Metallo-enzyme model in pure water: Cyclodextrin-lanthanide tris(perfluoroalkanesulfonyl)methide and bis(perfluoroalkanesulfonyl)amide complexes

Article abstract of DOI:10.1055/s-2002-34234

Inclusion complexes of cyclodextrin/cyclodextrin copolymer and lanthanide tris(perfluorobutanesulfonyl)methide/bis(perfluorobutanesulfonyl)amide, namely metallo-enzyme model, are efficient and recyclable super Lewis acid catalysts, which can promote Diels

Full text of DOI:10.1055/s-2002-34234

LETTER
1613
Metallo-Enzyme Model in Pure Water: Cyclodextrin-Lanthanide Tris(per-
fluoroalkanesulfonyl)methide and Bis(perfluoroalkanesulfonyl)amide
Complexes
M
etallo-E
o
nzym
e
Mode
j
l
in Pu
i
re
W
ater Nishikido,*a Masayuki Nanbo,a Akihiro Yoshida,a Hitoshi Nakajima,a Yousuke Matsumoto,b Koichi Mikami*b
a
The Noguchi Institute, Tokyo 173-0003, Japan
b
Department of Applied Chemistry, Tokyo Institute of Technology, Meguro-ku, Tokyo 152-8552
Fax +81(3)57342776; E-mail: kmikami@o.cc.titech.ac.jp
Received 1 July 2002
Metallo-enzyme Model: CDP-Ln[X(SO2C4F9)n]3
Abstract: Inclusion complexes of cyclodextrin/cyclodextrin co-
polymer and lanthanide tris(perfluorobutanesulfonyl)methide/
bis(perfluorobutanesulfonyl)amide, namely metallo-enzyme mo-
del, are efficient and recyclable super Lewis acid catalysts, which
can promote Diels–Alder and Mukaiyama-aldol reactions in pure
water.
H2O
Key words: cyclodextrin, Lewis acids, catalysis, lanthanides,
aqueous reactions
fluorous
"ponytail"
F3C
CF2
O
X
diene & dienophile
F2C
S
F2C
Ln
O
O
Enzymes are gigantic proteins that function as catalysts
for biological reactions particularly in water. These en-
zymes include the structure of the hydrophobic pocket for
inclusion of organic apolar substrates, and the reaction ki-
netics increased at the hydrogen bonding or metallo-com-
plexation sites. A wide variety of Lewis acid metal
complexes have thus been developed to realize unique re-
activities and high selectivities close to those attained by
enzymes, however, without any hydrophobic pocket.1,2
Here we report a metallo-enzyme model consisting of hy-
drophobic pocket and Lewis acid metal complex, as a re-
cyclable catalyst in pure water.
cyclodextrin
copolymer
(CDP)
X = N or C, n = 2 or 3
Ln = lanthanide metal
Figure 1
outside the hydrophobic pockets of CD. Thus, organic
substrates are expected to be readily activated by coordi-
nation of the center metal in the inclusion complexes.
First, the synthesis of CD- and CD copolymer (CDP)-Ln
methide and amide inclusion complexes were examined.
CD and -CD/epichlorohydrin copolymer (CDP)16 were
suspended in water at room temperature, and then Ln me-
thide or amide was added to this solution or suspension.
The complexes of - and -CD with Ln Cn-methide and
Cn-amide (n = 4) were precipitated as inclusion complex-
es, with the exception of -CD, washed with water, and
dried at 60 °C under 0.1 mmHg.
How can we design a metallo-enzyme model consisting
of Lewis acid catalysts and hydrophobic pocket, and im-
mobilization thereof in pure water?3,4 Cyclodextrin (CD)
is a naturally occurring host molecule and can form insol-
uble crystalline inclusion complexes with organic mole-
cules.5–8 Thus, we designed CD inclusion complexes of
trivalent lanthanide [Ln(III)] tris(perfluoroalkane-
sulfonyl)methide9 [abbreviated as Ln(Cn-methide)3] and
bis(perfluoroalkanesulfonyl)amide9 [abbreviated as
Ln(Cn-amide)3] as super Lewis acidic and completely re-
cyclable catalysts. Particularly, ytterbium and scandium
methide and amide complexes with fluorous pony
tails10–13 (Figure 1) effectively formed the inclusion
complex14 with CD. It was reported that CD forms inclu-
sion complexes with fluorocarbon surfactants, due to hy-
drophobic interaction.5,15 Since the chain length of
perfluorobutane group is nearly equal to the length of cy-
clodextrin ring, it is assumed that the metal locates just
Scanning transmission electron microscopy (STEM)
micrographs17 or Yb, F, S energy-dispersive X-ray (EDX)
maps of CD- and CDP-Yb bis(perfluorobutanesulfo-
nyl)amide [abbreviated as Yb(C4-amide)3]13 thus obtained
are shown in Figure 2 and Figure 3, respectively. The Yb
amide was found to be equally dispersed and immobilized
in the hydrophobic cavity of CD and CDP, as observed by
Yb, F and S mapping. The amount of Ln(C4-methide)3 or
Ln(C4-amide)3 in the cavity of CDP could be controlled to
be ca. 50% by varying the amount of the Ln complexes.18
Lanthanide triflates, bis(trifyl)amides and tris(trifyl)me-
thides did not form any inclusion complex with -CD or
-CD. These results indicate that CD forms inclusion
complexes selectively with Ln[C(SO2CnF2n+1)3]3 and
Ln[N(SO2CnF2n+1)2]3, (n = 4).
Synlett 2002, No. 10, Print: 01 10 2002.
Art Id.1437-2096,E;2002,0,10,1613,1616,ftx,en;U03002ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1614
J. Nishikido et al.
LETTER
ethane layer was analyzed by GC using n-nonane as an in-
ternal standard. The chemical yield was 99% (entry 9).
Under the same reaction conditions, the adduct was ob-
tained in only low yields (9%, 9%) in the presence of
Yb(OTf)3 (entry 5) or Yb(NTf2)3 (entry 6). Both 20 mol%
of CDP itself (entry 7) and Yb C4-methide catalyst (entry
8) gave the adduct in low yields (12% and 39%). Thus, the
CDP-Yb methide complex gave a much higher yield than
either CDP or Yb methide complex did. These results
clearly show that the Yb methide complex-catalyzed reac-
tion is further accelerated by hydrophobic association of
the D–A substrates within the inclusion complex in water.
The Yb methide complex was completely (>99.9%) re-
covered as determined by atomic emission spectrometry
analysis.
0.2 mm
F
STEM
S
Yb
O
O
Cat. (10 mol%)
Figure 2 Scanning transmission electron microscopy (STEM);
micrograph and Yb, F, S energy-dispersive X-ray (EDX); map of CD-
Yb bis(perfluorobutanesulfonyl)amide
+
r.t., 5 h
H2O (6 mL)
2 mmol
2.2 mmol
Scheme 1
0.3 mm
Table 1 Diels–Alder Reactions in Water
Entry
Catalysta
Yield (%)d
F
STEM
1
2
None
8
8
D-glucoseb
-CDb
3
9
4
-CDb
9
5
Yb(OTf)3
9
6
Yb(NTf2)3
CDPb
9
S
Yb
7
12
39
99
25
8
Yb(C4-methide)3
CDP-Yb(C4-methide)3
CDP-Yb(C4-methide)3
9
Figure 3 Scanning transmission electron microscopy (STEM);
micrograph and Yb, F, S energy-dispersive X-ray (EDX); map of
CDP-Yb bis(perfluorobutanesulfonyl)amide
c
10
a CDP: -CD/epichlorohydrin copolymer; Yb(C4-methide)3:
Yb[C(SO2-n-C4F9)3]3; CDP-Yb(C4-methide)3: CDP complex of
Yb(C4-methide)3.
The catalytic activities and recycling of the CDP-Ln com-
plexes were then examined for C–C bond-forming reac-
tions such as the Diels–Alder (D–A) reaction
(Scheme 1),19,20 since the D–A reaction catalyzed by CD
in water has been reported by Breslow. 21,22 The D–A re-
action of 2,3-dimethyl-1,3-butadiene with methyl vinyl
ketone was carried out in the presence of a catalytic
amount of CDP-Yb C4-methide complex in pure water
(Table 1). Typical experimental procedure is as follows:
To a mixture of 2,3-dimethyl-1,3-butadiene (0.16 g, 2
mmol) and methyl vinyl ketone (0.15 g, 2.2 mmol) in wa-
ter (6 mL) was added 10 mol% of CDP-Yb(C4-methide)3
[0.2 mmol of Yb(C4-methide)3] at room temperature.
After stirring for 5 hours at that temperature, D–A adduct
was extracted by 1,2-dichloroethane. The 1,2-dichloro-
b Catalyst (20 mol%) was used.
c The reaction was carried out in dichloromethane (6 mL).
d Calculated by GC analysis using n-nonane as an internal standard.
The recycling was then conducted in the D–A reaction at
room temperature (25 °C) for 8 hours using the CDP-
Sc(C4-methide)3 complex (5 mol%) in water (Table 2,
Scheme 1). The D-A adduct was obtained in good isolated
yield (90%). The Sc C4-methide complex was completely
(>99.9%) recovered as determined by atomic emission
spectrometry analysis, and used in a recyclable manner
without any loss of catalytic activity of CDP-Sc methide
complex (yields: 1st run: 95%; 2nd run: 94%; 3rd run:
95%; 4th run: 94%).
Synlett 2002, No. 10, 1613–1616 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Metallo-Enzyme Model in Pure Water
1615
Table 2 Diels–Alder Reactions Catalyzed by CDP-Sc(C4-
OSiMe3
OMe
Me3SiO
Ph
O
methide)3a in Water
O
Cat. (2 mol%)
+
OMe
r.t., 1 h
CH2Cl2 (5 mL)
Ph
H
Cycleb
Yield (%)c
2 mmol
2.2 mmol
1
2
3
4
95
Scheme 3
94
95
Table 4 Mukaiyama-aldol Reactions Catalyzed by CDP-Yb(C4-
amide)3 in Dichloromethane
94 (90)d
Cycleb
Yield (%)c,d
a CDP-Sc(C4-methide)3: CDP complex of Sc(C4-methide)3.
b The catalyst was recycled by filtration.
c Calculated by GC analysis using n-nonane as an internal standard.
d Isolated yield.
1
2
3
4
5
99
99
99
98
99
The CDP-Yb methide complex was also completely recy-
cled for Mukaiyama-aldol reaction of benzaldehyde with
ketene silyl acetal (KSA) derived from methyl isobutyrate
in water (yields: 1st run: 74%; 2nd run: 72%; 3rd run:
73%) (Scheme 2, Table 3). The inclusion complex is thus
an efficient and immobilized Lewis acid catalyst despite
unstable KSA in water.
a CDP-Yb(C4-amide)3: CDP complex of Yb(C4-amide)3.
b The catalyst was recycled by filtration.
c Based on benzaldehyde.
d Calculated by GC analysis using n-nonane as an internal standard.
OSiMe3
OMe
HO
O
O
Cat. (5 mol%)
Continuous-flow system was finally examined in dichlo-
romethane using a column packed with CDP-Yb(C4-
amide)3 complex (column volume: 5 mL, flow rate: 30
mL/h, contact time: 10 min, the amount of catalyst:
Yb(C4-amide)3, 1 mmol, otherwise in the same concentra-
tion as shown in Scheme 3) for the Mukaiyama-aldol re-
action (Figure 4).23,24 The catalytic activity of the present
immobilized catalyst did not decrease even after 44 hours
(conversion of benzaldehyde: continuously 98–99%). The
turn over number of the Lewis acid catalyst [TON: aldol
product (mol)/Lewis acid catalyst (mol)] reached up to
517–523 after 44 hours.
+
Ph
OMe
r.t., 1 h
H2O (5 mL)
Ph
H
2 mmol
2.2 mmol
Scheme 2
Table 3 Mukaiyama-aldol Reactions Catalyzed by CDP-Yb(C4-
amide)3 in Water
Cycleb
Yield (%)c,d
1
2
3
74
72
73
Continuous-flow System
product
a CDP-Yb(C4-amide)3: CDP complex of Yb(C4-amide)3.
b The catalyst was recycled by filtration.
c Based on benzaldehyde.
d Calculated by GC analysis using n-nonane as an internal standard.
flow
column packed with catalyst
To prevent KSA from decomposing, we attempted
Mukaiyama-aldol reaction in organic solvent (Scheme 3,
Table 4). Surprisingly, the aldol product was obtained
quantitatively in dichloromethane (entry 1), in contrast to
D–A reaction product. Moreover, the CDP-Yb amide
complex was completely recycled in dichloromethane
(yields: 1st run: 99%; 2nd run: 99%; 3rd run: 99%; 4th
run: 98%; 5th run: 99%). After the reaction, no Yb com-
plex was detected in dichloromethane by atomic emission
spectrometry analysis. The inclusion complex is thus an
extremely efficient and immobilized Lewis acid catalyst
even in an organic solvent. It is conceivable that Yb amide
complex can be immobilized in the hydrophobic cavity of
CDP because of its low solubility in dichloromethane.
CDP-Yb(C4-amide)3
starting material
Figure 4
In summary, we have disclosed that Ln methide or amide
as CDP or CD inclusion complexes are extremely effi-
cient and immobilized Lewis acid catalysts due to the
powerful electron-withdrawing ability of the perfluoro-
alkyl ponytails effectively included in the hydrophobic
cavity of CDP or CD. The inclusion complexes give much
Synlett 2002, No. 10, 1613–1616 ISSN 0936-5214 © Thieme Stuttgart · New York

1616
J. Nishikido et al.
LETTER
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or simple lanthanide catalyst form. Not only batch system
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Synlett 2002, No. 10, 1613–1616 ISSN 0936-5214 © Thieme Stuttgart · New York