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“Micellar” catalysis in the aqueous intermolecular diels-alder reaction: rate acceleration and enhanced selectivity
Tetrahedron Letters,Vol.24,No.l8,Tp Printed in Great Britain
"MICELLAR"
CATALYSIS
1897-1900,1953
IN THE AQUEOUS
RATE ACCELERATION Paul A. Grieco,* Department
of Chemistry,
O@O-4039/?3/181997-04$03.00/0 01983 Peqamon Press Ltd.
INTERMOLECULAR
AND ENHANCED
DIELS-ALDER
Philip Garner and Zhen-min
Indiana University,
REACTION:
SELECTIVITY
Bloomington,
He Indiana 47405
Summary: The intermolecular Diels-Alder reactions employing dienophiles k and 2 with diene < have been examined in water. The significantly enhanced rates, as well as the improved selectivity observed in water stand in sharp contrast to the results observed in hydrocarbon solvents:
As a consequence of the Diels-Alder <
R=Et)3 proceeds
of our continuing
adduct
Intermolecular
(2).
in benzene
amount of recovered
importantly, water.5
improve
dienophile.4
(see Table)
In an attempt
that when the Diels-Alder
the ratio of 140-isomer
(288 h versus
,$ over the 14a-isomer
dienophile
quantities
,$' and diene
to shorten
the reaction
time and, more
between ,$ and z (R=Et) was examined
reaction
of
in a ratio of I:I.2, along with a sub-
is carried
t [0.85 (benzene)
1897
between
substantial
giving after 288 h, a 52% yield
168 h, entry 3).
+
we required
reaction
and t (R=Et), mp 93.5-94.O"C,
is more than doubled
Me0
Diels-Alder
upon the isomer ratio, the reaction
The Table reveals
the reaction
in quassinoids,l
at room temperature
adducts 2 (R=Et), mp 129-13O"C, stantial
interest
out in water the rate of
Also notable versus
in
is the increase
1.3 (water)].
It is of
in
1898
interest
to note that the rate of the above aqueous
the rate of reaction
of 2 and 2 (R=Et) conducted
reaction
is not substantially
in the absence
of solvent
different
(cf. Table,
from
entries
2
and 3). Diels-Alder is sluggish solvent
reaction
(60% complete
results
between
reaction
roughly
after 17 h (see Table,
cosolvents
cause a five-fold
factors
other than concentration
reduction
at room temperature
On the other hand, use of water as entry 6).
twice as fast as the neat reaction
soluble
The most dramatic
A and diene acid z (R=H) in toluene
after 168 h, see Table, entry 4).
in complete
[J, + 2 (R=H)] proceeds
dienophile
That the aqueous
reaction
(30 h, entry 5) and that water
in rate (cf. entries
7 and 8) suggest
that additional
may be involved.
results were observed
during
the reaction
of ,1.with the sodium salt of diene
acid & (R=Na) in water at room temperature
under vigorous
complete
in 8h giving
of adducts 2 (R=H) and t (R=H) in a ratio of 2:l.
observed
rate increase
of reactants,
by varying
that some type of micellar
for the enhanced
of diene. doubled
of Dienophile
in support
(cf. entries
The reaction
resulting
in mutual
was The
binding
of some sort of aggrega-
When the reaction
3:l ratio of adducts 2 and ,$ which were obtained
Reaction
(entry iO).6
catalysis,
rates. 7 Evidence
the concentration
2 M in diene the rate is approximately
the observed TABLE.
suggests
is responsible
tion was obtained ducted
rise to an 83% yield
stirring
of 4 + 2 (R=Na) is con-
10 and 11).
in quantitative
Of significance yield
(entry 11).
is A
4 with Diene ,2.
R
solvent
concentration of diene
timeb
yieldC
14eH/14aHd
1
Et
benzene
1.0 M
288 h
52%e
0.85
2
Et
neat
_____
144 h
69%
1.3
3
Et
water
1.0 M
168 h
82%
1.3
entrya
-
4
H
toluene
1.0 M
168 h
46%e
0.7
5
H
neat
____-
30 h
80%
1.4
6
H
water
1.0 M
17 h
85%
1.5
104 h
100%
97 h
99%
2.0
46%e
0.9
7
H
water-dioxane
8
H
water-MeOH
9
Na
water
10
Na
11
Na
(1:l)
(1:l)
1.0 p1 1.0
!j
0.8
0.1 fl
120 h
water
1.0 M
ah
83%
2.0
water
2.0 M
5h
100%
3.0
abAll reactions were run at room temperature employing a five-fold excess of diene over dineophile. cYields reported are for chromatographically Reactions were judged to be complete by TLC analysis. eStarting dienophile was recovered: dRatios were determined by NMR. pure mixtures of CII, epimers. entry 1 (29%), entry 4 (40%), and entry 9 (14%).
1899
greater
than fifteen-fold
entries
9 and 10).
Analogous toluene]
decrease
results were obtained
required
In sharp contrast
heating
in a ratio of 3:l.
with dienophile
when the reaction
was conducted
was complete
Of significance
as solvent versus
the reaction
2. ' Reaction
at 100°C for 36 h to provide
diene 2 (R=Na), the reaction
of toluene
in rate accompanies
of Q and 2 in a ratio of 1:l.l.
(1.0 tJ) at room temperature
in 4.5 h giving rise to a 90% yield
once again
3.0 utilizing
is the change
(compare
of 2 with diene x (R=Et) [l.O H in
a 97% yield
in water
that is 0.1 J$ in diene
employing
of adducts
Q and x
in the ratio of Q:z, 0.9 in the case
water.
5
6
The observed the reactants We speculate
7
rate increases
in a micelle,
encountered
thus lowering
that the observed
increases
above may be ascribed
the entropy
in the 14sH/14aH
the Table, and the above results with dienophile volume, wherein volume
the transition
that that leading
through more efficient
state leading
to the 14aH adduct,
aggregation
requirements
(micellar
2) might
to formation
ratios
orientation
for the bimolecular (compare
be explained
entries
unfavorable
of
reaction.
1 and 4 to 11 in
in terms of transition
of the 14sH isomer would occupy
thus minimizing packing).
to the relative
hydrophobic
state
a smaller
interactions
1900
Acknowledgements:
This investigation
(CA 28865) from the National come helpful
Cancer
was supported
Institute.
by a Public Health
We thank Professor
Service
F. Menger
Research
Grant
(Emory University)
for
suggestions.
References
1.
Grieco,
P.A.; Ferrino,
R .; Ferrino, 2.
S.; Jaw, J.-Y.
Enone t, mp 101-103°C dioxane]
S., Vidari, G.
3. Am. Chem. Sot., 1980, 102,
J. Org. Chem., u,
was prepared
from the known octalone
7586.
Grieco,
P.A.; Lis,
47_, 601.
[(a) Li, NH,, THF, t-BuOH;
(b) NaH, DME, HC03Et;
(c) DDQ,
j,."
Me0
i 3.
Grieco,
4.
The reaction
P.A.; Vidari,
For a recent
study on the hydrophobic
Also see, Steinbach,
see:
toluene
acceleration
Rideout,
D.D.; Rossana,
Due to the heterogeneous reactions
Tetrahedron
Lett., 1980, 21, 1619. goes to completion
in ~a. 40 h giving
rise
2 and $ in a ratio of 1:1.2.
water and cyclodextrins,
6.
S.
of t and ; (R=Et) in refluxing
(90%) to adducts 5.
G.; Ferrino,
D.M.
D.C.; Breslow,
R.
in water,
with the aid of an ultrasonic
Diels-Alder
J. Am. Chem. Sot.,
1982 104 ibid *,___*____,
nature of this system
can be conducted
of an intermolecular
reaction
in
1980, 102, 7816.
5853.
vigorous
stirring
is essential.
bath giving rise to essentially
The iden-
tical results. 7.
Cf. Fendlet-, J.H.;
Fendler,
Press, New York, 1975. 8.
Details
Menger,
for the preparation
(Received
E.J.
"Catalysis F.M.
in Micellar
1983)
Systems",
Act. Chem. Res., 1979, 12, 111.
of 2 will be published
in USA 27 January
and Macromolecular
in the full account
of this work.
Academic
"MICELLAR"
CATALYSIS
1897-1900,1953
IN THE AQUEOUS
RATE ACCELERATION Paul A. Grieco,* Department
of Chemistry,
O@O-4039/?3/181997-04$03.00/0 01983 Peqamon Press Ltd.
INTERMOLECULAR
AND ENHANCED
DIELS-ALDER
Philip Garner and Zhen-min
Indiana University,
REACTION:
SELECTIVITY
Bloomington,
He Indiana 47405
Summary: The intermolecular Diels-Alder reactions employing dienophiles k and 2 with diene < have been examined in water. The significantly enhanced rates, as well as the improved selectivity observed in water stand in sharp contrast to the results observed in hydrocarbon solvents:
As a consequence of the Diels-Alder <
R=Et)3 proceeds
of our continuing
adduct
Intermolecular
(2).
in benzene
amount of recovered
importantly, water.5
improve
dienophile.4
(see Table)
In an attempt
that when the Diels-Alder
the ratio of 140-isomer
(288 h versus
,$ over the 14a-isomer
dienophile
quantities
,$' and diene
to shorten
the reaction
time and, more
between ,$ and z (R=Et) was examined
reaction
of
in a ratio of I:I.2, along with a sub-
is carried
t [0.85 (benzene)
1897
between
substantial
giving after 288 h, a 52% yield
168 h, entry 3).
+
we required
reaction
and t (R=Et), mp 93.5-94.O"C,
is more than doubled
Me0
Diels-Alder
upon the isomer ratio, the reaction
The Table reveals
the reaction
in quassinoids,l
at room temperature
adducts 2 (R=Et), mp 129-13O"C, stantial
interest
out in water the rate of
Also notable versus
in
is the increase
1.3 (water)].
It is of
in
1898
interest
to note that the rate of the above aqueous
the rate of reaction
of 2 and 2 (R=Et) conducted
reaction
is not substantially
in the absence
of solvent
different
(cf. Table,
from
entries
2
and 3). Diels-Alder is sluggish solvent
reaction
(60% complete
results
between
reaction
roughly
after 17 h (see Table,
cosolvents
cause a five-fold
factors
other than concentration
reduction
at room temperature
On the other hand, use of water as entry 6).
twice as fast as the neat reaction
soluble
The most dramatic
A and diene acid z (R=H) in toluene
after 168 h, see Table, entry 4).
in complete
[J, + 2 (R=H)] proceeds
dienophile
That the aqueous
reaction
(30 h, entry 5) and that water
in rate (cf. entries
7 and 8) suggest
that additional
may be involved.
results were observed
during
the reaction
of ,1.with the sodium salt of diene
acid & (R=Na) in water at room temperature
under vigorous
complete
in 8h giving
of adducts 2 (R=H) and t (R=H) in a ratio of 2:l.
observed
rate increase
of reactants,
by varying
that some type of micellar
for the enhanced
of diene. doubled
of Dienophile
in support
(cf. entries
The reaction
resulting
in mutual
was The
binding
of some sort of aggrega-
When the reaction
3:l ratio of adducts 2 and ,$ which were obtained
Reaction
(entry iO).6
catalysis,
rates. 7 Evidence
the concentration
2 M in diene the rate is approximately
the observed TABLE.
suggests
is responsible
tion was obtained ducted
rise to an 83% yield
stirring
of 4 + 2 (R=Na) is con-
10 and 11).
in quantitative
Of significance yield
(entry 11).
is A
4 with Diene ,2.
R
solvent
concentration of diene
timeb
yieldC
14eH/14aHd
1
Et
benzene
1.0 M
288 h
52%e
0.85
2
Et
neat
_____
144 h
69%
1.3
3
Et
water
1.0 M
168 h
82%
1.3
entrya
-
4
H
toluene
1.0 M
168 h
46%e
0.7
5
H
neat
____-
30 h
80%
1.4
6
H
water
1.0 M
17 h
85%
1.5
104 h
100%
97 h
99%
2.0
46%e
0.9
7
H
water-dioxane
8
H
water-MeOH
9
Na
water
10
Na
11
Na
(1:l)
(1:l)
1.0 p1 1.0
!j
0.8
0.1 fl
120 h
water
1.0 M
ah
83%
2.0
water
2.0 M
5h
100%
3.0
abAll reactions were run at room temperature employing a five-fold excess of diene over dineophile. cYields reported are for chromatographically Reactions were judged to be complete by TLC analysis. eStarting dienophile was recovered: dRatios were determined by NMR. pure mixtures of CII, epimers. entry 1 (29%), entry 4 (40%), and entry 9 (14%).
1899
greater
than fifteen-fold
entries
9 and 10).
Analogous toluene]
decrease
results were obtained
required
In sharp contrast
heating
in a ratio of 3:l.
with dienophile
when the reaction
was conducted
was complete
Of significance
as solvent versus
the reaction
2. ' Reaction
at 100°C for 36 h to provide
diene 2 (R=Na), the reaction
of toluene
in rate accompanies
of Q and 2 in a ratio of 1:l.l.
(1.0 tJ) at room temperature
in 4.5 h giving rise to a 90% yield
once again
3.0 utilizing
is the change
(compare
of 2 with diene x (R=Et) [l.O H in
a 97% yield
in water
that is 0.1 J$ in diene
employing
of adducts
Q and x
in the ratio of Q:z, 0.9 in the case
water.
5
6
The observed the reactants We speculate
7
rate increases
in a micelle,
encountered
thus lowering
that the observed
increases
above may be ascribed
the entropy
in the 14sH/14aH
the Table, and the above results with dienophile volume, wherein volume
the transition
that that leading
through more efficient
state leading
to the 14aH adduct,
aggregation
requirements
(micellar
2) might
to formation
ratios
orientation
for the bimolecular (compare
be explained
entries
unfavorable
of
reaction.
1 and 4 to 11 in
in terms of transition
of the 14sH isomer would occupy
thus minimizing packing).
to the relative
hydrophobic
state
a smaller
interactions
1900
Acknowledgements:
This investigation
(CA 28865) from the National come helpful
Cancer
was supported
Institute.
by a Public Health
We thank Professor
Service
F. Menger
Research
Grant
(Emory University)
for
suggestions.
References
1.
Grieco,
P.A.; Ferrino,
R .; Ferrino, 2.
S.; Jaw, J.-Y.
Enone t, mp 101-103°C dioxane]
S., Vidari, G.
3. Am. Chem. Sot., 1980, 102,
J. Org. Chem., u,
was prepared
from the known octalone
7586.
Grieco,
P.A.; Lis,
47_, 601.
[(a) Li, NH,, THF, t-BuOH;
(b) NaH, DME, HC03Et;
(c) DDQ,
j,."
Me0
i 3.
Grieco,
4.
The reaction
P.A.; Vidari,
For a recent
study on the hydrophobic
Also see, Steinbach,
see:
toluene
acceleration
Rideout,
D.D.; Rossana,
Due to the heterogeneous reactions
Tetrahedron
Lett., 1980, 21, 1619. goes to completion
in ~a. 40 h giving
rise
2 and $ in a ratio of 1:1.2.
water and cyclodextrins,
6.
S.
of t and ; (R=Et) in refluxing
(90%) to adducts 5.
G.; Ferrino,
D.M.
D.C.; Breslow,
R.
in water,
with the aid of an ultrasonic
Diels-Alder
J. Am. Chem. Sot.,
1982 104 ibid *,___*____,
nature of this system
can be conducted
of an intermolecular
reaction
in
1980, 102, 7816.
5853.
vigorous
stirring
is essential.
bath giving rise to essentially
The iden-
tical results. 7.
Cf. Fendlet-, J.H.;
Fendler,
Press, New York, 1975. 8.
Details
Menger,
for the preparation
(Received
E.J.
"Catalysis F.M.
in Micellar
1983)
Systems",
Act. Chem. Res., 1979, 12, 111.
of 2 will be published
in USA 27 January
and Macromolecular
in the full account
of this work.
Academic