substituents on the para-position of the aryl group on cinnamyl
chain could be tolerated and afforded products 6b-6f in good to
high yields (Scheme 3). Substrates with ortho-substituents on
cinnamyl aryl group could also generate the corresponding
products 6g-6i. In addition, 3-(naphthalen-1-yl)allyl sulfonamide
produced 6j in 77% yield. In contrast, substrate with a methyl
group on the meta-position of aryl group gave rise to 6k as a 1:1
mixture of regioisomers. Cinnamyl sulfonamide with gem-
dimethyl groups on its C1-position afforded 6l in 55% yield.
We then started to investigate the reaction scope. It was found
that both the electron-withdrawing and electron-donating
a,b
R
Me
Br
OMe
R = H, 6a, 74%
R = Cl, 6b, 73%
R = F, 6c, 70%
R = CF3, 6d, 68%
R = Me, 6e, 72%
R = MeO, 6f, 78%
NTs
NTs
6g, 59%
NTs
NTs
NTs
6j, 77%
X-ray of 6a
6h, 73%
6i, 57%
diastereoselectivity study:
Me(H)
Me
H
Ph
H
H
H
H
Me
H
(Me)H
Me
Ph
iPr
Me
NTs
NTs
NTs
NTs
NTs
NTs
NTs
c,d
6p
6q
78% (1.5:1 dr)
57% (3:1 dr)
a
c
a
6k, 79%
(1:1 isomers)
6l, 55%
6m, 78%
(1.5:1 dr)
6n, 58%
6o, 60%
(10:1 dr)
89% (3:1 dr)
60% (3:1 dr)
(1.5:1 dr)
c
MeO
H
H
H
H
H
Me
Me
H
H
H
H
Me
H
H
Me
Me
H
N
Ts
N
Ts
N
Ts
N
H
H
H
N
Ts
Ts
6r, 67%
6s, 65%
6t, 59%
X-ray of 6t
6u, 47%
6v, 65%
N-heterocyclic rings:
other ring size:
OMe
OMe
NTs
Me
N
N
NTs
N
Ts
N
Ts
TsN
NTs
NTs
6w, 40%
X-ray of 6w
6x, 41%
6y, 40%
6z, 71%
6aa, 65%
6bb, 31%
Scheme 3. Substrate scope. a conditions A: slow addition of a solution of 1a (0.6 mmol) in PhCl (10 mL) to a suspension of 5 (0.3 mmol), Cs2CO3 (1.8 mmol), and
18-c-6 (0.6 mmol) in PhCl (20 mL) at 130oC over 1 h; b isolated yields; c conditions B: slow addition of a solution of 1k (0.6 mmol) in toluene (10 mL) to a suspension
of 5 (0.3 mmol), Cs2CO3 (1.8 mmol), and 18-c-6 (0.6 mmol) in toluene (20 mL) at 100oC over 1 h; d 38% of 6n with (1.5:1 dr) was obtained using conditions A.
A distinct property by employing styrene as diene arynophile is
its potential to generate stereocenters on different sites of the
[6,5,6,6]-tetracyclic core, particularly in view of the convenient
preparation of substituted cinnamyl sulfonamides. It was found
that diastereoselectivity was affected by the substituent on the
C1-position of cinnamyl chain. Substrates with both methyl and
phenyl group on C1-position gave rise to 6m and 6n as 1.5:1
mixture of diastereoisomers (Scheme 3). Due to the instability of
the substrate in PhCl at 130oC (conditions A), 6n was prepared in
toluene at 100oC using 1k as domino aryne precursor (conditions
B). Pleasingly, cinnamyl sulfonamide with a sterically congested
isopropyl group on its C1-position afforded 6o in 60% yield with
10:1 diastereoselectivity. Substituents on the benzylic position of
cinnamyl chain were then examined. Both products 6p and 6q
could be obtained in good to high yields, whereas with low
diastereoselectivity no matter what conditions were utilized. A
series of Ts-protected 3-phenylcyclohex-2-en-1-amines were
then prepared from cyclohexane-1,3-diones by incorporating both
C1 and benzylic positions into a six-membered ring. Pleasingly,
these substrates could give rise to products 6r-6v as single
isomer in moderate to good yields. Distinctively, highly fused
[6,5,6,6,6]-pentacyclic system was readily assembled with
concomitant formation of three consecutive chiral centers in
exclusive diastereoselective control, the relative stereostructure
of which was confirmed by the X-ray crystal structure of 6t.
Notably, this [6,5,6,6,6]-pentacyclic core cannot be easily
accessed through conventional methods, underlining the potential
of this domino aryne nucleophilic, [4+2] cycloaddition protocol in
preparing complex structural architectures.
Substrates containing heterocyclic rings were then studied.
When 3-(pyridin-2-yl)allyl sulfonamides were examined, it was
found that a 6-methoxy group on the pyridine ring was necessary,
producing 6w and 6x in ~40% yields (Scheme 3). In the absence
of 6-methoxy group, no desired product could be obtained at all.
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COMMUNICATION
a.
b.
Cs2CO3, 18-c-6
It is noteworthy that 6w and 6x possess an identical skeleton with
that of ergot alkaloids (Scheme 2b).[11] Although enormous efforts
have been tried to optimize these reactions, no further
enhancement in yield could be reached (please see Table S2 in
supporting information for details). Based on our experimental
observation, we hypothesized that it might be attributed by a
mismatch between either the reactivity or stability of these
substrates and several highly active intermediates involved in this
multistep process. Moreover, substrate with pyrrole heterocycle
could afford product 6y in 40% yield as well. Beyond cinnamyl
sulfonamides, we also investigated substrates with longer linkers.
It was found that 6z and 6aa could be obtained in 71% and 65%
yields, respectively (Scheme 3). In contrast, compound 6bb with
a [6,7,6,6]-tetracyclic ring system was only produced in 31% yield.
The formation of 6z-6bb demonstrates that this protocol owns
broad potential in constructing other polycyclic ring systems.
Substituted domino aryne precursors were then examined. As
shown in Scheme 4, the corresponding tetracyclic framework 7a-
7c were obtained in good yields from 1u-1w. Unexpectedly, aryne
precursor 1x with a distal chloride gave no desired product 7d at
all. Unsymmetrical domino aryne precursors 1y-1bb could all
afford the corresponding product 7e-7h in regiospecific manner,
which was attributed by a better leaving tendency of the OTf group
than that of the OTs group.
+ 1a
NHTs
5a
(1g scale)
6a
Ph
PhCl, 130oC
70%
886 mg
conditions B with 1k: 45%
conditions A with 1a: 32%
NHTs
Ph
8
NTs
c.
9
DDQ
DDQ
toluene-H2O
reflux, 95%
toluene-H2O
reflux, 96%
O
NTs
NTs
10
6a
d.
OMe
N
NMe
NMe
i. MeOTf
iii. Na-naphthalene
THF, -78oC
K2CO3, DCM, rt
ii. then NaBH4
DCM-MeOH
(91% in two steps)
iv. then MnO2
DCM, rt
(81% in two steps)
NTs
NH
NTs
6w
11
12
Scheme 5. Further investigations.
As shown in Scheme 5a, we could carry out this reaction in
gram-scale to afford 6a in 70% yield. Further investigation
revealed that 3-phenylprop-2-yn-1-yl sulfonamide 8 could take
part in nucleophilic, Diels-Alder reaction with 1k under conditions
B to afford phenanthrene 9 in 45% yield, whereas only 32% of 9
was obtained under conditions A (Scheme 5b).[13] As has been
shown in Scheme 2b, because naphthoxindoles are structural
analogues of bioactive natural products, they have attracted
attention from different synthetic groups.[8a, 9] We found that our
products could readily access naphthoxindoles as well. By
treating 6a with DDQ in toluene-H2O, naphthoxindole 10 was
obtained in 95% yield (Scheme 5c).[14] Meanwhile, compound 9
could be also converted to naphthoxindole 10 in excellent yield
using DDQ in toluene-H2O. Moreover, compound 6w was found
to be converted to ergot alkaloid skeleton (Scheme 2b).[11] As
shown in Scheme 5d, a one-pot, two-step operation on 6w
afforded compound 11 in 91% yield, transforming the pyridine ring
to piperidine moiety. Pleasingly, the methoxy group on 6w was
readily removed with excess amount of NaBH4 along with
concomitant reduction of the pyridine ring.[15] After one-pot
removal of the Ts group, followed by oxidative dehydration
reaction, compound 12 was prepared in 81% yield. This synthetic
route, in combination with our diastereoselectivity study in
a,b
OTs
Cs2CO3
18-c-6
TMS
OTf
+
Ph
NHTs
PhCl, 130oC
slow addition
of 1
R
R
5a
NTs
1
7
OTs
OTs
TMS
OTf
TMS
OTf
Me
Ph
NTs
NTs
Me
Ph
1v
1u
7a, 74%
7b, 71%
OTs
OTs
TMS
OTf
TMS
OTf
TBS
Cl
NTs
NTs
NTs
NTs
TBS
Cl
1w
1x
7c, 70%
7d, not observed
OTs
OTs
TMS
Me
TMS
OTf
Me
OTf
NTs
Me
1z
Scheme 3, might provide
a convenient approach toward
1y
Me
7e, 72%
7f, 72%
derivatization of biologically active framework of ergot alkaloid.
In summary, a convenient preparation of various highly fused
ring systems has been developed via a domino aryne process.
This cascade transformation involves a sequential nucleophilic
reaction and an intramolecular Diels-Alder reaction with styrene-
type diene moiety, featuring a concomitant formation of three
chemical bonds and two benzofused rings under transition metal-
free conditions. In-depth investigations were carried out on both
domino aryne precursors and diastereoselectivity of the cascade
process. This protocol provides a means to prepare structurally
complex molecules from easily achievable substrates, some of
which are otherwise not easy to access. Future work includes the
exploration of various arynophiles in domino aryne processes as
well as in-depth mechanistic study.
OTs
OTs
TMS
OTf
i-Pr
TMS
OTf
i-Pr
NTs
i-Pr
i-Pr
7h, 77%
1aa
1bb
7g, 76%
Scheme 4. Reactions with substituted aryne precursors. a conditions A: slow
addition of a solution of 1 (0.6 mmol) in PhCl (10 mL) to a suspension of 5a (0.3
mmol), Cs2CO3 (1.8 mmol), and 18-c-6 (0.6 mmol) in PhCl (20 mL) at 130oC
over 1 h. b isolated yields.
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10.1002/anie.201911730
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COMMUNICATION
Acknowledgements
Tf
Ar
Ar
HN
OTf
NTf
NTf
CsF
+
+
+
TPBT 1b
O
+
O
O
MeCN
CN
NTf
Ar
The authors gratefully acknowledge research support of this work
by NSFC (21772017), Basic and Frontier Research Project of
Chongqing (cstc2018jcyjAX0357), and Fundamental Research
Funds for the Central Universities (2018CDXZ0003).
1.0: 1.0
a
c
b
a: b: c = 1.9: 1.0: 1.4
[7]
[8]
To our knowledge, it is the first time that an allene species, instead of
[4+2] cycloadducts, could be generated from 1,3-diene in aryne reactions.
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Keywords: Aryne • Domino aryne • Benzdiyne • Cascade
reaction • Arene trisubstitution
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+
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This article is protected by copyright. All rights reserved.

10.1002/anie.201911730
Angewandte Chemie International Edition
COMMUNICATION
COMMUNICATION
Jia He, Zizi Jia, Hongcheng Tan,
Xiaohua Luo, Dachuan Qiu, Jiarong Shi,
Hai Xu, and Yang Li*
Page No. – Page No.
Arene Trifunctionalization with Highly
Fused Ring Systems through Domino
Aryne Nucleophilic, Diels-Alder
Cascade
A convenient and efficient domino aryne process was developed under transition
metal-free conditions, featuring a group of tetra- and pentacyclic ring systems.
This article is protected by copyright. All rights reserved.