Modular Amino Alcohol Ligands
(2S,3S)-3-(1-Adam an tyl)-2-ben zyloxym eth yloxir an e, 6c.
The same procedure described above for 5b was followed using
the following amounts of reagents: epoxy alcohol 6a (160 mg,
0.768 mmol), NaH (50 mg, ca. 0.998 mmol), and benzyl bromide
(165 µL, 1.152 mmol) in anhydrous DMF (2 mL). After the
usual workup and purification by column chromatography, 211
mg (92% yield) of 6c was isolated as an oil: [R]D -10.4 (c 1.47,
pyrrolidine (1.9 mL, 22.70 mmol) in dry acetonitrile (15 mL).
After 4 days at reflux, the reaction was quenched and treated
as described for 11a to give 11e in quantitative yield: [R]D
+5.0 (c 1.16, CHCl3); 1H NMR (200 MHz, CDCl3) δ 0.95 (s,
9H), 1.92 (m, 4H), 3.10 (m, 2H), 3.42 (m, 2H), 3.66 (s, 1H),
3.70-3.90 (m, 2H), 4.52 (s, 2H), 7.33 (m, 5H); 13C NMR (50
MHz, CDCl3) δ 23.1 (CH2), 26.2 (CH3), 35.2 (C), 45.5 (CH2),
47.3 (CH2), 51.4 (CH2), 64.2 (CH), 68.0 (CH2), 73.7 (CH2), 77.5
(CH), 127.9 (CH), 128.0 (CH), 128.4 (CH), 137.1 (C); IR (film)
3429, 2956, 1625, 1455, 1098 cm-1; MS (CI, NH3) m/z 292
(C18H29NO2‚H+, 100); HRMS (CI) calcd for C18H29NO2‚H+
292.2276, found 292.2280.
1
CH2Cl2); H NMR (300 MHz, CDCl3) δ 1.53 (m, 6H), 1.67 (m,
6H), 1.97 (m, 3H), 2.47 (d, J ) 2 Hz, 1H), 3.13 (m, 1H), 3.42
(dxd, J ) 13 Hz, J ′ ) 6 Hz, 1H), 3.70 (dxd, J ) 13 Hz, J ′ ) 3
Hz, 1H), 4.56 (m, 2H), 7.32 (m, 5H); 13C NMR (75 MHz, CDCl3)
δ 27.9 (CH), 32.1 (C), 36.8 (CH2), 38.5 (CH2), 52.5 (CH), 64.0
(CH), 70.9 (CH2), 73.0 (CH2), 127.5 (CH), 127.6 (CH), 128.2
(CH) 137.9 (C); IR (film) 3050, 2906, 2850, 1453, 1100, 893,
(1S,2R)-1-ter t-Bu tyl-2-p ip er id in o-3-tr ip h en ylm eth oxy-
1-p r op a n ol, 11d . The same procedure described above for 5d
was followed, using the following amounts of reagents: 11a
(520 mg, 2.41 mmol) and N-triphenylmethylpyridinium tet-
rafluoroborate (1.43 g, 3.48 mmol) in dry acetonitrile (10 mL).
After column chromatography, 635 mg (60% yield) of 11d was
obtained: [R]D -56.4 (c 1.96, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 0.73 (s, 9H), 1.32 (m, 2H), 1.45 (m, 4H), 2.05 (m, 2H),
2.34 (m, 4H), 3.48 (m, 1H), 3.63 (d, J ) 5 Hz, 1H), 7.10-7.60
(m, 15H); 13C NMR (75 MHz, CDCl3) δ 23.9 (CH2), 25.9 (CH2),
26.7 (CH3), 35.4 (C), 54.9 (CH2), 61.0 (CH2), 69.8 (CH), 84.2
(CH), 87.2 (C), 126.9 (CH), 127.5 (CH), 129.2 (CH), 144.9 (C);
735 cm-1; MS (CI, NH3) m/z 316 (C20H26O2 + 18, 100), 299
+
(C20H26O2‚H+, 7).
(1S,2R)-1-ter t-Bu tyl-2-p ip er id in o-1,3-p r op a n d iol, 11a .
Piperidine (7.6 mL, 76.8 mmol) was added via syringe into a
mixture of 5a (1.0 g, 7.68 mmol) and LiClO4 (12 g, 115.2 mmol)
in acetonitrile (20 mL) under N2. The resulting mixture was
heated at reflux. After 24 h, the solution was cooled to room
temperature, and water (40 mL) was added. The solution was
extracted with CH2Cl2 (3 × 30), and the combined organic
phases were dried (MgSO4) and concentrated in vacuo. The
residual crude was purified by column chromatography using
hexane/EtOAc as the eluent to give 1.42 g (86% yield) of 11a
as a dense oil: [R]D +18.0 (c 1.18, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 0.98 (s, 9H), 1.57 (m, 6H), 2.51 (m, 6H), 3.44 (d, J )
5 Hz, 1H), 3.79 (m, 1H); 13C NMR (50 MHz, CDCl3) δ 24.1
(CH2), 26.0 (CH3), 26.7 (CH2), 34.2 (C), 54.7 (CH2), 61.0 (CH2),
66.3 (CH), 81.5 (CH); IR (film) 3408, 2939, 1443, 1391, 1279,
1119, 897 cm-1; MS (EI) m/z 128 (C5H10NC+HCH2OH, 29), 98
(C5H10NC+H2, 100); HRMS (CI) calcd for C12H25NO2‚H+
216.1963, found 216.1963.
(1S ,2R )-1-t er t -Bu t yl-3-m e t h oxy-2-p ip e r id in o-1-p r o-
p a n ol, 11b. The same procedure described above for 11a was
followed, except that the reaction was carried out in a selaed
tube, using the following amounts of reagents: epoxy ether
5b (700 mg, 4.85 mmol), LiClO4 (8.9 g, 83.2 mmol), and
piperidine (5.5 mL, 55.5 mmol) in acetonitrile (20 mL). After
5 days at reflux, the reaction was quenched and treated as
described for 11a to give 625 mg (56% yield) of 11b: [R]D -23.8
(c 1.10, CHCl3); 1H NMR (200 MHz, CDCl3) δ 0.94 (s, 9H), 1.49
(m, 6H), 2.45 (m, 2H), 2.65 (m, 3H), 3.33 (s, 3H), 3.47 (m, 1H),
3.64 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 24.7 (CH2), 26.2
(CH3), 26.5 (CH2), 35.4 (C), 50.8 (CH2), 58.8 (CH3), 64.4 (CH),
70.7 (CH2), 78.7 (CH); IR (film) 3487, 2933, 2805, 1457, 1364,
1106 cm-1; EM (EI) m/z 184 (tBuCHOHC+HNC5H10, 27), 142
(C5H10NC+HCH2OCH3, 100); HRMS (CI) calcd for C13H27NO2‚
H+ 230.2120, found 230.2107.
IR (film) 3460, 3090, 2939, 1490, 1450,1219, 1115, 1048 cm-1
;
MS (FAB+) m/z 458.3 (C31H39NO2‚H+, 14), 242.9 (C+Ph3, 100);
HRMS (CI) calcd for C31H39NO2‚H+ 458.3059, found 458.3052.
(1S,2R)-1-ter t-Bu tyl-3-ter t-bu tyld ip h en ylsilyloxy-2-p i-
p er id in o-1-p r op a n ol, 11f. A solution of 11a (500 mg, 2.32
mmol), tert-butyldiphenylsilyl chloride (700 mg, 2.55 mmol),
and imidazole (348 mg, 5.10 mmol) in anhydrous DMF (30 mL)
was heated at 65 °C for 24 h under N2. The reaction mixture
was cooled to room temperatue, and Et2O (20 mL) and brine
(20 mL) were added. The aqueous layer was extracted with
ether (2 × 20 mL). The combined organic extracts were dried
(MgSO4) and concentrated in vacuo. The residual oil was
purified by flash chromatography, affording 860 mg (82% yield)
of 11f as a dense oil: [R]D -37.2 (c 4.00, CHCl3); 1H NMR (200
MHz, CDCl3) δ 0.85 (s, 9H), 1.03 (s, 9H), 1.28 (m, 2H), 1.40
(m, 4H), 2.13 (m, 2H), 2.28 (m, 2H), 2.41 (dxd, J ) 13 Hz, J ′
) 3 Hz, 1H), 2.62 (dxd, J ) 13 Hz, J ′ ) 7 Hz, 1H), 3.43 (d, J
) 5 Hz, 1H), 3.78 (m, 1H), 7.30-7.80 (m, 10H); 13C NMR (75
MHz, CDCl3) δ 19.3 (C), 23.9 (CH2), 25.8 (CH2), 26.6 (CH3),
27.0 (CH3), 34.9 (C), 55.0 (CH2), 63.8 (CH2), 69.7 (CH), 85.2
(CH), 127.4 (CH), 127.6 (CH), 129.5 (CH), 129.7 (CH), 133.5
(CH), 134.3 (C), 135.8 (CH), 135.9 (CH); IR (film) 3107, 3072,
2936, 1474, 1428, 1113 cm-1; MS (CI, NH3) m/z 455 (C28H43
-
NO2Si‚H+ + 1, 35), 454 (C28H43NO2Si‚H+, 100); HRMS (CI)
calcd for C28H43NO2Si‚H+ 454.3141, found 454.3140.
(1S ,2R )-1-(1-Ad a m a n t y l)-2-p ip e r id in o -1,3-p r o p a n -
d iol, 12a . The same procedure described above for 11a was
followed, using the following amounts of reagents: 6a (200
mg, 0.96 mmol), piperidine (1.1 mL, 10.4 mmol), and LiClO4
(1.7 g, 14.4 mmol) in dry acetonitrile (3 mL). After 24 h at
reflux, the reaction was quenched and treated as described
for 11a to give 278 mg (98% yield) of 12a as a dense oil: [R]D
+16.4 (c 0.98, CH2Cl2); 1H NMR (300 MHz, CDCl3) δ 1.45-
1.68 (m, 18H), 1.97 (m, 3H), 2.75 (m, 4H), 3.10 (b s, 2H), 3.29
(d, J ) 5 Hz, 1H), 3.37 (m, 1H), 3.50 (m, 1H), 3.93 (m, 1H);
13C NMR (75 MHz, CDCl3) δ 23.5 (CH2), 25.2 (CH2), 28.3 (CH),
36.2 (C), 37.1 (CH2), 38.6 (CH2), 54.7 (CH2), 60.9 (CH2), 65.4
(CH), 82.2 (CH); IR (film) 3481, 2904, 2850, 1453, 1098, 623
cm-1; MS (EI) m/z 98 (C5H10NC+H2, 100); HRMS (CI) calcd
for C18H31NO2 - H2O 275.2249, found 275.2259.
(1S,2R)-1-(1-Adam an tyl)-3-m eth oxy-2-piper idin o-1-pr o-
p a n ol, 12b. The same procedure described above for 11a was
followed, using the following amounts of reagents: 6b (160
mg, 0.72 mmol), piperidine (1 mL, 10.1 mmol), and LiClO4 (770
mg, 7.20 mmol) in dry acetonitrile (4 mL). After 4 days at
reflux, the reaction was quenched and treated as described
for 11a to give 170 mg (77% yield) of 12b: [R]D -5.5 (c 1.40,
CHCl3); 1H NMR (200 MHz, CDCl3) δ 1.40-1.68 (m, 18H), 1.98
(1S,2R)-3-Ben zyloxy-1-ter t-b u t yl-2-p ip er id in o-1-p r o-
p a n ol, 11c. The same procedure described above for 11a was
followed, using the following amounts of reagents: epoxy ether
5c (600 mg, 2.72 mmol), LiClO4 (4.3 g, 40.8 mmol), and
piperidine (2.7 mL, 27.2 mmol) in dry acetonitrile (10 mL).
After 4 days at reflux, the reaction was quenched and treated
as described for 11a to give 705 mg (85% yield) of 11c as a
dense oil: [R]D -15.4 (c 1.25, CHCl3); 1H NMR (200 MHz,
CDCl3) δ 0.94 (s, 9H), 1.48 (m, 6H), 2.42 (m, 2H), 2.68 (m, 2H),
2.86 (d, J ) 9 Hz, 1H), 3.45 (m, 1H), 3.73 (d, J ) 6 Hz, 2H),
4.51 (s, 2H), 7.33 (m, 5H); 13C NMR (50 MHz, CDCl3) δ 24.8
(CH2), 26.2 (CH3), 26.7 (CH2), 35.5 (C), 50.8 (CH2), 64.5 (CH),
68.2 (CH2), 73.3 (CH2), 78.9 (CH), 127.5 (CH), 127.6 (CH), 128.3
(CH), 137.8 (C); IR (film) 3494, 2934, 1455, 1362, 1090, 1003,
735 cm-1; MS (EI) m/z 306 (C19H31NO2‚H+, 1), 218 (C5H10NC+-
HCH2OCH2Ph, 58), 184 (tBuCHOHC+HNC5H10
, 24), 91
(PhCH2+, 100); HRMS (CI) calcd for C19H31NO2‚H+ 306.2433,
found 306.2418.
(1S,2R)-3-Ben zyloxy-1-ter t-b u t yl-2-p yr r olid in o-1-p r o-
p a n ol, 11e. The same procedure described above for 11a was
followed, using the following amounts of reagents: epoxy ether
5c (500 mg, 2.27 mmol), LiClO4 (3.6 g, 34.05 mmol), and
J . Org. Chem, Vol. 68, No. 8, 2003 3137