Converting exo-Selective Diels-Alder Reaction to endo-Selective in Chloroloaluminate Ionic Liquids

Article abstract of DOI:10.1021/jo035038j

The endo:exo ratio of 0.35:1 for the reaction of cyclopentadiene with methyl methacrylate observed in organic solvents can be converted to 3:1 in chloroaluminate ionic liquids with their effective reuse in Diels-Alder reactions.

Full text of DOI:10.1021/jo035038j

Con ver tin g exo-Selective Diels-Ald er
Rea ction to en d o-Selective in
Ch lor oloa lu m in a te Ion ic Liqu id s
Anil Kumar* and Sanjay S. Pawar
Physical Chemistry Division, National Chemical
Laboratory, Pune 411 008, India
F IGURE 1.
akumar@ems.ncl.res.in
Received J uly 18, 2003
stereoisomer 3a (for example, endo ) 84% in ethanol),
whereas that with methyl methacrylate 2b results in a
higher amount of exo-stereoisomer 4b (for example exo
)
65% in ethanol). Slightly higher amounts of endo-
products 5a (for example, endo ) 62% in ethanol) are
noted for the reaction of 1 with methyl trans-crotonate
2c.6
Abstr a ct: The endo:exo ratio of 0.35:1 for the reaction of
cyclopentadiene with methyl methacrylate observed in
organic solvents can be converted to 3:1 in chloroaluminate
ionic liquids with their effective reuse in Diels-Alder
reactions.
In this Note, we show that the reaction of 1 with 2b,
which gives more exo-product in conventional organic
solvents, offers more endo-product in the chloroaluminate
ionic liquid. In the past, ionic liquids have been used to
further increase the endo-product of the known endo-
The effect of solvents and their salt solutions on the
rates and stereoselectivities of Diels-Alder reactions has
7
1
selective Diels-Alder reactions. Enhanced endo-product
been a subject of intense study since the pioneering work
2
has been reported for the reaction of 1 with 2a in
chloroaluminates.7d The reversal of an exo-selective reac-
tion to an endo-selective reaction in the Diels-Alder
of Breslow, who discovered the special effect of water in
enhancing the endo:exo ratios and rates of Diels-Alder
reactions. Considering an urgent need of replacing con-
ventional organic solvents due to environmental problems
caused by them, room temperature ionic liquids have
8
reaction of furan with 2a was reported in an ionic liquid.
The usual endo:exo ratio of 1:2 in a conventional organic
solvent was successfully converted into 2.3:1.
We carried out the reaction of 1 with 2b in both BPC-
and EMIC-containing chloroaluminates with varying
lately emerged as potential substitutes with their use in
a variety of reactions.3
The chloroaluminates (Figure 1) are ambient temper-
AlCl
entry 1, exo ) 74%) was observed in the BPC-chloroalu-
minate with 45% AlCl as compared to that in 2,2,4-
trimethylpentane, a nonpolar solvent (entry 9, exo )
6%). This reaction, when conducted in the BPC-contain-
ing chloroaluminate ionic liquid with 60% AlCl gave 25%
3
compositions (Table 1). No change in exo-product
ature ionic liquids with composition AlCl
MCl is either N-1-butylpyridinium chloride (BPC) or
-ethyl-3-methyl-1H-imidazolium chloride (EMIC). Chlo-
3
:MCl, where
(
1
3
roaluminates are versatile agents because their nature
can easily be altered from basic (EMIC or BPC in excess)
7
3
to acidic (AlCl in excess) by manipulating their composi-
3
4
exo-product (entry 8, Table 1). The endo-product was,
therefore, enhanced by about three times from 26% (in
tion. The rationale to employ chloroaluminates in this
connection is based on the fact that Lewis acid catalysis
is known to influence the kinetics of Diels-Alder reac-
tions.5
4
3 3
5% AlCl ) to 75% (in 60% AlCl ) in the BPC-chloroalu-
The Diels-Alder reaction of cyclopentadiene 1 with
methyl acrylate 2a offers a higher amount of endo-
(5) (a) Forman, M. A.; Dailey, W. P. J . Am. Chem. Soc. 1991, 113,
761. (b) Desimoni, G.; Faita, G.; Righetti, P. P. Tetrahedron 1991,
7, 8399. (c) Springer, G.; Kabalka, G. W.; Bains, S.; Plesco, S.; Wilson,
2
4
J .; Bartmess, J . J . J . Org. Chem. 1993, 58, 3130. (d) Springer, G.; Elam,
C.; Edwards, A.; Bowe, C.; Boyles, D.; Bartmess, J . J .; Chandler, M.;
West, K.; Williams, J .; Green, J .; Pagni, R. M.; Kabalka, G. W. J . Org.
Chem. 1999, 64, 2202.
(6) (a) Berson, J . A.; Hamlet, Z.; Mueller, W. A. J . Am. Chem. Soc.
1962, 84, 297. (b) Cativiela, C.; Garcia, J . I.; Mayoral, J . A.; A. J . Royo,
Salvatella; Assfeld, X.; Ruiz-Lopez, M. F. J . Phys. Org. Chem. 1992, 5,
230. (c) Cativiela, C.; Garcia, J . I.; Mayoral, J . A.; Salvatella, L. J .
Chem. Soc., Perkin Trans. 2 1994, 847.
(7) For example, see: (a) J aeger, D. A.; Tucker, C. E. Tetrahedron
Lett. 1989, 30, 1785. (b) Howarth, J .; Hanlon, K.; Fayne, D.; McCormac,
P. Tetrahedron Lett. 1997, 38, 3097. (c) Fischer, T.; Sethi, A.; Welton,
T.; Woolf, J . Tetrahedron Lett. 1999, 40, 793. (d) Lee, C. W. Tetrahedron
Lett. 1999, 40, 2461. (e) Earle, M. J .; McCormac, P. B.; Seddon, K. R.
Green Chem. 1999, 1, 23. (f) Song, C. E.; Shim, W. H.; Roh, E. J .; Lee,
S.-G.; Choi, J . H. Chem. Commun. 2001, 1122. (g) Abbott, A. P.; Capper,
G.; Davies, D. L.; Rasheed, R. K.; Tambyrajah, V. Green Chem. 2002,
4, 24. (h) Aggarwal, A.; Lancaster, N. L.; Sethi, A. R.; Welton, T. Green
Chem. 2002, 4, 517. Use of these ionic liquids offered similar endo:exo
*
To whom correspondence should be addressed. Fax: +91 20
5
2
893044.
(1) For example, see: (a) Lindstrom, U. M. Chem. Rev. 2002, 102,
751. (b) Kumar, A. Chem. Rev. 2001, 101, 1. (c) Organic Synthesis in
Water; Grieco, P. A., Ed.; Blackie: Glassgow, 1998. (d) Cativiela, C.;
Garcia, J . I.; Mayoral, J . A.; Salvatella, L. Chem. Soc. Rev. 1996, 209.
(
e) Lubineau, A.; Auge, J .; Queneau, Y. Synthesis 1994, 741. (f)
Casaschi, A.; Desimoni, G.; Faita, G.; Invernizzi, A. G.; Lanati, S.;
Righetti, P. P. J . Am. Chem. Soc. 1993, 115, 8002. (g) Pindur, U.; Lutz,
G.; Otto. C. Chem. Rev. 1993, 93, 741. (h) Rizzo, C. A. J . Org. Chem.
992, 57, 6382. (i) Grieco, P. A.; Nunes, J . J .; Gaul, M. D. J . Am. Chem.
Soc. 1990, 112, 4595. (j) Breslow, R.; Guo, T. J . Am. Chem. Soc. 1988,
10, 5613. (k) Schneider, H.-J .; Sangwan, N. K. J . Chem. Soc., Chem.
Commun. 1986, 1787.
1
1
(
2) Rideout, D. C.; Breslow, R. J . Am. Chem. Soc. 1980, 102, 7816.
(3) For example, see: (a) Tzschucke, C. C.; Markert, C.; Bannwarth,
W.; Roller, S.; Hebel, A.; Haag, R. Angew. Chem., Int. Ed. 2002, 41,
964. (b) Wassercheid, P.; Wilhelm, K. Angew Chem., Int. Ed. 2000,
9, 3772. (c) Sheldon, R. Chem. Commun. 2001, 2399. (d) Gordon, M.
3
3
4
ratios for these Diels-Alder reactions as performed in LiClO -diethyl
ether (LPDE). For example see: Grieco, P. A.; Nunes, J . J .; Gaul, M.
D. J . Am. Chem. Soc. 1990, 112, 4595.
(8) Hemeon, I.; DeAmicis, C.; J enkins, H.; Scammells, P.; Singer,
R. D. Synlett 2002, 1815.
Appl. Catal., A 2001, 222, 101. (e) Welton, T. Chem. Rev. 1999, 99,
071. (f) Seddon, K. R. Kinet. Katal. 1996, 37, 693.
4) Hussey, C. L. Pure Appl. Chem. 1988, 60, 1763 and references
therein.
2
(
1
0.1021/jo035038j CCC: $27.50 © 2004 American Chemical Society
Published on Web 01/21/2004
J . Org. Chem. 2004, 69, 1419-1420
1419

SCHEME 1
TABLE 1. Rea ction of 1 w ith 2b in Ch lor oa lu m in a te
TABLE 3. Yield s Obta in ed a s a Resu lt of Reu se of 60%
AlCl3/BP C- a n d EMIC-Ch lor oa lu m in a tes for Rea ction s of
1
a
Ion ic Liqu id
w ith 2b a n d 2ca
BPC
EMIC
1
+ 2b
EMIC
1 + 2c
EMIC
a
entry
mol % AlCl3
exo, %
yield, %
exo, %
yield, %
cycle
BPC
BPC
1
2
3
4
5
6
7
8
9
45
47
49
51
53
55
57
60
d
74
75
72
68
65
60
49
25
76
40
18
18
18
22
25
30
35
47
15
34
73
74
74
70
63
53
40
18
20
20
20
26
30
35
41
fresh reaction
47
45
44
42
40
40
38
58
56
56
54
52
50
50
57
54
52
52
50
48
46
68
66
66
64
61
63
62
1
2
3
4
5
6
b
c
58
a
Reaction conditions specified in the text.
1
0
e
a
Isolated yields. b 90 min. c 75 min. d 2,2,4-Trimethylpentane.
e
AlCl3; no further changes in endo- or exo-products and yields after
chloroaluminates leads to a decrease in exo-product and
therefore an enhanced endo-product. The effect of Lewis
acid catalysis on Diels-Alder reaction is further sup-
ported by the observation that the basic conditions in
the times reported.
TABLE 2. Rea ction of 1 w ith 2c in Ch lor oa lu m in a te
Ion ic Liqu id
a
4
5%, 47%, and 49% of AlCl
selectivity of the reaction.
The reactions conducted in AlCl
3
do not influence the stereo-
BPC
EMIC
a
entry mol % AlCl3 endo, % yield, % endo, % yield, %
alone enhanced the
3
endo-product to 60% as compared to 24% obtained in
2,2,4-trimethylpentane (Table 1).
The reaction of 1 with 2c, which is endo-selective in
organic solvents, was also carried out in the ionic liquid
1
2
3
4
5
6
7
8
9
1
45
47
49
51
53
55
57
60
d
48
50
50
53
57
62
74
86
52
53
16
16
17
20
27
37
47
57
10
16
49
48
50
57
63
70
80
92
17
18
17
29
40
50
58
68
to give endo-product up to 86% and 92% in 60% AlCl
3
with BPC- and EMIC-chloroaluminates, respectively
(entry 8, Table 2). Higher endo:exo ratios of 6:1 and 11.5:1
were obtained in the BPC- and EMIC-chloroaluminates
b
c
0
e
(with 60% AlCl
3 3
), respectively. The same reaction in AlCl
a
Isolated yields. b 90 min. c 75 min. d 2,2,4-Trimethylpentane.
alone gave 53% endo-product.
e
AlCl3; no further changes in endo- or exo-products and yields after
the times reported.
The reactions of 1 with 2b and 2c in organic solvents
were sluggish and gave about 10% yield in 10 and 23 h,
respectively. The same reactions when conducted in
chloroaluminates gave 47-68% yield (Tables 1 and 2,
entry 8) in just 1-2 h.
Finally, it was possible to recover the chloroaluminates
from the mixture by diluting it with diethyl ether. The
reactions of 1 with 2b and with 2c when conducted in
the recovered ionic liquid gave 50-65% yields (Table 3).
3
minates.The reaction in the 60% AlCl /EMIC-chloroalu-
minate yielded 18% exo-product (entry 8, Table 1). As the
exo-product is reduced by about four times in the 60%
3
AlCl /EMIC-chloroaluminate, the endo-product is en-
hanced by the same order of magnitude (Table 1). This
shows that the EMIC-chloroaluminate ionic liquid is a
more efficient ionic liquid than the one containing BPC.
3
The use of higher concentrations of AlCl offered lower
exo-product.
Ack n ow led gm en t. This investigation is supported
by a generous grant-in-aid (no. SR/S1/PC-13/2002) from
DST, New Delhi, India. The comments of the reviewers
on the original version were helpful in improving the
presentation of this work.
In short, we obtained endo:exo ratio of 3:1 for the
reaction of 1 with 2b in 60% AlCl /BPC-chloroaluminate
as compared to that (endo:exo ) 0.35:1) noted in 45%
AlCl /BPC-chloroaluminate. Higher degree of reversal in
the endo:exo ratios (4.55:1) is, however, seen in the 60%
AlCl /EMIC-chloroaluminate.
3
3
Su p p or tin g In for m a tion Ava ila ble: The synthesis of
chloroaluminates and experimental method to carry out the
reactions. This material is available free of charge via the
Internet at http://pubs.acs.org.
3
This reversal in the stereselectivity seems to be
controlled by the Lewis acid effect caused by the presence
of AlCl
3
as the increasing concentration of AlCl
3
in the
J O035038J
1
420 J . Org. Chem., Vol. 69, No. 4, 2004