Synthesis of Enantiomerically Pure 2-Acyl Aziridines
Anal. Calcd for C17H16ClNO: C, 71.45; H, 5.64; N, 4.90.
Found: C, 71.48; H, 5.53; N, 4.80.
(d, J ) 6.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 144.4, 138.0,
129.4, 128.4, 128.3, 127.2, 126.6, 126.3, 69.6, 69.2, 41.4, 41.2,
29.7, 23.2; HRMS(EI) calcd for C18H21NO 267.1623, found
267.1623. Anal. Calcd for C26H41NO: C, 81.41; H, 10.77; N,
Rep r esen ta tive Exa m p le of th e Ster eoselective Re-
d u ction to 1,2-er yth r o-Am in o Alcoh ols. P r ep a r a tion of
4a -er yth r o. To the solution of 3a (74 mg, 0.39 mmol) in 2.0
mL of MeOH at -78 °C was added ZnCl2 (80.0 mg, 0.59 mmol).
The solution was stirred for 30 min, and NaBH4 (29.6 mg, 0.78
mmol) was added at -78 °C. The mixture was stirred for 30
min, and 2.0 mL of water was added. The organic layer was
separated. The aqueous layer was extracted with CH2Cl2 (4
mL × 5), and the combined organic extracts were dried,
filtered, and concentrated in vacuo. Purification by silica gel
flash chromatography (EtOAc/n-hexane, 3:7) provided 4a as
3.65. Found: C, 81.38; H, 10.99; N, 3.66.
1
4i: [R]26 ) +58.7 (c 0.95, CHCl3); mp 88-90 °C; H NMR
D
(200 MHz, CDCl3) δ 7.31-7.26 (m, 10H), 4.66 (d, J ) 3.2 Hz,
1H), 2.67 (q, J ) 6.5 Hz, 1H), 2.12 (d, J ) 3.4 Hz, 1H), 1.84(m,
1H), 1.43 (d, J ) 6.5 Hz,3H), 1.41 (d, J ) 6.2 Hz, 1H); 13C
NMR (50.3 MHz, CDCl3) δ 144.4, 141.8, 128.5, 128.3, 128.0,
127.8, 127.5, 127.2, 126.6, 126.1, 70.1, 69.1, 43.0, 29.4, 23.3.
Anal. Calcd for C17H19NO: C, 80.60; H, 7.56; N, 5.53. Found:
C, 80.42; H, 7.80; N, 5.56.
a white solid (73 mg, 97%): [R]24 ) +38.1 (c 0.81, CHCl3);
4j: [R]29D ) +6.2 (c 0.10, CHCl3); 1H NMR (500 MHz, CDCl3)
δ 7.26-7.32 (m, 5H), 7.18 (d, J ) 8.3 Hz, 2H), 6.81 (d, J ) 8.8
Hz, 2H), 4.61 (d, J ) 2.9 Hz, 1H), 3.78 (s, 3H), 2.65 (q, J ) 6.4
Hz, 1H), 2.14 (d, J ) 3.9 Hz, 1H), 1.79 (m, 1H), 1.59 (m, 1H),
1.43 (d, J ) 6.4 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 159.1,
144.3, 133.7, 128.4, 127.4, 127.3, 127.1, 126.5, 113.7, 69.7, 69.0,
55.2, 42.9, 29.4, 23.3. Anal. Calcd for C18H21NO2: C, 76.29; H,
7.47; N, 4.94. Found: C, 76.10; H, 7.37; N, 4.96.
D
mp 64-66 °C; 1H NMR (200 MHz, CDCl3) δ 7.33-7.22 (m, 5H),
3.69 (m, 1H), 2.59 (q, J ) 6.6 Hz, 1H), 1.95 (d, J ) 3.4 Hz,
1H), 1.55 (m, 1H), 1.42 (d, J ) 6.6 Hz, 3H), 1,39 (d, J ) 6.9
Hz, 1H), 1.00 (d, J ) 6.2 Hz, 3H); 13C NMR (75.4 MHz, CDCl3)
δ 144.7, 128.5, 127.3, 126.7, 69.2, 64.5, 42.7, 29.1, 22.9, 19.6.
Anal. Calcd for C12H17NO: C, 75.35; H, 8.96; N, 7.32. Found:
C, 75.17; H, 8.67; N, 7.03.
4b: [R]25D ) +61.1 (c 1.00, CHCl3); mp 105-106 °C; 1H NMR
(300 MHz, CDCl3) δ 7.31 (m, 5H), 3.31 (dd, J ) 3.02, 3.30 Hz,
1H), 2.68 (bs, OH), 2.62 (q, J ) 6.59 Hz, 1H), 1.97 (d, J ) 3.57
Hz, 1H), 1.62 (m, 1H), 1.56 (m, 2H), 1.42 (d, J ) 6.59 Hz, 3H),
0.85 (d, J ) 6.87 Hz, 6H); 13C NMR (75.0 MHz, CDCl3) δ
144.47, 128.38, 127.06, 126.48, 72.26, 69.17, 39.95, 32.37,
29.29, 23.37, 18.25, 17.92. Anal. Calcd for C14H21NO: C, 76.67;
H, 9.65; N, 6.39. Found: C, 76.65; H, 9.66; N, 6.38.
4k : [R]23 ) +60.0 (c 0.23, CHCl3); mp 98-100 °C; 1H NMR
D
(200 MHz, CDCl3) δ 7.45-7.00 (m, 9H), 4.60 (d, J ) 3.6 Hz,
1H), 2.66 (q, J ) 6.6 Hz, 1H), 2.07 (d, J ) 3.6 Hz, 1H), 1.79
(m, 1H), 1.44 (d, J ) 6.6 Hz, 1H), 1.44 (d, J ) 6.6 Hz, 3H); 13
C
NMR (75.4 MHz, CDCl3) δ 144.3, 140.3, 133.4, 128.6, 128.5,
127.5, 127.3, 126.6, 69.5, 69.0, 42.5, 29.2, 23.0. Anal. Calcd
for C17H18ClNO: C, 70.95; H, 6.30; N, 4.87. Found: C, 70.89;
H, 6.30; N, 4.73.
4c: [R]27 ) +25.0 (c 0.50, CHCl3); 1H NMR (200 MHz,
D
P r ep a r a tion of 4g-th r eo. To the solution of 3g (139 mg,
0.36 mmol) in 2.0 mL of THF under nitrogen at -78 °C was
added L-Selectride (1.0 M, 0.72 mL, 0.72 mmol) in THF. The
mixture was stirred for 30 min at -70 °C and warmed to room
temperature. The reaction mixture was treated with 10%
aqueous NaOH solution, and the organic layer was separated.
The aqueous layer was extracted with CH2Cl2 (4 mL × 5), and
the combined organic extracts were dried, filtered, and con-
centrated in vacuo. Purification by silica gel flash chromatog-
raphy (EtOAc/n-hexane, 3:7) provided 4g-th r eo as a white
CDCl3) δ 7.41-7.20 (m, 5H), 3.55 (m, 1H), 2.58 (q, J ) 6.5 Hz,
1H), 2.45 (s, 1H), 1.95 (d, J ) 3.5 Hz, 1H), 1.57 (duint, J ) 3.5
Hz, 1H), 1.42 (d, J ) 6.6 Hz, 3H), 1.40 (m, 2H), 1.30 (m, 5H),
0.85(m, 3H); 13C NMR (50.3 MHz, CDCl3) δ 144.8, 128.4, 127.1,
126.9, 69.4, 68.5, 42.0, 34.4, 29.4, 27.4, 23.1, 22.8, 13.9. Anal.
Calcd for C15H23NO: C, 77.21; H, 9.93; N, 6.00. Found: C,
77.28; H, 10.16; N, 6.21.
4d : [R]24D ) +0.2 (c 0.50, CHCl3); 1H NMR (200 MHz, CDCl3)
δ 7.33-7.22 (m, 5H), 3.31 (d, J ) 2.2 Hz, 1H), 2.64 (q, J ) 6.5
Hz, 1H), 2.03 (d, J ) 3.6 Hz, 1H), 1.59 (m, 1H), 1.43 (d, J )
6.3, Hz, 1H), 1.41 (d, J ) 6.5 Hz, 3H), 0.86 (s, 9H); 13C NMR
(75.4 MHz, CDCl3) δ 144.8, 128.5, 127.1, 126.6, 74.0, 69.0, 38.1,
34.2, 29.3, 25.6, 23.3. Anal. Calcd for C15H23NO: C, 77.21;
solid (118 mg, 84%): [R]24 ) +38.2 (c 1.0, CHCl3); mp 31.5-
D
32.9 °C; 1H NMR (500 MHz, CDCl3) δ 7.35-7.25 (m, 5H), 3.15
(m, 1H), 2.46 (q, J ) 6.50 Hz, 1H), 1.89 (d, J ) 3.00 Hz, 1H),
1.66 (d, J ) 5.00, 1H), 1.50 (m, 3H), 1.44 (d, J ) 6.50 Hz, 1H),
1.30-1.13 (m, 26H), 0.88 (t, J ) 7.00 Hz, 3H); 13C NMR (125
MHz, CDCl3) δ 144.54, 128.62, 127.52, 126.89, 71.48, 69.73,
42.89, 35.40, 31.91, 31.76, 29.68, 29.65, 29.63, 29.57, 29.53,
29.46, 29.35, 25.36, 22.68, 22.51, 14.11; HRMS(EI) calcd for
H,9.93; N, 6.00. Found: C, 77.24; H, 9.73; N, 5.94.
1
4e: [R]24 ) +35.9 (c 1.00, CHCl3); mp 51-53 °C; H NMR
D
(500 MHz, CDCl3) δ 7.34-7.23 (m, 5H), 5.71 (m, 1H), 5.01 (m,
1H), 4.99 (m, 1H), 3.54 (m, 1H), 2.57 (q, J ) 6.6 Hz, 1H), 2.06
(m, 2H), 1.97 (m, 1H), 1.59 (m, 1H), 1.42 (m, 4H); 13C NMR
(75.4 MHz, CDCl3) δ 144.4, 134.3, 128.4, 127.2, 126.6, 117.4,
69.3, 68.2, 41.4, 39.2, 29.9, 23.1. Anal. Calcd for C14H19NO:
C, 77.38; H, 7.36; N, 6.45. Found: C, 77.38; H, 7.47; N, 6.41.
C
26H45NO 387.3501, found 387.3528.
P r ep a r a tion of 2(S)-[1(R)-P h en yleth yla m in o]octa d e-
ca n e-1,3-d iol 6 a n d 7. To the solution of 4g-th r eo (227 mg,
0.590 mmol) in 2.90 mL of methylene chloride was added 0.17
mL (2.93 mmol) of acetic acid. The mixture was stirred for 14
h and then quenched by 1 mL of saturated NaHCO3 solution.
The organic layer was separated, and the aqueous layer was
extracted with methylene chloride (4 mL × 3). The combined
organic extracts were dried over anhydrous MgSO4, filtered,
and concentrated, and 2.90 mL of EtOH was added. To the
solution was added KOH (67 mg, 1.18 mmol), and the reaction
mixture was stirred at room temperature for 3 h. The mixture
was concentrated in vacuo and then was treated with 1.0 mL
of water and 1.0 mL of methylene chloride. The organic layer
was separated, and the aqueous layer was extracted with
methylene chloride (3 mL × 4). The combined organic extracts
were washed with 1.0 mL of brine, dried over anhydrous
MgSO4, filtered, and concentrated in vacuo. Short silica gel
4f: [R]25 ) +37.0 (c 1.00, CHCl3); 1H NMR (500 MHz,
D
CDCl3) δ 7.32 (m, 5H), 4.30 (t, J ) 1,71 Hz, 1H), 2.62 (q, J )
6.4 Hz, 1H), 2.54 (brs, 1H), 2.12 (m, 3H), 1.82 (m, 1H), 1.50
(d, J ) 6.4 Hz, 1H), 1.43 (d, J ) 6.8 Hz, 3H), 1.20-1.34 (m,
22H), 0.89 (t, J ) 7.1 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
144.2, 128.4, 127.2, 126.6, 86.0, 78.3, 69.1, 60.3, 41.8, 31.9, 30.2,
29.7, 29.7, 29.6, 29.6, 29.5, 29.3, 29.1, 28.8, 28.5, 23.1, 22.7,
18.7, 14.1. Anal. Calcd for C26H41NO: C, 81.41; H, 10.77; N,
3.65. Found: C, 81.38; H, 10.99; N, 3.66.
1
4g: [R]24 ) +19.04 (c 1.00, CHCl3); mp 49.8-51.0 °C; H
D
NMR (500 MHz, CDCl3) δ 7.38-7.23 (m, 5H), 3.53 (m, 1H),
2.59 (q, J ) 6.50 Hz, 1H), 2.46 (br, 1H), 1.95 (d, J ) 3.50 Hz,
1H), 1.57 (m, 1H), 1.42 (d, J ) 6.50, 3H), 1.38 (d, J ) 6.00,
Hz, 1H), 1.37-1.19 (m, 28H), 0.88 (t, J ) 7.00 Hz, 3H); 13C
NMR (125 MHz, CDCl3) δ 144.48, 128.38, 127.09, 126.57,
69.26, 68.33, 41.85, 34.64, 31.91, 29.72, 29.68, 29.65, 29.64,
29.56, 29.50, 29.39, 29.34, 25.21, 23.20, 22.67, 14.05; HRMS-
(EI) calcd for C26H45NO 387.3501, found 387.3501.
chromatography provided 235 mg (98%) of 6 as a white solid.
1
6: [R]24 ) +30.0 (c 1.00, CHCl3); mp 57.4-59.0 °C; H NMR
D
(500 MHz, CDCl3) δ 7.33-7.22 (m, 5H), 3.91 (q, J ) 6.50 Hz,
1H), 3.81 (dd, J ) 10.5, 3.00 Hz, 1H), 3.56 (m, 2H), 2.61 (br,
2H), 2.29 (m, 1H), 1.39 (d, J ) 6.50 Hz, 3H), 1.32-1.22 (m,
28H), 0.88 (t, J ) 7.00 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ
145.03, 128.47, 127.11, 126.77, 72.82, 61.32, 58.52, 55.30,
4h : [R]25 ) +27.0 (c 1.00, CHCl3); 1H NMR (500 MHz,
D
CDCl3) δ 7.31-7.12 (m, 10H), 3.73 (m, 1H), 2.58 (m, 3H), 1.98
(d, J ) 3.5 Hz, 1H), 1.58 (m, 1H), 1.44 (d, J ) 6.3 Hz 1H), 1.42
J . Org. Chem, Vol. 68, No. 20, 2003 7679