Efficient Diels-Alder reaction of 1,2-benzoquinones with arynes and its utility in one-pot reactions

Article abstract of DOI:10.1021/ol302997q

A new protocol for the efficient Diels-Alder reaction of 1,2-benzoquinones with arynes is reported. The aryne generated by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)aryl triflates undergoes a facile Diels-Alder reaction with 1,2-benzoquinones, affording the dioxobenzobicyclooctadienes in moderate to excellent yields. In addition, this methodology has been applied to the one-pot synthesis of benzoquinoxalinobarrelene and naphthalene derivatives.

Full text of DOI:10.1021/ol302997q

ORGANIC
LETTERS
XXXX
Vol. XX, No. XX
000–000
Efficient DielsꢀAlder Reaction
of 1,2-Benzoquinones with Arynes
and Its Utility in One-Pot Reactions
Trinadh Kaicharla, Sachin Suresh Bhojgude, and Akkattu T. Biju*
Organic Chemistry Division, CSIR-National Chemical Laboratory (CSIR-NCL),
Dr. Homi Bhabha Road, Pune-411008, India
at.biju@ncl.res.in
Received October 31, 2012
ABSTRACT
A new protocol for the efficient DielsꢀAlder reaction of 1,2-benzoquinones with arynes is reported. The aryne generated by the fluoride-induced
1,2-elimination of 2-(trimethylsilyl)aryl triflates undergoes a facile DielsꢀAlder reaction with 1,2-benzoquinones, affording the dioxobenzobicyclooctadienes
in moderate to excellent yields. In addition, this methodology has been applied to the one-pot synthesis of benzoquinoxalinobarrelene and naphthalene
derivatives.
1,2-Benzoquinones are a class of compounds endowed
with a broad range of interesting reactivity patterns.1 Since
the first report on the DielsꢀAlder reaction of 1,2-benzo-
quinones by Smith and Hac in 1936,2 this versatile class
of compounds is known to take part in DielsꢀAlder reac-
tions in four different modes: as carbodiene, heterodiene,
carbodienophile, and heterodienophile.3 Depending on
the substituents and the reaction conditions, 1,2-benzo-
quinone can act as an excellent carbodiene or heterodiene
with a variety of dienophiles. Although the reactivity of
1,2-benzoquinones as a 4π-component with a variety of
dienophiles is well-documented (Scheme 1, eq 1),3,4 appli-
cation of1,2-benzoquinones in DielsꢀAlder reactionswith
the highly electrophilic CꢀC triple bond of arynes has
received only scant attention.5 The latter will be attractive
because it leads to the direct synthesis of dioxobenzobicy-
clooctadiene derivatives, which are potentially amenable
to a number of synthetic transformations.6 This includes
various photochemical reactions of the bicyclo[2.2.2]-
octadiene moiety as well as the reaction of the 1,2-diketo
group. Herein, we report an efficient and facile Dielsꢀ
Alder reaction of 1,2-benzoquinones with arynes generated
by the fluoride-induced 1,2-elimination of 2-(trimethylsilyl)-
aryl triflates (eq 2).7 In addition, the synthetic utility of
this methodology has been demonstrated by the one-pot
(1) (a) Finley, K. T. In The Chemistry of Quininoid Compounds; Patai,
S., Rappoport, Z., Eds.; John Wiley & Sons: New York, 1988; Vol. 2, p 636.
(b) Kharisov, B. I.; Mendez-Rojas, M. A.; Garnovskii, A. D.; Ivakh-
nenko, E. P.; Ortiz-Mendez, U. J. Coord. Chem. 2002, 55, 745.
(2) (a) Smith, L. I.; Hac, L. R. J. Am. Chem. Soc. 1936, 58, 229. For a
related report, see: (b) Horner, L.; Spietschka, W. Ann. 1953, 579, 159.
(3) For reviews, see: (a) Nair, V.; Menon, R. S.; Biju, A. T.; Abhilash,
K. G. Chem. Soc. Rev. 2012, 41, 1050. (b) Nair, V.; Radhakrishnan,
K. V. In Science of Synthesis; Griesbeck, A., Ed.; Georg Thieme: Stuttgart,
Germany, 2006; Vol. 28, p 181. (c) Nair, V.; Kumar, S. Synlett 1996, 1143.
(4) For selected reports, see: (a) Bekele, T.; Shah, M. H.; Wolfer, J.;
Abraham, C. J.; Weatherwax, A.; Lectka, T. J. Am. Chem. Soc. 2006,
128, 1810. (b) Nair, V.; Sethumadhavan, D.; Nair, S. M.; Rath, N. P.;
Eigendorf, G. K. J. Org. Chem. 2002, 67, 7533. (c) Nair, V.; Maliakal, D.;
Treesa, P. M.; Rath, N. P.; Eigendorf, G. K. Synthesis 2000, 850. (d)
Nair, V.; Kumar, S. Tetrahedron 1996, 52, 4029. (e) Nair, V.; Kumar, S.;
Anilkumar, G.; Nair, J. S. Tetrahedron 1995, 51, 9155. (f) Ansell, M. F.;
Gosden, A. F.; Leslie, V. J.; Murray, R. A. J. Chem. Soc. C 1971, 1401.
(5) Ried, W.; Eng, J. T. S. Liebigs Ann. Chem. 1969, 727, 219.
(6) (a) Boyer, J. H.; Srinivasan, K. G. J. Chem. Soc., Perkin Trans 1.
1976, 1583. (b) Boyer, J. H.; Srinivasan, K. G. J. Chem. Soc., Chem.
Commun. 1973, 699. (c) Srinivasan, K. G.; Boyer, J. H. J. Chem. Soc.,
Chem. Commun. 1974, 1026.
(7) For the generation of arynes from 2-(trimethylsilyl)aryl triflates,
see: (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
1211. For a modified procedure for the synthesis of the triflate, see: (b)
~
ꢀ
ꢀ
Pena, D.; Cobas, A.; Perez, D.; Guitian, E. Synthesis 2002, 1454.
r
10.1021/ol302997q
XXXX American Chemical Society

synthesis of benzoquinoxalinobarrelene and naphthalene
derivatives. Interestingly, 1,2-benzoquinones manifest car-
bodiene-type reactivity in the DielsꢀAlder reactions with
arynes.
dienes. Recently, many of the traditional aryne reactions
have been revisited using Kobayashi’s method for aryne
generation, that is, by the treatment of 2-(trimethylsilyl)-
aryl triflates with a fluoride source, and this protocol has
led to a general enhancement in yields.7,10 We have recently
developed an efficient and practical DielsꢀAlder reaction of
pentafulvenes with arynes leading to the formation of benzo-
norbornadiene derivatives in high yields and broad scope.11
In the context of our interest in the chemistry of arynes,
the present study was initiated with the treatment of
3,5-di-tert-butyl 1,2-benzoquinone 1a with the aryne gene-
rated in situ from 2-(trimethylsilyl)aryl triflate 2a using
2.0 equiv each of KF and 18-crown-6. Interestingly, the
reaction afforded the 1,3-di-tert-butyl-1,4-dihydro-1,4-ethano
naphthalene-9,10-dione 3a in 94% yield (based on 1H NMR
spectroscopy, Table 1, entry 1). Other fluoride sources, such
as CsF, furnished comparable results (entry 2), but the use of
tetrabutylammonium fluoride (TBAF) was not found to be
helpful (entry 3). Increasing the amount of 1a improved the
yield of 3a (entry 4). Finally, increasing the amount of aryne
precursor 2a to 1.2 equiv and employing 2.4 equiv each of KF
and 18-crown-6 improved the reactivity, with 3a isolated in
98% yield (entry 5).12,13
Scheme 1. DielsꢀAlder Reaction of 1,2-Benzoquinones
Arynes are highly reactive intermediates, which holds
potential for numerous applications in organic synthesis
for the construction of multisubstituted arenes of structur-
al diversity and intricacy.8 One of the important reactions
of arynes is the DielsꢀAlder reaction, which is a powerful
tool for constructing various carbocycles and heterocycles
ofsynthetic importance.9 Due totheir highelectrophilicity,
arynes have been shown to react with a wide variety of
Table 1. Optimization of the Reaction Conditionsa
(8) For reviews, see: (a) Tadross, P. M.; Stoltz, B. M. Chem. Rev.
2012, 112, 3550. (b) Gampe, C. M.; Carreira, E. M. Angew. Chem., Int.
Ed. 2012, 51, 3766. (c) Bhunia, A.; Yetra, S. R.; Biju, A. T. Chem. Soc.
Rev. 2012, 41, 3140. (d) Okuma, K. Heterocycles 2012, 85, 515. (e) Chen,
Y. Larock, R. C. In Modern Arylation Methods; Ackermann, L., Ed.;
Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2009; p 401.
(f) Sanz, R. Org. Prep. Proced. Int. 2008, 40, 215. (g) Yoshida, H.;
Ohshita, J.; Kunai, A. Bull. Chem. Soc. Jpn. 2010, 83, 199. (h) Wenk,
H. H.; Winkler, M.; Sander, W. Angew. Chem., Int. Ed. 2003, 42, 502.
(i) Pellissier, H.; Santelli, M. Tetrahedron 2003, 59, 701. (j) Kessar, S. V.
In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon Press: New York, 1991; Vol. 4, p 483. For highlights, see: (k)
Bhojgude, S. S.; Biju, A. T. Angew. Chem., Int. Ed. 2012, 51, 1520. (l)
yield of
entry
variation from the standard conditionsa
none
3a (%)b
1
2
94
91
CsF instead of KFand 18-crown-6, CH3CN as
the solvent
3 c
4
5 d
TBAF instead of KF and 18-crown-6
1.2 equiv of 1a instead of 1.0 equiv
1.2 equiv of 2a instead of 1.0 equiv, 2.4 equiv
each of KF and 18-crown-6
<5
97
>99 (98)
~
ꢀ
ꢀ
Pena, D.; Perez, D.; Guitian, E. Angew. Chem., Int. Ed. 2006, 45, 3579.
For a recent account, see: (m) Yoshida, H.; Takaki, K. Synlett 2012, 23,
1725.
a Standard conditions: 1a (0.25mmol), 2a (0.25 mmol), KF (2.0 equiv),
18-crown-6 (2.0 equiv), THF (1.0 mL), 0 °C to rt and 12 h. b Yields were
determined by 1H NMR analysis of crude products using CH2Br2 as the
internal standard. Isolated yield at 0.50 mmol scale in parentheses.
c Decomposition of 1a was observed. d Reaction mixture stirred at rt
for 2 h.
(9) For selected recent reports, see: (a) Xie, C.; Zhang, Y. Org. Lett.
2007, 9, 781. (b) Shou, W.-G.; Yang, Y.-Y.; Wang, Y.-G. J. Org. Chem.
~
ꢀ
2006, 71, 9241. (c) Criado, A.; Pena, D.; Cobas, A.; Guitian, E. Chem.;
Eur. J. 2010, 16, 9736. (d) Buszek, K. R.; Luo, D.; Kondrashov, M.;
Brown, N.; VanderVelde, D. Org. Lett. 2007, 9, 4135. (e) Ikawa, T.;
Takagi, A.; Kurita, Y.; Saito, K.; Azechi, K.; Egi, M.; Kakiguchi, K.;
Kita, Y.; Akai, S. Angew. Chem., Int. Ed. 2010, 49, 5563. (f) Dockendroff,
C.; Sahil, S.; Olsen, M.; Milhau, L.; Lautens, M. J. Am. Chem. Soc. 2005,
127, 15028. (g) Li, J.; Wang, N.; Li, C.; Jia, X. Org. Lett. 2012, 14, 4994. (h)
Im, G.-Y.; Bronner, S. M.; Goetz, A. E.; Paton, R. S.; Cheong, P. H.-Y.;
Houk, K. N.; Garg, N. K. J. Am. Chem. Soc. 2010, 132, 17933.
With these optimized reaction conditions in hand, we
then examined the substrate scope of this 1,2-benzoquinone
aryne DielsꢀAlder reaction (Scheme 2).14 The 3,5-di-tert-
butyl 1,2-benzoquinone 1a worked well, and disubstitution
(10) For selected recent reports, see: (a) Rodrıguez-Lojo, D.; Cobas,
~
ꢀ
ꢀ
A.; Pena, D.; Perez, D.; Guitian, E. Org. Lett. 2012, 14, 1363. (b) Fang,
Y.; Rogness, D. C.; Larock, R. C.; Shi, F. J. Org. Chem. 2012, 77, 6262.
(c) Li, P.; Wu, C.; Zhao, J.; Rogness, D. C.; Shi, F. J. Org. Chem. 2012,
77, 3149. (d) Rogness, D. C.; Markina, N. A.; Waldo, J. P.; Larock, R. C.
J. Org. Chem. 2012, 77, 2743. (e) Lu, C.; Dubrovskiy, A. V.; Larock,
R. C. J. Org. Chem. 2012, 77, 2279. (f) Kim, J. M.; Stoltz, B. M.
Tetrahedron Lett. 2012, 53, 4994. (g) Pirali, T.; Zhang, F.; Miller,
A. H.; Head, J. L.; McAusland, D.; Greaney, M. F. Angew. Chem.,
Int. Ed. 2012, 51, 1006. (h) Markina, N. A.; Dubrovskiy, A. V.; Larock,
R. C. Org. Biomol. Chem. 2012, 10, 2409. (i) Zhao, J.; Li, P.; Wu, C.;
Chen, H.; Ai, W.; Sun, R.; Ren, H.; Larock, R. C.; Shi, F. Org. Biomol.
Chem. 2012, 10, 1922.
(11) Bhojgude, S. S.; Kaicharla, T.; Bhunia, A.; Biju, A. T. Org. Lett.
2012, 14, 4098.
(12) For details, see the Supporting Information.
(13) The same yield was obtained from a 2.0 mmol scale reaction.
(14) The 1,2-benzoquinones were synthesized by the FriedelꢀCrafts
alkylation of catechol derivative followed by the oxidation using NaIO4.
For details, see ref 3b.
B
Org. Lett., Vol. XX, No. XX, XXXX

at various positions of the 1,2-benzoquinones was well-
tolerated and led to dioxobenzobicyclooctadienes in good
to excellent yield (3aꢀ3d). Interestingly, monosubstituted
1,2-benzoquinone resulted in the smooth formation of
cycloadduct 3e in 65% yield. Moreover, trisubstituted
1,2-benzoquinones also furnished good to excellent yields
of the desired products, further expanding the scope of this
1,2-benzoquinone aryne DielsꢀAlder reaction. It is note-
worthy, however, that in preliminary experiments com-
mercially available 1,2-benzoquinones such as o-chloranil
failed to undergo this cycloaddition under the optimized
reaction conditions.15
Table 2. DielsꢀAlder Reaction of 3,5-Di-tert-butyl 1,2-Benzo-
quinone with Arynes
Scheme 2. DielsꢀAlder Reaction of 1,2-Benzoquinones with
Benzynea
a General conditions: 1 (0.50 mmol), 2a (0.60 mmol), KF (2.4 equiv),
18-crown-6 (2.4 equiv), THF (2.0 mL), 0 °C to rt and 2 h. Yields of the
isolated products are given. b Reaction mixture stirred for 3 h at rt.
c Reaction was run on 0.25 mmol scale. d 1.5 equiv of 2d was used. e The
regioisomer ratio was determined by 1H NMR analysis of the crude
reaction mixture.
a General conditions: 1 (0.50 mmol), 2a (0.60 mmol), KF (2.4 equiv),
18-crown-6 (2.4 equiv), THF (2.0 mL), 0 °C to rt and 2 h. Yields of the
isolated products are given. b 1H NMR yield of the product is given.
c Reaction was carried out using 1.0 equiv of 2a and 1.5 equiv of 1e and
2.0 equiv each of KF and 18-crown-6.
benzoquinoxalinobarrelene derivatives.16 Thus treatment
of 1,2-benzoquinones 1 with aryl triflates 2 under the
optimized reaction conditions followed by the addition
of 1,2-phenylenediamine resulted in the one-pot synthesis
of benzoquinoxalinobarrelenes 4 ingood toexcellentyields
(Scheme 3). The disubstituted 1,2-benzoquinones and even
monosubstituted 1,2-benzoquinones worked well in the
one-pot operation, leading to good to excellent yield of the
product (4a, 4b).17 In addition, a symmetric aryne pre-
cursor 2c derived from sesamol resulted in the smooth
conversion to the bicyclic product in 95% yield (4c),
further expanding the scope of this one-pot reaction.
Evidently, the one-pot reaction has advantages over the
two-step reaction as it allows the rapid construction of
benzoquinoxalinobarrelenes, thus reducing labor, waste,
affording the same/better yield compared to a stepwise
In view of these interesting results, we next examined
theeffectof varying the substituentson the aryne precursor
2 (Table 2). Electronically dissimilar 4,5-disubstituted
symmetrical aryne precursors 2bꢀd readily furnished the
dioxobenzobicyclooctadienes 3iꢀk in good to excellent
yields (entries 1ꢀ3). Moreover, the 3,6-dimethyl-substi-
tuted symmetrical aryne precursor 2e worked well to afford
product 3l in 72% yield (entry 4). Additionally, the reaction
of the unsymmetrical aryne generated from 2f resulted in
the formation of an inseparable mixture of regioisomers
3m/3m0 in a 1:1 ratio (entry 5). Furthermore, the unsymme-
trical naphthalyne derived from 2g underwent efficient
cycloaddition to deliver an inseparable mixture of regio-
isomers 3n and 3n0 in 95% overall yield (entry 6).
The synthetic utility of the aryne DielsꢀAlder reaction
has been demonstrated by the efficient one-pot synthesis of
(16) Benzoquinoxalinobarrelenes are potential candidates for
photochemical rearrangement reactions. For details, see refs 6a
and 6c.
(15) It may be noted that commercially available 1,2-quinones such
as acenaphthenequinone and phenanthrenequinone did not show any
heterodiene reactivity with arynes under the optimized conditions.
(17) Interestingly, the synthesis of 4b from the corresponding 1,2-
benzoquinone resulted in 65% overall yield for the two steps, whereas
the one-pot operation afforded the product in 78% yield.
Org. Lett., Vol. XX, No. XX, XXXX
C

process, and utilizing the use of more readily available
starting materials.18
Scheme 4. One-Pot Synthesis of Naphthalenes from
1,2-Benzoquinones and Triflates 2a
Scheme 3. One-Pot Synthesis of Benzoquinoxalinobarrelenes
from 1,2-Benzoquinones and Triflates 2a
a General conditions: 1 (0.50 mmol), 2a (0.60 mmol), KF (2.4 equiv),
18-crown-6 (2.4 equiv), THF (2.0 mL), 0 °C to rt and 2 h, then dilution
(THF, 12.0 mL) and irradiation at 254 nm for 1 h. Yields of the isolated
products are given. b Reaction was run on 0.25 mmol scale.
a General conditions: 1 (0.50 mmol), 2a (0.60 mmol), KF (2.4 equiv),
18-crown-6 (2.4 equiv), THF (2.0 mL), 0 °C to rt and 2 h, followed
by addition of o-phenylenediamine (1.5 equiv) in MeOH/AcOH (1:1).
Yieldsof the isolated productsare given. b Reactionwas runon0.25 mmol
scale.
In conclusion, we have developed an efficient and
practical DielsꢀAlder reaction of 1,2-benzoquinones with
arynes, leading to dioxobenzobicyclooctadiene derivatives
in high yields. It is noteworthy that dioxobenzobicyclo-
octadienes are potentially amenable to a number of syn-
thetic transformations. In addition, the application of this
mild cycloaddition reaction has been demonstrated by the
one-pot synthesis of benzoquinoxalinobarrelene and naphtha-
lene derivatives. Efforts to expand the DielsꢀAlder reac-
tion of arynes with challenging dienes are ongoing in our
laboratory.
The synthetic potential of the 1,2-benzoquinone aryne
[4 þ 2] cycloaddition reaction was further examined by the
one-pot synthesis of naphthalene derivatives. It should be
noted that naphthalene derivatives are ubiquitously pre-
sent in many natural products and pharmaceuticals.19 The
reaction of 1,2-benzoquinones 1 with triflates 2 under the
optimized reaction conditions followed by the irradiation
of the reaction mixture at 254 nm afforded the one-pot
synthesis of naphthalene derivatives (Scheme 4).20 This
one-pot reaction works well with mono-, di-, and even
trisubstituted 1,2-benzoquinones to deliver the function-
alized naphthalenes in moderate to good yields (5aꢀ5c).
Moreover, the symmetric aryne precursor 2c was also well-
tolerated to furnish the tetrasubstituted naphthalene 5d
in 61% yield in a one-pot operation. It may be noted that
the mechanistic details of the decarbonylation of similar
adducts was known as early as 2002.21
Acknowledgment. Generous financial support from
CSIR-NCL (start-up grant to A.T.B., MLP022426),
CSIR-New Delhi (Network project ORIGIN, and for
the award of SPM Fellowship to T.K., and Junior
Research Fellowship to S.S.B.) is gratefully acknowl-
edged. We thank Dr. P.R. Rajamohanan (CSIR-NCL)
for the NMR spectra, Dr. C.S. Gopinath (CSIR-NCL)
for extending the facility for conducting the photochem-
ical reactions, and Ms. B. Santhakumari (CSIR-NCL)
for HRMS data.
(18) For recent reviews on one-pot reactions, see: (a) Albrecht, Ł.;
Jiang, H.; Jørgensen, K. A. Angew. Chem., Int. Ed. 2011, 50, 8492. (b)
Climent, M. J.; Corma, A.; Iborra, S. Chem. Rev. 2011, 111, 1072. (c)
Walji, A. M.; MacMillan, D. W. C. Synlett 2007, 1477.
(19) For selected reviews, see: (a) Kilian, P.; Knight, F. R.; Woollins,
J. D. Chem.;Eur. J. 2011, 17, 2302. (b) Cai, Y.-S.; Guo, Y.-W.; Krohn,
K. Nat. Prod. Rep. 2010, 27, 1840.
(20) For a related bisdecarbonylation of bicyclic adducts derived
from 1,2-benzoquinones and acetylenic compounds, see: Thomas, A.;
Anilkumar, G.; Nair, V. Tetrahedron 1996, 52, 2481.
Supporting Information Available. Experimental pro-
cedures and full spectroscopic data for all compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(21) Nair, V.; Maliakal, D. Res. Chem. Intermed. 2002, 28, 337.
The authors declare no competing financial interest.
D
Org. Lett., Vol. XX, No. XX, XXXX