Synthesis of Benzo[b]fluoranthenes and Spiroacridines from Fluorene-Derived Alkenes and N-Arylimines via a Tandem Reaction with Benzynes

Article abstract of DOI:10.1021/acs.orglett.9b00659

Two tandem processes involving the cycloaddition of benzynes have been developed for the synthesis of polyaromatic hydrocarbons. Benzynes react with fluorene-derived alkenes through a tandem Diels-Alder reaction/dehydrogenation process to afford benzo[b]f

Full text of DOI:10.1021/acs.orglett.9b00659

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Synthesis of Benzo[b]fluoranthenes and Spiroacridines from
Fluorene-Derived Alkenes and N‑Arylimines via a Tandem Reaction
with Benzynes
Weihua Wang, Hongwei Wan, Guangfen Du, Bin Dai, and Lin He*
Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical
Engineering, Shihezi University, Shihezi, Xinjiang Uygur Autonomous Region 832000, China
S
* Supporting Information
ABSTRACT: Two tandem processes involving the cyclo-
addition of benzynes have been developed for the synthesis of
polyaromatic hydrocarbons. Benzynes react with fluorene-derived
alkenes through a tandem Diels−Alder reaction/dehydrogen-
ation process to afford benzo[b]fluoranthenes in 35−87% yields.
In addition, an unprecedented [2 + 2] cycloaddition/ring-
opening sequence of benzynes and fluorene-derived N-arylimines
provides facile access to spiroacridines in 38−79% yields.
he past two decades have witnessed remarkable progress
in benzyne chemistry.1 As one of the most reactive
remarkable progress made in this research field, development
of an efficient and straightforward method for the synthesis of
PAHs and SPAHs via the cyclization of benzynes is still highly
desirable.
T
organic species, benzyne has been used widely in synthetic
chemistry, medicinal chemistry, and advanced functional
materials. Owing to their distinct electronic properties,
benzynes can serve as dienophiles in a series of pericyclic
reactions,2 insertion-cyclizaton,3 and multicomponent coupling
reactions.4 In particular, the Diels−Alder reaction of benzynes5
provides a powerful tool for the rapid construction of various
carbocycles and heterocycles.
With our continuing interest in benzyne chemistry14 and
spirofluorene chemistry,15 we postulated that benzynes could
undergo [4 + 2] cycloaddition with fluorene-derived alkenes to
form intermediate A, the dehydrogenation of which would lead
to the formation of benzo[b]fluoranthene (Scheme 1).
Both polycyclic aromatic hydrocarbons (PAH) and spiro-
functionalized polycyclic aromatic hydrocarbons (SPAH) are
important structural motifs found in many natural products
and biologically active compounds.6 In particular, owing to
their unique photophysical and electrochemical properties,
these versatile molecules have been utilized widely in
optoelectronic materials.7 Therefore, the development of
efficient methods for the synthesis of PAHs and SPAHs is
highly desirable. In 2007, Xie and Zhang8 reported the
synthesis of anthracene derivatives via a tandem reaction of
Scheme 1. Working Hypothesis
We first tested the Diels−Alder reaction of fluorene-derived
alkene 1a with 1.5 equiv of Kobayashi’s reagent16 2a and 4.5
equiv of CsF in acetonitrile at room temperature. Indeed, the
desired PAH product 3a was successfully obtained in 29% yield
(Table 1, entry 1). When KF/18-crown-6 was substituted for
CsF, only 18% yield was obtained (Table 1, entry 2). Other
fluoride sources, such as TBAF, TMAF, and TBAT, only led to
the generation of a trace amount of 3a (Table 1, entries 3−5).
The yield of the product increased to 39% when 3.0 equiv of
benzyne precursor 2a and 12.0 equiv of CsF were used (Table
1, entry 6). A brief screening of the reaction solvent showed
that THF gave the greatest reaction yield (Table 1, entries 7−
10). In separate attempts, raising the reaction temperature to
70 °C or lowering the reaction temperature to 0 °C did not
imidazole and benzyne that involves a Diels−Alder reaction. In
9
́
2010, Guitian and co-workers developed a domino Diels−
Alder reaction of benzyne for the preparation of perylene
derivatives. Subsequently, the same group10 further reported
that perylene operated as a diene to undergo a Diels−Alder
reaction with benzyne. Following Pd-catalyzed trimerization,
this afforded a 22-ring aromatic hydrocarbon. Recently, Biju
and co-workers11 reported an efficient Diels−Alder reaction
between benzyne and styrenes for the construction of
dihydropheanthrenes. Very recently, Pen
̃
a and co-workers12
developed a novel [4 + 2] cycloaddition/on-surface deoxyge-
nation cascade process of benzynes, which provided facile
access to decacene. In addition, Gidron and co-workers13
reported an interesting sequential Diels−Alder reaction of
benzynes and oligofurans to construct oligoarenes. Despite
Received: February 21, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b00659
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
a
Table 1. Optimization of Reaction Conditions
Scheme 2. Synthesis of Benzo[b]fluoranthene
b
time
(h)
temp
(°C)
yield
entry
solvent
additives
(%)
c
1
CH3CN CsF (4.5 equiv)
CH3CN KF+18-C-6 (4.5 equiv)
CH3CN TBAT (4.5 equiv)
CH3CN TBAF (4.5 equiv)
CH3CN TMAF (4.5 equiv)
CH3CN CsF (12.0 equiv)
60
60
30
60
60
40
45
60
36
70
40
136
36
rt
rt
rt
rt
rt
rt
rt
rt
rt
rt
70
0
29
18
trace
trace
trace
39
trace
45
trace
trace
23
c
2
c
3
c
4
5
6
7
8
DCM
THF
toluene
DMF
THF
CsF (12.0 equiv)
CsF (12.0 equiv)
CsF (12.0 equiv)
CsF (12.0 equiv)
CsF (12.0 equiv)
CsF (12.0 equiv)
9
10
11
12
13
THF
44
37
THF
CsF (12.0 equiv), Cs2CO3
(1.0 equiv)
rt
14
15
16
17
18
19
20
21
22
THF
THF
THF
THF
THF
THF
THF
THF
THF
CsF (12.0 equiv), MnO2
(15.0 equiv)
CsF (12.0 equiv), MnO2
(15.0 equiv)
CsF (12.0 equiv), DDQ
(15.0 equiv)
CsF (12.0 equiv), Bu4NI
(15.0 equiv)
CsF (12.0 equiv), KHSO5
(15.0 equiv)
CsF (12.0 equiv), KMnO4
(15.0 equiv)
CsF (12.0 equiv), K2Cr2O7
(15.0 equiv)
CsF (12.0 equiv), K2S2O8
(15.0 equiv)
48
48
48
48
48
48
48
48
48
rt
38
85
70
70
70
70
70
70
70
70
trace
11
<10
<10
12
45
CsF (12.0 equiv), KClO3
(15.0 equiv)
10
23
24
THF
THF
CsF (12.0 equiv), O2
CsF (12.0 equiv), MnO2
(10.0 equiv)
48
48
70
70
13
58
a
General conditions: 1 (0.10 mmol), 2 (0.30 mmol), CsF (1.20
mmol), MnO2 (1.50 mmol), anhydrous tetrahydrofuran (2.0 mL), 70
25
THF
CsF (12.0 equiv), MnO2
(20.0 equiv)
48
70
71
b
°C, and 48 h. The yields reported are isolated yields. Regioisometric
1
a
ratio (r.r.) was determined by H NMR analysis.
Standard conditions: 1a (0.10 mmol), 2a (0.30 mmol), solvent: 2.0
mL. MnO2 (commercial manganese dioxide was calcined in a muffle
furnace under air at 200 °C for 5 h with a heating rate of 5 °C/min).
corresponding PAH products in high yields (Scheme 2, 3a−
3e). The electronic properties and substitution positions of the
substituents had no apparent impact on the reaction yield
(Scheme 2, 3f−3l). Bulky naphthyl-derived alkene 1m
underwent the cycloaddition in moderate yield (Scheme 2,
3m). In addition, the heteroaryl-derived dienes17 coupled with
benzyne smoothly to afford 3n and 3o in 74 and 48% yields,
respectively (Scheme 2, 3n−3o). Notably, alkyl-substituted
alkenes were competent substrates for the reaction, producing
the corresponding products in good yields (Scheme 2, 3p−
3q). Symmetrical benzynes with electron-withdrawing or
electron-donating substituents efficiently coupled with a
fluorene-derived alkene to provide the desired products in
moderate to good yields (Scheme 2, 3r−3t). Unsymmetrical 3-
methoxybenzyne, α,β-naphthalene, and 3-methylbenzyne
performed the cycloaddition well to furnish the corresponding
PAHs with excellent regioselectivity (Scheme 2, 3u−3w).
When unsymmetrical 4-chlorobenzyne was employed for the
reaction, two regioisomers were obtained as an inseparable
b
c
Isolated yield. 1a (0.10 mmol), 2a (0.15 mmol).
improve the reaction yield (Table 1, entries 11 and 12), and
the addition of a base or an oxidant had no apparent effect
(Table 1, entries 13 and 14). However, to our great delight, on
the addition of 15.0 equiv of MnO2, the reaction proceeded
efficiently in THF at 70 °C, affording 3a in 85% yield (Table 1,
entry 15). Encouraged by this success, other common organic
and inorganic oxidants were subsequently evaluated for the
cycloaddition. Unfortunately, only K2S2O8 promoted the
reaction, whereas other oxidants proved to be inefficient
(Table 1, entries 16−23). Surprisingly, both increasing and
reducing the amount of MnO2 lowered the yield of 3a (Table
1, entries 24 and 25).
Having evaluated the optimal reaction conditions, we then
explored the substrate scope of this reaction (Scheme 2). Both
electron-donating- and electron-withdrawing-group-substituted
alkenes participated in the cycloaddition well, producing the
B
DOI: 10.1021/acs.orglett.9b00659
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
mixture with 44% overall yield (Scheme 2, 3x/3x′). The 2,7-
dibromofluorene-derived alkene reacted with benzyne to afford
dibromo-substituted benzo[b]fluoranthene 3y in 56% yield
(Scheme 2, 3y).
Scheme 4. Synthesis of Spiroacridines
The structure of 3a was unambiguously confirmed by single
crystal X-ray analysis (Figure 1). (See the back matter of this
paper for relevant CCDC codes).
Figure 1. Single crystal X-ray structure for 3a.
Benzynes can undergo aza-Diels−Alder reactions or [2 + 2]
cycloadditions with imines and 2-aza-dienes.18 In order to
further demonstrate the application of our method, the
cycloaddition between fluorene-derived N-aryl imines and
benzynes was next investigated (Scheme 3). To our surprise,
a
General conditions: 4 (0.10 mmol), 2 (0.15 mmol), KF + 18-C-6
(0.45 mmol), anhydrous acetonitrile (2.0 mL), 81 °C, and 24 h. The
Scheme 3. Reaction Mechanism
b
yields reported are isolated yields. Regioisometric ratio (r.r.) was
1
determined by H NMR analysis.
For imine 4f, there is only one N-ortho position on the N-aryl
ring that can undergo nucleophilic attack at the azetidine ring.
Therefore, spiroacridine 5f was furnished as the only product
(Scheme 4, 5f). On the other hand, imine 4g has two N-ortho
positions on the N-aryl ring, so the formation of inseparable
regioisomers 5g and 5g′ in a 2:1 ratio was achieved with 75%
overall yield (Scheme 4, 5g and 5g′). Owing to the steric
hindrance of the bulky isopropyl group, 5h was afforded as the
only regioisomer in 45% yield when imine 4h was employed
for the reaction (Scheme 4, 5h). Dimethyl- and difluoro-
substituted symmetrical benzynes provided the corresponding
spiroacridines in moderate yields (Scheme 4, 5g−5i). Once
again, the use of the unsymmetrical 3-methoxybenzyne led to
complete regioselectivity and yielded 5j as the sole product
(Scheme 4, 5j). Unsymmetrical 4-chlorobenzyne and α,β-
naphthlene underwent the reaction to afford the corresponding
products in 65 and 79% yield, respectively with moderate
regioselectivity (Scheme 4, 5d/5d′ and 5k/5k′). In both cases,
the major regioisomer could be isolated by column
chromatography. Dibromo-substituted imine 4l was also
employed for the cascade process, and the desired product
5l was isolated in 38% yield (Scheme 4, 5l).
The structure of 5b was also confirmed by X-ray
crystallographic analysis (Figure 2). (See the back matter of
this paper for relevant CCDC codes).
In order to shed light on the reaction mechanism, several
other imines were prepared and tested for the tandem reaction
with benzyne (Scheme 5). Both of the N-ortho positions of the
N-aryl ring in substrate 4m, derived from mesidine, are
blocked by methyl groups, and no desired spiroacridine was
detected (Scheme 5, eq 1). Fluorene-derived N-alkyl imine 4n
neither [4 + 2] or [2 + 2] cycloaddition products were
observed, and an unexpected spiroacridine 5a was obtained as
the major product. We postulated that benzyne undergoes [2 +
2] cycloaddition with imine 4a to generate an azetidine
intermediate B. The high ring strain of the four-membered ring
then enables a fast intramolecular ring-opening reaction
through the nucleophilic attack of the N-ortho position of
the N-aryl ring and forms a quinomethide imine intermediate
C. The subsequent intramolecular aza-Diels−Alder reaction of
C leads to the formation of D, and afterward, the fluoride
anion assisted tautomerization to produce spiroacridine 5a
(Scheme 3).
After a brief screening of different reaction parameters,19
including the fluoride source, solvent, temperature, and molar
ratio of reactants, the optimal reaction conditions were
evaluated as 1.5 equiv of benzyne precursor 2 and 4.5 equiv
of KF/18-crown-6 at 81 °C in acetonitrile. The generality of
the reaction was then examined under the optimized reaction
conditions. As shown in Scheme 4, fluorene-derived imines
with both electron-donating and electron-withdrawing sub-
stituents on the N-aryl ring afforded the corresponding
products in moderate to good yields (Scheme 4, 5b−5e).
C
DOI: 10.1021/acs.orglett.9b00659
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44
1223 336033.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: helin@shzu.edu.cn.
ORCID
Bin Dai: 0000-0001-9254-6606
Lin He: 0000-0003-1767-9980
Notes
Figure 2. Single crystal X-ray structure for 5b.
The authors declare no competing financial interest.
Scheme 5. Investigation of Different Imine Substrates
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (No. 21462034), the Excellent Young
Teachers Plan of Bingtuan (2017CB001, CZ027203), and the
International Cooperation Project of Shihezi University
(No.GJHZ201801). We also thank Ms. C. Gregson of
University of Bristol for proofreading of this paper.
REFERENCES
■
(1) For reviews on benzynes, see: (a) Bhojgude, S. S.; Bhunia, A.;
Biju, A. T. Acc. Chem. Res. 2016, 49, 1658−1670. (b) Bhunia, A.;
Yetra, S. R.; Biju, A. T. Chem. Soc. Rev. 2012, 41, 3140−3152.
(c) Bhojgude, S. S.; Biju, A. T. Angew. Chem., Int. Ed. 2012, 51, 1520−
1522. (d) Tadross, P. M.; Stoltz, B. M. Chem. Rev. 2012, 112, 3550−
3577. (e) Dubrovskiy, A. V.; Markina, N. A.; Larock, R. C. Org.
Biomol. Chem. 2013, 11, 191−218. (f) Wu, C.; Shi, F. Asian J. Org.
Chem. 2013, 2, 116−125. (g) Roy, T.; Biju, A. T. Chem. Commun.
2018, 54, 2580−2594. (h) Shi, J.-R.; Li, Y.-Y.; Li, Y. Chem. Soc. Rev.
2017, 46, 1707−1719. (i) Takikawa, H.; Nishii, A.; Sakai, T.; Suzuki,
has no N-aryl group and therefore cannot undergo the tandem
reaction (Scheme 5, eq 2). In contrast to fluorene-derived N-
aryl imines, benzophenone-derived imine 4o and cyclo-
pentanone-derived imine 4p gave no desired product (Scheme
5, eqs 3, 4). This result indicates that the nature of the fluorene
structure palys a crucial role to the success of the tandem
reactions.
In conclusion, we have developed an efficient and
straightforward method for the synthesis of benzo[b]-
fluoranthenes via a tandem Diels−Alder reaction/dehydrogen-
ation of benzynes and fluorene-derived alkenes. We have also
described a novel protocol for the preparation of spiroacridines
that proceeds via a [2 + 2] cycloaddition/ring-opening
sequence. This strategy provides a powerful tool for the
construction of valuable polyaromatic skeletons. Further
studies on a broader substrate scope and the application of
this strategy are currently underway in our laboratory.
́
K. Chem. Soc. Rev. 2018, 47, 8030−8056. (j) García-Lopez, J.-A.;
Greaney, M. F. Chem. Soc. Rev. 2016, 45, 6766−6798.
(2) For selected examples, see: (a) Shi, F.; Waldo, J. P.; Chen, Y.;
Larock, R. C. Org. Lett. 2008, 10, 2409−2412. (b) Fang, Y.; Larock, R.
C.; Shi, F. Asian J. Org. Chem. 2014, 3, 55−57. (c) Ikawa, T.; Takagi,
A.; Goto, M.; Aoyama, Y.; Ishikawa, Y.; Itoh, Y.; Fujii, S.; Tokiwa, H.;
Akai, S. J. Org. Chem. 2013, 78, 2965−2983. (d) Swain, S. P.; Shih, Y.
C.; Tsay, S. C.; Jacob, J.; Lin, C. C.; Hwang, K. C.; Horng, J. C.; Hwu,
J. R. Angew. Chem., Int. Ed. 2015, 54, 9926−9930. (e) Gouthami, P.;
Chavan, L. N.; Chegondi, R.; Chandrasekhar, S. J. Org. Chem. 2018,
83, 3325−3332. (f) Corsello, M. A.; Kim, J.-Y.; Garg, N. K. Nat.
Chem. 2017, 9, 944−949. (g) Li, Y.-M.; Muck-Lichtenfeld, C.; Studer,
̈
A. Angew. Chem., Int. Ed. 2016, 55, 14435−14438.
(3) For selected examples of the insertion-cyclization reaction of
benzynes, see: (a) Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am.
Chem. Soc. 2008, 130, 1558−1559. (b) Li, Y.-Y.; Qiu, D.-C.; Gu, R.-
R.; Wang, J.-L.; Shi, J.-R.; Li, Y. J. Am. Chem. Soc. 2016, 138, 10814−
10817. (c) Shi, J.-R.; Qiu, D.-C.; Wang, J.; Xu, H.; Li, Y. J. Am. Chem.
Soc. 2015, 137, 5670. (d) Rao, B.; Tang, J.; Wei, Y.; Zeng, X. Chem. -
Asian J. 2016, 11, 991. (e) Rao, B.; Tang, J.; Zeng, X. Org. Lett. 2016,
18, 1678−1681. (f) Sundalam, S. K.; Nilova, A.; Seidl, T. L.; Stuart, D.
R. Angew. Chem., Int. Ed. 2016, 55, 8431−8434. (g) Thangaraj, M.;
Bhojgude, S. S.; Jain, S.; Gonnade, R. G.; Biju, A. T. J. Org. Chem.
2016, 81, 8604−8611. (h) Tao, Y.; Zhang, F.; Tang, C.-Y.; Wu, X.-Y.;
Sha, F. Asian J. Org. Chem. 2014, 3, 1292−1301. (i) Li, B.-N.; Mai, S.-
Y.; Song, Q.-L. Org. Chem. Front. 2018, 5, 1639−1642. (j) Xu, D.-Y.;
Zhao, Y.-L.; Song, D.-P.; Zhong, Z.-L.; Feng, S.-B.; Xie, X.-G.; Wang,
X.-L.; She, X.-G. Org. Lett. 2017, 19, 3600−3603. (k) Mei, G.-J.; Xu,
S.-L.; Zheng, W.-Q.; Bian, C.-Y.; Shi, F. J. Org. Chem. 2018, 83, 1414−
1421. (l) Torres-Ochoa, R. O.; Buyck, T.; Wang, Q.; Zhu, J.-P. Angew.
Chem., Int. Ed. 2018, 57, 5679−5683. (m) Huang, X.; Zhang, T. J.
Org. Chem. 2010, 75, 506−509. (n) Dubrovskiy, A. V.; Larock, R. C.
Org. Lett. 2010, 12, 3117−3119. (o) Fang, Y.; Rogness, D. C.; Larock,
R. C.; Shi, F. J. Org. Chem. 2012, 77, 6262−6270.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b00659.
Experimental details and spectroscopic data (PDF)
Accession Codes
CCDC 1891551, 1891561, and 1908380−1908382 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
D
DOI: 10.1021/acs.orglett.9b00659
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
́
(10) Schuler, B.; Collazos, S.; Gross, L.; Meyer, G.; Perez, D.;
(4) For selected examples of multicomponent reactions of benzynes,
see: (a) Suh, S.-E.; Chenoweth, D. M. Org. Lett. 2016, 18, 4080−
4083. (b) Bhojgude, S. S.; Baviskar, D. R.; Gonnade, R. G.; Biju, A. T.
Org. Lett. 2015, 17, 6270−6273. (c) Zeng, Y.-W.; Li, G.-Y.; Hu, J.-B.
Angew. Chem., Int. Ed. 2015, 54, 10773−10777. (d) Sha, F.; Huang, X.
Angew. Chem., Int. Ed. 2009, 48, 3458. (e) Yoshida, H.; Asatsu, Y.;
Mimura, Y.; Ito, Y.; Ohshita, J.; Takaki, K. Angew. Chem., Int. Ed.
2011, 50, 9676. (f) Wang, Z.; Addepalli, Y.; He, Y. Org. Lett. 2018, 20,
644−647. (g) Singh, R.; Nagesh, K.; Yugandhar, D.; Prasanthi, A. V.
G. Org. Lett. 2018, 20, 4848−4853. (h) Tan, J.-J.; Liu, B.-B.; Su, S.-S.
Org. Chem. Front. 2018, 5, 3093−3097. (i) Ross, S. P.; Hoye, T. R.
Org. Lett. 2018, 20, 100−103. (j) Xiao, X.; Woods, B. P.; Xiu, W.;
Hoye, T. R. Angew. Chem., Int. Ed. 2018, 57, 9901−9905. (k) Zheng,
T.; Tan, J.-J.; Fan, R.; Su, S.; Liu, B.; Tan, C.; Xu, K. Chem. Commun.
2018, 54, 1303−1306. (l) Chen, J.-H.; Palani, V.; Hoye, T. R. J. Am.
Chem. Soc. 2016, 138, 4318−4321.
́
Guitian, E.; Pena, D. Angew. Chem., Int. Ed. 2014, 53, 9004−9006.
̃
(11) Bhojgude, S. S.; Bhunia, A.; Gonnade, R. G.; Biju, A. T. Org.
Lett. 2014, 16, 676−679.
̈
(12) Kruger, J.; García, F.; Eisenhut, F.; Skidin, D.; Alonso, J. M.;
́
́
Guitian, E.; Perez, D.; Cuniberti, G.; Moresco, F.; Pena, D. Angew.
̃
Chem., Int. Ed. 2017, 56, 11945−11948.
(13) Gadakh, S.; Shimon, L. J. W.; Gidron, O. Angew. Chem., Int. Ed.
2017, 56, 13601−13605.
(14) (a) Pian, J.-X.; He, L.; Du, G.-F.; Guo, H.; Dai, B. J. Org. Chem.
2014, 79, 5820−5826. (b) He, L.; Pian, J.-X.; Shi, J.-F.; Du, G.-F.;
Dai, B. Tetrahedron 2014, 70, 2400−2405. (c) Liu, K.; Liu, L.-L.; Gu,
C.-Z.; Dai, B.; He, L. RSC Adv. 2016, 6, 33606−33610. (d) Jian, H.;
Wang, Q.; Wang, W.-H.; Li, Z.-J.; Gu, C.-Z.; Dai, B.; He, L.
Tetrahedron 2018, 74, 2876−2883. (e) Li, Z.-J.; Wang, W.-H.; Jian,
H.; Li, W.-J.; Dai, B.; He, L. Chin. Chem. Lett. 2019, 30, 386−388.
(15) Xing, F.; Feng, Z.-N.; Wang, Y.; Du, G.-F.; Gu, C.-Z.; Dai, B.;
He, L. Adv. Synth. Catal. 2018, 360, 1704−1710.
(16) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
12, 1211−1214.
(17) Fluorene-derived alkenes involving other heterocycles, such as
furan, pyrrole, pyridine, and thiazole, were also tested for the reaction,
but we did not get the desired products. See the Supporting
Information for details.
(5) For selected examples of Diels−Alder reactions of benzynes, see:
(a) Li, J.; Wang, N.; Li, C.; Jia, X. Org. Lett. 2012, 14, 4994.
(b) Siyang, H.-X.; Wu, X.; Liu, H.; Wu, X.; Liu, P. J. Org. Chem. 2014,
79, 1505−1510. (c) Su, S.; Wang, N.; Li, C.; Song, B.; Jia, X.; Li, J.
Asian J. Org. Chem. 2014, 3, 269−272. (d) Castillo, J. C.; Quiroga, J.;
Abonia, R.; Rodriguez, J.; Coquerel, Y. Org. Lett. 2015, 17, 3374−
3377. (e) Reddy, R. S.; Lagishetti, C.; Chen, S.; Kiran, I. N. C.; He, Y.
Org. Lett. 2016, 18, 4546−4549. (f) Bhojgude, S. S.; Thangaraj, M.;
(18) (a) Nakayama, J.; Midorikawa, H.; Yoshida, M. Bull. Chem. Soc.
Jpn. 1975, 48, 1063. (b) Fishwick, C. W. G.; Gupta, R. C.; Storr, R. C.
J. Chem. Soc., Perkin Trans. 1 1984, 1, 2827. (c) Aly, A. A.; Mohamed,
N. K.; Hassan, A. A.; Mourad, A.-F. E. Tetrahedron 1999, 55, 1111.
(d) Singal, K. K.; Kaur, J. Synth. Commun. 2001, 31, 2809. (e) Aly, A.
A.; Mourad, A.-F. E.; El-Shaieb, K. M.; Hopf, H. Synth. Commun.
2001, 31, 637. (f) Shou, W.-G.; Yang, Y.-Y.; Wang, Y.-G. J. Org. Chem.
2006, 71, 9241. (g) Castillo, J.-C.; Quiroga, J.; Abonia, R.; Rodriguez,
J.; Coquerel, Y. Org. Lett. 2015, 17, 3374. (h) Castillo, J.-C.; Quiroga,
J.; Abonia, R.; Rodriguez, J.; Coquerel, Y. J. Org. Chem. 2015, 80,
9767. (i) Chen, J.-D.; Chen, Y.-L.; Wang, X.-L.; Kong, K.-D.; Cao, W.-
G.; Chen, J. Tetrahedron 2015, 71, 5130−5136. (j) Kiran, I. N. C.;
Reddy, R. S.; Lagishetti, C.; Xu, H.-C.; Wang, Z.; He, Y. J. Org. Chem.
2017, 82, 1823−1832. (k) Kopchuk, D. S.; Nikonov, I. L.; Khasanov,
A. F.; Giri, K.; Santra, S.; Kovalev, I. S.; Nosova, E. V.; Gundala, S.;
Venkatapuram, P.; Zyryanov, G. V.; Majee, A.; Chupakhin, O. N. Org.
Biomol. Chem. 2018, 16, 5119−5135. (l) Reddy, R. S.; Lagishetti, C.;
Chen, S.; Kiran, I. N. C.; He, Y. Org. Lett. 2016, 18, 4546−4549.
(m) Shin, J.; Lee, J.; Ko, D.; De, N.; Yoo, E. J. Org. Lett. 2017, 19,
2901−2904. (n) Wang, Z.; Xu, H.-C.; Su, Q.; Hu, P.; Shao, P.-L.; He,
Y.; Lu, Y.-X. Org. Lett. 2017, 19, 3111−3114. (o) Yoshida, H.; Kuriki,
H.; Fujii, S.; Ito, Y.; Osaka, I.; Takaki, K. Asian J. Org. Chem. 2017, 6,
973−976.
́
Suresh, E.; Biju, A. T. Org. Lett. 2014, 16, 3576−3579. (g) Prevost, S.;
Dezaire, A.; Escargueil, A. J. Org. Chem. 2018, 83, 4871−4881.
(h) Serum, E. M.; Selvakumar, S.; Zimmermann, N.; Sibi, M. P. Green
Chem. 2018, 20, 1448−1454. (i) Bhojgude, S. S.; Kaicharla, T.;
Bhunia, A.; Biju, A. T. Org. Lett. 2012, 14, 4098−4101. (j) Kaicharla,
T.; Bhojgude, S. S.; Biju, A. T. Org. Lett. 2012, 14, 6238−6241.
(k) Tao, Y.; Zhang, F.; Tang, C.-Y.; Wu, X.-Y.; Sha, F. Asian J. Org.
Chem. 2014, 3, 1292−1301.
(6) (a) Harvey, R. G. Polycyclic Aromatic Hydrocarbons; Wiley-VCH:
New York, 1997. (b) Kovacs, A.; Vasas, A.; Hohmann, J.
Phytochemistry 2008, 69, 1084. (c) Burtoloso, A. C. B.; Bertonha,
A. F.; Rosset, I. G. Curr. Top. Med. Chem. 2013, 14, 191. (d) Zheng,
Y.; Tice, C. M.; Singh, S. B. Bioorg. Med. Chem. Lett. 2014, 24, 3673.
(7) For reviews, see: (a) Segawa, Y.; Maekawa, T.; Itami, K. Angew.
Chem., Int. Ed. 2015, 54, 66. (b) Figueira-Duarte, T. M.; Mullen, K.
̈
̇
́
́
Chem. Rev. 2011, 111, 7260. (c) Stępien, M.; Gonka, E.; Zyła, M.;
Sprutta, N. Chem. Rev. 2017, 117, 3479−3716. (d) Ball, M.; Zhong,
Y.; Wu, Y.; Schenck, C.; Ng, F.; Steigerwald, M.; Xiao, S.; Nuckolls, C.
Acc. Chem. Res. 2015, 48, 267. (e) Saragi, T. P. I.; Spehr, T.; Siebert,
A.; Fuhrmann-Lieker, T.; Salbeck, J. Chem. Rev. 2007, 107, 1011−
1065. for selected examples, see: (f) Chen, Z.-P.; Wang, D.-Q.;
Zhang, M.; Wang, K.; Shi, Y.-Z.; Chen, J.-X.; Tao, W.-W.; Zheng, C.-
J.; Tao, S.-L.; Zhang, X.-H. Adv. Opt. Mater. 2018, 6, 1800935. (g) Li,
M.-H.; Hsu, C.-W.; Shen, P.-S.; Cheng, H.-M.; Chi, Y.; Chen, P.; Guo,
T.-F. Chem. Commun. 2015, 51, 15518−15521. (h) Zhu, X.-D.; Ma,
X.-J.; Wang, Y.-K.; Li, Y.; Gao, C.-H.; Wang, Z.-K.; Jiang, Z.-Q.; Liao,
L.-S. Adv. Funct. Mater. 2018, 1807094. (i) Li, L.; Hong, Y.; Lin, Y.;
Xiao, W.; Lin, M. Chem. Commun. 2018, 54, 11941−11944.
(19) See the Supporting Information for details on the evaluation of
reaction conditions.
̈
(j) Baumgartner, K.; Meza Chincha, A. L.; Dreuw, A.; Rominger,
F.; Mastalerz, M. Angew. Chem., Int. Ed. 2016, 55, 15594−15598.
(k) Hou, Z.-W.; Mao, Z.-Y.; Song, J.; Xu, H.-C. ACS Catal. 2017, 7,
5810−5813. (l) Ren, Y.-M.; Sun, D.-Y.; Cao, Y.-M.; Tsao, H. N.;
̈
Yuan, Y.; Zakeeruddin, S. M.; Wang, P.; Gratzel, M. J. Am. Chem. Soc.
2018, 140, 2405−2408. (m) Cui, L.-S.; Xie, Y.-M.; Wang, Y.-K.;
Zhong, C.; Deng, Y.-L.; Liu, X.-Y.; Jiang, Z.-Q.; Liao, L.-S. Adv. Mater.
2015, 27, 4213−4217. (n) Wan, W.-M.; Tian, D.; Jing, Y.-N.; Zhang,
X.-Y.; Wu, W.; Ren, H.; Bao, H.-L. Angew. Chem., Int. Ed. 2018, 57,
15510−15516.
(8) (a) Xie, C.-S.; Zhang, Y.-H. Org. Lett. 2007, 9, 781−784. (b) Hu,
J.-T.; Zheng, B.; Chen, Y.-C.; Xiao, Q. Org. Chem. Front. 2018, 5,
2045−2050.
́
̃
a, D.; Cobas, A.; Guitian, E. Chem. - Eur. J.
(9) (a) Criado, A.; Pen
2010, 16, 9736−9740. (b) Rodríguez-Lojo, D.; Pen
́
a, D.; Perez, D.;
̃
́
Guitian, E. Synlett 2015, 26, 1633−1637.
E
DOI: 10.1021/acs.orglett.9b00659
Org. Lett. XXXX, XXX, XXX−XXX