Supramolecular Activation of Hydrogen Peroxide in the Selective Sulfoxidation of Thioethers by a Self-Assembled Hexameric Capsule

Article abstract of DOI:10.1002/adsc.201600430

An efficient metal-free organocatalytic activation of hydrogen peroxide (H₂O₂) towards thioethers leading to the corresponding sulfoxides in high yields at room temperature within hours was promoted by the hexameric capsule formed by

Full text of DOI:10.1002/adsc.201600430

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DOI: 10.1002/adsc.201600430
Supramolecular Activation of Hydrogen Peroxide in the Selective
Sulfoxidation of Thioethers by a Self-Assembled Hexameric
Capsule
Giorgio La Sorella,a Laura Sperni,a Giorgio Strukul,a and Alessandro Scarsoa,*
a
Dipartimento di Scienze Molecolari e Nanosistemi, Universitꢀ Ca’ Foscari di Venezia, via Torino 155, 30172 Mestre (VE),
Italy
Fax : (+39)-041-234-0517; phone: (+39)-041-234-8569; e-mail: alesca@unive.it
Received: April 22, 2016; Revised: July 29, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600430.
Abstract: An efficient metal-free organocatalytic ac- tion inside the cavity. Inactivation of the supramolec-
tivation of hydrogen peroxide (H2O2) towards thio- ular organocatalyst was observed by using competi-
ethers leading to the corresponding sulfoxides in tive ammonium guests, mimicking the inactivation of
high yields at room temperature within hours was enzymes by competitive inhibitors.
promoted by the hexameric capsule formed by the
self-assembly of resorcin[4]arene units. The capsule Keywords: hydrogen peroxide; metal-free conditons;
plays a dual role of activating the oxidant through organocatalysis; sulfoxidation; supramolecular catal-
hydrogen bonding and favouring the oxidation reac- ysis
Introduction
of self-assembled capsules operating in organic media
and displaying catalytic activity is somehow a more
Homogeneous catalysis is widening the way molecules challenging task since substrate binding and activation
are made taking inspiration from natural enzymes by is strictly related to the specific interactions of the
exploring the use of organocatalysts,[1] the develop- latter with the internal surface of the supramolecular
ment of artificial enzyme mimetic catalysts[2] and catalyst and interferences with the self-assembling
supramolecular catalysis.[3] All these approaches are process may occur. After the seminal works of Rebek
characterized by the implementation of weak inter- concerning the Diels–Alder cycloaddition reaction
molecular forces in substrate recognition and activa- promoted by the hydrogen bonded softball dimeric
tion. These phenomena are favoured by a large con- capsule,[8] other examples of catalytically active capsu-
tact surface between catalyst and substrates where les have indeed been rare.
weak intermolecular forces can deploy.[4] A wide
The hexameric capsule obtained by the aggregation
range of catalytically active hosts have been devel- of six resorcin[4]arene 1 molecules with eight water
oped in the recent years ranging from covalent uni- molecules through a seam of sixty hydrogen bonds
ACHTUNGTRENNUNG
molecular tubular,[5] to vase-shaped[6] to capsular provides an assembly characterized by a large cavity
structures and self-assemblies.[3] The self-assembly of about 1375 ꢁ3 (Scheme 1)[9,10] that has been recent-
strategy has the intrinsic advantage of reducing the ly exploited for catalytic purposes.
number of synthetic steps yielding a simple in situ for-
mation of the supramolecular structure.
The assembly efficiently complements cationic
guests like organic ammonium and phosphonium
As far as self-assembled capsules are concerned, ions[11] or metal species[12] stabilized through cation-
the size, shape and intrinsic features of the cavity play p[13] interactions. Alternatively the capsule, thanks to
a crucial role in catalytic activity. Although the its extended network of hydrogen bonds, proved to
number of water-soluble self-assembled capsules is bind species like carboxylic acids, amino acids,[14] alco-
not so large, impressive examples exploiting the pref- hols,[15] often used in large molar excess. The hexamer
erential binding of hydrophobic substrates with size has been employed (i) as a nano-reactor where
and shape matching the dimensions of the cavity lead- trapped transition metal catalysts showed modulation
ing to unexpected selectivities and activities have al- of catalytic activity[16] as well as steering of products[17]
ready been reported.[7] Conversely, the development and substrate selectivity[18] or (ii) directly as a cata-
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Scheme 1. Sulfoxidation of thioethers 2 with 30% H2O2
leading to the corresponding sulfoxides 3 mediated by the
capsule 16·8H2O and inhibited by competitive guest tetra-
Figure 1. 1H NMR spectra in water-saturated chloroform-d:
A) dibutyl sulfide 2a (60 mM); B) 2a (60 mM) and 16·8H2O
(6 mM); C) 2a (60 mM) with H2O2 (1.2 equiv.) and 16·8H2O
(6 mM) after 25 minutes; D) 2a (60 mm) with H2O2
(1.2 equiv.) and 16·8H2O (6 mM) after 65 minutes; E) 2a
(60 mM) with H2O2 (1.2 equiv.) after 90 minutes; F) 2a
(60 mM) with H2O2 (1.2 equiv.), 16·8H2O (6 mM) and 4
(60 mM) after 90 minutes; G) dibutyl sulfoxide 3a (60 mM)
and 16·8H2O (6 mM); H) dibutyl sulfoxide 3a (60 mM); fl
dibutyl sulfide, › free dibutyl sulfoxide, m encapsulated di-
butyl sulfoxide.
ACHTUNGTRENNUNGethylammonium tetrafluoroborate 4.
lyst.[19] Examples of the latter case are the Diels
–Alder reaction in fluorinated solvents using a fluori-
nated analogue of resorcin[4]arene 1,[20] the diethyl
acetal hydrolysis within the hexameric 16·8H2O,[21] the
hydration of isonitriles to the corresponding forma-
mides,[22] the synthesis of tetrazoles from isonitriles,[23]
the 1,3-dipolar cycloaddition between diazoacetate
esters and electron-poor alkenes leading to 4,5-dihy-
dro-1H-pyrazoles,[24] the intramolecular hydroalkoxy-
lation of unactivated hydroxy olefins[25] and very re-
cently the terpene cyclization.[26] In all cases, the en-
capsulation of reagents turned out to be pivotal to
promote the reaction. It is worthy of note that, to the
best of our knowledge, no examples of activation in
oxidation reactions has ever been reported with hy-
drogen bonded self-assembled capsules.
Herein we present a very efficient metal-free supra-
molecular H2O2 activation by the hexameric capsule
16·8H2O for the oxidation of thioethers efficiently
leading to the corresponding sulfoxides under mild
conditions within hours (Scheme 1). The reaction
occurs within the cavity of the supramolecular capsule
showing inhibition of the catalytic activity in the pres-
ence of competitive tetraethylammonium guests 4, all
features reminiscent of enzymatic catalysis.
Table 1. Catalytic tests for the sulfoxidation of 2a with 30%
H2O2.[a]
Entry
16·8H2O
4
Time [min]
3a [%][b]
1
2
3[c]
4[d]
5
À
+
À
À
+
À
À
À
À
À
+
+
90
65
90
90
65
90
10
>98
21
28
46
6
15
[a]
[1]=36 mM, [2a]=60 mM, 30% H2O2 1.2 equiv.; [tetra-
ethylammonium tetrafluoroborate 4]=60 mM, water-sa-
AHCTUNGTRENNUNG
turated chloroform-d 1.5 mL, T=room temperature. +:
presence; À: absence.
[b]
[c]
[d]
1
Determined by H NMR.
[acetic acid]=6 mM (1 equiv. with respect to 16·8H2O).
[resorcinol]=144 mM (24 equiv. with respect to
16·8H2O).
Results and Discussion
entry 1), while rapid formation of dibutyl sulfoxide 3a
(Table 1, entry 2) was observed in the presence of
The oxidation reaction of dibutyl sulfide 2a as sub-stoichiometric amounts of capsule (10 mol%)
a model substrate was investigated in the presence of with quantitative formation of the sulfoxide 3a ob-
1.2 equivalents of a 35% aqueous solution of H2O2 tained within 65 minutes (Figure 1D).
observing only 10% yield after 90 minutes for the
It was initially observed that no resonances for the
spontaneous reaction (Figure 1E and Table 1, encapsulated species were found in the 1H NMR spec-
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trum upon addition of ten equivalents of dibutyl sul- effect by ammonium, seem to suggest that the reac-
fide 2a to a solution of the hexamer 16·8H2O in tion, rather than by substrate activation, is favoured
chloroform-d (Figure 1A). In the presence of capsule by the capsule through a dual synergic effect: (i) the
and H2O2, apart from the resonances at 2.7 ppm cor- displacement of the bridging water molecules in the
responding to free 3a, the spectrum showed the ap- H-bond seam by H2O2 that becomes more electrophil-
pearance of new up-field shifted resonances in the ic (oxidant activation) and (ii) the stabilization of the
range À0.75 to À1.5 ppm (Figure 1C and D). To con- polar transition state typical of the electrophilic sulf-
firm the nature of the encapsulated species, experi-
ACHTUNGTRENoNUGN xidation inside the self-assembled capsule exerted by
ments were carried out adding increasing amounts of its electron-rich internal surface, even if conclusive
sulfoxide 3a to a solution of 16·8H2O observing the experimental evidence in this respect is missing.
formation of exactly the same up-field shifted reso-
The chemoselectivity of the oxidation reaction was
nances (Figure 1G) recorded during the oxidation re- demonstrated by repeating the reaction under the
action, thus confirming that sulfoxide 3a is a suitable same experimental conditions as in Table 1, entry 2
guest for the capsule.
using the sulfoxide 3a as substrate in place of the thio-
It is widely accepted that the electrophilic oxidation ether 2a. No conversion to sulfone was observed even
reaction of thioethers with H2O2 typically occurs via after 24 hours at room temperature, in agreement
activation of the oxidant by means of metal cata- with the electrophilic nature of the oxygen transfer
lysts[27] as well as protonation or hydrogen bond acti- step typical of the sulfoxidation reaction.
vation with organic molecules like alcohols, phenols,
The scope of the reaction was investigated observ-
ureas, sulfoxides,[28] surfactants[29] and many others[30] ing excellent yields in sulfoxides 3 within a few hours
also in the enantioselective form.[31] Recently Tiefen- with bis-aliphatic thioethers such as the analogue of
bacher and co-workers demonstrated that the hexa- the warfare agent mustard gas 2b and tert-butyl
mer behaves as a weak acid assembly with a pKa of methyl sulfide 2c (Table 2, entries 1 and 2). Alkyl aryl
about 5.5,[21] while resorcinol alone has a pKa of 9.15. sulfides are intrinsically less reactive giving from good
In order to ascertain whether the activation of H2O2 to excellent sulfoxide yields as a function of the elec-
was due to the Brønsted acidity of the hexamer, we tronic properties of the substrates (Table 2, entries 3–
performed the oxidation reaction with one equivalent 15). Substrates bearing electron-donating groups like
of acetic acid (pKa 4.7) with respect to the capsule ob- methyl, methoxy, phenoxy and acetamido showed
serving only 21% of sulfoxide 2a after 90 min good reactivity in the presence of the supramolecular
(Table 1, entry 3). Moreover, since commercially catalyst 16·8H2O, while substrates bearing electron-
available 35% H2O2 solution has an apparent pH <2, withdrawing groups like halogen atoms, acetyl, cyano
activation due to protonation by the capsule seems and pyridyl moieties required longer reaction times to
very unlikely. Activation of H2O2 by simple hydrogen ensure good product formation. Even larger sub-
bonding to the capsule could not justify the reactivity strates like 2o and 2p reacted readily forming the cor-
observed as confirmed by testing the reaction with responding sulfoxides under the usual conditions,
24 equivalents of disassembled resorcinol that led to showing the well-known importance of the electron
only 28% yield of 3a after 90 min (Table 1, entry 4). density on the S atom for this reaction.
To investigate the effect of the capsule cavity in pro-
Diaryl sulfides turned out to be poorly reactive as
moting this oxidation, we repeated the reaction observed in the oxidation of the substrate 2q where
adding ten equivalents of tetraethylammonium tetra- the presence of the dimethylamino moiety increases
fluoroborate 4 as a competitive cationic guest to a so- the electron density of the S atom favouring its sul-
lution of 2a, H2O2 and capsule.[32] The ammonium foxidation (Table 2, entry 16). Finally, p-tolyl disulfide
guests was rapidly encapsulated as demonstrated by 2r was used as substrate observing the chemoselective
the appearance of a broad resonance at À0.05 ppm oxidation to the mono-sulfoxide in 51% yield after
(Figure 1F) and its effect was to reduce the catalytic 18.5 h using a large amount of oxidant.
activity (Table 1, entry 5), even if to a lower extent
Comparable inhibition effects due to competitive
with respect to other catalytic reactions where the in- occupation of cavity of the hexamer by 4 were ob-
hibition was complete. Compound 4 turned out to be served in all the substrates investigated in Table 2. In
intrinsically unable to promote the oxidation reaction particular, it is worth noting that larger differences in
(Table 1, entry 6) even though recent examples of am- sulfoxide yield between free and occupied capsule
monium salt catalysis for sulfoxidation have been re- were observed with less electron-rich substrates due
ported in the case of some weakly acidic cations to their intrinsic lower reactivity. In fact, substrates
having H-bond donor and acceptors moieties in the like 2c and 2h showed no or little difference between
ion pairs.[33]
free and occupied cavity, while electron-poor sub-
The lack of macroscopic encapsulation of the sul- strates like the series 2i–2n showed a marked de-
fide, the absence of evidence of acidic activation of crease of the catalytic activity in the presence of the
hydrogen peroxide, as well as the moderate inhibition ammonium competitive guest 4. Moreover, the same
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Table 2. Sulfoxidation of thioethers 2b–2r with H2O2 mediated by 16·8H2O and inhibited by the presence of the competitive
cationic guest 4.
[a]
Experimental conditions: [2b–2r]=60 mM, 30% H2O2 1.2 equiv.; [1]=36 mM, water-saturated chloroform-d 1.5 mL, T=
room temperature.
Determined by H NMR.
[4]=60 mM.
Sulfone oxidation product.
Determined by GC.
H2O2 (5.0 equiv.).
[b]
[c]
[d]
[e]
[f]
1
trend was observed moving from small substrates to ments at constant capsule concentration with increas-
larger ones like 2o and 2p, indicating that the residual ing amounts of substrate p-chlorothioanisole 2i
space left in the cavity by the competitive ammonium chosen because of its moderate reactivity under the
guest allows oxidation of smaller substrates that can selected experimental conditions. The results ob-
be more likely co-encapsulated along with the ammo- served showed that the capsule maintained its catalyt-
nium species still fitting the best packing coefficient ic activity in the presence 10, 25 and 50 equivalents of
of 0.45–0.55 typical of supramolecular encapsulation 2i observing almost superimposable plots of the yield
phenomena.[34]
of 3i with time (Figure 2A). Only when the amount of
With the aim of investigating the possible effect of substrate was drastically increased to 200 equivalents
the preferential encapsulation of the sulfoxides in the with respect to the capsule, did the reaction profile
oxidation reaction we carried out a series of experi- show a reduction in yield over time that after 400 min
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the electrophilic character of the oxidant. At the
same time, the large capsule stabilizes the polar tran-
sition state derived by the combination of the oxidant
and the substrate that can be suitably hosted in the
presence of competitors like ammonium cations or
the sulfoxide product. Both effects proved fundamen-
tal to obtain an efficient, chemoselective metal-free
catalytic system for sulfoxide production with a cata-
lytic activity among the best known for organocatalyt-
ic systems using H2O2.[36] The results reported here
compare well in terms of yields and versatility of the
reaction with some of the best metal catalysts in this
field and, albeit with some intrinsic limitations in
terms of practicality, represent an important proof of
concept demonstration of the potentialities of supra-
molecular organocatalysis.
Experimental Section
General Reagents and Materials
1H NMR spectra were recorded at 298 K, unless otherwise
stated, on a Bruker AVANCE 300 spectrometer operating
at 300.15 MHz. d values in ppm are relative to SiMe4. GC
analysis were performed on HP Series II 5890 equipped
with a HP5 column (30 m, I. D. 0.25 m, film 0.25 mm) using
He as gas carrier and FID. GC-MS analyses were performed
on a GC Trace GC 2000 equipped with an HP5-MS column
(30 m, I.D. 0.25 mm, film 0.25 mm) using He gas carrier and
coupled with a quadrupole MS Thermo Finnigan Trace MS
with the Full Scan method.
Figure 2. A) Conversion of different equivalents of 2i to the
corresponding sulfoxide 3i over time. [1]=36 mM, H2O2/2i=
1.2, water-saturated chloroform-d 1.5 mL, room tempera-
ture. B) Initial rate for the oxidation reaction of 2i to the
corresponding sulfoxide 3i as a function of the initial con-
centration of 2i. [1]=36 mM, H2O2 =1.2 equivalents, water-
saturated chloroform-d 1.5 mL, room temperature.
Solvents and reactants were used as received; otherwise
they were purified as reported in the literature.[37] TLC anal-
ꢃ
ysis were performed on TLC Polygram Sil G/UV254 of
0.25 mm thickness and flash chromatography separations
were performed on silica gel Merk 60, 230–400 mesh.[38]
is only slightly above 50%. Whether or not this is in-
dicative of inhibition by product is doubtful in view of
an analysis of the initial rates that can be extracted
and plotted against the substrate concentration be-
cause the concentration of H2O2 in chloroform can be
assumed as constant and corresponding to saturation,
the system being two-phase. A first-order dependence
is evident (Figure 2B) as is generally the case for this
oxidation reaction[35] while at high substrate concen-
tration a sharp departure from linearity appears. This
kinetic effect is typical of enzymes and is a good indi-
cation of an association process, with the oxygen
transfer step occurring inside the capsule.
Substrates and Capsule
Dibutyl sulfide, 2-chloroethyl ethyl sulfide, tert-butyl methyl
sulfide, thioanisole, 4-methoxythioanisole, 4-chlorothioani-
sole, 4-bromothioanisole, 4-acetylthioanisole, 4-(methylthio)-
benzonitrile, 4-nitrothioanisole, benzyl phenyl sulfide, 2-
(methylthio)naphthalene, 4-mercaptopyridine, tetraethylam-
monium tetrafluoroborate, hydrogen peroxide, resorcinol,
acetic acid are all commercially available products and were
used as received without any further purification.
Resorcin[4]arene[39] was prepared as reported in the litera-
ture. All the sulfoxidation products were identified by GC-
1
MS and H NMR analysis.
The substrates 1-(methylsulfanyl)-2-phenoxybenzene,
N-[4-(methylsulfanyl)phenyl]acetamide,
[40]
[41]
4-[(4-bromophe-
bis(4-methylphenyl)
Conclusions
[42]
nyl)sulfanyl]-N,N-dimethylaniline,
disulfide[43] were synthesized following reported procedures.
In conclusion, have we reported an example of supra-
molecular activation of H2O2 by the hexameric capsu-
le 16·8H2O leading to the selective oxidation of thio-
ethers 2 to the corresponding sulfoxides 3 where hy-
drogen peroxide likely displaces water molecules in
Catalytic Studies
Water-saturated solvent was prepared by shaking chloro-
form-d with bidistilled water at room temperature in a sepa-
the network of H-bonds in 16·8H2O and this enhances ration funnel. Resorcin[4]arene 1 (6 equivalents, 36 mM)
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was placed in a screw-capped vial equipped with silicone
septum and dissolved in the water-saturated chloroform-d
(1.5 mL) by stirring for a few minutes. To this solution, the
chosen thioether (10 equivalents, 60 mM), and 30% H2O2
(1.2 equivalents) were added. The reaction was left under
vigorous stirring at room temperature and the reaction prog-
ress was monitored by periodically sampling directly 50 mL
of solution and diluting it into 450 mL of chloroform-d and
[11] a) A. Shivanyuk, J. Rebek Jr, Proc. Natl. Acad. Sci.
USA 2001, 98, 7662–7665; b) I. E. Philip, A. E. Kaifer,
J. Am. Chem. Soc. 2002, 124, 12678–12679.
[12] G. Bianchini, A. Scarso, G. La Sorella, G. Strukul,
Chem. Commun. 2012, 48, 12082–12084.
[13] D. A. Dougherty, Acc. Chem. Res. 2013, 46, 885–893.
[14] a) Y. Aoyama, Y. Tanaka, Y. H. Toi, H. Ogoshi, J. Am.
Chem. Soc. 1988, 110, 634–635; b) Y. Aoyama, Y.
Nonaka, Y. Tanaka, H. Toi, H. Ogoshi, J. Chem. Soc.
Perkin Trans. 2 1989, 1025–1029.
[15] a) S. Slovak, Y. Cohen, Chem. Eur. J. 2012, 18, 8515–
8520; b) S. Slovak, L. Avram, Y. Cohen, Angew. Chem.
2010, 122, 438–441; Angew. Chem. Int. Ed. 2010, 49,
428–431; c) B. Schnatwinkel, I. Stoll, A. Mix, M. V. Re-
kharsky, V. V. Borovkov, Y. Inoue, J. Mattay, Chem.
Commun. 2008, 3873–3875.
1
subsequent immediate H-NMR ad GC analysis.
Conversion, product assignment and distribution were de-
1
termined by direct GC, GC-MS and H NMR analysis of the
reaction mixture as the average of three experiments.
Acknowledgements
[16] G. Bianchini, A. Scarso, G. La Sorella, G. Strukul,
The authors acknowledge MIUR, Universitꢀ Ca’ Foscari di
Venezia and Consorzio Interuniversitario Nazionale per la
Scienza e Tecnologia dei Materiali for support.
Chem. Commun. 2012, 48, 12082–12084.
[17] A. Cavarzan, A. Scarso, P. Sgarbossa, G. Strukul,
J. N. H. Reek, J. Am. Chem. Soc. 2011, 133, 2848–2851.
[18] a) A. Cavarzan, J. N. H. Reek, F. Trentin, A. Scarso, G.
Strukul, Cat. Sci. Technol. 2013, 3, 2898–2901; b) S.
Giust, G. La Sorella, L. Sperni, G. Strukul, A. Scarso
Chem. Commun. 2015, 51, 1658–1661.
References
[19] L. Catti, Q. Zhang, K. Tiefenbacher, Synthesis 2016, 48,
313–328.
[20] S. Shimizu, A. Usui, M. Sugai, Y. Suematsu, S. Shiraka-
wa, H. Ichikawa, Eur. J. Org. Chem. 2013, 4734–4737.
[21] Q. Zhang, K. Tiefenbacher, J. Am. Chem. Soc. 2013,
135, 16213–16219.
[22] G. Bianchini, G. La Sorella, N. Canever, A. Scarso, G.
Strukul, Chem. Commun. 2013, 49, 5322–5324.
[23] S. Giust, G. La Sorella, L. Sperni, F. Fabris, G. Strukul,
A. Scarso, Asian J. Org. Chem. 2015, 4, 217–220.
[24] G. La Sorella, L. Sperni, G. Strukul, A. Scarso, Chem-
CatChem 2015, 7, 291–296.
[25] L. Catti, K. Tiefenbacher, Chem. Commun. 2015, 51,
892–894.
[26] Q. Zhang, K. Tiefenbacher, Nat. Chem. 2015, 7, 197–
202.
[27] a) M. Mba, L. J. Prins, C. Zonta, M. Cametti, A. Valko-
nen, K. Rissanen, G. Licini, Dalton Trans. 2010, 39,
7384–7392; b) M. Mba, L. J. Prins, G. Licini, Org. Lett.
2007, 9, 21–24; c) M. Mba, M. Pontini, S. Lovat, C.
Zonta, G. Bernardinelli, E. P. Kꢅndig, G. Licini, Inorg.
Chem. 2008, 47, 8616–8618; d) F. Romano, A. Linden,
M. Mba, C. Zonta, G. Licini, Adv. Synth. Catal. 2010,
352, 2937–2942.
[1] a) S. Bertelsen, K. A. Jørgensen, Chem. Soc. Rev. 2009,
38, 2178–2189; b) A. Dondoni, A. Massi, Angew.
Chem. 2008, 120, 4716–4739; Angew. Chem. Int. Ed.
2008, 47, 4638–4660.
[2] a) H. Wei, E. Wang, Chem. Soc. Rev. 2013, 42, 6060–
6093; b) Y. Lin, J. Ren, X. Qu, Acc. Chem. Res. 2014,
47, 1097–1105.
[3] a) M. Raynal, P. Ballester, A. Vidal-Ferran, P. W. N. M.
van Leeuwen, Chem. Soc. Rev. 2014, 43, 1660–1733;
b) M. Raynal, P. Ballester, A. Vidal-Ferran, P. W. N. M.
van Leeuwen, Chem. Soc. Rev. 2014, 43, 1734–1787;
c) P. Dydio, J. N. H. Reek, Chem. Sci. 2014, 5, 2135–
2145.
[4] S. H. A. M. Leenders, R. Gramage-Doria, B. de Bruin,
J. N. H. Reek, Chem. Soc. Rev. 2015, 44, 433–448.
[5] a) R. Breslow, S. D. Dong, Chem. Rev. 1998, 98, 1997–
2012; b) K. I. Assaf, W. M. Nau, Chem. Soc. Rev. 2015,
44, 394–418.
[6] J.-N. Rebilly, B. Colasson, O. Bistri, D. Over, O. Rein-
aud, Chem. Soc. Rev. 2015, 44, 467–489.
[7] a) J. H. Jordan, B. C. Gibb, Chem. Soc. Rev. 2015, 44,
547–585; b) C. J. Hastings, R. G. Bergman, K. N. Ray-
mond, J. Am. Chem. Soc. 2010, 132, 6938–6940; c) M.
Yoshizawa, J. K. Klosterman, M. Fujita, Angew. Chem.
2009, 121, 3470–3490; Angew. Chem. Int. Ed. 2009, 48,
3418–3438; d) D. Fiedler; D. H. Leung;, R. G. Berg-
man;, K. N. Raymond Acc. Chem. Res. 2005, 38, 351–
360; e) O. Bistri, O. Reinaud, Org. Biomol. Chem.
2015, 13, 2849–2865.
[8] a) J. Kang, J. Rebek Jr, Nature 1997, 385, 50; b) J.
Kang, G. Hilmersson, J. Santamarꢄa, J. Rebek Jr, J. Am.
Chem. Soc. 1998, 120, 3650–3656; c) J. Kang, J. Santa-
marꢄa, G. Hilmersson, J. Rebek Jr, J. Am. Chem. Soc.
1998, 120, 7389–7390.
[28] F. Shi, M. K. Tse, H. M. Kaiser, M. Beller, Adv. Synth.
Catal. 2007, 349, 2425–2430.
[29] H. Firouzabadi, N. Iranpoor, A. A. Jafari, E. Riazy-
montazer, Adv. Synth. Catal. 2006, 348, 434–438.
[30] a) K. S. Ravikumar, J.-P. Begue, D. Bonnet-Delpon,
Tetrahedron Lett. 1998, 39, 3141–3144; b) K. S. Raviku-
mar, Y. M. Zhang, J.-P. Begue, D. Bonnet-Delpon, Eur.
J. Org. Chem. 1998, 2937–2940; c) W. L. Xu, Y. Z. Li,
Q. S. Zhang, H. S. Zhu, Synthesis 2004, 227–232.
[31] A. Russo, C. De Fusco, A. Lattanzi, ChemCatChem
2012, 4, 901–916.
[9] E. S. Barrett, T. J. Dale, J. Rebek Jr, J. Am. Chem. Soc.
2007, 129, 3818–3819.
[10] L. R. MacGillivray, J. L. Atwood, Nature 1997, 389,
469–472.
[32] Three molecules of tetraethylammonium tetrafluorobo-
rate 4 are accommodated within the hexamer: L. C.
Adv. Synth. Catal. 0000, 000, 0 – 0
6
ꢂ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
asc.wiley-vch.de
Palmer, A. Shivanyuk, M. Yamanaka, J. Rebek Jr,
Chem. Commun. 2005, 857–858.
[33] F. Secci, A. Frongia, P. P. Piras, Tetrahedron Lett. 2014,
55, 603–605.
[38] W. C. Still, M. Khan, A. Mitra, J. Org. Chem. 1978, 43,
2923–2925.
[39] Y. Aoyama, Y. Tanaka, S. Sugahara, J. Am. Chem. Soc.
1989, 111, 5397–5404.
[34] S. Mecozzi, J. Rebek Jr, Chem. Eur. J. 1998, 4, 1016–
1022.
[40] H. Y. Li, L. J. Xing, M. M. Lou, H. Wang, R. H. Liu, B.
Wang, Org. Lett. 2015, 17, 1098–1101.
[35] B. Plesnicar, in: Oxidation in Organic Chemistry, Vol.
5C, (Ed.: W. S. Trahanovsky), Academic Press, New
York, 1978, Chap. III, p 211.
[41] D. Antonow, T. Marrafa, I. Dawood, T. Ahmed, M. R.
Haque, D. E. Thurston, G. Zinzalla, Chem. Commun.
2010, 46, 2289–2291.
[36] K. A. Stingl, S. B. Tsogoeva, Tetrahedron: Asymmetry
[42] P. Santosh Kumar Reddy, P. Rama Krishna, Green
2010, 21, 1055–1074.
[37] D. D. Perrin, W. L. F. Armarego, Purification of labora-
tory chemicals, 3rd edn., Pergamon Press, 1993.
Chem. 2015, 17, 4068–4072.
[43] Z. Li, F. Ke, H. Deng, H. Xu, H. Xiang, X. Zhou, Org.
Biomol. Chem. 2013, 11, 2943–2946.
Adv. Synth. Catal. 0000, 000, 0 – 0
7
ꢂ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!

FULL PAPERS
8 Supramolecular Activation of Hydrogen Peroxide in the
Selective Sulfoxidation of Thioethers by a Self-Assembled
Hexameric Capsule
Adv. Synth. Catal. 2016, 358, 1 – 8
Giorgio La Sorella, Laura Sperni, Giorgio Strukul,
Alessandro Scarso*
Adv. Synth. Catal. 0000, 000, 0 – 0
8
ꢂ 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ÞÞ
These are not the final page numbers!