Immobilized Analogue of (R)-2-Piperidino-1,1,2-triphenylethanol
FULL PAPERS
(S)-4-(3,3-Diphenyloxiranyl)-benzaldehyde (6): A solution
of DIBALH (61 mL, 61 mmol) in hexane was added dropwise
Anchoring (R)-2-(4-Hydroxymethylphenyl)-1,1-
diphenyl-2-piperidin-1-ylethanol (2) to Merrifield
Resins
to a solution of (S)-5 (4.50 g, 15.1 mmol) in hexane at À 788C.
After 2.25 h, ethyl acetate (20 mL) was slowly added, and the
reaction mass was allowed to warm to room temperature, when
a saturatedsolution of NH4Cl was added. Theresultingmixture
was kept at 258C for 2 h, the crude was filtered through Celite,
the two phases were separated, the aqueous phase was
extracted with ethyl acetate, and the combined organic phases
were dried and concentrated under vacuum. The residual solid
was purified by chromatography to afford the aldehyde (S)-6 as
a white solid; yield: 3.73 g (82%); [a]D23: 60.9 (c 1.01 in CHCl3);
1H NMR (200 MHz, CDCl3): d 4.39 (s, 1H), 7.19 7.37 (m,
12H), 7.65 (d, J 8.4 Hz, 2H), 9.87 (s, 1H); 13C NMR (50 MHz,
CDCl3): d 67.3 (CH), 68.7 (C), 126.2 (CH), 127.1 (CH), 127.7
(CH), 127.9 (CH), 128.0 (CH), 128.3 (CH), 128.8 (CH), 129.1
(CH), 135.0 (C), 135.6 (C), 140.2 (C), 142.2 (C), 191.7 (CH); IR
(NaCl, film): n 3060, 2851, 2747, 1699 cmÀ1; MS (CI, NH3): m/
Resin 7a (1% DVB, fmax: 0.52) from Chloromethylated
Polystyrene (1% DVB, f0: 0.63): A solution of 2 (0.11 g,
0.28 mmol) in DMF (1 mL) was added to a suspension of
sodium hydride (7 mg, 0.29 mmol) in DMF (1 mL) at 0 8C
under N2. The mixture was stirred for 20 min and quickly
poured into a smoothly stirred suspension of the Merrifield
resin (0.40 g, 0.25 mmol of active Cl) in DMF (2 mL) at 0 8C.
After 15 h, the suspension was filtered, washed with DMF (4 Â
10 mL) and CH2Cl2 (4 Â 10 mL) and concentrated under
vacuum to constant weight to afford the functionalized resin
7a (1% DVB, f 0.37); yield: 0.43 g (93%); 13C gel-phase NMR
(75.4 MHz, CDCl3): d 24.1 (CH2), 26.8 (CH2), 40.3 (CH), 43.8
(CH2), 54.4 (CH2), 71.4 (2 CH2), 77.4 (CH), 78.6 (C); anal.
calcd. for fmax: N 0.72; found: N 0.52.
Resin 7b (1% DVB, fmax: 0.98) from Chloromethylated
Polystyrene (1% DVB, f0: 1.49): Compound 2 (0.24 g,
0.62 mmol) in DMF (2 mL), sodium hydride (15 mg,
0.6 mmol) in DMF (2 mL) and the Merrifield resin (0.40 g,
0.56 mmol of active Cl) in DMF (2 mL) were treated as
described for 7a to afford a poorly functionalized resin; yield:
0.42 g (82%). The anchoring step was repeated for 45 min at
25 8C, starting from the partially functionalized resin (0.42 g,
f 0.51) in DMF (1.3 mL), compound 2 (0.17 g, 0.43 mmol) in
DMF (1.3 mmol) and sodium hydride (10 mg, 0.4 mmol) in
DMF (1.3 mL). After both anchoring steps resin 7b (1% DVB,
f 0.85) was obtained; yield: 0.43 g (72%); 13C gel-phase NMR:
the set of data was fully coincident with the one described
above; anal. calcd. for fmax: N 1.36; found: N, 1.19.
Resin 7c (2% DVB, fmax: 0.65) from Chloromethylated
Polystyrene (2% DVB, f0: 0.84): A solution of 2 (1.00 g,
2.6 mmol) in DMF (8 mL) was added to asuspension of sodium
hydride (62 mg, 2.6 mmol) in DMF (7 mL) at 08C under N2.
The mixture was stirred for 20 min and quickly poured into a
smoothly stirred suspension of the Merrifield resin (2.80 g,
2.35 mmol of active Cl) in DMF (9 mL) at room temperature.
After 2 h, the suspension was filtered, and treated as described
for 7a to afford the functionalized resin 7c (1% DVB, f 0.39);
yield: 2.80 g (85%); 13C gel-phase NMR: the set of data was fully
coincident with the one described above; anal. calcd. for fmax: N
0.90, found: N 0.54.
e 318 [(M NH4) , 100].
(S)-[4-(3,3-Diphenyloxiranyl)-phenyl]-methanol (3): Por-
tions of NaBH4 (3.69 g, 12.3 mmol) were slowly added to a
solution of (S)-6 in ethanol (95 mL). After 1 h at room
temperature, saturated aqueous NH4Cl solution was added
dropwise, and the resulting aqueous phase was extracted with
CH2Cl2 (3 Â 50 mL). The combined organic phases were
washed with water (3 Â 50 mL), dried and concentrated under
vacuum. The residual solid was purified by chromatography to
afford (S)-3 as a white solid; yield: 3.47 g (94%); [a]D23: 55.4 (c
1.02 in CHCl3); 1H NMR (200 MHz, CDCl3): d 1.62 (bs, 1H),
4.32 (s, 1H), 4.59 (s, 2H), 7.04 7.35 (m, 14H); 13C NMR
(50 MHz, CDCl3): d 64.9 (CH2), 67.9 (CH), 68.7 (C), 126.2
(CH), 126.3 (CH), 126.9 (CH), 127.5 (CH), 127.7 (CH), 127.8
(CH), 128.3 (CH), 129.1 (CH), 134.7 (C), 135.6 (C), 140.2 (C),
140.8 (C). IR (NaCl, film): n 3363, 3060, 3031, 2927 cmÀ1; MS
(CI, NH3): m/e 320 [(M NH4) , 100]; anal. calcd. for
C21H18O2: C 83.42, H 6.00; found: C 83.35, H 5.94.
(R)-2-(4-Hydroxymethylphenyl)-1,1-diphenyl-2-piperidin-
1-ylethanol (2): A mixture of (S)-3 (3.40 g, 11.2 mmol), LiClO4
(14.4 g, 0.13 mol) and piperidine (55 mL, 0.56 mol) was heated
at 80 8C under N2. After 48 h, the reaction mixture was cooled
to room temperature, CH2Cl2 (30 mL) was added, the organic
phase was washed with water (3 Â 200 mL), dried and con-
centrated under vacuum. The residual solid was purified by
chromatography to afford (R)-2 as a white solid; yield: 4.25 g
(98%); mp 125 1278C; [a]D23: À 127.6 (c 0.98 in CHCl3);
1H NMR (300 MHz, CDCl3): d 1.2 1.3 (m, 2H), 1.3 1.5 (m,
4H), 1.8 2.1 (m, 2H), 2.25 2.5 (m, 2H), 4.5 (s, 1H), 4.6 (s, 2H),
6.8 7.4 (m, 12H), 7.5 7.7 (m, 2H); 13C NMR (75.4 MHz,
CDCl3): d 24.1 (CH2), 26.8 (CH2), 54.4 (CH2), 65.0 (CH2),
77.3 (CH), 78.6 (C), 125.6 (CH), 125.7 (CH), 126.0 (CH), 126.2
(CH), 126.8 (CH), 127.2 (CH), 127.9 (CH), 131.4 (CH), 136.7
(C), 139.3 (C), 145.6 (C), 149.1 (C); IR (NaCl, film): n 3262,
2934, 2805, 1449, 746, 702 cmÀ1; MS (CI, NH3): m/e 387
Anchoring (R)-2-(4-Hydroxymethylphenyl)-1,1-
diphenyl-2-piperidin-1-ylethanol (2) to Barlos Resins
Resin 12a (fmax: 1.02) from Barlos Resin with Initial Substitu-
tion Level 1.60 mmol Cl/g: DIEA (0.17 mL, 1.0 mmol) was
added to a mixture of alcohol 2 (260 mg, 0.67 mmol) and the
resin (300 mg, 0.48 mmol of active Cl) in CH2Cl2 (3 mL), under
nitrogen, at room temperature. After smoothly stirring for
24 h, the resulting mixture was filtered, washed with DMF (2 Â
10 mL), DMF:water 1:1 (4 Â 10 mL), water (4 Â 10 mL), pH 9
bicarbonate buffer (4 Â 10 mL), water (8 Â 10 mL), MeOH
(4 Â 10 mL), toluene (4 Â 10 mL) and CH2Cl2 (4 Â 10 mL), and
concentrated under vacuum to constant weight to afford 12a
(f 0.93); yield: 0.36 g (80%); 13C gel-phase NMR (75.4 MHz,
CDCl3): d 24.0 (CH2), 26.6 (CH2), 40.4 (CH), 54.3 (CH2), 65.7
[(M H) , 100]; anal. calcd. for C26H29NO2: C 80.59, H 7.54, N
3.61; found: C 80.75, H 7.51, N 3.51.
Adv. Synth. Catal. 2003, 345, 1305 1313
asc.wiley-vch.de
¹ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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