Pd-Catalyzed Annulation of β-Iodovinyl Sulfones with 2-Halophenols: A General Route for the Synthesis of 3-Sulfonyl Benzofuran Derivatives

Article abstract of DOI:10.1002/adsc.201901550

The palladium-catalyzed annulation between β-iodovinyl sulfones and 2-halophenols or 1-bromo-2-naphthol or 2-bromo-3-pyridinol is presented. The annulation process involving oxa-Michael addition-elimination and intramolecular Heck reaction leading to form

Full text of DOI:10.1002/adsc.201901550

Title: Pd-Catalysed Annulation of beta-Iodovinyl Sulfones with 2-
Halophenols: A General Route for the Synthesis of 3-Sulfonyl
Benzofuran Derivatives
Authors: Raju Jannapu Reddy, Jagadesh Kumar Jangam , Haritha
Kumari Arram , and Rama Krishna Gamidi
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901550
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
COMMUNICATION
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Pd-Catalyzed Annulation of Iodovinyl Sulfones with 2-
Halophenols: A General Route for the Synthesis of 3-Sulfonyl
Benzofuran Derivatives
Raju Jannapu Reddy,*,a Jangam Jagadesh Kumar,†,a Arram Haritha Kumari,†,a and
Gamidi Rama Krishna b
a
Department of Chemistry, University College of Science, Osmania University, Hyderabad 500 007, India.
Centre for X-ray Crystallography, CSIR-National Chemical Laboratory, Pune 411 008, India.
b
E-mail: rajuchem77@osmania.ac.in; rajuchem08@yahoo.co.in
† These authors contributed equally.
This work is dedicated to Dr. Paul W. Davies, School of Chemistry, University of Birmingham, UK for his significant
contribution in gold-catalyzed transformations.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
functional groups on benzofuran scaffold is highly
desirable.
Abstract. The palladium-catalyzed annulation between
-iodovinyl sulfones and 2-halophenols or 1-bromo-2-
naphthol or 2-bromo-3-pyridinol is presented. The
annulation process involving oxa-Michael addition-
elimination and intramolecular Heck reaction leading to
form 2,3-disubstituted benzofurans (aryl benzofuryl
sulfones) in good to high yields. The regioselective
tandem construction of C-O and C-C bonds has been
achieved with
a variety of substitution patterns.
Moreover, the tandem process is reliable at gram-scale
reactions and a plausible mechanism is also proposed.
Keywords: Benzofurans; Heck Reaction;-Iodovinyl
sulfones; Naphthofurans; oxa-Michael addition
Figure 1. Biologically important 2,3-disubstituted benzo-
furan derivatives.
Among the various natural and synthetic
benzofuran derivatives,[1] the 2,3-disubstituted
benzofurans are widely distributed in numerous
natural products[2] and pharmaceutical chemistry.[3]
The sulfones are yet another class of prevalent
scaffolds, which are extremely useful in organic
synthesis as well as in medicinal chemistry.[13]
Therefore, incorporation of the sulfone functionality
into benzofuran frameworks may nurture their
biological properties extensively. Indeed, our
attention drawn to design a new synthetic route
toward sulfonyl derived benzofuran variants. During
our work being in progress, Banwell et al. reported
the tandem construction of benzofuran derivatives
via Pd/Cu-catalyzed Ullmann-Goldberg coupling and
cyclopalladation of 3-haloenones with 2-halophenols
(Scheme 1a).[14] To the best of our knowledge, there
is no general method for the synthesis of aryl
benzofuryl sulfones.[15] Nevertheless, a general and
straight-forward method for the preparation of 3-
sulfonyl benzofuran derivatives is high demand.
Thus, we envisioned that the multifunctional -
iodovinyl sulfones could be the right starting material
To mention
a
few representative examples,
benzbromarone (uricosuric agent),[4] amiodarone
(antiarrhythmic agent),[5] obovaten (antitumor
activity),[6] saprisartan (treatment of hypertension)[7]
and anigopreissin A (antimicrobial activity)[8] as
presented in Figure 1. Due to the aforementioned
biological significance, several effective strategies
have been devoted for assembly of 2,3-disubstituted
benzofurans in recent years.[9-12] In this context, the
most promising strategy involving base-mediated
nucleophilic conjugate addition followed by Heck-
type cyclization of 2-halophenols with activated
alkynes.[12] However, these approaches are suffering
from poor regioselectivity, require to use strong
oxidants, expensive ligands and limitation of a
variety substitutions. Therefore, the development of a
rapid and convergent method that allows for diverse
1
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
for the synthesis of benzofuran derivatives.
Accordingly, we sought to investigate the possibility
of annulation between -iodovinyl sulfones and 2-
halophenols to form 2,3-disubstituted benzofurans
(Scheme 1b). As we assumed the reactions may
proceed through the tandem process involving oxa-
Michael addition and intramolecular Heck coupling,
which is an interesting and challenging endeavour in
organic synthesis. As part of our ongoing research
programme on organosulfur chemistry,[16] we, herein,
report an efficient and unique palladium-catalysed
annulation of -iodovinyl sulfones with 2-
halophenols to produce 3-sulfonyl benzofuran
derivatives through the tandem construction of C-O
and C-C bonds in a single synthetic operation. Thus,
the required -iodovinyl sulfones are easily
accessible from broadly available alkynes,[17] but
their synthetic utility has not been much
explored.[16b,17f,g]
the results were summarised in Table 1 (also see
Table S1 in the Supporting Information for an
extensive survey of reaction conditions). We were
pleased to found that the best reaction conditions: 1a
(1.0 equiv) with 2a (1.5 equiv) in the presence of
Pd(OAc)2 (10 mol%), Ph3P (20 mol%) and Cs2CO3
o
(2 equiv) in DMF at 120 C for 4 h, affording the
desired 2-phenyl-3-tosylbenzofuran (3aa) in 89%
yield (entry 1). The use of K2CO3 instead of Cs2CO3,
the product yield slightly decreased (entry 2).
Reducing the catalyst loading, lowering the Cs2CO3
(1.5 equiv) and 2a (1.2 equiv
) affected the
outcome (entries 3-5). Further screening of solvents
(DMA, chlorobenzene and toluene) offered the
product 3aa in diminished yields (entries 6-8).
Likewise, changing the catalysts, PdCl2(Ph3P)2 and
Pd(Ph3P)4 delivered 3aa in 64% and 76% yields,
respectively (entries 9 and 10). The use of CuI (10
mol%); absence of triphenylphosphine and role of
concentration were unsuccessful in improving the
o
product yield (entries 11-13). The reaction at 90 C
and the reverse equimolar quantities of 1a (1.5 equiv)
and 2a (1.0 equiv) led to lower yields (entries 14 and
15).
Table 1. Optimization for the synthesis of 2-phenyl-3-
tosyl-benzofuran (3aa).[a]
Yield
Entry Deviation from the standard conditions
3aa[b]
Scheme 1. Strategy for tandem construction of benzofuran
derivatives.
1
2
3
4
5
6
7
8
standard conditions
89%
81%
78%
76%
59%
66%
47%
53%
64%
76%
74%
77%
83%
59%
K2CO3 instead of Cs2CO3
5 mol% Pd(OAc)2; 10 mol% Ph3P
with 1.5 equiv of Cs2CO3
with 1.2 equiv of 2a
To test our hypothesis depicted in Scheme 1, our
investigations commenced with (E)-1-[(2-iodo-2-
phenylvinyl)sulfonyl]-4-methylbenzene 1a and 2-
bromophenol 2a as model substrates (Scheme 2).
Initial experiments were conducted in a step-wise
manner. The oxa-Michael addition of 1a with 2a in
the presence of K2CO3 gave the anticipated aryloxy
vinylsulfone ether (3a) in 83% yield with E-major
isomer (see the Supporting Information).[18]
Subsequently, the cyclopalladation of 3a to furnish
the desired 2-phenyl-3-sulfonyl-benzofuran 3aa in
71% yield under unoptimized conditions.
DMA instead of DMF
Chlorobenzene instead of DMF
Toluene instead of DMF
PdCl2(Ph3P)2 instead of Pd(OAc)2
Pd(Ph3P)4 instead of Pd(OAc)2
CuI (10 mol%) instead of Ph3P
without Ph3P
9[c]
10[c]
11
12
13
14
2 mL of DMF used instead of 1 mL
at 90 oC for 6 h
use of 1a (1.5 equiv) and 2a (1.0
equiv)
15
61%
[a] Unless otherwise specified, all reactions were performed
on a 0.2 mmol scale 1a (1.0 equiv), 2a (1.5 equiv) in solvent
(1.0 mL) under N2 at 120 oC for 4 h.
[b] Isolated yield. DMA = N,N-Dimethylacetamide.
[c] Without Ph3P.
Scheme 2. Step-wise synthesis of 2-phenyl-3-tosyl-
benzofuran (3aa).
With the optimized reaction conditions in hand,
we next proceeded to explore the generality of the
tandem process (Scheme 3). The reaction works well
for an array of -iodovinyl sulfones with 2-
bromophenol (2a) and accessed the corresponding
benzofuran derivatives in 45-87% yields. A variety
of substitutions on aromatic sulfonyl derived
Encouraged by this result, we questioned whether
it could be possible to conduct the two steps in a one-
pot operation. Accordingly, several experiments were
performed to identify the best reaction conditions and
2
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
benzofurans 3(a-d)a were obtained in high yields.
The structure of 3aa was unambiguously
confirmed by single-crystal X-ray data analysis
(see the Supporting Information).[19] The
naphthalene-sulfonyl
3ea and 3fa were produced in 78% and 80% yields,
respectively. The 2-thiophenyl substituted
vinylsulfone 1g was also compatible substrate, gave
the desired product 3ga in 63% yield. Additionally,
different aromatic substitutions (4-iPr, 4-Cl, 3- and 4-
OMe) at C2-position of benzofuran derivatives 3(h-
k)a were obtained in relatively low yields. The C2-
naphthyl benzofuran products 3la and 3ma were
obtained with a little effect on the outcome. The 4-
bromoaryl vinylsulfone 1n led to form mixture under
the same reaction conditions. The cyclopropyl
derived vinylsulfone 1o gave the expected product
3oa in 45% yield. Further, we established additional
versatility by using 2-bromo-3-pyridinol 2b under the
same reaction conditions. The anticipated pyridine
fused furan derivatives (3a,b,k)b were accessed
smoothly in 56-67% yields. In contrast, the butyl
substituted vinylsulfone (1p) was not a suitable
substrate for this tandem transformation.
(Scheme 4). The palladium-catalyzed annulation of
2-bromophenols with representative -iodovinyl
sulfones proceeded smoothly under the same reaction
conditions. The 5-methyl and 5-chloro derived
benzofuran motifs (3ac, 3fc, 3lc, 3ad and 3fd) were
obtained in good to high yields. In light of the
biological significance of organofluoro compounds,
we then proceeded successfully to afford the 5-
flouro- and 6-flouro benzofuran derivatives (3ae, 3oe,
3af, 3bf and 3mf) in 42-76% yields. Further, tandem
process progressed with 2g for the synthesis of
naphthofuran analogues (3ag, 3bg, 3fg, 3hg and
3mg), pleasingly the desired products were obtained
in satisfactory yields. Unambiguously, the structure
of 3ag was confirmed by single-crystal X-ray
data analysis (see the Supporting Information).[19]
derived
benzofurans
Scheme 4. Substrate Scope for benzo- and naphtha-furan
derivatives.[a,b]
Scheme 3. Substrate scope for fused furan derivatives.[a,b]
[a] Reactions were performed on a 0.5 mmol scale of 1 (1.0
equiv), 2c-g (1.5 equiv), Pd(OAc)2 (10 mol%), Ph3P (20
mol%), Cs2CO3 (2.0 equiv) in DMF (2.5 mL) under N2 at 120
oC for 4 h.
[b] Isolated yield.
As proof of the versatility and applicability of the
present methodology, other suitable substrates also
examined (Scheme 5). Accordingly, the reactions
were carried out between -iodovinyl sulfones (1a-c)
and 2-iodophenol (2h), surprisingly, the desired
products 3(a-c)a afforded only in modest (40-57%)
yields as compared. As expected, the use of 2-
chlorophenol (2i) resulted in only corresponding enol
ether (4) in 68% yield. We also verified 2-
bromothiophenol (2j) and 2-bromoaniline (2k),
disappointingly the corresponding heterocycles were
not formed under the optimal reaction conditions.
Additionally, the -bromovinyl sulfone (1q) afforded
3aa only in 18% yield under standard reaction
conditions.
[a]
Reactions were performed on a 0.5 mmol scale of 1a-p
(1.0 equiv), 2a/b (1.5 equiv), Pd(OAc)2 (10 mol%), Ph3P (20
mol%), Cs2CO3 (2.0 equiv) in DMF (2.5 mL) under N2 at 120
oC for 4-6 h.
[b] Isolated yield.
[c]
3kb contaminated with corresponding -keto sulfone[16b]
(see the Supporting Information).
Next, we sought to evaluate the scope of various
substituted 2-bromophenols (2c-f) and 1-bromo-2-
naphthol (2g) under the standard reaction conditions
3
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
To highlight the viability of the annulation process,
functionality and the geometry of 3a would be
indispensable for cyclopalladation process.
the reactions performed in a gram-scale under the
similar conditions. As illustrated in Scheme 6, a four
mmol reaction scale of -iodovinyl sulfone 1a with
2-bromophenol 2a in the presence 5 mol% of
Pd(OAc)2, 10 mol% Ph3P and Cs2CO3 (2 equiv) to
produce 3aa in 81% (1.13 g) yield. An economical
point of view, K2CO3 is used instead of Cs2CO3
yielded 3aa in 75% (1.04 g) and 3ba in 71% (0.95 g),
respectively with a slight deviation on efficiency.
Scheme 7. Control experiments.
Based on the above experimental results and the
literature precedent,[14,20,21] a plausible mechanism for
this tandem process is proposed (Scheme 8). Firstly,
base-promoted oxa-Michael addition of -iodovinyl
sulfone (1a)[16b,17f] with 2-bromophenol 2a could form
enol ether (E-3a). Secondly, the mechanism starts
with the consist of oxidative insertion of E-3a to the
in situ generated zerovalent palladium (PdLn) species
to form the arylpalladium complex (A).[14,21] The
intra-molecular coordination with olefin moiety via
π–bond complexation to form the intermediary
(B).[21a] Subsequent carbopalladation generates the
organo-palladium species (C)[20,21] followed by -
hydride elimination lead to desired product 3aa and
active palladium(0)catalyst would be regenerated in
the presence of base for the further catalytic process.
Scheme 5. Study of diverse substrate scope.
Scheme 6. Gram-scale reactions for the synthesis of 3-
sulfonyl benzofurans.
To gain valuable insight into understanding the
reaction mechanism, we performed a few control
experiments (Scheme 7). Initially, the reaction
employed with phenol 2l under the standard reaction
conditions provided phenoxy vinylsulfone 5 in 74%
yield; however, the desired product 3aa was not
detected (Scheme 7a). The reaction of 1a with aryl
bromide 2m was not afford either 3aa or cross-
coupling product 6 (Scheme 7b). According to
known procedure, the Z-enol ether (3a)[18] was
prepared and subjected to cyclopalladation process
(Scheme 7c). To our surprise, the desired benzofuran
3aa was formed in 13% yield. Thus, it was assumed
the coordination of palladium to alkene moiety
through -system complexation may allow to partial
isomerization (Z to E) (see the Supporting
Information).[20] Moreover, the reaction between
alkynyl sulfone (7)[17b] and 2-bromophenol 2a under
the same conditions, unsuccessful to provide 3a or
3aa (Scheme 7d). Further, we have successfully
prepared the desired deuterated starting material 1a-
D (98%-d) to perform isotopic experiments (see the
Supporting Information). The rate of the reaction
slow as compared and the reaction completed in 6 h
under standard conditions (Scheme 1 e). Overall,
these control experiments evidenced that the 2-bromo
Scheme 8. Plausible mechanism for tandem process.
4
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
In summary, we have successfully developed a
Catalan, T. E. Gedris, W. Herz, Phytochemistry 1997,
46, 1077; c) Z. Xu, S. Zhao, Z. Lv, L. Feng, Y. Wang,
F. Zhang, L. Bai, J. Deng, Eur. J. Med. Chem. 2019,
162, 266.
general and efficient method for the construction 3-
sulfonyl benzofuran derivatives from readily
available starting materials. For the first time, the
new tandem conjugate addition and cyclopalladation
resulted in accessing three types of fused furan
analogues: benzofurans, naphtho[2,1-b]furans and
furo[3,2-b]pyridines in moderate to high yields,
which were difficult prepare by other methods.
Notably, the efficacy of the process proved at gram-
scale reactions. The synthetic exploration of -
iodovinyl sulfones and 3-sulfonyl benzofurans[22]
being in progress in our laboratory.
[4] a) M. F. Wempe, P. Jutabha, B. Quade, T. J. Iwen, M.
M. I. R. Frick, Ross, P. J. Rice, N. Anzai, H. Endou, J.
Med. Chem. 2011, 54, 2701; b) H. J. Shin, M. Takeda,
A. Enomoto, M. Fujimura, H. Miyazaki, N. Anzai, H.
Endou, Nephyology 2011, 16, 156.
[5] a) S. Matsui, Z.-P. Zong, J.-F. Han, S. Katsuda, N.
Yamaguchi, M. L. X. Fu, Eur. J. Pharmacol. 2003,
469, 165; b) T. Kodawara, S. Masuda, H. Wakasugi, Y.
Uwai, T. Futami, H. Saito, T. Abe, K. Inui, Pharm. Res.
2002, 19, 738.
Experimental Section
[6] a) C.-L. Kao, J.-W. Chern, J. Org. Chem. 2002, 67,
6772; b) I.-L. Tsai, C.-F. Hsieh, C.-Y. Duh,
Phytochemistry 1998, 48, 1371.
General procedure for synthesis of 3-sulfonyl benzofurans:
A heat gun-dried Schlenk tube was charged β-iodovinyl
sulfones 1a-q (0.5 mmol, 1.0 equiv), 2-halophenols 2a-h
(0.75 mmol, 1.5 equiv), Pd(OAc)2 (0.05 mmol, 10 mol%),
Ph3P (0.1 mmol, 20 mol%) and Cs2CO3 (1.0 mmol, 2
equiv) in DMF (2.5 mL) under nitrogen atmosphere. The
[7] a) G. K. Aulakh, R. K. Sodhi, M. Singh, Life Sci. 2007,
81, 615; b) A. Hilditch, A. A. Hunt, A. Travers, J.
Polley, G. M. Drew, D. Middlemiss, D. B. Judd, B. C.
Ross, M. J. Robertson, J. Pharmacol. Exp. Ther. 1995,
272, 750.
o
mixture was stirred at 120 C for 4 h and monitored by
TLC either complete or appeared to be proceeding no
further progress. The mixture was quenched by addition of
water (20 mL) followed by extraction with EtOAc (3x30
mL). The combined organic layers were washed with brine
(2x30 mL), dried over anhydrous Na2SO4 and the solvent
was removed under reduced pressure. The resulting
residue was subjected to flash chromatography (silica gel
100-200 mesh, eluted with 15% to 20% ethyl
acetate/petether) to afford desired 3-sulfonyl benzofuran
derivatives.
[8] a) R. Brkljaꢀa, J. M. White, S. Urban, J. Nat. Prod.
2015, 78, 1600; b) L. Chiummiento, M. Funicello, M.
T. Lopardo, P. Lupattelli, S. Choppin, F. Colobert, Eur.
J. Org. Chem. 2012, 188.
[9] Selected reports on transition-metal catalyzed synthesis
of 2,3-disubstituted benzofurans, see: a) Z. Xia, V.
Corcé, F. Zhao, C. Przybylski, A. Espagne, L. Jullien,
T. L. Saux, Y. Gimbert, H. Dossmann, V. Mouriès-
Mansuy, C. Ollivier, L. Fensterbank, Nature Chem.
2019, 11, 797; b) C. Zhang, L. Zhen, Z. Yao, L. Jiang,
Org. Lett. 2019, 21, 955; c) S. Ohno, K. Takamoto, H.
Fujioka, M. Arisawa, Org. Lett. 2017, 19, 2422; d) S. S.
K. Boominathan, R.-J. Hou, W.-P. Hu, P.-J. Huang, J.-
J. Wang, Adv. Synth. Catal. 2016, 358, 2984; e) Z. Xia,
O. Khaled, V. Mouriés-Mansuy, C. Ollivier, L.
Fensterbank, J. Org. Chem. 2016, 81, 7182; f) S.
Agasti, S. Maity, K. J. Szabo, D. Maiti, Adv. Synth.
Catal. 2015, 357, 2331; g) J. H. Lee, M. Kim, I. Kim, J.
Org. Chem. 2014, 79, 6153; h) B. Anxionnat, G. D.
Pardo, G. Ricci, K. Rossen, J. Cossy, Org. Lett. 2013,
15, 3876; i) N. Isono, M. Lautens, Org. Lett. 2009, 11,
1329; j) C. Eidamshaus, J. D. Burch, Org. Lett. 2008,
10, 4211; k) B. Lu, B. Wang, Y. Zhang, D. Ma, J. Org.
Chem. 2007, 72, 5337; l) M. Nakamura, L. Ilies, S.
Otsubo, E. Nakamura, Org. Lett. 2006, 8, 2803; m) I.
Nakamura, Y. Mizushima, Y. Yamamoto, J. Am. Chem.
Soc. 2005, 127, 15022.
Acknowledgements
This work funded by CSIR-EMR-II [File No. 02(0340)/18/EMR-
II], New Delhi. RJR thanks to UGC for faculty position under
Faculty Recharge Programme. JJK and AHK thanks to DST
Inspire and CSIR-EMR-II, New Delhi, respectively for their
research fellowship.
References
[1] Recent review articles: a) S. Agasti, A. Dey, D. Maiti,
Chem. Commun. 2017, 53, 6544; b) M. M. Heravi, V.
Zadsirjan, H. Hamidi, P. H. T. Amiri, RSC Adv. 2017,
7, 24470; c) M. R. Patil, K. R. Chethana, K. Chand, M.
A. Santos, R. S. Keri, RSC Adv. 2015, 5, 96809; d) K.
Chand, Rajeshwari, A. Hiremathad, M. Singh, M. A.
Santos, R. S. Keri, Pharmacol. Rep. 2017, 69, 281; e)
B. A. Keay, P. W. Dibble, Furans and their Benzo
Derivatives:
Applications,
In
Comprehensive
Heterocyclic Chemistry II, Vol. 2; A. R. Katritzky,
Rees, C. W.; Scriven, E. F. V., Eds.; Pergamon:
Oxford, 1996, 395.
[10] Selected papers based on metal-free synthesis of 2,3-
disubstituted benzofurans, see: a) Y.-C. Liou, P.
Karanam, Y.-J. Jang, W. Lin, Org. Lett. 2019, 21,
8008; b) Q. Sha, H. Liu, Y. Li, Adv. Synth. Catal. 2019,
361, 1627; c) B. Harish, M. Subbireddy, O. Obulesu, S.
Suresh, Org. Lett. 2019, 21, 1823; d) H. Zhang, C. Ma,
Z. Zheng, R. Sun, X. Yu, J. Zhao, Chem. Commun.
2018, 54, 4935; e) A. C. Mantovani, J. G. Hernꢁndez,
C. Bolm, Eur. J. Org. Chem. 2018, 2458; f) W. Liu, N.
Chen, X. Yang, L. Li, C.-J. Li, Chem. Commun. 2016,
[2] a) A. Goel, A. Kumar, A. Raghuvanshi, Chem. Rev.
2013, 113, 1614; b) W. Wang, Y. Y. Zhao, H. Liang, Q.
Jia, H. B. Chen, J. Nat. Prod. 2006, 69, 876; c) Y.
Fukuyama, M. Nakahara, H. Minami, M. Kodama,
Chem. Pharm. Bull. 1996, 44, 1418.
[3] For a review, see: a) R. J. Nevagi, S. N. Dighe, S. N.
Dighe, Eur. J. Med. Chem. 2015, 97, 561 and
references herein; b) M. E. P. de Lampasona, C. A. N.
5
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
52, 13120; g) P. Tharra, B. Baire, Chem. Commun.
Waheed, J. J. Kumar, RSC Adv. 2018, 8, 40446; e) R. J.
Reddy, Md. Waheed, T. Karthik, A. Shankar, New J.
Chem. 2018, 42, 980; f) R. J. Reddy, A. Shankar, Md.
Waheed, J. B. Nanubolu, Tetrahedron Lett. 2018, 59,
2014.
2016, 52, 14290; h) T. B. Grimaldi, D. F. Back, G.
Zeni, J. Org. Chem. 2013, 78, 11017; i) S. Anwar, W.-
Y Huang, C.-H. Chen, Y.-S. Cheng, K. Chen, Chem.
Eur. J. 2013, 19, 4344; j) Y.-T. Lee, Y.-J. Jang, S.-e.
Syu, S.-C. Chou, C.-J. Lee, W. Lin, Chem. Commun.
2012, 48, 8135.
[17] Recent articles on the syntheses of β-halovinyl
sulfones, see: a) K. Zeng, L. Chen, Y. Liu, Y. Zhou,
C.-T. Au, S.-F. Yin, Adv. Synth. Catal. 2017, 359, 841;
b) Y. Sun, A. Abdukader, L. Dong, H. Zhang, C. Liu,
Green Chem. 2017, 19, 1255; c) R. Kumar, V. Dwivedi,
M. S. Reddy, Adv. Synth. Catal. 2017, 359, 2847; d) C.
Tong, B. Gan, Y. Yan, Y.-Y. Xie, Syn. Commun. 2017,
47, 1927; e) Y. Ma, K. Wang, D. Zhang, P. Sun, Adv.
Synth. Catal. 2019, 361, 597; For utility of β-halovinyl
sulfones, see: f) Y. Liang, S. H. Suzol, Z. Wen, A. G.
Artiles, L. Mathivathanan, R. G. Raptis, S. F. Wnuk,
Org. Lett. 2016, 18, 1418; g) C. Zhang, C. J. Ballay II,
M. L. Trudell, J. Chem. Soc. Perkin Trans. 1 1999, 675.
[11] Selective examples on oxidative annulation for
benzofuran synthesis, see: a) C. Sreenivasulu, A. G. K.
Reddy, G. Satyanarayana, Org. Chem. Front. 2017, 4,
972; b) J. Li, C. Li, S. Yang, Y. An, W. Wu, H. Jiang,
J. Org. Chem. 2016, 81, 2875; c) J. Liao, P. Guo, Q.
Chen, Catalysis Commun. 2016, 77, 22; d) R. Zhu, J.
Wei, Z. Shi, Chem. Sci. 2013, 4, 3706; e) W. Zeng, W.
Wu, H. Jiang, L. Huang, Y. Sun, Z. Chen, X. Li, Chem.
Commun. 2013, 49, 6611; f) M. R. Kuram, M.
Bhanuchandra, A. K. Sahoo, Angew. Chem. Int. Ed.
2013, 52, 4607; g) V. S. Thirunavukkarasu, M. Donati,
L. Ackermann, Org. Lett. 2012, 14, 3416; h) J.
Bonnamour, M. Piedrafita, C. Bolm, Adv. Synth. Catal.
2010, 352, 1577; i) X. Guo, R. Yu, H. Li, Z. Li, J. Am.
Chem. Soc. 2009, 131, 17387.
[18] See for the Z-enol ether (3a): M. Y. Ansari, N.
Kumar, A. Kumar, Org. Lett. 2019, 21, 3931.
[19] The single X-ray crystal structures (CCDC
Deposition Numbers 1963190-1963191) contain the
supplementary crystallographic data for compounds
3aa and 3ag. These data can be obtained free of charge
from the Cambridge Crystallographic Data Centre.
[12] a) H. Yuan, K.-J. Bi, B. Li, R.-C. Yue, J. Ye, Y.-H.
Shen, L. Shan, H.-Z. Jin, Q.-Y. Sun, W.-D. Zhang, Org.
Lett. 2013, 15, 4742; b) J.-R. Wang, K. Manabe, J. Org.
Chem. 2010, 75, 5340; c) T. Konno, J. Chae, T.
Ishihara, H. Yamanaka, Tetrahedron, 2004, 60, 11695;
d) R. C. Larock, E. K. Yum, M. J. Doty, K. K. C. Sham,
J. Org. Chem. 1995, 60, 3270.
[20] A review on palladium-catalyzed cascade cyclizations,
see: J. Biemolt, E. Ruijter, Adv. Synth. Catal. 2018,
360, 3821 and references therein for cyclopalladation
process.
[13] a) N. S. Simpkins, Sulfones in Organic Synthesis;
Pergamon Press: Oxford, 1993; b) K. G. Petrov, Y.
Zhang, M. Carter, G. S. Cockerill, S. Dickerson, C. A.
Gauthier, Y. Guo, R. A. Mook, D. W. Rusnak, A. L.
Walker, E. R. Wood, K. E. Lackey, Bioorg. Med.
Chem. Lett. 2006, 16, 4686; c) Y. Li, Y. Fan, Synth.
Commun. 2019, 49, 3227.
[21] a) M. Mori, K. Chiba, Y. Ban, Tetrahedron Lett. 1977,
1037; b) A review on intramolecular Heck reaction,
see: S. E. Gibson, R. J. Middleton, Contemp. Org.
Synth. 1996, 3, 447.
[22] As per the reviewer-2 suggestion, we have performed
the Kumada-type C-S bond coupling, unfortunately,
our efforts were unsuccessful (see the SI).
[14] F. Khan, M. Fatima, M. Shirzaei, Y. Vo, M.
Amarasiri, M. G. Banwell, C. Ma, J. S. Ward, M. G.
Gardiner, Org. Lett. 2019, 21, 6342.
[15] a) J. Liu, Z. Liu, P. Liao, X. Bi, Org. Lett. 2014, 16,
6204; b) Y. Liu, H. K. Jacobs, A. S. Gopalan,
Tetrahedron Lett. 2011, 52, 2935.
[16] a) R. J. Reddy, A. Shankar, A. H. Kumari, Asian J.
Org. Chem. 2019, 8, 2269; b) R. J. Reddy, J. J. Kumar,
A. H. Kumari, Eur. J. Org. Chem. 2019, 3771; c) R. J.
Reddy, A. H. Kumari, J. J. Kumar, J. B. Nanubolu, Adv.
Synth. Catal. 2019, 361, 1587; d) R. J. Reddy, Md.
6
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10.1002/adsc.201901550
Advanced Synthesis & Catalysis
COMMUNICATION
Pd-Catalysed Annulation of -Iodovinyl
Sulfones with 2-Halophenols: A General Route
for the Synthesis of 3-Sulfonyl Benzofuran
Derivatives
Adv. Synth. Catal. Year, Volume, Page – Page
Raju Jannapu Reddy,* Jangam Jagadesh Kumar,
Arram Haritha Kumari, and Gamidi Rama Krishna
7
This article is protected by copyright. All rights reserved.