Domino Grignard Addition and Oxidation for the One-Pot Synthesis of C2-Quaternary 2-Hydroxyindoxyls

Article abstract of DOI:10.1021/acs.orglett.9b03022

We herein delineate an unexplored reactivity of 3-hydroxyoxindoles toward Grignard addition enabling a rapid access to a broad range of unnatural C2-quaternary 2-hydroxyindoxyls in high yields. The reaction proceeds via a mechanistically intriguing one-pot 1,2-hydride shift followed by autoxidation pathway. The utility of this method is demonstrated by the synthesis of a new class of bis-indoxyl spirofuran derivatives.

Full text of DOI:10.1021/acs.orglett.9b03022

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Domino Grignard Addition and Oxidation for the One-Pot Synthesis
of C2-Quaternary 2‑Hydroxyindoxyls
Tirtha Mandal, Gargi Chakraborti, Subhadip Maiti, and Jyotirmayee Dash*
School of Chemical Sciences, Indian Association for the Cultivation of Science, 2A & 2B Raja S. C. Mullick Road, Jadavpur, Kolkata
700032, India
S
* Supporting Information
ABSTRACT: We herein delineate an unexplored reactivity of 3-hydroxyoxindoles toward Grignard addition enabling a rapid
access to a broad range of unnatural C2-quaternary 2-hydroxyindoxyls in high yields. The reaction proceeds via a
mechanistically intriguing one-pot 1,2-hydride shift followed by autoxidation pathway. The utility of this method is
demonstrated by the synthesis of a new class of bis-indoxyl spirofuran derivatives.
he oxindole moiety is present in a large number of natural
reported oxidation of 2-substituted N-acylindoles by MoO5·
HMPA to directly obtain 1-acetyl-2-hydroxyindoxyls. Later,
Jimenez et al. used oxodiperoxo molybdenum complexes to
improve the yield.17 The oxidation of 2,3,6-trimethyl-4-(1H)-
quinolinone by NaOCl18 and 2-methyl-3-phenylquinolinone
by acidic potassium permanganate19 has also been used to
access the corresponding indoxyls. However, long reaction
times and low yields render such approaches less attractive.
Other reported approaches for the synthesis of 2-hydrox-
yindoxyls involve base-mediated ring contraction of 3-hydroxy-
2,4(1H,3H)-quinolinediones,20 acidic hydrolysis of a 3-
acetoxy-2-phenylindole precursor,21 butyllithium-promoted
tandem cyclization, and autoxidation of 2-(benzylamino)-
benzamide derivatives (Scheme 1).22 Recently, Zhu and co-
workers reported the synthesis of a 2-hydroxyindoxyl derivative
by using a Cu(I)-catalyzed intramolecular C (sp3)−H
amidation of 2-aminoacetophenone utilizing O2 as the oxidant
at high temperature (Scheme 1).23 Later, Yang et al. developed
an oxidative cyclization of 2-aminophenyl-1,3-dione using
CAN and TEMPO as oxidants for the synthesis of 2-
hydroxyindoline-3-ones (Scheme 1).24 Nevertheless, the syn-
thesis of 2-hydroxyindoxyls from readily available starting
materials with high flexibility in their substitution pattern is yet
to be addressed. Therefore, an easy-to-implement protocol to
access a large panel of 2-indoxyl derivatives with a C2-
quartenary tertiary alcohol moiety would be of great
importance in synthetic organic chemistry.
1
Tproducts and biologically active molecules. The motif
has also been used as a versatile synthetic intermediate for
various organic transformations.1,2 On the contrary, 2-
hydroxyindoxyl, a pseudooxindole moiety, has remained less
explored. The indoxyl ring system bearing a C2-quaternary
center is a privileged structural unit present in various natural
products like brevianamide A and B,3 rupicoline,4 iboluteine,5
austamide,6 phytoaliexin, erucalexin,7 and matemone,8 as well
as biologically active compounds (Figure 1). For instance, 2-
hydroxyindoxyl alkaloid melochicorin, isolated from the plant
Melochia corchorifolia,9 shows hepatoprotective and antioxidant
activity.10
Figure 1. Some biologically active indoxyl derivatives.
While 3-substituted 3-hydroxy-2-oxindoles can be easily
synthesized by reported methods,11 the preparation of
unnatural 2-substituted 2-hydroxyindoxyls remains a synthetic
challenge. Until now, only a few convenient methods are
available for the synthesis of pseudooxindole 2-hydroxyindox-
yls. Generally, oxidation of indoles using m-CPBA,12
monoperphthalic acid,13 and DMDO14 produces 2-hydrox-
yindoxyls as byproducts. Davis’ reagent has been used to
improve the yield of 2-hydroxyindoxyls.15 Sakamoto et al.16
Recently, we have reported the synthesis of 2,2-diallylox-
indoles as well as substituted indole derivatives via the
formation of indolinium ion intermediates using Grignard
addition.25 We envisioned that Grignard addition of 3-
hydroxyoxindoles would lead to 2-substituted indoxyls via
Received: August 24, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03022
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Previous Study and Our Strategy
Table 1. Reaction Development
c
2a
temp
(°C)
time
(h)
conversion
b
yield of 3a
entry (equiv)
solvent
(3a/4a)
(%)
1
2
3
4
5
6
7
8
3
4
5
2
4
4
4
4
4
4
4
4
THF
THF
THF
THF
THF
THF
THF
THF
ether
dioxane
diglyme
THF
25
25
25
25
70
0
25
25
25
25
25
25
3
3
3
3
3
3
6
12
6
6
80:20
90:10
90:10
80:20
90:10
80:20
90:10
90:10
80:20
80:20
80:20
90:10
60
68
67
48
66
40
74
70
42
9
10
11
12
20
Trace
72
6
6
d
a
Reaction conditions: 1a (1.0 equiv, 0.5 mmol), 2a (1 M in THF).
b
Conversion is calculated by 1H NMR analysis of crude reaction
c
d
mixture. Yield calculated are isolated yields. Preparative-scale
experiment.
explored for the synthesis of 2-hydroxyindoxyls 3. Various
functionalized 3-hydroxy-2-oxindoles 1 were subjected to the
Grignard reaction with different aromatic and aliphatic
Grignard reagents 2 (Table 2). The oxindoles having different
N-substituents could be effectively converted to the corre-
sponding products 3a−3f, 3j, and 3q. Oxindoles bearing 4-
trifluoromethylphenyl and propyl bromide groups as the N-
substituent provided the indoxyls 3e and 3f in excellent yields.
The reaction also worked well with the substrates having
halides at different positions in the aromatic ring of the
oxindole motif delivering the products 3g−3k and 3u with
good yields. The structure of 2-hydroxyindoxyl 3g was
confirmed by single-crystal X-ray analysis (Table 2, CCDC
1919407; Figure S1). The 4,7-dichloro-3-hydroxyoxindole
derivative provided the corresponding indoxyl 3i in 64%
yield. These halo indoxyls can be used as precursors for further
synthetic transformations by cross-coupling reactions. Hydrox-
yindoxyls 3l−3p, 3x, and 3b′ having electron rich Me and
OMe and electron deficient trifluoromethyl functional groups
were obtained in excellent yields irrespective of their position
in the aromatic ring (Table 2). Oxindole with a bulky 4-
methoxyphenyl substituent at the C5 position provided the
desired indoxyl 3o in good yield. The substrate scope was then
evaluated with different Grignard reagents 2. Apart from
phenylmagnesium bromide 2a, 4-methoxyphenyl-, allyl-, and
benzylmagnesium bromides (2b, 2c, and 2d) furnished the
corresponding indoxyls 3v−3x, 3p−3u, and 3y−3z, respec-
tively, in good yields (Table 2). Notably, aliphatic Grignard
reagents were found to be less reactive for this transformation.
Methylmagnesium bromide 2e underwent smooth reaction
providing the desired indoxyls 3a′−3b′ in good yields.
1,2-hydride shift of the indolinium ion intermediate which after
air oxidation would provide the desired 2-hydroxyindoxyls
(Scheme 1). This protocol will allow an easy access to 2-
functionalized-2-hydroxyindoxyls starting from easily synthe-
sizable starting materials with wide substrate scope.
In order to examine the feasibility of our proposed approach,
a variety of N-protected 3-hydroxy-2-oxindoles 1 were
prepared from N-protected isatin derivatives (see Scheme
S1). We began the oxidative Grignard reaction with phenyl-
magnesium bromide 2a (1 M in THF) addition to 3-hydroxy-
1-methylindolin-2-one 1a. We were delighted to find that the
product 3a was obtained in 60% yield along with 4a as a minor
product by using 3 equiv of 2a in THF for 3 h at room
temperature (Table 1, entry 1). Encouraged by this result, a
systematic study was conducted to selectively obtain indoxyl
derivative 3a. Using 4 equiv of 2a, the formation of 4a was
decreased, and the yield of 3a was increased up to 68% (entry
2). The yield of 3a was not improved further by increasing the
amount of Grignard reagent 2a (entry 3). However, by
lowering the equivalence of 2a, the yield of 3a was decreased
(entry 4). The yield of the desired product did not improve
when the reaction was performed under reflux at 70 °C (entry
5). The yield of 3a was dropped to 40% when the reaction was
carried out at 0 °C (entry 6). By increasing the reaction time to
6 h, 3a was obtained in 74% yield (entry 7). Carrying out the
reaction for a prolonged time did not alter the outcome (entry
8). Further reaction optimization studies were then carried out
by employing different solvents generally used in the Grignard
reaction. The yield of 3a was found to be decreased
considerably by using diethyl ether, dioxane, or diglyme as
the solvent instead of THF (entries 9−11). It is worth noting
that the reaction could be scaled (1.0 g of 1a) without a loss of
yield under the ambient conditions (entry 12).
However, the reaction with ethyl, pentyl, 2-ethylhexyl, and
cyclohexyl Grignard reagents (2f, 2g, 2h, and 2i) were carried
out at 70 °C, providing 3c′, 3d′, 3e′, 3f′, and 3g′ in acceptable
yields (Table 2); relatively low yields of the products were
obtained at room temperature. Gram-scale experiments using 1
g of 1 were also successful in obtaining the corresponding 2-
indoxyls 3 in good yields (Table 2, 3g and 3r; Schemes S2 and
Having established the optimal reaction conditions, the
scope and generality of this methodology was subsequently
B
DOI: 10.1021/acs.orglett.9b03022
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Organic Letters
Letter
a
Table 2. Substrate Scope
a
b
Reaction conditions: 1 (1.0 mmol), 2 (1 M in THF, 4 equiv), in THF (6 mL) at rt; isolated yields. Reaction performed with 1 g of 3-
c
d
hydroxyindoline-2-ones 1 for 10 h. Reaction performed with 3 equiv of 2. Reaction performed at 70 °C.
S3). However, the reaction did not proceed with phenylethynyl
and vinyl Grignard reagents.
generates C3-carbonyl indolinium intermediate I that under-
goes peroxide hydrogen oxidation to give compound 3.
The formation of the minor product 2,2-disubstituted
oxindole 4 could be explained via the intermediate J. The
Grignard reagent can simultaneously act as a base as well as
nucleophile, and thus, it can abstract the acidic C3-hydrogen as
well as attack at the C2-center of the indolinium intermediate
C (Scheme 2). Following workup, the autoxidation of
carbanion intermediate K produces 4 (Scheme 2). The
reaction of carbanion K with oxygen produces intermediate
L, which upon protonation followed by elimination of
hydrogen peroxide provides compound 4 (Scheme 2).
To examine whether the oxidation of D occurred during or
after workup, deuteriated experiments were performed
(Scheme 3, a). Quenching the reaction with D2O following
phenylmagnesium bromide 2a addition to 1c provided
exclusively 3b without any D incorporation in the final
product. If air oxidation of intermediate D would have taken
place before workup to generate the intermediate N, then
deuterium labeled product 5 should have been obtained when
the reaction was quenched with D2O (Scheme 3, a). But no
such products were observed, which clearly indicates that
intermediate N does not form under the reaction conditions
and the aerial oxidation of intermediate D occurs following
workup. Furthermore, it was found that addition of radical-
trapping reagents TEMPO and galvinoxyl did not inhibit the
reaction, indicating that the autoxidation step is an anion-
mediated reaction (Scheme 3, b).
We propose that the reaction of 3-hydroxy-2-oxindoles 1
initiates with the formation of the intermediate A.22,25,26 The
Grignard addition to the intermediate A provides the
intermediate B, which subsequently generates the indolinium
ion intermediate C (Scheme 2). Then aromatization-driven
C3-hydrogen abstraction provides indole intermediate D25b
that tautomerizes by capturing the proton lost during the
aromatization to generate indoxyl intermediate E. Thus, a 1,2-
hydride shift of indolinium ion intermediate C generates the
indoxyl E (Scheme 2). Air-stable indoxyl derivatives like
intermediate E are reported in the literature.27 Therefore, aerial
oxidation of intermediate E takes place under the reaction
conditions to provide the desired 2-hydroxyindoxyls 3 as
previously reported.22,26b We presume that intermediate E can
suffer ready enolization due to extensive conjugation and exist
as indole intermediate D. The stability of intermediate D may
be attributed to the presence of acidic C2-hydrogen and
activated carbonyl group, and therefore, no Grignard addition
product to the C3-carbonyl group of the intermediate E is
detected.
Finally, the intermediate D undergoes rapid air oxidation
during workup to provide 2-hydroxyindoxyls 3 (Scheme 2).
This autoxidation pathway presumably initiates with the
reaction of the carbanion F, generated on workup, with
oxygen to form the peroxide intermediate G (Scheme 2).28
Subsequent protonation and elimination of hydroperoxide
C
DOI: 10.1021/acs.orglett.9b03022
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Organic Letters
Letter
Scheme 2. Probable Mechanism of the Reaction
Scheme 4. Synthetic Transformations of 2-Hydroxyindoxyls
3
Scheme 3. Control Experiments
corresponding oxindole derivatives 7c−e in good yields
(Scheme 4, c; Scheme S6). Moreover, indoxyls 3 upon
treatment with sodium hydride followed by methyl iodide
afforded the corresponding 3-substituted 3-methoxy deriva-
tives 8a,b in a one-pot manner (Scheme 4, d).
Interestingly, methylmagnesium bromide addition of 1
provided bis-indoxyl spirofurans 9a,b via instant aerial
oxidation of the in situ generated 2-Me-2-hydroxyindoxyl
derivatives 3 (Scheme 4, e).30 2-Methyl-2-hydroxyindoxyls 3
were unstable; we could isolate only 3a′ and 3b′ (Table 2).
Upon standing, 3a′ was also converted to the spiro-indoxyl
dimer 9c (Scheme 4, f). The structure of 9c was confirmed by
X-ray crystal analysis (Scheme 4, f; CCDC 1919771, Figure
S2).
In conclusion, we have developed a one-pot approach to
pseudooxindole 2-hydroxyindoxyls by simple Grignard addi-
tion to 3-hydroxyoxindoles. The reaction presumably proceeds
via 1,2-hydride shift to provide 2-indoxyls, which on
autoxidation furnish N-substituted 2-hydroxyindoxyls. Notable
aspects of this domino nucleophilic addition−oxidation
protocol include simple substrates, excellent yield, scalability,
broad substrate scope, and operational ease. Moreover, 2-
hydroxyindoxyls are effectively used as precursors for the
synthesis of 2,2′-differentially substituted 3-oxindoles and a
new class of bis-indoxyl spirofurans. We believe that this work
We were next intrigued to demonstrate the synthetic
potentials of the method by the preparation of functionalized
oxindoles. Previously, we have reported the synthesis of 2,2-
diallyl-3-oxindoles via Grignard addition of isatins (Scheme 4,
a).25a In this work, 2,2′-differentially substituted 3-oxindoles
6a,b containing a C2-allyl group are obtained in good yields via
allyl Grignad addition to C2-alkyl or aryl substituted indoxyls 3
that proceeds through a 1,2-allyl shift (Scheme 4, b).
Furthermore, the 2-hydroxyindoxyl derivatives 3 bearing a
C2-allyl or aryl group on reaction with sodium hydride
provided the corresponding more stable 3-allyl- or aryl-3-
hydroxyoxindole derivatives 7a,b in excellent yields via an α-
ketol rearrangement (Scheme 4, c).20,26,29 In addition,
sequential treatment of the N-protected 3-hydroxy-2-oxindoles
1 with allyl or arylmagnesium bromide followed by the
reaction of crude products with sodium hydride provided the
D
DOI: 10.1021/acs.orglett.9b03022
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
(5) Dickel, D. F.; Holden, C. L.; Maxfield, R. C.; Paszek, L. E.;
Taylor, W. I. J. Am. Chem. Soc. 1958, 80, 123.
(6) (a) Steyn, P. S. Tetrahedron Lett. 1971, 12, 3331. (b) Steyn, P. S.
Tetrahedron Lett. 1973, 29, 3331.
will provide a new platform to explore the synthetic application
of a diverse class of unnatural 2-hydroxyindoxyls and their
enantiopure analouges.
(7) Pedras, M. S. C.; Okinyo, D. P. O. Chem. Commun. 2006, 1848.
(8) Carletti, I.; Banaigs, B.; Amade, P. J. Nat. Prod. 2000, 63, 981.
(9) Bhakuni, R. S.; Shukla, Y. N.; Thakur, R. S. Phytochemistry 1991,
30, 3159.
(10) Rao, B. G.; Rao, Y. V.; Rao, T. M. Asian Pac. J. Trop. Med. 2013,
6, 537.
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b03022.
■
S
(11) For a review, see: (a) Dalpozzo, R.; Bartoli, G.; Bencivenni, G.
Chem. Soc. Rev. 2012, 41, 7247. (b) Kumar, A.; Chimni, S. S. RSC
Adv. 2012, 2, 9748. (c) Cao, Z.-Y.; Zhou, F.; Zhou, J. Acc. Chem. Res.
2018, 51, 1443. For other examples see: (d) Ren, Q.; Huang, J.;
Wang, L.; Li, W.; Liu, H.; Ziang, X.; Wang, J. ACS Catal. 2012, 2,
2622. (e) Sai Prathima, P.; Rajesh, P.; Venkateswara Rao, J.; Sai
Kailash, U.; Sridhar, B.; Mohan Rao, M. Eur. J. Med. Chem. 2014, 84,
155. (f) Bai, M.; You, Y.; Chen, Y.-Z.; Xiang, G.-Y.; Xu, X.-Y.; Zhang,
X.-M.; Yuan, W.-C. Org. Biomol. Chem. 2016, 14, 1395.
Experimental procedures, 1H and 13C NMR spectra, and
X-ray crystal data (PDF)
Accession Codes
CCDC 1919407 and 1919771 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.
́
(12) Bourlot, A. S.; Desarbre, E.; Merour, J. Y. Synthesis 1994, 1994,
411.
(13) Braudeau, E.; David, S.; Fischer, J.-C. Tetrahedron 1974, 30,
1445.
(14) Zhang, X.; Foote, C. S. J. Am. Chem. Soc. 1993, 115, 8867.
(15) Wang, Z.; Jimenez, L. S. J. Am. Chem. Soc. 1994, 116, 4977.
(16) Chien, C.-S.; Takanami, T.; Kawasaki, T.; Sakamoto, M. Chem.
Pharm. Bull. 1985, 33, 1843.
(17) Altinis Kiraz, C. I.; Emge, T. J.; Jimenez, L. S. J. Org. Chem.
2004, 69, 2200.
(18) Staskun, B. J. Org. Chem. 1988, 53, 5287.
(19) Rees, C. W.; Sabet, C. R. J. Chem. Soc. 1965, 870.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: ocjd@iacs.res.in.
ORCID
Jyotirmayee Dash: 0000-0003-4130-2841
Notes
The authors declare no competing financial interest.
́
̌
(20) Kafka, S.; Klasek, A.; Kosmrlj, J. J. Org. Chem. 2001, 66, 6394.
(21) Hewitt, M. C.; Shao, L. ARKIVOC 2006, 39.
ACKNOWLEDGMENTS
(22) Coldham, I.; Adams, H.; Ashweek, N. J.; Barker, T. A.; Redder,
A. T.; Skilbeck, M. C. Tetrahedron Lett. 2010, 51, 2457.
(23) Huang, J. B.; Mao, T. T.; Zhu, Q. Eur. J. Org. Chem. 2014,
2014, 2878.
(24) Wen, S.-S.; Zhou, Z.-F.; Xiao, J.-A.; Li, J.; Xiang, H.; Yang, H.
New J. Chem. 2017, 41, 11503.
(25) (a) Dhara, K.; Mandal, T.; Das, J.; Dash, J. Angew. Chem., Int.
Ed. 2015, 54, 15831. (b) Mandal, T.; Chakraborti, G.; Karmakar, S.;
Dash, J. Org. Lett. 2018, 20, 4759.
(26) (a) Desarbre, E.; Savelon, L.; Cornec, O.; Merour, J. Y.
Tetrahedron 1996, 52, 2983. (b) Cariou, K.; Ronan, B.; Mignani, S.;
Fensterbank, L.; Malacria, M. Angew. Chem., Int. Ed. 2007, 46, 1881.
(c) Bott, T. M.; Atienza, B. J.; West, F. G. RSC Adv. 2014, 4, 31955.
(d) Huang, P.-Q.; Ou, W.; Ye, J.-L. Chin. J. Chem. 2015, 33, 655.
(27) Guo, J.; Lin, Z.-H.; Chen, K.-B.; Xie, Y.; Chan, A. S. C.; Weng,
J.; Lu, G. Org. Chem. Front. 2017, 4, 1400.
(28) (a) Liang, Y.-F.; Jiao, N. Angew. Chem., Int. Ed. 2014, 53, 548.
(b) Chaudhari, M. B.; Sutar, Y.; Malpathak, S.; Hazra, A.;
Gnanaprakasam, B. Org. Lett. 2017, 19, 3628. (c) Shen, J.; You, Q.;
Fu, Q.; Kuai, C.; Huang, H.; Zhao, L.; Zhuang, Z. Org. Lett. 2017, 19,
5170. (d) Liang, Y. F.; Jiao, N. Acc. Chem. Res. 2017, 50, 1640.
(e) Luo, K.; Zhao, Y.; Zhang, J.; He, J.; Huang, R.; Yan, S.; Lin, J.; Jin,
Y. Org. Lett. 2019, 21, 423.
(29) Sukari, M. A.; Vernon, J. M. J. Chem. Soc., Perkin Trans. 1 1983,
2219.
(30) Suarez Castillo, O. R.; Melendez-Rodriguez, M.; Aristeo-
Dominguez, A.; Contreras-Martinez, Y. M. A.; Suarez-Ramirez, L.;
Trejo-Carbajal, N.; Joseph-Nathan, P. Heterocycles 2013, 87, 1249.
■
J.D. thanks DST for a SwarnaJayanti fellowship. This work was
supported by DST and CSIR-India for funding. T.M. and G.C.
thank CSIR, India for research fellowships. We thank Mr.
Partha Mitra and Mr. Manish Jana, IACS for helping with
single crystal X-ray analysis.
DEDICATION
■
Dedicated to Professor Vinod K. Singh on the occasion of his
60th birthday.
REFERENCES
■
(1) For review see: (a) Marti, C.; Carreira, E. M. Eur. J. Org. Chem.
2003, 2003, 2209. (b) Galliford, C. V.; Scheidt, K. A. Angew. Chem.,
Int. Ed. 2007, 46, 8748. (c) Trost, B. M.; Brennan, M. K. Synthesis
2009, 3003. (d) Cheng, D.; Ishihara, Y.; Tan, B.; Barbas, F. C. ACS
Catal. 2014, 4, 743. For other references see: (e) Garcia Gimenez,
D.; Garcia Prado, E.; Saenz Rodriguez, T.; Fernandez Arche, A.; De la
Puerta, R. Planta Med. 2010, 76, 133. (f) Antonchick, A. P.; Gerding-
̈
Reimers, C.; Catarinella, M.; Schurmann, M.; Preut, H.; Zieglar, S.;
Rauh, D.; Waldmann, H. Nat. Chem. 2010, 2, 735. (g) Ahmad, R.;
Salim, F. Stud. Nat. Prod. Chem. 2015, 45, 485.
(2) For review, see: (a) Sumpter, W. C. Chem. Rev. 1945, 37, 443.
(b) Shen, K.; Liu, X.; Lin, L.; Feng, X. Chem. Sci. 2012, 3, 327.
(c) Ziarani, G. M.; Gholamzadeh, P.; Lashgiri, N.; Hajiabbasi, P.
ARKIVOC 2013, 470. For other examples see: (d) Han, W.-Y.; Li, S.-
W.; Wu, Z.-J.; Zhang, X.-M.; Yuan, W.-C. Chem. - Eur. J. 2013, 19,
5551. (e) Jia, F.-C.; Xu, C.; Zhou, Z.-W.; Cai, Q.; Wu, Y.-D.; Wu, A.-
X. Org. Lett. 2016, 18, 5232. (f) Di Gregorio, G.; Mari, M.; Bartolucci,
S.; Bartoccini, F.; Piersanti, G. Org. Chem. Front. 2018, 5, 1622.
(g) Jia, Z.-J.; Shan, G.; Daniliuc, C. G.; Antonchick, A. P.; Waldmann,
H. Angew. Chem., Int. Ed. 2018, 57, 14493.
(3) Finefield, J. M.; Frisvad, J. C.; Sherman, D. H.; Williams, R. M. J.
Nat. Prod. 2012, 75, 812.
(4) Niemann, C.; Kessel, J. W. J. Org. Chem. 1966, 31, 2265.
E
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