Silica gel-immobilised chiral 1,2-benzenedisulfonimide: a Br?nsted acid heterogeneous catalyst for enantioselective multicomponent Passerini reaction

Article abstract of DOI:10.1039/d1ra05297g

A chiral heterogeneous catalyst derivative of (?)-4,5-dimethyl-3,6-bis(1-naphthyl)-1,2-benzenedisulfonimide is proven here to be efficient in a three-component asymmetric Passerini protocol, carried out in a deep eutectic solvent. Reaction conditions are mild and green, while enantioselectivity is excellent. The catalyst was easily recovered and reused with no decrease in its catalytic activity.

Full text of DOI:10.1039/d1ra05297g

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Silica gel-immobilised chiral 1,2-
benzenedisulfonimide: a Brønsted acid
heterogeneous catalyst for enantioselective
multicomponent Passerini reaction†
Cite this: RSC Adv., 2021, 11, 26083
ab
a
Francesco Marraa and Stefano Dughera
*
Achille Antenucci,
A
chiral
heterogeneous
catalyst
derivative
of
(À)-4,5-dimethyl-3,6-bis(1-naphthyl)-1,2-
Received 9th July 2021
Accepted 23rd July 2021
benzenedisulfonimide is proven here to be efficient in a three-component asymmetric Passerini
protocol, carried out in a deep eutectic solvent. Reaction conditions are mild and green, while
enantioselectivity is excellent. The catalyst was easily recovered and reused with no decrease in its
catalytic activity.
DOI: 10.1039/d1ra05297g
rsc.li/rsc-advances
catalysis: the use of chiral species to modify the solid surface,8
homogeneous formation of a chiral complex before reaction at
the solid surface9 and the graing of a chiral catalytic complex
on a solid support, namely the heterogenised homogeneous
catalyst.10
Our previous studies have seen 1,2-benzenedisulfonimide (1)
and its chiral derivatives (À)-2 and (À)-3 used as excellent,
versatile, safe and eco-friendly homogeneous Brønsted acid
catalysts (Fig. 1).11a–f
More generally, chiral disulfonimides have received recently
signicant attention as robust and effective catalysts in asym-
metric synthesis.12 In fact, they are not only more acidic11g than
phosphoric acids but they also have real C2 symmetry which
facilitates, especially in the presence of bulky substituents close
to the acid site, an increase of stereochemical communication
between the catalyst and the substrate.12a Furthermore, three
chiral derivatives of disulfonimides namely adducts 4, 5 and 6
(Fig. 2) are commercially available from Sigma-Aldrich.
In continuation of our research, we anchored, through an
amide bond, an appropriately functionalised derivative of 1,
namely 1,2-benzenedisulfonimide-4-yl propionic acid (8), to a 3-
Introduction
Organocatalysis has become a highly dynamic research area.1
From the various groups of possible catalysts, Brønsted acids
stand out as they present a range of benets, including a lack of
sensitivity to moisture and oxygen, ready availability, low cost
and low toxicity.2 The importance of catalysis also highlights the
fact that the ninth principle (use of catalysts should be preferred
wherever possible) of Green Chemistry3 is devoted exclusively to
this issue. In light of these, one of the key challenges for organic
synthesis is to design and develop new and efficient catalysts
that are active under mild and sustainably conditions.4 In order
to develop increasingly sustainable and eco-compatible proce-
dures,
a widespread practice in catalysis is to convert
a successful homogeneous organocatalyst into an heteroge-
neous catalytic system.5
By using efficient heterogeneous catalysts, many processes
can be carried out under milder conditions, signicantly
simplifying the usually cost-intensive and energy-consuming
removal of the catalyst aer reaction.6 Moreover, such cata-
lysts create the possibility of their effective and simple recycling.
For these reasons, heterogeneous Brønsted acid organocatalysts
can be used effectively as a toolbox for Green Chemistry.7
The preparation of enantiopure chemicals has been one of
the most rapid growth areas in chemistry over the last decade
with heterogeneous catalysis being recognised as providing new
possibilities.7 A plethora of different strategies has been devel-
oped to obtain enantioselectivity through heterogeneous
a
`
Dipartimnto di Chimica, Universita di Torino, C.so Massimo d'Azeglio 48, 10125
Torino, Italy
b
`
NIS Interdepartmental Centre, Reference Centre for INSTM, Universita di Torino, via
Gioacchino Quarello 15/A, 10135 Torino, Italy
† Electronic supplementary information (ESI) available: See DOI:
10.1039/d1ra05297g
Fig. 1 1,2-Benzenedisulfonimide (1) and its chiral derivative (À)-2 and (À)-3.
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Scheme 2 Synthesis of chiral heterogeneous catalyst 11.
benzene ring. This objective was easily achieved by oxidising the
methyl groups of (À) 3 with KMnO4 in a basic environment
(Scheme 2), obtaining in this way (À)-4,5-dicarboxy-3,6-bis(1-
naphthyl)-1,2-benzenedisulfonimide (10). As reported in our
previous paper,13 the condensation between NH2 and COOH
groups was promoted by N-(3-dimethylaminopropyl)-N-ethyl-
carbodiimide hydrochloride (EDC; Scheme 2). The material
Fig. 2 Commercial disulfonimides.
aminopropyl functionalized silica gel support (7) thus obtaining
a new specie having increased robustness and recyclability with
respect to (1), furthermore paving the way for its successful
employment in heterogeneous catalysis (9; Scheme 1).13
¨
obtained was isolated via ltration over Buchner funnel and was
washed rstly with dilute hydrochloric acid in order to fully
restore the acid function of the sulfonimide and then with
acetone in order to remove any possible organic residue.
The analysis of the IR spectrum of this solid, compared with
that of 10 and with that of 7, conrmed that the anchoring
occurred with the formation of an amide bond (Fig. 3). In fact,
In the IR spectrum of 11, two bands were evident at 1633 and
1542 cmÀ1. The band at 1633 cmÀ1 is due to the CO stretching
Result and discussion
Preparation of the catalyst 11
Encouraged by above results, in order to transform homoge-
neous chiral catalysts (À)-3 into an efficient heterogeneous
catalytic system, our rst goal was to immobilize (À)-3 by means
a strong covalent bond, namely an amide bond, on 3-amino-
propyl functionalized silica gel (7; 1 mmol gÀ1 NH2 loading),
selected as the solid support because of its commercial avail-
ability, chemical inertness and low toxicity. Moreover, it
displays excellent chemical stability, high thermal and
mechanical robustness. In order to form an amide bond, we
needed to presence of two carboxyl groups on the central
Scheme 1 Synthesis of heterogeneous catalyst 9.
26084 | RSC Adv., 2021, 11, 26083–26092
Fig. 3 IR spectra of 7, 10 and 11.
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As a stereocenter is formed, the development of enantiose-
lective protocols has become a major goal. Although the liter-
ature highlights a number of examples of diastereoselective
Passerini reactions17 or asymmetric Passerini-like reactions,18
only few examples are reported for asymmetric classic three-
component passserini reactions.19 These include, notably,
a study by X.-Y. Liu, B. Tan et al.,19d involving the use of BINOL-
based chiral phosphoric acids that efficiently catalyze the
reaction, allowing for excellent enantiomeric excesses to be
obtained. It must be stressed that this is the only example in
which a homogeneous chiral Brønsted acid catalyst was applied
in Passerini reactions. In light of this, an asymmetric and green
version of classic Passerini reactions with a broad scope to
application still remains a major goal to be achieved to date.
Scheme 3 Passerini reaction.
vibration, while the band at 1542 cmÀ1 is due to NH bending
vibration of secondary amides. The weak band observed at
1595 cmÀ1 is probably associated to NH bending vibration of
sulfonimide NH.
Once 11 was obtained, we decided to disfruit it as an
heterogeneous chiral catalyst in order to develop a green
asymmetric protocol for Passerini reaction (Scheme 3).14
Optimization of the reaction conditions
Use of the catalyst 11 in asymmetric Passerini reactions
Passerini reactions are usually carried out in common organic
Multicomponent reactions (MCRs) are chemical trans- aprotic solvents.14 However, in the last years, several optimiza-
formations in which more than two reagents afford a new tions have been implemented in order to minimise the
product which incorporates all of the atoms of the reagents, ecological impact of this reaction, carrying out it in green
with an efficient one-step and high atom economy approach to solvents such ionic liquids,20 water21 or deep eutectic solvents
building up complex molecules in compliance to the rst (DESs).22 DESs23 are considered to be a non-toxic, environmen-
principle of green chemistry.15 In light of this, MCRs are a valid tally benign, sustainable and easily accessible alternative to
tool for achieving the goal of sustainable and eco-compatible conventional organic solvents. They not only possess the
chemistry. The Passerini reaction, rst described about advantages of ionic liquids, such as designability, chemical
a century ago, is one of the oldest MCRs and it is the rst stability, and negligible vapour pressure, but they also provide
isocyanide-based MCR.14 It consists in one-pot, three compo- many other advantages, such as tunability, low-cost and easily
nent reaction of carboxylic acids 12 with aldehydes 13 (or sourced raw materials, as well as green and simple synthesis
ketones) and isocyanides 14, offering an inexpensive and rapid without using other organic solvents. Therefore, DESs appear to
way to generate a wide library of a-acyloxy carboxamides 15. be a good alternative to volatile organic solvents, and it can
These compounds are present in the structures of many natural denitely be said that DESs have every chance of becoming “the
products, such as pharmacologically active depsipeptides and reaction media of the century”.23b In fact, since 2016,24a DESs
can lead to potentially bioactive peptidomimetics compounds.16 have been protably used as solvents for reactions carried out in
Table 1 Trial reactions
Entry
Solvent
Temp (ꢀC)
Time (h)
Yield (%) of 15aa,b
1
2
3
4
5
6
7
8
DCM
Toluene
THF
DMSO
EtOH
H2O
Neat
Neat
Glycerol/choline chloride 4 : 1
Glycerol/choline chloride 4 : 1
Urea/choline chloride 2 : 1
Urea/choline chloride 2 : 1
Rt
Rt
Rt
Rt
Rt
Rt
Rt
60
Rt
60
Rt
60
16
18
36
36
36
36
36
16
26
24
36
14
90
85
c
—
c
—
c
—
87
c
—
45
c
9
—
10
11
12
77
87
88
a
Yields refer to pure and isolated 15a. b The reaction was carried out with 1 mmol of 12a, 13a and 14a. c Aer 36 h the reaction was not complete.
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Table 2 Screening for solvents for chiral catalyst
toluene (Table 1; entry 2) THF (Table 1, entry 3), DMSO (Table 1;
entry 4), EtOH (Table 1; entry 5) and in H2O (Table 1; entry 6). It
was not possible to carry out the reaction in neat conditions at
room temperature (Table 1; entry 7). Furthermore, two different
kinds of DESs were used, formed by a glycerol and choline
chloride (GL/CC; ratio 4 : 1; Table 1, entries 9 and 10) and by
urea and choline chloride (U/CC; 2 : 1 ratio; Table 1, entries 11
and 12) respectively. It is evident that U/CC DES is a good
solvent for this reaction, providing yields of 15a comparable to
those obtained with toluene and DCM, though the reactions
carried out in DCM or toluene are much faster than those
carried out in DESs.
At the end of the reaction carried out in U/CC DES (Table 1;
entry 11), aer adding H2O a white solid precipitated, which was
separated by ltration and washed with small amounts of
diethyl ether. In this way, pure 15a was obtained without further
purication. Aer this optimization, choosing U/CC DES as the
privileged solvent, the scope of this reaction was extended using
different carboxylic acids 12, aldehydes 13 and isocyanides 14.
The results of these reactions are showed in a Table included in
ESI† (Page 6). A number of aromatic 12a–d or heteroaromatic
carboxylic acids 12g and aromatic aldehydes 13a–e containing
both electron-donating and electron-withdrawing groups were
used and afforded excellent yields of 15. Acids 12e–f and alde-
hydes 13f–g were also applied successfully in this reaction.
Finally, it must be stressed that the reactions proceeded effec-
tively with both aromatic 14b and aliphatic isocyanides 14a. On
Entry Solvent
Temp (ꢀC) Time (h) Yield (%) of 15aa,b eec (%)
1
2
3
4
5
DCM
Toluene
H2O
U/CC 2 : 1 Rt
U/CC 2 : 1 60
Rt
Rt
Rt
8
87
90
88
87
90
94.0
94.2
65.2
94.8d
22.3
10
24
20
12
a
b
Yields refer to pure and isolated 15a. The reaction was carried out
c
with 1 mmol of 12a, 13a, 14a and 5 mol% of catalyst 11. Ee was
d
determined by chiral analyses on HPLC. The same results were
obtained using 10 mol% of catalyst 11.
the presence of organic catalysts.24b However, despite these
advantages, the employment of DESs in asymmetric organo-
catalyzed reactions remains very scarce24c but, given their
promising features, it may be expected that many applications
in these areas will appear in the coming years.
On this basis, a model reaction between benzoic acid (12a),
benzaldehyde (13a), and tert-butyl isocyanide (14a) was studied
(Table 1) at room temperature without any catalyst in several
common organic solvents including DCM (Table 1; entry 1),
Table 3 Scope of the Passerini reaction carried out in U/CC DES with chiral heterogeneous catalyst 11
Entry
R1 in RCOOH 12
R2 in RCHO 13
R3 in RNC 14
Time (h)
15
Yielda (%)
Eeb (%)
1
2
3
4
5
6
7
8
Ph; 12a
Ph; 12a
Ph; 12a
Ph; 12a
Ph; 12a
Ph; 12a
Ph; 12a
4-NO2C6H4; 12b
4-MeOC6H4; 12c
4-ClC6H4; 12d
Me; 12e
PhCH2; 12f
3-Pyridyl; 12g
Ph; 12a
Ph; 12a
Me; 12e
Me; 12e
Ph; 13a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
t-Bu; 14a
20
24
20
22
24
28
20
24
30
20
20
22
24
20
20
24
22
15a
15b
15c
15d
15e
15f
15g
15h
15i
15j
15k
15l
15m
15n
15o
15p
15q
87c
93
85
93
87
86
87
84
87
90
86
87
78
87
83
84
86
94.8
96.4
96.8
96.9
97.6
92.7
95.5
95.6
95.9
96.8
96.5
93.1
96.5
98.4
95.3
97.6
96.1
3-NO2C6H4; 13b
4-MeOC6H4; 13c
4-ClC6H4; 13d
4-MeC6H4; 13e
PhCH]CH; 13f
i-Pr; 13g
Ph; 13a
Ph; 13a
Ph; 13a
Ph; 13a
Ph; 13a
4-ClC6H4; 13d
Ph; 13a
4-ClC6H4; 13d
3-NO2C6H4; 13b
i-Pr; 13g
9
10
11
12
13
14
15
16
17
t-Bu; 14a
2-Naphthyl; 14b
2-Naphthyl; 14b
2-Naphthyl; 14b
2-Naphthyl; 14b
a
Yields refer to pure and isolated 15. Times and yields refer to the reactions carried out with 1 mmol of 12a, 13a, 14a with chiral catalyst 11 (5%
mol). b Enantiomeric excess was determined by chiral analyses on HPLC (ee). c The same results were obtained using 10 mol% of catalyst 11.
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Table 4 Recovery and reuse of catalyst 11
Recovery
of 11
ee (%)
in 15a
Entry
Time (h)
Yield (%) of 15aa,b
1
2
3
4
5
24
24
24
28
28
87
85
87
88
84
0.06 gc
0.06 gd
0.06 ge
0.05 gf
0.05 g
94.8
95.0
93.2
93.1
94.0
Fig. 4 Key intermediates for chiral phosphoric acid catalysed Passerini
reaction.
a
b
Yields refer to the pure and isolated product. The reaction was
performed at room temperature with 1 mmol of 12a, 13a, 14a and
c
5 mol% of 11. Recovered 11 was used as a catalyst in entry 2.
d
e
Recovered 11 was used as a catalyst in entry 3. Recovered 11 was
listed in Table 4, where it can be seen that the yields of 15a and the
enantioselectivity were consistently good over the various runs.
Furthermore, also the solvent system U/CC was easily
recovered at the end of the reactions (for details see Experi-
mental) and was used in three consecutive runs, without
observing a decrease in the yield of 15a and in the enantiose-
lectivity of the reaction.
f
used as a catalyst in entry 4. Recovered 11 was used as a catalyst in
entry 5.
the contrary, the reaction of acetophenone (13h) could not
reach completion.
Whit these optimized conditions in hand, we chose four
kinds of solvents, namely DCM, toluene, H2O and DES urea/
choline chloride and we carried out the reactions in the pres-
ence of heterogeneous chiral catalysts 11. We successfully
gained good enantiomeric excesses in the reaction carried out
with both DCM or toluene (Table 2; entries 1 and 2) and U/CC
DES (Table 2; entry 4) at room temperature. It is interesting to
note that the reaction times are signicantly lower than the
reactions carried out in the absence of a catalyst.
Then, using U/CC at room temperature as favorite and green
solvent, we expanded the reaction to the same terms previously
used, obtaining approximately the same yields as the reactions
carried out in the absence of catalyst and excellent enantiomeric
excesses, always higher than 92% (Table 3). The heterogeneous
catalyst 11 was almost completely recovered by easy ltration on
Mechanism of the reaction
Although Passerini's reaction has been known for nearly
a century, some uncertainties remain regarding its exact
mechanism.25 It has been hypothesized that the reaction can
proceed either via an “open chain” mechanism (where the key
intermediates is a nitrilium ion) or via a “concerted mecha-
nism” (where an intermediate nitrilium ion is not formed;
Scheme 4). In polar solvents such as methanol or water, the
reaction should proceed with an “open chain mechanism”26 via
protonation of the carbonyl component followed by nucleo-
philic addition of the isocyanide and carboxylate residue, respec-
tively. The resultant intermediate undergoes acyl group transfer to
give the a-acyloxyamide. In nonpolar solvents, a “concerted
mechanism” should be favored: a trimolecular reaction between
the isocyanide, the carboxylic acid, and the carbonyl in a sequence
¨
a Buchner funnel and reused four consecutive runs. The results are
Scheme 4 Proposed mechanisms for Passerini reaction.
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Regarding the Passerini reactions carried out in the presence
of 11, we believe that two possible mechanisms can be
hypothesized. In the rst and, in particular, in the reactions
carried out with DCM and toluene (apolar or not very polar
solvents), heterogeneous catalyst 11 could act similarly to
phosphoric acid. In fact, if the structure of sulfonimides is
compared with that of the phosphoric acids, it is clear that both
have acidic and basic sites. Indeed, if the phosphoric acid can
be considered a bidentate system, sulfonimides, thanks to the
presence of the SO2 group, can be considered a multidentate
system that can form ve hydrogen bonds (Fig. 5).28
Moreover, the high acidity of catalyst 11 (higher than that of
a phosphoric acid) could, on the one hand, facilitate the
formation of the heterodimer and, on the other hand, make the
carboxylic acid more nucleophilic, and therefore more reactive.
Indeed, the reaction times carried out in the presence of 11 (8 h.
Table 3; entry 1) were signicantly lower than those carried out
without 11 (16 h. Table 1; entry 1). Therefore, thanks to the
formation of the heterodimer 16 and its interaction with aldehyde
13, a chiral fashion is created, facilitating the enantioselective
attack of the nucleophile isocyanate 14, with the formation of
a nitrilium intermediate 17. It then undergoes nucleophilic attack
by the acid 12; nally, Mumm rearrangement of the imidate 18
leads to the formation of the nal product 15 (Scheme 5). In
a recent review of Passerini reaction mechanism, Morokuma
demonstrated, using DFT calculations, that the nitrilium inter-
mediate is stable in solution and the rate of the reactions is
signicantly higher in low-polar solvents (e.g. DCM) not because
the nitrilium ion is not formed, as is commonly believed, but
because a network of hydrogen bonds makes its formation more
difficult.24 This could be conrmed by our experimental data: the
reactions carried out in DCM (8 h. Table 3; entry 1) are much faster
than the reactions carried out in DES (20 h. Table 2; entry 1). In his
mechanism hypothesis, Morokuma believes that the Mumm
rearrangement can be catalyzed by a second carboxylic acid
Fig. 5 Disulfonimide 11 as multidentate system.
of nucleophilic additions has been proposed, without the forma-
tion of a real nitrilium intermediate. The transition state is
depicted as a 5-membered ring. The last step (Mumm rearrange-
ment) includes the acyl migration to the neighbouring hydroxyl
group to produce the desired ester.
In the already mentioned elegant paper by Liu and Tan,15d an
efficient enantioselective Passerini reaction was developed in
the presence of a chiral phosphoric acid catalyst, deriving from
BINOL. The authors proposed an interesting mechanism in
which, inspired by List's previous studies,27 a key intermediate,
such as heterodimer, could form between the chiral phosphoric
acid catalyst and carboxylic acid, creating a chiral environment
suitable for asymmetric induction of the reaction (Fig. 4).
Scheme 5 Proposed mechanism of Passerini reaction in DCM catalysed by 11.
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Scheme 6 Proposed mechanism of Passerini reaction in DES catalysed by 11.
molecule. Therefore, it might be is possible that the acid catalyst be stressed that the use of chiral disulfonimides as acid catalysts in
also plays a role in facilitating Mumm rearrangement. asymmetric synthesis, thanks to the important advantages they
On the other hand, it is dubious that the reaction occurs the provide, is now widely consolidated. However, the synthetic
same way in DES. The polarity of U/CC DES,29 far superior to that of protocols for obtaining such catalysts can be quite complex; this is
DCM or toluene, should favour an “open chain” mechanism. proven by the fact that the cost of the commercially available
Therefore, we assume that, in DES, the reaction could occur precisely disulfonimides is very high. Therefore, a disulfonimide which acts
with this mechanism (Scheme 6). We think that the activation of as a heterogeneous catalyst and which can be used several times
aldehyde is due to the action of 11, mainly by means of the acid site of without losing its catalytic activity, certainly represents an added
the sulfonimide (NH group), but also with those belonging to the value for this family of catalysts.
silica support. The weak basicity of U/CC DES30 should not hinder this
activation Aer its formation, 19 undergoes the enantioselective
attack of 14 with the formation of the intermediate 20 which, in turn,
Experimental
undergoes the nucleophilic attack of the OH of 12. The intermediate
18 is obtained and nally the latter, by means of Mumm rearrange-
ment, gives the product 15. Assuming the above mechanism, this
reaction may therefore be counted as an asymmetric counteranion-
directed catalysis (ACDC), according to list classication.31
General remarks
Analytical grade reagents were used and reactions were moni-
tored by GC, GC-MS. Column chromatography were performed
on Merck silica gel 60 (70–230 mesh ASTM) and GF 254,
respectively. Petroleum ether (PE) refers to the fraction boiling
ꢀ
in the range 40–70 C. Mass spectra were recorded on an HP
5989B mass selective detector connected to an HP 5890 GC with
a cross-linked methyl silicone capillary column. HRMS analyses
Conclusions
In this paper, a sustainable version of asymmetric three were performed on an Orbitrap Fusion instrument. HPLC
component Passerini reaction has been proposed. In our analyses were performed on HPLC Waters 1525 connected to
conditions, we are able to achieve important green benets, a column Chiralpack IG-SFC. 1H NMR and 13C NMR spectra
including the use of a DES as a solvent at room temperature, the were recorded on a Jeol ECZR spectrometer at 600 and 150 MHz
use of a novel and safe heterogeneous catalyst, its complete respectively. IR spectra were recorded on a IR PerkinElmer
recovery and reuse, stoichiometric reagent ratio and mild reaction UATR-two spectrometer. Alternatively, IR spectra of 7, 10 and 11
conditions. High yields of target products (17 examples) and were recorded in the form of self-supporting pellets (using the
excellent enantiomeric excess (17 examples; average 96%) have powders either as such or in KBr dispersion) by means of
been obtained; furthermore, they are obtained in adequate purity, a Bruker IFS Vector 22 spectrophotometer (resolution 4 cmÀ1),
making further chromatographic purication unnecessary. It must equipped with a MCT cryodetector. For the determination of
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optical rotations, a Jasco P-2000 polarimeter was used. (À)-4,5- 14 (1 mmol) was added. The mixtures were stirred at room
Dimethyl-3,6-bis(1-naphthyl)-1,2-benzenedisulfonimide (3) was temperature for the times listed in Table 3 (yield in bracket and
synthesized as previously reported by us.11d Urea/choline chlo- in blue), until the GC and GC-MS analyses showed the complete
ride DES were prepared as reported in the literature.32 All disappearance of starting compounds and the complete
reagents were purchased from Sigma-Aldrich or Alfa-Aesar. formation of a-acyloxyamide 15. In order to recover the catalyst,
Structures and purity of all the products obtained in this the reaction mixture was ltered on a Hirsch funnel and
research were conrmed by their spectral (NMR, MS, IR) data. recovered solid was washed with of H2O. Recovered catalyst was
Yields and enantiomeric excesses of the pure (GC, GC-MS and dried in oven at 70 ꢀC. Aer this treatment the recovered catalyst
NMR) and isolated 15 are reported in Table 2. Satisfactory (0.06 g, 100% of recovery) was reused in other four consecutive
microanalyses were obtained for new compounds.
catalytic runs as reported in Table 4. The yield and the enan-
tiomeric excess of 15a and the recovery of 11 were always
consistently good. Cold H2O (5 mL) was added to the ltrate,
under vigorous stirring. A white solid formed and was recovered
by ltration on a Hirsch funnel. It was washed with additional
cold H2O and diethyl ether (2 mL each). Virtually pure (GC, GC-
MS, 1H NMR, 13C NMR) 15 was obtained. The liquid residue was
collected and, in order to remove H2O and diethyl ether, was
evaporated under reduced pressure. The recovered U/CC solvent
system showed NMR and IR spectra almost identical to the
initial one (ESI†). Physical and spectral data of adducts 15 are
reported in ESI.† Aer the above work-up, enantiomeric
excesses were measured. However, in order to verify the accu-
racy of these measures, the crude residue of 15a, obtained aer
extraction with DCM, was chromatographed on a short column
(eluent: EP–EtOEt, 4 : 1) and then enantiomeric excess was
determined. The values were identical (96.4% on HPLC).
Synthesis of (À)-4,5-dicarboxy-3,6-bis(1-naphthyl)-1,2-
benzenedisulfonimide 10
To
a
solution of (À)-4,5-Dimethyl-3,6-bis(1-naphthyl)-1,2-
benzenedisulfonimide (3, 1 mmol, 0.50 g) in H2O (15 mL) were
added KMnO4 (26 mmol, 4.11 g) and Na2CO3 (18 mmol, 1.91 g).
ꢀ
The resulting mixture was heated at 100 C for 24 h. In order to
¨
remove KMnO4, the mixture was ltered on a Buchner funnel and
the purple ltrate was decoloured with charcoal. H2O was evapo-
rated under reduced pressure. The crude residue, dissolved in H2O
was passed through a Dowex (HCR-W2) column (H2O), affording
pure 10 (0.56 g, 100% yield) as a grey waxy solid.
[a]2D2-25.6 (c 0.15 in CH2Cl2). Found: C, 60.48; H, 3.41; N 2.38.
Calc. for C28H17NO8S2: C, 60.10; H, 3.06; N, 2.50. nmax/cmÀ1 3012
(OH), 1695 (CO). dH (600 MHz, D2O) 7.85–7.49 (m, 6H), 7.47–
7.34 (m, 8H). dC (150 MHz, D2O) 167.9, 136.2, 133.7, 133.5,
132.0, 129.6, 128.5, 128.3, 127.8, 127.8, 126.4, 126.2, 125.9.
HRMS (ESI, m/z): 560.05 (M + H+).
Author contributions
AA was responsible of the chiral analyses; FM took care of the
synthesis of the heterogeneous chiral catalyst. SD coordinated
the research. From the experimental point of view he performed
the Passerini reactions with the chiral catalyst and he took care
of the writing of the paper.
4,5-Dicarboxy-3,6-bis(1-naphthyl)-1,2-benzenedisulfonimide
immobilized on 3-aminopropyl functionalized silica gel (11)
Adduct 10 (0.5 mmol, 0.28 g) and N-(3-dimethylaminopropyl)-N-
ethylcarbodiimmide hydrochloride (EDC, 1.5 mmol, 0.28 g)
were added to a stirred suspension of 3-aminopropyl function-
alized silica gel 7 (1 g; 1 mmol gÀ1 NH2) in H2O (5 mL). The
reaction mixture was vigorously stirred at r.t. for 5 h. The resulting
Conflicts of interest
¨
white solid was ltered over Buchner funnel. Firstly was washed
There are no conicts to declare.
with 10 mL of 2 N HCl (in order to fully restore the sulfonimide
acidity) and then with 10 mL of acetone (in order to remove
eventual organic residues arising from 11 and catalyst); lastly, it
was dried in oven at 70 ꢀC overnight. Aer this treatment, 1.10 g of
11 was obtained (87% yield). Aqueous and acetone washings were
collected and evaporated under reduced pressure. No traces of
possible unreacted 10 were detected. In a collateral proof 2 (1 g)
and 10 (0.5 mmol, 0.28 g) were reacted without EDC. IR spectrum
of the obtained solid (0.99 g), included in ESI.† (Page 5), was
markely different from that of 11 and the characteristic bands of
the amide bond were not present.
Acknowledgements
`
This work was supported by Ministero dell'Universita e della
Ricerca and by University of Torino.
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26092 | RSC Adv., 2021, 11, 26083–26092
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