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nol (0.88 mmol, 25 wt%), and AIBN (0.04 mmol, 1 wt%); loading=
0.3 mmolgÀ1
Synthesis of catalyst SIL–QNb
Mercaptopropyl silica 11 was prepared according to a published
procedure.[26] Before the reaction, unfunctionalized silica (1.9 g,
Apex Prepsil Silica Media 8 mm) was dried under high vacuum at
1008C for 1 h. Then, under hydrogen atmosphere dry toluene
(19 mL) and dry triethylamine (0.57 mmol) were added. After
5 min, mercaptopropyltrimethoxysilane (MPTMS) (5.7 mmol) was
added dropwise. The mixture was stirred at 808C for 24 h. After
the reaction time, the solid was filtered and washed with methanol
(10 mL) and dichloromethane (10 mL) and then dried under high
vacuum for 3 h. The organic layer was concentrated under vacuum
and unreacted MPTMS was recovered (3.8 mmol). 11 was obtained
as a white solid (1.85 g, 1.0 mmolgÀ1). Loading of 11 was deter-
mined by the amount of MPTMS recovered after the reaction.
Catalyst PS–QNc was prepared from monomer 4 (0.68 mmol,
11 wt%),
(10.28 mmol, 32 wt%), 1-dodecanol (5.38 mmol, 34 wt%), and AIBN
(0.17 mmol, 1 wt%); loading=0.7 mmolgÀ1
divinylbenzene
(5.00 mmol,
22 wt%),
toluene
.
Catalyst PS–QNd was prepared from monomer 5 (0.78 mmol,
11 wt%), divinylbenzene (3.88 mmol, 22 wt%), toluene (7.97 mmol,
32 wt%), 1-dodecanol (4.19 mmol, 34 wt%), and AIBN (0.14 mmol,
1 wt%); 0.26 mmol of monomer 5 recovered from the organic
phase, loading=0.8 mmolgÀ1
.
Silica compound 11 (620 mg) was suspended in dry toluene
(10 mL) under nitrogen atmosphere and then a solution of 5
(0.56 mmol, g) and AIBN (0.56 mmol) in dry chloroform (3 mL) was
added slowly. The mixture was stirred at 808C for 24 h under inert
atmosphere. After reaction time, the solid was filtered and washed
with CH2Cl2 (10 mL) and methanol (10 mL) and then it was dried
under high vacuum for 3 h. The organic layer was concentrated
Synthesis of catalyst PEG–QN
To a DMF solution (10 mL) of compound 7 (1 mmol), previously
dried under vacuum at 808C for 1 h, a solution of 6 (4 mmol) in
dry DMF (30 mL) and Cs2CO3 (8 mmol) were added. After 48 h stir-
ring at 708C, the mixture was cooled at RT, the solvent was evapo-
rated under vacuum, the residue was dissolved in CH2Cl2 (10 mL)
and the solution was filtered on a short pad of celite. The mixture
was concentrated under vacuum until few ml solution which was
poured dropwise in cold Et2O (250 mL). The precipitated was fil-
tered, washed with Et2O (5 mL), and dried under vacuum to give
5.5 g of PEG–QN as a brown solid; quantitative yield, loading
0.19 mmolgÀ1. To recover the excess of 6, the ether solution was
treated with TFA (4 mmol), concentrated under vacuum and puri-
fied by flash column chromatography on silica-gel (AcOEt/MeOH=
1:1, with 1% Et3N).
under vacuum and unreacted compound
5 was recovered
(0.26 mmol). Catalyst SIL–QNb was obtained as a yellowish solid
(600 mg, 0.5 mmolgÀ1). Loading of SIL–QNb was determined by
the amount of unreacted compound 5 recovered from the organic
layer.
General procedure for the addition of isobutyric aldehyde
to trans-b-nitrostyrene with PS–QNc.
1H NMR (300 MHz, CDCl3): d=8.74 (d, J2’,3’ =4.5 Hz, 1H) (H-2’), 8.02
(d, J8’,7’ =9.2 Hz, 1H) (H-8’), 7.63 (bs, 1H) (H-5’), 7.45 (d, 1H) (H-3’),
7.39 (dd, 1H) (H-7’), 7.13 (d, J13,12 =8 Hz, 2H) (H-13), 6.85 (d, 2H) (H-
12), 5.80 (ddd, J10,11 =7.4 Hz, 1H) (H-10), 5.00 (d, 1H) (H-11 A), 4.96
(d, 1H)(H-11B), 4.56 (d, J9,8 =10.7 Hz, 1H) (H-9), 3.40 (dd, 2H) (H-
16),3.38 (s, 3H) (PEGÀOCH3), 3.27 (dd, J2,3 =9.9 Hz, 1H)(H-2 A), 3.19
(m, 3H) (H-2B), 3.05 (m, 1H) (H-8), 2.82 (m, 1H) (H-14), 2.75 (m, 2H)
(H-6), 2.3 (bs, 2H) (NH2), 2.16 (m,2H) (H-15), 1.61 (bs,1H) (H-4), 1.52
(m, 2H) (H-5), 1.40 (m, 1H) (H-7A), 0.75 ppm (dd, J7,8 =7.8 Hz,
1H)(H-7B). (See Supporting Information).
Into
a
vial, the solid-supported catalyst PS–QNc (60 mg,
0.042 mmol) was suspended in dry toluene (0.5 mL) under nitrogen
atmosphere and benzoic acid (5 mg, 0.042 mmol) and nitroalkene
(21 mg, 0.14 mmol) were added. After 10 min the carbonyl com-
pound (50 mg, 0.7 mmol) was added, the vial was sealed and the
mixture was allowed to stir at 258C for the indicated reaction time.
The mixture was then diluted with methanol (8 mL) and the
heterogeneous catalyst was precipitated by centrifugation. The
solid was washed twice with methanol (8 mL), then it was trans-
ferred into a round-bottom flask and dried under vacuum for 1 h.
The combined organic layers were concentrated under vacuum.
The crude product was purified by flash column chromatography
on silica gel. The enantiomeric excess of the final product was de-
termined by HPLC on chiral stationary phase.
Synthesis of catalyst SIL–QNa
Compound 9 (1.3 mmol) was dissolved in dry toluene (13 mL)
under nitrogen atmosphere, then unfunctionalized silica was
added (1.00 g, Apex Prepsil Silica Media 8 mm). The mixture was
stirred at 808C for 48 h and then it was filtered. The solid was
washed with dichloromethane (10 mL) and methanol (10 mL), and
then it was recovered and dried under high vacuum for 3 h. The
organic phase was concentrated under vacuum and unreacted
compound 9 was recovered. Loading of 10 was determined by
weight difference of silica before and after the reaction. Com-
pound 10 was obtained as a yellowish solid (1.26 g, 0.5 mmolgÀ1).
Compound 10 (300 mg) was suspended in EtOH (3 mL) under ni-
trogen atmosphere and then methylamine was added (3 mL, 33%
wt ethanol solution). The mixture was stirred at 408C for 6 h, then
the solid was filtered and washed with methanol (10 mL) and di-
chloromethane (10 mL). Finally it was dried under high vacuum for
3 h; catalyst SIL–QNa was obtained as a yellowish solid (280 mg).
General procedure for the addition of isobutyric aldehyde
to trans-b-nitrostyrene with PEG–QN
Into a two-necks flask the catalyst PEG–QN (0.036 mmol, 200 mg)
was dried under vacuum at 808C for 1 h, then dry toluene (1 mL)
was added and after the total solubilization of PEG–QN under ni-
trogen atmosphere, benzoic acid was added (4 mg, 0.036 mmol)
under stirring; after 5 min the nitroalkene (18 mg, 0.12 mmol) and
the carbonyl compound (43 mg, 0.6 mmol) were added. The mix-
ture was left to react at 258C for the indicated reaction time. Then
the solvent was evaporated under vacuum and the residue was
dissolved in CH2Cl2 (0.5 mL) and this solution was poured dropwise
in Et2O (50 mL). The filtered solution was concentrated under
vacuum and purified by flash column chromatography on silica
gel. The enantiomeric excess of the final product was determined
by HPLC on chiral stationary phase.
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