Angewandte
Communications
Chemie
Host–Guest Systems
Hot Paper
Iminium Catalysis inside a Self-Assembled Supramolecular Capsule:
Modulation of Enantiomeric Excess
Abstract: The noncovalent combination of a supramolecular
host with iminium organocatalysis is described. Due to cation–
p interactions the reactive iminium species is held inside the
host and reacts in this confined environment. The products
formed differ up to 92% ee from the control experiments
without added host. A model rationalizing the observed
difference is presented.
C
atalysis in self-assembled supramolecular structures has
Figure 1. Structure of resorcinarene 1 and capsule I.
attracted great interest.[1] Chemists are intrigued by the
possibility of performing reactions in small spaces (nm3 scale),
in which the reactivities and selectivities differ from those in
solution.[2] In artificial systems, product inhibition poses
a great challenge. Nevertheless, a variety of reactions includ-
ing hydroformylations,[3] hydrolysis,[4] hydrations,[5] hydro-
alkoxylations,[6] aza-Cope rearrangements,[7] Diels–Alder
reactions, Nazarov[8] and, Prins[9] cyclizations, isomeriza-
tions,[10] and terpene cyclizations[11] were catalyzed success-
fully. The majority of these examples involve monomolecular
reactions, or reactions catalyzed by an encapsulated metal
catalyst. We herein report the catalysis of a complex multi-
molecular reaction inside the supramolecular host I. Capsule
I, first reported by the Atwood group,[12] self-assembles from
six resorcinarene units
1 and eight water molecules
(Figure 1).[13] Its behavior in solution was studied exten-
sively.[14]
Figure 2. Proposed pathway of the iminium-catalyzed reaction inside
capsule I.
Recently, we reported that I acts as a Brønsted acid[4g] and
is able to catalyze cationic reactions.[6c,11] We now explored
the possibility of controlling iminium reactions[15] inside this
host. If the reaction is to occur inside the cavity of I, rapid
encapsulation of the reactive iminium species 4 (Figure 2) is
essential. Since capsule I displays a high affinity towards
ammonium ions due to cation–p interactions,[14b,c,e–h,m] we
speculated that a suitably sized iminium species would also be
an excellent guest to yield complex A. After uptake of
a nucleophile (complex B) and reaction (complex C),
hydrolysis would regenerate the catalysts amine 2 and capsule
I.
To the best of our knowledge, no iminium catalysis has
been reported inside supramolecular structures. The Rebek
group reported the acceleration of a Knoevenagel reaction by
an amine catalyst bound to a cavitand, where the reaction
took place outside of the open cavity.[16] The Bergman and
Raymond groups reported the stabilization of an iminium ion
inside a supramolecular container but no conversion.[17] The
fact that intramolecular cation–p interactions can play a sig-
nificant role in iminium catalysis was demonstrated by the
Gilmour group.[18] We herein show that intermolecular
cation–p stabilization and the resulting encapsulation inside
a supramolecular host can dramatically influence the reac-
tion.
[*] M. Sc. T. M. Bräuer, M. Sc. Q. Zhang
As a model reaction, the organocatalytic reduction of a,b-
unsaturated aldehyde 3a (Figure 3) was investigated.[19] The
Department of Chemistry, Technical University of Munich
Lichtenbergstrasse 4, 85747 Garching (Germany)
Prof. Dr. K. Tiefenbacher
Department of Chemistry, University of Basel
St. Johannsring 19, CH-4056 Basel (Switzerland)
E-mail: konrad.tiefenbacher@unibas.ch
Supporting information and the ORCID identification number(s) for
Figure 3. Iminium-catalyzed 1,4-reduction investigated.
7698
ꢀ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2016, 55, 7698 –7701