COMMUNICATION
A polymer-supported Cinchona-based bifunctional sulfonamide catalyst:
a highly enantioselective, recyclable heterogeneous organocatalystw
Sung Hun Youk,a Sang Ho Oh,a Ho Sik Rho,ab Je Eun Lee,a Ji Woong Leea
and Choong Eui Song*ac
Received (in Cambridge, UK) 1st December 2008, Accepted 9th February 2009
First published as an Advance Article on the web 6th March 2009
DOI: 10.1039/b821483b
The design, synthesis, and catalytic application of a highly
enantioselective and indefinitely stable polymer-supported
Cinchona-based bifunctional sulfonamide is reported.
large-scale applications. Thus, it would be highly desirable to
develop heterogeneous analogues of soluble organocatalysts
I or II that could simplify the work-up procedure required for
purification of the product, and allow for easy recovery of the
catalyst and its potential recycling. It has been reported that
thiourea catalysts tend to degrade under thermal conditions.5
In fact, we also observed during our ongoing study6 on
Currently, there is much interest in organocatalysts, as
they tend to be less toxic and more environmentally
friendly than traditional metal-based catalysts.1 They can be
used with a wider range of substrates than enzymes, as well as
in various organic solvents. Although much progress has
been made, developing chiral organocatalysts that are as
reactive and stereoselective as some of the best transition
metal-based catalysts or enzymes still remains a significant
challenge. In order to obtain reasonable reaction rates and
thiourea-based organocatalysts that
I can be rapidly
decomposed under radical polymerization conditions (e.g.,
110 1C in chlorobenzene; see the ESIw). Thus, we decided to
prepare
a polymeric analogue of the thermally robust
sulfonamide catalyst, II. Herein, we report the design,
synthesis and catalytic application of the polymer-supported
Cinchona-based sulfonamide, IV.
stereoselectivities with organocatalysts,
a large catalyst
Polymeric catalyst IV was designed with the following
criteria: (1) the monomeric moiety should mimic the structure
of II; (2) the polymerization site should be located far
enough from the catalytic sites (acidic sulfonamide proton
and quinuclidine base) to minimize the detrimental changes
in the conformational preference of the reactant–catalyst
intermediates; and (3) the morphology of the resin should be
such that no limitation on mass transfer arises, with all of its
active sites being freely accessible.
loading is often required. One way to address this difficulty
is to design bifunctional or multifunctional organocatalysts,
with functional groups that work cooperatively to stabilize
the transition state and accelerate the rate of the reaction.2
It has been shown that Cinchona-based bifunctional
thiourea I3 or sulfonamide II4 (Fig. 1) organocatalysts are
highly effective in facilitating a variety of useful asymmetric
reactions.
However, in spite of the versatility of this class of bifunc-
tional organocatalyst, these homogeneous catalysts still
provide relatively low turnover numbers and are costly to
prepare. Moreover, a tedious work-up procedure is often
required to purify the product. The possible contamination
of the product by the catalyst may also restrict their use in
Polymeric catalyst IV was simply prepared, as depicted in
Scheme 1, by the reaction of 9-amino-(9-deoxy)-epiquinine5
with 4-vinylbenzylsulfonyl chloride7 in the presence of
triethylamine, affording the monomeric moiety, III, followed
by suspension copolymerization of III with styrene and
Fig.
1 Cinchona-based bifunctional thiourea and sulfonamide
organocatalysts I and II.
a Department of Chemistry, Sungkyunkwan University,
300 Cheoncheon, Jangan, Suwon, Gyeonggi, 440-746, Korea.
E-mail: s1673@skku.edu; Fax: (+82) 31-290-7075
b R&D Center, AmorePacific Corporation, Yongin, 446-729, Korea
c Department of Energy Science, Sungkyunkwan University,
300 Cheoncheon, Jangan, Suwon, Gyeonggi, 440-746, Korea
w Electronic supplementary information (ESI) available: Synthetic
details and characterization data. See DOI: 10.1039/b821483b
Scheme 1 The synthesis of polymer-supported sulfonamide catalyst
IV: (a) 4-vinylbenzene sulfonyl chloride, NEt3, CH2Cl2, RT, 2 h, 79%
yield; (b) styrene, 1,4-divinylbenzene (2 mol%), AIBN (2 mol%),
chlorobenzene–H2O, 110 1C, 12 h.
ꢀc
This journal is The Royal Society of Chemistry 2009
2220 | Chem. Commun., 2009, 2220–2222