Synthesis of 2-Amino-2′-hydroxy-1,1′-biaryls via Cascade Benzannulation and C-N Bond Cleavage Sequence

Article abstract of DOI:10.1021/acs.orglett.0c02749

A serendipitous synthesis of N-substituted 2-amino-2′-hydroxy-1,1′-biaryls through an aryne annulation with indolyl β-ketonitrile/ester in a cascade manner is demonstrated. The reaction sequence involves benzyne-mediated [2 + 2] Stoltz-type cycloaddition-cleavage and intramolecular Michael addition followed by C-N bond cleavage under transition-metal-free reaction conditions. Interestingly, while [4 + 2] Diels-Alder reaction is a possible pathway, no traces of the regioisomer was isolated.

Full text of DOI:10.1021/acs.orglett.0c02749

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Letter
Synthesis of 2‑Amino-2′-hydroxy-1,1′-biaryls via Cascade
Benzannulation and C−N Bond Cleavage Sequence
Raju Adepu,* Jadhav Rahul Dhanaji, Polasani Samatha, Prathama S. Mainkar,
and Srivari Chandrasekhar*
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ABSTRACT: A serendipitous synthesis of N-substituted 2-amino-
2′-hydroxy-1,1′-biaryls through an aryne annulation with indolyl β-
ketonitrile/ester in a cascade manner is demonstrated. The
reaction sequence involves benzyne-mediated [2 + 2] Stoltz-type
cycloaddition−cleavage and intramolecular Michael addition
followed by C−N bond cleavage under transition-metal-free
reaction conditions. Interestingly, while [4 + 2] Diels−Alder
reaction is a possible pathway, no traces of the regioisomer was
isolated.
or naphthalene/indole ring connected to a substituted benzene
ring with rotational restriction.
unctionalized biaryl structural motifs are found in a variety
Fof natural products including bioactives and catalysts.
The methods for the synthesis of this class of compounds
include transition-metal-catalyzed cross couplings (e.g., Miz-
oroki−Heck, Suzuki−Miyaura, etc.), C−H oxidative direct
arylation, acid-mediated reactions, etc. with the use of a
naphthalene core as one of the partners.3−5 The naphthalene
partner is usually obtained from coal tar or by annulation of
benzyne through a cycloaddition process.6−8 Recently, Shu et
al. have demonstrated the use of a multicomponent reaction to
initiate Stoltz’s β-keto ester insertion to benzyne, followed by
cycloaddition to generate a substituted naphthalene skeleton
(Scheme 1a).9 Dubrovskiy and Larock were able to synthesize
chromanones and flavanones via an aryne insertion/annulation
strategy (Scheme 1b).10 Our research group has been engaged
in developing new applications for Stoltz’s β-keto ester
insertion onto arynes.11 Toward this end, we envisaged that
β-keto ester/nitrile appended onto the indole ring allowing the
insertion−Michael addition−aromatize deamination (C−N
bond cleavage)12 reaction sequence to provide 2-amino-2′-
hydroxy-1,1′-biaryl skeleton 3 under transition-metal-free
catalysis (path A) (Scheme 1c). The formation of biaryl
skeleton 3′ is also possible if the reaction goes through [4 + 2]
cycloaddition followed by aromatization via C−N bond
cleavage13 (path B) (Scheme 1c). Pleasantly, we encountered
the formation of biaryl 3 exclusively, indicating that Stoltz’s β-
They have a wide range of applications in pharmaceuticals,
agrochemicals, and novel organic materials such as liquid
crystals and conducting polymers.1 The presence of hindered
C−C bond rotation in biaryl compounds (e.g., BINAP,
BINOL, NOBIN, and their derivatives, etc.) imparts them
the property of becoming excellent ligands in asymmetric
catalysis and chiral drugs (Figure 1) such as TMC-95A, (R)-
streptonigrin, etc.2 Most of the axially chiral biaryls have
naphthalene rings connected by a rotationally restricted bond
Received: August 17, 2020
Figure 1. Representative examples of biaryl motif ligands and
bioactive compounds.
https://dx.doi.org/10.1021/acs.orglett.0c02749
© XXXX American Chemical Society
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A

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a
Scheme 1. Previous and Present Aryne Insertion/
Annulation
Table 1. Optimization of Reaction Conditions
b
c
entry
fluoride source
additive
solvent
THF
THF
THF
THF
THF
THF
CH3CN
1,4-dioxane
Toluene
THF
THF
THF
yield (%)
1
2
3
CsF
CsF
CsF
KF
68
72
72
56
63
e
64
58
48
51
20
18-crown-6
18-crown-6
d
4
5
6
7
8
9
10
11
12
13
KF
18-crown-6
TBAF
CsF
CsF
CsF
CsF
CsF
CsF
f
18-crown-6
18-crown-6
18-crown-6
g
h
i
THF
a
Standard reaction conditions: 1a (1.0 equiv), 2a (1.2 equiv), and
b
fluoride source (3.0 equiv) in solvent (0.1 M) at 60 °C for 16 h. 3.0
c
d
equiv used. Yield of isolated product. 1.5 equiv of 2a used.
e
f
g
keto ester/nitrile insertion onto arynes is dominating against
the inverse Diels−Alder reaction in the present annulation
reaction conditions. The product thus obtained has an
electron-withdrawing group and electron-donating phenol
group para to each other instead of ortho to each other if
the reaction has to operate by [4 + 2] cycloaddition. The
details are presented herein.
Complex mixture. Reaction performed at 80 °C. Reaction time 3 h.
h
i
Reaction performed at room temperature. Without CsF.
methoxy-substituted arynes also tolerated the reaction
conditions well to produce the corresponding compounds 3c
and 3d in good yields. The electron-poor difluoro-substituted
aryne gave slightly lower yield (Table 2, entry 3e). Further, we
turned our attention to examine the substitutions on phenyl
ring in N-Boc indole β-ketonitrile 1. The halogen-substituted
indoles 1 (6-Cl, 5-Br and 4-Br), also underwent the reaction,
without any electronic effect, to deliver the required
compounds 3f−3n in good yields (59−72%). The compound
with an electron-donating group on indole 1 (5-OMe) also
participated in the reaction very well to provide the desired
compound in good yield (Table 2, entry 3o). Notably, 2-
methyl-substituted indole 1 delivered the corresponding
product 3p in 58% yield without any steric hindrance. The
reaction of unsymmetrical aryne precursors such as 3-methoxy
aryl triflate, 3-methoxy-5-methyl aryl triflate, and naphthyl
triflate provided the regioisomeric products that are consistent
with the literature reports.14 The molecular structure of a
representative compound 3a was confirmed by single-crystal X-
ray crystallography (Table 2).
To expand further the scope of the present annulation,
reaction of N-alkyl indole β-ketonitrile 1 with benzyne
precursors 2 were investigated. Under optimized reaction
conditions, N-methyl indole β-ketonitrile 1g with benzyne
precursor 2a resulted in a mixture of the insertion product 5
and arylation product 6 (Scheme 2a). The reason might be the
less electrophilic nature of C-2 position in N-methyl indole
compared to N-Boc indole due to the inductive effect of
corresponding groups. To overcome this problem, reaction
temperature was increased to 105 °C and 1,4-dioxane was used
as a solvent, which furnished the desired product 3q in good
yield (Scheme 2b). Next, we investigated the generality of the
reaction with respect to diversely substituted alkyl indoles
(Table 3). The substitutions such as methyl, benzyl, and allyl
groups on indole nitrogen were well tolerated and afforded the
Initially, the cascade aryne annulation reaction of in situ
generated benzyne from 2a with N-Boc indole β-ketonitrile 1a
was carried out in THF as solvent using 3.0 equiv of CsF as a
fluoride source at 60 °C. To our delight, the desired product
3a was obtained in 68% yield (Table 1, entry 1). The
optimization of conditions was attempted to improve the yield.
The yield of the product 3a slightly increased with the addition
of 18-crown-6 to reaction mixture (Table 1, entry 2). We did
not observe any improvement of yield with 1.5 equiv of
benzyne precursor 2a (Table 1, entry 3). However, the
reaction with different fluoride sources such as KF and TBAF
failed to improve the yield (Table 1, entries 4−6). Screening of
solvents such as acetonitrile, 1,4-dioxane, and toluene were
found to be inefficient to increase the product yield when
compared to the THF (Table 1, entries 7−9). Increasing the
reaction temperature led to a decrease in the product yield
(Table 1, entry 10). Control experiments revealed that
temperatures higher than ambient and CsF were needed for
the present cascade aryne annulation reaction (Table 1, entries
11−13). Overall, a combination of N-Boc indole β-ketonitrile
1a (1.0 equiv), aryl triflate 2a (1.2 equiv), CsF (3.0 equiv), and
18-crown-6 (3.0 equiv) in THF at 60 °C for 16 h were found
to be the optimum reaction conditions.
With the optimized conditions in hand, we then examined
the scope of present cascade reaction with a variety of
substitution patterns. As summarized in Table 2, the
annulation of N-Boc indole β-ketonitrile 1 with arynes
proceeded smoothly, irrespective of substitution patterns on
both substrates. The reaction with dimethyl-substituted aryne
participated in the aryne annulation reaction smoothly to
provide the desired compound 3b in 56% yield. Moreover,
B
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Table 2. Substrate Scope of N-Boc-indole (1) and Benzyne
Precursors (2)
Table 3. Substrate Scope of N-Alkylindole (1) and Benzyne
Precursors (2)
a b
,
a b
,
a
Reaction conditions: 1 (1.0 equiv), 2 (1.2 equiv), CsF (3.0 equiv),
and 18-crown-6 (3.0 equiv) in 1,4-dioxane (0.1 M) at 105 °C for 16
b
h. Yield of isolated product.
having a β-ketoester also participated well and gave the desired
product 3w in 45% yield, while the indole having 1,3-diketone
failed to produce the desired product 3x.15 It is worth
mentioning that when the reaction was performed with indole
β-ketonitrile 4 without N-protection in the presence of excess
benzyne precursor 2a, the desired biaryl products with N-
arylation 3y and 3z were observed in 57% and 52% yields,
respectively (Scheme 3).
Scheme 3. Reaction of Indole (4) and Aryl Triflate (2a)
a
Reaction conditions: 1 (1.0 equiv), 2 (1.2 equiv), CsF (3.0 equiv),
b
and 18-crown-6 (3.0 equiv) in THF (0.1 M) at 60 °C for 16 h. Yield
of isolated product.
Scheme 2. Reaction of N-Methylindole (1g) and Aryl
Triflate (2a)
A gram-scale synthesis of compound 3a was also
demonstrated in Scheme 4a. To see the distribution of
deuterium atoms in the product, a control experiment was
performed using 2 equiv of D2O in the reaction mixture, and
no deuterium incorporation was found in the product (Scheme
4b). Further, an aryne insertion intermediate 5 was converted
to compound 3q under standard conditions in 81% yield
(Scheme 4c). It clearly indicated that the reaction is going
through β-ketonitrile insertion onto arynes. Based on the
outcome of above experiment (Scheme 4c) and known
literature,6,8 a plausible reaction mechanism was proposed
(Scheme 5). The mechanism involves the [2 + 2] cyclo-
addition of transient benzyne A, generated in situ from o-silyl
aryl triflate 2a and N-Boc indole β-ketonitrile 1a to give a
strained four membered ring intermediate, B. The ring opening
of intermediate B generates the insertion product C, which
would further undergo intramolecular Michael addition to give
tetracyclic intermediate D, followed by aromatization via C−N
corresponding biaryls 3q−3u in good yields (49−68%). The
benzo[g]indole β-ketonitrile involved in aryl annulation
provided the binaphthyl product 3v in 56% yield. The indole
C
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Scheme 4. Gram-Scale Synthesis and Control Experiments
AUTHOR INFORMATION
Corresponding Authors
■
Raju Adepu − Department of Organic Synthesis and Process
Chemistry, CSIR-Indian Institute of Chemical Technology,
Hyderabad 500007, India; Academy of Scientific and
Innovative Research (AcSIR), Ghaziabad 201002, India;
orcid.org/0000-0002-4437-1597; Email: dr.rajuadepu@
gmail.com
Srivari Chandrasekhar − Department of Organic Synthesis and
Process Chemistry, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India; Academy of Scientific
and Innovative Research (AcSIR), Ghaziabad 201002, India;
orcid.org/0000-0003-3695-4343; Email: srivaric@
iict.res.in
Authors
Jadhav Rahul Dhanaji − Department of Organic Synthesis and
Process Chemistry, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India; Academy of Scientific
and Innovative Research (AcSIR), Ghaziabad 201002, India
Polasani Samatha − Department of Organic Synthesis and
Process Chemistry, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India
Prathama S. Mainkar − Department of Organic Synthesis and
Process Chemistry, CSIR-Indian Institute of Chemical
Technology, Hyderabad 500007, India; Academy of Scientific
and Innovative Research (AcSIR), Ghaziabad 201002, India
Scheme 5. Plausible Mechanism
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c02749
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank the Council of Scientific and Industrial
Research (CSIR), Ministry of Science and Technology, Govt.
of India. R.A. thanks the Department of Science & Technology
(DST) New Delhi for an Inspire Faculty fellowship and grant
(DST/INSPIRE/04/2018/001635). J.R.D. thanks CSIR for a
research fellowship. S.C. thanks the Science and Engineering
Research Board (SERB), Government of India for the J C Bose
fellowship (SB/S2/JCB-002/2015) and (VI-D8P/513/2014-
15/TDT(G)). We gratefully acknowledge Dr. Balasubrama-
nian Sridhar, Laboratory of X-ray Crystallography, CSIR-IICT,
for X-ray analysis. CSIR-IICT manuscript number IICT/
Pubs./2020/229.
bond cleavage leads to N-Boc-2-amino-2′-hydroxy-1,1′-biaryl
3a.
In summary, we have developed a simple protocol for the
synthesis of N- substituted-2-amino-2′-hydroxy-1,1′-biaryls
using a one pot aryne annulation strategy. Intramolecular
Michael addition and subsequent C−N bond cleavage are key
reactions in this annulation.
REFERENCES
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c02749.
■
■
(1) (a) Loxq, P.; Manoury, E.; Poli, R.; Deydier, E.; Labande, A.
Coord. Chem. Rev. 2016, 308, 131. (b) Bringmann, G.; Gulder, T.;
Gulder, T. A. M.; Breuning, M. Chem. Rev. 2011, 111, 563.
(c) Bringmann, G.; Mortimer, A. J. P.; Keller, P. A.; Gresser, M. J.;
Garner, J.; Breuning, M. Angew. Chem., Int. Ed. 2005, 44, 5384.
(d) Hassan, J.; Sevignon, M.; Gozzi, C.; Schulz, E.; Lemaire, M. Chem.
Rev. 2002, 102, 1359.
sı
Experimental procedures, characterization details, 1H
and 13C NMR spectra of new compounds (PDF)
(2) (a) Lu, S.; Ng, S. V. H.; Lovato, K.; Ong, J.-Y.; Poh, S. B.; Ng, X.
̈
Q.; Kurti, L.; Zhao, Y. Nat. Commun. 2019, 10, 3061. (b) Lebedev, Y.;
Accession Codes
CCDC 2009564 contains 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 Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
Polishchuk, I.; Maity, B.; Guerreiro, M. D. V.; Cavallo, L.; Rueping,
M. J. Am. Chem. Soc. 2019, 141, 19415. (c) Uraguchi, D.; Nakashima,
D.; Ooi, T. J. Am. Chem. Soc. 2009, 131, 7242. (d) Huang, H.; Okuno,
T.; Tsuda, K.; Yoshimura, M.; Kitamura, M. J. Am. Chem. Soc. 2006,
128, 8716. (e) Brunel, J. M. Chem. Rev. 2005, 105, 857. (f) Ding, K.;
Li, X.; Ji, B.; Guo, H.; Kitamura, M. Curr. Org. Synth. 2005, 2, 499.
D
https://dx.doi.org/10.1021/acs.orglett.0c02749
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(g) Kocovsky, P.; Vyskocil, S.; Smrcina, M. Chem. Rev. 2003, 103,
3213.
3768. (k) Ma, Z.-X.; Feltenberger, J. B.; Hsung, R. P. Org. Lett. 2012,
14, 2742. (l) Allan, K. M.; Gilmore, C. D.; Stoltz, B. M. Angew. Chem.,
Int. Ed. 2011, 50, 4488; Angew. Chem. 2011, 123, 4580. (m) Huang,
X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S.-F.; Wang, F.; Li, J.-H. Org. Lett.
2008, 10, 1525. (n) Blackburn, T.; Ramtohul, Y. K. Synlett 2008,
2008, 1159. (o) Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am.
Chem. Soc. 2008, 130, 1558.
(8) Selected references for aryne insertion−annulation: (a) Singh, S.;
Samineni, R.; Pabbaraja, S.; Mehta, G. Tetrahedron 2019, 75, 2923.
(b) Ghotekar, G. S.; Shaikh, A. C.; Muthukrishnan, M. J. Org. Chem.
2019, 84, 2269. (c) Hu, W.; Zhang, C.; Huang, J.; Guo, Y.; Fu, Z.;
Huang, W. Org. Lett. 2019, 21, 941. (d) Welin, E. R.; Ngamnithiporn,
A.; Klatte, M.; Lapointe, G.; Pototschnig, G. M.; McDermott, M. S. J.;
Conklin, D.; Gilmore, C. D.; Tadross, P. M.; Haley, C. K.; Negoro,
(3) Selected reviews on biaryl syntheses: (a) Zhang, Y.-F.; Shi, Z.-J.
Acc. Chem. Res. 2019, 52, 161. (b) Wencel-Delord, J.; Panossian, A.;
Leroux, F. R.; Colobert, F. Chem. Soc. Rev. 2015, 44, 3418.
(c) McGlacken, G. P.; Bateman, L. M. Chem. Soc. Rev. 2009, 38,
2447. (d) Kozlowski, M. C.; Morgan, B. J.; Linton, E. C. Chem. Soc.
Rev. 2009, 38, 3193. (e) Alberico, D.; Scott, M. E.; Lautens, M. Chem.
Rev. 2007, 107, 174. (f) Bringmann, G.; Walter, R.; Weirich, R. Angew.
Chem., Int. Ed. Engl. 1990, 29, 977; Angew. Chem. 1990, 102, 1006.
(4) (a) Zhu, S.; Chen, Y.-H.; Wang, Y.-B.; Yu, P.; Li, S.-Y.; Xiang, S.-
H.; Wang, J.-Q.; Xiao, J.; Tan, B. Nat. Commun. 2019, 10, 4268.
(b) Wang, J.-Z.; Zhou, J.; Xu, C.; Sun, H.; Kurti, L.; Xu, Q.-L. J. Am.
̈
Chem. Soc. 2016, 138, 5202. (c) Cheng, D.-J.; Yan, L.; Tian, S.-K.;
Wu, M.-Y.; Wang, L.-X.; Fan, Z.-L.; Zheng, S.-C.; Liu, X.-Y.; Tan, B.
Angew. Chem., Int. Ed. 2014, 53, 3684; Angew. Chem. 2014, 126, 3758.
(5) Selective references for the synthesis of NOBIN and its
derivatives: (a) Yuan, H.; Du, Y.; Liu, F.; Guo, L.; Sun, Q.; Feng, L.;
Gao, H. Chem. Commun. 2020, 56, 8226. (b) Guo, L.; Liu, F.; Wang,
L.; Yuan, H.; Feng, L.; Lu, H.; Gao, H. Org. Chem. Front. 2020, 7,
1077. (c) Ding, W.-Y.; Yu, P.; An, Q.-J.; Bay, K. L.; Xiang, S.-H.; Li,
S.; Chen, Y.; Houk, K. N.; Tan, B. Chem. 2020, 6, 2046. (d) Guo, L.;
K.; Glibstrup, E.; Grunanger, C. U.; Allan, K. M.; Virgil, S. C.;
̈
Slamon, D. J.; Stoltz, B. M. Science 2019, 363, 270. (e) Takikawa, H.;
Nishii, A.; Suzuki, K. Synthesis 2016, 48, 3331. (f) Kranthikumar, R.;
Chegondi, R.; Chandrasekhar, S. J. Org. Chem. 2016, 81, 2451.
(g) Okuma, K.; Horigami, K.; Nagahora, N.; Shioj, K. Synthesis 2015,
47, 2937. (h) Okuma, K.; Hirano, K.; Tanabe, Y.; Itoyama, R.; Miura,
A.; Nagahora, N.; Shioji, K. Chem. Lett. 2014, 43, 492. (i) Okuma, K.;
Itoyama, R.; Sou, A.; Nagahora, N.; Shioj, K. Chem. Commun. 2012,
48, 11145. (j) Allan, K. M.; Hong, B. D.; Stoltz, B. M. Org. Biomol.
Chem. 2009, 7, 4960. (k) Huang, X.; Xue, J. J. Org. Chem. 2007, 72,
3965. (l) Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127,
5340.
Liu, F.; Wang, L.; Yuan, H.; Feng, L.; Kurti, L.; Gao, H. Org. Lett.
̈
2019, 21, 2894. (e) Qi, L.-W.; Li, S.; Xiang, S.-H.; Wang, J.; Tan, B.
Nat. Catal. 2019, 2, 314. (f) Yang, G.; Guo, D.; Meng, D.; Wang, J.
Nat. Commun. 2019, 10, 3062. (g) Chang, X.; Zhang, Q.; Guo, C.
Org. Lett. 2019, 21, 4915. (h) Forkosh, H.; Vershinin, V.; Reiss, H.;
Pappo, D. Org. Lett. 2018, 20, 2459. (i) Chen, Y.-H.; Qi, L.-W.; Fang,
F.; Tan, B. Angew. Chem., Int. Ed. 2017, 56, 16308; Angew. Chem.
2017, 129, 16526. (j) Gao, H.; Xu, Q.-L; Keene, C.; Yousufuddin, M.;
(9) Shu, W.-M.; Liu, S.; He, J.-X.; Wang, S.; Wu, A.-X. J. Org. Chem.
2018, 83, 9156.
(10) Dubrovskiy, A. V.; Larock, R. C. Org. Lett. 2010, 12, 3117.
(11) Kallepu, S.; Sanjeev, K.; Chegondi, R.; Mainkar, P. S.;
Chandrasekhar, S. Org. Lett. 2018, 20, 7121.
Ess, D. H.; Kurti, L. Angew. Chem., Int. Ed. 2016, 55, 566; Angew.
̈
(12) Selected references for indole C−N bond cleavage:
(a) Uruvakili, A.; Swamy, K. C. K. Org. Biomol. Chem. 2019, 17,
3275. (b) Lvov, A. G.; Shirinian, V. Z.; Zakharov, A. V.; Krayushkin,
M. M.; Kachala, V. V.; Zavarzin, I. V. J. Org. Chem. 2015, 80, 11491.
(13) One example of [4 + 2] cycloaddition followed by
aromatization via indole C−N bond cleavage has been reported;
see: Tao, Y.; Zhang, F.; Tang, C.-Y.; Wu, X.-Y.; Sha, F. Asian J. Org.
Chem. 2014, 3, 1292.
(14) (a) Mirzaei, S.; Khosravi, H. Tetrahedron Lett. 2017, 58, 3362.
(b) Tadross, P. M.; Gilmore, C. D.; Bugga, P.; Virgil, S. C.; Stoltz, B.
M. Org. Lett. 2010, 12, 1224.
(15) Reaction of arynes with aroylacetones leads to formation of 4-
aryl-2-naphthols and 3-aryl-1-naphthols via aryne insertion followed
by an intramolecular aldol reaction and dehydration; see: Okuma, K.;
Itoyama, R.; Sou, A.; Nagahora, N.; Shioj, K. Chem. Commun. 2012,
48, 11145.
Chem. 2016, 128, 576. (k) Berkessa, S. C.; Clarke, Z. J. F.; Fotie, J.;
Bohle, D. S.; Grimm, C. C. Tetrahedron Lett. 2016, 57, 1613. (l) Lu,
S.; Poh, S. B.; Zhao, Y. Angew. Chem., Int. Ed. 2014, 53, 11041; Angew.
Chem. 2014, 126, 11221. (m) Shirakawa, S.; Wu, X.; Maruoka, K.
Angew. Chem., Int. Ed. 2013, 52, 14200; Angew. Chem. 2013, 125,
14450. (n) Gao, H.; Ess, D. H.; Yousufuddin, M.; Kurti, L. J. Am.
̈
Chem. Soc. 2013, 135, 7086. (o) Chandrasekharam, M.; Chiranjeevi,
B.; Gupta, K. S. V.; Sridhar, B. J. Org. Chem. 2011, 76, 10229.
(p) Singer, R. A.; Brock, J. R.; Carreira, E. M. Helv. Chim. Acta 2003,
86, 1040. (q) Korber, K.; Tang, W.; Hu, X.; Zhang, X. Tetrahedron
Lett. 2002, 43, 7163. (r) Ding, K.; Wang, Y.; Yun, H.; Liu, J.; Wu, Y.;
Terada, M.; Okubo, Y.; Mikami, K. Chem. - Eur. J. 1999, 5, 1734.
(s) Smrcina, M.; Vyskocil, S.; Polivkova, J.; Polakova, J.; Kocovsky, P.
Collect. Czech. Chem. Commun. 1996, 61, 1520.
(6) Selected references for aryne review: (a) Roy, T.; Biju, A. T.
Chem. Commun. 2018, 54, 2580. (b) Bhojgude, S. S.; Bhunia, A.; Biju,
A. T. Acc. Chem. Res. 2016, 49, 1658. (c) Bhojgude, S. S.; Biju, A. T.
Angew. Chem., Int. Ed. 2012, 51, 1520; Angew. Chem. 2012, 124, 1550.
(d) Bhunia, A.; Yetra, S. R.; Biju, A. T. Chem. Soc. Rev. 2012, 41, 3140.
(e) Tadross, P. M.; Stoltz, B. M. Chem. Rev. 2012, 112, 3550. (f) Sanz,
R. Org. Prep. Proced. Int. 2008, 40, 215. (g) Pellissier, H.; Santelli, M.
Tetrahedron 2003, 59, 701. (h) Wenk, H. H.; Winkler, M.; Sander, W.
Angew. Chem., Int. Ed. 2003, 42, 502; Angew. Chem. 2003, 115, 518.
(i) Heaney, H. Chem. Rev. 1962, 62, 81.
(7) Selected references for aryne annulation: (a) John, J.;
Omanakuttan, V. K.; Aneeja, T.; Suresh, C. H.; Jones, P. G.; Hopf,
H. J. Org. Chem. 2019, 84, 5957. (b) Singh, R.; Nagesh, K.;
Yugandhar, D.; Prasanthi, A. V. G. Org. Lett. 2018, 20, 4848.
(c) Neog, K.; Das, B.; Gogoi, P. Org. Biomol. Chem. 2018, 16, 3138.
(d) Gouthami, P.; Chavan, L. N.; Chegondi, R.; Chandrasekhar, S. J.
Org. Chem. 2018, 83, 3325. (e) Thangaraj, M.; Bhojgude, S. S.; Jain,
S.; Gonnade, R. G.; Biju, A. T. J. Org. Chem. 2016, 81, 8604. (f) Gesu,
A.; Pozzoli, C.; Torre, E.; Aprile, S.; Pirali, T. Org. Lett. 2016, 18,
1992. (g) Shu, W.-M.; Zheng, K.-L.; Ma, J.-R.; Wu, A.-X. Org. Lett.
2016, 18, 3762. (h) Shu, W.-M.; Ma, J.-R.; Zheng, K.-L.; Wu, A.-X.
Org. Lett. 2016, 18, 196. (i) Bhunia, A.; Kaicharla, T.; Porwal, D.;
Gonnade, R. G.; Biju, A. T. Chem. Commun. 2014, 50, 11389. (j) Liu,
F.-L.; Chen, J.-R.; Zou, Y.-Q.; Wei, Q.; Xiao, W.-J. Org. Lett. 2014, 16,
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