7.0 Hz, Jb =7.0 Hz, 1H), 7.94–7.88 (m, 1H), 7.72 (d, J=7.5 Hz, 2H),
7.58a, 7.53b (2ꢂd, Ja =7.4 Hz, Jb =7.5 Hz, 2H), 7.40–7.29, 7.25–7.22,
7.02–6.97 (3 m, 5H), 6.62a, 6.24b (2ꢂd, Ja =6.3 Hz, Jb =5.9 Hz, 1H),
6.41 (d, J=1.3 Hz, 1H), 4.70a, 4.46b (2ꢂd, Ja =5.0 Hz, Jb =6.4 Hz,
2H), 4.24–4.18 (m, 1H), 3.89, 3.85 (2 s, 2H), 3.63–3.56, 3.28–3.17
(2 m, 2H), 2.92–2.87, 2.49–2.42 ppm (2 m, 2H); 13C NMR (150 MHz,
CDCl3): d=172.9, 156.4, 155.8, 143.8, 141.4, 141.3, 140.1, 128.2,
127.8, 127.7, 127.2, 127.0, 124.9, 124.6, 120.0, 116.9, 116.7, 113.7,
113.5, 96.4, 67.7, 66.8, 49.9, 49.7, 49.3, 47.4, 47.2, 34.0, 33.9 ppm; IR
(NaCl): n=3438, 2952, 1699, 1647, 1477, 1447, 1218, 1180, 1123,
oxazolidinone (1.9 g, 6.8 mmol). Compound 8b was obtained as
a colorless solid (3.7 g, 80%). Spectroscopic characterization data
were identical to those obtained for the enantiomer 8a: [a]D25
+94.6 (c=1.07 in CHCl3).
=
(S)-3-((R)-2-{[(Benzyloxy)carbonyl]amino})methyl-4-[4-(tert-butyl)-
diphenylsilyl)-phenyl]-1-oxobutyl)-4-isopropyl-5,5-diphenyloxa-
zolidin-2-one (9a): To a solution of 8a (3.6 g, 5.0 mmol) in CH2Cl2
(27 mL), TiCl4 (0.86 mL, 5.8 mmol) and then NEt3 (0.86 mL,
5.8 mmol) was added at ꢀ158C. The resulting dark-red solution
was stirred at ꢀ158C for 0.5 h. Benzyl-N-[(benzyloxy)-methyl]carba-
mate (CbzNHCH2OBn; 1.64 g, 5.8 mmol) and TiCl4 (0.67 mL,
5.8 mmol) were dissolved in CH2Cl2 (13 mL) in an ice bath, and the
resulting solution was added to the mixture via cannula. The reac-
tion mixture was stirred at 08C for 4.5 h, treated with saturated aq
NaHCO3 and CH2Cl2. The organic extract was washed with 1n HCl
(2ꢂ), 1n NaOH (1ꢂ) and brine (1ꢂ), dried (MgSO4), filtered and
evaporated. Flash column chromatography (EtOAc/hexane, 1:4) af-
forded 9a as a colorless solid (2.72 g, 61%, d.r.: 19): mp: 59–618C;
1H NMR (600 MHz, CDCl3): d=7.74–7.69 (m, 4H), 7.47–7.26 (m,
18H), 7.16 (dd, J=7.9, 7.9 Hz, 2H), 7.02 (dd, J=7.4, 7.4 Hz, 1H),
6.55–6.50 (m, 2H), 6.42–6.35 (m, 2H), 5.34 (d, J=3.4 Hz, 1H), 5.18
(bs, 1H), 5.06 (s, 2H), 3.79–3.71 (m, 1H), 3.59–3.47, 3.39–3.32 (2 m,
2H), 2.03–1.86 (m, 3H), 1.67–1.59 (m, 2H), 1.09 (s, 9H), 0.83 (d, J=
7.1 Hz, 3H), 0.70 ppm (d, J=6.9 Hz, 3H); 13C NMR (150 MHz, CDCl3):
d=174.5, 156.2, 153.6, 153.0, 142.2, 137.7, 136.5, 135.5, 133.4,
133.2, 133.1, 129.8, 128.9, 128.7, 128.70, 128.6, 128.5, 128.4, 128.1,
128.0, 128.00, 127.7, 125.7, 125.3, 119.3, 89.6, 66.7, 65.3, 42.9, 42.5,
31.7, 31.3, 29.6, 26.5, 25.9, 21.6, 19.4 ppm; IR (NaCl): n=2931, 2858,
1783, 1722, 1607, 1509, 1450, 1428, 1362, 1316, 1252, 1175, 1113,
1051, 1000, 913, 822 cmꢀ1; MS (ESI): m/z 868.1 [M+Na]+; HRMS-
ESI: m/z [M+Na]+ calcd for C53H56N2O6Si: 867.3800, found:
867.3792.
759, 739 cmꢀ1 MS (ESI): m/z 442.2 [M+H]+; HRMS-ESI: m/z
;
[M+Na]+ calcd for C26H23N3O4: 464.1581, found: 464.1575.
4-{4-[(tert-Butyl)diphenylsilyl]phenyl}butanoic acid (7): To a solu-
tion of 4-(4-hydroxyphenyl)butanoic acid[23] (3.13 g, 17 mmol) and
imidazole (5.2 g, 76 mmol) in DMF (45 mL), tert-butyl-diphenylsilyl-
chloride (9.9 mL, 38 mmol) was added dropwise and stirred at RT
for 4.5 h. After addition of brine (450 mL), the reaction mixture was
extracted with Et2O (3ꢂ). The combined organic extracts were
washed with ice-cold 1n HCl and brine, dried (MgSO4), filtered and
concentrated in vacuo. The residue was redissolved in MeOH/THF
(1:1, 144 mL) and 10% aq K2CO3 (22.5 mL) and stirred at RT for 1 h.
After evaporation, the residue was diluted with brine (180 mL),
acidified with 1n HCl and extracted with Et2O (3ꢂ). Organic ex-
tracts were washed with brine, dried (MgSO4), filtered and concen-
trated in vacuo. Crude product was purified by flash column chro-
matography (hexane/Et2O, 4:1+0.5% HCO2H) to yield acid 7 as
1
a colorless oil (6.9 g, 98%): H NMR (390 MHz, CDCl3): d=7.73–7.68
(m, 4H), 7.43–7.39 (m, 2H), 7.37–7.33 (m, 4H), 6.90–6.86 (m, 2H),
6.69–6.66 (m, 2H), 2.52 (t, J=7.6 Hz, 2H), 2.29 (t, J=7.6 Hz, 2H),
1.92–1.86 (m, J=7.6 Hz, 2H), 1.09 ppm (s, 9H); 13C NMR (150 MHz,
CDCl3): d=179.3, 153.8, 133.5, 133.1, 129.8, 129.1, 127.7, 119.5,
34.1, 33.1, 26.5, 26.3, 19.4 ppm; IR(NaCl): n=3431, 3072, 2931,
2856, 1705, 1608, 1500, 1428, 1254, 1117, 922, 822 cmꢀ1; MS(ESI):
m/z 441.7 [M+Na]+.
(R)-3-((S)-2-{[(Benzyloxy)carbonyl]amino})methyl-4-[4-(tert-butyl)-
diphenylsilyl)-phenyl]-1-oxobutyl)-4-isopropyl-5,5-diphenyloxa-
zolidin-2-one (9b): Compound 9b was synthesized according to
the procedure described for 9a starting with 8b (3.5 g, 5.0 mmol).
Compound 9b was obtained as a colorless solid (2.3 g, 53%, d.r.:
19). Spectroscopic characterization data were identical to those ob-
tained for the enantiomer 9a.
(S)-3-{4-[4-(tert-Butyl)diphenylsilyl)phenyl]-1-oxobutyl}-4-isopro-
pyl-5,5-diphenyl-oxazolidin-2-one (8a): A solution of 7 (1.34 g,
2 mmol) and NEt3 (1.11 mL, 7.9 mmol) in THF (15 mL) was cooled
to ꢀ308C, and pivaloyl chloride (PivCl, 0.4 mL, 3.2 mmol) was
added dropwise. The white suspension was stirred for 1.5 h, and
LiCl (0.15 g, 3.5 mmol) and (4S)-4-(1-methylethyl)-5,5-diphenyl-2-ox-
azolidinone (0.86 g, 3.2 mmol) were added and stirred overnight,
allowing to warm to RT. The reaction mixture was diluted with
Et2O and saturated aq NH4Cl. The organic phase was washed with
1n HCl (2ꢂ), 1n NaOH (1ꢂ) and brine (1ꢂ), dried (MgSO4), filtered
and evaporated. Flash column chromatography (EtOAc/hexane,
1:4) afforded 8a as a colorless solid (2.06 g, 99%): mp: 57–608C;
[a]2D5 =ꢀ95.4 (c=1.05 in CHCl3); 1H NMR (600 MHz, CDCl3): d=
7.74–7.66 (m, 4H), 7.49–7.17 (m, 18H), 6.80–6.74 (m, 2H), 6.65–6.59
(m, 2H), 5.35 (d, J=3.4 Hz, 1H), 2.91–2.77, 2.77–2.64 (2 m, 2H),
2.45–2.37 (m, 2H), 2.01–1.91 (m, 1H), 1.82–1.72 (m, 2H), 1.09 (s,
9H), 0.86 (d, J=6.8 Hz, 3H), 0.74 ppm (d, J=6.8 Hz, 3H); 13C NMR
(150 MHz, CDCl3): d=172.9, 153.7, 153.0, 142.4, 138.2, 135.5, 133.8,
133.2, 129.8, 129.0, 128.9, 128.6, 128.4, 127.9, 127.7, 125.9, 125.6,
119.4, 89.3, 64.5, 34.4, 34.0, 29.8, 26.6, 26.3, 21.7, 19.4 ppm; IR
(NaCl): n=3072, 2930, 2932, 2857, 1791, 1703, 1607, 1500, 1452,
1429, 1362, 1318, 1254, 1175, 1118, 998, 919, 843, 822 cmꢀ1; MS
(ESI): m/z 705.2 [M+Na]+; HRMS-ESI: m/z [M+Na]+ calcd for
C44H47NO4Si: 704.3167, found: 704.3171.
(S)-3-[(R)-2-({[(Benzyloxy)carbonyl]amino})methyl-4-(4-hydroxy-
phenyl)-1-oxobutyl]-4-isopropyl-5,5-diphenyloxazolidin-2-one
(10a): A mixture of 9a (1.3 g, 1.5 mmol) in THF (12 mL) and tetra-
n-butylammonium fluoride (TBAF, 1.8 mL, 1m in THF) was stirred at
RT for 4 h. The mixture was diluted with EtOAc, washed with H2O
(1ꢂ) and brine (1ꢂ). The combined organic extracts were dried
(MgSO4), filtered and evaporated. Flash column chromatography
(EtOAc/hexane, 1:3!1:2) afforded 10a as colorless solid (0.8 g,
86%, d.r.: 19): mp: 75–768C; 1H NMR (360 MHz, CDCl3): d=7.56–
7.50 (m, 2H), 7.45–7.27 (m, 12H), 7.22–7.16 (m, 1H), 6.68–6.61 (m,
2H), 6.59–6.54 (m, 2H), 5.39 (d, J=3.5 Hz, 1H), 5.24 (bs, 1H), 5.15
(s, 1H), 5.10–5.00 (m, 2H), 3.86–3.79 (m, 1H), 3.59–3.50, 3.41–3.34
(2 m, 2H), 2.04–1.93 (m, 3H), 1.76–1.63, 1.48–1.35 (2 m, 2H), 0.85
(d, J=7.0 Hz, 3H), 0.72 ppm (d, J=6.7 Hz, 3H); 13C NMR (150 MHz,
CDCl3): d=174.6, 156.3, 153.7, 153.1, 142.2, 137.7, 136.4, 133.0,
129.2, 129.0, 128.8, 128.5, 128.4, 128.1, 128.0, 125.8, 125.7, 125.5,
115.1, 89.8, 66.7, 65.3, 43.0, 42.5, 31.6, 30.9, 29.6, 21.7 ppm; IR
(NaCl): n=3381, 2965, 1782, 1701, 1614, 1515, 1450, 1362, 1317,
1212, 1176, 1052, 989, 912 cmꢀ1; MS (ESI): m/z 615.4 [M+Na]+;
HRMS-ESI: m/z [M+Na]+ calcd for C37H38N2O6: 629.2622, found:
629.2619.
(R)-3-{4-[4-(tert-Butyl)diphenylsilyl)phenyl]-1-oxobutyl}-4-isopro-
pyl-5,5-diphenyloxazolidin-2-one (8b): Compound 8b was syn-
thesized according to the procedure described for 8a starting
from 7 (3.0 g, 7.2 mmol) and (4R)-4-(1-methylethyl)-5,5-diphenyl-2-
ꢁ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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