I2-Promoted Multicomponent Dicyclization and Ring-Opening Sequences: Direct Synthesis of Benzo[ e][1,4]diazepin-3-ones via Dual C-O Bond Cleavage

Article abstract of DOI:10.1021/acs.orglett.9b02789

A novel and efficient formal [4 + 2+1] annulation of aryl methyl ketones and 2-aminobenzyl alcohols for the synthesis of benzo[e][1,4]diazepin-3-ones is reported. This reaction successfully affords diverse seven-membered ring lactams via dual C-O bond cleavage. A preliminary mechanistic study showed that a multicomponent dicyclization and ring-opening sequence might occur, with the introduction of methyl sulfide proposed as the last step. This efficient strategy with mild reaction conditions and a broad substrate scope has potential applications in chemistry and medicine.

Full text of DOI:10.1021/acs.orglett.9b02789

Letter
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
pubs.acs.org/OrgLett
I ‑Promoted Multicomponent Dicyclization and Ring-Opening
2
Sequences: Direct Synthesis of Benzo[e][1,4]diazepin-3-ones via
Dual C−O Bond Cleavage
Xiao Geng, Can Wang, Chun Huang, Peng Zhao, You Zhou, Yan-Dong Wu,* and An-Xin Wu*
Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University,
Wuhan 430079, P. R. China
*
S Supporting Information
ABSTRACT: A novel and efficient formal [4 + 2+1] annulation of aryl methyl ketones and 2-aminobenzyl alcohols for the
synthesis of benzo[e][1,4]diazepin-3-ones is reported. This reaction successfully affords diverse seven-membered ring lactams
via dual C−O bond cleavage. A preliminary mechanistic study showed that a multicomponent dicyclization and ring-opening
sequence might occur, with the introduction of methyl sulfide proposed as the last step. This efficient strategy with mild
reaction conditions and a broad substrate scope has potential applications in chemistry and medicine.
he 1,4-benzodiazepine skeleton, first discovered in the
significant progress has been achieved in multicomponent
1
T
1960s, exhibits an indispensible role in the field of
reactions involving 2-aminobenzyl alcohols, they remain
2
10−12
10
pharmaceutical chemistry owing to its biological activity. In
the last several decades, the variety of 1,4-aryldiazepine-
containing compounds has been greatly enriched, with some
rare.
For example, the Wu group presented a novel
copper-catalyzed three-components reaction for the synthesis
of diverse 2-substituted quinazolines via formal [4 + 2]
annulation (Scheme 1a). Furthermore, several multicompo-
3
shown to be effective as pharmaceutical drugs. Notably,
11
several marketed drugs feature 1,4-benzodiazepine cores,
nent cascade cyclizations have been achieved. Recently, Yu
4
including diazepam (among the most successful drugs for
and co-workers reported an acid-promoted three-component
cascade reaction of glyoxal monohydrates, amine alcohols, and
KSCN to construct a wide range of bicyclization products
under mild conditions. Notably, this efficient strategy was
green, with a short reaction time followed by a group-assisted
purification (GAP) chemistry process (Scheme 1b). Later, our
treating a wide spectrum of central nervous system disorders),
5
bretazenil (a partial agonist for GABAA receptors),
6
flumazenil (a high-affinity GABAA-BZ site antagonist), and
7
devazepide (a cholecystokinin (CCK) antagonist). Owing to
their medicinal value, further developing direct strategies for
the synthesis of novel 1,4-benzodiazepine-containing com-
pounds, particularly efficient and practical multicomponent
cyclization, is highly valuable and urgent.
12
group described a novel four-component tandem cyclization
process to construct fused heterocycles from commercially
available glyoxal monohydrates and 2-aminobenzyl alcohols.
Unfortunately, only the major stereoisomers were isolated in
moderate yields (Scheme 1c). Although these reports are
elegant and important, they have focused on the construction
of six-membered rings. Using 2-aminobenzyl alcohols to access
medium-sized rings via multicomponent reactions is an
underdeveloped approach. Therefore, further exploring the
reactivity of 2-aminobenzyl alcohols for the construction of
medium-sized rings remains a valuable and challenging
research area. In continuation of the hot research topic in
The construction of N-containing fused heterocycles by
direct annulation of o-substituted aniline derivatives is a
8
fascinating topic owing to their high reactivity and easy
availability. Among these substrates, 2-aminobenzyl alcohols
are among the most popular reagents for the construction of
N-heterocyclic compounds owing to their versatile reactivity.
9
According to numerous documented works, 2-aminobenzyl
alcohols are usually used as four-atom or five-atom
components to construct N,O/N-containing heterocyclic
compounds via formal [5 + 1], [4 + 1], or [4 + 2]
cycloadditions. However, most of these studies have focused
on two-component reactions, which limit the complexity of
products and novelty of reactions to some extent. Although
13
building diverse heterocycles, we herein disclose an iodine-
Received: August 7, 2019
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b02789
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Multicomponent Reactions Involving 2-
Aminobenzyl Alcohols
Table 1. Representative Optimization Conditions
temp
(°C)
yield of 3aa
yield of 4aa
b
b
entry I2 (equiv)
additive
(%)
(%)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1.6
1.6
1.6
1.6
0.4
1.0
2.0
3.0
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
1.6
90
100
110
120
100
100
100
100
100
100
100
100
100
100
100
100
100
52
56
48
43
0
50
17
trace
47
17
19
18
15
trace
20
23
16
22
23
18
25
21
0
8
TFA
HI
FeCl3
0
1
2
3
4
5
49
trace
trace
trace
0
66
73
Cu(OAc)2
oxone
f
T3P
c
DMS
DMS
DMS
d
6
trace
trace
e
7
74
promoted multicomponent dicyclization and ring-opening
sequence of aryl methyl ketones, 2-aminobenzyl alcohol, and
in situ generated dimethyl sulfide (DMS) for the construction
of a variety of novel benzo[e][1,4]diazepin-3-ones, which have
not been reported in previous works (Scheme 1d).
a
Reaction conditions: 1a (0.5 mmol), 2a (1.0 mmol), I (x mmol),
additive (0.5 mmol, 1.0 equiv), indicated temperature, DMSO 3 mL,
unless otherwise noted. Isolated yields. DMS (2.0 equiv, liquid,
2
b
c
d
e
>
99%). f DMS (4.0 equiv, liquid, >99%). DMS (6.0 equiv, liquid,
>99%). T P (propylphosphonic acid anhydride).
3
The study was initiated using acetophenone (1a) and 2-
aminobenzyl alcohol (2a) as model substrates. Fortuitously, 1a
and 2a underwent multicomponent reactions, affording
products 3aa (X-ray of 3aa in the SI) and 4aa in 52% and
a
,
b
Scheme 2. Scope of Aryl Methyl Ketones
1
7% yields, respectively (Table 1, entry 1). We next tested
various conditions to improve the yield of 3aa. First, different
temperatures were examined, with 100 °C found to be the
optimal temperature (Table 1, entries 1−4). Further screening
of different amounts of iodine showed that 1.6 equiv was the
best choice (Table 1, entries 5−8). To further improve the
yield of 3aa, diverse additives were evaluated, including TFA,
HI, FeCl , Cu(OAc) , oxone, and T P, but gave inferior yields
3
2
3
(
Table 1, entries 9−14). We speculated that the low
concentration of in situ generated DMS was a main factor in
the unsatisfactory yields of 3aa. Therefore, we examined the
effect of the amount of DMS on the reaction. When 4.0 equiv
of DMS (liquid, >99%) was added, 3aa was obtained in 73%
yield with trace amounts of 4aa. However, the yield of 3aa
showed no significant increase when the amount of DMS was
further increased to 6.0 equiv (Table 1, entries 15−17).
With optimal conditions in hand, we examined the scope of
aryl and heteroaryl methyl ketone substrates in this four-
component reaction. Diversely substituted methyl ketones
underwent formal [4 + 2 + 1] annulations to furnish the
desired seven-membered ring products in moderate to good
yields. As shown in Scheme 2, aryl methyl ketone substrates
bearing electron-rich groups afforded the cyclization products
in good yields (66%−75%, 3aa−3ga). Aryl methyl ketones
bearing halogen functional groups (4-F, 4-Cl, 4-Br, and 3,4-di-
Cl) gave the desired compounds in satisfactory yields (68%−
7
6%, 3ha−3ka). Furthermore, electron-deficient substrates
bearing phenyl, methylsulfonyl, or cyano groups at the para-
position or a nitryl group at the meta-position reacted
smoothly to give the desired products in moderate yields
a
b
0
.5 mmol scale. Isolated yield of products 3.
B
DOI: 10.1021/acs.orglett.9b02789
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(
58%−77%, 3la−3oa). Pleasingly, when 3-acetylthiophene 1p
Scheme 4. Synthetic Utilities of the Current Protocol
and 1-(2,5-dimethylthiophen-3-yl)ethanone 1q were used as
substrates, desired products 3pa and 3qa were obtained in 73%
and 71% yields, respectively.
To further examine the generality of this four-component
reaction, a brief screening of other commercially available 2-
aminobenzyl alcohols was conducted (Scheme 3). For
Scheme 3. Scope of 2-Aminobenzyl Alcohols ,
a b
and hydrated species 1ac in quantitative yield via iodination
and Kornblum oxidation (Scheme 5a). When hydrated species
Scheme 5. Control Experiments
a
b
0
.5 mmol scale. Isolated yield of products 3.
example, substrates with methyl and halogen groups (F, Cl,
and Br) at the 5-position were compatible, affording the
corresponding products in moderate isolated yields (63%−
7
6%, 3ab−3ae). Substrates with methyl groups at the 4- or 3-
positions were also well tolerated, affording 3af and 3ag in 75%
and 70% yields, respectively. Substrates with Br at the 4-
position were also tolerated (66%, 3ah). Furthermore, 5-
methyl-2-aminobenzyl alcohol reacted smoothly with aryl
methyl ketones bearing methoxy, fluorine, chlorine, and phenyl
groups at the para-position to give the corresponding products
in good to moderate yields (70%−75%; 3cb, 3mb, 3hb, and
1ac were mixed with 2a under the optimized conditions,
desired product 3aa was obtained in 52% yield with product
4aa in 7% yield (Scheme 5b). However, desired product 3aa
was not obtained when 2a was replaced with 8a (Scheme 5c),
confirming that 8a was not the intermediate in this four-
component reaction. Meanwhile, pre-prepared substrate A
reacted smoothly with substrate 2a to afford product 3aa in
59% yield (Scheme 5d). This result implied that A was an
intermediate in this transformation. A deuterium-labeling
experiment was also performed, affording 3aa-D in satisfactory
yield (Scheme 5e), which clearly confirmed that in situ
generated DMS participated in this four-component reaction.
3
ib).
To demonstrate the synthetic potential of this method, a
gram-scale reaction was conducted under standard conditions,
affording 3aa in 65% yield. With 3aa in hand, late-stage
oxidation was briefly implemented by treating 3aa with m-
CPBA (1.5 equiv) in DCM at 25 °C to give sulfone-containing
product 6a in 83% yield (Scheme 4b).
To gain insight into the mechanism of this novel formal [4 +
+ 1] annulation reaction, a series of control experiments were
2
conducted to better understand the reaction pathway. Initially,
acetophenone 1a reacted smoothly to give phenylglyoxal 1ab
C
DOI: 10.1021/acs.orglett.9b02789
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
However, 4aa could not be transformed into 3aa under the
optimized conditions (Scheme 5f). This indicated that 4aa was
a byproduct rather than an intermediate. To further study the
source of oxygen in the target product, 1a and 2a were mixed
ASSOCIATED CONTENT
Supporting Information
■
*
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b02789.
1
8
under optimal conditions with the addition of H O (4.0
2
18
18
equiv). However, no O-labeled product ( O-3aa) was
detected, while O-4aa was obtained in 33% yield (Scheme
g). These results indicated that the oxygen atom of 3aa was
1
8
Experimental procedures, product characterizations,
crystallographic data, and copies of the H and
NMR spectra (PDF)
1
13
5
C
derived from 2-aminobenzyl alcohol (2a) via C−O bond
cleavage.
Accession Codes
On the basis of the current results and reported
9
,11,12,14
literature,
a plausible mechanism for this multi-
CCDC 1937301 and 1937306 contain the supplementary
crystallographic 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.
component reaction was proposed, as shown in Scheme 6.
Scheme 6. Proposed Mechanism
AUTHOR INFORMATION
Corresponding Authors
■
*
*
E-mail: chwuyd@mail.ccnu.edu.cn.
E-mail: chwuax@mail.ccnu.edu.cn.
ORCID
An-Xin Wu: 0000-0001-7673-210X
Author Contributions
All authors have given approval to the final version of the
manuscript.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (Grants 21602070, 21472056, and
21772051). This work was supported by “The Fundamental
Research Funds for the Central Universities” (CCNU15ZX002
and CCNU18QN011). This work was also supported by the
Phenylglyoxal 1ab and corresponding hydrated species 1ac are
readily generated from acetophenone 1a via iodination and
Kornblum oxidation. Intermediate 1ab then undergoes a [5 +
111 Project B17019.
REFERENCES
■
1
] cycloaddition with 2-aminobenzyl alcohol 2a to furnish the
(
1) Fryer, R. I. Bicyclic Diazepines, The Chemistry of Heterocyclic
Compounds; Wiley: New York, 1991; Chapter 7.
first cyclized intermediate A, which reacts with 2a to give imine
intermediate B. Intermediate B then undergoes intramolecular
nucleophilic substitution to form the second cyclized
intermediate C (detected by GC-MS), which is subsequently
activated by acid to form intermediate D. A ring-opening
process then occurs between intermediate D and DMS,
followed by oxidation to furnish intermediate E. Finally,
intermediate E undergoes elimination of MeI to give desired
product 3aa. Furthermore, byproduct 4aa can be obtained
(2) (a) Hunt, J. T.; Ding, C. Z.; Batorsky, R.; Bednarz, M.; Bhide, R.;
Cho, Y.; Chong, S.; Chao, S.; Gullo-Brown, J.; Guo, P.; Kim, S. H.;
Lee, F. Y. F.; Leftheris, K.; Miller, A.; Mitt, T.; Patel, M.; Penhallow,
B. A.; Ricca, C.; Rose, W. C.; Schmidt, R.; Slusarchyk, W. A.; Vite, G.;
Manne, V. J. Med. Chem. 2000, 43, 3587. (b) Costantino, L.; Barlocco,
D. Curr. Med. Chem. 2006, 13, 65.
(3) (a) Hosmane, R. S.; Bhan, A.; Karpel, R. L.; Siriwardane, U.;
Hosmane, N. S. J. Org. Chem. 1990, 55, 5882. (b) Funke, C.; Es-
Sayed, M.; de Meijere, A. Org. Lett. 2000, 2, 4249. (c) Deaudelin, P.;
Lubell, W. D. Org. Lett. 2008, 10, 2841. (d) Boutard, N.; Dufour-
Gallant, J.; Deaudelin, P.; Lubell, W. D. J. Org. Chem. 2011, 76, 4533.
(e) Baraldi, P. G.; Manfredini, S.; Periotto, V.; Simoni, D.; Guarneri,
M.; Borea, P. A. J. Med. Chem. 1985, 28, 683.
from intermediate D and H O through a similar process.
2
In summary, we have developed an iodine-promoted
multicomponent reaction for the synthesis of diverse benzo-
[
e][1,4]diazepin-3-ones under mild conditions. This work
(4) (a) Baenninger, A.; Costa e Silva, J. A.; Hindmarch, I.; Moeller,
represents an efficient strategy for constructing seven-
membered ring lactams. Furthermore, this novel protocol
enriches the reactivity of 2-aminobenzyl alcohols to formal [4
H. J.; Rickels, K. Good Chemistry: The Life and Legacy of Valium
Inventor Leo Sternbach; McGraw Hill: New York, 2004. (b) Valium
(
Diazepam), Physician’s Desk Reference Online. http://www.pdr.
net/drug-summary/valium?druglabelid=2100 (accessed December
0, 2013.
+
2 + 1] annulations. Notably, mechanistic studies showed that
a cascade dicyclization and ring-opening process might occur
in the reaction. Further studies toward the construction of such
medium-sized rings are currently underway in our laboratory.
2
(5) Tashma, Z.; Raveh, L.; Liani, H.; Alkalay, D.; Givoni, S.; Kapon,
J.; Cohen, G.; Alcalay, M.; Grauer, E. J. Appl. Toxicol. 2001, 21, S115.
D
DOI: 10.1021/acs.orglett.9b02789
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(
6) (a) Lancel, M.; Steiger, A. Angew. Chem., Int. Ed. 1999, 38, 2852.
Z.; Wang, Y.; Wu, X.; Zhang, J.; Wu, A. Adv. Synth. Catal. 2018, 360,
1364. (d) Geng, X.; Wang, C.; Zhao, P.; Zhou, Y.; Wu, Y. D.; Wu, A.
X. Org. Lett. 2019, 21, 4939. (e) Zhao, P.; Wu, X.; Zhou, Y.; Geng, X.;
Wang, C.; Wu, Y. D.; Wu, A. X. Org. Lett. 2019, 21, 2708. (f) Wang,
C.; Geng, X.; Zhao, P.; Zhou, Y.; Wu, Y. D.; Cui, Y. F.; Wu, A. X.
Chem. Commun. 2019, 55, 8134. (g) Geng, X.; Wu, X.; Wang, C.;
Zhao, P.; Zhou, Y.; Sun, X.; Wang, L. J.; Guan, W. J.; Wu, Y. D.; Wu,
A. X. Chem. Commun. 2018, 54, 12730. (h) Geng, X.; Wu, X.; Zhao,
P.; Zhang, J.; Wu, Y. D.; Wu, A. X. Org. Lett. 2017, 19, 4179. (i) Wu,
X.; Zhao, P.; Geng, X.; Zhang, J.; Gong, X.; Wu, Y. D.; Wu, A. X. Org.
Lett. 2017, 19, 3319. (j) Zhang, J.; Wu, X.; Gao, Q.; Geng, X.; Zhao,
P.; Wu, Y. D.; Wu, A. Org. Lett. 2017, 19, 408. (k) Zheng, K. L.; You,
M. Q.; Shu, W. M.; Wu, Y. D.; Wu, A. X. Org. Lett. 2017, 19, 2262.
(l) Cai, Q.; Li, D. K.; Zhou, R. R.; Shu, W. M.; Wu, Y. D.; Wu, A. X.
Org. Lett. 2016, 18, 1342. (m) Jia, F. C.; Zhou, Z. W.; Xu, C.; Wu, Y.
D.; Wu, A. X. Org. Lett. 2016, 18, 2942. (n) Xiang, J. C.; Wang, Z. X.;
Cheng, Y.; Ma, J. T.; Wang, M.; Tang, B. C.; Wu, Y. D.; Wu, A. X. J.
Org. Chem. 2017, 82, 13671. (o) Xu, C.; Jiang, S. F.; Wen, X. H.;
Zhang, Q.; Zhou, Z. W.; Wu, Y. D.; Jia, F. C.; Wu, A. X. Adv. Synth.
Catal. 2018, 360, 2267. (p) Qin, X. Y.; He, L.; Li, J.; Hao, W. J.; Tu, S.
J.; Jiang, B. Chem. Commun. 2019, 55, 3227. (q) Wang, A. F.; Hao, W.
J.; Zhu, Y. L.; Li, G.; Zhou, P.; Tu, S. J.; Jiang, B. ACS Omega 2018, 3,
(
b) Moran, M. D.; Wilson, A. A.; Elmore, C. S.; Parkes, J.; Ng, A.;
Sadovski, O.; Graff, A.; Daskalakis, Z. J.; Houle, S.; Chapdelaine, M.
J.; Vasdev, N. Bioorg. Med. Chem. 2012, 20, 4482.
(
7) Evans, B. E.; Rittle, K. E.; Bock, M. G.; DiPardo, R. M.;
Freidinger, R. M.; Whitter, W. L.; Lundell, G. F.; Veber, D. F.;
Anderson, P. S.; Chang, R. S. L.; Lotti, V. J.; Cerino, D. J.; Chen, T.
B.; Kling, P. J.; Kunkel, K. A.; Springer, J. P.; Hirshfield, J. J. Med.
Chem. 1988, 31, 2235.
(
8) For selected examples, see: (a) Wu, X.; Geng, X.; Zhao, P.; Wu,
Y. D.; Wu, A. X. Org. Lett. 2017, 19, 4584. (b) Min, L.; Pan, B.; Gu, Y.
Org. Lett. 2016, 18, 364. (c) Khong, S.; Kwon, O. J. Org. Chem. 2012,
7
7, 8257. (d) Rode, N. D.; Abdalghani, I.; Arcadi, A.; Aschi, M.;
Chiarini, M.; Marinelli, F. J. Org. Chem. 2018, 83, 6354. (e) Patil, N.
T.; Nijamudheen, A.; Datta, A. J. Org. Chem. 2012, 77, 6179.
(
f) Arnold, J. S.; Mwenda, E. T.; Nguyen, H. M. Angew. Chem., Int. Ed.
014, 53, 3688. (g) Wang, L.; Ferguson, J.; Zeng, F. Org. Biomol.
2
Chem. 2015, 13, 11486. (h) Wang, Z.; Chen, G.; Zhang, X.; Fan, X.
Org. Chem. Front. 2017, 4, 612. (i) Yan, Y.; Wang, Z. Chem. Commun.
2
011, 47, 9513. (j) Feng, C.; Li, Y.; Xu, Q.; Pan, L.; Liu, Q.; Xu, X. J.
Org. Chem. 2018, 83, 1232. (k) Nguyen, T. B.; Retailleau, P. Org. Lett.
017, 19, 3887. (l) Nguyen, T. B.; Retailleau, P.; Al-Mourabit, A. Org.
Lett. 2013, 15, 5238. (m) Zhang, Y.; Donahue, J. P.; Li, C. J. Org. Lett.
2
1
482. (r) Ji, C. L.; Hao, W. J.; Zhang, J.; Geng, F. Z.; Xu, T.; Tu, S. J.;
Jiang, B. Org. Lett. 2019, 21, 6494.
14) (a) Yin, G.; Zhou, B.; Meng, X.; Wu, A.; Pan, Y. Org. Lett.
006, 8, 2245. (b) Gao, Q.; Wu, X.; Li, Y.; Liu, S.; Meng, X.; Wu, A.
2
007, 9, 627. (n) An, Y.; Zheng, D.; Wu, J. Chem. Commun. 2014, 50,
(
2
1
1746. (o) Pan, X.; Luo, Y.; Wu, J. Org. Biomol. Chem. 2012, 10, 1969.
(
(
(
p) Jillella, R.; Oh, D. H.; Oh, C. H. New J. Chem. 2018, 42, 16886.
q) Pan, X.; Luo, Y.; Wu, J. Chem. Commun. 2011, 47, 8967.
r) Arcadi, A.; Chiarini, M.; D’Anniballe, G.; Marinelli, F.;
Adv. Synth. Catal. 2014, 356, 2924. (c) Liu, S.; Xi, H.; Zhang, J.; Wu,
X.; Gao, Q.; Wu, A. Org. Biomol. Chem. 2015, 13, 8807. (d) Wang,
M.; Xiang, J. C.; Cheng, Y.; Wu, Y. D.; Wu, A. X. Org. Lett. 2016, 18,
Pietropaolo, E. Org. Lett. 2014, 16, 1736. (s) Guo, C. X.; Zhang,
W. Z.; Liu, S.; Lu, X. B. Catal. Sci. Technol. 2014, 4, 1570. (t) Zhang,
T. S.; Wang, R.; Cai, P. J.; Hao, W. J.; Tu, S. J.; Jiang, B. Org. Chem.
Front. 2019, 6, 2968. (u) Li, G.; Jiang, J.; Zhang, F.; Xiao, F.; Deng, G.
Org. Biomol. Chem. 2017, 15, 10024. (v) Zhang, B. S.; Li, Y.; Zhang,
Z.; An, Y.; Wen, Y. H.; Gou, X. Y.; Quan, S. Q.; Wang, X. G.; Liang, Y.
M. J. Am. Chem. Soc. 2019, 141, 9731. (w) Ali, S.; Li, Y. X.; Anwar, S.;
Yang, F.; Chen, Z. S.; Liang, Y. M. J. Org. Chem. 2012, 77, 424.
5
24. (e) Wang, M.; Tang, B. C.; Ma, J. T.; Wang, Z. X.; Xiang, J. C.;
Wu, Y. D.; Wang, J. G.; Wu, A. X. Org. Biomol. Chem. 2019, 17, 1535.
f) Gao, Q.; Wang, Y.; Wang, Q.; Zhu, Y.; Liu, Z.; Zhang, J. Org.
Biomol. Chem. 2018, 16, 9030.
(
(
9) For selected examples for [4 + 2] annulation, see: (a) Saunthwal,
R. K.; Patel, M.; Verma, A. K. J. Org. Chem. 2016, 81, 6563. (b) Putta,
V. P. R. K.; Gujjarappa, R.; Tyagi, U.; Pujar, P. P.; Malakar, C. C. Org.
Biomol. Chem. 2019, 17, 2516. (c) Li, L. Z.; Wang, C. S.; Guo, W. F.;
Mei, G. J.; Shi, F. J. Org. Chem. 2018, 83, 614. (d) Das, S.; Maiti, D.;
De Sarkar, S. J. Org. Chem. 2018, 83, 2309. (e) Chakraborty, G.;
Sikari, R.; Das, S.; Mondal, R.; Sinha, S.; Banerjee, S.; Paul, N. D. J.
Org. Chem. 2019, 84, 2626. (f) Genc,
Gunnaz, S.; Cetinkaya, B.; Gulcemal, D. J. Org. Chem. 2019, 84, 6286.
g) Saunthwal, R. K.; Patel, M.; Verma, A. K. Org. Lett. 2016, 18,
̧ S.; Arslan, B.; Gulcemal, S.;
̈
̈
̧
̈
(
2
3
200. (h) Wang, R.; Fan, H.; Zhao, W.; Li, F. Org. Lett. 2016, 18,
558. (i) Xiong, B.; Jiang, J.; Zhang, S.; Jiang, H.; Ke, Z.; Zhang, M.
Org. Lett. 2017, 19, 2730. (j) Xie, F.; Chen, Q. H.; Xie, R.; Jiang, H.
F.; Zhang, M. ACS Catal. 2018, 8, 5869. (k) Mastalir, M.; Glatz, M.;
Pittenauer, E.; Allmaier, G.; Kirchner, K. J. Am. Chem. Soc. 2016, 138,
1
5543. (l) Fan, J.; Wan, C.; Sun, G.; Wang, Z. J. Org. Chem. 2008, 73,
8
608. (m) Chen, M.; Zhang, M.; Xiong, B.; Tan, Z.; Lv, W.; Jiang, H.
Org. Lett. 2014, 16, 6028. For selected examples for [5 + 1]
annulation, see: (n) Parua, S.; Sikari, R.; Sinha, S.; Chakraborty, G.;
Mondal, R.; Paul, N. D. J. Org. Chem. 2018, 83 (18), 11154.
(
o) Bakthadoss, M.; Mushaf, M. RSC Adv. 2018, 8, 12152. (p) Naidu,
S.; Reddy, S. R. RSC Adv. 2016, 6, 62742. For selected examples for
4 + 1] annulation, see: (q) Kuznetsov, A.; Makarov, A.; Rubtsov, A.
E.; Butin, A. V.; Gevorgyan, V. J. Org. Chem. 2013, 78, 12144.
10) Chen, Z.; Chen, J.; Liu, M.; Ding, J.; Gao, W.; Huang, X.; Wu,
H. J. Org. Chem. 2013, 78, 11342.
11) Chen, E.; Shao, J.; Tang, P.; Shu, K.; Chen, W.; Yu, Y. Green
Chem. 2018, 20, 3696.
12) Wang, J.; Zhou, R.; Zhuang, S.; Wu, A. Tetrahedron 2018, 74,
283.
13) (a) Gao, Q.; He, S.; Wu, X.; Zhang, J.; Bai, S.; Wu, Y.; Wu, A.
[
(
(
(
7
(
Org. Chem. Front. 2018, 5, 765. (b) Gao, Q.; Yan, H.; Wu, M.; Sun, J.;
Yan, X.; Wu, A. Org. Biomol. Chem. 2018, 16, 2342. (c) Gao, Q.; Liu,
E
DOI: 10.1021/acs.orglett.9b02789
Org. Lett. XXXX, XXX, XXX−XXX