Dual functionalities of hydrogen-bonding self-assembled catalysts in chelation-assisted hydroacylation

Article abstract of DOI:10.1021/jo800862q

(Figure Presented) A recyclable catalyst for chelation-assisted hydroacylation of an olefin with primary alcohol was developed using hydrogen-bonding self-assembled catalysts consisting of 2,6-diaminopyridine and barbiturate phosphine - rhodium(I) complex. Upon heating, these two catalysts act as homogeneous catalysts due to cleavage of the hydrogen bond, and these associate to form supramolecular assemblies via hydrogen bonding that can be separated from immiscible product phase upon cooling after the reaction.

Full text of DOI:10.1021/jo800862q

3
,4
Dual Functionalities of Hydrogen-Bonding
Self-Assembled Catalysts in Chelation-Assisted
Hydroacylation
tion and suppresses decarbonylation. This protocol was
further applied to the use of primary alcohol instead of
aldehyde.
3
,5
The recovery and reuse of transition metal catalysts have
recently attracted much attention in organometallic chemistry.
6
Jung-Woo Park, Ji-Hye Park, and Chul-Ho Jun*
Various methods using supports such as hyperbranched poly-
7
8
9
mers, dendrimers, and hybrid materials or tagging the catalyst
Department of Chemistry, Center for BioactiVe Molecular
Hybrid (CBMH), Yonsei UniVersity, Seoul 120-749,
Republic of Korea
10
to the solid or soluble supports have been developed. In our
first attempt to recycle hydroacylation catalysts, we demonstrated
the reuse of a rhodium complex by employing polystyrene-based
phosphine in which the catalytic reaction showed low reactivity
compared with the corresponding homogeneous catalytic reac-
junch@yonsei.ac.kr
11
tion. Covalently bonded solid-supported catalysts often suffer
from low efficiency because of reduced homogeneity during
the reaction. Here we wish to report a new recyclable self-
assembling organic catalyst capable of reversibly binding with
the metal-phosphine ligand.
ReceiVed April 21, 2008
Hydrogen bonding is useful here since the adducts show
reversible temperature-dependent dissociation on heating. On
the basis of this phenomenon, we have developed a hydrogen-
bond-controlled system for the recycling catalysts. For example,
a hydrogen-bonding mixed solvent system, consisting of 4,4′-
dipyridyl and phenol, was devised for recovery of organic and
3
,12
organometallic catalysts.
Another interesting system is a
supported recyclable catalyst system consisting of a barbiturate
bearing a phosphine ligand (BA-PPh2, 1a) with Rh(I), one
connecting a 2-aminopyridin-4-yl group (BA-2-AP, 1b), and
A recyclable catalyst for chelation-assisted hydroacylation
of an olefin with primary alcohol was developed using
hydrogen-bonding self-assembled catalysts consisting of 2,6-
diaminopyridine and barbiturate phosphine-rhodium(I) com-
plex. Upon heating, these two catalysts act as homogeneous
catalysts due to cleavage of the hydrogen bond, and these
associate to form supramolecular assemblies via hydrogen
bonding that can be separated from immiscible product phase
upon cooling after the reaction.
5
-hexyl-2,4,6-triaminopyrimidine (TP, 2a) as a polymeric
hydrogen-bonding mediator for hydroacylation as shown in
3,13
Scheme 1.
without organic catalyst BA-2-AP (1b), hydroacylation of
-alkene with benzyl alcohol could be achieved in the presence
However, it was unexpectedly found that, even
1
(
3) Our recent account on chelation-assisted C-H and C-C bond activation
and its application to recyclable catalysis: Park, Y. J.; Park, J.-W.; Jun, C.-H.
Acc. Chem. Res. 2008, 41, 222.
(4) (a) Jun, C.-H.; Lee, H.; Hong, J.-B. J. Org. Chem. 1997, 62, 1200. (b)
Jun, C.-H.; Lee, D.-Y.; Lee, H.; Hong, J.-B. Angew. Chem., Int. Ed. 2000, 39,
070. (c) Jun, C.-H.; Moon, C. W.; Lee, D.-Y. Chem.—Eur. J. 2002, 8, 2423.
Transition-metal-catalyzed activation of C-H bonds is
considered to be a good method for generating new C-C
3
(d) Jun, C.-H.; Jo, E.-A.; Park, J.-W. Eur. J. Org. Chem. 2007, 1869.
1
(5) (a) Jun, C.-H.; Huh, C.-W.; Na, S.-J. Angew. Chem., Int. Ed. 1998, 37,
bonds in organic synthesis. In particular, hydroacylation is
1
45. (b) Jun, C.-H.; Hwang, D.-C. Polymer 1998, 39, 7143.
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02, 3215-3892.
a powerful tool for the direct synthesis of ketones from
2
1
aldehyde and alkene in an atom-economical way. We have
(7) (a) Bergbreiter, D. E. Catal. Today 1998, 42, 389. (b) Bergbreiter, D. E.;
developed an efficient chelation-assisted hydroacylation using
a cocatalyst system consisting of a rhodium complex and
Osburn, P. L.; Liu, Y.-S. J. Am. Chem. Soc. 1999, 121, 9531. (c) Wentworth,
P., Jr.; Janda, K. D. Chem. Commun. 1999, 1917. (d) Buchmeiser, M. R.; Wurst,
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van Koten, G. Angew. Chem., Int. Ed. 2000, 39, 3445. (f) Bergbreiter, D. E.;
Osburn, P. L.; Wilson, A.; Sink, E. M. J. Am. Chem. Soc. 2000, 122, 9058. (g)
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2
-amino-3-picoline, which facilitates the C-H bond activa-
(
1) (a) Crabtree, R. H. Chem. ReV. 1985, 85, 245. (b) Shilov, A. E.; Shul’pin,
G. B. Chem. ReV. 1997, 97, 2879. (c) Dyker, G. Angew. Chem., Int. Ed. 1999,
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Kamer, P. C. J.; van Leeuwen, P. W. N. M. Angew. Chem., Int. Ed. 2001, 40,
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Organic Synthesis; Murai, S. Ed.; Springer: Berlin, 1999; p 97. (e) Kakiuchi,
F.; Murai, S. Acc. Chem. Res. 2002, 35, 826. (f) Ritleng, V.; Sirlin, C.; Pfeffer,
M. Chem. ReV. 2002, 102, 1731. (g) Labinger, J. A.; Bercaw, J. E. Nature 2002,
(9) Lindner, E.; Schneller, T.; Auer, F.; Mayer, H. A. Angew. Chem., Int.
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Meijer, E. W.; van Leeuwen, P. W. N. M. J. Am. Chem. Soc. 2001, 123, 8453.
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5
598 J. Org. Chem. 2008, 73, 5598–5601
10.1021/jo800862q CCC: $40.75  2008 American Chemical Society
Published on Web 06/21/2008

SCHEME 1. (a) Self-Assembly of TP (2a) with BA-PPh
1a) and BA-2-AP (1b) and (b) Chelation-Assisted C-H
Bond Cleavage by TP
2
SCHEME 2. (a) Hydrogen-Bonding Interaction of BA-PPh
(1a) with bis-DAP (2b) and (b) Two Possible
2
(
Hydrogen-Bonding Modes of Interaction between BA-PPh
1a) and DAP (2c)
2
(
1
4
of 1a and 2a to give a small amount of product. It can be
speculated that 2a has dual functionalities: hydrogen-bonding
mediator with barbiturate 1a-Rh and chelation assistant auxiliary
for hydroacylation.
On the basis of the above result, catalytic activities of some
potential organic catalysts with dual functionalities, such as
1
3
15
N ,N -bis(6-aminopyridin-2-yl)isophthalamide (bis-DAP, 2b)
and 2,6-diaminopyridine (DAP, 2c) were tested for hydroacy-
lation (Table 1). Since the 2,6-diaminopyridine (DAP) unit
interacts with barbiturate via three hydrogen bonds, the expected
hydrogen bonding network of each DAP derivative and barbi-
turate are illustrated in Scheme 2.
TABLE 1. Isolated Yield (GC Yield) of Chelation-Assisted
Hydroacylation Using Different Organic Catalyst 2
The catalytic activities of these DAP derivatives as well as
TP (2a) for hydroacylation were compared with that of 2-amino-
4
-picoline (Table 1). Benzyl alcohol (3a) was treated with 3,3-
dimethyl-1-butene (4a) at 130 °C for 1 h in the presence of
Rh(I)/PPh3 catalyst and 2a to give 4,4-dimethyl-1-phenylpentan-
1-one (6a) in a 28% isolated yield (entry 1). When the identical
reaction was carried out with bis-DAP (2b), product 6a was
isolated in a 27% yield. However, with DAP (2c), a 72% isolated
yield of 6a was obtained. This result is comparable to that of
2
-amino-4-picoline. As a result, 2c was chosen as a chelation-
assisted recyclable catalyst for hydroacylation.
As stated earlier, two possible modes of hydrogen-bonding
self-assemblies from 1a and 2c are shown in Scheme 2b.
Although the structural arrangement of [DAP]-[BA-
PPh2]-[DAP] (1/2 ratio of 1a/2c) seems to be reasonable, that
of [DAP]-[BA-PPh2]-[BA-PPh2]-[DAP] (1/1 ratio) is also
possible based on the single-crystal X-ray structural analysis
of the similar type of 2,6-diaminopyridine-platinum(II) barbi-
1
6
turate complex previously reported. For the clear structural
determination in solution, the interaction of BA-PPh2 (1a) with
DAP (2c) was studied by H NMR spectroscopy in CDCl3.
1
a
GC yields are given in parentheses.
(
13) (a) Kim, D.-W.; Lim, S.-G.; Jun, C.-H. Org. Lett. 2006, 8, 2937. For
Hydrogen bonding between 1a and 2c was evidenced by marked
downfield shifts in the signal corresponding to the N-H of 2c.
orthoalkylation: (b) Yoon, J. H.; Park, Y. J.; Lee, J. H.; Yoo, J.; Jun, C.-H. Org.
Lett. 2005, 7, 2889.
1
(
14) Reaction of benzyl alcohol (3a) and 3,3-dimethyl-1-butene (4a) was
The Job plot determined by H NMR experiments revealed that
2 2 2
carried out in the presence of [(COE) RhCl] (5, 5 mol %), BA-PPh (1a, 40
a 1:1 complex such as [DAP]-[BA-PPh2]-[BA-PPh2]-[DAP]
might be formed between 1a and 2c (Figure 1a; see Supporting
Information). Moreover, the resulting organometallic complexes
may be highly cross-linked by coordinating Rh(I) to phos-
mol %), TP (2a, 40 mol %), cyclohexylamine (10 mol %), and benzoic acid (20
mol %) in 1,4-dioxane at 130 °C to afford 6a in a 24% GC yield after 1 h.
(
15) Several reports of hydrogen-bonding network of 2b derivatives with
barbiturates: (a) Chang, S. K.; Hamilton, A. D. J. Am. Chem. Soc. 1988, 110,
318. (b) Chang, S. K.; Engen, D. V.; Fan, E.; Hamilton, A. D. J. Am. Chem.
Soc. 1991, 113, 7640. (c) Motesharei, K.; Myles, D. C. J. Am. Chem. Soc. 1998,
20, 7328. (d) Al-Sayah, M. H.; McDonald, R.; Branda, N. R. Eur. J. Org.
Chem. 2004, 173.
16) Knizek, J.; Krossing, I.; N o¨ th, H.; Plener, V.; Schmidt, M.; Weigand,
W. Z. Naturforsch. B 1998, 53b, 1135.
1
1
7
phines, which results in the formation of insoluble hydrogen-
bonding assemblies (Figure 1b).
1
(
(17) Yamada, Y. M. A.; Maeda, Y.; Uozumi, Y. Org. Lett. 2006, 8, 4259.
J. Org. Chem. Vol. 73, No. 14, 2008 5599

a
TABLE 2. Recycle of Catalysts 1a-Rh and 2c for Hydroacylation of 4 with 3
isolated yield of product (%)
1
2
entry
R (3)
R (4)
ketone (6)
rxn time (h)
1
2
3
4
5
6
t
1
2
3
4
H (3a)
3a
CF3 (3b)
MeO (3c)
C4H9 (4a)
C4H9 (4b)
6a
6b
6c
6d
6
6
6
3
78
70
83
77
83
84
89
71
86
84
81
81
76
78
77
78
76
75
77
72
77
80
82
78
n
4a
4a
a
At 1st and 4th runs, 25 mol % of benzoic acid was added, and cyclohexylamine was added in every run.
FIGURE 2. (a) Schematic illustration of the recycling organometallic
and organic catalysts, 1a-Rh with 2c for hydroacylation. (b) Homo-
geneous phase consisting of 1a-Rh, 2c, 3a, 4a, benzoic acid, and Cy-
1
FIGURE 1. (a) Job plot between 1a and 2c (determined by H NMR
spectroscopy in CDCl and (b) expected structure of the resulting
2
NH in 1,4-dioxane at high temperature (130 °C). (c) Separation of
3
reaction mixture (liquid/liquid) from Figure 2b after cooling to room
temperature (25 °C). (d) Supramolecular solid obtained upon addition
of n-pentane to the sample shown in Figure 2c for decanting the product.
supramolecular assembly after addition of rhodium complex.
This self-assembly system of BA-PPh2 (1a) and DAP (2c)
was applied to the reaction of benzyl alcohol (3a) with 3,3-
dimethyl-1-butene (4a) in the presence of [(COE)2RhCl]2 (5,
and the yield of product 6a was sustained (Table 2, entry 1).
Other alcohols 3 and olefins 4 were applied to this reaction,
affording the corresponding ketones with good to moderate
yields for the repeated use of catalysts without loss of the
reactivity (entries 2-4). In particular, 4-methoxybenzyl alcohol
1
0 mol % [Rh]), cyclohexylamine (Cy-NH2, 10 mol %), and
1
8
benzoic acid (25 mol %) at 130 °C for 6 h in 1,4-dioxane
Figure 2a). The ratio of 1a and 2c was adjusted to 1:1 to form
(
a supramolecular hydrogen-bonding complex. During the reac-
tion at high temperature, the system was homogeneous because
a hydrogen-bonding network cannot be established (Figure 2b),
but it was heterogenized at room temperature to form two phases
after the reaction due to the formation of a hydrogen-bonding
network (Figure 2c). After the addition of n-pentane, a lower
phase was precipitated to form a yellow solid. It was found
that barbiturate 1a-Rh remained in the lower solid phase
assembled with 2c, while the product 6a was separated from
the self-assembled mixture of 1a-Rh and 2c by decanting the
upper layer and washing the lower layer with n-pentane (Figure
(
3c) showed better reactivity than the other substrates since the
reaction time could be reduced from 6 to 3 h (entry 4).
To confirm whether product ketones were completely sepa-
rated from the lower solid catalyst mixtures, the reactions were
performed using different substrates in every cycle (Table 3).
It was found that only a trace amount of ketone in the previous
run remained in the next run. The first reaction was carried out
using 3b and 4a to give 6c in an 80% isolated yield (88% GC
yield) due to its reduced reactivity compared with that of 3a
and 3c. The separated barbiturates 1a-Rh and 2c were reused
for the next reaction of 3a and 4b to afford 6b in a 91% isolated
yield (100% GC yield) while detecting less than 1% of 6c. In
the third run using 3c and 4a, a 92% isolated yield of 6d and
2
d).
The remaining barbiturate 1a-Rh and DAP (2c) were recycled
for the next reaction with addition of substrates and solvent.
This process was repeated up to the sixth catalytic reaction,
6
b was obtained with a ratio of 99:1.
In conclusion, a novel recyclable organic catalyst system for
chelation-assisted hydroacylation of an olefin with primary
2
(18) CyNH and benzoic acid are additives for accelerating the hydroacylation
reaction.
alcohol was developed using 2,6-diaminopyridine (DAP, 2c)
5
600 J. Org. Chem. Vol. 73, No. 14, 2008

TABLE 3. Hydroacylation with Different Substrates Showing
dimethyl-1-butene (4a), 10.8 mg (0.015 mmol) of [(COE)
5), 65.0 mg (0.12 mmol) of barbiturate 1a, 14.7 mg (0.12 mmol)
of 2,6-diaminopyridine (2c), 3 mg (0.03 mmol) of cyclohexylamine,
.0 mg (0.0075 mmol) of benzoic acid, and 50 mg of 1,4-dioxane
2 2
RhCl]
a
Complete Separation of the Product in Each Run
(
9
in a dry box. The reaction mixture was stirred for 6 h in an oil
bath that was preheated at 130 °C. After cooling to room
temperature, n-pentane (1 mL) was added to the reaction mixture,
which was stirred and centrifuged. The upper n-pentane layer
was decanted using a pipet. This process was repeated three
times. The solvent in combined solution was evaporated, and
the resulting residue was purified by column chromatography
run
reactants (3, 4)
isolated yield (%)
1
2
t
1
2
3
R ) CF3 (3b), R ) C4H9 (4a)
80 (6c)
91 (6b:6c ) 99:1)
92 (6d:6b ) 99:1)
1
2
n
R ) H (3a), R ) C4H9 (4b)
1
2
t
R ) MeO (3c), R ) C4H9 (4a)
(
2
SiO , n-hexane) to give 44.5 mg (78% yield) of 6a. To the
a
At first run, 25 mol % of benzoic acid was added, and cyclo-
hexylamine was added in every run.
remaining solid layer were added 32.4 mg (0.3 mmol) of benzyl
alcohol (3a), 126 mg (1.5 mmol) of 3,3-dimethyl-1-butene (4a),
3
mg (0.03 mmol) of cyclohexylamine, and 50 mg of 1,4-dioxane
as a chelation auxiliary catalyst and barbiturate bearing phos-
phine-Rh (1a-Rh) as a self-assembling partner. The self-
assembly of DAP and BA-PPh2 expressed one of two func-
tionalities (catalysis and hydrogen-bonding self-assembly support)
depending on the applied thermal condition. During the reaction
at high temperature, the system is homogeneous and shows good
catalytic activity. After the reaction, the system is heterogenized
at room temperature to form two immiscible phases for the facile
recovery of catalysts. We are currently investigating further
applications of this recycling catalysis protocol for other catalytic
reactions.
for the next reaction. The reaction procedure was repeated, and
the results are shown in entry 1, Table 2.
Acknowledgment. This work was supported by the Korea
Research Foundation Grant funded by the Korea Government
(
MOEHRD) (KRF-2005-201-C00024). J.-W.P. acknowledges
the fellowship of the BK21 program from the Ministry of
Education and Human Resources Development and the Seoul
Science Fellowship Program and CBMH.
Supporting Information Available: Experimental details of
Job plot. This material is available free of charge via the Internet
at http://pubs.acs.org.
Experimental Section
A screw-capped pressure vial (1 mL) was charged with 32.4 mg
(
0.3 mmol) of benzyl alcohol (3a), 126 mg (1.5 mmol) of 3,3-
JO800862Q
J. Org. Chem. Vol. 73, No. 14, 2008 5601