Merging [2+2] Cycloaddition with Radical 1,4-Addition: Metal-Free Access to Functionalized Cyclobuta[a]naphthalen-4-ols

Article abstract of DOI:10.1002/anie.201707615

A metal-free [2+2] cycloaddition and 1,4-addition sequence induced by S-centered radicals has been achieved by treating benzene-linked allene-ynes with aryldiazonium tetrafluoroborates and DABCO-bis(sulfur dioxide) in a one-pot procedure. The reaction provides a greener and more practical access to functionalized cyclobuta[a]naphthalen-4-ols with valuable applications. More than 50 examples are demonstrated with excellent diastereoselectivity and chemical yields. The reaction pathway is proposed to proceed by the following steps:[2+2] cycloaddition, insertion of SO₂, 1,4-addition, diazotization, and tautomerization.

Full text of DOI:10.1002/anie.201707615

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Accepted Article
Title: Merging [2 + 2] Cycloaddition with Radical 1,4-Addition: Metal-
Free Access to Functionalized Cyclobuta[a]naphthalen-4-ols
Authors: Bo Jiang, Feng Liu, Jia-Yin Wang, Peng Zhou, guigen Li,
Wen-Juan Hao, and Shu-Jiang Tu
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10.1002/anie.201707615
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COMMUNICATION
Merging [2 + 2] Cycloaddition with Radical 1,4-Addition: Metal-
Free Access to Functionalized Cyclobuta[a]naphthalen-4-ols
Feng Liu,[a],1 Jia-Yin Wang,[a],1 Peng Zhou,[b] Guigen Li,*,[b],[c] Wen-Juan Hao,[a],Shu-Jiang Tu,*,[a] and Bo
Jiang*,[a],[c]
Dedicated this work to Prof. Dr.h.c. mult Robert Huber on occasion of his 80th birthday
Abstract: Metal-free [2 + 2] cycloaddition and S-centered radical-
induced 1,4-addition cascades have been achieved by treating
benzene-linked allene-ynes with aryldiazonium tetrafluoroborates and
DABCO-bis(sulfur dioxide) in a one-pot procedure; the reaction
provides a greener and more practical access to functionalized
cyclobuta[a]naphthalen-4-ols with valuable applications. More than 50
examples are demonstrated with excellent diastereoselectivity and
chemical yields. The reaction pathway is proposed to proceed through
the following: sequence of [2 + 2] cycloaddition, insertion of SO2, 1,4-
Scheme 1. Profiles of radical additions
addition, diazotization and tautomerization.
Sulfones are a valuable class of sulfur-containing molecules, and
are widely prevalent in bioactive natural products and
pharmaceuticals.[1] Among them, aryl sulfones are common
constituents in many drugs and pesticides, such as antimigraine
Vioxx3,[2a] antibacterial Dapsone,[2b] and antiandrogen Casodex[2c]
herbicides Mesotrione and Cafenstrole,[3] etc. In the past decade,
substantial efforts have been made toward identifying efficient
incorporation of arylsulfonyl groups into organic and medicinal
targets.[4] In fact, the generation of aryl sulfonyl radical, starting
from aryldiazonium salts and DABCO-bis(sulfur dioxide)
(DABSO) via its addition onto alkenes and alkynes has been well
documented, providing an efficient access to a variety of
arylsulfones.[5] Similarly, widespread chemical and biomedical
applications of azo compounds have inspired the rapid
development of greener methods for their preparations,[6] for
which aryldiazonium salts have proven to be a powerful radical
acceptor for the synthesis of azo products.[7] During conducting
ongoing and related projects, we speculated that aryldiazonium
salts would act as both aryl radical donor and azo sources
capable of being intercepted by DABSO and unsaturated carbon-
carbon bonds so as to install sulfonyl and azo functionalities into
molecular frameworks.
,
Scheme 2. [2 + 2] Cycloaddition/ insertion of SO2 cascades for the synthesis of
cyclobuta[a]naphthalen-4-ols
synthetic strategy for the rapid creation of challenging and unique
cyclic targets of chemical and biological importance.[8] So far, the
majority of work in this field has been focused on radical addition-
cyclization cascades, in which a radical species favors the
triggering of an addition with unsaturated chemical bonds,
followed by intramolecular cyclization to access cyclic compounds
(Scheme 1a).[9] However, new reactivity modes of cyclization-
radical addition sequence have received much less attention, and
as such remains an unsolved challenge due to the inherent
difficulty of controlling radicals’ behavior (Scheme 1b).[10] Recently,
our group has been studying a series of radical cyclization
cascades for the formation of multiple functional rings with great
success.[11] During our preparation of allene-yne-anchored
starting materials[12] serving as radical acceptors, we surprisingly
encountered a tandem [2 + 2] cycloaddition of benzene-linked
allene-ynes 1 (R3 = H),[13] which was followed by the interception
of arylsulfonyl radicals and aryldiazonium species affording
cyclobuta[a]naphthalen-4-ols 4 containing both sulfonyl and azo
functionalities (Scheme 2). Exchanging allene-ynes for benzene-
It is well-known that cascade cyclizations, particularly those
involving a radical mechanism, are a reliable and straightforward
[a]
[b]
[c]
F. Liu, J.-Y. Wang, Dr. W.-J. Hao, Prof. S.-J. Tu, Prof. Dr. B. Jiang
School of Chemistry & Materials Science
Jiangsu Normal University, Xuzhou, Jiangsu 221116, (China)
E-mail: laotu@jsnu.edu.cn (SJT); jiangchem@jsnu.edu.cn (BJ)
P. Zhou, Prof. Dr. G. Li
Institute of Chemistry & BioMedical Sciences, Collaborative
Innovation Center of Chemistry for Life Sciences, Nanjing
University, Nanjing 210093, P. R. China. email:guigen.li@ttu.edu
Prof. Dr. G. Li and Prof. Dr. B. Jiang
linked allene-yne esters
5 = ester) resulted in the
(R3
corresponding cyclobuta[a]naphthalen-4-ols 6 with generally
good yields and high diastereoselectivity (up to >99:1 dr, Scheme
2). The current protocol represents the first multicomponent
bicyclization strategy for the direct synthesis of new
cyclobuta[a]naphthalen-4-ols by merging [2 + 2] cycloaddition
Department of Chemistry and Biochemistry, Texas Tech University,
Lubbock, Texas 79409-1061, United States;
1These authors contributed equally
Supporting information for this article is given via a link at the end of
the document.((Please delete this text if not appropriate))
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with S-centered radical-induced conjugated 1,4-addition in a one-
pot protocol without any additional oxidant. Herein, we report our
efforts to elaborate on this serendipitous discovery.
At the outset of our investigation, benzene-tethered allene-yne 1a
was selected as a radical acceptor and subjected to the reaction
with p-methoxyphenyldiazonium tetrafluoroborate (2a) and
DABSO (3) in 1:2:2 mole ratio. The reaction proceeded smoothly
in 1,2-dichloroethane (DCE) at 50 oC under inner conditions,
enabling intramolecular [2 + 2] cycloaddition and radical 1,4-
addition to deliver unexpected cyclobuta[a]naphthalen-4-ol 4a in
74% yield (Table S1, entry S2). Slightly higher conversion of 1a
to 4a was observed when the reaction was performed at room
temperature (entry S2). Interestingly, the fine-tuning of the ratio of
reactants to 1:3:3 led to a remarkably higher yield (90%, entry S3).
Changing solvents to acetonitrile (CH3CN), toluene,
tetrahydrofuran (THF) and N,N-dimethylformamide (DMF)
revealed no pronounced solvent effects and thus failed to provide
enhanced yields (entries S4-S7). The reaction under aerobic
conditions gave a relatively inferior outcome as compared with Ar
conditions, although 78% yield was afforded for 4a case (entry
S8).
With these optimized reaction conditions in hand, we turned to
systematic study of generality of this reaction by examining
allene-yne and aryldiazonium tetrafluoroborate components
(Scheme 3). Allene-ynes with diverse functionalities were first
evaluated in combination with p-methoxyphenyl (PMP) diazonium
tetrafluoroborate (2a) and DABSO (3). Both electron-rich and
electron-poor substituents at different positions of the arylalkynyl
(R2) moiety could be accommodated, generating the
corresponding products 4a-4k in 52-90% yields. Moreover,
groups, such as methyl (1b and 1c), ethyl (1d), t-butyl (1e),
fluoride (1f), chloride (1g and 1h), and bromide (1i) were
compatible with these optimized conditions. The presence of
strongly electron-withdrawing groups (like fluoride) seemed to
decrease the efficiency of the reaction as shown by 4f in which a
lower yield (52%) was afforded. A sterically encumbered
naphthalen-1-yl (1-Np) counterpart was also proven to be a
suitable reaction partner, and underwent a similar cyclization
process toward the formation of cyclobuta[a]naphthalen-4-ol 4j in
78% yield. Similarly, the 2-thienyl analogue showed high reactivity,
giving access to the corresponding 2-thienyl substituted product
4k in 60% yield. Allene-ynes 1 bearing either electron-donating
(Me) or withdrawing (F and Cl) substituents (R1) at C4 or C5-
position of the internal arene ring were successfully engaged in
Scheme 3. Substrate scope for forming products 4. i) Reaction conditions:
benzene-tethered allene-ynes (1, 0.2 mmol, 1.0 equiv), aryldiazonium
tetrafluoroborates (2, 0.6 mmol), DABSO (3a, 0.6 mmol), DCE (3.0 mL), room
temperature, Ar, 5 hours. ii) Isolated yields in parentheses based on 1.
To expand the utility of this methodology, we devoted our next
efforts to exploring the diastereoselectivity of the reaction by
installing an ester group into the allene unit. As anticipated, the
reaction of the preformed benzene-linked allene-yne esters 5 with
aryldiazonium tetrafluoroborates 2 and DABSO (3) in 1:3:3 mole
ratio under the standard conditions accessed structurally diverse
cyclobuta[a]naphthalen-4-ols 6a-6y with generally good yields
and high diastereoselectivity (up to >99:1 dr) except for 6j
(Scheme 4). Allene-yne esters 5 possessing electron-neutral (H,
5a), electron-rich (Me, 5b; Et, 5c; t-Bu, 5d; and MeO, 5e) and
electron-deficient (Cl, 5f and 5g; and Br, 5h) groups attached to
the arylalkynyl (R2) moiety can participate in the current
bicyclization-addition chemistry, leading to the corresponding
products 6a-6h in 40%-92% yields and 10:1 to >99:1 dr. However,
substrate 5j with a cyclopropyl group on the alkynyl moiety was
an inefficient substrate, as the corresponding product 6j was
generated in only trace amounts. Alternatively, functional groups
(R1) including methyl, methoxy and chloro located at the internal
arene ring of substrates 5k-5m proved to be suitable for this
transformation. Furthermore, the reaction proceeded readily with
a variety of functional groups on the arene ring of aryldiazonium
tetrafluoroborates, giving access to products 6n-6y with 53-94%
the current cyclization cascades, enabling
a
metal-free
sulfonylation and diazotization approach to functionalized
cyclobuta[a]naphthalen-4-ols 4l-4p in 38%-69% yields.
Interestingly, pyridine-tethered allene-yne 1q was also smoothly
converted into cyclobuta[h]quinolin-5-ol 4q. Next, the scope with
respect to the aryldiazonium tetrafluoroborate component was
investigated. The reaction was found to tolerate various
aryldiazonium tetrafluoroborates 2b-2i carrying electron-neutral
(H, 2b), electron-rich (Me, 2c; Et, 2d; t-Bu, 2e; and EtO, 2f) and
electron-deficient (F, 2g; Cl, 2h; and Br, 2i) groups at the para-
position of the arene ring, leading to the formation of
cyclobuta[a]naphthalen-4-ols 4r-4cc with yields ranging from 41%
to 92%. However, aryldiazonium tetrafluoroborate 2j containing a
nitro group was not shown effective under the standard conditions
(Scheme 3, 4dd).
yields,
most
of
which
proceeded
with
excellent
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10.1002/anie.201707615
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diastereoselectivity (e.g., 6n-6p, 6s, and 6w-6x). The
stereoscopic structure of 6v was determined by single crystal X-
ray diffraction experiments.[14]
the reaction mechanism might involve the in situ generation of aryl
radicals. Upon treatment of 1,1-diphenylethylene and DABSO
under
standard
reaction
conditions,
(2-((4-
was
methoxyphenyl)sulfonyl)ethene-1,1-diyl)dibenzene
8
generated in 40% yield (Scheme 5b), suggesting that the
transformation involves sulfonyl radicals, derived directly from the
combination of DABSO and aryldiazonium tetrafluoroborates. As
radical acceptors, aryldiazonium salts have previously been
proven to be converted into radical cations of azo compounds via
radical cross coupling with radical species, which trend to gain an
electron to facilitate access to azo compounds through a single
electron transfer (SET) process.7 Therefore, we believe that
during this reaction, both DABSO and arylsulfonyl radicals act as
reduction reagents, and are oxidized and trapped by fluoride
anion to access sulfuryl difluoride 9 and arylsulfonyl fluoride 10
via a SET process (Scheme 5c), in which sulfuryl difluoride exists
in the gas phase. To probe the above analysis, and to support a
redox pathway, when potassium bromide (KBr) and potassium
iodide (KI) were subjected with the reaction of 1a (or 5a) with 2a
and DABSO under the standard conditions, respectively
(Schemes 5d and 5e), both sulfuryl dibromide (11) and sulfuryl
diiodide (12) were detected by LC-MS analysis.
Scheme 4. Substrate scope for forming products 6. i) Reaction conditions:
Benzene-tethered allene-yne esters (5, 0.3 mmol, 1.0 equiv), aryldiazonium
tetrafluoroborates (2, 0.9 mmol), DABSO (3a, 0.9 mmol), dry DCE (6.0 mL),
room temperature, Ar, 1 hour. ii) Isolated yields in parentheses based on 5.
Scheme 6. Plausible Reaction Pathways.
Combining analysis with previous literature reports,[5]
a
reasonable mechanism is depicted in Scheme 6. At first, the
reaction of arydiazonium cations with DABSO gives the radical
cation intermediates A, SO2, and aryl radicals via the homolytic
cleavage of the N-S bond and SET process.[5,14] Then, aryl
radicals are intercepted by SO2 to generate the sulfonyl radicals
trapped by adducts B which is generated from intramolecular [2 +
2] cycloaddition of allene-ynes 1 (or allene-yne esters 5), leading
to the formation of intermediates
C with generally high
diastereoselectivity due to steric hindrance. A subsequent radical
cross coupling between C and arydiazonium cations affords
radical cation intermediates D, followed by SET with arylsulfonyl
radicals or DABSO 3 to give cyclobuta[a]naphthalen-4(2H)-ones
E and arylsulfonyl fluoride in the presence of fluoride anion or
radical cations of DABSO. Intermediates E are converted into final
products 4 and 6 through tautomerization. In the presence of the
radical cation intermediates A and tetrafluoroborate anions,
Scheme 5. Investigation of the mechanism.
To gain mechanistic insights into this process, several control
experiments were conducted. The reaction between allene-yne
1a and 2a in the presence of 3.0 equivalents of 2,2,6,6-
tetramethyl-1-piperidinyloxy (TEMPO) afforded only a trace
amount of the expected product 4a, together with a TEMPO-PMP
adduct detected by LC-MS analysis (Scheme 5a), indicating that
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Hayter, M. C. Willis, Angew. Chem., Int. Ed. 2013, 52, 12679; c) C. S.
Richards-Taylor, D. C. Blakemore, M. C. Willis, Chem. Sci. 2014, 5, 222;
d) C. C. Chen, J. Waser, Org. Lett. 2015, 17, 736; e) D. C. Lenstra, V.
Vedovato, E. F. Flegeau, J. Maydom, and M. C. Willis, Org. Lett. 2016,
18, 2086; f) H, Wang, Q.-q. Lu, C.-W. Chiang, Y. Luo, J.-F. Zhou, G.-Y.
Wang, A. Lei, Angew. Chem., Int. Ed. 2017, 56, 595; g) W. Wei, J.-W
Wen, D.-S Yang, M.-Y Guo, Y. -Y Wang, J. -M You and H. Wang, Chem.
Commun. 2015, 51, 768; h) L. -L Wang, H. -L Yue, D. -S. Yang, H. -H
Cui, M. -H, Zhu, J. -M Wang, W. Wei, H. Wang, J. Org. Chem. 2017, 82,
6857.
radical cations of DABSO are transformed into sulfuryl difluorides
and DABCO through a SET process. In addition, the potential
formation of O-centered radicals from D via H abstraction may
react with DABSO to deliver the sulfonate products, followed by
nucleophilic substitution with fluoride anion to final products 4 or
6.
In conclusion, we have established an unprecedented [2 + 2]
cycloaddition/S-centered radical-induced 1,4-addition cascade of
benzene-linked allene-ynes (or allene-yne esters) under mild and
redox neutral conditions. Notably, aryldiazonium salts play dual
roles in both the initiation and termination of this reaction, allowing
both sulfonyl and azo functionality to be installed into the
molecular frameworks via radical cascade processes. The former
enabled direct metal-free insertion of SO2 with allene-ynes into
cyclobuta[a]naphthalen-4-ols with a wide diversity in substituents
with concomitant construction of multiple C−C, C-S and C−N
bonds; the latter led to highly diastereoselective formation of
cyclobuta[a]naphthalen-4-ols by treating aryldiazonium salt and
DABSO with allene-yne esters in a one-pot protocol. The present
reaction provides a convenient and metal-free approach to a
range of richly decorated cyclobuta[a]naphthalen-4-ols with
sulfone and azo functionalities. Further investigation of its
mechanism and applications will be reported in due course.
[5]
[6]
a) Y. Luo, X. Pan, C. Chen, L. Yao and J. Wu, Chem. Commun. 2015,
51, 180; b) D. Zheng, J. Yu, and J. Wu, Angew. Chem., Int. Ed. 2016, 55,
11925; c) Y. Xiang, Yunyan K., Jie W., Chem.– Eur. J. 2017, 23, 6996;
d) K. Zhou, H. Xia, J. Wu, Org. Chem. Front. 2017, 4, 1121.
a) K. Hunger, Industrial Dyes: Chemistry, Properties, Applications; Wiley-
VCH: Weinheim, 2003; b) G. S. Kumar, D. C. Neckers, Chem. Rev. 1989,
89, 1915; c) T. J. Ikeda, Mater. Chem. 2003, 13, 2037; d) T. Fehrentz, M.
Schꢀnberger, D. Trauner, Angew. Chem., Int. Ed. 2011, 50, 12156; e) A.
A. Beharry, G. A. Woolley, Chem. Soc. Rev. 2011, 40, 4422.
[7]
[8]
H. Jiang, Y. Chen, B. Chen, H. Xu, W. Wan, H. Deng, K. Ma, S. Wu, and
J. Hao, Org. Lett. 2017, 19, 2406.
For selected reviews and examples, see: a) B. B. Snider, Chem. Rev.
1996, 96, 339; b) A. J. Clark, Chem. Soc. Rev. 2002, 31, 1; c) H. Yi, G.
Zhang, H. Wang, Z. Huang, J. Wang, A. K. Singh, A. Lei, Chem. Rev.
2017, 117, 9016; d) H. Miyabe, A. Kawashima, E. Yoshioka, S. Kohtani,
Chem. – Eur. J. 2017, 23, 6225; e) J.-R. Chen, X.-Q. Hu, L.-Q. Lu, W.-J.
Xiao, Acc. Chem. Res. 2016, 49, 1911; f) J. Xuan, A. Studer, Chem. Soc.
Rev. 2017, 46, 4329; (g) A. Studer, D. P. Curran, Angew. Chem., Int. Ed.
2016, 55, 58; (h) D. Alpers, M. Gallhof, J. Witt, F. Hoffmann, M. Brasholz,
Angew. Chem., Int. Ed. 2017, 56, 1402.
Acknowledgements
[9]
For selected reviews, see: a) A. J. Clark, Eur. J. Org. Chem. 2016, 13,
2231; b) J.-T. Yu, C. Pan, Chem. Commun. 2016, 52, 2220. For selected
examples, see: c) M. Hu, J.-H. Fan, Y. Liu, X.-H. Ouyang, R.-J. Song, J.-
H. Li, Angew. Chem., Int. Ed. 2015, 54, 9577; d) M. Hu, R.-J. Song, J.-
H. Li, Angew. Chem., Int. Ed. 2015, 54, 608; e) W. Kong, N. Fuentes, A.
García-Domínguez, E. Merino, C. Nevado, Angew. Chem. Int. Ed. 2015,
54, 2487; f) N. Fuentes, W. Kong, L. Fernꢁndez-Sꢁnchez, E. Merino, and
C. Nevado, J. Am. Chem. Soc. 2015, 137, 964.
We are grateful for financial support from the NSFC (Nos.
21332005, 21232004, and 21472071), PAPD of Jiangsu Higher
Education Institutions, the Outstanding Youth Fund of JSNU
(YQ2015003), NSF of Jiangsu Province (BK20151163), Robert A.
Welch Foundation (D-1361, USA), Texas Tech University
research promotion fund (to BJ).
[10] J. Sun, J.-K. Qiu, Y.-N. Wu, W.-J. Hao, C. Guo, G. Li, S.-J. Tu, and B.
Jiang, Org. Lett. 2017, 19, 754.
Keywords: [2 + 2] Cycloaddition • Radical 1,4-Addition •
Sulfonylation • Diazotization • Allene-ynes
[11] a) J.-K. Qiu, B. Jiang, Y.-L. Zhu, W.-J. Hao, D.-C. Wang, J. Sun, P. Wei,
S.-J. Tu, G. Li, J. Am. Chem. Soc. 2015, 137, 8928; b) Z.-Z. Chen, S. Liu,
W.-J. Hao, G. Xu, S. Wu, J.-N. Miao, B. Jiang, S.-L. Wang, S.-J. Tu, G.
Li, Chem. Sci. 2015, 6, 6654; c) Y.-L. Zhu, B. Jiang, W.-J. Hao, J.-K. Qiu,
J. Sun, D.-C. Wang, P. Wei, A.-F. Wang, G. Li, S.-J. Tu, Org. Lett. 2015,
17, 6078; d) Y.-L. Zhu, B. Jiang, W.-J. Hao, A.-F. Wang, Qiu, J.-K. P.
Wei, D.-C. Wang, G. Li, S.-J. Tu, Chem. Commun. 2016, 52, 1907.
[12] H. Wei, H. Zhai, P.-F. Xu, J. Org. Chem. 2009, 74, 2224.
[13] For selected examples, see: a) Q. Shen, G. B. Hammond, J. Am. Chem.
Soc. 2002, 124, 6534; b) H. Ohno, T. Mizutani, Y. Kadoh, K. Miyamura,
T. Tanaka, Angew. Chem., Int. Ed. 2005, 44, 5113; c) M. R. Siebert, J.
M. Osbourn, K. M. Brummond, D. J. Tantillo, J. Am. Chem. Soc. 2010,
132, 11952; d) B.-L. Lu, M. Shi, Angew. Chem., Int. Ed. 2011, 50, 12027;
e) K. M. Brummond, D. Chen, Org. Lett. 2005, 7, 3473; f) S. Yang, Q. Xu,
M. Shi, Tetrahedron 2016, 72, 584; g) H. Ohno, T. Mizutani, Y. Kadoh,
A. Aso, K. Miyamura, N. Fujii, T. Tanaka, J. Org. Chem. 2007, 72, 4378.
[14] CCDC 1563761 (4u), 1563762 (6u) and 1563763 (7，see Supporting
Information) contain the supplementary crystallographic data for this
paper. These data can be obtained free of charge from The Cambridge
Crystallographic Data Centre.
References
[1]
a) Y. Harrak, G. Casula, J. Basset, G. Rosell, S. Plescia, D. Raffa, M. G.
Cusimano, R. Pouplana, M. D. Pujol, J. Med. Chem. 2010, 53, 6560; b)
D. A. Smith, R. M. Jones, Curr. Opin. Drug Discovery Dev. 2008, 11, 72;
c) Y. Noutoshi, M. Ikeda, T. Saito, H. Osada, K. Shirasu, Front. Plant Sci.
2012, 3, 245; d) J. Drews, Science 2000, 287, 1960.
[2]
P. Prasit, Z. Wang, C. Brideau, C. C. Chan, S. Charleson, J. Y. Gauthier,
R. Gordon, J. Guay, M. Gresser, S. Kargman, B. Kennedy, Y. Leblanc,
S. Leger, J. Mancini, G. P. O’Neill, M. Ouellet, M. D. Percival, H. Perrier,
D. Riendeau, I. Rodger, P. Tagari, M. Therien, P. Vickers, E. Wong, L. J.
Xu, R. N. Young, R. Zamboni, Bioorg. Med. Chem. Lett. 1999, 9, 1773;
b) M. Artico, R. Silvestri, E. Pagnozzi, B. Bruno, E. Novellino, G. Greco,
S. Massa, A. Ettorre, A. Giulia Loi, F. Scintu, P. La Colla, J. Med. Chem.
2000, 43, 1886; c) R. L. Lopez de Compadre, A. Pearlstein, R. A. J.
Hopfinger, J. K. Seyde, J. Med. Chem. 1987, 30, 900.
[3]
[4]
P. Tfelt-Hansen, P. De Vries, P. R. Saxena, Drugs 2000, 60, 1259; b) P.
F. Schnellhammer, Expert Opin. Pharmacother. 2002, 3, 1313; c) G.
Mitchell, D. W. Bartlett, T. E. M. Fraser, T. R. Hawkes, D. C. Holt, J. K.
Townson and R. A. Wichert, Pest Manage. Sci. 2001, 57, 120; d) P.
Boger, J. Pestic. Sci. 2003, 28, 324.
[15] F. Eugène, B. Langlois, E. Laurent, J. Org. Chem. 1994, 59, 2599.
For selected examples, see: a) S. Deeming, A. Russell, A. J. C. J.
Hennessy, M. C. Willis, Org. Lett. 2014, 16, 150; b) E. J. Emmett, B. R.
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Entry for the Table of Contents (Please choose one layout)
Layout 2:
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Feng Liu, Jia-Yin Wang, Peng Zhou,
Guigen Li,* Wen-Juan Hao, Shu-Jiang
Tu,* and Bo Jiang*
Page No. – Page No.
Merging [2 + 2] Cycloaddition with
Radical 1,4-Addition: Metal-Free
Access to Functionalized
Cyclobuta[a]naphthalen-4-ols
A new metal-free [2 + 2] cycloaddition/S-centered radical-induced 1,4-addition
cascades of benzene-linked allene-ynes has been established by treatment with
aryldiazonium tetrafluoroborates and DABCO-bis(sulfur dioxide) under convenient
conditions, providing a practical access to functionalized cyclobuta[a]naphthalen-4-
ols of chemical and biomedical importance.
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