An efficient one-pot synthesis of spiro dihydrofuran fluorene and spiro 2-hydroxytetrahydrofuran fluorene derivatives via [3+2] oxidative cycloaddition mediated by CAN

Article abstract of DOI:10.1016/j.tetlet.2008.10.011

Spiro dihydrofuran fluorene derivatives were prepared via [3+2] oxidative cycloaddition of 1,3-dicarbonyl compounds to 9-benzylidene-9H-fluorene and 2-(9H-fluorene-9-ylidene)-1-phenylethanone derivatives mediated by ceric ammonium nitrate. In the case of

Full text of DOI:10.1016/j.tetlet.2008.10.011

Tetrahedron Letters 49 (2008) 7260–7263
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An efficient one-pot synthesis of spiro dihydrofuran fluorene and spiro
2-hydroxytetrahydrofuran fluorene derivatives via [3+2] oxidative
cycloaddition mediated by CAN
*
G. Savitha, R. Sudhakar, P. T. Perumal
Organic Chemistry Division, Central Leather Research Institute, Adyar, Chennai 600 020, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Spiro dihydrofuran fluorene derivatives were prepared via [3+2] oxidative cycloaddition of 1,3-dicar-
bonyl compounds to 9-benzylidene-9H-fluorene and 2-(9H-fluorene-9-ylidene)-1-phenylethanone
derivatives mediated by ceric ammonium nitrate. In the case of the reaction of 9-benzylidene-9H-fluo-
rene with acyclic 1,3-dicarbonyl compounds, spiro 2-hydroxytetrahydrofuran fluorene derivatives were
obtained.
Received 27 June 2008
Revised 25 September 2008
Accepted 3 October 2008
Available online 7 October 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Fluorene-based derivatives have been extensively investigated
for electronic and photonic applications, such as light emitting
diodes, charge-transfer agents, field effect transistors, sensors,
and more recently, two-photon absorbing materials.1
When compared to unsubstituted fluorene, 9,9-disubstituted
fluorene building blocks containing oligomers and polymers have
higher solubility and thermal stability.2 Also the optical, thermal,
and electrochemical properties of oligofluorenes are known to be
changed by varying the substitution patterns or by introducing a
spiro-configured structure at the C-9 position of the fluorenyl
ring.3
Spiro-functionalization at the C-9 position of a fluorene unit not
only improves the emission spectral quality but also prevents the
aggregation of the polymer at the ground state, and thereby mini-
mizes excimer formation in solid films.4 One such spiro-configured
fluorene system is spiro bi-fluorene, which was introduced by Tour
and co-workers.5 Since then, there has been a continuous exploita-
tion of spiro bi-fluorene building blocks in the construction of oligo-
mers and polymers.6 Also, research continues in the structural
modification of the spiro-bifluorene unit either by introducing a
heteroatom in the structural frame or by linking the spiro unit to
To contribute to this area of research, herein, we describe an
efficient one-pot synthesis of novel spiro dihydrofuran fluorene
derivatives by the [3+2] oxidative cycloaddition of cyclic and
acyclic 1,3-dicarbonyl compounds to 9-benzylidene-9H-fluorene
and 2-(9H-fluorene-9-ylidene)-1-phenylethanone derivatives
mediated by ceric ammonium nitrate, in which a substituted
dihydrofuran unit is spirally attached to the C-9 position of the
fluorene ring.
Initially, the reaction was explored by treating 1,3-dicarbonyl
compound 2a with 1 equiv of 1a at 0 °C in the presence of 2.5 equiv
of CAN and 3 equiv of NaHCO3 in acetonitrile (Scheme 1, Table 1).
The reaction proceeded smoothly within 15 min to afford 3a as a
single regioisomer in 80% yield after purification by column chro-
matography. No other isomer could be detected.
In the 1H NMR spectrum of 3a the benzylic proton appeared as a
singlet at d 4.85 ppm, and in the 13C NMR spectrum a signal due to
the spiro carbon at d 98.7 ppm confirmed the formation of 3a.9 The
structure of 3a was also confirmed by X-ray diffraction studies
(Fig. 1). In the ortep diagram of compound 3a the, C-6 atom is
disordered over two positions with occupancy factors of 0.3
a
heteroaromatic ring in order to improve and extend its
applications.7
O
R
Incorporating heteroaryl groups, for example, thiophene, pyr-
idine, and carbazole into spiro compounds will be a useful strategy
to expand the application of spiro compounds. Recently, Xie et al.
synthesized novel thiophene-containing ter [9,90-spiro bifluorene]
analogue.8
CAN/NaHCO3
O
+
R1
R1
CH3CN/0 ºC
O
H
O
R1
R
R1
1
2
3
1a) R = Cl, 1b) R = H, 1c) R = OMe, 1d) R = Me
2a) R1 = H, 2b) R1 = Me
* Corresponding author. Tel.: + 91 44 24911386; fax: +91 44 24911589.
E-mail address: ptpetumal@gmail.com (P. T. Perumal).
Scheme 1.
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.10.011

G. Savitha et al. / Tetrahedron Letters 49 (2008) 7260–7263
7261
Table 1
corresponding to one proton each with coupling constants of J
13.75 Hz were found which confirmed that these protons were
located adjacent to one another with trans stereochemistry.
Based on these results and further information from the 13C
NMR spectrum, the structure of the product was assigned as spiro
2-hydroxytetrahydrofuran fluorene derivative 6b.11 Further, the
molecular formula was confirmed from mass spectrometer. The
relative stereochemistry of the substituents on the tetrahydrofuran
ring was assigned based on NOE experiments. In the 1H NMR spec-
trum of 6b, a singlet at d 1.87 ppm was attributed to methyl group
attached to the tetrahydrofuran ring, and the two doublets at d
4.87 ppm and d 3.99 ppm were attributed to Ha and Hb, respec-
tively (Fig. 2). While irradiating the proton Hb, a little enhance-
ment was observed in the signal at d 1.87 ppm and no such
enhancement was observed in the signal at d 4.87 ppm, which sug-
gests a trans relationship between the protons Ha and Hb and a cis
relationship between the proton Hb and the methyl group (Fig. 2).
To further confirm this, single crystals of compound 6e were ob-
tained by recrystallisation, and the stereochemistry was confirmed
unambiguously by X-ray diffraction studies (Fig. 3).12
Synthesis of spiro dihydrofuran fluorene derivatives from 9-benzylidene-9H-fluorene
derivatives
Entry
9-Benzylidene-9H-
fluorene derivative 1
1,3-Dicarbonyl
compound 2
Productsa
R
3
Yield
(%)
R1
1
2
3
4
5
6
1a
1a
1b
1c
1c
1d
2a
2b
2a
2b
2a
2a
3a
3b
3c
3d
3e
3f
Cl
Cl
H
OMe
OMe
Me
H
Me
H
Me
H
H
80
82
83
78
79
83
a
All the reactions were complete in 15 min.
Similar products were obtained while treating other (9-benzyl-
idene-9H-fluorene) derivatives with acyclic 1,3-dicarbonyl com-
pounds. The results are summarized in Table 2. A plausible
mechanism for the formation of 5 and 6 is given in Scheme 3.
As the first step, Ce4+ ion abstracts an electron from the 1,3-dicar-
bonyl compound (4), generating radical (i) which in turn reacts with
9-benzylidene-9H-fluorene derivative to form the radical (ii). Again
another Ce4+ ion abstracts an electron from radical (ii) affording car-
bocation (iii). The carbocation (iii) thus formed can undergo reaction
following two different path ways namely A and B to furnish the
products 5 and 6, respectively. In path A, the expected product 5 is
formed from carbocation (iii) via deprotonation. In path B, the prod-
uct 6 is formed from carbocation (iii) by the attack of water molecule
on the carbonyl carbon followed by cyclization.
The formation of 3 as the only product in the reaction of cyclic
1,3-dicarbonyl compound 2 with 1 (Scheme 1) clearly supports the
mechanistic pathways. In the case of cyclic 1,3-dicarbonyl com-
pound, the water molecule could not easily approach the carbonyl
carbon to afford the 2-hydroxy tetrahydrofuran derivative (Path B)
due to steric factors, thereby the competing deprotonation reaction
(Path A) takes place rapidly to give the expected spiro dihydrofuran
fluorene derivative 3 as the only product (Scheme 1). Whereas in
Figure 1. Ortep diagram of 3a.
(C6A) and 0.7 (C6B) because of large thermal vibration of this
atom.10 Similar products were obtained in good yields using a vari-
ety of substituted (9-benzylidene-9H-fluorene) derivatives under
similar conditions. The results are summarized in Table 1.
Treating 1b with acyclic 1,3-dicarbonyl compound 4a under
similar reaction conditions gave the corresponding expected spiro
[dihydrofuran-fluorene] derivative (5b) in a 1:1 ratio with a com-
pound whose molecular weight exceeded by 18 units that of the
expected product (Scheme 2). In the IR spectrum, the appearance
of a peak at 3435 cmꢀ1 confirmed the presence of an OH group.
The OH proton could not be detected in the 1H NMR spectrum,
but an additional proton in the aliphatic region was observed.
Instead of a singlet, two doublets at d 3.99 ppm and 4.87 ppm
O
Hb
CH3
Ha
OH
O
CH3
Figure 2. Characteristic nOe of compound 6b.
O
O
R
R
CAN/NaHCO3
CH3CN/0 ºC
+
O
R3
O
+
H
R2
R2
H
CH3
OH
O
O
CH3
R
R3
R3
R2
6
5
4
1
4a) R3 = Me, 4b) R3 = OEt
1a) R = Cl,R2 = H, 1b) R = H, R2 = H, 1e) R = Cl, R2 = Cl
Scheme 2.

7262
G. Savitha et al. / Tetrahedron Letters 49 (2008) 7260–7263
In the case of the reaction of dimedone (2b) with 1 equiv of 7b
in the presence of 2.5 equiv of CAN and 3 equiv of NaHCO3 at 0 °C
in acetonitrile (Scheme 4, Table 3), 8d was obtained as a single
isomer in 82% yield after purification through column chromato-
graphy. In the 1H NMR spectrum, the proton of the dihydrofuran
ring appeared as a singlet at d 5.26 ppm, and in the 13C NMR spec-
trum the spiro carbon appeared at d 95.9 ppm which confirmed the
formation of the product.13 Similar products were obtained with
other 2-(9H-fluorene-9-ylidene)-1-phenylethanone derivatives.
The results are summarized in Table 3.
In conclusion, we have successfully prepared the spiro-config-
ured fluorene derivatives in which a functionalized furan is spirally
attached to the C-9 position of the fluorene ring. Further utilization
of this spiro unit as a building block to prepare oligomers and poly-
mers and the investigation of its photoluminescence properties are
underway.
O
O
CAN/NaHCO3
O
CH3CN/0 ºC
Figure 3. Ortep diagram of 6e.
R1
+
O
H
O
R1
O
R
R1
Table 2
Synthesis of spiro dihydrofuran fluorene and spiro 2-hydroxytetrahydrofuran fluo-
R1
rene derivatives from 9-benzylidene-9H-fluorene derivatives
R
8
Productsa,b 5, 6
Yieldc
(%)
2
Entry 9-Benzylidene-9H- 1,3-Dicarbonyl
fluorene derivative 1 compound 4
7
R
R2 R3
1
) R = H, ) R1 = Me
2a
2b
7a) R = H, 7b) R = Cl
1
2
3
4
5
1a
1b
1b
1e
1e
4a
4a
4b
4a
4b
5a, 6a
5b, 6b
5c, 6c
5d, 6d Cl Cl
5e, 6e Cl Cl
Cl
H
H
H
H
H
Me
Me
81
80
OEt 83
Me 78
OEt 79
Scheme 4.
Table 3
a
b
c
All the reactions were completed within 15 min.
Products 5 and 6 were obtained in 1:1 ratio.
Isolated overall yield.
Synthesis of spiro dihydrofuran fluorene derivatives from 2-(9H-fluorene-9-ylidene)-
1-phenylethanone derivatives
Entry
2-(9H-Fluoren-9-ylidene) -
1-phenylethanone 7
1,3-Dicarbonyl
compound 2
Productsa
R
8
Yield
(%)
R1
the case of acyclic 1,3-dicarbonyl compound, both the competing
reaction pathways A and B (deprotonation and attack of the water
molecule on the carbonyl carbon followed by cyclization) takes
place, resulting in the formation of products 5 and 6 in (1:1) ratio
(Scheme 2).
1
2
3
4
7a
7a
7b
7b
2a
2b
2a
2b
8a
H
H
Cl
Cl
H
Me
H
85
84
80
82
8b
8c
8d
Me
a
All the reactions were complete within 15 min.
O
O
O
O
O
Ph
Ph
Ce4+
H
R3
R3
R3
4
i
ii
O
Ce4+
-H+
Path A
O
Ph
+
Path B
Ph
O
CH3
5
O
Ph
HO
O
H
CH3
a
O
R3
R3
O
CH3
b
H2O
6
iii
Scheme 3.

G. Savitha et al. / Tetrahedron Letters 49 (2008) 7260–7263
7263
6.89 (t, 1H, J = 7.65 Hz), 6.72 (d, 2H, J = 8.4 Hz), 6.54 (d, 1H, J = 7.65 Hz), 4.85 (s,
1H), 2.55–2.76 (m, 4 H), 2.23–2.29 (m, 2H).
Acknowledgment
13C NMR (125 MHz, CDCl3): d 194.6, 179.7, 147.5, 141.2, 140.5, 139.5, 136.3,
132.9, 130.3, 129.7, 129.5, 128.8, 128.3, 127.4, 126.5, 122.9, 120.2, 119.9, 115.4,
98.7, 53.1, 37.2, 24.8, 22.0. MS (EI) m/z = 398 (M+), 400 (M++2). Anal. Calcd for
C26H19ClO2: C, 78.29; H, 4.80. Found: C, 77.89; H, 4.68.
One of the authors G.S. expresses her gratitude to the Council of
Scientific and Industrial Research, New Delhi, for a research
fellowship.
10. Crystallographic data for the compound 3a in this Letter have been deposited
with the Cambridge Crystallographic Data centre as Supplemental Publication
No. CCDC 702989. Copies of the data can be obtained, free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax: +44 01223
336033 or email: deposit@ccdc.cam.ac.uk).
References and notes
11. General procedure for 5b and 6b: Following the general procedure as described
above, 5b and 6b were obtained from 9-benzylidene-9H-fluorene (1b)
(1.18 mmol, 0.3 g), acetyl acetone (4a) (1.18 mmol, 0.118 g, 1 equiv), and
NaHCO3 (3.54 mmol, 0.297 g, 3 equiv) in the presence of ceric ammonium
nitrate (2.95 mmol, 1.62 g, 2.5 equiv) as a crude mixture, which was purified
and separated by column chromatography on silica gel, with ethyl acetate–
hexane (3:7) as eluent to afford the product 5b 0.166 g and 6b 0.175 g.
1. (a) Belfield, K. D.; Bondar, M. V.; Morales, A. R.; Yavuz, O.; Przhonska, O. V. J.
Phys. Org. Chem. 2003, 16, 194–201; (b) Perepichka, D. F.; Bryce, M. R.;
Perepichka, I. F.; Lyubchik, S. B.; Christensen, C. A.; Godbert, N.; Batsa-nov, A. S.;
Levillian, E.; McInnes, E. J. L.; Zhao, J. P. J. Am. Chem. Soc. 2002, 124, 14227–
14238; (c) Burgi, L.; Richards, T. J.; Friend, R. H.; Sirringhaus, H. J. Appl. Phys.
2003, 94, 6129–6137; (d) Gaylor, B. S.; Heeger, G. C. J. Am. Chem. Soc. 2003, 125,
896–900; (e) Belfield, K. D.; Hagan, D. J.; Van Stryland, E. W.; Schafer, K. J.;
Negres, R. A. Org. Lett. 1999, 1575–1578.
2. (a) Rodriguez, J. G.; Tejedor, J. L.; Parra, T. L.; Diaz, C. Tetrahedron 2006, 62,
3355; (b) Wong, W.-Y.; Lu, G.-L.; Choi, K.-H.; Lin, Z. Eur. J. Org. Chem. 2003, 365
and references cited therein; (c) Promarak, V.; Saengsuwan, S.; Jungsuttiwong,
S.; Sudyoadsuk, T.; Keawin, T. Tetrahedron Lett. 2007, 48, 89–93.
3. (a) Zhou, X. H.; Yan, J.-C.; Pei, J. Org. Lett. 2003, 5, 3543–3546; (b) Katsis, D.;
Geng, Y. H.; Ou, J. J.; Culligan, S. W.; Trajkovska, A.; Chen, S. H.; Rothberg, L. J.
Chem. Mater. 2002, 14, 1332–1339.
4. Zeng, G.; Yu, W.-L.; Chua, S.-J.; Huang, W. Macromolecules 2002, 35, 6907–6914.
5. Wu, R.; Schumm, J. S.; Pearson, D. L.; Tour, J. M. J. Org. Chem. 1996, 61, 6906.
6. (a) Salbeck, J.; Yu, N.; Bauer, J.; Neissortel, F.; Bestgen, H. Synth. Met. 1997, 91,
209; (b) Pudzich, R.; Salbeck, J. Synth. Met. 2003, 138, 21.
Spectral data for compound 5b (Table 2): mp = 146 °C. IR:
mmax = 1374, 1450,
1595, 1664, 1715, 2929, 3061 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.69 (d, 1H,
.
J = 7.65 Hz), 7.61–7.66 (m, 1H), 7.41–7.52 (m, 3 H), 7.27–7.33 (m, 2H), 7.17–
7.20 (m, 3H), 6.79–7.02 (m, 2H), 6.44 (d, 1H, J = 7.65 Hz), 4.78 (s, 1H), 2.56 (s,
3H), 1.98 (s, 3H). 13C NMR (125 MHz, CDCl3): d 195.5, 171.1, 148.5, 141.4,
140.6, 139.5, 139.1, 134.8, 130.1, 129.5, 128.7, 128.5, 127.6, 127.2, 126.7, 122.5,
120.2, 119.7, 115.3, 96.4, 57.5, 29.8, 15.6. MS (EI) m/z = 352 (M+). Anal. Calcd for
C25H20O2: C, 85.20; H, 5.72. Found: C, 84.78; H, 5.50.
Spectral data for compound 6b (Table 2): mp = 102 °C. IR:
mmax = 1354, 1450,
1494, 1601, 1693, 2922, 3033, 3435 cmꢀ1 1H NMR (500 MHz, CDCl3): d 7.92 (d,
.
1H, J = 7.65 Hz), 7.46–7.47 (m, 1H), 7.37–7.41 (m, 2H), 7.28–7.32 (m, 2H), 7.07–
7.12 (m, 2H), 6.88–6.93 (m, 3H), 6.60 (d, 2H, J = 6.9 Hz), 4.87 (d, 1H,
J = 13.75 Hz), 3.99 (d, 1H, J = 13.75 Hz), 2.25 (s, 3H), 1.89 (s, 3 H). 13C NMR
(125 MHz, CDCl3): d 206.9, 147.4, 145.2, 140.6, 139.8, 134.7, 129.5, 129.3,
128.9, 128.3, 127.9, 127.2, 127.1, 125.0, 124.6, 119.8, 119.7, 104.2, 93.5, 63.7,
56.3, 30.3, 27.6. MS (EI) m/z = 370 (M+). Anal. Calcd for C25H22O3: C, 81.06; H,
5.99. Found: C, 80.9; H, 5.63.
7. (a) Katsis, D.; Geng, Y. H.; Ou, J. J.; Culligan, s. W.; Trajkovska, A.; Chen, S. H.;
Rothberg, L. J. Chem. Mater. 2002, 14, 1332; (b) Wong, K.-T.; Chien, Y.-Y.; Chen,
R.-T.; Wang, C.-F.; Lin, Y.-T.; Chiang, H.-H.; Hsieh, P.-Y.; Wu, C.-C.; Chou, C. H.;
Su, Y. O.; Lee, G.-H.; Peng, S.-M. J. Am. Chem. Soc. 2002, 124, 11576; (c) Kim, Y.
H.; shin, D. C.; Kim, S. H.; Ko, C. H.; Yu, H. S.; Chae, Y. S.; Kwon, S. K. Adv. Mater.
2001, 13, 1690; (d) Wong, K.-T.; Chen, R.-T.; Fang, F.-C.; Wu, C.-C.; Lin, Y.-T. Org.
Lett. 2005, 7, 1979–1982.
12. Crystallographic data for the compound 6e in this Letter have been deposited
with the Cambridge Crystallographic Data centre as Supplemental Publication
No. CCDC 702995. Copies of the data can be obtained, free of charge on
application to CCDC, 12 Union Road, Cambridge CB2 1EZ,UK (fax: +44 01223
336033 or email: deposit@ccdc.cam.ac.uk).
8. Xie, L.-H.; Fu, T.; Hou, X.-Y.; Tang, C.; Hua, Y.-R.; Wang, R.-J.; Fan, Q.-L.; Peng, B.;
Wei, W.; Huang, W. Tetrahedron Lett. 2006, 47, 6421–6424.
9. General procedure for 3a: To a stirred mixture of 9-(4-chlorobenzylidene)-9H-
fluorene (1a) (1.03 mmol, 0.3 g), 1,3-dicarbonyl compound 2a (1.03 mmol,
0.115 g, 1 equiv), and NaHCO3 (3.09 mmol, 0.260, 3 equiv) in acetonitrile
(10 mL), ceric ammonium nitrate (2.58 mmol, 1.412 g, 2.5 equiv) dissolved in
acetonitrile (5 mL) was added dropwise at 0 °C under N2. The reaction mixture
was stirred until completion of the reaction as monitored by TLC. Water was
added to the mixture and the product was extracted into ethyl acetate
(2 ꢁ 20 mL) and then dried over anhydrous Na2SO4. Removal of the solvent
under reduced pressure gave a crude product, which was purified by column
chromatography on silica gel, with ethyl acetate–hexane (4:6) as eluent to
afford the 0.328 g pure product (80%) as a white crystalline solid. Single
crystals of 3a were obtained by recrystallization from ethyl acetate.
13. General procedure for 8d: Following the general procedure as described above,
8d was obtained from 1-(4-chlorophenyl)-2-(9H-fluoren-9-ylidene)ethanone
(7b) (1 mmol, 0.316 g), dimedone (2b) (1 mmol, 0.14 g, 1 equiv), and NaHCO3
(3 mmol, 0.252 g, 3 equiv) in the presence of ceric ammonium nitrate
(2.5 mmol, 1.37 g, 2.5 equiv) in 82% (0.373 g) yield as a light yellow solid.
Spectral data for compound 8d (Table 3): mp = 186 °C. IR:
mmax = 1369, 1447,
1631, 1585, 1660, 2937, 3087 cmꢀ1 1H NMR (500 MHz, CDCl3): d 8.31 (d, 1H,
.
J = 8.45 Hz), 7.57–7.63 (m, 2H), 7.48 (t, 1H, J = 7.65 Hz), 7.32–7.43 (m, 3H),
7.14–7.19 (m, 3H), 6.99–7.05 (m, 2H), 5.26 (s, 1H), 2.38–2.61 (m, 4H), 1.36 (s,
3H), 1.25 (s, 3H). 13C NMR (125 MHz, CDCl3): d 193.9, 193.8, 177.9, 146.4,
140.7, 140.1, 139.8, 139.3, 134.9, 130.7, 130.4, 129.4, 129.2, 128.4, 128.1, 126.7,
123.1, 120.3, 120.0, 112.7, 95.9, 55.3, 51.1, 38.3, 34.8, 28.9, 28.5. MS (EI)
m/z = 454 (M+), 456 ((M++2). Anal. Calcd for C29H23ClO3: C, 76.56; H, 5.10.
Found: C, 76.00; H, 4.89.
Spectral data for compound 3a (Table 1): mp = 150 °C. IR:
m
max = 1390, 1483,
7.61(d, 1H,
1630, 1716, 2923, 3040 cmꢀ1 1H NMR (500 MHz, CDCl3):
.
d
J = 7.65 Hz), 7.53 (d, 1H, J = 7.65 Hz), 7.51 (d, 1H, J = 7.65 Hz), 7.43 (t, 1H, J =
6.85 Hz), 7.32 (t, 1H, J = 6.85 Hz), 7.21 (t, 1H, J = 7.6 Hz), 7.06 (d, 2H, J = 8.4 Hz),