An efficient access to fluorescent 2,3,4-tricyanofurans from α-cyano ketones using DDQ as maleonitrile building block

Article abstract of DOI:10.1055/s-0033-1339501

An efficient synthetic method was developed for the synthesis of 2,3,4-tricyanofurans from α-cyano ketones using DDQ as maleonitrile building block under very mild conditions. This methodology allows for the construction of a new kind of fluorescent core framework. Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0033-1339501

LETTER
▌2003
lAettner Efficient Access to Fluorescent 2,3,4-Tricyanofurans from α-Cyano Keto-
nes Using DDQ as Maleonitrile Building Block
One-Step Synthesis of 2,3,4-Tricyanofurans with DDQ
Jiang-Sheng Li,*a Yuan Xue,a Zhi-Wei Li,*a Wei-Dong Liu,b Cui-Hong Lu,a Pei-Xia Zhaoa
a
Hunan Provincial Key Laboratory of Materials Protection for Electric Power and Transportation, School of Chemistry and Biological
Engineering, Changsha University of Science & Technology, Changsha 410114, P. R. of China
Fax +86(731)85258733; E-mail: jslichem@gmail.com; E-mail: lizwhn@126.com
b
National Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry, Changsha 410007, P. R. of China
Received: 28.05.2013; Accepted after revision: 11.07.2013
furan scaffold using DDQ as maleonitrile building block
Abstract: An efficient synthetic method was developed for the syn-
(Scheme 1) and a surprising discovery of a new series of
thesis of 2,3,4-tricyanofurans from α-cyano ketones using DDQ as
fluorescent core frameworks.
maleonitrile building block under very mild conditions. This meth-
odology allows for the construction of a new kind of fluorescent
core framework.
Initially, the reaction of 2-cyanoacetophenone (1a) with
DDQ was used as the model to optimize the reaction pa-
rameters. The results are summarized in Table 1. Treat-
ment of 1a with DDQ was firstly performed in acetonitrile
Key words: furans, cyano ketones, DDQ, cyclization, fluorescent
cores
at room temperature. With 3.0 equivalents of DDQ being
used, the reaction went smoothly to completion, furnish-
Furans are not only an important class of heterocycles
prevalent in natural products, pharmaceuticals, flavors,
and agrochemicals but also versatile intermediates in or-
ganic synthesis.1 Up to date, myriad approaches to access
furans are well documented.2 Generally, they can be cate-
gorized into three main strategies. The first involves the
direct functionalization of the existing furan rings using
Heck, Stille, Suzuki, and Negishi coupling reactions.2b
However, the corresponding tin, silicon, and boron inter-
mediates are not easy to access, although direct oxidative
coupling based on C–H and C–halogen bond activation
has been achieved.3 The second relates to the construction
of ring itself from acyclic precursors2a,c such as 1,4-dike-
tones, alkyne-containing substrates or their equivalents,
which necessitates the complicated functionalization of
basic chemical materials. The third is the one-pot synthe-
sis of the furan scaffold from easily accessible substrates
without prefunctionalization.4 Due to its high atom-econ-
omy, operational ease, and good availability, this synthet-
ic strategy has proven to be one of the most attractive
methods; however, the known reports are very limited.4,5
ing 2,3,4-tricyano-5-phenylfuran (2a) in 81% yield (Table
1, entry 1). When the equivalents of DDQ were lowered
to 2.5, 2.0, and 1.2, the ketone 1a remained partly unfin-
ished and the product 2a was obtained in the yield of 76%,
51%, and 30%, respectively (Table 1, entries 2–4). Fur-
thermore, several other solvents including dichlorometh-
ane, benzene, ethyl acetate, nitromethane, and ethanol
were tested for this transformation (Table 1, entries 5–9).
To our delight, all tested solvents except ethanol gave
good yields. The use of acetonitrile and ethyl acetate gave
a similar yield (81% vs. 80%). Considering the cost and
environmental friendliness, ethyl acetate was chosen as
the best solvent for this transformation.
CN
O
Cl
Cl
CN
CN
O
O
CN
CN
R
R
CN
O
1
DDQ
2
Scheme 1 Synthesis of 2,3,4-tricyanofurans using DDQ
2,3-Dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) is a
well-known dehydrogenative oxidizing reagent in organic
synthesis6 and has been successfully used for constituting
new C–C and C–heteroatom bonds via C–H activation.7
To the best of our knowledge, however, DDQ rarely
serves as reactant precursor.8 The importance of fluores-
cent molecules has been well documented in various
fields of research.9 The use of new synthetic methodolo-
gies to discover novel fluorescent core frameworks has at-
tracted great interest.10 Herein, we wish to report a facile
and efficient methodology for the construction of the
With the optimized conditions in hand, we set out our in-
vestigations into the scope of the annulation of various α-
cyano ketones with DDQ, and the results are summarized
in Table 2.11 All the tested substrates including aryl and al-
iphatic ketones reacted well to give the corresponding fu-
rans in moderate to good yields (28–87%). For aryl
ketones, those bearing electron-releasing and electron-
withdrawing groups underwent smoothly. In spite of this,
subtle electronic effects were observed. For example,
electron-withdrawing groups gave higher yields (Table 2,
entries 2 and 4), while the presence of electron-rich
groups decreased the selectivity and offered lower yields
(Table 2, entries 8–11). Evidently, the electron-rich aro-
matic ring competed with α-CH2 in molecules 1, making
SYNLETT 21709013, 2415, 2003–2005
Advanced online publication: 14.08.2013
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339501; Art ID: ST-2013-W0490-L
© Georg Thieme Verlag Stuttgart · New York

2004
J.-S. Li et al.
LETTER
Table 2 Syntheses of 2,3,4-Tricyanofurans with DDQa
Table 1 Optimization of the Reaction Conditionsa
CN
CN
O
O
O
O
DDQ (3.0 equiv), EtOAc
r.t., overnight
CN
DDQ, solvent
CN
CN
CN
R
R
CN
2a
CN
1
2
1a
Entry
Product
1 R
Yield (%)b
Entry
DDQ/1ab
Solventc
Yield (%)d
1
2
2a
2b
2c
2d
2e
2f
Ph
80
87
72
83
63
60
56
42
45
32
28
45
63
77
1
2
3
4
5
6
7
8
9e
3.0
2.5
2.0
1.2
3.0
3.0
3.0
3.0
3.0
MeCN
MeCN
MeCN
MeCN
CH2Cl2
benzene
EtOAc
MeNO2
EtOH
81
76
51
30
77
75
80
68
20
4-ClC6H4
2-ClC6H4
4-BrC6H4
4-MeC6H4
3-MeC6H4
2-MeC6H4
3
4
5
6
7
2g
2h
2i
8
4-MeOC6H4
2-MeOC6H4
9
10
11
12
13
14
2j
2,4-(MeO)2C6H3
3,4-(MeO)2C6H3
furyl-2
a 1a (0.5 mmol) was treated with DDQ at 25 °C overnight.
b Molar ratio.
2k
2l
c Dried using standard methods.
d Isolated yield.
e Unidentified contaminant dominates.
2m
2n
(E)-C6H4CH=CH
Me
the reaction more complicated (giving unidentified impu-
rities). Also, steric effects were found. When the substitu-
ents such as chloro or methyl group were on the ortho
position of the aromatic ring, the reaction gave lower yield
(Table 2, entries 3 and 7). Notably, the halo groups were
well tolerated under annulation conditions, which allows
for the derivation of the furans via the palladium- or cop-
per-catalyzed coupling reactions reported previously.12
Besides, this transformation worked well not only with
electron-rich furyl ketone but also with the enone derived
from cinnamic acid (Table 2, entries 12 and 13).
a Reaction conditions: ketones 1 (0.5 mmol), DDQ (1.5 mmol),
stirred in EtOAc at 25 °C overnight.
b Isolated yield.
NMR and GC–MS (see Figure S1 in the Supporting Infor-
mation). Moreover, this speculation can be rationalized by
the fact that the use of a cold 5% NaHCO3 solution to
wash the reaction mixture can give almost pure corre-
sponding furans. The annulation was also proven by the
X-ray molecular structure 2a (Figure 1).
To assess whether radical species are formed in this reac-
tion, the radical scavenger TEMPO was employed
(Scheme 2). The reactions are completely inhibited by six
equivalents of TEMPO. This result indicates that such a
transformation may involve radical intermediates.
OH
OH
O
CN
CN
CN
CN
Cl
Cl
Cl
Cl
R
O
O
DDQ
R
R
CN
H
CN
CN
O
OH
O
CN
DDQ
DDQH2
DDQ (3.0 equiv), EtOAc
no 2a detected
TEMPO (6.0 equiv)
r.t., overnight
O
NC
CN
O
1a
Cl
retro-DA reaction
O
R
R
Scheme 2 Radical-trapping experiment
NC
Cl
CN
CN
CN
O
O
The mechanism for this protocol is yet unknown, but it is
presumably subjected to single electron transfer (SET)
cycloaddition and subsequent retro-Diels–Alder reaction,
eventually giving out 2,3-dichloromaleic anhydride
(Scheme 3). This resulting anhydride was identified by
O
Cl
Cl
Cl
H2O
O
Cl
O
O
Scheme 3 Proposed mechanism for the annulation
Synlett 2013, 24, 2003–2005
© Georg Thieme Verlag Stuttgart · New York

LETTER
One-Step Synthesis of 2,3,4-Tricyanofurans with DDQ
2005
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Figure 1 ORTEP representation of 2a
It is worth mentioning that 5-aryl-substituted 2,3,4-tricya-
nofurans were found to exhibit significantly strong pho-
tonic fluorescence both in solution and in solid state (see
Figure S2 in the Supporting Information). Moreover, their
photophysical properties can be tuned by changing the
substituents of 5-position phenyl ring. Compounds 2b and
2d can be readily converted by the known metal-catalyzed
coupling with N,N-dialkylamines to mimic a ‘push–pull’
π-electron mode.
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In summary, we have developed a facile and efficient syn-
thetic pathway that allows the construction of 5-substitut-
ed 2,3,4-tricyanofurans in moderate to good yields and
good functional-group tolerance. More importantly, this
approach has resulted in the discovery of a library of flu-
orophores. The application of this protocol, modification
of such fluorescence core framework, and investigation of
2,3,4-tricyanofurans as fluorescence probes are currently
ongoing.
Acknowledgment
Supports for this work by National Natural Science Foundation of
China (21202010), Hunan Provincial Natural Science Foundation
of China (12JJ4021), and Hunan Provincial Science and Technolo-
gy Project (2009GK3015) are gratefully acknowledged.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.SnoIufproig
m
iotSrat
ungIifoop
r
t
(11) Experimental Procedure
References and Notes
DDQ (341 mg, 1.5 mmol) was added to α-cyano ketone (0.5
mmol) in EtOAc (2 mL). The resulting reaction mixture was
stirred overnight during which time a yellow solid
precipitated. EtOAc (30 mL) was added, and the resultant
mixture was subsequently washed with cold aq 5% NaHCO3
(3 × 10 mL) and brine. Silica gel (0.5 g) was added and the
mixture rotary evaporated. The resulting powder was added
to the top of a short silica gel column and purified using PE–
EtOAc in a 10:1 to 7:1 ratio (v/v) as the eluent to afford the
desired product.
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© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 2003–2005

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