Rhodium-Catalyzed Selective Oxidative (Spiro)annulation of 2-Arylindoles by Using Benzoquinone as a C2 or C1 Synthon

Article abstract of DOI:10.1021/acs.orglett.9b02336

Rhodium-catalyzed substrate-tunable oxidative annulation and spiroannulation reactions of 2-arylindoles with benzoquinone leading to 9H-dibenzo[a,c]carbazol-3-ols and new spirocyclic products are reported. Intriguingly, with 2-aryl-substituted indoles, be

Full text of DOI:10.1021/acs.orglett.9b02336

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
Rhodium-Catalyzed Selective Oxidative (Spiro)annulation of
2
‑Arylindoles by Using Benzoquinone as a C2 or C1 Synthon
Shenghai Guo,* Yangfan Liu, Lu Zhao, Xinying Zhang, and Xuesen Fan*
Henan Key Laboratory of Organic Functional Molecules and Drug Innovation, Collaborative Innovation Center of Henan Province
for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education,
School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, Henan 453007, China
*
S Supporting Information
ABSTRACT: Rhodium-catalyzed substrate-tunable oxidative annulation and spiroannulation reactions of 2-arylindoles with
benzoquinone leading to 9H-dibenzo[a,c]carbazol-3-ols and new spirocyclic products are reported. Intriguingly, with 2-aryl-
substituted indoles, benzoquinone could act as a C2 synthon to afford dibenzo[a,c]carbazoles. On the contrary, when 2-aryl-3-
substituted indoles were used, benzoquinone switched to act as a C1 synthon to furnish spirocyclic compounds. In addition,
further transformations of the obtained products demonstrate the synthetic utility of the present protocol.
used carbazole derivatives have attracted much attention
Scheme 1. Transition Metal-Catalyzed Oxidative Annulation
Reactions of 2-Arylindoles
F
because they are privileged scaffolds in numerous naturally
1
2
occurring alkaloids, bioactive organic molecules, and novel
3
organic electroluminescent materials. As a result, a number of
synthetic routes toward fused carbazole derivatives have been
4
documented. For example, dibenzo[a,c]carbazoles can be
prepared through a palladium-catalyzed intramolecular annu-
5
lation of 2-(2-bromoaryl)-3-arylindoles, a dual C−H
6
functionalization of indoles with cyclic diaryliodoniums, a
7
cascade reaction of 2-arylindoles with diaryliodoniums, or an
intermolecular cyclization of 2-(2-halophenyl)-indoles with
8
iodobenzenes. Whereas these existing routes are usually
efficient and reliable, the development of new methods for the
synthesis of dibenzo[a,c]carbazoles starting from easy-to-
obtain substrates is still in high demand.
Recently, a transition-metal-catalyzed heteroatom-containing
moiety-directed C−H functionalization/intramolecular cycliza-
tion cascade turned out to be one of the most powerful
9
strategies for the construction of complex polycyclic scaffolds.
In this regard, the NH indole moiety has emerged as a versatile
functionalizable directing group for the synthesis of various
indole-containing polycyclic compounds. For example, NH
indole-directed oxidative annulations of 2-arylindoles with
1
0
used in the direct construction of several hard-to-prepare cyclic
skeletons reported by Xu, Wang, and Ison’s groups.
However, to our knowledge, a Rh(III)-catalyzed NH indole-
directed oxidative (spiro)annulation with benzoquinone has
different coupling partners, such as diazo compounds,
1
6
11
12
13
14
sulfoxonium ylides, ketenes, carbon monoxide, alkynes,
1
5
or alkenes, could be successfully utilized for the selective
synthesis of benzocarbazole, isoindoloindolone, indoloisoqui-
noline, or isoindoloindole derivatives (Scheme 1). On the
contrary, Rh(III)- or Ir(III)-catalyzed C−H functionalization
reactions using benzoquinone as a coupling partner have been
Received: July 6, 2019
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Table 1. Optimization of Reaction Conditions for the Synthesis of 3a
b
entry
catalyst
additive
base
solvent
yield (%)
1
2
3
4
5
6
7
8
9
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*IrCl2]2
Cu(OAc)2
AgOAc
NaOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
toluene
o-xylene
dioxane
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
PhCl
30
29
30
36
70
37
47
46
42
25
43
37
44
9
Et N
3
Et NH
2
DIPA
Na CO3
2
K CO3
2
10
11
12
13
14
15
16
17
18
19
20
21
2
K PO4
3
Et N
3
Et N
3
Et N
3
Et N
3
Cp*Co(CO)I2
Et N
3
0
0
0
0
[RuCl (p-cymene)]
Et N
3
2
2
Pd(OAc)2
Et N
3
Et N
3
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
Et N
3
0
c
CsOAc
CsOAc
CsOAc
Et N
3
58
53
72
d
Et N
3
e
2
Et N
3
a
Reactions were run with 1a (0.4 mmol), 2a (1.2 mmol), catalyst (0.02 mmol), additive (0.8 mmol), base (1.2 mmol), solvent (10 mL), 140 °C, 22
b
c
d
e
h. Isolated yield. [Cp*RhCl ] (0.01 mmol). 120 °C. 2a (0.8 mmol), 10 h.
2
2
not been reported. As part of our interest in the Rh(III)-
(entries 18 and 19). Decreasing the loading of [Cp*RhCl ] to
2 2
17
catalyzed oxidative annulations, we herein report a tunable
oxidative (spiro)annulation of 2-arylindoles with benzoqui-
none, leading to two different types of indole-containing fused
or spirocyclic products (Scheme 1). Interestingly, benzoqui-
none acted as either an efficient C2 synthon or a C1 synthon in
this Rh(III)-catalyzed oxidative annulation reaction with 2-
substituted or 2,3-disubstituted indoles as the substrates.
Initially, a mixture of 2-phenyl-1H-indole 1a (0.4 mmol) and
benzoquinone 2a (1.2 mmol) in PhCl was treated with
2.5 mol % or lowering the reaction temperature to 120 °C
resulted in a lower yield of 3a (entries 20 and 21). Finally, the
treatment of 1a with 2a (2.0 equiv) at 140 °C for 10 h could
afford 3a in 72% yield (entry 22).
With the optimized conditions (Table 1, entry 22), we next
examined the generality of this novel synthesis of 9H-
dibenzo[a,c]carbazol-3-ols (3) (Scheme 2). With benzoqui-
none (2a), the substrate scope of various 2-arylindoles (1) was
first investigated. The experimental results suggested that 1b−
g bearing different types of R substituents (including Me,
[
Cp*RhCl ] (5 mol %) and Cu(OAc) (0.8 mmol) at 140 °C
2 2 2
for 22 h. It was observed that the desired Rh(III)-catalyzed
oxidative annulation reaction with 2a proceeded smoothly to
provide 9H-dibenzo[a,c]carbazol-3-ol (3a) in 30% yield (Table
MeO, F, Cl, Br, and CF ) at the para position of the 2-phenyl
3
ring of 1 reacted well with 2a to give 3b−g in 56−73% yield. In
1
addition, different R groups (such as CH , Cl, and Br)
3
1
, entry 1). To improve the efficiency, AgOAc, NaOAc, or
attached at the ortho and meta positions of the 2-phenyl ring
of 1 were all tolerated with the standard conditions to provide
3h−m in modest to good yield. To our surprise, the oxidative
annulation reaction of meta-chloro-substituted indole (1l) with
2a afforded two regioisomers (10:7), whereas with meta-
methyl- and meta-bromo-substituted indoles (1k) and (1m),
the reactions occurred exclusively at the less hindered position
to give 3k and 3m in 78 and 66% yield. With 2-(naphthalen-1-
yl)-1H-indole (1n), this reaction also proceeded smoothly to
afford 3n in 47% yield. When 2-(furan-2-yl)-1H-indole (1o)
and 2-(thiophen-2-yl)-1H-indole (1p) were subjected to the
reaction conditions, 3o and 3p could be obtained, albeit in
CsOAc was tried as an additive (entries 2−4). Among them,
CsOAc provided the best result (36%). Notably, using Et N
3
(
3.0 equiv) as the coadditive remarkably improved the reaction
efficiency (entry 5). Next, the effect of bases, including Et NH,
DIPA, Na CO , K CO , and K PO , on this reaction was
investigated; it turned out that all of them were less effective
than Et N (entry 5 vs 6−10). In addition, with the use of
toluene, o-xylene, or 1,4-dioxane as the solvent, this reaction
gave 3a in a lower yield (entry 5 vs 11−13). Then, we also
examined the effect of different catalysts on this reaction, and it
was observed that [Cp*IrCl ] gave 3a in 9% yield (entry 14),
2
2
3
2
3
3
4
3
2
2
2
whereas [Cp*Co(CO)I ], [RuCl (p-cymene)] , and Pd-
lower yield. Next, the effect of different R groups on this
2
2
2
(
OAc) failed to provide 3a (entries 15−17). Furthermore,
reaction was investigated, and indoles 1q−u having either
electron-rich methyl or electron-deficient fluoro, chloro, and
bromo groups at different positions of the indole’s phenyl ring
2
control experimental results suggested that the formation of 3a
was not observed in the absence of [Cp*RhCl ] or CsOAc
2
2
B
DOI: 10.1021/acs.orglett.9b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 2. Synthesis of 9H-Dibenzo[a,c]carbazol-3-ols
with benzoquinone as a C1 synthon smoothly proceeded to
give a spiro compound 11′-phenylspiro[cyclohex[3]ene-1,6′-
isoindolo[2,1-a]indole]-2,5-dione (4a) in 74% yield, whose
structure was unambiguously confirmed by X-ray single-crystal
diffraction (Scheme 3). Literature searching suggested that the
,
a b
(
3)
Scheme 3. Rh(III)-Catalyzed Oxidative Spiroannulation of
2
,3-Diphenyl-1H-indole with 2a
newly formed indole-containing spirocyclic skeleton has not
yet been reported. Therefore, the development of an efficient
strategy for the preparation of the above-mentioned spiro
18
products with potential bioactivities is in high demand. Thus
the scope of this novel oxidative spiroannulation was studied
(
Scheme 4). Various 2,3-disubstituted-1H-indoles (1) with a
,
a b
Scheme 4. Synthesis of N-Spiro Compounds (4)
a
Reaction conditions: 1 (0.4 mmol), 2 (0.8 mmol), [Cp*RhCl2]2
0.02 mmol), CsOAc (0.8 mmol), Et N (1.2 mmol), PhCl (10 mL),
(
3
b
c
1
40 °C, 10 h. Isolated yields. Two regioisomers (10:7) were
d
obtained, and the major isomer is given. CCDC 1936367.
were compatible with the reaction conditions to afford 3q−u
in 70−89% yield. It is noted that the structure of 3t was
unambiguously confirmed by X-ray single-crystal diffraction.
Subsequently, the scope of benzoquinones (2) was studied,
and we found that the reactions of 2-methylbenzoquinone
(
2b) and 1,4-naphthoquinone (2c) with 1a smoothly
proceeded to provide 3v and 3w in 45 and 32% yield. In
contrast, other benzoquinones (2), such as 2-chlorobenzoqui-
none, 2-bromobenzoquinone, 2,5-dimethylbenzoquinone,
methyl 3,6-dioxocyclohexa-1,4-dienecarboxylate, and 1,2-ben-
zoquinone, could not react with 1a. Finally, we also tried the
reactions of 2-phenyl-1H-pyrrole and 2-phenyl-1H-benzo[d]-
imidazole with 2a, and it was observed that 2-phenyl-1H-
pyrrole worked well to afford 3x in 79% yield, whereas 2-
phenyl-1H-benzo[d]imidazole could not participate in this
reaction.
Having established an efficient route to dibenzo[a,c]-
carbazoles (3) through the Rh(III)-catalyzed oxidative
annulation of 1 with 2, we envisioned that if the C3 position
of indoles is occupied by a substituent, then the annulation
might switch to take place on the N-1 position of indoles, thus
leading to the formation of a new N-1 annulation product,
indolo[1,2-f ]phenanthridine. To verify the hypothesis, 2,3-
diphenyl-1H-indole was treated with benzoquinone for 0.5 h
under the optimized reaction conditions for the synthesis of 3a
a
Reaction conditions: 1 (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2
(0.01 mmol), CsOAc (0.4 mmol), Et N (0.6 mmol), PhCl (4 mL),
3
b
c
1
40 °C, 0.5 h. Isolated yields. Two regioisomers (2.3:1) were
d
obtained, and the major isomer is given. No reaction occurred.
e
f
1
Reaction became messy. Unknown product was obtained, and H
NMR spectra was messy.
1
2
different R or R group reacted with 2a to generate 4a−j in
modest to good yield. Next, the effect of the R substituent on
this spiroannulation was also tested. When 3-methyl-
substituted indole was used instead of 3-aryl-substituted
indole, this spiroannulation also proceeded smoothly to furnish
4k in 64% yield. It is noteworthy that indoles having a Br,
CHO, or CN group (R) at position 3 could not take part in
this reaction. In addition, we also investigated the spiroannu-
(
Table 1, entry 22). To our surprise, the envisioned N-1
annulation leading to indolo[1,2-f ]phenanthridine (A) was not
observed. However, an unexpected N-spiroannulation reaction
C
DOI: 10.1021/acs.orglett.9b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
lation of different benzoquinones (2) with 2,3-diphenyl-1H-
indole. With 2-methylbenzoquinone (2b), this spiroannulation
smoothly proceeded to afford two regioisomers (2.3:1). When
Scheme 6. Possible Reaction Mechanisms
1
,4-naphthoquinone (2c) was used, 4m was obtained in 66%
yield. Indoles having different aryl groups on the C2 and C3
positions could also undergo this spiroannulation to give 4n
and 4o in 57 and 50% yield. Finally, it turned out that 7-
methyl-2,3-diphenyl-1H-indole, 2,3-bis(3-chlorophenyl)-1H-
indole, and 2,3-di(thiophen-2-yl)-1H-indole failed to give the
corresponding spiro products (4).
To gain some insight into the mechanisms, we performed
the following control experiments (Scheme 5). First, when N-
Scheme 5. Mechanistic Studies
Rh(I) species. The Rh(I) species is oxidized to the active
16a
Rh(III) catalyst by benzoquinone in the presence of HOAc.
To demonstrate the synthetic applications, the further
transformations of 3a and 4a were carried out (Scheme 7).
Scheme 7. Transformations of Products 3a and 4a
methyl-substituted indole (5) was employed, no reaction was
observed, and 5 was recovered in 98% yield, indicating that the
indolyl NH unit plays a key role for the aryl C−H activation
(
Scheme 5a). Second, a H/D exchange of indole (1a) was
performed in the presence of CD OD. From this reaction, 1a
3
was recovered in 96% yield and H/D exchanges at the ortho
position (78% D) of the 2-phenyl ring and at the indolyl C3
1
position (21% D) were observed by H NMR analysis
2
(
Scheme 5b), implying that the C(sp )-H activation of the
2
-phenyl unit of indole is reversible. Third, two side-by-side
reactions using 1a and 1a-d were run for 30 min, from which
3
5
1
a and 3a-d were obtained in a ratio of 0.6:0.4 by H NMR
The treatment of 3a with Tf O afforded triflate 6 in 62% yield.
4
2
analysis and a parallel kinetic isotope effect (KIE) value of 1.5
was observed (Scheme 5c). A similar KIE value (1.8) for the
spiroannulation was also obtained (Scheme 5d). These results
indicated that the aryl C−H cleavage process might be
involved in the turnover-limiting step.
Palladium-catalyzed cross-coupling of 6 with boronic acid
could afford the 3-(p-tolyl)-9H-dibenzo[a,c]carbazole 7.
Moreover, the TfO group of 6 could be removed in the
presence of Pd(PPh ) Cl and HCOOH to furnish the 9H-
3 2
2
On the basis of the above results and the literature
precedent, possible reaction mechanisms are proposed
Scheme 6). First, a Rh(III)-catalyzed dual N−H/C−H
dibenzo[a,c]carbazole 8. On the contrary, the Diels−Alder
cycloaddition of 4a with cyclopentadiene was run, from which
the bridged cycle 9 was obtained in 85% yield. Next, with the
use of hydrogen peroxide as the oxidant, 4a could be converted
to the epoxide 10. Finally, the Pd(0)-catalyzed hydrogenation
of 4a with hydrogen could afford 11 in 73% yield.
In summary, we have developed an efficient and practical
procedure for the selective preparation of 9H-dibenzo[a,c]-
carbazol-3-ols and indole-containing spirocyclic compounds
through a Rh(III)-catalyzed substrate-dependent oxidative
annulation or spiroannulation reaction of 2-arylindoles with
benzoquinone as either a C2 or C1 synthon. In addition, a
possible catalytic cycle is also proposed. Further application of
benzoquinone to construct fused and spirocyclic skeletons is in
progress.
1
6
(
bond cleavage of indole (1) occurs to afford a rhodacycle I.
Then, the coordination of benzoquinone (2a) to I yields II,
which undergoes a migratory insertion of the coordinated
benzoquinone into the Rh−C bond to furnish III. With 3-
unsubstituted indole (R = H), the protonolysis of III with two
equivalents of HOAc generates IV and regenerates the Rh(III)
catalyst. Finally, IV undergoes a selective C3 nucleophilic
addition, dehydration, and aromatization cascade to provide
3
a. On the contrary, with 2,3-disubstituted indole (R ≠ H), it
is proposed that III undergoes a selective Rh−C protonolysis
with one equivalent of HOAc to afford the key intermediate V.
Subsequently, with the promotion of Et N, a nucleophilic
3
attack of the tertiary α-C atom on the Rh center generates VI,
which undergoes a C−N reductive elimination to give 4 and a
D
DOI: 10.1021/acs.orglett.9b02336
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
2
018, 360, 3318−3330. (c) Fan, X.; Yu, L.-Z.; Wei, Y.; Shi, M. Org.
ASSOCIATED CONTENT
Supporting Information
■
Lett. 2017, 19, 4476−4479. (d) Parisien-Collette, S.; Cruche, C.;
́
*
S
Abel-Snape, X.; Collins, S. K. Green Chem. 2017, 19, 4798−4803.
(e) Sha, F.; Tao, Y.; Tang, C.-Y.; Zhang, F.; Wu, X.-Y. J. Org. Chem.
2015, 80, 8122−8133. (f) Yang, J.; Zhang, Q.; Zhang, W.; Yu, W. RSC
Adv. 2014, 4, 13704−13707. (g) Xia, X.-F.; Wang, N.; Zhang, L.-L.;
Song, X.-R.; Liu, X.-Y.; Liang, Y.-M. J. Org. Chem. 2012, 77, 9163−
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02336.
Experimental procedure, mechanistic studies, X-ray
crystal structures of 3t and 4a, characterization, and
spectral data (PDF)
9
(
170.
5) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Iazzetti, A. Org. Biomol.
Chem. 2012, 10, 9142−9147.
6) Wu, Y.; Peng, X.; Luo, B.; Wu, F.; Liu, B.; Song, F.; Huang, P.;
Wen, S. Org. Biomol. Chem. 2014, 12, 9777−9780.
7) Bhunia, S. K.; Polley, A.; Natarajan, R.; Jana, R. Chem. - Eur. J.
(
Accession Codes
CCDC 1936367−1936368 contain the supplementary crys-
tallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(
2015, 21, 16786−16791.
(8) Wu, L.; Deng, G.; Liang, Y. Org. Biomol. Chem. 2017, 15, 6808−
6812.
(
9) (a) Ackermann, L. Acc. Chem. Res. 2014, 47, 281−295.
b) Chen, Z.; Wang, B.; Zhang, J.; Yu, W.; Liu, Z.; Zhang, Y. Org.
Chem. Front. 2015, 2, 1107−1295. (c) Song, G.; Li, X. Acc. Chem. Res.
015, 48, 1007−1020.
10) (a) Li, B.; Zhang, B.; Zhang, X.; Fan, X. Chem. Commun. 2017,
3, 1297−1300. (b) Zhang, Z.; Liu, K.; Chen, X.; Su, S.-J.; Deng, Y.;
Zeng, W. RSC Adv. 2017, 7, 30554−30558.
11) Chen, G.; Zhang, X.; Jia, R.; Li, B.; Fan, X. Adv. Synth. Catal.
018, 360, 3781−3787.
12) Yang, X.; Li, Y.; Kong, L.; Li, X. Org. Lett. 2018, 20, 1957−
1960.
(
2
(
5
AUTHOR INFORMATION
Corresponding Authors
■
*
*
E-mail: shguo@htu.cn (S.G.).
E-mail: xuesen.fan@htu.cn (X.F.).
ORCID
(
2
(
Shenghai Guo: 0000-0002-2797-4281
Xinying Zhang: 0000-0002-3416-4623
Xuesen Fan: 0000-0002-2040-6919
Notes
(
13) Huang, Q.; Han, Q.; Fu, S.; Yao, Z.; Su, L.; Zhang, X.; Lin, S.;
Xiang, S. J. Org. Chem. 2016, 81, 12135−12142.
(
14) (a) Morimoto, K.; Hirano, K.; Satoh, T.; Miura, M. Org. Lett.
2
010, 12, 2068−2071. (b) Ackermann, L.; Wang, L.; Lygin, A. V.
Chem. Sci. 2012, 3, 177−180.
15) (a) Xia, Y.-Q.; Li, C.; Liu, M.; Dong, L. Chem. - Eur. J. 2018, 24,
474−5478. (b) Xia, Y.-Q.; Dong, L. Org. Lett. 2017, 19, 2258−2261.
c) Han, Q.; Guo, X.; Tang, Z.; Su, L.; Yao, Z.; Zhang, X.; Lin, S.;
Xiang, S.; Huang, Q. Adv. Synth. Catal. 2018, 360, 972−984.
16) With benzoquinone as a C1 or C2 synthon, see: (a) Zhou, T.;
The authors declare no competing financial interest.
(
5
(
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
21202040), China Postdoctoral Science Foundation
2015T80771), Henan Science and Technology Research
Project (192102310296), Plan for Scientific Innovation
■
(
(
(
Li, L.; Li, B.; Song, H.; Wang, B. Org. Lett. 2015, 17, 4204−4207.
(b) Mukherjee, K.; Shankar, M.; Ghosh, K.; Sahoo, A. K. Org. Lett.
2018, 20, 1914−1918. (c) Engelman, K. L.; Feng, Y.; Ison, E. A.
Organometallics 2011, 30, 4572−4577. (d) Yang, W.; Wang, J.; Wei,
Z.; Zhang, Q.; Xu, X. J. Org. Chem. 2016, 81, 1675−1680. (e) Yang,
W.; Wang, S.; Zhang, Q.; Liu, Q.; Xu, X. Chem. Commun. 2015, 51,
Talents of Henan Province (184200510012), and 111 Project
D17007) for financial support.
(
REFERENCES
■
6
(
61−664.
(
1) (a) Schmidt, A. W.; Reddy, K. R.; Knolker, H.-J. Chem. Rev.
̈
17) (a) Zhang, B.; Li, B.; Zhang, X.; Fan, X. Org. Lett. 2017, 19,
2
012, 112, 3193−3328. (b) Shen, D.-Y.; Chan, Y.-Y.; Hwang, T.-L.;
2
294−2297. (b) Guo, S.; Sun, L.; Wang, F.; Zhang, X.; Fan, X. J. Org.
Juang, S.-H.; Huang, S.-C.; Kuo, P.-C.; Thang, T. D.; Lee, E.-J.;
Chem. 2018, 83, 12034−12043. (c) Guo, S.; Sun, L.; Liu, Y.; Ma, N.;
Damu, A. G.; Wu, T.-S. J. Nat. Prod. 2014, 77, 1215−1223.
Zhang, X.; Fan, X. Org. Lett. 2019, 21, 4082−4086.
(
c) Knolker, H.-J.; Reddy, K. R. Chem. Rev. 2002, 102, 4303−4427.
̈
(
18) For the known indole spirocyclic alkaloids and drug molecules,
(
2) (a) Gu, W.; Qiao, C.; Wang, S.-F.; Hao, Y.; Miao, T.-T. Bioorg.
see: (a) Ishikura, M.; Abe, T.; Choshi, T.; Hibino, S. Nat. Prod. Rep.
Med. Chem. Lett. 2014, 24, 328−331. (b) Gu, W.; Wang, S. Eur. J.
Med. Chem. 2010, 45, 4692−4696. (c) Wang, Y.-Q.; Li, X.-H.; He, Q.;
Chen, Y.; Xie, Y.-Y.; Ding, J.; Miao, Z.-H.; Yang, C.-H. Eur. J. Med.
Chem. 2011, 46, 5878−5884. (d) Oishi, S.; Watanabe, T.; Sawada, J.-
i.; Asai, A.; Ohno, H.; Fujii, N. J. Med. Chem. 2010, 53, 5054−5058.
2
015, 32, 1389−1471. (b) Wilson, M. C.; Nam, S.-J.; Gulder, T. A.
M.; Kauffman, C. A.; Jensen, P. R.; Fenical, W.; Moore, B. S. J. Am.
Chem. Soc. 2011, 133, 1971−1977. (c) Trost, B. M.; Brennan, M. K.
Synthesis 2009, 2009, 3003−3025. (d) Wang, Y.; Lu, H.; Xu, P.-F. Acc.
Chem. Res. 2015, 48, 1832−1844.
(
e) Conchon, E.; Anizon, F.; Aboab, B.; Prudhomme, M. J. Med.
Chem. 2007, 50, 4669−4680. (f) Balasubramanian, B. N.; St. Laurent,
D. R.; Saulnier, M. G.; Long, B. H.; Bachand, C.; Beaulieu, F.; Clarke,
W.; Deshpande, M.; Eummer, J.; Fairchild, C. R.; Frennesson, D. B.;
Kramer, R.; Lee, F. Y.; Mahler, M.; Martel, A.; Naidu, B. N.; Rose, W.
C.; Russell, J.; Ruediger, E.; Solomon, C.; Stoffan, K. M.; Wong, H.;
Zimmermann, K.; Vyas, D. M. J. Med. Chem. 2004, 47, 1609−1612.
(
3) (a) Lee, J.; Park, J. Org. Lett. 2015, 17, 3960−3963. (b) Ogawa,
N.; Yamaoka, Y.; Takikawa, H.; Tsubaki, K.; Takasu, K. J. Org. Chem.
2
018, 83, 7994−8002. (c) Tsuchimoto, T.; Matsubayashi, H.;
Kaneko, M.; Nagase, Y.; Miyamura, T.; Shirakawa, E. J. Am. Chem.
Soc. 2008, 130, 15823−15835.
(
4) For selected examples, see: (a) Gao, H.; Xu, Q.-L.; Yousufuddin,
M.; Ess, D. H.; Ku
b) Wu, F.; Huang, W.; Yiliqi; Yang, J.; Gu, Y. Adv. Synth. Catal.
̈
rti, L. Angew. Chem., Int. Ed. 2014, 53, 2701−2705.
(
E
DOI: 10.1021/acs.orglett.9b02336
Org. Lett. XXXX, XXX, XXX−XXX