A novel cyclization reaction between 2,3-bis(trimethylsilyl)buta-1,3-diene and acyl chlorides with straightforward formation of polysubstituted furans

Article abstract of DOI:10.1039/b705257j

A novel cyclization process of 2,3-bis(trimethylsilyl)buta-1,3-diene with various acyl chlorides in the presence of aluminium trichloride affords 2,5-disubstituted or 2,3,5-trisubstituted furans in short reaction time; a subsequent acylation process of th

Full text of DOI:10.1039/b705257j

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A novel cyclization reaction between 2,3-bis(trimethylsilyl)buta-1,3-
diene and acyl chlorides with straightforward formation of
polysubstituted furans{
Francesco Babudri,ab Stefania R. Cicco,b Gianluca M. Farinola,a Linda C. Lopez,a Francesco Naso*ab and
Vita Pintoa
Received (in Cambridge, UK) 10th April 2007, Accepted 28th June 2007
First published as an Advance Article on the web 9th July 2007
DOI: 10.1039/b705257j
positions in the reaction with the ArCOCl/AlCl3 electrophile
follows a different and very useful synthetic pathway.
A novel cyclization process of 2,3-bis(trimethylsilyl)buta-1,3-
diene with various acyl chlorides in the presence of aluminium
trichloride affords 2,5-disubstituted or 2,3,5-trisubstituted
furans in short reaction time; a subsequent acylation process
of the furan ring occurs if the reaction time is prolonged.
As a starting point we studied the reaction of 46 with the
benzoyl chloride 5a/aluminium trichloride complex, following the
protocol described for the corresponding reaction of 1,4-bis(tri-
methyilsilyl)buta-1,3-diene 1a.2a Accordingly, the freshly prepared
benzoyl chloride 5a/AlCl3 complex was slowly added to a solution
of the diene 4 in 1.1:1 molar ratio, maintaining the temperature at
0 uC. After 18 h reaction time, 4 was only partially converted
(46%) and the unexpected 2-methyl-5-phenylfuran 7a (Scheme 2)
was isolated in 48% yield after work-up and chromatography on
silica gel column.7
In the frame of our studies dealing with synthesis of polyconju-
gated compounds,1 we have extensively used unsaturated silanes as
convenient starting materials.2 Among them, (1E,3E)-1,4-bis(tri-
methylsilyl)buta-1,3-diene 1a and (1E,3E,5E)-1,6-bis(trimethyl-
silyl)hexa-1,3,5-triene 1b were subjected to formal cross-coupling
processes2f,g and to substitution reactions with various electro-
philes.2a–c.e In particular, we reported a convenient approach to
ketosilanes with a conjugated (all-E) diene 2a or triene 2b structure
via a highly chemoselective substitution of one trimethylsilyl group
of the butadiene 1a or hexatriene 1b with acyl chlorides in the
presence of AlCl3. Subsequent substitution of the second silyl
group with another acyl chloride in the same reaction flask led
to the corresponding dicarbonyl compounds with a conjugated
diene 3a or triene 3b structure (Scheme 1).2a This methodology
was successfully applied to the synthesis of several compounds
of biological interest2b,f and to precursors of more extended
polyenes.2e With this background, we addressed our attention to
the acylation reaction of 2,3-bis(trimethylsilyl)buta-1,3-diene 4.
The butadiene 4 is easily available by various synthetic methodo-
logies3 but, with the exception of Diels–Alder reactions,3d,e
addition of chlorocarbenes4 and polymerization processes,5 its
reactivity has not yet been explored. Now we wish to report that
the 2,3-bis-substituted diene 4 with the silyl groups in the internal
Functionalized furans are common structural units in many
natural molecules and pharmaceuticals,8 flavours and fragrance
compounds9 and are broadly used as building blocks in organic
synthesis10 and materials science.11 Common synthetic approaches
are based either on cyclization of acyclic precursors or on trans-
formation of furan rings by various functionalization processes.12
Much attention has been paid to the former type of strategy,
because of its broader potential and versatility.13 In view of these
considerations, we decided to investigate the reaction of Scheme 2
as a novel method for the synthesis of functionalized furans.
Different experimental conditions were tested to lead the
reaction to completion. We found that a 1 : 2 molar ratio between
the starting diene 4 and the benzoyl chloride 5a/AlCl3 complex was
necessary to complete the conversion of 4 affording, after 18 h
reaction time, 7a in 40% yield together with two regioisomeric
products 8a,b (15% yield), deriving from the acylation of the furan
ring (Scheme 3). A further increase of the 4 : 5a/AlCl3 ratio to 1 : 4
led, after a comparable reaction time, to the complete acylation of
7a affording exclusively 8a,b (62% yield) (Scheme 3). Higher yield
of 2,5-disubstituted furan 7a (56%) was obtained by increasing the
4 : 5a/AlCl3 ratio up to 1 : 6 and shortening the reaction time
(40 min) to prevent further acylation of the furan ring (Scheme 3).
A simple change of the experimental conditions allowed us to
carry out the reaction with a more convenient stoichiometry: slow
addition of the diene 4 to the pre-formed benzoyl chloride 5a/AlCl3
complex in 1 : 1.5 4 : 5a/AlCl3 molar ratio at 0 uC followed by
Scheme 1
aDipartimento di Chimica, Universita` degli Studi di Bari, via Orabona,
4 I-70126, Bari, Italy
bCNR ICCOM Bari, Dipartimento di Chimica Universita` degli Studi di
Bari, Bari, Italy. E-mail: f.naso@chimica.uniba.it
{ Electronic supplementary information (ESI) available: Spectral data for
all the furans synthesized and detailed experimental procedures. NOE
experiments for compounds 6a–e. See DOI: 10.1039/b705257j
Scheme 2
3756 | Chem. Commun., 2007, 3756–3758
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Table 1 Synthesis of polysubstituted furans
5/AlCl3
Entry RCOCl
equiv.
Silylated furan 6
Furan 7
1
1.5
—
2
3
1.5
Scheme 3
immediate quenching with a saturated solution of ammonium
chloride led to reaction completion without further acylation of the
furan ring. The furan 7a was isolated as the sole reaction product
in 63% yield by silica gel column chromatography.14 GC-MS
analysis of the reaction mixture before quenching and chromato-
graphic purification revealed the presence of a mixture of 7a and a
trimethylsilyl-substituted 7a, as already observed in the first
experiment described.7 Different experimental conditions had to
be used to isolate this elusive silylated intermediate: quenching the
reaction with a sodium carbonate saturated aqueous solution and
chromatographic purification on basic alumina column afforded,
besides furan 7a (43% yield), a silylated derivative (21% yield),
3b
4
5
1.5
2d
1
which was identified via H NMR spectroscopy as 2-methyl-3-
trimethylsilyl-5-phenyl furan 6a. The position of the trimethylsilyl
group on the furan ring was unambiguously determined by NOE
experiments (see ESI{). From these data it seems reasonable that
6a is formed as the first cyclization product, which then undergoes
an easy desilylation in the acidic work up conditions and during
the chromatography on silica gel column (Scheme 4).
6
7
1.5
1.5
—
—
The reaction was extended to various acyl chlorides 5b–g in
similar experimental conditions (Scheme 4) and the results are
summarized in Table 1.
When acyl chlorides 5b–e were used (entries 2–5, Table 1), the
corresponding silylated furans 6b–e, whose structure was con-
firmed by NOE experiments, survived work-up and silica gel
chromatographic purification and were isolated as the sole reaction
products. They were subsequently subjected to quantitative
desilylation in the presence of BF3?etherate (Scheme 4). An
increase of the acylation complex : diene ratio to 2 : 1 and to 3 : 1
was necessary for chlorides 5e and 5c, respectively, to optimize the
reaction yields, and longer reaction times were needed in the case
of the acyl chlorides 5b and 5c to lead the reaction to completion.
Although further studies are necessary to elucidate the
mechanism of the process, the tentative pathway reported in
Scheme 5 would involve: (i) acylation of diene 4 at the terminal
carbon atom with formation of allyl cation A;15(ii) deprotonation
of A with formation of bis(trimethylsilyl) ketodiene B; (iii)
protonation of B to generate allyl cation C;15 (iv) cyclization of
aReaction time 95 min including diene addition (20 min).b 4 : 5c/
AlCl3 ratio = 1 : 3 was necessary to optimize the reaction yield
(1 : 1.5 ratio and 1 : 2 ratio afforded 32 and 40% yield, respectively).
cReaction time 50 min including diene addition (20 min).d 4 : 5e/
AlCl3 ratio = 1 : 2 was necessary to lead reaction to completion
C to cyclic allyl cation D;15 (v) desilylation of D affording the
silylated furan 6a.
In summary, we have reported our preliminary results on a
novel cyclization process of the bis-silylated diene 4 and acyl
chlorides promoted by aluminium trichloride, which appears
suitable as a general protocol for the synthesis of 2,5-disubstituted
and, in many cases, 2,3,5-trisubstituted furans. The method
compares well with other cyclization processes for the synthesis
Scheme 4
Scheme 5
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Chemistry, ed. G. Gribble and J. Joulet, Elsevier Science, Amsterdam,
2005, vol. 17, pp. 142–171.
9 Common Fragrance and Flavour Materials, ed. K. Bauer and D. Garbe,
VCH, Weinheim, 1985.
of substituted furans, in view of the easy experimental procedure
and availability of starting compounds. The isolation, in many
cases, of 3-trimethylsilyl-substituted furans represents another
advantage of our approach, in consideration of the possibility,
explored in the recent literature,12b to use the trimethylsilyl group
for the regioselective introduction of functional groups on the
furan ring.
10 B. H. Lipshutz, Chem. Rev., 1986, 86, 795; H.-K. Lee, K.-F. Chan,
C.-W. Hui, H.-K. Yim, X.-W. Wu and H. N. C. Wong, Pure Appl.
Chem., 2005, 77, 139.
11 C.-F. Lee, L.-M. Yang, T.-Y. Hwu, A.-S. Feng, J.-C. Tseng and
T.-Y. Luh, J. Am. Chem. Soc., 2000, 122, 4992; C.-F. Lee, C.-Y. Liu,
H.-C. Song, S.-J. Luo, J.-C. Tseng, H.-H. Tso and T.-Y. Luh, Chem.
Commun., 2002, 2824; M. D. Burke, E. M. Berger and S. L. Schreiber,
J. Am. Chem. Soc., 2004, 126, 14095; H.-C. Lin, W.-Y. Lin, H.-T. Bai,
J.-H. Chen, B.-Y. Jin and T.-Y. Luh, Angew. Chem., Int. Ed., 2007, 46,
897.
12 For selected reviews on furan synthesis, see: (a) X. L. Huo,
H. Y. Cheung, T. Y. Hong, P. L. Kwan, T. H. Lo, S. P. Tong and
H. N. C. Wong, Tetrahedron, 1998, 54, 1955; (b) B. A. Keay, Chem. Soc.
Rev., 1999, 28, 209; (c) T. L. Gilchrist, J. Chem. Soc., Perkin Trans. 1,
1999, 2849; R. C. D. Brown, Angew. Chem., Int. Ed., 2005, 44, 850; (d)
F. S. Kirsh, Org. Biomol. Chem., 2006, 28, 2076.
The authors thank Dr Vito Sgobba for preliminary experiments.
This work was financially supported by Ministero dell’Istruzione,
dell’Universita` e della Ricerca (MIUR), Italian MIUR ‘‘Progetto
FIRB 2003 SYNERGY RBNE 3S7XZ’’ and by Universita` degli
Studi di Bari.
Notes and references
1 For a recent review, see: F. Babudri, G. M. Farinola and F. Naso,
J. Mater. Chem., 2004, 14, 11.
13 For selected examples of recent work: P. Forgione, P. D. Wilson and
A. G. Fallis, Tetrahedron Lett., 2000, 41, 17; S. Ma and J. Zhang, Chem.
Commun., 2000, 117; K. Takai, R. Morita and S. Sakamoto, Synlett,
2001, 1614; J. M. Auerrocoechea, E. Perez and M. Solay, J. Org. Chem.,
2001, 66, 564; A. V. Kel’in and V. Gevorgyan, J. Org. Chem., 2002, 67,
95; Y. Nishibayashi, M. Yoshikawa, Y. Inada, M. D. Milton, M. Hidai
and S. Uemura, Angew. Chem., Int. Ed., 2002, 42, 2861; S. Ma, J. Zhang
and L. Lu, Chem. Eur. J., 2003, 9, 2447; A. Arcadi, S. Cacchi, G. Fabrizi,
F. Marinelli and L. M. Parisi, Tetrahedron, 2003, 59, 4661;
M. Nakamura, M. Yamane, H. Sakurai and N. Koichi, Heterocycles,
2003, 59, 333; J. Tae and K.-O. Kim, Tetrahedron Lett., 2003, 44, 2125;
A. W. Stromek, A. V. Kel’in and V. Gevorgyan, Angew. Chem., Int. Ed.,
2004, 43, 2280; X. Han and R. A. Widenhoefer, J. Org. Chem., 2004, 69,
1738; C.-K. Jung, J.-C. Wang and M. J. Krische, J. Am. Chem. Soc.,
2004, 1265, 4118; T. Yao, X. Zhang and R. C. Larock, J. Am. Chem.
Soc., 2004, 126, 11164; C. P. Casey and N. A. Strotman, J. Org. Chem.,
2005, 70, 2576; K. Y. Lee, M. J. Lee and J. N. Kim, Tetrahedron, 2005,
61, 8705; H. Imagawa, T. Kurisaki and M. Nishizawa, Org. Lett., 2005,
7, 451; A. Sniady, K. A. Wheeler and R. Dembinski, Org. Lett., 2005, 7,
1769; M. H. Suhre, M. Reif and S. F. Kirsch, Org. Lett., 2005, 7, 3925;
Y. Liu, F. Song, Z. Song, M. Liu and B. Yan, Org. Lett., 2005, 7, 5409;
T. Yao, X. Zhang and R. C. Larock, J. Org. Chem., 2005, 70, 7679;
C.-Y. Zhou, P. W. Chan and C.-M. Che, Org. Lett., 2006, 8, 325; B. Xu
and G. B. Hammond, J. Org. Chem., 2006, 71, 3518.
2 (a) F. Babudri, V. Fiandanese, G. Marchese and F. Naso, J. Chem.
Soc., Chem. Commun., 1991, 237; (b) F. Babudri, V. Fiandanese and
F. Naso, J. Org. Chem., 1991, 56, 6245; (c) F. Babudri, V. Fiandanese,
F. Naso and A. Punzi, Synlett, 1992, 221; (d) G. M. Farinola,
V. Fiandanese, L. Mazzone and F. Naso, J. Chem. Soc., Chem.
Commun., 1995, 2523; (e) F. Babudri, A. R. Cicciomessere,
G. M. Farinola, V. Fiandanese, G. Marchese, R. Musio, F. Naso
and O. Sciacovelli, J. Org. Chem., 1997, 62, 3291; (f) F. Babudri,
G. M. Farinola, V. Fiandanese, L. Mazzone and F. Naso, Tetrahedron,
1998, 54, 1085; (g) F. Babudri, G. M. Farinola, F. Naso and D. Panessa,
J. Org. Chem., 2000, 65, 1554; (h) F. Babudri, G. M. Farinola,
L. C. Lopez, M. G. Martinelli and F. Naso, J. Org. Chem., 2001, 66,
3878; (i) R. Ancora, F. Babudri, G. M. Farinola, F. Naso and R. Ragni,
Eur. J. Org. Chem., 2002, 4127.
3 (a) H. Bock and H. Seidl, J. Am. Chem. Soc., 1968, 90, 5694; (b)
R. F. Cunico and Y.-K. Han, J. Organomet. Chem., 1979, 174, 247; (c)
H. J. Reich, K. E. Yelm and I. L. Reich, J. Org. Chem., 1984, 49, 3438;
(d) P. J. Garratt and A. Tsotinis, Tetrahedron Lett., 1986, 27, 2761; (e)
H. Reich, I. L. Reich, K. E. Yelm, J. E. Holladay and D. Gschneider,
J. Am. Chem. Soc., 1993, 115, 6625; (f) T. Takahashi, Z. Xi, R. Fisher,
S. Huo, C. Xi and K. Nakajima, J. Am. Chem. Soc., 1997, 119, 4561.
4 W. E. Billups, M. M. Haley, R. Boese and D. Bla¨ser, Tetrahedron, 1994,
50, 10693.
5 Y.-X. Ding and W. P. Weber, J. Organomet. Chem., 1988, 341, 267.
6 The diene 4 employed for our reactions was prepared according to
ref. 3a.
7 GC-MS analysis of the reaction mixture at different reaction times
revealed the presence of a second product with molecular mass
corresponding to that of 7a with an hydrogen atom substituted by a
trimethylsilyl group. This compound, subsequently identified as
2-methyl-3-trimethylsilyl-5-phenyl furan 6a, was not isolated as it was
converted into 7a during work-up and chromatographic purification on
silica gel column (see below and ESI{).
8 Comprehensive Heterocyclic Chemistry II, ed. A. R. Katrizky, C. W.
Rees and E. F. V. Scriven, Pergamon, New York, 1996, vol. 2; pp. 259–
295 (R. Benassi), pp. 297–350 (H. Heaney), pp. 351–393
(W. Friedrishsen), pp. 395–436 (B. A. Keay); X.-L. Hou, Z. Yang
and H. N. C. Wong, in Progress in Heterocyclic Chemistry, ed. G. W.
Gribble and T. L. Gilchrist, Pergamon, Oxford, 2003, vol. 15, pp. 167–
205; D. L. Wright, in Progress in Heterocyclic Chemistry, ed. G. Gribble
and J. Joulet, Pergamon, Oxford, 2005, vol. 17, pp. 1–32; X.-L. Hou,
Z. Yang, K.-S. Yeung and H. N. C. Wong, in Progress in Heterocyclic
14 The experimental procedure used was the following: a CH2Cl2 solution
(18 ml) of freshly distilled benzoyl chloride 5a (0.319 g, 2.27 mmol) was
added, under a nitrogen atmosphere, to a cold (0 uC) stirred suspension
of anhydrous AlCl3 (0.303 g, 2.27 mmol) in 6 ml of CH2Cl2. When the
mixture became clear, a CH2Cl2 solution (6 ml) of 2,3-bis(trimethyl-
silyl)buta-1,3-diene 4 (0.300 g, 1.51 mmol) was slowly (about 20 min)
added maintaining the temperature at 0 uC. Immediately after addition
completion, the reaction was quenched with saturated aqueous NH4Cl
solution (30 ml) and extracted with CH2Cl2 (3 6 40 ml). The organic
extracts were washed several times with saturated aqueous Na2CO3
solution, dried over Na2SO4 and concentrated. The residue was purified
by column chromatography (petroleum ether–ethyl acetate 9.8 : 0.2 as
eluent) obtaining 7a as a white solid (0.150 g, 63% yield) which was fully
characterized by NMR spectroscopy and mass spectrometry (see ESI{).
15 The stabilizing effect of silyl groups on b carbocations is well
documented (b effect) while the effect of silyl substituents in a position
is still debated: see, for example, Silicon in Organic, Organometallic and
Polymer Chemistry, ed. M. A. Brook, Wiley Interscience, New York,
2000, pp. 483–496.
3758 | Chem. Commun., 2007, 3756–3758
This journal is ß The Royal Society of Chemistry 2007