2228
R. Badorrey et al. / Tetrahedron: Asymmetry 20 (2009) 2226–2229
(2.89 mL, 22.8 mmol) and stirring was continued for 10 min at the
same temperature. A 1 M solution of BnMgCl (45.6 mL, 45.6 mmol)
in ether was added and the reaction mixture was stirred for 5 h at
ꢁ20 °C. The reaction mixture was treated at 0 °C with saturated
aqueous NaHCO3 (25 mL) and water (25 mL). The mixture was
filtered through a CeliteÒ pad, which was washed with Et2O
(2 ꢂ 30 mL). The organic phase was separated and the aqueous
layer was extracted with Et2O (2 ꢂ 60 mL). The combined organic
layers were dried over anhydrous MgSO4, filtered and concen-
trated to give 3 as a 90/10 anti/syn mixture of diastereoisomers.
Purification of the crude product by column chromatography
(1st eluent: Et2O/hexanes 1:3, 2nd eluent: Et2O/hexanes 1:1) affor-
ded 5.10 g (72%) of diastereomerically pure 3 with the anti config-
4.5. (2S,3S)-3-(tert-Butoxycarbonyl)amino-4-phenyl-1,2-butane-
diol 6
A solution of compound 5 (850 mg, 2.65 mmol) in 3:1 MeOH/
H2O (20 mL) was treated with TFA (19
for 24 h at room temperature. Then an additional portion of TFA
(19 L, 0.26 mmol) was added and stirring was continued for
lL, 0.26 mmol) and stirred
l
24 h at room temperature. Saturated aqueous NaHCO3 was added
until the pH was basic and the solution was concentrated in vacuo.
The concentrate was diluted with water (10 mL). The aqueous
phase was extracted with CH2Cl2 (3 ꢂ 30 mL) and the combined or-
ganic layers were dried over anhydrous MgSO4, filtered and evap-
orated in vacuo. Purification of the crude product by column
chromatography (1st eluent: Et2O/hexanes 1:1, 2nd eluent: EtOAc)
afforded 670 mg (90%) of compound 6 as a white solid. Mp = 124–
uration as a pale yellow oil. ½a D25
¼ þ18:1 (c 0.64, CHCl3); IR (neat,
ꢃ
cmꢁ1): max 3335; 1H NMR (400 MHz, CDCl3) d 1.26 (s, 3H), 1.36 (s,
m
3H), 2.70 (dd, J = 14.0, 6.8 Hz, 1H), 2.79 (dd, J = 14.0, 4.8 Hz, 1H),
2.84–2.90 (m, 1H), 3.63 (d, J = 13.2, 1H), 3.68 (d, J = 13.2, 1H),
3.79–3.86 (m, 2H), 3.88–3.95 (m, 1H), 7.15–7.27 (m, 10H); 13C
NMR (100 MHz, CDCl3) d 25.0, 26.5, 36.2, 51.5, 59.6, 66.7, 77.0,
108.5, 126.0, 126.6, 127.7, 128.0, 128.2, 129.3, 137.9, 140.2; HRMS
(ESI+): m/z [M+H+] calcd for C20H26NO2 (MH+) 312.1958, found
312.1946.
125 °C (lit.7c mp = 118–125 °C); ½a 2D5
ꢃ
¼ þ12:6 (c 1.00, CHCl3) [lit.7c
½
a 2D5
ꢃ
¼ þ8:6 (c 0.62, CHCl3)]; IR (KBr, cmꢁ1): mmax 3356, 1688; 1H
NMR (500 MHz, CDCl3, 333 K) d 1.38 (s, 9H), 2.86 (dd, J = 14.0,
8.5 Hz, 1H), 3.05 (d, J = 8.0 Hz, 1H), 3.07 (dd, J = 14.0, 4.5 Hz, 1H),
3.14 (br s, 1H), 3.44–3.48 (m, 1H), 3.66–3.71 (m, 2H), 3.83–3.90
(m, 1H), 4.64 (br d, 1H), 7.20–7.35 (m, 5H); 13C NMR (100 MHz,
CDCl3, 333 K) d 28.2, 36.4, 52.4, 63.0, 73.1, 80.2, 126.5, 128.5,
129.4, 137.4, 156.9. Elemental Anal. Calcd for C15H23NO4: C, 64.0;
H, 8.2; N, 5.0. Found: C, 64.0; H, 8.1; N, 5.10; HRMS (ESI+): m/z
[M+Na+] calcd for C15H23NNaO4 (MNa+) 304.1519, found 304.1512.
4.3. (S)-N-Benzyl-N-tert-butoxycarbonyl-1-[(S)-2,2-dimethyl-
1,3-dioxolan-4-yl]-2-phenylethanamine 4
To a solution of compound 3 (1.52 g, 4.9 mmol) in a solution of
10% Et3N in MeOH (30 mL) was added Boc2O (2.13 g, 9.8 mmol)
and the mixture was stirred for 90 min at 45 °C. Then an additional
portion of Boc2O (2.13 g, 9.8 mmol) was added and stirring was
continued for 90 min at 45 °C. After completion of the reaction,
the solution was concentrated in vacuo. Purification of the crude
product by column chromatography (1st eluent: Et2O/hexanes
1:8, 2nd eluent: Et2O/hexanes 1:4) afforded 1.93 g (96%) of com-
4.6. (2S,3S)-3-(tert-Butoxycarbonyl)amino-4-phenyl-1-tosyloxy-
2-butanol 7
To a solution of compound 6 (290 mg, 1.03 mmol) in dry CH2Cl2
(4 mL) at room temperature were added successively n-Bu2SnO
(8 mg, 0.03 mmol), a solution of Et3N (171 lL, 1.24 mmol) in dry
CH2Cl2 (4 mL) and TsCl (236 mg, 1.24 mmol) and the reaction mix-
ture was stirred for 6 h at room temperature. The reaction mixture
was treated with saturated aqueous NaCl (5 mL). The organic phase
separated and the aqueous layer was extracted with CH2Cl2
(3 ꢂ 15 mL). The combined organic layers were dried over anhy-
drous MgSO4, filtered and evaporated in vacuo. Purification of the
crude product by column chromatography (1st eluent: Et2O/hex-
anes 1:1, 2nd eluent: Et2O) afforded 416 mg (93%) of compound 7
pound 4 as a colourless oil. ½a D25
¼ ꢁ26:1 (c 1.00, CHCl3); IR (neat,
ꢃ
cmꢁ1): mmax 1695; 1H NMR (300 MHz, C6D6, 353 K) d 1.34 (s, 3H),
1.42 (s, 9H), 1.46 (s, 3H), 3.12–3.27 (m, 1H), 3.36 (dd, J = 14.1,
3.9 Hz, 1H), 3.67–3.79 (m, 1H), 3.80–3.84 (m, 1H), 4.30–4.50 (m,
4H), 7.10–7.30 (m, 10H); 13C NMR (125 MHz, C6D6, 353 K) d 25.7,
27.1, 28.4, 36.2, 50.8, 62.4, 68.0, 78.2, 79.8, 109.6, 126.4, 127.3,
127.9, 128.1, 128.3, 128.5, 129.7, 137.9, 155.9; HRMS (ESI+): m/z
[M+Na+] calcd for C25H33NNaO4 (MNa+) 434.2302, found 434.2290.
as a white solid. Mp = 118–119 °C; ½a D25
¼ þ6:8 (c 1.00, CHCl3); IR
ꢃ
(KBr, cmꢁ1): mmax 3384, 1686, 1361; 1H NMR (400 MHz, CDCl3) d
1.36 (s, 9H), 2.46 (s, 3H), 2.83–2.94 (m, 2H), 3.82–3.90 (m, 2H),
4.01 (dd, J = 10.2, 6.3 Hz, 1H), 4.11 (dd, J = 10.2, 3.6 Hz, 1H), 4.64
(d, J = 8.0 Hz, 1H), 7.15–7.31 (m, 2H), 7.34–7.37 (m, 2H), 7.78–7.82
(m, 2H); 13C NMR (100 MHz, CDCl3) d 21.6, 28.1, 35.7, 53.8, 71.2,
71.5, 80.0, 126.6, 128.0, 128.5, 129.3, 129.9, 132.3, 137.1, 145.1,
156.1. Elemental Anal. Calcd for C22H29NO6S: C, 60.7; H, 6.7; N,
3.2; S, 7.4. Found: C, 60.7; H, 6.6; N, 3.4; S, 7.5; HRMS (ESI+): m/z
[M+Na+] calcd for C22H29NNaO6S (MNa+) 458.1608, found 458.1601.
4.4. (S)-N-tert-Butoxycarbonyl-1-[(S)-2,2-dimethyl-1,3-
dioxolan-4-yl]-2-phenylethanamine 5
To a solution of compound 4 (1.15 g, 2.8 mmol) in dry Et2O
(25 mL) and liquid ammonia (25 mL) at ꢁ50 °C was added lithium
in small portions until the colour of the solution remained blue.
The reaction mixture was treated with saturated aqueous NH4Cl
(15 mL) and the ammonia was evaporated. The reaction mixture
was diluted with water (15 mL). The aqueous phase was extracted
with Et2O (3 ꢂ 30 mL), the combined organic layers were dried
over anhydrous MgSO4, filtered and evaporated in vacuo. Purifica-
tion of the crude product by column chromatography (eluent:
Et2O/hexanes 1:2) afforded 860 mg (96%) of compound 5 as a
4.7. (2S,3S)-3-(tert-Butoxycarbonyl)amino-1,2-epoxy-4-
phenylbutane 1
To a solution of compound 7 (391 mg, 0.90 mmol) in dry MeOH
(10 mL) at 0 °C was added anhydrous K2CO3 (149 mg, 1.08 mmol)
and the mixture was stirred for 2 h at room temperature. The reac-
tion mixture was treated with saturated aqueous NH4Cl (5 mL) and
water (10 mL) and extracted with CH2Cl2 (3 ꢂ 20 mL). The com-
bined organic layers were dried over anhydrous MgSO4, filtered
and evaporated in vacuo. Purification of the crude product by col-
umn chromatography (eluent: Et2O/hexanes 1:2) afforded 232 mg
(98%) of compound 1 as a white solid. Mp = 124–125 °C (lit.11
white solid. Mp = 125–126 °C; ½a D25
¼ ꢁ1:0 (c 1.00, CHCl3); IR
ꢃ
(KBr, cmꢁ1): mmax 3358, 1686; 1H NMR (500 MHz, CDCl3, 333 K) d
1.39 (s, 3H), 1.39 (s, 9H), 1.50 (s, 3H), 2.84 (dd, J = 8.4, 4.5 Hz,
1H), 3.01 (dd, J = 8.4, 2.7 Hz, 1H), 3.84–3.89 (m, 1H), 3.90–3.96
(m, 1H), 3.98–4.05 (m, 2H), 4.38 (br s, 1H), 7.15–7.35 (m, 5H);
13C NMR (125 MHz, CDCl3, 333 K) d 25.3, 26.6, 28.3, 37.2, 54.1,
67.1, 77.2, 79.5, 109.6, 126.4, 128.4, 129.5, 137.6, 155.3. Elemental
Anal. Calcd for C18H27NO4: C, 67.3; H, 8.5; N, 4.4. Found: C, 67.4; H,
8.5; N, 4.3; HRMS (ESI+): m/z [M+Na+] calcd for C18H27NNaO4
(MNa+) 344.1832, found 344.1824.
mp = 122–124.5 °C); ½a D25
ꢃ
¼ þ8:0 (c 1.00, CHCl3) [lit.11
½
a 2D5
ꢃ
¼
þ6:9 (c 0.62, CHCl3)]; IR (KBr, cmꢁ1): mmax 3377, 1680; 1H NMR
(400 MHz, CDCl3) d 1.30 (s, 9H), 2.65–2.69 (m, 1H), 2.71 (dd,