Supramolecular catalysis of 1,4-thiol addition by salophen-uranyl complexes [12]

Full text of DOI:10.1021/ja9819920

12688
J. Am. Chem. Soc. 1998, 120, 12688-12689
Supramolecular Catalysis of 1,4-Thiol Addition by
Salophen-Uranyl Complexes
Valeria van Axel Castelli, Antonella Dalla Cort, and
Luigi Mandolini*,‡
Dipartimento di Chimica and
Centro CNR Meccanismi di Reazione
UniVersita` La Sapienza
Box 34, Roma 62, 00185 Roma, Italy
David N. Reinhoudt*,§
Department of Supramolecular Chemistry and Technology
MESA Research Institute
UniVersity of Twente, P.O. Box 217, 7500
AE Enschede, The Netherlands
ReceiVed June 8, 1998
center provides an ester carbonyl with Lewis acid activation
toward nucleophilic addition.
An exciting challenge of supramolecular chemistry is the
construction of abiotic catalysts of reasonably low molecular
weight that share with the natural enzymes a number of
fundamental features related to efficient catalysis.1 Enzyme
properties such as preferential stabilization of the transition state
over reactant state (large rate enhancements), selective binding
and recognition of the substrate over reaction product (low product
inhibition), and high turnover values (low catalyst-to-substrate
ratios) are worth mimicking in synthetic catalytic systems.
Although some beautiful enzyme models have been developed,2
systems that mimic all of the above characteristics are rare.3
We report here that the robust complexes 1 and 24 are effective
catalysts of 1,4-thiol addition with high turnover efficiency and
low product inhibition. The model reaction of thiophenol with
2-cyclopenten-1-one in the presence of Et3N in chloroform (eq
1) was chosen for our studies. Despite the importance of the
The binding properties of 1 and 2 have been assessed by a
UV-vis titration technique.11 From the results listed in Table 1
the following conclusions can be drawn: (i) because of the strong
conjugation of the double bond with the carbonyl group, the R,â-
unsaturated ketone is a stronger Lewis base than the saturated
ketones, (ii) interaction of the ketone guests with the aromatic
cleft walls reinforces the binding, and (iii) the weaker binding of
3-(phenylthio)cyclopentanone to 2 compared to cyclopentanone
points to an adverse influence of the bulky 3-phenylthio sub-
stituent. The picture that emerges is clearly one in which the
ketone guests are coordinated to the metal center and, in the case
of 2, are situated between the cleft walls as shown in 4. This
picture is further confirmed by IR and 1H NMR data (see footnote
b to Table 1) and is in agreement with previous findings.4
The catalytic activities of 1 and 2 are illustrated by the time-
concentration profiles shown in Figure 1.12 Ten turnovers are seen
in these experiments, in which the catalyst amount was 10 mol
%. In other experiments13 a quantity as low as 1 mol % of catalyst
was enough for the catalyzed reaction to occur significantly faster
than the reference reaction.
Michael-type addition of thiols both in biochemical processes5
and in synthesis,6 to the best of our knowledge this is the first
quantitative study of metal-ion catalysis of this class of reactions.7
Our catalyst design was based on the well-known property of
salophen-uranyl complexes8 to bind donor groups (D), such as
anions9 and polar neutral molecules,10 in an equatorial coordination
site (3) as well as on our recent finding11 that a neighboring uranyl
The accepted mechanism14 of the tertiary base (B)-catalyzed
thiol addition to electron-poor olefins in apolar aprotic solvents
involves the rate-limiting addition of the thiolate portion of a 1:1
complex of thiol and base, followed by fast proton transfer (eq
2). Since there is insignificant formation of the thiol-base
‡ Fax: 39 (06) 490-421. E-mail: lmandolini@axrma.uniroma1.it.
§ Fax: Int. code + (53)4894645. E-mail: d.n.reinhoudt@ct.utwente.nl.
(1) Lehn, J.-M. Supramolecular Chemistry; VCH: Weinheim, 1995; pp
55-67.
(2) (a) Feiters, M. C. In ComprehensiVe Supramolecular Chemistry;
Atwood, J. L., Davies, J. E. D., MacNicol, D. D., Vo¨gtle, F. Eds.; Pergamon:
Oxford, 1996; Vol. 10, pp 267-360. (b) Breslow, R. Acc. Chem. Res. 1995,
28, 146-153. (c) Kirby, A. J. Angew. Chem., Int. Ed. Engl. 1996, 35, 707-
724. (d) Murakami, Y.; Kikuchi, J.; Hisaeda, Y.; Hayashida, O. Chem. ReV.
1996, 96, 721-758.
(3) See, for example: (a) Hosseini, M. W.; Lehn, J.-M.; Jones, K. C.; Plute,
K. E.; Bowman Mertes, K.; Mertes, M. P. J. Am. Chem. Soc. 1989, 111, 6330-
6335. (b) Fenniri, H.; Dellaire, C.; Funeriu, D. P.; Lehn, J.-M. J. Chem. Soc.,
Perkin Trans. 2 1997, 2073-2081. (c) Zhang, B.; Breslow, R. J. Am. Chem.
Soc. 1997, 119, 1676-1681.
(4) van Doorn, A. R.; Bos, M.; Harkema, S.; van Eerden, J.; Verboom,
W.; Reinhoudt, D. N. J. Org. Chem. 1991, 56, 2371-2380.
(5) (a) Fluharty, A. L. In The Chemistry of the Thiol Group, part 2; Patai,
S., Ed.; Wiley: New York, 1974; pp 589-668. (b) Thomas, B. E., IV;
Kollman, P. A. J. Org. Chem. 1995, 60, 8375-8381 and references therein.
(6) (a) Wynberg, H. In Topics in Stereochemistry; Eliel, E. L., Wilen, S.
H., Allinger, N. L., Eds.; Wiley: New York, 1986; Vol. 16, pp 87-129. (b)
Emori, E.; Arai, T.; Sasai, H.; Shibasaki, M. J. Am. Chem. Soc. 1998, 120,
4043-4044 and references therein.
(7) For a quantitative study of the acceleration of the 1,4-thiol addition to
a maleimide due to multiple hydrogen bonding to the carbonyl group, see:
Fan, E.; Vicent, C.; Hamilton, A. D. New J. Chem. 1997, 21, 81-85.
adduct,14 the mechanism of eq 2 leads to a simple third-order
(8) (a) Bandoli, G.; Clemente, D. A.; Croatto, U.; Vidali, M.; Vigato, P.
A. J. Chem. Soc., Chem. Commun. 1971, 1330-1331. (b) van Staveren, C.
J.; van Eerden, J.; van Veggel, F. C. J. M.; Harkema, S.; Reinhoudt, D. N. J.
Am. Chem. Soc. 1988, 110, 4994-5008.
(9) (a) Rudkevich, D. M.; Huck, W. T. S.; van Veggel, F. C. J. M.;
Reinhoudt, D. N. In Transition Metals in Supramolecular Chemistry; Fabbrizzi,
L., Poggi, A., Eds.; NATO ASI Series, No. 448; Kluwer: Dordrecht, 1994;
pp 329-349. (b) Rudkevich, D. M.; Verboom, W.; Brozka, Z.; Palys, M. J.;
Stauthamer, W. P. R. V.; van Hummel, G. J.; Franken, S. M.; Harkema, S.;
Engbersen, J. F. J.; Reinhoudt, D. N. J. Am. Chem. Soc. 1994, 116, 4341-
4351.
(10) (a) van Doorn, A. R.; Verboom, W.; Reinhoudt D. N. In AdVances of
Supramolecular Chemistry; Gokel, G. W., Ed.; JAI Press: Greenwich, 1993;
Vol. 3, pp 159-206. (b) van Straaten-Nijenhuis, W. F.; van Doorn, A. R.;
Reichwein, A. M.; De Jong, F.; Reinhoudt, D. N. J. Org. Chem. 1993, 58,
2265-2271.
(11) van Axel Castelli, V.; Cacciapaglia, R.; Chiosis, G.; van Veggel, F.
C. J. M.; Mandolini, L.; Reinhoudt, D. N. Inorg. Chim. Acta 1996, 246, 181-
193.
10.1021/ja9819920 CCC: $15.00 © 1998 American Chemical Society
Published on Web 11/20/1998

Communications to the Editor
J. Am. Chem. Soc., Vol. 120, No. 48, 1998 12689
Table 1. Equilibrium Constants K (M-1)a for 1:1 Association
between Ketones and Salophen-Uranyl Complexes 1 and 2 in
Chloroform at 25.0 °C
the metal-catalyzed reactions, for which we propose a mechanism
(eq 4) involving rate-limiting thiol addition on an enone-catalyst
KE
kcat
z E‚cat [T][B]8 P‚cat y
\K z P + cat
(4)
1
2
E + cat y\
2-cyclopenten-1-one
3-(phenylthio)cyclopentanone
cyclopentanone
14 ( 2
<2
460 ( 20b
68 ( 12
136 ( 18
P
<2
complex (E‚cat) and inhibition due to formation of a product-
catalyst complex (P‚cat). Equation 4 translates into the rate
expression of eq 5,
a Data from UV-vis titration of 0.1 mM metal complexes with
ketones. b Upon addition of 2 to a CHCl3 solution of 2-cyclopenten-
1-one (IR ) 1708 cm-1, CdO) a new band appears at 1657 cm-1
,
whose intensity increases upon increasing 2. 1H NMR (300 MHz)
titration of 1 mM 2-cyclopenten-1-one with 2 in CDCl3 at 25 °C showed
upfield shifts of the methylene H(5) protons that were consistent with
fast 1:1 complexation, K ) 520 ( 80 M-1, ∆δ∞ ) -0.38 ppm.
Analogous behavior was exhibited by the methylene H(4) protons
(∆δ∞ ) -0.30) and the H(2) vinylic proton (∆δ∞ ) -0.17).
kcatKE[B][T][E][cat]tot
V )
(5)
1 + KE[E] + KP[P]
from which eq 6 is obtained by integration. Since KE and KP are
Table 2. Addition of Thiophenol (0.050 M) to
2-cyclopenten-1-one (0.010 M) in the Presence of Et3N (1.00 mM)
in CDCl3 at 25.0 °C.a Catalytic Parameters
1 + [T]oKP [T]o
1 + [E]oKP [E]o
KE -
ln
+
ln
)
(
)
(
)
[T]o - [E]o
[T]t
[T]o - [E]o
[E]t
c
kcat
kcat/ko
kcatKE
KT*
tfd
kcatKE[B][cat]tott (6)
catalystb
(s-1 M-2
)
(s-1 M-3
)
(M-1
)
(s-1
)
1
2
14.3 × 102 9.5 × 102 2.0 × 104 1.3 × 104 1.43
6.3 × 102 4.2 × 102 2.9 × 105 1.9 × 105 0.63
independently known (Table 1), eq 6 contains kcat as the only
unknown quantity. Numerical values of kcat were obtained from
the least-squares slopes of plots of the left side of eq 6 against
time. The close adherence of data points to the calculated profiles
(Figure 1) indicates the validity of the proposed mechanism.
a ko ) 1.51 s-1 M-2 b The catalyst concentration is 1.00 mM.
.
c Calculated as (kcat/ko)KE. d Turnover frequency at 1 M thiophenol and
1 mM Et3N.
The kinetic parameters for the metal-catalyzed reactions are
collected in Table 2. The kcat/ko values show that the complexes
with 1 and 2 are 950 and 420 times more reactive, respectively,
than the uncomplexed 2-cyclopenten-1-one. It seems likely that
this difference is due to the same factor that makes 3-(phenylthio)-
cyclopentanone a weaker ligand of 2 than cyclopentanone.
Whereas kcat is higher for 1 than for 2, the reverse order is found
in the kcatKE product. This finding has important consequences
on the relative efficiency of the two catalysts. Under subsaturating
conditions (KE[E] , 1) the catalytic process is governed by
kcatKE and 2 is more efficient than 1. But under conditions
approaching saturation (KE[E] . 1) the catalytic process is
governed by kcat and the reactivity order is 1 > 2. Indeed we
found that experiments run at higher concentration showed the
expected inversion of catalytic efficiency.13
The quantity KT*, operationally defined as (kcat/ko)KE, has the
meaning of the binding constant of the catalyst to the transition
state.15 The calculated values in Table 2, compared with the
corresponding values in Table 1, show to what an extent the
transition state, on account of its enolate character, binds to the
catalysts more tightly than both the reactant and product. The
last column in Table 2 shows that in a minute each catalyst
molecule delivers several tens of activated enone molecules to
the tiny amount of thiol-base complex formed at 1 M thiol and
1 mM base.
Figure 1. Time-concentration profiles for reaction 1. Reaction conditions
are defined in Table 2. (O) Et3N alone (t1/2 162 min); (9) Et3N + 1 (t1/2
13.4 min); (2) Et3N + 2 (t1/2 3.8 min). The points are experimental, and
the curves are calculated from the second-order rate equation for reactions
carried out with Et3N alone and from eq 6 when in the presence of metal
catalyst.
equation (eq 3), in which E denotes the enone substrate and T
V ) ko[B][E][T]
(3)
the thiol. The reaction was actually reported to obey third-order
kinetics,14 first-order in each of the reactants and in the base.
Consistent with the above findings, the reference reaction was
found to display a clean second-order time dependence (Figure
1). The pseudo-second-order rate constant was translated into the
third-order rate constant ko ) 1.51 s-1 M-2. Not surprisingly, the
second-order rate equation gave a very poor fit to data points for
In conclusion, our catalysts mimic the behavior of a metal-
loenzyme, in that they bind 2-cyclopenten-1-one and promote
reaction of the bound substrate. Release of the addition product,
followed by preferential binding to another enone molecule,
ensures the onset of a catalytic cycle with high turnover efficiency.
The salophen-uranyl unit will prove useful in the design and
construction of more elaborate metallocatalysts with ligase
activity. Most promising in this perspective is metallocleft 2, for
which an interesting property such as shape selectivity is easily
foreseen.
(12) The kinetics were monitored by 1H NMR spectroscopy. The decrease
as a function of time of the intensity of the signal of the R-vinylic proton of
the enone at δ 6.2 was accompanied by an increase in intensity of the signal
of the H(3) proton of 3-(phenylthio)cyclopentanone at δ 3.9. No extra peaks
due to side products were observed.
(13) Kinetic experiments run at the following initial concentrations [E]o )
0.1 M, [T]o ) 0.2 M, [B] ) 1 mM, [cat] ) 1 mM, showed a half-life of 6.6
min for 1 and 10.4 min for 2. The half-life for the reference reaction was 38
min. The enone concentration at which the two catalysts show the same
efficiency in terms of initial rate is calculated from eq 5 to be 0.042 M.
(14) (a) Dmuchovsky, B.; Vineyard, B. D.; Zienty, F. B. J. Am. Chem.
Soc. 1964, 86, 2874-2877. (b) Hiemstra, H.; Wynberg, H. J. Am. Chem. Soc.
1981, 103, 417-430.
Acknowledgment. Short-term missions of V.v.A.C. at the University
of Twente have been supported by CNR and COST Chemistry D7.
JA9819920
(15) Kurz, J. L. J. Am. Chem. Soc. 1963, 85, 987-991.