K. Makino et al. / Tetrahedron: Asymmetry 19 (2008) 2816–2828
2825
hydrogen pressure (100 atm) for 48 h. The solvent was removed in
4.7.4. Benzyl (2S,3S)-2-benzoylamino-3-cyclopentyl-3-hydroxy-
propionate (2S,3S)-15c
vacuo to afford 14, which was used for the next step without any
purification. Benzoyl chloride (0.13 mL, 1.12 mmol) and triethyl-
amine (0.44 mL, 3.16 mmol) were added dropwise to a stirred solu-
tion of crude 14 in THF (2.0 mL) at 0 °C. After stirring the mixture
for 1 h at 23 °C, the reaction was quenched with water and the
resulting mixture was extracted with EtOAc/n-hexane (5/1). The
organic layer was washed with 1 M hydrochloric acid, water, satu-
rated aqueous sodium hydrogen carbonate, and brine, dried over
sodium sulfate, filtered, and concentrated in vacuo. The residue
was purified by silica gel column chromatography to give 15.
Prepared according to the general procedure using n-PrOH in-
stead of dichloromethane, and was purified by silica gel column
chromatography (n-hexane/EtOAc = 2/1) to give 15c (310 mg,
85%, 96% de, 95% ee) as a white powder: ½a D24
¼ þ20:5 (c 1.00,
ꢃ
CHCl3); mp 109–111 °C; IR (KBr) 3414, 3342, 2938, 2867, 1746,
1644, 1521, 1488, 1195 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.38–
;
1.88 (m, 9H), 2.95 (d, J = 8.0 Hz, 1H), 3.78 (dt, J = 2.8, 8.8 Hz, 1H),
4.92 (dd, J = 2.8, 7.2 Hz, 1H), 5.21 (d, J = 12.4 Hz, 1H), 5.31 (d,
J = 12.4 Hz, 1H), 7.19 (d, J = 6.4 Hz, 1H), 7.34–7.39 (m, 5H), 7.43–
7.47 (m, 2H, 7.51–7.56 (m, 1H), 7.81–7.84 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 25.1, 25.5, 29.0, 29.8, 43.5, 57.3, 67.5, 78.0,
127.2, 128.4, 128.6, 132.0, 133.4, 135.0, 167.6, 170.5; HRMS (FAB,
NBA) calcd for C22H26NO4 368.1862 (M+H+), found 368.1870. Anal.
Calcd for C22H25NO4: C, 71.91; H, 6.86; N, 3.76. Found: C, 71.71; H,
6.74; N, 3.76. HPLC analysis: CHIRALPAK AD, (n-hexane/i-
PrOH = 90/10, 1.0 mL/min), tR = 23.5 min ((2R,3R)-isomer, minor)
and 28.4 min ((2S,3S)-isomer, major).
4.7.1. Methyl (2S,3S)-2-benzoylamino-3-hydroxy-4-methyl-
pentanoate (2S,3S)-8a
Prepared according to the general procedure, and was purified
by silica gel column chromatography (n-hexane/EtOAc = 2/1) to
give 8a (103 mg, 38%, 98% de, 95% ee) as
¼ þ35:4 (c 0.99, CHCl3); IR (neat) 3417, 2962, 1747, 1633,
1538, 1455, 1372, 1062, 1011 cmꢀ1 1H NMR (400 MHz, CDCl3) d
a colorless oil:
½ ꢃ
a 2D5
;
1.02 (d, J = 6.8 Hz, 3H), 1.05 (d, J = 6.6 Hz, 3H), 1.77 (sep,
J = 6.6 Hz, 1H), 2.91 (d, J = 8.2 Hz, 1H), 3.62 (dt, J = 3.3, 8.6 Hz,
1H), 3.82 (s, 3H), 4.97 (dd, J = 3.3, 7.3 Hz, 1H), 7.14 (d, J = 6.6 Hz,
1H), 7.44–7.48 (m, 2H), 7.52–7.56 (m, 1H), 7.82–7.85 (m, 2H);
HRMS (FAB, NBA) calcd for C14H20NO4 266.1392 (M+H+), found
266.1408. HPLC analysis: CHIRALCEL OD-H, (n-hexane/i-
PrOH = 85/15, 0.5 mL/min), tR = 10.6 min ((2R,3R)-isomer, minor)
and 15.6 min ((2S,3S)-isomer, major).
4.7.5. Benzyl (2S,3S)-2-benzoylamino-3-cyclohexyl-3-hydroxy-
propionate (2S,3S)-15d
Prepared according to the general procedure, and was purified
by silica gel column chromatography (n-hexane/EtOAc = 3/1) to
give 15d (325 mg, 85%, >99% de, 97% ee) as a white powder, which
was recrystallized from n-hexane–EtOAc to give an analytical sam-
ple: ½a 2D5
ꢃ
¼ þ14:8 (c 1.1, CHCl3); mp 125–127 °C; IR (KBr) 3403,
2929, 2849, 1742, 1647, 1521, 1483, 1211 cmꢀ1
;
1H NMR
4.7.2. Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-4-methyl-
pentanoate (2S,3S)-8d
(400 MHz, CDCl3) d 0.95–1.78 (m, 10 H), 1.99 (m, 1H), 2.78 (d,
J = 8.8 Hz, 1H), 3.66 (dt, J = 3.2, 8.8 Hz, 1H), 4.99 (dd, J = 2.9,
7.3 Hz, 1H), 5.18 (d, J = 12.2 Hz, 1H), 5.34 (d, J = 12.2 Hz, 1H), 7.17
(d, J = 6.8 Hz, 1H), 7.32–7.56 (m, 8H), 7.81–7.83 (m, 2H); 13C
NMR (100 MHz, CDCl3) d 25.6, 26.1, 29.0, 29.2, 40.9, 55.7, 67.5,
77.9, 127.2, 128.5, 128.6, 131.9, 133.5, 135.0, 167.4, 170.8; HRMS
(FAB, NBA) calcd for C23H28NO4 382.2018 (M+H+), found
382.1993. Anal Calcd for C23H27NO4: C, 72.42; H, 7.13; N, 3.67.
Found: C, 72.15; H, 7.16; N, 3.64. HPLC analysis for the crude sam-
ple: CHIRALPAK AD, (n-hexane/i-PrOH = 90/10, 1.0 mL/min),
tR = 23.5 min ((2R,3R)-isomer, minor) and 28.4 min ((2S,3S)-iso-
mer, major).
Prepared according to the general procedure, and was purified
by silica gel column chromatography (n-hexane/EtOAc = 2/1) to
give 8d (286 mg, 84%, >99% de, 98% ee) as a white powder:
½
a 2D4
ꢃ
¼ þ33:9 (c 1.00, CHCl3); mp 95.5–96 °C; IR (KBr) 3414,
2961, 2935, 2858, 1749, 1647, 1519, 1192, 1064 cmꢀ1 1H NMR
;
(400 MHz, CDCl3) d 0.95 (d, J = 6.6 Hz, 3H), 1.13 (d, J = 6.6 Hz, 3H),
1.71 (m, 1H), 2.92 (d, J = 8.4 Hz, 1H), 3.63 (dt, J = 3.1, 8.4 Hz, 1H),
4.99 (dd, J = 3.3, 7.3 Hz, 1H), 5.23 (d, J = 12 Hz, 1H), 5.29 (d,
J = 12 Hz, 1H), 7.14 (d, J = 7.3 Hz, 1H), 7.34–7.39 (m, 5H), 7.43–
7.47 (m, 2H), 7.52–7.56 (m, 1H), 7.81–7.83 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 18.9, 19.0, 31.5, 56.2, 67.6, 78.9, 127.2, 128.4,
128.6, 128.7, 132.0, 133.4, 134.9, 167.5, 170.8; HRMS (FAB, NBA)
calcd for C20H24NO4 342.1705 (M+H+), found 342.1682. Anal. Calcd
for C20H23NO4: C, 70.36; H, 6.79; N, 4.10. Found: C, 70.26; H, 6.82;
N, 4.06. HPLC analysis: CHIRALCEL OD-H, (n-hexane/i-PrOH = 90/
10, 0.5 mL/min), tR = 21.6 min ((2R,3R)-isomer, minor) and
30.3 min ((2S,3S)-isomer, major).
4.7.6. Benzyl (2S,3S)-2-benzoylamino-3-cycloheptyl-3-hydroxy-
propionate (2S,3S)-15e
Prepared according to the general procedure using n-PrOH in-
stead of dichloromethane, and was purified by silica gel column
chromatography (n-hexane/EtOAc = 2/1) to give 15e (341 mg,
86%, 94% de, 97% ee) as a white powder: ½a D25
¼ þ12:9 (c 1.00,
ꢃ
CHCl3); IR (KBr) 3418, 3064, 3033, 2925, 2854, 1734, 1646, 1539,
4.7.3. Benzyl (2S,3S)-2-benzoylamino-3-cyclobutyl-3-hydroxy-
propionate (2S,3S)-15b
1190, 1082 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.24–1.64 (m,
;
11H), 1.76–1.89 (m, 2H), 2.79 (m, 1H), 3.70 (dt, J = 3.2, 8.8 Hz,
1H), 5.01 (dd, J = 3.2, 7.2 Hz, 1H), 5.18 (d, J = 12.0 Hz, 1H), 5.32 (d,
J = 12.0 Hz, 1H), 7.13 (d, J = 7.0 Hz, 1H), 7.32–7.40 (m, 5H), 7.42–
7.46 (m, 2H), 7.51–7.55 (m, 1H), 7.80–7.82 (m, 2H); 13C NMR
(100 MHz, CDCl3) d 26.1, 26.2, 28.2, 28.9, 30.6, 42.3, 55.8, 67.5,
77.6, 127.2, 128.5, 128.6, 131.9, 133.5, 135.0, 167.4, 170.9; HRMS
(FAB, NBA) calcd for C24H30NO4 396.2175 (M+H+), found:
396.2195. Anal. Calcd for C24H29NO4: C, 72.89; H, 7.39; N, 3.54.
Found: C, 72.83; H, 7.34; N, 3.53. HPLC analysis: CHIRALCEL OD-
H, (n-hexane/i-PrOH = 90/10, 0.5 mL/min), tR = 30.5 min ((2R,3R)-
isomer, minor) and 34.7 min ((2S,3S)-isomer, major).
Prepared according to the general procedure using n-PrOH in-
stead of dichloromethane, and was purified by silica gel column
chromatography (n-hexane/EtOAc = 2/1) to give 15b (92%, anti/
syn = 82/18, 81% ee (anti)) as a white powder, which was recrystal-
lized from EtOAc–n-hexane to give pure 15b: mp 94–95 °C;
½
a 2D3
ꢃ
¼ þ22:3 (c 1.00, CHCl3); IR (KBr) 3407, 1745, 1727, 1639,
1527, 1195 cmꢀ1 1H NMR (400 MHz, CDCl3) d 1.6–2.1 (m, 6H),
;
2.3–2.5 (m, 1H), 3.15–3.35 (br s, 1H), 4.00 (dd, J = 2.8, 8.0 Hz,
1H), 4.87 (dd, J = 2.8, 6.8 Hz, 1H), 7.1–7.2 (br d, 1H), 7.3–7.6 (m,
8H), 7.82 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) d 18.3,
24.6, 25.0, 37.9, 56.6, 67.6, 77.2, 127.2, 128.1, 128.4, 128.5, 128.6,
128.6, 128.7, 132.0, 133.3, 134.8, 167.9, 170.3. Anal. Calcd for
C21H23NO4: C, 71.37; H, 6.56; N, 3.96. Found: C, 71.23; H, 6.50;
N, 3.91. HPLC analysis: CHIRALPAK OD-H, (n-hexane/i-PrOH = 90/
10, 0.5 mL/min), tR = 26.1 min ((2R,3R)-isomer, minor) and
32.0 min ((2S,3S)-isomer, major).
4.7.7. Benzyl (2S,3S)-2-benzoylamino-3-hydroxy-pentanoate
(2S,3S)-15f
Prepared according to the general procedure using (R)-MeO-
BIPHEP at 23 °C instead of (S)-BINAP at 50 °C, and was purified
by silica gel column chromatography (n-hexane/EtOAc = 2/1) to