1990
D. Hoppe et al.
PAPER
2,2,4,4-Tetramethyl-1,3-oxazolidine-3-carboxylic Acid (1S,2S)-
2-(N,N-Dibenzylamino)-5-(N,N-diisopropylcarbamoyloxy)-1-
methylpent-1-yl Ester (10c)
According to general procedure B, the product was formed by the
reaction of 5c (240 mg, 0.41 mmol), (–)-sparteine (13; 193 mg,
0.83 mmol, 2.0 equiv), s-BuLi (0.64 mL, 0.83 mmol, 2.0 equiv)
and MeI (0.20 mL, 2.48 mmol, 6.0 equiv) in Et2O (10 mL). Aque-
ous workup and purification by FCC (Et2O–PE, 1:4) yielded 10c.
No other isomers were detected in the 1H NMR spectrum.
13C NMR (75 MHz, CDCl3): d = 21.0 (Cb-CH3), 21.8 (C-4), 23.9,
24.1, 24.7, 24.9, 25.3, 25.4, 26.3, 26.6 (Cby-CH3), 26.6 (C-3), 35.5
(C-1¢), 45.8 (Cb-CH), 54.6 [(PhCH2)2N], 58.3 (C-1¢¢), 59.5 (61.2)
[NC(CH3)2CH2], 59.8 (C-2), 64.6 (C-5), 70.6 (C-1), 75.9 (76.5)
(Cby-CH2), 94.6 (96.3) [NC(CH3)2O], 127.0, 128.2, 128.9 (Cphenyl),
139.6 (Cq, Cphenyl), 152.9 (153.6) (Cby-NC=O), 155.7 (Cb-NC=O).
MS (ESI): m/z = 626.4 [M + H]+, 648.4 [M + Na]+.
Anal. Calcd for C36H55N3O6: C, 69.09; H, 8.86; N, 6.71. Found: C,
68.86; H, 9.04; N, 6.59.
20
Yield: 209 mg, 0.35 mmol (87%); colourless oil; [a]D +0.2 (c
1.40, CHCl3); Rf = 0.39 (Et2O–PE, 1:1).
Methyl (2R,5S,6S)-5-(N,N-Dibenzylamino)-2-(N,N-diisopropyl-
carbamoyloxy)-8-(methoxycarbonyloxy)-6-(2,2,4,4-tetrameth-
yl-1,3-oxazolidine-3-carbonyloxy)octanoate (15)
IR (film): 3086, 3063, 3029, 2972, 2939, 2871, 1695, 1682, 1456,
750, 700 cm–1.
According to general procedure B, the product was formed by the
reaction of 14 (152 mg, 0.24 mmol), (–)-sparteine (13; 0.20 mL,
0.85 mmol, 3.5 equiv), s-BuLi (0.77 mL, 0.85 mmol, 3.5 equiv)
and methyl chloroformate (0.13 mL, 1.70 mmol, 7.0 equiv) in Et2O
(10 mL). Aqueous workup and purification by FCC (Et2O–PE,
1:3→1:1) gave 15 as a regio- and diastereomerically pure colourless
resin.
1H NMR (300 MHz, CDCl3): d = 1.19, 1.22 (2 × d, 3JCbCH–CbCH3
=
6.8 Hz, 12 H, Cb-CH3), 1.28, 1.30, 1.44, 1.54 (4 × s, 12 H, Cby-
3
CH3), 1.29 (d, J1–1-CH3 = 6.4 Hz, 3 H, 1-CH3), 1.40–1.59 (m,
3J4–5 = 6.7 Hz, 2 H, H-3A, H-4B), 1.70–1.80 (m, 2 H, H-3B, H-4B),
2
2.69 (m, 1 H, H-2), 3.65, 3.78 [2 × d, Jgem = 13.4 Hz, 2 × 2 H,
3
(PhCH2)2N], 3.69 (s, 2 H, Cby-CH2), 3.90 (m, JCbCH–CbCH3
=
6.8 Hz, 2 H, Cb-CH), 4.01 (t, 3J4–5 = 6.7 Hz, 2 H, H-5), 5.32 (dq,
3
20
3J1–1-CH3 = 6.4 Hz, J1–2 = 3.9 Hz, 1 H, H-1), 7.17–7.35 (m, 10 H,
Yield: 102 mg, 0.14 mmol (57%); [a]D –18.5 (c 1.02, CHCl3);
Hphenyl).
Rf = 0.56 (Et2O).
13C NMR (75 MHz, CDCl3): d = 17.7 (1-CH3), 20.8 (Cb-CH3),
23.1, 24.8, 24.9, 25.2, 25.3, 26.2 (Cby-CH3), 23.4 (C-4), 26.5 (C-3),
45.5 (Cb-CH), 54.2 [(PhCH2)2N], 59.1 (60.6) [NC(CH3)2CH2], 60.2
(C-2), 64.5 (C-5), 69.9 (C-1), 75.8 (76.2) (Cby-CH2), 94.2 (95.8)
[NC(CH3)2O], 126.6, 127.8, 128.7 (Cphenyl), 139.7 (Cq, Cphenyl),
151.2 (151.9) (Cby-NC=O), 155.5 (Cb-NC=O).
IR (film): 3088, 3064, 3029, 2969, 2934, 2872, 1760, 1747, 1691,
1681, 752, 700 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.22 (m, 12 H, Cb-CH3), 1.27,
1.34, 1.39, 1.42, 1.52, 1.56, 1.57, 1.70 (8 × s, 12 H, Cby-CH3), 1.48–
1.60 (m, 1 H, H-4A), 1.75 (m, 3J3A–2 = 4.8 Hz, 1 H, H-3A), 1.87 (m,
1 H, H-4B), 1.91 (m, 3J3B–2 = 6.3 Hz, 1 H, H-3B), 1.95 (m, 1 H, H-
7A), 2.11 (m, 1 H, H-7B), 2.64 (m, 1 H, H-5), 3.56, 3.87 [2 × d,
2Jgem = 13.4, 14.2 Hz, 2 × 2 H, (PhCH2)2N], 3.64–3.76 (m, 2 H,
Cby-CH2), 3.71 [s, 3 H, O(CO)OCH3], 3.75 [s, 3 H,
CH2(CO)OCH3], 4.04 (m, 2 H, Cb-CH), 4.04 (m, 2 H, H-8), 5.03
(dd, 3J3A–2 = 4.8 Hz, 3J3B–2 = 6.3 Hz, 1 H, H-2), 5.33 (m, 1 H, H-6),
7.19–7.31 (m, 10 H, Hphenyl).
13C NMR (100 MHz, CDCl3): d = 20.5 (Cb-CH3), 20.5 (C-3), 23.3,
23.9, 24.1, 24.4, 25.3, 25.5, 26.4, 27.6 (Cby-CH3), 29.0 (C-4), 31.6
(C-7), 45.7, 46.7 (Cb-CH), 51.9 (OCH3), 54.4 [(PhCH2)2N], 54.6
(OCH3), 59.4 (61.0) [NC(CH3)2CH2], 60.1 (C-5), 64.2 (C-8), 70.3
(C-6), 72.4 (C-2), 75.9 (76.4) (Cby-CH2), 94.4 (96.2) [NC(CH3)2O],
127.0, 128.2, 129.0 (Cphenyl), 139.5 (Cq, Cphenyl), 151.1 (152.0)
(Cby-NC=O), 154.7 (Cb-NC=O), 155.5 [O(CO)OCH3], 171.2
[CH2(CO)OCH3].
MS (ESI): m/z = 596.5 [M + H]+, 618.5 [M + Na]+.
Anal. Calcd for C35H53N3O5: C, 70.55; H, 8.97; N, 7.05. Found: C,
70.60; H, 8.98; N, 6.93.
2,2,4,4-Tetramethyl-1,3-oxazolidine-3-carboxylic Acid (1S,2S)-
2-(N,N-Dibenzylamino)-5-(N,N-diisopropylcarbamoyloxy)-1-
(2-hydroxyethyl)pent-1-yl Ester (14)
5c (1.004 g, 1.73 mmol) and (–)-sparteine (13; 0.56 mL,
2.42 mmol, 1.4 equiv) were dissolved in Et2O (50 mL). The mixture
was cooled to –78 °C, s-BuLi (1.93 mL, 2.42 mmol, 1.4 equiv) was
added dropwise and, after stirring for 7 h, the mixture became dark
red-brown. A precooled solution (–78 °C) of ethylene oxide [pre-
pared by condensing ethylene oxide (228 mg, 5.18 mmol,
3.0 equiv) in a flask at –78 °C and dissolving the condensate in Et2O
(5 mL)] was added. After a few minutes BF3·OEt2 (0.33 mL,
2.59 mmol, 1.5 equiv) was added rapidly and the mixture became
colourless. The mixture was warmed over night to r.t., then H2O
(10 mL) was added, the aqueous layer was washed with Et2O (2 ×
10 mL), and the combined organic layers were dried over Na2SO4.
After filtration, the solvent was removed under vacuum and purified
by FCC (n-pentane–Et2O, 1:1→Et2O) to give 14.
MS (ESI): m/z = 742.5 [M + H]+, 764.6 [M + Na]+, 780.5 [M + K]+.
Anal. Calcd for C40H59N3O10: C, 64.76; H, 8.02; N, 5.66. Found: C,
64.71; H, 8.27; N, 5.51.
2,2,4,4-Tetramethyl-1,3-oxazolidine-3-carboxylic Acid
(1S,2S,5R)-2-(N,N-Dibenzylamino)-5-(N,N-diisopropylcarbam-
oyloxy)-6-hydroxy-1-(2-hydroxyethyl)hex-1-yl Ester (4c)
To a solution of 15 (399 mg, 0.54 mmol), dissolved in THF (10 mL)
and cooled to –78 °C, was added a solution of DIBAL-H (1.0 M in
hexane, 3.23 mL, 3.23 mmol, 6.0 equiv). After stirring for 1 h at
–78 °C, the mixture was warmed to 0 °C and stirred for 2 h. MeOH
(5 mL) and H2O (3 mL) were added and the mixture was stirred for
1 h at 0 °C, then warmed to r.t. MgSO4 was added and, after filtra-
tion, the solvent was removed under vacuum. Purification by FCC
(Et2O–PE, 1:1→Et2O) gave 4c.
20
Yield: 713 mg, 1.14 mmol (66%); colourless resin; [a]D +7.7 (c
1.44, CHCl3); Rf = 0.43 (Et2O).
IR (film): 3339, 3086, 3063, 3028, 2974, 2937, 2875, 1690, 1667,
1493, 1453, 750, 701 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.21, 1.22 (2 × d, 3JCbCH–CbCH3
=
6.7 Hz, 12 H, Cb-CH3), 1.24, 1.25, 1.39, 1.42, 1.44, 1.55, 1.59, 1.62
(8 × s, 12 H, Cby-CH3), 1.45–1.65 (m, 3J4–5 = 5.7 Hz, 2 H, H-3A, H-
3
4A), 1.74 (m, J1¢–1¢¢ = 5.8 Hz, 2 H, H-4B, H-1¢A), 1.87 (m, 1 H, H-
20
3B), 1.97 (m, 1 H, H-1¢B), 2.76 (m, 1 H, H-2), 3.25 (m, 1 H, OH),
Yield: 347 mg, 0.53 mmol (98%); colourless resin; dr = 97:3; [a]D
+16.9 (c 0.97, CHCl3); Rf = 0.12 (Et2O).
3
3.43 (t, J1¢–1¢¢ = 5.8 Hz, 1 H, H-1¢¢A), 3.60, 3.85 [2 × d,
2Jgem = 13.5 Hz, 2 × 2 H, Ph(CH2)2N], 3.65 (m, 1 H, H-1¢¢B), 3.70
IR (film): 3422, 3090, 3066, 3032, 2974, 2940, 2878, 1685, 1670,
1654, 1456, 1438, 750, 700 cm–1.
3
(m, 2 H, Cby-CH2), 3.90 (m, JCbCH–CbCH3 = 6.7 Hz, 2 H, Cb-CH),
4.04 (t, 3J4–5 = 5.7 Hz, 2 H, H-5), 5.00 (m, 1 H, minor diastereomer,
dr >97:3), 5.39 (dt, 3J1–2 = 11.3 Hz, 3J1–1¢ = 3.0 Hz, 1 H, H-1), 7.19–
7.35 (m, 10 H, Hphenyl).
1H NMR (400 MHz, CDCl3): d = 1.23, 1.24 (2 × d, 3JCbCH–CbCH3
6.8 Hz, 12 H, Cb-CH3), 1.38, 1.41, 1.43, 1.54, 1.59 (5 × s, 12 H,
=
Synthesis 2007, No. 13, 1984–1994 © Thieme Stuttgart · New York