Use of FeCl3 and FeCl3 adsorbed on silica as efficient Lewis acid catalyst in ionic Diels-Alder reactions of α,β-unsaturated acetals

Article abstract of DOI:10.1055/s-2001-13375

The efficiency of FeCl₃ adsorbed on silica, as conventional Lewis acid catalyst in Diels-Alder reaction of α,β-enals, enones including their acetals with 1,3-dienes is described.

Full text of DOI:10.1055/s-2001-13375

LETTER
667
Use of FeCl3 and FeCl3 Adsorbed on Silica as Efficient Lewis Acid Catalyst in
Ionic Diels-Alder Reactions of , -Unsaturated Acetals
Subhash P. Chavan,* Anil K. Sharma
Division of Organic Chemistry:Technology, National Chemical Laboratory, Pune-411008, India
Fax +91-20- 5893614; E-mail: spchavan@dalton.ncl.res.in
Received 8 February 2001
Table 1 Cycloaddition Reactions of Dienes and Dienophiles using
FeCl3 as Catalyst15
Abstract: The efficiency of FeCl3 adsorbed on silica, as conven-
tional Lewis acid catalyst in Diels-Alder reaction of , -enals,
enones including their acetals with 1,3-dienes is described.
Key words: acetals, Diels-Alder reactions, Lewis acids, regioselec-
tivity, stereoselectivity
The Diels-Alder reaction is a very powerful tool in the ar-
senal of synthetic chemists. This reaction, due to its gen-
erality, efficiency and excellent regio- and stereocontrol
has been extensively utilized for construction of six-mem-
bered rings. The ionic Diels-Alder reaction, which was
first observed by Gassman et al.1 is another variant of the
Diels-Alder reaction which involves ionic intermediates
(cations) as extremely powerful dienophiles. Advantages
of the ionic Diels-Alder reaction over conventional Diels-
Alder reactions is the excellent stereo, and regioselectivity
exhibited by them. Dienophiles utilised in ionic Diels-Al-
der reactions are neutral species which are transiently con-
verted to charged species in situ and undergo facile Diels-
Alder reaction to furnish the neutral adducts. Thus, the di-
enophiles which are unstable and/or undergo polymeriza-
tion under normal Diels-Alder reaction conditions can be
handled efficiently and conveniently as their acetals
which are stable and can be stored without decomposition.
A variety of Bronsted Acids and Lewis acid TfOH,2
BF3(OEt)2,3 TMSOTf,4 CF3SO3H,5 CF3SO3Si(CH3)3,6
LiClO4,7 TiCl4-Ti(O-i-Pr)4,8 I2,9 electrogenerated acid,10
11b
LiClO4 (or Nafion-H)11a and very recently InCl3 have
been utilised as catalysts to effect [4+2] cycloadditions.
Although a variety of acids5-8,10,11 are known to catalyse
the ionic Diels-Alder reactions, most of them are either
very strong, employ harsh conditions, or involve hazard-
ous reagents, thereby limiting their usage.
FeCl3 is a unique reagent which can function efficiently
both as a Lewis acid as well as an oxidant. During the
course of our study in the Diels-Alder reaction we became
interested in exploring the utility of FeCl3 as a Lewis acid
due to its ready availability and its price. The use of FeCl3
as Lewis acid is very well documented in the litera-
ture,12a-d however, its utility has not been explored in ionic
Diels-Alder reactions. We subjected , -unsaturated ace-
tals to Diels-Alder reactions with both cyclic and acyclic
dienes. It was observed that reaction of 2 equivalents of
cyclopentadiene (1) with 2-(1-propenyl)-1,3-dioxolane
(2) as the dienophile in dry dichloromethane at
room temperature for 4 h using 0.1 equivalent of FeCl3
Method:1a. diene:dienophile, 2:1, FeCl3, (0.1eq.), DCM, RT, 4 h;
1b. diene:dienophile, 10:1, FeCl3, (0.1eq.), DCM, 0 C, 4 h 1c. die-
ne:dienophile, 2:1, FeCl3, (0.15eq.), DCM, RT, 4 h 1d. diene:dieno-
phile, 1.25:1, FeCl3, (0.3eq.), DCM, 0 ºC-RT, 1.5 h; 6:1
(regioisomers).
* Reported in the literature (ref. 10).
**Reported in the literature (ref. 11b).
Synlett 2001 No. 5, 667–669 ISSN 0936-5214 © Thieme Stuttgart · New York

668
S. P. Chavan, A. K. Sharma
LETTER
Table 2 Cycloaddition Reactions of Dienes and Dienophiles using
furnished 2-(bicyclo 2.2.1 hept-5-ene-2-yl 3-methyl) di-
FeCl3 Adsorbed on Silica as Catalyst16,17
oxolane (3) in 82% yield. The product was formed as a
1
mixture of exo and endo adducts. In the H NMR spec-
trum, the emergence of doublets at 4.2 and 4.7 indicated
that the ratio of endo to exo is 5.7:1. (the values of endo
and exo isomers were in accordance with the values re-
ported in the literature.11a A similar trend is observed in
other acetals as well).
In order to test the generality and limitations of our meth-
odology, we subjected , -unsaturated acetals (entries 1,
2 and 3) substituted at different positions to reactions with
a variety of cyclic and acyclic dienes. Excellent to moder-
ate yields were obtained as shown in Table 1, entries 1-9.
It was observed that acetals derived from aldehydes as
well as ketones participated well in the ionic Diels-Alder
reaction (entries 1-3, Table 1). When using isoprene (8) as
diene (10 eq., entry 6) in the reaction with 2-(1-propenyl)-
1,3-dioxolane (2) as dienophile at 0 C, the adduct 2-(1,5
dimethyl-1-cyclohexen-4-yl) dioxolane (11) was obtained
in only 37% yield, but on increasing the amount of cata-
lyst to 0.3 eq., and decreasing the amount of diene from 10
eq. to 1.5 eq. and reaction time to 1.5 h, the yield was in-
creased to 65%. Further increasing the amount of catalyst
furnished only polymerized product. It is pertinent to
mention that the yield obtained with the reaction of 2,3-
dimethyl butadiene with 6 using FeCl3 as the catalyst was
better than the one obtained by the use of electrogenerated
acid10 as well as Yb(OTf)3 and Sc(OTf)311b which were re-
cently shown to be inactive in ionic Diels-Alder reactions
with a similar dienophile (entry 8). In general, it was ob-
served that cyclic dienes participate better compared to
acyclic dienes.
Methods: IIa: diene:dienophile, 2:1, FeCl3 (1.0 mol%) adsorbed on
silica (5% by wt.), DCM, -70 C 2 h; IIb: diene:dienophile, 2:1, FeCl3
(0.5 mol%) adsorbed on silica (5% by wt.), DCM, 0 C-RT, 4 h; IIc:
diene:dienophile, 2:1, FeCl3 (0.6 mol%) adsorbed on silica (5% by
wt.), DCM, 0 C-RT 2 h; IId: diene:dienophile, 2:1, FeCl3 (1.0
mol%) adsorbed on silica (5% by wt.), DCM, 0 C-RT 4 h.
*Reported in the literature ref. 4.
**Reported in the literature ref. 10.
***Reported in the literature ref. 14.
diethoxymethyl)bicyclo 2.2.1 hept-2-ene4 (18) in excel-
lent yield (86%), with very high endo selectivity
(endo:exo = 98:2). When the same reaction was per-
formed at room temperature the yield was increased
(92%), however, it was accompanied by a slight erosion
of endo selectivity (endo:exo = 96:4) Employing 2-ethe-
nyl-1,3-dioxolane (15) as the dienophile with cyclopenta-
diene (1) using 0.5 mol% FeCl3 adsorbed on silica (5% by
wt.), the corresponding adduct 2-(bicyclo[2.2.1]-hept-5-
ene-2-dioxolane10 (19) was obtained in 90% yield as a
mixture of endo:exo (2.75:1) isomers with the endo ad-
duct being major. The difference in diastereoselectivity
between 15 and 17 with cyclopentadiene may be attribut-
ed to the steric interaction of the complexed 17 with Lewis
acid with cyclopentadiene in the transition state. It was
also observed that the reaction between cyclopentadiene
(1) with 3,3-diethoxy-1-propene (17) using only silica as
catalyst (500% by wt.) did not furnish the desired product
even in traces. This confirms that it is only FeCl3 which
acts as catalyst in ionic Diels-Alder reactions, but its ac-
tivity can be reduced on its adsorption on silica. In an at-
tempt to increase the yield of the ionic Diels-Alder
reaction, acyclic dienes (viz. isoprene, 2,3-dimethyl buta-
diene) were subjected to treatment with the acetal 2-(1-
propenyl)-1,3-dioxolane (2) in the presence of FeCl3/
SiO2. However, no improvement in the yield of the adduct
was observed, instead yields were drastically reduced to
Another point worthy of note is that the reaction of an acy-
clic dienophile, i.e. 3, 3-diethoxy-1-propene (17), with
acyclic dienes under similar reaction conditions as com-
pared with the corresponding cyclic acetal, 2-ethenyl-1,3-
dioxolane (15), furnished only polymerised product with
FeCl3 (0.1 eq.) as the catalyst. Extensive polymerisation
was also observed when the reaction between 3,3-di-
ethoxy-1-propene (17) and cyclopentadiene (2 eq.) (1)
was performed using 0.1 eq. of catalyst. Decreasing the
amount of catalyst and lowering the reaction temperature
to -70 C did not lead to the formation of the desired prod-
uct.
Having failed to obtain the desired cycloaddition product,
it was thought that the very high reactivity of the in situ
generated dienophile, its tendency to undergo facile un-
desired reactions, coupled with the harsh nature of the
Lewis acid, were responsible for these polymerisation re-
actions. The reactivity of FeCl3 could be readily moderat-
ed by its adsorption on silica, which acted as solid support
for this Lewis acid catalyst. The use of FeCl3 adsorbed on
silica is well known for other chemical transforma-
tions.13a-e It was gratifying to note that dramatic results
were achieved (Table 2) when 0.1 mol% FeCl3 adsorbed
on silica (5% by wt.) was used in the reaction between cy-
clopentadiene (1) with 3,3-diethoxy-1-propene (17) at
-70 C, to produce the corresponding cycloadduct, 5-(1,1-
Synlett 2001, No. 5, 667–669 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Use of FeCl3 and FeCl3 Adsorbed on Silica as Efficient Lewis Acid Catalyst
669
(13) a) Keinan, E.; Mazur, Y. J. Org. Chem. 1978, 43, 1022. b)
Kim, K. S.; Song, Y. H.; Lee, B. H.; Hahn, C. S. J. Org. Chem.
1986, 51, 404. c) Fadel, A.; Salaun, J. Tetrahedron 1985, 41,
413. d) Patney, H. K. Tetrahedron Lett. 1991, 2259. e) Jempty,
T. C.; Gogins, K. A.; Mazur, Y.; Miller, L. L. J. Org. Chem.
1981, 46, 4545.
5% when 1 mol% catalyst was used. This may be attribut-
ed to the enhanced reactivity of the cyclic dienes due to
their locked cisoid geometry as compared to the acyclic
dienes which can freely rotate around the single bond.
Therefore, FeCl3/SiO2 as the catalyst not only increased
the efficiency of the above reactions but its utility could be
readily extended to the cycloaddition of the enones and
enals. Thus, the reaction of cyclopentadiene (1) with cro-
tonaldehyde (20) using 1 mol% of FeCl3 on silica pro-
duced the corresponding adduct14 21 in 80% yield (entry
(14) Ishihara, K.; Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc.
1996, 118, 3049.
(15) Typical Procedure using FeCl3 catalyst (Table 1, entry 2) 2-
(bicyclo[2.2.1]hept-5-en-2-yl 3-phenyl) dioxolane (5): To a
freshly cracked stirred solution of 0.33g (5 mmol) of
cyclopentadiene (1) in 20 mL of anhyd dichloromethane
under N2 atmosphere at 0 C, was added 0.44g (2.5 mmol) of
2-(3-phenyl-2-vinyl)-1, 3-dioxolane (4), followed by the
addition of 40 mg (0.1 eq.) of FeCl3. The reaction mixture was
stirred at room temperature for 4 h. After completion of the
reaction, usual workup and column chromatography (SiO2)
furnished 0.44g of 2-(bicyclo[2.2.1]hept-5-en-2-yl 3-phenyl)
dioxolane (5) in 73% yield.
1
13, Table 2). The ratio of endo:exo as determined by H
NMR was 3:1. An analogous reaction of the dienophile
cinnamaldehyde (22) with cyclopentadiene (1) in the
presence of 1 mol% of catalyst furnished a 3:1 mixture of
endo and exo isomers14 in 78% yield (entry 14, Table 2).
In conclusion, we have demonstrated the utility of FeCl3
as an efficient Lewis acid catalyst and established a mild
protocol for the ionic Diels-Alder reaction of 1,3-dienes
with various dienophiles. Additionally, one can moderate
and fine-tune the reactivity of FeCl3 by adsorbing it on sil-
ica gel. FeCl3 adsorbed on silica not only avoids polymer-
isation but also enhances the endo selectivity in Diels-
Alder reactions yields. The heterogeneous nature of the
catalyst coupled with its potential reuse makes the workup
procedure extremely simple involving mere filtration.
1H NMR (200 MHz, CDCl3) :1.6 (d, 1H, J = 8 Hz), 1.8 (d,
1H, J = 8 Hz), 2.3 (m, 1H), 2.55 (m, 1H), 2.9 (br s, 1H), 3,2 (br
s, 1H), 3.75-4.05 (m, 4H, -OCH2CH2O-), 4.45 (d, 1H, J = 10.8
Hz), 6.3 (dd, 1H, J = 6 Hz, olefinic), 6.45 (dd, 1H, J = 6 Hz,
olefinic) 7.00-7.6 (m, 5H, aromatic). Exo isomer showed
distinct peaks at 0.8 (d, 1H, J = 8 Hz) and at 4.9 (d, 1H, J = 8
Hz) along with other peaks which overlapped with the peaks
of endo isomer.
13C NMR (50 MHz, CDCl3) : 44.7 (d), 46.4 (d), 46.8 (t), 48.9
(d), 50.8 (d), 64.7 (t), 108.4 (d), 125.5 (d), 127.6 (d), 128 (d),
134.8 (d), 137.9 (d), 144.7 (s).
We believe that the methodology developed by us would
be a useful addition to the repertoire of synthetic organic
chemists in the area of ionic Diels-Alder reactions.
MS (m/e): 242, 176, 104, 91, 66.
IR (neat) cm-1: 2970, 1681, 1625, 1600, 1496, 1404, 1332,
1145, 1109.
(16) Preparation of Catalyst (FeCl3 adsorbed on silica): Silica
gel (1g 60-120 mesh s. d. Fine Chemicals Ltd. India) is added
to a solution of anhydrous FeCl3 (50 mg) in DCM at room
temperature. The solvent is removed on a rotary evaporator to
achieve homogenous adsorption. Finally, the yellow residue
was dried under vacuum (0.1 mm Hg) for 30 min to furnish a
yellow powder.
Acknowledgement
AKS thanks CSIR, New Delhi (India) for the award of fellowship.
Funding under YSA scheme from CSIR, India is gratefully acknow-
ledged. We are thankful to Dr. M. K. Gurjar, Head, Division of Or-
ganic Chemistry: Technology, National Chemical Laboratory, Pune
411008, INDIA for encouragement.
(17) Typical Procedure using FeCl3 adsorbed on silica (Table 2,
entry 12) 2-(bicyclo[2.2.1] hept-5-en-2-yl)-1,3 dioxolane
(19): To a freshly cracked stirred solution of 0.33g (5 mmol)
of cyclopentadiene (1) in 20 mL DCM at 0 C under N2
atmosphere, was added 0.25g (2.5 mmol) of 2-vinyl-1,3-
dioxolane (15) follwed by the addition of 0.6 mol% of FeCl3
adsorbed on silica (5% by wt.). The reaction mixture was
stirred for 2 h, and monitored by TLC. After completion of
reaction, the reaction mixture was quenched with 20 mL of
water, then extracted with dichloromethane (3 25 mL), dried
over anhydrous sodium sulphate and finally concentrated
under reduced pressure. Column chromatography (SiO2) of
the residue using 5% ethyl acetate-petroleum ether as eluent
furnished 0.374g of 2-(bicyclo[2.2.1] hept-5-en-2-yl)-1,3
dioxolane (19) as a viscous oil in 90% yield.
References and Notes
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106, 6085.
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S. P. J. Am. Chem. Soc. 1987, 109, 2182.
(3) Gassman, P. G.; Chavan, S. P. J. Chem. Soc., Chem. Commun.
1989, 837.
(4) Gassman, P. G.; Chavan, S. P. J. Org. Chem. 1988, 53, 2392.
(5) Gassman, P. G.; Chavan, S. P.; Fertel, L. B. Tetrahedron Lett.
1990, 31, 6489.
(6) Gassman, P. G.; Chavan, S. P. Tetrahedron Lett. 1989, 29,
3407.
(7) Grieco, P. A.; Collins, J. L. Handy, S. T. Synlett 1995, 1155.
(8) Samakia, T.; Berliner, M. A. J. Org. Chem. 1994, 59, 6890.
(9) Kitagawa, O.; Aoki, K.; Inove, T.; Taguchi, T. Tetrahedron
Lett. 1995, 36, 593.
(10) Inokuchi, T.; Tanigawa S.; Toru, S. J. Org. Chem. 1990, 55,
3958.
(11) a) Vankar, P. S.; Reddy, M. V.; Kumareswaran, R.; Pitre, S.
V.; Roy, R.; Vankar, Y. D. Tetrahedron 1999, 55, 1099- 1110.
b) Reddy, G.; Kumareswaran, R.; Vankar, Y. D. Tetrahedron
Lett. 2000, 41, 10333.
(12) a) Denmark, S. E.; Klix, R. C. Tetrahedron 1988, 44, 4043. b)
Tietze, L. F.; Beifuss, U. Synthesis 1988, 359. c) Snider, B. B.;
Roush, D. M. J. Org. Chem. 1979, 49, 4229. d) Mahe, L.;
Cabral, J.; Laszlo, P. Tetrahedron Lett. 1989, 30, 3969.
1H NMR (200 MHz, CDCl3) : 0.92 (m, 1H), 1.40 (m, 1H),
1.24 (d, 1H), 1.40 (m, 1H), 2.19 (m, 1H), 2.82 (br s, 1H), 2.97
(br s, 1H), 3.7-4.0 (m, 4H, -OCH2CH2O-), 4.2 (d, 1H, J = 10.8
Hz), 5.97 (dd, 1H, J = 6 Hz, J = 2H, olefinic), 6.15 (dd, 1H,
J = 6 Hz, J = 2 Hz, olefinic). The emergence of peaks at 4.2
and 4.7 in the ratio of 2.75:1 clearly established the formation
of endo and exo isomers respectively.
MS (m/e): 166, 125, 100, 99, 91, 86, 77, 73, 66, 55.
IR (neat) cm-1: 3065,1630, 1335, 1107, 980, 835.
Article Identifier:
1437-2096,E;2001,0,05,0667,0669,ftx,en;S01801ST.pdf
Synlett 2001, No. 5, 667–669 ISSN 0936-5214 © Thieme Stuttgart · New York