Studies on the radical cyclization of 3-oxopropanenitriles and alkenes with cerium(IV) ammonium nitrate in ether solvents

Article abstract of DOI:10.1002/hlca.201000440

The radical cyclization of 3-oxopropanenitriles 1a-1e and alkenes 2a-2g with cerium(IV) ammonium nitrate (CAN) in ether solvents was investigated (Tables 1 and 2). In the optimization study, 1,3-dioxolane, 1,4-dioxane, 1,2-dimethoxyethane, Et₂O

Full text of DOI:10.1002/hlca.201000440

Helvetica Chimica Acta – Vol. 94 (2011)
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Studies on the Radical Cyclization of 3-Oxopropanenitriles and Alkenes with
Cerium(IV) Ammonium Nitrate in Ether Solvents
by Mehmet Yılmaz
Department of Chemistry, Faculty of Arts and Sciences, Kocaeli University, TR-41380 Umuttepe,
Kocaeli (fax: þ 90-262-3032003; e-mail: mehmet.yilmaz@kocaeli.edu.tr)
The radical cyclization of 3-oxopropanenitriles 1a – 1e and alkenes 2a – 2g with cerium(IV)
ammonium nitrate (CAN) in ether solvents was investigated (Tables 1 and 2). In the optimization study,
1,3-dioxolane, 1,4-dioxane, 1,2-dimethoxyethane, Et2O, and THF were used as ether-based solvents, and
the latter was found to be the most effective solvent in radical cyclizations mediated by cerium(IV). This
system (cerium(IV)/THF) was applied to cyclizations of various 3-oxopropanenitriles and 1,3-dicarbonyl
compounds with alkenes resulting in the formation of 4,5-dihydrofurans in high yields (Table 2 and
Scheme 2). The results of the cerium(IV)/THF radical cyclization were compared with those obtained
with manganese(III) acetate/AcOH; the cerium(IV)/THF system turned out to be much more efficient.
Introduction. – During the last three decades, manganese(III) acetate dihydrate
(MAH) [1] and cerium(IV) ammonium nitrate (CAN) [2] have been used as efficient
radical oxidants. These oxidants have the ability for a one-electron transfer and are
used in organic synthesis for constructing CꢀC bonds. Both CAN and MAH are well
known for dihydrofuran formation by radical cyclization of 1,3-dicarbonyl compounds
with alkenes. Dihydrofurans show a wide range of biological activities and form the
basic structure of many natural compounds [3].
Our research group has studied the radical cyclization of 1,3-dicarbonyl compounds
and 3-oxopropanenitriles with alkenes, alkynes, unsaturated amides, and dienes in the
presence of manganese(III) acetate [4]. Very recently, we have reported that some 4,5-
dihydrofuran-3-carbonitriles show antibacterial and antifungal activity [5]. These
carbonitriles are available by oxidative cyclization of 3-oxopropanenitriles with
conjugated alkenes [4f][4g] and unsaturated amides [4h]. In these reactions, MAH/
AcOH gives good results, whereas CAN is not efficient when MeOH or MeCN are used
as solvents. Hence, we performed an optimization using ether-based solvents and CAN
which were more effective. We applied the optimized conditions (CAN/THF, 40 – 608)
to a study of the cyclization of 3-oxopropanenitriles and 1,3-dicarbonyl compounds
with alkenes. Additionally, we compared cyclizations induced by CAN/THFand MAH/
AcOH. The CAN/THF method gave 4,5-dihydrofurans in high yields.
Results and Discussion. – All 3-oxopropanenitriles were prepared according to
[4g][4h][6]. The 1,1-diphenylbut-1-ene (2e) [7], 1,1-bis(4-fluorophenyl)ethene (2f)
[8], and 1,1-bis(4-methylphenyl)ethene (2g) [9] were synthesized by dehydration of the
corresponding alcohols obtained from Grignard reactions of suitable arylmagnesium
bromides and ketones. The other alkenes, CAN, and reagents are commercial materials
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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and were purchased in highest purity. Crude products were purified by column
chromatography or/and prep. thin-layer chromatography (TLC). All novel compounds
were characterized by IR, 1H- and 13C-NMR, MS, and microanalysis. The other
products were characterized by 1H-NMR.
The proposed mechanism for the radical cyclization of 3-oxopropanenitriles with
alkenes mediated by CAN and the formation of 4,5-dihydrofuran-3-carbonitriles is
displayed in Scheme 1. According to this mechanism, [CeIV(enolato)] complex B is
formed with the enol form A of 3-oxopropanenitriles 1a – 1e and CAN. While Ce4þ is
reduced to Ce3þ, a radical at C(a) is formed resulting in structure C. The radical
intermediate D is obtained by an electrophilic radical addition of C on the alkene. A
[Ce3þ(enolato)] complex is formed by removing HꢀC(a) from structure D, and the
radical is oxidized to carbocation E with CAN. The intramolecular cyclization of E
forms 4,5-dihydrofuran-3-carbonitrile F.
Scheme 1. Mechanism for the Formation of 4,5-Dihydrofuran-3-carbonitriles
The synthesis of 4,5-dihydro-2,5,5-triphenylfuran-3-carbonitrile (3a) was used as
model reaction. This compound 3a was previously obtained by cyclization of 3-phenyl-
3-oxopropanenitrile (1a) with 1,1-diphenylethene (2a) mediated by MAH in 65% yield
[10]. For this model reaction, 1,3-dioxolane, 1,4-dioxane, 1,2-dimethoxyethane, Et2O,
and THF were used as ether solvents as well as MeOH and MeCN, which are
traditionally used in reactions of CAN. The syntheses of 3a were performed with a
molar ratio 1a/2a/CAN of 1.2 :1:3, under N2 at different temperatures for 10 min. The
results are given in Table 1.
The formation of 3a with CAN in MeOH at 08 and 608 failed, and compound 3a
could not be isolated. Dihydrofuran 3a was formed in low yields in MeCN under the
same reaction conditions. However, when 1,3-dioxolane and 1,4-dioxane were used at
40 – 508, 3a was obtained in 52 and 83% yield, respectively. At higher temperatures,
lower yields were observed. In 1,2-dimethoxyethane at 40 – 508, the yield of 3a
amounted to 73%. On the other hand, product 3a was obtained in 84% yield in Et2O
under reflux for 24 h instead of 10 min (due to the poor solubility of CAN). The
optimum yield of 97% was obtained in THF at 40 – 508 after 10 min reaction time.
These results indicated that ether solvents can be used more efficiently in reactions of

Helvetica Chimica Acta – Vol. 94 (2011)
1337
Table 1. Solvent- and Temperature-Optimization Study of the Radical Cyclization
Solvent
T [8]
Yield [%]a)
Solvent
T [8]
Yield [%]a)
MeOH
MeOH
MeCN
MeCN
1,3-Dioxolane
1,3-Dioxolane
0
60
0
60
40 – 50
50 – 60
–
–
23
46
52
50
1,3-dioxolane
1,4-dioxane
1,4-dioxane
1,2-dimethoxyethane
Et2O
60 – 70
40 – 50
60 – 70
40 – 50
36
48
83
52
73
84
97
THF
40 – 50
a) Yield of isolated product based on alkene 2a.
CAN. These optimum conditions were applied to the reactions of various 3-
oxopropanenitriles, and the results were compared to the reactions performed with
MAH/AcOH (Table 2).
While the radical cyclization of 3-(furan-2-yl)-3-oxopropanenitrile (1b) mediated
by MAH gave 3b in 50% yield, the new method (CAN/THF) produced 3b in 90% yield
(Table 2, Entry 2). Similarly, radical cyclizations of 3-(1-benzofuran-2-yl)-3-oxopro-
panenitrile (1c) and 4,4-dimethyl-3-oxopentanenitrile (1d) with 2a in the presence of
CAN gave the corresponding dihydrofurans in high yield (Entries 3 and 4). Reactions
of 1a with styrene (2b) and (1E)-1-phenylprop-1-ene (2c) which are less reactive than
2a, furnished 3e (42%) and 3f (75%) in moderate to good yield (Entries 5 and 6).
Whereas the reaction of 2-phenylprop-1-ene (2d) with 1a and MAH/AcOH produced
3h in 25% yield, the same reaction with CAN resulted in 80% yield (Entry 8). The
reactions of the 3-oxopropanenitriles 1b, 1c, and 1e with 2d gave remarkable results
(Entries 9 – 11). These facts evidently demonstrate that CAN/THF is a method superior
to MAH/AcOH. Radical cyclizations of 1a and 1e with sterically hindered alkene 2e
showed again that CAN/THF is more efficient (Table 2, Entries 12 and 13). Moreover,
3-oxopropanenitriles 1a and 1d and alkenes 2f and 2g with 4-F and 4-Me substituents,
respectively, gave 4,5-dihydrofuran-3-carbonitriles in similarly high yields (Entries 14
and 19).
This method could also be employed for other 1,3-diketones. The reaction of 4-
hydroxycoumarin (4) and 2d with CAN/THF at 40 – 508 for 10 min gave 2-methyl-2-
phenyl-4H-furo[3,2-c][1]benzopyran-4-one (4a) in 72% yield (Scheme 2). Ketone 4a
has been synthesized in lower yields in the presence of Ag/Celite (37% [11] and 46%
[12]) as well as in the presence of CAN under different reaction conditions (62% [2c]
and 70% [2k]). Moreover, the radical cyclization of ethyl 3-oxobutanoate (5) with 2d
under the same conditions (CAN/THF) gave ethyl 4,5-dihydro-2,5-dimethyl-5-phenyl-
furan-3-carboxylate (5a) in 79% yield. This compound has been obtained in the ionic
liquid [bmim][BF4]/CH2Cl2 1:9 as a solvent in the same yield but after 2 h (bmim ¼ 1-
butyl-9-methyl-1H-imidazolium) [2k]. A similar radical cyclization with 1,1-diphenyl-

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Table 2. Radical Cyclization of 3-Oxopropanenitriles and Alkenes with CAN/THF
Entry Nitrile R1
Alkene R2
R3
Ph
R4 Product Yield [%]a) Yield [%]b)
MAH/AcOH
1
2
1a
1b
1c
1d
1a
1a
1e
1a
1b
1c
1e
1a
1e
1a
1b
1c
1e
1b
1d
1e
Ph
furan-2-yl
2a
2a
Ph
H
3a
3b
3c
3d
3e
97
90
96
90
42
75
77
80
77
81
86
83
80
86
82
88
85
82
80
87
65
50
3
4
1-benzofuran-2-yl 2a
tBu
2a
2b
2c
2c
2d
2d
62
12
5
Ph
Ph
Ph
H
H
H
6
Ph
Me 3f
7
8
2-thienyl
Ph
3g
Ph
Me
H
3h
3i
25
9
furan-2-yl
10
11
12
13
14
15
16
17
18
19
20
1-benzofuran-2-yl 2d
2-thienyl
Ph
2-thienyl
Ph
furan-2-yl
3j
3k
2d
2e
2e
2f
2f
Ph
Ph
Et 3l
3m
63
44
62
4-FC6H4
4-FC6H4
H
3n
3o
3p
3q
3r
3s
3t
1-benzofuran-2-yl 2f
2-thienyl
furan-2-yl
tBu
2f
2g
2g
2g
4-MeC6H4 4-MeC6H4
H
2-thienyl
a) Yields of isolated product based on the alkene. b) Yields taken from [10][4f].
ethylene (2a) produced 5b in 81% yield, which has been obtained in 75% yield in ionic
liquid [2k] and in 44% yield in MeCN by CAN [13].
Conclusions. – In this study, CAN was applied to the radical cyclizations of 3-
oxopropanenitriles 1a – 1e with alkenes 2a – 2g for the first time. MeOH and MeCN,
generally used for the reactions of CAN, either were not sufficiently effective or failed
to form the products. An optimization study with ether solvents established that THF,
Et2O, and 1,4-dioxane are highly efficient in the reactions of CAN. Furthermore, 4,5-
dihydrofuran-3-carbonitriles were obtained in higher yields with CAN than with MAH.
The high efficiency of CAN/THF in radical cyclizations can be explained by the low
solubility of CAN in THF that causes a stepwise release of Ce4þ ions into the reaction
medium and thus prevents the formation of possible by-products.
The author is grateful to the TUBITAK (108T305) and the Kocaeli University Science Research
Foundation (BAP 2008/28) for their financial support.

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Scheme 2. Radical Cyclization of 4 and 5 with Alkenes
Experimental Part
General. All solvents were dried by standart methods. Column chromatography (CC): silica gel
(SiO2; 230 – 400 mesh; Merck). TLC: anal. aluminium plates coated with SiO2 60 F254–366 (0.2 mm;
Merck). M.p.: electrothermal melting point apparatus; uncorrected. IR Spectra: FT-IR Matson-1000
.
instrument; KBr pellets; 400 – 4000 cmꢀ1 range with 4 cmꢀ1 resolution; ˜n in cmꢀ1 1H- and 13C-NMR
Spectra: Mercury-400 high-performance digital FT-NMR insrument; in CDCl3; d in ppm rel. to Me4Si as
internal standard, J in Hz. LC/ESI-MS: Waters-2695-Alliance-Micromass-ZQ instrument; in m/z (rel.
%).
4,5-Dihydrofuran-3-carbonitriles 3a – 3t. General Procedure. To a soln. of 3-oxopropanenitrile
(1.2 mmol) and alkene (1 mmol) in THF (10 ml) under N2, a mixture of CAN (3 mmol) and NaHCO3
(3 mmol) was added at 408. Then, the temp. was slowly increased to 608. The reaction was completed
when the orange color of CAN had disappeared (10 – 30 min) or when the alkene spot on TLC had
completely vanished. H2O was added to the soln., and the mixture was extracted with CHCl3 (3 ꢁ 20 ml).
The combined org. phase was dried (Na2SO4) and concentrated and the crude product purified by CC
(SiO2, 230 – 400 mesh) or prep. TLC (20 ꢁ 20 cm plates, 2 mm thickness, hexane/AcOEt 5 :1).
4,5-Dihydro-2,5,5-triphenylfuran-3-carbonitrile (3a): Yield 0.313 g (97%). Colorless solid. M.p.
134 – 1368 (hexane/AcOEt). 1H-NMR: 8.10 (dd, J ¼ 7.0, 2.7, 2 arom. H); 7.50 – 7.28 (m, 13 arom. H); 3.78
(s, CH2(4)).
2-(Furan-2-yl)-4,5-dihydro-5,5-diphenylfuran-3-carbonitrile (3b): Yield 0.282 g (90%). Pale yellow
oil. 1H-NMR: 7.63 (d, J ¼ 1.6, 1 H); 7.40 – 7.30 (m, 12 arom. H); 7.11 (d, J ¼ 3.5, 1 H); 6.56 (dd, J ¼ 3.5, 1.6,
1 H); 3.73 (s, CH2(4)).
2-(Benzofuran-2-yl)-4,5-dihydro-5,5-diphenylfuran-3-carbonitrile (3c): Yield 0.348 g (96%). Yellow
solid. M.p. 165 – 1678 (hexane/AcOEt). IR: 3061, 2200 (CN), 1648 (C¼C), 1180 (CꢀOꢀC), 829, 750, 698.
1H-NMR: 7.67 (d, J ¼ 7.8, 1 H); 7.62 (d, J ¼ 8.2, 1 H); 7.47 – 7.44 (m, 6 arom. H); 7.40 – 7.35 (m, 4 arom. H);
7.38 – 7.28 (m, 3 arom. H); 3.79 (s, CH2(4)). 13C-NMR: 157.0 (C(2)); 155.7; 144.9; 143.5; 128.8; 128.5;
127.5; 127.2; 125.9; 124.1; 122.5; 121.1; 116.2 (CN); 112.3; 110.3; 94.5; 81.2 (C(5)); 45.5 (C(4)). LC/ESI-
MS: 364 (100, [M þ H]þ). Anal. calc. for C25H17NO2: C 82.63, H 4.72, N 3.85; found: C 82.86, H 4.37, N
4.05.
2-(tert-Butyl)-4,5-dihydro-5,5-diphenylfuran-3-carbonitrile (3d): Yield 0.273 g (90%). Yellow oil.
1H-NMR: 7.40 – 7.48 (m, 10 arom. H); 3.58 (s, CH2(4)); 1.36 (s, tBu).

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1
4,5-Dihydro-2,5-diphenylfuran-3-carbonitrile (3e): Yield 0.103 g (42%). Yellow oil. H-NMR: 8.02
(dd, J ¼ 8.0, 5.0, 2 arom. H); 7.48 – 7.36 (m, 8 arom. H); 5.83 (dd, J ¼ 11.2, 8.4, HꢀC(5)); 3.53 (dd, J ¼ 14.8,
10.8, HaꢀC(4)); 3.10 (dd, J ¼ 14.8, 8.4, HbꢀC(4)).
4,5-Dihydro-4-methyl-2,5-diphenylfuran-3-carbonitrile (3f): Yield 0.195 g (75%). Yellow oil. IR:
1
3030, 2207 (CN), 1646 (C¼C), 1232 (CꢀOꢀC), 758, 706. H-NMR: 8.02 (dd, J ¼ 8.0, 2.0, 2 arom. H);
7.50 – 7.36 (m, 8 arom. H); 5.25 (d, J ¼ 8.8, HꢀC(5)); 3.37 (dq, J ¼ 8.8, 6.8, HꢀC(4)); 1.44 (d, J ¼ 6.8, Me).
13C-NMR: 166.0 ((C(2)); 139.7; 131.7; 129.1; 129.0; 128.9; 128.1; 127.4; 125.9; 117.4 (CN); 91.8; 85.7
(C(5)); 47.9 (C(4)); 18.8 (Me). LC/ESI-MS: 262 (100, [M þ H]þ). Anal. calc. for C18H15NO: C 82.73, H
5.79, N 5.36; found: C 82.42, H 5.76, N 5.53.
4,5-Dihydro-4-methyl-5-phenyl-2-(2-thienyl)furan-3-carbonitrile (3g): Yield 0.205 g (77%). Yellow
oil. IR: 3026, 2207 (CN), 1650 (C¼C), 1244 (CꢀOꢀC), 758, 702. 1H-NMR: 7.90 (dd, J ¼ 3.6, 0.8, 1 arom.
H); 7.52 (dd, J ¼ 5.2, 1.2, 1 arom. H); 7.42 – 7.36 (m, 5 arom. H); 7.15 (dd, J ¼ 5.2, 4.4, 1 arom. H); 5.26 (d,
J ¼ 8.4, HꢀC(5)); 3.36 (dq, J ¼ 8.4, 6.4, HꢀC(4)); 1.43 (d, J ¼ 6.4, Me). 13C-NMR: 161.4 (C(2)); 139.4;
130.3; 130.2; 130.1; 129.15; 129.1; 128.3; 126.0; 117.1 (CN); 92.5; 84.1 (C(5)); 47.7 (C(4)); 18.8 (Me). LC/
ESI-MS: 268 (100, [M þ H]þ). Anal. calc. for C16H13NOS: C 71.88, H 4.90, N 5.24, S 11.99; found: C 71.74,
H 4.68, N 5.40, S 12.32.
4,5-Dihydro-5-methyl-2,5-diphenylfuran-3-carbonitrile (3h): Yield 0.209 g (80%). Yellow oil.
1H-NMR: 8.05 (dd, J ¼ 7.81, 1.95, 2 arom. H); 7.49 – 7.31 (m, 8 arom. H); 3.31 (d, J ¼ 14.5, HaꢀC(4));
3.23 (d, J ¼ 14.5, HbꢀC(4)); 1.40 (s, Me).
4,5-Dihydro-5-methyl-5-phenyl[2,2’-bifuran]-3-carbonitrile (3i): Yield 0.193 g (77%). Yellow oil. IR:
3061, 2209 (CN), 1648 (C¼C), 1180 (CꢀOꢀC), 758, 702. 1H-NMR: 7.61 (d, J ¼ 1.2, 1 arom. H); 7.39 – 7.32
(m, 5 arom. H); 7.06 (d, J ¼ 3.6, 1 arom. H); 6.65 (dd, J ¼ 3.6, 1.6, 1 arom. H); 3.26 (d, J ¼ 14.4, HaꢀC(4));
3.19 (d, J ¼ 14.8, HbꢀC(4)); 1.08 (s, Me). 13C-NMR: 156.9 (C(2)); 145.2; 144.7; 143.7; 128.6; 127.8; 124.1;
116.6 (CN); 113.9; 111.8; 91.1; 77.5 (C(5)); 45.2 (C(4)); 28.9 (Me). LC/ESI-MS: 252 (100, [M þ H]þ).
Anal. calc. for C16H13NO2: C 76.48, H 5.21, N 5.57; found: C 76.76, H 5.01, N 5.64.
2-(1-Benzofuran-2-yl)-4,5-dihydro-5-methyl-5-phenylfuran-3-carbonitrile (3j): Yield 0.244 g (81%).
Pale yellow solid. M.p. 104 – 1068 (hexane/AcOEt). IR: 3082, 2198 (CN), 1619 (C¼C), 1211 (CꢀOꢀC),
856, 760, 696. 1H-NMR: 7.66 (d, J ¼ 7.6, 1 arom. H); 7.61 (d, J ¼ 8.0, 1 arom. H); 7.43 – 7.37 (m, 5 arom. H);
7.35 – 7.28 (m, 3 arom. H); 3.32 (d, J ¼ 15.2, HaꢀC(4)); 3.25 (d, J ¼ 14.8, HbꢀC(4)); 1.85 (s, Me). 13C-NMR:
157.2 (C(2)); 155.6; 145.1; 144.8; 128.9; 128.1; 127.5; 127.1; 124.3; 124.0; 122.4; 116.5 (CN); 112.3; 110.2;
91.6; 80.7 (C(5)); 45.8 (C(4)); 29.1 (Me). LC/ESI-MS: 302 (100, [M þ H]þ). Anal. calc. for C20H15NO2: C
79.72, H 5.02, N 4.65; found: C 79.84, H 4.88, N 4.89.
4,5-Dihydro-5-methyl-5-phenyl-2-(2-thienyl)furan-3-carbonitrile (3k): Yield 0.229 g (86%). Yellow
oil. IR: 3026, 2970, 2201 (CN), 1635 (C¼C), 1180 (CꢀOꢀC), 764, 702. 1H-NMR: 7.09 (dd, J ¼ 4.0, 0.8, 1
arom. H); 7.50 (dd, J ¼ 5.2, 0.8, 1 arom. H); 7.38 – 7.36 (m, 4 arom. H); 7.30 (t, J ¼ 3.2, 1 arom. H); 7.14 (dd,
J ¼ 4.8, 4.0, 1 arom. H); 3.26 (d, J ¼ 14.4, HaꢀC(4)); 3.19 (d, J ¼ 14.8, HbꢀC(4)); 1.79 (s, Me). 13C-NMR:
161.2 (C(2)); 145.1; 130.6; 130.1; 129.8; 128.9; 128.3; 128.0; 124.3; 117.6 (CN); 91.1; 77.2 (C(5)); 45.8
(C(4)); 28.8 (Me). LC/ESI-MS: 268 (100, [M þ H]þ). Anal. calc. for C16H13NOS: C 71.88, H 4.90, N 5.24,
S 11.99; found: C 71.61, H 4.76, N 5.17, S 12.13.
4-Ethyl-4,5-dihydro-2,5,5-triphenylfuran-3-carbonitrile (3l): Yield 0.291 g (83%). Pale yellow solid.
M.p. 139 – 1418 (hexane/AcOEt). 1H-NMR: 8.26 (dd, J ¼ 7.4, 1.7, 2 arom. H); 7.76 (dd, J ¼ 7.5, 1.5, 2 arom.
H); 7.68 – 7.66 (m, 3 arom. H); 7.56 (tt, J ¼ 7.0, 1.6, 2 arom. H); 7.52 – 7.44 (m, 6 arom. H); 4.04 (dd, J ¼ 7.7,
5.9, HꢀC(4)); 1.59 – 1.52 (m, MeCH2); 1.14 (t, J ¼ 7.4, MeCH2).
4-Ethyl-4,5-dihydro-5,5-diphenyl-2-(2-thienyl)furan-3-carbonitrile (3m): Yield 0.257 g (72%). Yel-
low oil. 1H-NMR: 7.88 (d, J ¼ 3.8, 1 arom. H); 7.51 (d, J ¼ 7.2, 1 arom. H); 7.48 (d, J ¼ 5.0, 1 arom. H); 7.32
(t, J ¼ 7.8, 1 arom. H); 7.26 – 7.19 (m, 7 arom. H); 7.09 (t, J ¼ 4.8, 1 arom. H); 3.76 (t, J ¼ 6.9, HꢀC(4));
1.34 – 1.25 (m, MeCH2); 0.89 (t, J ¼ 7.4, MeCH2).
5,5-Bis(4-fluorophenyl)-4,5-dihydro-2-phenylfuran-3-carbonitrile (3n): Yield 0.308 g (86%). Yellow
oil. 1H-NMR: 7.41 – 7.38 (m, 5 arom. H); 7.36 (dd, J ¼ 9.0, 5.0, 4 arom. H); 7.12 (t, J ¼ 8.4, 1 arom. H); 3.62
(s, CH2(4)).
5,5-Bis(4-fluorophenyl)-4,5-dihydro[2,2’-bifuran]-3-carbonitrile (3o): Yield 0.286 g (82%). Yellow
oil. IR: 3063, 2200 (CN), 1623 (C¼C), 1253 (CꢀOꢀC), 829, 702. 1H-NMR: 7.65 (d, J ¼ 1.2, 1 arom. H);
7.40 – 7.36 (dd, J ¼ 9.0, 5.0, 4 arom. H); 7.13 (d, J ¼ 3.5, 1 arom. H); 7.08 (t, J ¼ 8.6, 4 arom. H); 6.59 (dd,

Helvetica Chimica Acta – Vol. 94 (2011)
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J ¼ 3.5, 1.6, 1 arom. H); 3.71 (s, CH2(4)). 13C-NMR: 163.6 – 161.4 (d, 1J(C,F) ¼ 246.9, CꢀF); 156.7 (C(2));
145.8; 143.5; 139.2 (d, 4J(C,F) ¼ 3.2); 127.8 (d, 3J(C,F) ¼ 8.3); 116.2 (CN); 115.8 (d, 2J(C,F) ¼ 21.8); 114.5;
112.2; 93.4; 78.1 (C(5)); 45.3 (C(4)). LC/ESI-MS: 350 (100, [M þ H]þ). Anal. calc. for C21H13F2NO2: C
72.20, H 3.75, N 4.01; found: C 72.44, H 3.52, N 4.30.
2-(1-Benzofuran-2-yl)-5,5-bis(4-fluorophenyl)-4,5-dihydrofuran-3-carbonitrile (3p): Yield 0.351 g
(88%). Yellow solid. M.p. 104 – 1068 (hexane/AcOEt). IR: 3059, 2200 (CN), 1643 (C¼C), 1172
(CꢀOꢀC), 835, 754, 700. 1H-NMR: 7.65 (d, J ¼ 7.6, 1 arom. H); 7.59 (dd, J ¼ 8.4, 0.8, 1 arom. H); 7.44 (s,
1 H); 7.41 – 7.36 (m, 5 arom. H); 7.29 (t, J ¼ 7.6, 1 H); 7.06 (t, J ¼ 8.4, 4 H); 3.73 (s, CH2(4)). 13C-NMR:
1
4
3
163.9 – 161.4 (d, J(C,F) ¼ 246.9, CꢀF); 156.8 (C(2)); 144.6; 139.1 (d, J(C,F) ¼ 3.1); 127.8 (d, J(C,F) ¼
7.7); 127.4; 127.3; 124.1; 122.5; 115.8 (d, 2J(C,F) ¼ 21.3); 115.9 (CN); 112.3; 110.6; 93.6; 81.1 (C(5));
45.6 (C(4)). LC/ESI-MS: 400 (100, [M þ H]þ). Anal. calc. for C25H15F2NO2: C 75.18, H 3.79, N 3.51;
found: C 75.52, H 3.66, N 3.42.
5,5-Bis(4-fluorophenyl)-4,5-dihydro-2-(2-thienyl)furan-3-carbonitrile (3q): Yield 0.310 g (85%).
Yellow oil. IR: 3028, 2194 (CN), 1606 (C¼C), 1257 (CꢀOꢀC), 835, 702. 1H-NMR: 7.95 (d, J ¼ 3.9,
1 H); 7.56 (d, J ¼ 4.7, 1 H); 7.37 (dd, J ¼ 9.0, 5.08, 4 H); 7.18 (t, J ¼ 3.9, 1 H); 7.06 (t, J ¼ 8.6, 4 H); 3.65 (s,
CH2(4)). 13C-NMR: 163.8 – 161.4 (d, 1J(C,F) ¼ 246.8, CꢀF); 160.8 (C(2)); 139.3 (d, 4J(C,F) ¼ 3.2); 130.4;
130.2; 130.0; 128.5; 127.7 (d, 3J(C,F) ¼ 8.4); 116.9 (CN); 115.9 – 115.7 (d, 2J(C,F) ¼ 21.1); 93.1; 77.6
(C(5)); 45.6 (C(4)). LC/ESI-MS: 366 (100, [M þ H]þ). Anal. calc. for C21H13F2NOS: C 69.03, H 3.59, N
3.83, S 8.78; found: C 69.14, H 3.68, N 3.70, S 8.96.
4,5-Dihydro-5,5-bis(4-methylphenyl)[2,2’-bifuran]-3-carbonitrile (3r): Yield 0.280 g (82%). Yellow
oil. IR: 3017, 2198 (CN), 1608 (C¼C), 1255 (CꢀOꢀC), 835, 704. 1H-NMR: 7.62 (d, J ¼ 1.5, 1 H); 7.26 (d,
J ¼ 7.8, 4 H); 7.16 (d, J ¼ 7.6, 1 H); 7.08 (d, J ¼ 3.5, 1 H); 6.54 (dd, J ¼ 3.5, 1.56, 1 H); 3.68 (s, CH2(4)); 2.33
(s, 2 Me). 13C-NMR: 157.0 (C(2)); 145.6; 143.9; 138.1; 129.4; 125.8; 116.7 (CN); 114.2; 112.1; 94.3; 78.1
(C(5)); 45.1 (C(4)); 21.2 (Me). LC/ESI-MS: 342 (100, [M þ H]þ). Anal. calc. for C23H19NO2: C 80.92, H
5.61, N 4.10; found: C 81.22, H 5.77, N 4.02.
2-(tert-Butyl)-4,5-dihydro-5,5-bis(4-methylphenyl)furan-3-carbonitrile (3s): Yield 0.265 g (80%).
Yellow oil. IR: 3032, 2922, 2203 (CN), 1617 (C¼C), 1111 (CꢀOꢀC), 827, 706. 1H-NMR: 7.27 (d, J ¼ 8.0,
4 H); 7.14 (d, J ¼ 7.6, 4 H); 3.55 (s, CH2(4)); 2.33 (s, 2 Me). 13C-NMR: 177.7 (C(2)); 141.8; 137.8; 129.3;
125.6; 117.5 (CN); 92.3; 77.4 (C(5)); 64.0; 35.0 (C(4)); 28.3; 21.2 (Me). LC/ESI-MS: 332 (100, [M þ H]þ).
Anal. calc. for C23H25NO: C 83.34, H 7.60, N 4.23; found: C 83.54, H 7.46, N 4.36.
4,5-Dihydro-5,5-bis(4-methylphenyl)-2-(2-thienyl)furan-3-carbonitrile (3t): Yield 0.310 g (87%).
Yellow oil. IR: 3078, 2205 (CN), 1618 (C¼C), 1238 (CꢀOꢀC), 835, 696. 1H-NMR: 7.92 (dd, J ¼ 4.0,
0.8, 1 H); 7.52 (dd, J ¼ 4.4, 0.4, 1 H); 7.27 (d, J ¼ 8.0, 4 H); 7.15 (d, J ¼ 7.6, 4 H); 3.70 (s, CH2(4)); 2.32 (s,
3 Me). 13C-NMR: 160.8 (C(2)); 140.8; 137.9; 130.2; 129.9; 129.7; 129.2; 128.1; 125.5; 117.1 (CN); 93.8; 77.4
(C(5)); 45.3 (C(4)); 21.0 (Me). LC/ESI-MS: 358 (100, [M þ H]þ). Anal. calc. for C23H19NOS: C 77.28, H
5.36, N 3.92, S 8.97; found: C 77.38, H 5.11, N 4.11, S 9.12.
2,3-Dihydro-2-methyl-2-phenyl-4H-furo[3,2-c][1]benzofuran-4-one (4a): Yield 0.200 g (72%). Col-
1
orless solid. M.p. 114 – 1168. H-NMR: 7.71 (dd, J ¼ 6.3, 1.5, 1 H); 7.5 (td, J ¼ 8.65, 1.59, 1 H); 7.37 – 7.26
(m, 7 arom. H); 3.35 (d, J ¼ 15.4, HaꢀC(3)); 3.26 (d, J ¼ 15.1, HbꢀC(3)); 1.83 (s, Me).
Ethyl 4,5-Dihydro-2,5-dimethyl-5-phenylfuran-3-carboxylate (5a): Yield 0.195 g (79%). Yellow oil.
1H-NMR: 7.42 (d, J ¼ 8.0, 2 H); 7.34 (t, J ¼ 7.6, 2 H); 7.30 (dd, J ¼ 8.0, 1.2, 1 H); 3.41 (d, J ¼ 15.0,
HaꢀC(4)); 3.35 (d, J ¼ 15.0, HbꢀC(4)); 4.22 (q, J ¼ 7.2, MeCH2); 2.63 (s, Me); 1.34 (t, J ¼ 7.2, MeCH2).
Ethyl 4,5-Dihydro-2-methyl-5,5-diphenylfuran-3-carboxylate (5b): Yield 0.250 g (81%). Yellow oil.
1H-NMR: 8.05 (d, J ¼ 7.6, 1 H); 7.51 – 7.34 (m, 8 arom. H); 3.32 (s, CH2(4)); 4.32 (q, J ¼ 7.6, MeCH2); 2.65
(s, Me); 1.35 (t, J ¼ 7.6, MeCH2).
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Received November 30, 2010