Bronsted acid mediated heterogeneous addition reaction of 1,3-dicarbonyl compounds to alkenes and alcohols

Article abstract of DOI:10.1002/anie.200504609

(Chemical Equation Presented) The unique acidity of a proton-exchanged montmorillonite catalyst (H-mont) was exploited in the nucleophilic addition of 1,3-dicarbonyl compounds to simple alkenes (see scheme). The benzylation and allylation of 1,3-dicarbony

Full text of DOI:10.1002/anie.200504609

Angewandte
Chemie
Heterogeneous Catalysis
DOI: 10.1002/anie.200504609
Brønsted Acid Mediated Heterogeneous Addition
Reaction of 1,3-Dicarbonyl Compounds to
Alkenes and Alcohols**
Ken Motokura, Noriaki Fujita, Kohsuke Mori,
Tomoo Mizugaki, Kohki Ebitani, and
Kiyotomi Kaneda*
From the standpoint of atom efficiency,[1] nucleophilic addi-
tions to alkenes or alcohols instead of alkyl halides are
attractive salt-free methods (Scheme 1). Simple alkenes are
readily accessible and abundant carbon-atom sources, but
intermolecular additions of 1,3-dicarbonyl compounds to
simple alkenes remain problematic. In traditional acid- or
base-catalyzed Michael reactions of 1,3-dicarbonyl com-
[*] Dr. K. Motokura, N. Fujita, Dr. K. Mori, Dr. T. Mizugaki, Dr. K. Ebitani,
Prof. Dr. K. Kaneda
Department of Materials Engineering Science
Graduate School of Engineering Science
Osaka University
1-3 Machikaneyama, Toyonaka, Osaka 560-8531 (Japan)
Fax: (+81)6-6850-6260
E-mail: kaneda@cheng.es.osaka-u.ac.jp
[**] This investigation was supported by a Grant-in-Aid for Scientific
Research from the Ministry of Education, Culture, Sports, Science,
and Technology of Japan (16206078). We thank the Center of
Excellence (21COE; “Creation of Integrated Ecochemistry” pro-
gram, Osaka University). We are also grateful to Prof. Dr. S. Namba
(Teikyo University) for catalyst preparation and Dr. K. Mori, Dr. Y.
Senga, and Dr. S. Yamakita (Bel Japan) for TPD measurement. K.M.
thanks the JSPS for a Research Fellowship for Young Scientists.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
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hydrogen chloride (see Experimental Section). X-ray diffrac-
tion verified retention of a layered structure. The degree of
exchange of the sodium cations in the H-mont was 98.9%.
NH3-TPD (temperature programmed desorption) analysis
revealed the strength (DH)[8,9] and quantity of the acid sites in
the H-mont to be 111 kJmolÀ1 and 0.86 mmolgÀ1, respec-
tively. Other zeolites, such as H-USY, H-mordenite, and H-
ZSM-5, were commercially available. Al-MCM-41, which has
large pores, was prepared according to the literature.[10]
The reaction of acetyl acetone (1a) with norbornene (2a)
was examined in the presence of several acid catalysts
(Table 1). The H-mont catalyst displayed excellent activity
and gave 3a in 83% yield (Table 1, entry 1). Substitution of
Scheme 1. A comparison of nucleophilic additions to halides (with salt
formation) and to alkenes or alcohols (without salt formation).
pounds, only reactive, electron-deficient alkenes, such as a,b-
unsaturated ketones, have been utilized. Attempts to over-
come this limitation have focused mainly on the development
of homogeneous metal catalysts to which the alkenes can
coordinate;[2,3] however, these catalyst systems require expen-
sive metals and halogenated solvents. We have pursued a new
Table 1: Addition of 1a to 2a in the presence of various acid catalysts.[a]
concept that involves dual activation of the olefinic double
[4]
À
bond and the reacting C H bond of the nucleophile by
catalytic sites to promote a highly efficient intermolecular
addition reaction.
Entry Catalyst
Acid sites
[mmolgÀ1 [b]
Pore size Conv.
[Š]
Yield
A
]
2a [%][c] 3a [%][c]
Recently, solid acid catalysts based on montmorillonites
(monts)[5] and zeolites,[6] which have uniformly sized pores
and voids, have received attention. Their adjustable acidity
derived from enwrapped protons enables a variety of highly
selective organic reactions. The use of solid montmorillonite
and zeolite catalysts in liquid-phase organic synthesis also
allows a simple workup and the potential to recycle catalysts
in an environmentally acceptable process. Previously, we
reported that montmorillonites that enwrap metal cations
(Mn+-monts) act as strong solid acid catalysts for various
organic transformations.[7] Herein, we describe a novel
synthetic method in which montmorillonites are used in
addition reactions of 1,3-dicarbonyl compounds to alkenes
(Scheme 2). Not only does this heterogeneous catalytic
system enable a simple workup and the use of recyclable
catalysts, but it also has high activity owing to unique acid
sites in the montmorillonite. Furthermore, the catalytic
system can be used for the benzylation and allylation of 1,3-
dicarbonyl compounds with alcohols and for the nucleophilic
addition of carboxylic acids to alkenes.
1
2
3
4
5
6
7
8
9
H-mont
H-USY
0.86
0.53
0.25
0.15
1.07
0.87
n.m.
n.m.
–
–
87
37
9
83
37
8
5
7.4”7.4
–
27”27
6.5”7.0
mont K10
Al-MCM-41
H-mordenite
H-ZSM-5
SO42À/ZrO2
Na+-mont
7
11
n.r.
n.r.
n.r.
29
n.r.
n.r.
trace[d]
n.r.
n.r.
n.r.
4
5.1”5.5
–
–
–
–
–
[e]
H2SO4
10
11
p-TsOH·H O[e]
–
–
n.r.
n.r.
2
none
[a] Reaction conditions: 1a (1.3 mmol), 2a (1.0 mmol), catalyst (0.03 g),
n-heptane (2 mL), 0.5 h, 1508C. [b] Estimated from the h and h+ peaks in
the NH3-TPD spectra. [c] Determined by GC analysis and 1H NMR
spectroscopy. [d] Oligomers of 2a are the main products. [e] Quantity
used: 0.1 mmol. n.m.=not measured, n.r.=no reaction.
H-mont for H-USY led to just a moderate yield of the product
(Table 1, entry 2). Other solid acids, such as mont K-10, Al-
MCM-41, and H-mordenite, were significantly less active
(Table 1, entries 3–5). The reaction scarcely occurred in the
presence of H-ZSM-5 as a result of its restricted pore size
(Table 1, entry 6). The homogeneous acids H2SO4 and p-
toluenesulfonic acid were not effective catalysts under these
reaction conditions (Table 1, entries 9 and 10).
Proton-exchanged montmorillonite (H-mont) was pre-
pared from Na+-mont by using an aqueous solution of
The H-mont-catalyzed addition reaction was extended to
other 1,3-dicarbonyl compounds and alkenes, as shown in
Table 2. Compound 2a reacted with a variety of b-diketones
to afford the addition products in excellent yields (Table 2,
entries 1–3 and 6). Notably, the reactions of b-ketoesters and
a b-lactone proceeded smoothly; the hydrodecarboxylation of
the ester groups was suppressed (Table 2, entries 4, 5, and
7).[11] Intermolecular additions of b-ketoesters to norbornene
were previously unknown. Interestingly, less reactive cyclic
alkenes, such as cyclopentene (2b) and cyclohexene (2c),
were good substrates for this H-mont catalyst system (Table 2,
entries 8–10). The reaction of the terminal aliphatic olefins 1-
pentene (2d) and 1-hexene (2e) gave the dione compounds in
Scheme 2. Use of a proton-exchanged montmorillonite as the catalyst
in addition reactions of 1,3-dicarbonyl compounds to alkenes.
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Table 2: Addition reaction of 1,3-dicarbonyl compounds 1 to alkenes 2.[a]
Table 3: Reuse of the H-mont catalyst for the addition reaction of 1a to
2a.[a]
Recycle number
Yield of 3a [%][b]
fresh
93
1
2
3
4
5
6
7
92
93
93
92
94
92
93
[a] Reaction conditions: 1a (1 mmol), 2a (1.3 mmol), H-mont (0.15 g),
n-heptane (2 mL), 1 h, 1508C. [b] Determined by GC analysis.
Entry
1
2
t [h]
T [8C]
Yield [%][b]
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1 f
1g
1c
1b
1c
1c
1c
1e
1 f
2a
2a
2a
2a
2a
2a
2a
2b
2c
2c
2d
2e
2 f
1
1
1
1
1
150
150
150
150
150
150
150
180
180
180
150
150
150
150
90
88
93
(71)
74
83
87
(66)
78
(80)
53, 9:1[f]
60, 5:1[f]
72[h]
72[h]
Table 4: a-Benzylation and allylation of 1,3-dicarbonyl compounds 1 by
treatment with alcohols.[a]
1
1
Entry
1
Alcohol
T [8C]
Yield [%][b]
8[c]
9[c]
10[c]
11[d,e]
12[d,e]
13[e,g]
14[i]
24
24
24
24
24
3
R, R’
1
2
1a
1a
1a
1a
Ph, Me
100
150
150
100
90
80
72
91
p-Cl-C6H4, Me
2-naphthyl, Me
Ph, Ph
3[c]
4
2g
3
5
1a
90
80[d]
[a] Reaction conditions: 1 (1 mmol), 2 (1.3 mmol), H-mont (0.15 g), n-
heptane (2 mL). [b] Yield of the isolated product based on the dicarbonyl
starting material. Values in parentheses are yields as determined by GC
analysis. Diastereomers were formed in a 1:1 ratio from asymmetric
dicarbonyl compounds (1H NMR). Only the exo product was isolated in
the reaction of 2a. [c] Quantity of 2: 5 mmol. [d] Quantity of 2: 15 mmol.
[e] The alkene was added in portions. [f] Ratio of the 2-adduct to the 3-
adduct (1H NMR). [g] Quantity of 1e: 3 mmol, 2 f: 1 mmol. [h] Yield of
the isolated product based on the alkene. [i] Quantity of 1 f: 1.3 mmol,
2g: 1 mmol.
6[e]
7[c]
8
1b
1 f
1d
1e
Ph, Me
Ph, Me
Ph, Me
Ph, Me
100
150
100
100
86[f]
86[f]
88[f]
51[f]
9
10
1d
90
48[f]
[a] Reaction conditions:
1 (1.5 mmol), alcohol (1 mmol), H-mont
(0.15 g), n-heptane (2 mL), 1 h, 1008C. [b] Yield of the isolated product
based on the alcohol. [c] Reaction time: 0.5 h. [d] Yield as determined by
GC analysis. [e] Quantity of 1b: 1 mmol. [f] Diastereomers were formed
in a 1:1 ratio (1H NMR).
moderate yields along with small amounts of isomerization
products (Table 2, entries 11 and 12). Styrene derivatives also
functioned as good substrates in the H-mont-catalyzed
addition reaction (Table 2, entries 13 and 14).[12]
The high activity of the H-mont catalyst system and the
simplicity of the workup procedure are exemplified by the
following: After the reaction of dibenzoylmethane (1c;
22.4 g, 0.10 mol) with 2a (11.3 g, 0.12 mol) at 1508C for 3 h
in the presence of the H-mont catalyst (0.3 g), the spent
catalyst was readily separated from the reaction mixture.
Direct recrystallization then gave pure 2-(bicyclo-
in 90% yield (Table 4, entry 1). The sterically hindered
alcohol 1-(2-napthyl)ethanol was also a good substrate for
this reaction (Table 4, entry 3). In the case of 2-cyclohexen-1-
ol, a-allylation proceeded efficiently (Table 4, entries 5 and
10). Furthermore, b-ketoesters underwent both benzylation
(Table 4, entries 8 and 9) and allylation (Table 4, entry 10).
Halides are usually used for the a-benzylation and allylation
of active methylene groups;[13] methods in which an alcohol is
used as a benzylating or allylating reagent are highly atom
efficient candidates.[14,15] Unfortunately, reactions with pri-
mary alcohols resulted in low yields owing to the formation of
ethers under the present reaction conditions.
In the reaction of 1a with 2a, the addition of the radical
trap 2,6-di-tert-butyl-p-cresol to the reaction medium had
hardly any influence.[16] The IR spectrum of the H-mont upon
treatment with pyridine showed a new peak at 1543 cmÀ1 due
to protonated pyridine molecules.[9,17] The catalytic activity of
a variety of Brønsted acids was shown not to depend on their
acidity, as determined by NH3-TPD (Table 1); H-mordenite,
which has strong Brønsted acidity (DH = 160 kJmolÀ1) was
less active than the H-mont and H-USY catalysts, which have
DH values of 111 and 122 kJmolÀ1, respectively.[8,9] These
results suggest that a suitable strength of the Brønsted acid
sites is required for efficient addition reactions of 1,3-
dicarbonyl compounds to alkenes. In the intermolecular
A
(31.3 g,
98% yield of the isolated product).[9] The turnover number
(TON) and turnover frequency (TOF) of this catalytic
reaction (TON: 380, TOF: 127 hÀ1, based on the active acid
sites of the H-mont) were considerably greater than those of a
previously reported homogeneous AuCl3/AgOTf catalyst
system (TON: 16, TOF: 3.2 hÀ1).[3a] Additionally, the recov-
ered H-mont catalyst could be reused at least seven times
without any loss of its activity (Table 3). Dimethyl malonate,
which has a high pKa value, did not react.
The high reactivity of 1,3-dicarbonyl compounds in the H-
mont-catalyzed reactions prompted investigations of the a-
benzylation and allylation of the 1,3-dicarbonyl compounds
by treatment with alcohols (Table 4). The reaction of 1a with
1-phenylethanol in the presence of the H-mont catalyst gave
the a-benzylated product 3-(1-phenylethyl)pentane-2,4-dione
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competitive reaction of 2a with an equimolar mixture of 1a
Furthermore, the higher activity of the H-mont catalyst
relative to that of the homogeneous acids can be attributed to
concentrated protonic acid sites in the interlayer space of the
H-mont.
(pKa = 9.0)[18] and nitroethane (pKa = 8.6),[18] the H-mont
catalyst favored the formation of 3a (97% yield) exclusively
(Scheme 3).
The strong protonation ability of the H-mont catalyst is
further applicable to the addition reactions of carboxylic acids
to alkenes (Scheme 5). For example, the reaction of benzoic
Scheme 3. Intermolecular competitive reaction of 2a with an equimo-
lar mixture of 1a and nitroethane under H-mont catalysis.
After treatment of the H-mont catalyst with 1a, I R
absorptions due to both the keto and enol forms of 1a
(1537
detected, similar to those found for adsorbed 1a onto the
Brønsted acid site of Z12H zeolite (1540(enol), 1592(enol),
and 1700
(keto) cmÀ1).[19] A proposed reaction path involves
A
(enol), and 1698
U
Scheme 5. The H-mont-catalyzed addition of carboxylic acids to
alkenes. Tol=tolyl.
the dual activation of the alkene and the 1,3-dicarbonyl
compound: 1) protonation of an alkene at an acid site and
coordination of a 1,3-dicarbonyl compound to a neighboring
H+ site;[20] 2) formation of an activated enol intermediate;
3) nucleophilic attack of the enol (Scheme 4). Kinetic studies
showed first-order dependence on 2a and an inverse first-
order relationship with respect to 1a,[9] and thus indicated that
alkene protonation may be a rate-determining step that is
impeded by adsorbed 1,3-dicarbonyl compounds. The neg-
atively charged silicate layers are capable of acting as
delocalized counter anions to stabilize cationic intermediates.
acid with 2a in the presence of the H-mont catalyst gave 2-
benzoyloxynorbornane in 89% yield. Even with less reactive
simple alkenes, such as cyclopentene and cyclohexene, the
corresponding esters were obtained in excellent yields.
Furthermore, the H-mont catalyst promoted the intramolec-
ular reaction of 2-cyclopentene-1-acetic acid in excellent
yield.
In summary, environmentally benign addition reactions of
various 1,3-dicarbonyl compounds to alkenes and alcohols in
the presence of solid acid catalysts have been described.
Unique acid sites with delocalized counter anions of two-
À
dimensional silicate sheets will allow additional novel C C
bond-forming reactions.
Experimental Section
A
mixture of the parent Na+-montmorillonite (3.0 g;
Na0.66(OH)4Si8(Al3.34Mg0.66Fe0.19)O20; Na 2.69, Al 11.8, Fe 1.46, Mg
1.97%; Kunipia F, Kunimine Industry, Japan) and aqueous HCl
(1.1 wt%, 200 mL) was stirred at 908C for 24 h. The slurry obtained
was filtered and washed with distilled water (1 L) to remove chlorine,
then dried at 1108C in air to afford the H-mont as a whitish-gray
powder. Elemental analysis: Na 0.03, Mg 1.73, Al 10.1, Fe 1.34%.
Typical procedure: H-mont (0.15 g), n-heptane (2 mL), 1a
(1 mmol), and 2a (1.3 mmol) were placed in a pressure tube, and
the resulting mixture was stirred vigorously at 1508C. After 1 h, the
catalyst was separated by filtration. GC analysis of the filtrate showed
that 3a had formed in 93% yield. The filtrate was concentrated by
evaporation, and the crude product was purified by column chroma-
tography on silica (diethyl ether/n-hexane 1:9) to afford the pure
product (90% yield). The recovered catalyst could be reused at least
seven times without appreciable loss of activity and selectivity: The
yields of the first, second, and seventh runs were 92, 93, and 93%,
respectively.
Scheme 4. A proposed dual-activation reaction pathway for the addi-
tion of 1,3-dicarbonyl compounds to alkenes or alcohols in the
presence of the H-mont catalyst.
Received: December 29, 2005
Published online: March 17, 2006
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[16] For the radical addition of active methylene compounds to
Keywords: 1,3-dicarbonyl compounds · addition reactions ·
alcohols · alkenes · heterogeneous catalysis
.
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[17] For
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when the H-mont catalyst was used.
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