Rhodium-Catalyzed Spiro Indenyl Benzoxazine Synthesis via C-H Activation/Annulation of 3-Aryl-2H-Benzo[b][1,4]oxazines and Alkynes

Article abstract of DOI:10.1002/ejoc.202000668

The rhodium (III)-catalyzed annulation of 3-Aryl-2H-Benzo[b][1,4]oxazines with alkynes via C–H activation has been developed. This reaction afforded a series of spiro indenyl benzoxazine in high yields under mild reaction condition with good functional group tolerance.

Full text of DOI:10.1002/ejoc.202000668

European Journal of Organic Chemistry
Accepted Article
Accepted Article
Title: Rhodium-Catalyzed Spiro Indenyl Benzoxazine Synthesis via C-
H activation/ Annulation of 3-Aryl-2H-Benzo[b][1,4]oxazines and
Alkynes
Authors: Heng Tan, Ronibala Devi Laishram, Xuexin Zhang, Guangrui
Shi, Kangkui Li, and Jingchao Chen
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To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000668
Link to VoR: https://doi.org/10.1002/ejoc.202000668
01/2020

10.1002/ejoc.202000668
European Journal of Organic Chemistry
COMMUNICATION
Rhodium-Catalyzed Spiro Indenyl Benzoxazine Synthesis via C-H
activation/ Annulation of 3-Aryl-2H-Benzo[b][1,4]oxazines and
Alkynes
Heng Tan, [a],† Ronibala Devi Laishram,[a],† Xuexin Zhang, [a] Guangrui Shi, [a] Kangkui Li, [a] Jingchao
Chen*[a]
[a]
H. Tan, Dr. R.D. Laishram, X.-X. Zhang, G.-R. Shi, K.-K. Li, Dr. J.-C. Chen
Key Laboratory of Chemistry in Ethnic Medicinal Resources,
Yunnan Minzu University
Kunming, Yunnan, 650500, China.
E-mail: chenjingchao84@163.com (Dr. Jingchao Chen)
https://www.x-mol.com/university/faculty/24937
Supporting information for this article is given via a link at the end of the document.((Please delete this text if not appropriate))
Abstract: The rhodium (III)-catalyzed annulation of 3-Aryl-2H-
Benzo[b][1,4]oxazines with alkynes via C-H activation has been
envisaged the synthesis of the spiroindenyl compounds
containing the aforementioned important bioactive fragments
using Rh (III) catalyst via C-H activation with benzoxazine and
developed. This reaction afforded
a series of spiro indenyl
benzoxazine in high yields under mild reaction condition with good
functional group tolerance.
Transition metal-catalyzed annulation reaction via C–H bond
activation has attracted much attention among the synthetic
chemist as a prevailing method because it obviates the prior
activation step with excellent atom economy.1 In particular,
transition metal-catalyzed directing group assisted C-H
functionalization and annulation with various unsaturated
systems such as alkenes, alkynes, and allenes in the
construction of carbocycles have become an attractive approach
for the synthesis of a wide range of complex compounds.2-9
Since the pioneering work of Takai’s group,10 many researchers
have explored imine-directed intermolecular annulations via C-H
bond activation in developing the indene ring by imine directed
annulation reaction via the C-H activation.11
Cramer,11f-h
Figure 1. Representives of bioactive indene.
Zhao,11i,j Cheng,11k Miura11l and Wang11m groups independently
demonstrated the transition metal-catalyzed annulation of
aromatic ketimines/ aldimines with alkynes via the C-H activation
for the generation of indene derivatives. Li,11n Deng11o and
Wang11p groups also independently disclosed the metal
catalyzed annulation with cyclic N-sulfonyl ketimines and
alkynes via C-H activation to afford spiro indenyl benzosultam.
alkynes as coupling partners.
We initiated our investigation by annulative coupling of
benzooxazine 1a with diphenyl acetylene 2a as the model
substrates (Table 1). The coupling of 1a with 2a under the
catalytic condition of [RhCp*Cl2]2 (5 mol%) and Cu(OAc)2 (10
mol%) in DCE at 100 °C for 8 h afforded exclusively the
spirooxazine-indene 3a in moderate yield (Table 1, entry 1).
Screening of solvents showed that MeCN was found to be an
optimal solvent forming the desired product 3aa in 99 % yield
(entries 1-6). Next, we screened additives; exclusion of additive
gave no product (entry 7). Other additives like NaOAc, AgOAc,
and Fe(OAc)2 were also checked but were not effective as
Cu(OAc)2 (entries 8-10). Other catalysts were also investigated
but found to be less effective in this transformation, [IrCp*Cl2]2
gave the product in 61 % yield while RhCl3·3H2O did not give
isolable product (entries 11, 12). The absence of catalyst also
gave no isolable product (entry 13). Next, we investigated the
effect of other reaction parameters like temperature and the
catalytic loading on the yield of the reaction. Lowering the
temperature lowered the yield of the reaction (entries 14-16).
However, to our delight, decrease in the loading of catalyst to
2.5 mol% gave the desired product in excellent yield (entry 17).
Dong’s group developed
a
novel spirocyclic indenyl
phosphoramides from N-phosphoryl ketimines and alkynes.11q
Li’s group again disclosed the generation of indene using Rh
(III)-catalyst via the C-H activation/ annulation of azomethane
ylides11r, N‑sulfonyl imines11s and arylnitrones11t with alkynes.
However, there is still a need for exploring the scope of imine in
designing indene motifs.
Indene motifs are considered as an important building block
for the construction of many functional materials,12 medicines,13
and biologically active compounds (Figure 1).14 They can also
be used as ligands for transition metals by deprotonation.15 It is
expected that the biologically important indene motifs when
combined with other biologically active systems like
benzoxazine16 could result in enhancing the pharmacological
activity while retaining high diversity and biological relevance.
Recently, our group has successfully reported the Rh (III)
catalyzed ring-opening addition of azabenzonorbornadienes with
cyclic N-sulfonyl ketimines via C-H activation.17 Thus, we
1
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10.1002/ejoc.202000668
European Journal of Organic Chemistry
COMMUNICATION
Thus, we have chosen these reaction conditions of entry 17 as
the optimal condition.
With the optimal reaction conditions in hand, we explored the
scope and generality of this annulation reaction. Various
electronically and sterically diverse benzooxazine 1 were
spirocyclic products 3la, 3ma and 3na respectively in good to
excellent yields. However, no 3oa was detected by using
benzoxazine with an ortho-substituted phenyl ring.
We further evaluated the scope of various internal alkynes (2)
under the optimal reaction conditions by coupling with
benzooxirane (1a) (Table 3). Pleasingly, all the alkynes
regardless of activated or unactivated gave the corresponding
Table 1. Optimizations of reaction conditions.[a]
annulated products in good to excellent yields. Symmetrically
Table 2. Substrate Scope of the Benzoozxazine.[a],[b]
Entry
Catalyst
Additive
Solvent
Time (h)
Yield
(%)[b]
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[IrCp*Cl2]2
RhCl3·3H2O
-
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
-
DCE
THF
8
48
72
9
54
66
1
2
Toulene
dioxane
MeCN
TFE
76
3
67
4
3
99
5
72
72
8
Trace
N.R.
89
6
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
7
NaOAc
8
AgOAc
8
95
9
Fe(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
8
95
10
11
12
13
14[c]
15[d]
16[e]
17[f]
72
72
72
8
61
N.D.
N.D.
89
[a] Under Ar atmosphere, [RhCp*Cl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%),
Cu(OAc)2 (3.6 mg, 0.02 mmol, 10 mol%), Imines (1a-m) (0.2 mmol), alkyne
(2a) (0.3 mmol), and MeCN (2 mL) were added sequentially to a 25 mL
Schlenk tube equipped with a magnetic stir bar. [b] All the yields are isolated
yields. [c] [RhCp*Cl2]2 (6.1 mg, 0.01 mmol, 5 mol%). [d] Regioisomer was
determined by NOESY.
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
[RhCp*Cl2]2
4
96
6
83
3
99
substituted diarylalkynes carrying electron-donating or electron-
withdrawing at the ortho, meta, and para-positions were good
coupling partners, giving the corresponding annulated products
in excellent yields (3ab-3ah). Aliphatic groups symmetrically
substituted in the alkynes were also compatible with the reaction
giving the desired products in good yields (3al-3an). The
unsymmetrical alkynes like 2-butynyl alcohol were also well-
tolerated, furnishing the corresponding spirocyclic product in
regioisomers (3ao and 3ao’) in 99% yield. Aryl-alkyl mixed
unsymmetrical alkynes also successfully afforded the desired
products (3ap, 3ap’ and 3ap, 3ap’) as the mixture of two
regioisomers in good yields.
[a] Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), [RhCp*Cl2]2 (0.01
mmol), additive (0.02 mmol), solvent (2 ml), 100 °C, 1-24h. [b] Yield of isolated
product. [c] The reaction was performed at 60 °C. [d] The reaction was
performed at 80 °C. [e] 1 mol% [RhCp*Cl2]2. [f] 2.5 mol% [RhCp*Cl2]2.
examined using internal alkyne 2a as a coupling partner (Table
2). Both electron-donating, as well as electron-withdrawing
groups on the para-position of the C3-phenyl ring of 1, smoothly
underwent the annulation reactions providing the corresponding
compounds 3ba-3ia in excellent yields, albeit electron-
withdrawing groups required longer reaction time under the
same reaction condition. CH3O-substituent at the meta-position
gave regioisomers (3ka and 3ka’) in 88% yields. Notably, the
annulation of sterically crowded ortho-substituted substrate also
underwent the reaction to afford the desired spiro compound 3ja
in moderate yield 58%. Disubstituted at the phenyl ring, napthyl
and biphenyl at the C3 position also gave the corresponding
Hydrogen-deuterium exchange and KIE experiments were
carried out to probe the mechanism of this catalytic reaction
(Scheme 1). First, we treated 1a with 10 equiv. of CH3COOD
under the standard reaction conditions; 49% hydrogen-
deuterium-exchange at ortho-position of 1a was observed
2
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10.1002/ejoc.202000668
European Journal of Organic Chemistry
COMMUNICATION
indicated by its 1H NMR. This result indicates significant
reversible C-H activation of 1a (eq 1). To further understand the
underlying nature of the mechanism of the present reaction, we
performed the parallel and competitive reaction of 1a and
deuterium labelled [D5]-1a with 2c under standard reaction
conditions and measured the kinetic isotopic effect (KIE) values.
An intermolecular parallel experiment of [D5]-1a with 2c showed
kH/kD = 1.6 (eq 2). While a KIE value of kH/kD = 4.0 was
observed for the intermolecular competition reaction of 1a and
deuterium-labelled [D5]-1a with 2c (eq 3). These suggested that
Table 3. Substrate Scope of the Alkynes.[a],[b]
Scheme 1. H/D Exchange and KIE Experiments
the C-H bond cleavage is involved in the rate-limiting step.
plausible catalytic cycle is proposed on the basis
A
literature9e,11i,o (Scheme 2). The imine nitrogen atom of the
benzooxazne directs the ortho C-H activation to form a five-
membered rhodacycle intermediate I which was followed by
subsequent insertion of alkyne to form seven-membered ring
intermediate II. The intermediate II then undergo Grignard-like
migration to the imine group to generate a rhodium intermediate
III. The proton generated from C-H activation was consumed by
intermediate III to generate the final product 3aa with the
regeneration of the rhodium catalyst.
[a] Under Ar atmosphere, [RhCp*Cl2]2 (3.1 mg, 0.005 mmol, 2.5 mol%),
Cu(OAc)2 (3.6 mg, 0.02 mmol, 10 mol%), Imine (1a) (0.2 mmol), alkynes (2b-
o) (0.3 mmol), and MeCN (2 mL) were added sequentially to a 25 mL Schlenk
tube equipped with a magnetic stir bar. [b] All the yields are isolated yields. [c]
[RhCp*Cl2]2 (6.1 mg, 0.01 mmol, 5 mol%). [d] Regioisomer was determined by
HMBC.
Scheme 2. Plausible mechanism for the annulation reaction of 1a with internal
alkyne 2a.
3
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10.1002/ejoc.202000668
European Journal of Organic Chemistry
COMMUNICATION
2013, 19, 6239–6244; k) G. Zhang, L. Yang, Y. Wang, Y. Xie, H. Huang,
J. Am. Chem. Soc. 2013, 135, 8850–8853; l) W. Dong, L. Wang, K.
Parthasarathy, F. Pan, C. Bolm, Angew. Chem. 2013, 125, 11787–
11790; Angew. Chem. Int. Ed. 2013, 52, 11573–11576; m) J. R.
Huckins, E. A. Bercot, O. R. Thiel, T.-L. Hwang, M. M. Bio, J. Am.
Chem. Soc. 2013, 135, 14492–14495; n) M.-N. Zhao, Z.-H. Ren, Y.-Y.
Wang, Z.-H. Guan, Org. Lett. 2014, 16, 608–611.
In summary, we have successfully developed a highly efficient
[RhCp*Cl2]2 catalyzed synthesis of novel spirocyclic
benzoxazine-indenes from benzoxazine and alkynes via imine
directed
C−H
alkenylation/annulation
reactions.
The
methodology could be applied to various benzoxazine and
alkynes giving the corresponding products in good yields.
6
a) A. S. Tsai, M. E. Tauchert, R. G. Bergman, J. A. Ellman, J. Am.
Chem. Soc. 2011, 133, 1248−1250; b) F. W. Patureau, T. Besset, N.
Kuhl and F. Glorius, J. Am. Chem. Soc. 2011, 133, 2154–2156; c) S. R.
Chidipudi, D. J. Burns, I. Khan and H. W. Lam, Angew. Chem. Int. Ed.
2015, 54, 13975−13979; d) S. Kujawa, D. Best, D. J. Burns, H. W. Lam,
Chem. Eur. J. 2014, 20, 8599−8602; e) S. Sharma, Y.-G. Oh, N. K.
Mishra, U. De, H. Jo, R. Sachan, H. S. Kim, Y. H. Jung, I.- S. Kim, J.
Org. Chem. 2017, 82, 3359−3367; f) M.-B. Zhou, R. Pi, M. Hu, Y. Yang,
R.-J. Song, Y. Xia, J.-H. Li, Angew. Chem. Int. Ed. 2014, 53, 11338–
11341; g) F.W. Patureau, T. Besset, N. Kuhl, F. Glorius, J. Am. Chem.
Soc. 2011, 133, 2154–2156; h) K. Muralirajan, K. Parthasarathy, C.-H.
Cheng, Angew. Chem. Int. Ed. 2011, 50, 4169–4172; i) S. Sharma, Y.
Oh, N. K. Mishra, U. De, H. Jo, R. Sachan, H. S. Kim, Y. H. Jung, I. S. J.
Kim, J. Org. Chem. 2017, 82, 3359−3367.
Acknowledgements
We are grateful to the National Natural Science Foundation of
China (21961045, 21572198), the Applied Basic Research
Project of Yunnan Province (2017FA004, 2018FB021), the
Department of Education of Yunnan Province (2019Y0198), and
Yunnan Provincial Key Laboratory Construction Plan Funding of
Universities for their financial support.
Keywords: Spirocycles • C-H activation • Annulation • Rhodium
7
a) R. K. Chinnagolla, M. Jeganmohan, Eur. J. Org. Chem. 2012,
417−423; b) J. D. Dooley, S. R. Chidipudi, H. W. Lam, J. Am. Chem.
Soc. 2013, 135, 10829−10836; c) S. R. Chidipudi, I. Khan, H. W. Lam,
Angew. Chem. Int. Ed. 2012, 51, 12115–12119.
catalyst
[1]
a) P. Gandeepan, P. Rajamalli, C.-H. Cheng, Chem Eur J. 2015, 21,
9198–9203; b) M. Wasa, K.M. Engle and J.-Q. Yu, J Am Chem Soc.
2010, 132, 3680–3681; c) E.J. Yoo, M. Wasa, J.-Q. Yu, J Am Chem
Soc. 2010, 132, 17378–17380; d) K. Takamatsu, K. Hirano, M. Miura,
Org Lett. 2015, 17, 4066–4069; e) J. Zheng, Y. Zhang, S. Cui, Org Lett.
2014, 16, 3560–3563; f) C. Zhu, C.-Q. Wang, C. Feng, Tetrahedron
Lett. 2018, 59, 430–3563 and the reference therein; g) R. Manoharan-
M. Jeganmohan, Org. Lett. 2017, 19, 5884−5887; h) S. Prakash, R.
Kuppusamy, C.-H. Cheng, Chem. Cat. Chem. 2018, 10, 683–705; i) N.
Senthilkumar, K. Parthasarathy, G. Parthasarathy, C.-H. Cheng, Chem.
Asian J. 2013, 8, 2175–2181; j) P. Williamson, A. Galvan, M. J. Gaunt,
Chem. Sci. 2017, 8, 2588–2591; k) H. Wang, Z.-X. Zhou, M. Kurmoo,
Y.-J. Liu, M.-H. Zeng, Org. Lett. 2019, 21, 2847-; l) M. Gulías, D.
Marcos-Atanes, J. L. Mascareñas, M. Font. Org. Pro. Res. Dev. 2019,
23,1669–1673; m) L.-L. Song, G.-L. Tian, E.V.Van der Eycken,
Molecular Cat. 2018, 459, 129–134; n) N. Yoshikai, Y. Wei, Asian J.
Org. Chem. 2013, 2, 466–478; o) J. Wencel-Delord, F. Glorius, Nat.
Chem. 2013, 5, 369–375.
8
9
a) F. Ling, Z. Xie, J.-C. Chen, C. Ai, H. Shen, Z. Wang, X. Yi, W.-H.
Zhong, Adv. Syn. Cat. 2019, 361, 3094–3101; b) T. Yamakawa, N.
Yoshikai, Org. Lett. 2013, 15, 196–199.
a) M. Nagamoto, K. Sakamoto, T. Nishimura, Adv. Synth. Catal. 2018,
360, 791−795; b) J. Huang, Q. Song, Y. Zhu, L. Qin, Z. Qian, L. Dong,
Chem. Eur. J. 2014, 20, 16882−16886; c) J. Huang, L. Qin, Y. Zhu, Q.
Song, L. Dong, Chem. Commun. 2015, 51, 2844−2847; d) K. Yan, Y.
Kong, B. Li, B.-Q. Wang, Org. Lett. 2019, 21, 7000−7003; e) V.
Vinayagam, A. Mariappan, M. Jana, M. Jeganmohan, J. Org. Chem.
2019, 84, 15590-15604.
10
11
a) Y. Kuninobu, A. Kawata, K. Takai, J. Am. Chem. Soc. 2005, 127,
13498−13499; b) Y. Kuninobu, Y. Tokunaga, A. Kawata, K. Takai, J.
Am. Chem. Soc. 2006, 128, 202−209; (c) Y. Kuninobu, Y. Nishina, M.
Shouho, K. Takai, Angew. Chem. Int. Ed. 2006, 45, 2766−2768; d) Y.
Kuninobu, P. Yu, K. R. Takai, Org. Lett. 2010, 12, 4274−4276.
a) B. Liu, P. Hu, Y. Zhang, Y. Li, D. Bai, X. Li, Org. Lett. 2017, 19,
5402−5405; b) C.-F. Zhu, J.-H. Luan, J. Fang, X. Zhao, X. Wu, Y.-G. Li,
Y.-F. Luo, Org. Lett. 2018, 20, 5960−5963; c) T. Nishimura, Y. Ebe, T.
Hayashi, J. Am. Chem. Soc. 2013, 135, 2092−2095; d) W. P. Liu, D.
Zell, M. John, L. Ackermann, Angew. Chem. Int. Ed. 2015, 54,
4092−4096; e) S. H. Han, N. K. Mishra, M. Jeon, S. Kim, H. S. Kim, S.-
Y. Jung, Y. H. Jung, J.-M. Ku, I. S. Kim, Adv. Synth. Catal. 2017, 359,
3900−3904; f) D. N. Tran, N. Cramer, Angew. Chem. 2010, 122, 8357–
8360; g) D. N. Tran and N. Cramer, Angew. Chem. 2011, 123, 11294–
11298; h) D. N. Tran and N. Cramer, Angew. Chem. Int. Ed. 2013, 52,
10630−10634; i) Z.-M. Sun, S.-P. Chen, P. Zhao, Chem. Eur. J. 2010,
16, 2619–2627; j) J. Zhang, A. Ugrinov, P. Zhao, Angew. Chem. 2013,
125, 6813–6816; Angew. Chem. Int. Ed. 2013, 52, 6681–6684; k) J.
Jayakumar, K. Parthasarathy,C.-H. Cheng, Angew. Chem. 2012, 124,
201–204; Angew. Chem. Int. Ed. 2012, 51, 197–200; l) T. Fukutani, N.
Umeda, K. Hirano, T. Satoh and M. Miura, Chem. Commun. 2009,
5141–5143; m) X.-Q. Jin, X.-X. Yang, Y.-H. Yang, C.-Y. Wang, Org.
Chem. Front. 2016, 3, 268–272; n) P. Zhao, F. Wang, K. Han, X.-W. Li,
Org. Lett. 2012, 14, 5506–5509; o) L. Dong, C.-H. Qu, J.-R. Huang, W.
Zhang, Q.-R. Zhang, J.-G. Deng, Chem. Eur. J. 2013, 19, 16537–
16540; p) H. Liu, J. Li, M. Xiong, J. Jiang, J. Wang, J. Org. Chem. 2016,
81, 6093−6099; q) S.-S. Li, L. Wu, L. Qin, Y.-Q. Zhu, F. Su, Y.-J. Xu, L.
Dong, Org. Lett. 2016, 18, 17, 4214−4217; r) Y. Chen, F. Wang, W.-C.
Zhen, X.-W. Li, Adv. Synth. Catal. 2013, 355, 353–359; s) P. Zhao, F.
Wang, K.-L. Han, and X.-W. Li, Org. Lett. 2012, 14, 5506−5509; t) Z. Qi,
M. Wang, X.-W. Li, Org. Lett. 2013, 15, 5440−5443.
2
For selected reviews covering directing-group-assisted metal-catalyzed
C-H functionalizations, see: a) K. M. Engle, J.-Q. Yu, J. Org. Chem.
2013, 78, 8927–8955; b) K. M. Engle, T.-S. Mei, M. Wasa, J.-Q. Yu,
Acc. Chem. Res. 2012, 45, 788–802; c) C. S. Yeung, V. M. Dong,
Chem. Rev. 2011, 111, 1215–1292; d) J. Wencel-Delord, T. Droege, F.
Liu, F. Glorius, Chem. Soc. Rev. 2011, 40, 4740–4761; e) L.
Ackermann, Chem. Rev. 2011, 111, 1315–1345; f) C.-L. Sun, B.-J. Li,
Z.-J. Shi, Chem. Commun. 2010, 46, 677–685; g) T. W. Lyons, M. S.
Sanford, Chem. Rev. 2010, 110, 1147–1169; h) D. A. Colby, R. G.
Bergman, J. A. Ellman, Chem. Rev. 2010, 110, 624–655.
3
a) T. Satoh, M. Miura, Chem. Eur. J., 2010, 16, 11212–11222; b) B.-J.
Li, H.-Y. Wang, Q.-L. Zhu, Z.-J. Shi, Angew. Chem. Int. Ed. 2012, 51,
3948–3952.
4
5
L. Ackermann, Acc. Chem. Res. 2014, 47, 281–295 and the reference
therein.
a) B. Li, N. Wang, Y. Liang, S. Xu, B. Wang, Org. Lett. 2013, 15, 136–
139; b) M. Deponti, S. I. Kozhushkov, D. S. Yufit, L. Ackermann, Org.
Biomol. Chem. 2013, 11, 142–148; c) L. Wang, L. Ackermann, Org. Lett.
2013, 15, 176–179; d) J. Li, L. Neuville, Org. Lett. 2013, 15, 1752–
1755; e) N. QuiÇones, A. Seoane, R. Garcia-Fandino, J. L.
Mascarenas, M. Gulias, Chem. Sci. 2013, 4, 2874–2879; f) S. Ding, Y.
Yan, N. Jiao, Chem. Commun. 2013, 49, 4250–4252; g) R. Kuram, M.
Bhanuchandra, A. K. Sahoo, Angew. Chem. 2013, 125, 4705–4710;
Angew. Chem. Int. Ed. 2013, 52, 4607–4612; h) M. C. Reddy, R.
Manikandan, M. Jeganmohan, Chem. Commun. 2013, 49, 6060–6062;
i) K. Muralirajan and C.-H. Cheng, Chem. Eur. J. 2013, 19, 6198–6202;
j) D. Zhao, Q. Wu, X. Huang, F. Song, T. Lv, J. You, Chem. Eur. J.
12
a) M. Gerhard, B. Tim, C.J.B. Jorg, S. Dagmar, B. Jurgen, Chem. A Eur.
J. 2017, 23, 703−710; b) S. Kumar, P. D. Thornton, T. O. Painter, P.
4
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Jain, J. Downard, J. T. Douglas and C. Santini, J. Org. Chem. 2013, 78,
6529−6539.
13
14
F.F. Taylor and W.W. Faloon, J. Clin. Endocrinol. Metab. 1959, 19,
1683−1687.
a) C. M. Marson, Chem. Soc. Rev. 2011, 40, 5514−5533; b) T.M.
Bohme, C. Keim, K. Kreutzmann, M. Linder, T. Dingermann, G.
Dannhardt, E. Mutschler, G. Lambrecht, J. Med. Chem. 2003, 46,
856−867.
15
16
N.Y.C. Chu, Can. J. Chem. 1983, 61, 300−305.
Selected examples: a) V. Sharma, N. Amarnath, S. Shukla, R. Ayana,
N. Kumar, N. Yadav, D. Kannan, S. Sehrawat, S. Pati, B. Lochab, S.
Singh, Bioorg. Med. Chem. Lett. 2018, 28, 1629–1637; b) R. D. Kamble,
S. V. Hese, R. J. Meshram, J. R. Kote, R. N. Gacche, B. S. Dawane,
Med. Chem. Res. 2015, 24, 1077–1088; c) R. Roy, D. Saha, A.
Mukherejee, P. Talukdar, Org. Lett. 2016, 18, 5864–5867; d) B. Blass,
ACS Med. Chem. Lett. 2013, 4, 1020–1021; e) B. P. Mathew, A. Kumar,
S. Sharma, P. K. Shukla, M. Nath, Eur. J. Med. Chem. 2010, 45, 1502–
1507; f) K. Weisser, E. Petrlikova, M. Perina, V. Klinesowa, J. Kumes,
K. Palat, J. Kanstova, H.-M. Dahseand U. Mollmann, Eur. J. Med.
Chem. 2010, 45, 2719–2725; g) S. Konda, S. Raparthi, K. Bhaskar, R.
K. Munaganti, V. Guguloth, L. Nagarapu and D. M. Akkewar, Bioorg.
Med. Chem. Lett. 2015, 25, 1643–1646; h) M. Arslan, B. Kiskan, Y.
Yagci, Macromolecules 2015, 48, 1329–1334; i) S. Kirschbaum, K.
Landfester, A. Taden, Macromolecules 2015, 48, 3811–3816; j) C.
Sawaryn, K. Landfester, A. Taden, Macromolecules 2011, 44, 5650–
5658; k) J. Liu, X. Lu, C. Zhou, Langmuir 2013, 29, 411–416; l) P.
Sharma, B. Lochab, D. Kumar, P. K. Roy, ACS Sustainable Chem. Eng.
2016, 4, 1085–1093; m) N. K. Sini, T. Endo, Macromolucules 2016, 49,
8466–8478.
17
X.-X. Zhang, Y. Gao, J.-C. Chen, R.-F. Fan, G.-R. Shi, Z.-X. He, B.-M.
Fan, Adv. Syn. Cat. 2019, 361, 4495–4499.
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10.1002/ejoc.202000668
European Journal of Organic Chemistry
COMMUNICATION
Entry for the Table of Contents
A highly efficient synthesis of novel spirocyclic benzoxazine-indenes from benzoxazine and alkynes via imine directed C−H
activation/annulation using rhodium catalyst was reported. The methodology could be applied to various benzoxazine and alkynes
giving the corresponding spiro indenyl benzoxazine as spirocycles products in good yields.
Key topic: C-H activation
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