Rasta resin as support for TBD in base-catalyzed organic processes

Article abstract of DOI:10.1016/j.jcat.2011.09.032

Although its intriguing features, such as uniform functionalization through the entire beads and a very high-loading capacity are suitable candidates for solid-phase synthesis and reagent-scavenging, the use of Rasta resin as support for organocatalysis has been little explored. In this contribution, Rasta polymer has been used to preparation of high-loading Rasta-TBD. This catalyst has been able to efficiently promote several organic transformations with constantly good and promising results.

Full text of DOI:10.1016/j.jcat.2011.09.032

Journal of Catalysis 285 (2012) 216–222
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Journal of Catalysis
journal homepage: www.elsevier.com/locate/jcat
Rasta resin as support for TBD in base-catalyzed organic processes
⇑
Simona Bonollo, Daniela Lanari , Tommaso Angelini, Ferdinando Pizzo, Assunta Marrocchi,
Luigi Vaccaro
⇑
Laboratory of Green Synthetic Organic Chemistry, CEMIN – Dipartimento di Chimica, Università di Perugia Via Elce di Sotto, 8, Perugia, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Although its intriguing features, such as uniform functionalization through the entire beads and a very
high-loading capacity are suitable candidates for solid-phase synthesis and reagent-scavenging, the
use of Rasta resin as support for organocatalysis has been little explored. In this contribution, Rasta poly-
mer has been used to preparation of high-loading Rasta-TBD. This catalyst has been able to efficiently
promote several organic transformations with constantly good and promising results.
Ó 2011 Elsevier Inc. All rights reserved.
Received 2 September 2011
Revised 22 September 2011
Accepted 24 September 2011
Available online 9 November 2011
Keywords:
Heterogeneous catalysis
Solvent-free conditions
1,5,7-Triazabicyclo[4.4.0]dec-5-ene (TBD)
Polymer-supported organocatalysts
1. Introduction
trated conditions running on multigram scale [4a–c,4e]. These re-
sults have proved that the combination of SolFC and polymer-
Over the last decades, fast-growing development of polymer-
supported reagents and catalysts led to a fascinating combination
of chemical efficiency and environmental sustainability [1]. To
have highly active and recoverable solid catalysts is certainly
highly desirable in order to minimize the waste associated with a
chemical process [2]. Anyway, an accurate choice must be made
to select the ideal support considering its cost and commercial
availability, its degree of functionalization and its influence on
the catalyst stability and efficiency. The reaction medium plays a
crucial role and its interactions with the support strongly influence
the efficiency of the solid catalyst. Representatively, it is well
known in the case of insoluble polymers, the access of reactants
to the catalytic sites is closely related to the ability of the reaction
medium to swell the matrix facilitating or hampering the process
[3].
We have contributed to the development of efficient procedures
based on the use of metal-free catalysts supported on Merrifield
resins [4], proving that resin swelling problems can be overcome
by eliminating the reaction medium [4]. Adoption of solvent-free
conditions (SolFC) have led to a markedly increased efficiency of
the anchored catalyst that was recovered and reused and generally
allowed the use of stoichiometric amounts of reactants with conse-
quent minimization of the waste associated with the processes [4].
To further reduce E-factor [2], our approach induced us to set cyclic
continuous-flow protocols operating in SolFC or highly concen-
supported organic catalyst is a promising approach to realize green
and efficient synthetic protocols.
Moving forward, we have directed our interest toward the
development of novel polymer supports to be used as alternatives
to classic Merrifield resins and more suitable for being used in Sol-
FC and in continuous-flow processes. At this purpose, high-loading
material is desirable to facilitate stirring in solvent-free heteroge-
neous reaction conditions.
We have directed our attention to a new class of polymer-sup-
ported material, namely RASTA resins 1, that have been developed
by Hodges et al. by using living free radical polymerization (LFRP)
of TEMPO methyl resin 2 with functionalized styrenyl monomers 3
(Scheme 1) [5].
Rasta resins 1 are often depicted as in Fig. 1 by a cartoon struc-
ture 4 to indicate that polymer chains emerge from the cross-
linked polystyrene core (as hair like appendages), or alternatively
by 5, wherein the shaded inner circle represents the original
cross-linked polystyrene (PS) core and the outer clear circle repre-
sents new polymer growth. Studies on the macromolecular archi-
tecture showed that Rasta resins 1 are uniformly functionalized
through the entire beads and have a very high-loading capacity
[6]. Such properties make Rasta resins suitable candidates for so-
lid-phase synthesis and reagent-scavenging [7]. For our purposes,
we have envisaged in their peculiar architectural structure a prom-
ising solid support for improving our approach to SolFC continu-
ous-flow chemistry.
Lately, Merck Research Laboratories have developed a new
microwave-initiated living free radical polymerization to deliver
⇑
Corresponding authors. Fax: +39 075 5855560.
E-mail address: luigi@unipg.it (L. Vaccaro).
0021-9517/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcat.2011.09.032

S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
217
R
Rasta-TBD catalysts 7a–c have been prepared starting from the
corresponding Rasta-Cl (6). Their morphology was observed with
SEM and compared with both starting Rasta-Cl 6 and commercially
available PS-TBD 8 [10].
N
O
O
N
R
n
2.2. Preparation of catalysts 7a–c
1
2
3
Scheme 1. Rasta resin retro-synthesis.
2.2.1. Rasta-TBD 7a
In a round-bottomed flask equipped with a magnetic stirrer,
TBD (2.0 g, 15 mmol) was dissolved in 1,4-dioxane (30 ml) and
Rasta-Cl (50–100 mesh, 1% cross-linked, 0.587 g, 5.11 mmol Cl/g,
3.0 mmol) was added. The mixture was left under stirring at
60 °C for 24 h, then allowed to reach room temperature. The poly-
mer beads were isolated by filtration, washed with methanol,
dichloromethane, and acetone, and then dried under vacuum for
15 h at 60 °C. The degree of functionalization was determined to
be 2.98 mmol TBD/g (Table 1, entry 4) by elemental analysis: C
76.00, H 8.20, N 12.66.
Rasta resins [8]. Such technique allowed the rapid gram-scale syn-
thesis of novel high-loading polymers such as Rasta amines [8].
On the other hand, an excellent work is being carried out by Toy
et al. on the use of Rasta-based catalysts that were synthesized by
thermal polymerization [9].
Besides Toy’s work in this field, and despite great expectations
hold by Rasta resins, we have found only few applications in liter-
ature so far, to our knowledge [7–9].
Herein, we report the synthesis of a novel Rasta resin catalyst
where 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is covalently
linked to the solid support (7a–c) and the study on its use as a base
in a variety of base-catalyzed reactions that proves its high effi-
ciency in SolFC processes. TBD was chosen as a representative
effective basic catalyst able to promote various transformations
under SolFC [4a-b,4e,4g-h].
2.2.2. Rasta-TBD 7b
In a round-bottomed flask equipped with a magnetic stirrer,
TBD (0.4 g, 3 mmol) was dissolved in 1,4-dioxane (30 ml) and Ras-
ta-Cl (6) (50–100 mesh, 1% cross-linked, 0.587 g, 5.11 mmol Cl/g,
3.0 mmol) was added. The mixture was left under stirring at
60 °C for 24 h, then allowed to reach room temperature. The poly-
mer beads were isolated by filtration, washed with methanol,
dichloromethane, and acetone, and then dried under vacuum for
15 h at 60 °C. The degree of functionalization was determined to
be 2.03 mmol TBD/g (Table 1, entry 6) by elemental analysis: C
68.92, H 7.14, N 8.53.
2. Experimental section
2.1. General remarks
All chemicals were purchased and used without any further
purification.
GC analyses were performed by using Hewett–Packard HP 5890
series II equipped with a capillary column SPB-5 (30 m, 0.25 mm),
a FID detector and hydrogen as gas carrier. GC-EIMS analyses were
carried out by using a Hewett–Packard HP 6890 Series GC system/
5973 Mass Selective Detector equipped with a electron impact ion-
izer at 70 eV. All 1H NMR and 13C NMR spectra were recorded at
200 MHz or 400 MHz, and at 50.3 or 100.6 MHz, respectively, using
a Bruker DRX-ADVANCE 200 MHz and a Bruker DRX-ADVANCE
400 MHz spectromers. Deuterated solvents were used with the
residual peak as internal standard, or TMS in the case of CDCl3.
Chemical shift was reported in ppm and coupling constants in
Hertz. All melting points were measured with Buchi Melting Point
510 apparatus and are uncorrected. Microanalyses were realized
by using a Carlo Erba Elemental analyzer mod. 1106. Thin-layer
chromatography analyses were performed on silica gel on alumi-
num plates, and UV and/or KMnO4 were used as revealing systems.
Column chromatographies were performed by using silica gel 230–
400 mesh and eluting as reported below. Scanning Electron
Microscopy (SEM) pictures of gold-coated polymers (instrument
EMITECH K55OX SPUTTER COATER) were taken on a SEM XL30
PHILIPS. FTIR spectra were recorded on a Bruker ISF 28. Thermo-
gravimetric (TG) and differential thermal analyses (DTA) analyses
were performed on a STA 449 C Jupiter (thermal analyzer).
2.2.3. Rasta-TBD 7c
In a round-bottomed flask equipped with a magnetic stirrer,
TBD (0.2 g, 1.5 mmol) was dissolved in 1,4-dioxane (30 ml) and
Rasta-Cl (6) (50–100 mesh, 1% cross-linked, 0.587 g,
5.11 mmol Cl/g, 3.0 mmol) was added. The mixture was left under
stirring at 60 °C for 24 h, then allowed to reach room temperature.
The polymer beads were isolated by filtration, washed with meth-
anol, dichloromethane, and acetone, and then dried under vacuum
for 15 h at 60 °C. The degree of functionalization was determined
to be 1.19 mmol TBD/g (Table 1, entry 7) by elemental analysis:
C 73.19, H 6.92, N 5.01.
2.3. General procedure for the Michael addition of dimethylmalonate
(9) to a,b-unsaturated ketones 10a–c for the preparation of 11a–c
In a screw-capped vial equipped with a magnetic stirrer, Rasta-
TBD (7a) (0.134 g, 0.4 mmol, 2.98 mmol/g), ketone 10 (2.0 mmol),
and dimethylmalonate (9) (2.0 mmol) were consecutively added
and the resulting mixture was left under vigorous stirring at
60 °C. After 15 h, ethyl acetate was added, the catalyst was recov-
ered by filtration, and the organic solvent was evaporated under
vacuum to give pure product 11 in 92–97% yield (see Section 3).
R
R
O
N
n
4
5
1
Fig. 1. Rasta resin cartoon architecture and shorthand representation.

218
S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
Table 1
Optimization of Rasta-TBD synthesis.
CH2TBD
CH2Cl
N
N
H
N
TBD-H
O
N
O
n
N
n
6
7
Entry
TBD (eq)
Solvent (M)
T (°C)
60
110
110
60
t (h)
La (mmol TBD/g)
1
2
3
4
5
6
7
8
9
2
2
2
5
10
1.0
0.5
10
10
8
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
MeOH/1,4-Dioxane
/
24
24
70
24
24
24
24
120
21
1
2.57
2.52
2.70
2.98
3.10
2.03
1.19
1.69
2.63
2.73
2.38
60
60
60
90/110
130
180b
180b
10
11
1,4-Dioxaneb
DMSOb
10
1
a
Loading of TBD calculated by elemental analysis.
Microwave-assisted reaction (250w).
b
0.45
1600 cm-1
Rasta-Cl6
0.40
Rasta-TBD 7a
Rasta-TBD 7b
Rasta-TBD 7c
0.35
0.30
0.25
1260 cm-1
1370 cm-1
668 cm-1
0.20
0.15
0.10
0.05
0.00
600
800
1000
1200
1400
1600
1800
Wavenumber (cm-1)
Fig. 2. FTIR spectra of Rasta-Cl 6 and Rasta-TBD 7.
Fig. 3. TG curves of Rasta-Cl (6) and catalysts 7a, 7b, and 7c.
2.4. General procedure for the Michael addition of nitroalkanes 12a–c
to ,b-unsaturated ketones 10a–c for the preparation of 13–21
(22) (0.678 ml, 5.0 mmol), and nucleophile (23a or 23b or 23c)
(5.0 mmol) were consecutively added and the resulting mixture
was left under vigorous stirring at 30 or 60 °C. After conversion
of 22 was complete, ethyl acetate was added, the catalyst was
recovered by filtration, and the organic solvent was evaporated un-
der vacuum to give the corresponding pure products (24–26) in
89–100% yield (see Section 3).
a
In a screw-capped vial equipped with a magnetic stirrer, Rasta-
TBD (7a) (0.134 g, 0.4 mmol, 2.98 mmol/g), ketone 10 (2.0 mmol),
and nitroalkane 12 (2.0 mmol) were consecutively added and the
resulting mixture was left under vigorous stirring at 30 or 60 °C.
After 3-30 h, ethyl acetate was added, the catalyst was recovered
by filtration, and the organic solvent was evaporated under vac-
uum. The reaction mixture was purified by silica gel column chro-
matography (95/5 Petroleum ether/EtOAc, 100/1 silica/sample) to
give the corresponding pure product (13–21) in 80–95% yield
(see Section 3).
2.6. Procedure for the tandem Michael–Henry reaction leading to
nitrochromene 29
In a screw-capped vial equipped with a magnetic stirrer, Rasta-
TBD (7a) (0.067 g, 0.2 mmol, 2.98 mmol/g), trans-b-nitrostyrene
(27) (0.149 g, 1.0 mmol), and salicylaldehyde (28) (0.107 ml,
1.0 mmol) were consecutively added and the resulting mixture
was left under vigorous stirring at 80 °C.
2.5. General procedure for the ring-opening of phenyl glycidyl ether
(22)
In a screw-capped vial equipped with a magnetic stirrer, Rasta-
After 15 h, ethyl acetate was added, the catalyst was recovered
TBD (7a) (0.084 g, 0.25 mmol, 2.98 mmol/g), phenyl glycidyl ether
by filtration, and the organic solvent was evaporated under

S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
219
Characterization data and copies of the 1H and 13C NMR spectra
for all compounds (11a–c, 13–21, 24–26 and 29) are reported as
Supplementary data.
3. Results and discussion
3.1. Catalysts preparation and characterization
Starting from Rasta-Cl resin 6, we have tried different reaction
conditions to yield the desired TBD-Rasta resin 7 with the highest
loading possible in view of its use under SolFC. Microwave activa-
tion did not work as good as we expected [8]. (Table 1, entries 10,
11) and according to Toy’s results thermal activation instead gave
encouraging results [9]. 1,4-Dioxane proved to be the best solvent
as it allowed a good polymer swelling and the setting of reaction
temperature as high as 110 °C. The best results at the end were ob-
tained at 60 °C when 5 eq of TDB were added to the chloromethy-
Fig. 4. DTA curves of Rasta-Cl (6) and catalysts 7a, 7b, and 7c.
lated Rasta resin
6 and Rasta-TBD 7 was obtained with a
satisfactory 2.98 mmol TBD/g loading (Table 1, entry 4). A slightly
better loading was obtained but only by using a larger excess of
TBD (10 eq) (Table 1, entry 5).
Afterward, three samples of Rasta-TBD (7a, 7b, 7c) with respec-
tive loading of 2.98 (7a) (Table 1, entry 4), 2.03 (7b) (Table 1, entry
6), and 1.19 (7c) mmol TBD/g (Table 1, entry 7) were prepared and
characterized by elemental analysis, IR spectroscopy, Thermogravi-
metric (TG) and differential thermal analysis (DTA), and Scanning
Electron Microscopy (SEM).
vacuum. The reaction mixture was purified by silica gel column
chromatography (95/5 Petroleum ether/EtOAc, 40/1 silica/sample)
to give 3-nitro-2-phenyl 2H-chromene (29) as a yellow oil (0.139 g,
55% yield).
Compounds 11a [11], 11c [12], 13 [4e], 14 [4e], 15 [4e], 16 [4e],
18 [13], 19 [4e], 20 [14], 21 [13], 24 [15], 25 [15], 26 [4b], 29 [16]
are known compounds, while compounds 11b, 17 are new
compounds.
Fig. 5. SEM images of: (a) Rasta-Cl 6. (b) Rasta-TBD 7c. (c) Rasta-TBD 7b. (d) Rasta-TBD 7a. (e) PS-TBD 8.
Table 2
Michael addition of dimethylmalonate (9) to
a
,b-unsaturated ketones (10a–c).
MeO2C
CO2Me
O
O
CO2Me
CO2Me
Cat (mol%)
60 °C, 15 h
R2
R2
R1
R1
10a-c
9
11a-c
a R1=H, R2=Me; b R1=Cl, R2=Me; c R1=H, R2=Ph
Entry
Ketone
Cat (mol%)
Medium
Conversiona (%)
Yieldb (%)
1
2
3
4
5
6
7
8
10a
10a
10a
10a
10a
10a
10b
10c
7a (20)
7a (20)
7a (20)
7a (20)
7a (5)
6 (5)
7a (20)
7a (20)
CH3CN
DCE
1,4-Dioxane
–
–
–
–
–
39
0
13
100
39
0
–
–
–
92
–
–
93
100
100
97, 96,c 97d
a
b
c
Measured by GLC analysis.
Yield of the isolated pure product.
Yield of the isolated pure product after first recycle.
Yield of the isolated pure product after second recycle.
d

220
S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
R3
R4
O
O2N
O
R3
R4
NO2
7a (20% mol)
R2
R2
60°C
R1
R1
(1 eq)
12a R3 = R4 = H
10a-c
13-21
12b R3 = H; R4 = Me
12c R3 = R4 = Me
O2N
O2N
O2N
O
O
O
O
Cl
13, 3 h, 88% yield
14, 4 h, 81% yield
15, 4 h, 80% yield
O2N
O2N
O
O2N
O
Cl
16a, 16 h, 84% yield
17a, 10 h, 92% yield
18a, 15 h, 93% yield
O2N
O
O2N
O
O2N
O
Cl
19, 30 h, 90% yield
20b, 24 h, 95% yield
21, 5 h, 90% yield
The representative reaction of 10a and 12a in the presence of 6 gave no conversion at all.
a Reaction performed at 30 °C. b 2 equiv of nitroalkane were used.
Scheme 2. Michael addition of nitroalkanes.
FTIR spectra confirm the presence of the immobilized TBD moi-
medium (Table 2, entries 1–3). On the other hand, by performing
the reaction 10a with 9 under SolFC at 60 °C, product 11a was ob-
tained in a 100% conversion and 92% isolated yield (Table 2, entry
4). The same reaction can be also performed under SolFC with
smaller amount of catalyst (Table 2, entry 5).
As expected, Rasta-Cl 6, that does not contain any strong basic
site, did not show any catalytic effect on the Michael addition of
9 to 10a (Table 2, entry 6).
The use of 7a (20 mol%) was extended to the addition of 9 to 4-
(40-chlorophenyl)-3-buten-2-one (10b) and trans-chalcone (10c),
and also in these cases, conversions were quantitative and pure
products 11b and 11c were isolated in 93% and 97% yields, respec-
tively (Table 2, entries 7 and 8).
ety. By comparing the Rasta-TBD 7 spectra with that of the Rasta-Cl
6 is clearly visible the gradual disappearing of the 1260 cmꢀ1 band
corresponding to the CH2Cl wagging vibration and the 670 cmꢀ1
band corresponding to the CACl stretching vibration going from
Rasta-Cl 6 to the more functionalized Rasta-TBD 7 (Fig. 2). More-
over, it can be noted the appearance of
a strong peak at
1600 cmꢀ1 relative to C@N stretching (the weak band observed
at the same frequency for Rasta-Cl 6 spectrum is due to benzene
skeleton) and a 1380 cmꢀ1 band corresponding to CAN stretching.
Elemental analyses were used to calculate the catalyst loading.
In Figs. 3 and 4 are shown Thermogravimetric (TG) and differen-
tial thermal analysis (DTA) curves of catalysts 7a, 7b, 7c compared
to starting material Rasta-Cl (6). It is clearly visible the different
initial mass loss in the case of the TBD-containing catalysts (7a,
7b, 7c) and the starting chloride resin 6.
Rasta-TBD catalyst 7a was also tested in Michael addition of
nitroalkanes 12a–c to a,b-unsaturated ketones 10a–c (Scheme 2).
Very good yields were obtained when 20 mol% of 7a were used.
Reactions with nitromethane (12a) and 2-nitropropane (12c) were
run at 60 °C, the more reactive nitroethane (12b) required a lower
temperature (30 °C). In this latter case, products 16–18 were iso-
lated as 53/47, 52/48, and 56/44 diasteromeric mixtures,
respectively.
Catalyst 7a proved to be effective also in the representative
nucleophilic ring-opening of phenyl glycidylether (22) by thiols
23a and 23b and by phenol (23c). Benzenethiol (23a) and n-
butanethiol (23b) reacted at 30 °C in the presence of 5 mol% of
7a, leading to the corresponding pure products 24 and 25, respec-
tively, in high yields. When phenol (23c) was employed as nucleo-
phile, the reaction needed longer reaction time and 60 °C to reach
complete conversion (Scheme 3). As expected [4b,17], the reac-
tions proceeded with complete regioselectivity and it was
Morphology of the Rasta-TBD samples (7a, 7b, 7c) was observed
with SEM and compared with both starting Rasta-Cl 6 and com-
mercially available PS-TBD 8 [10] (Fig. 5): the images, represented
with equal magnification, show that particles size was on the
micrometer scale, and Rasta resin beads are slightly bigger than
PS ones.
3.2. Catalytic activity
The efficiency of the new base-supported organocatalyst 7a has
been tested in several fundamental organic transformations.
In the case of the Michael addition of dimethylmalonate (9) to
(E)-benzylideneacetone (10a) (Table 2), poor results were obtained
in the presence of 20 mol% of catalyst 7a and of an organic reaction

S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
221
PhSH (23a) or nBuSH (23b)
7a (5 mol%)
OH
24: R=Ph
yield 100%
25: R=nBu
yield 96%
PhO
SR
6 h, 30 °C
O
PhO
PhOH (23c)
7a (20 mol%)
OH
22
PhO
OPh
26: yield 89%
32 h, 60 °C
a
The representative reaction of 22 and 23a in the esence of 6 ve no conversion at ll.
pr ga
Scheme 3. Ring-opening of phenyl glycidyl ether (22).
observed only the formation of the products coming from the at-
tack of the nucleophile to the less substituted b-carbon (C-3).
As a further example of the versatility of Rasta-TBD catalyst 7a,
we studied the reaction of nitrostyrene (27) with salicylaldehyde
(28) for the preparation of 29. The initially formed Michael adduct
gave intramolecular Henry reaction with subsequent water-elimi-
nation to form product 29 in 55% yield (Scheme 4). 3-Nitrochrom-
enes such as 29 belong to an important class of heterocycles
precursors of biologically active compounds [18].
O
NO2
Ph
NO2
7a (20 mol%)
80 °C, 15 h,
55% yield
H
+
O
OH
27
28
29
Scheme 4. Tandem Michael–Henry reaction for the synthesis of nitrochromene 29.
In order to evaluate the influence of Rasta support on the effi-
ciency of the processes herein investigated (specifically on the cat-
alytic activity and selectivity), immobilized Rasta-TBD 7a and the
corresponding homogeneous catalyst methyl-TBD (30) have been
compared and results are reported in Table 3.
The homogeneous MTBD (30) is a more efficient base than
Rasta-TBD (7a) and as expected the use of the immobilized catalyst
resulted in slower reactions. Anyway, the selectivity observed in
the addition of nitroethane (12b) to enones 10a–c was almost
identical (52–56/48–44 for Rasta-TBD, vs. 54–55/46–45 for MTBD)
and also the ring-opening of 22 with benzenethiol (23a) and phe-
nol (23c) gave in all cases a complete C-3 selectivity. These data
suggest that, although the catalytic efficiency of TBD nucleus is re-
duced by the presence of the polymeric support, the mechanisms
of the reactions considered are not influenced, and Rasta supports
allow to achieve the same regiochemical and stereochemical out-
comes than the free homogenous catalyst.
Table 3
Efficiency comparison of solid catalyst Rasta-TBD 7a and homogeneous Methyl-TBD
(MTBD) (30) under SolFC.a
Entry
Substrates
Cat
T (°C)
t (h)b
Yieldc (%)
1
2
3
4
5
6
7
8
10a + 9
10a + 9
MTBD (30)
Rasta-TBD (7a)
MTBD (30)
Rasta-TBD (7a)
MTBD (30)
Rasta-TBD (7a)
MTBD (30)
Rasta-TBD (7a)
MTBD (30)
Rasta-TBD (7a)
MTBD (30)
60
60
30
30
30
30
30
30
30
30
60
60
2
15
1
16
0.7
10
1
15
0.5
6
93
92
10a + 12b
10a + 12b
10b + 12b
10b + 12b
10c + 12b
10c + 12b
22 + 23a
22 + 23a
22 + 23c
22 + 23c
91d
84
91e
92
93d
93
9
100f,g
100f,g
90g
89g
10
11
12
4
32
Rasta-TBD (7a)
a
Rasta-TBD (7a) and MTBD (30) were used in 20 amounts. Measured by GLC
analysis.
b
Time for the complete conversion to products.
Yield of the isolated pure product (average over three experiments).
Catalysts were used in 5 mol% amount.
Diasteroisomeric ratio: 55/45.
Diasteroisomeric ratio: 54/46.
c
d
e
f
We have also evaluated the recovery and reuse of 7a. Both in
the ring-opening of epoxides and in the Michael addition of dim-
ethylmalonate (9) to a,b unsaturated ketones 10a–c, we have not
observed any decrease in its catalytic efficiency. The recovered cat-
alyst has been analyzed by Elemental Analysis, confirming the un-
g
Only product coming from the C-3 attack was observed.
Scheme 5. Schematic diagram of the cyclic continuous-flow reactor in the reaction of 10a or 10b and 9 catalyzed by 7a.

222
S. Bonollo et al. / Journal of Catalysis 285 (2012) 216–222
changed loading of TBD, and SEM image (see Supplementary data)
showed some expected crunching of the beads due to the mechan-
ical stirring used to perform the reactions.
Finally, to optimize the recovery and reuse of catalyst Rasta-
TBD 7a and to prove its application in continuous-flow processes
operating under solvent-free conditions, we have defined an auto-
mated protocol for the representative reactions of 9 with 10a and
10b (Scheme 5).
According to our previous reports in this field, the reactor has
been designed to minimize waste and in particular the amount
of organic solvent needed to isolate the final products [4a–c,4e].
The schematic diagram of the reactor is presented in Scheme 5
(thermostated box is not showed for clarity). The equimolar mix-
ture (50 mmol) of 9 and 10a or 10b was charged into a glass
column functioning as reservoir. Catalyst 7a (20 mol%,
corresponding to 10 mmol of TBD) was charged into a glass col-
umn, and the reaction mixture was continuously pumped through
it at 60 °C for 15 h, necessary for the complete conversion to 11a
and 11b.
At this point, the pump was left to run in order to recover the
reaction mixture into the reservoir. Then, EtOAc was added
(5 ꢁ 2 ml) to wash the catalyst and to isolate the pure products
11a or 11b in 95% and 94% yield, respectively.
The same protocol was repeated for five consecutive runs, and
the efficiency of the catalyst was unchanged. After 15 h, the con-
version of 10a or 10b to 11a or 11b was always complete and
the final products were recovered always in very high yields
(93–95%).
It should be highlighted that by using the cyclic continuous-
flow procedure, crunching of the catalyst was not anymore ob-
served and the recovered catalyst almost conserved is physical
integrity as showed by the SEM image reported in Supplementary
data.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jcat.2011.09.032.
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We gratefully acknowledge the Ministero dell’Istruzione,
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