MS 4A, an undesired dimeric product 3 was the sole product
in 70% yield (entry 7). Therefore, a combination of BF3‚
OEt2 and MS 4A turned out to be essential for obtaining the
ene product in good yield.3
At first we speculated that MS 4A would scavenge water
from incompletely dried reagents, solvents, or equipment that
coordinated to the Lewis acid to produce strong Brønsted
acids and that these strong acids would cause the polymer-
ization or isomerization of alkenes as side reactions. How-
ever, the use of a dehydrating agent, MgSO4, instead of MS
4A resulted in a low yield (22%) of 2a.
Another potential role of molecular sieves (zeolites) is to
trap acidic protons of the coordinated allylic alcohol (A) and
to retard the side reactions in Figure 1.4 We applied several
sodium ion exchanged zeolites with different Si/Al ratios
such as X- and Y-type zeolites and mordenite as well as
MS 4A (A-type zeolite) to the ene reaction (Table 2). Zeolites
Table 2. Carbonyl-Ene Reactions in the Presence of Zeolites
Having Various Amounts of Base Sitesa
Figure 1. Conceivable paths to side products via an ene-adduct.
have been known as good promoters for the carbonyl-ene
reaction,1 Me2AlCl gave very low yield in this case (entry
2). The reaction using BF3‚OEt2 also afforded complex
mixtures (entry 3). Interestingly, when MS 4A was added
to the reaction system with BF3‚OEt2, the ene adduct 2a was
obtained in good yield (entry 4). MS 4A and commercially
available solid acid K-10 independently did not promote the
reaction (entries 5 and 6). By the combined use of K-10 and
entry
zeolites
pore size6 (nm)
Si/Alc
yield (%)d
1b
2
3
MS 4A (NaA)
NaX
NaY
0.41
0.74
0.74
0.65 × 0.70
1.0
1.5
2.7
9.2
72
69
46
35
4
Na-mordenite
a
Zeolite (0.5 wt equiv to 1a), BF3‚OEt2 (2.0 equiv), (HCHO)n (2.0
equiv). b MS 4A (1.0 wt equiv), BF3‚OEt2 (1.2 equiv), (HCHO)n (1.0 equiv).
c The Si/Al ratios of zeolite. d Determined by 1H NMR using chloroacetone
as internal standard.
Table 1. Acid-Promoted Carbonyl-Ene Reactionsa
are crystalline aluminosilicates with intrinsic pore structures
and generally function as acid and base.5 Roughly speaking,
the total number of base sites on a zeolite is proportional to
the Al content in the zeolite framework. In other words, the
smaller the Si/Al ratio is, the more base sites exist in the
zeolite. Therefore, the order of base site amounts on the
zeolites is estimated as follows: MS 4A (NaA, Si/Al ) 1.0)
> NaX (1.5) > NaY (2.7) > Na-mordenite (9.2).
entry
acid (equiv)
H2SO4 (0.2)b
conditions
35 °C, 1.0 h
-10 to -5 °C, 3.0 h
-30 to -10 °C, 0.5 h
yield (%)d
1
2
3
4
5
6
7
46
28
tre
72
0f
0f
0g
Me2AlCl (1.0)
BF3‚OEt2 (1.2)
BF3‚OEt2 (1.2)/MS 4Ac -20 to -5 °C, 5.0 h
Table 2 clearly shows that the yield of 2a was increased
with an increase in the number of base sites on the zeolite.
MS 4Ac
K-10c
K-10/MS 4Ac
-20 °C to reflux, 5.0 h
0 °C to rt, 24.0 h
0 to 5 °C, 3.0 h
(3) Trioxane, which is more easily soluble in CH2Cl2 than paraformal-
dehyde, was unusable as formaldehyde precursor in this carbonyl-ene
reaction.
(4) (a) Mikami, K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1989, 111,
1940. (b) Mikami, K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1990, 112,
3949. (c) Mikami, K.; Terada, M.; Nakai, T. J. Am. Chem. Soc. 1994, 116,
2812. (d) Terada, M.; Matsumoto, Y.; Nakamura, Y.; Mikami, J. J. Mol.
Catal. A 1998, 132, 165.
a (HCHO)n, 1.0 equiv. b Solvent ) Ac2O. c One weight equivalent of
MS 4A (K-10) to 1a was used. d Determined by 1H NMR using chloro-
acetone as internal standard. e Complex mixtures were formed. f Styrene
1a was recovered. g Dimeric product 3 was formed.
(5) (a) Breck, D. W. In Zeolite Molecular SieVes; John Wiley & Sons:
New York, 1974. (b) Izumi, Y., Urabe, K., Onaka, M. In Zeolite, Clay,
and Heteropoly Acid in Organic Reactions; Kodansha: Tokyo, 1992. (c)
Onaka, M., Kawai, M., Izumi, Y. Bull. Chem. Soc. Jpn. 1986, 59, 1761.
(6) Baerlocher, Ch.; Meier, W. M.; Olson, D. H. Atlas of Zeolite
Framework Types, 5th ed.; Elsevier: New York, 2001.
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Org. Lett., Vol. 4, No. 10, 2002