L. Ma, P. G. Williard / Tetrahedron: Asymmetry 17 (2006) 3021–3029
3027
(
TLC), silica gel plates Merck 60 F254 were used and com-
4.3. General procedure for the synthesis of polymer-
supported amines
pounds were visualized by irradiation with UV light and/or
by treatment with a solution of phosphomolybdic acid in
ethanol followed by heating.
Merrifield resin (10 g, 1.30 mmol C1/g, DF = 0.14) was
fully swelled in DMF (100 mL) for 30 min, and then, to
this solution was added NaHCO3 (6.72 g, 80 mmol,
6.2 equiv), and (R)-1-phenyl-2-piperidinoethylamine or
(R)-1-phenyl-2-(4-methylpiperazinyl)ethylamine (40 mmol,
Elemental analysis was performed by Quantitative Tech-
nology, INC in order to determine the percentage of nitro-
gen or other significant elements. NMR spectra were
1
3
recorded on a Bruker 400 MHz spectrometer. For C gel
phase NMR, pulse width was 18 ls, delay between pulses
was 0.2 s, line broadening was 2 Hz. IR spectra were re-
corded on a Perkin–Elmer 1600 series FTIR from 50 mg
dry pellets with 1–2 mg of polymer. Gas chromatographic
analyses were carried out on a Hewlett Packard HP 6890
gas chromatograph equipped with a FID detector. All
GC analyses were run on a chiral stationary-phase column
3.1 equiv). The reaction mixture was stirred under N at
2
80 ꢁC for 2 days. The functionalized polymer resin was
then isolated by filtration, thoroughly washed with DMF
(50 mL · 2), acetone (50 mL · 3), methanol (50 mL · 3),
CH Cl (50 mL · 3), methanol/water (1:1, 50 mL · 3),
2
2
and methanol (50 mL · 3). The polymer was then dried
in vacuo for 16 h at 40–50 ꢁC to afford the title compound.
(
CP-Chirasil-DEX CB, 25 m, 0.32 mm) from Varian (Cat.
4.3.1. Compound 2a. Elemental analysis [(C H )
-
1
0
10 0.01
No. CP 7503). The column was held at a constant temper-
ature (injector 250 ꢁC, detector 275 ꢁC) with helium (2 mL/
min) as a carrier gas.
(C H ) (C H N ) ]: N, 2.97. Found: N, 2.67, corre-
8 8 0.85 22 28 2 0.14
1
3
sponding to 0.95 mmol amine/g.
C
NMR (gel,
100 MHz, CDCl ): d 145.1, 128.4, 66.5, 58.3, 55.1, 51.8,
3
4
1
7
0.4, 26.2, 24.6. IR (KBr) mmax 3304, 3023, 2903, 1943,
751, 1601, 1490, 1447, 1354, 1116, 1066, 1025, 904, 746,
4.2. General procedure for the synthesis of polymer-
supported aminoethers
À1
00, 532 cm
.
4
.3.2. Compound 2b. Elemental analysis [(C H )
-
A
solution of (S)-2-isopropylaminoalcohol (6 mmol,
10 10 0.01
(C H ) (C H N ) ]: N, 4.30. Found: N, 4.25, corre-
2
.2 equiv) in DMF (8 mL) was added via syringe to a sus-
8 8 0.85 22 29 3 0.14
1
3
sponding to 1.01 mmol amine/g.
C
NMR (gel,
pension of sodium hydride (0.25 g, 9 mmol, 3.2 equiv) in
1
5
1
7
00 MHz, CDCl ): d 142.5, 127.6, 65.6, 58.1, 55.2, 53.1,
DMF (25 mL) at 0 ꢁC under N . The mixture was stirred
3
2
1.1, 46.1, 40.5, 29.7. IR (KBr) mmax 3309, 3025, 2919,
at 0 ꢁC for 2–4 h, then quickly poured into a suspension
944, 1721, 1601, 1491, 1454, 1369, 1163, 1010, 906, 748,
of Merrifield resin (2 g, 1.39 mmol C1/g, DF = 0.16) in
À1
00, 532 cm
.
DMF (16 mL) at 0 ꢁC. The reaction was flushed with N ,
2
and smoothly stirred for 48 h at 120 ꢁC. The functionalized
polymer resin was then isolated by filtration, thoroughly
washed with DMF (10 mL · 3), acetone (10 mL · 3), meth-
anol (10 mL · 3), CH Cl (10 mL · 3), methanol/water
4.4. General procedure for the synthesis of polymer-
supported chiral amines with spacers
2
2
4.4.1. Etherification. To a round-bottomed flask were
(
1:1, 10 mL · 3), and methanol (10 mL · 3) until no detect-
À
added 1,6-hexanediol (2.32 g, 19.7 mmol, 3.5 equiv) and
TBAI (0.72 g, 1.92 mmol, 0.4 equiv). The flask was put
able Cl (by AgNO ). The polymer was then dried in vacuo
3
for 16 h at 40–50 ꢁC to afford the title compound.
under vacuum and back filled with N several times before
2
DMF (40 mL) was added. At 0 ꢁC, a NaH (0.44 g,
4
.2.1. Compound 1a. Elemental analysis [(C H )
-
1
0
10 0.01
1
8 mmol, 3.2 equiv) suspension in DMF (8 mL) was added
(
C H ) (C H NO) ]: N, 1.79. Found: N, 1.63, corre-
8 8 0.83 15 23 0.16
1
3
and then stirred at 0 ꢁC for 1 h. The resulting sodium
alkoxide was added to a fully swelled Merrifield resin
sponding to 1.16 mmol amine/g. C NMR (gel, 100 MHz,
CDCl ): d 127.8, 74.7, 73.0, 49.5, 45.3, 40.3, 24.0, 22.9,
1
1
3
(4 g, 1.39 mmol C1/g, DF = 0.16) in DMF (32 mL). The
8.0. IR (KBr) m 3451, 3319, 3019, 2920, 1945, 1745,
À1
reaction mixture was kept shaking at room temperature
for 2 days. The solvent was filtered off and the polymer
was washed with DMF (50 mL · 3), acetone (50 mL · 3),
methanol (50 mL · 3), CH Cl (50 mL · 3), methanol/
601, 1491, 1446, 1363, 1169, 1086, 748, 693, 532 cm
.
4
.2.2. Compound 1b. Elemental analysis [(C H )
-
1
0
10 0.01
2
2
(
C H ) (C H NO) ]: N, 1.73. Found: N, 1.54, corre-
8 8 0.83 17 27 0.16
water (1:1, 50 mL · 3), and methanol (50 mL · 3).
The polymer was then dried in vacuo for 16 h at 40–
50 ꢁC to yield 4.3 g of white beads. Elemental analysis
1
3
sponding to 1.10 mmol amine/g. C NMR (gel, 100 MHz,
CDCl ): d 126.9, 73.0, 70.7, 59.6, 46.5, 40.3, 29.5, 23.7,
2
1
5
3
3.5, 18.7, 18.6. IR (KBr) mmax 3452, 3026, 2926, 1934,
[(C H )
(C H ) (C H O ) ]: O, 4.09. Found: O,
8 8 0.83 15 22 2 0.16
1
0
10 0.01
1
3
801, 1602, 1485, 1450, 1366, 1175, 1094, 756, 698,
3.84, corresponding to 1.20 mmol alcohol/g. C NMR
À1
38 cm
.
(
gel, 100 MHz, CDCl ): d 128.3, 72.7, 70.1, 62.5, 40.3,
3
32.6, 29.6, 26.0, 25.5. IR (KBr) mmax 3595, 3472, 3023,
4
.2.3. Compound 1c. Elemental analysis [(C H ) -
10 0.01
2933, 1943, 1741, 1601, 1491, 1448, 1360, 1176, 1091,
1
0
À1
(
C H ) (C H NO) ]: N, 1.63. Found: N, 1.46, corre-
1016, 906, 749, 699, 532 cm
.
8
8 0.83 21 27
0.16
1
3
sponding to 1.04 mmol amine/g. C NMR (gel, 100 MHz,
CDCl ): d 139.2, 128.3, 73.1, 71.6, 55.9, 45.6, 40.3, 38.4,
4.4.2. Transhalogenation. In a round-bottomed flask, the
polymer (3.87 g, 1.20 mmol/g, 4.64 mmol alcohol) and
THF (76 mL) were added. After 30 min swelling, triphenyl-
phosphine (5.42 g, 20.1 mmol, 4.4 equiv), imidazole (3.0 g,
3
2
1
5
3.3. IR (KBr) mmax 3440, 3319, 3032, 2918, 1939, 1745,
601, 1490, 1448, 1363, 1169, 1081, 1020, 904, 753, 698,
À1
37 cm
.