S. A. A. El Bialy, H. Braun, L. F. Tietze
FULL PAPER
80.18 (C-4), 108.3 (C-2), 174.1 (C-7), 174.8 (C-5) ppm. C15H26O5
(286.37): calcd. C 62.91, H 9.15; found C 62.84, H 9.26.
(0.72 g, 4.3 mmol, 61 %) as an oil. Rf = 0.27 (PE/EtOAc, 1:1).
[α]2D0 = –17.5 (c = 1.0, MeOH). IR (MeOH): ν = 3030, 2960 (br),
˜
1
1716, 1469 cm–1. H NMR (300 MHz, C3D6O): δ = 2.84 (AB sys-
(2R,4R)-[2-(tert-Butyl)-4-(2-methylpropyl)-5-oxo-1,3-dioxolan-4-yl]-
acetic Acid (12c): According to General Procedure III alkene 10c
(2.56 g, 10 mmol) was hydrogenated to afford 12a (2.53 g,
9.8 mmol, 98%) as an oil. Rf = 0.27 (PE/EtOAc, 4:1). [α]2D0 = –25.3
tem, J = 16.5 Hz, 2 H, 5-H2), 3.32 (AB system, J = 13.5 Hz, 2 H,
3-H2), 7.20–7.32 (m, 5 H, Ar-H), 9.82 (br. s, 2 H, 1-H1, 4-H1) ppm.
13C NMR (C3D6O): δ = 43.01 (C-5), 45.54 (C-3), 75.51 (C-2), 127.4
(C-9), 128.5 (C-8, C-10), 131.3 (C-7, C-11), 136.5 (C-6), 172.2 (C-
4), 175.8 (C-1) ppm. C11H12O5 (224.21): calcd. C 58.93, H 5.39;
found C 58.88, H 5.31.
(c = 1.0, CHCl ). IR (CHCl ): ν = 2962, 1798, 1722, 1484 cm–1. 1H
˜
3
3
NMR (300 MHz, CDCl3): δ = 0.95 (s, 9 H, C(CH3)3), 0.98 (d, J =
6.0 Hz, 3 H, 11-H3), 1.01 (d, J = 6.0 Hz, 3 H, 10-H3), 1.68 (dd, J
= 6.0, 2.1 Hz, 2 H, 8-H2), 1.89 (sept, J = 6.0 Hz, 1 H, 9-H1), 2.92
(AB system, J = 10.2 Hz, 2 H, 6-H2), 5.15 (s, 1 H, 2-H1), 10.7 (br.
s, 1 H, 7-H1) ppm. 13C NMR (75 MHz, CDCl3): δ = 22.85 (C-11),
23.53 [C(CH3)3], 24.09 (C-9), 24.52 (C-10), 34.14 [C(CH3)3], 39.20
(C-8), 40.60 (C-6), 80.37 (C-4), 107.7 (C-2), 174.5 (C-7), 174.5 (C-
5) ppm. C13H22O5 (258.31): calcd. C 60.45, H 8.58; found C 60.39,
H 8.47.
Dimethyl (2R)-2-Benzyl-2-hydroxysuccinate (15b): 50 % H2SO4
(2 mL) was added to a solution of dioxolone 14 (1.54 g, 5.4 mmol)
in MeOH (10 mL). After stirring at 60 °C for 6 h, the solvent was
removed under vacuo. To the residue water (25 mL) was added and
the aqueous phase extracted with EtOAc (3×100 mL). The com-
bined organic phases were dried with MgSO4, the solvent removed
under vacuo, and the residue was purified by column chromatog-
raphy to give 15b (1.14 g, 5.2 mmol, 86%) as an oil. Rf = 0.27 (PE/
General Procedure IV – Cleavage of Acetals: 50% H2SO4 (2 mL)
was added to a solution of the dioxolone (5.4 mmol) in dioxane
(10 mL). After stirring at 60 °C for 24 h, the solvent was removed
under vacuo and water (15 mL) was added. The aqueous phase was
extracted with EtOAc (3×100 mL), the combined organic phases
were dried with Mg2SO4, the solvent was removed under vacuo and
the residue purified by column chromatography.
EtOAc, 1:10). [α]2D0 = –12.4 (c = 0.5, MeOH). IR (MeOH): ν =
˜
1
3569, 2963 (br), 1714, 1430 cm–1. H NMR (300 MHz, CDCl3): δ
= 2.87 (AB system, J = 16.2 Hz, 2 H, 3-H2), 2.98 (AB system, J =
13.5 Hz, 2 H, 3-H2), 3.65 (s, 3 H, OMe), 3.74 (s, 3 H, OMe), 7.16–
7.32 (m, 5 H, Ar-H) ppm. 13C NMR (CDCl3): δ = 42.75 (C-5),
45.20 (C-3), 51.80 (C–OMe), 52.68 (C–OMe), 75.76 (C-2), 127.1
(C-9), 128.1 (C-8, C10), 130.1 (C-7, C-11), 134.7 (C-6), 171.0 (C-
4), 174.6 (C-1) ppm. C13H16O5 (252.27): calcd. C 61.90, H 6.39;
found C 62.19, H 6.41.
(2R)-2-Hydroxy-2-(3-methylbutyl)succinic Acid (13a): According to
General Procedure IV acetal 12a (1.47 g, 5.4 mmol) was cleaved to
give 13a (0.95 g, 4.7 mmol, 86%) as a solid. Rf = 0.24 (PE/EtOAc,
1:1). M.p. 127–128 °C (PE/EtOAc). [α]2D0 = –12.4 (c = 0.5, MeOH).
Methyl (2R,4R)-[2-tert-Butyl-4-(3-methylbut-2-enyl)-5-oxo-1,3-di-
IR (MeOH): ν = 3569, 2963 (br), 1714, 1430 cm–1.1H NMR oxolan-4-yl]acetate (16a): According to General Procedure I 10b
˜
(300 MHz, C3D6O): δ = 0.86 (d, J = 6.6 Hz, 3 H, 9-H3), 0.88 (d, J
= 6.6 Hz, 3 H, 8-H3), 1.10 (ddd, J = 21.6, 9.6, 5.4 Hz, 1 H, 6-H1),
1.38 (ddd, J = 13.2, 6.6, 5.4 Hz, 1 H, 6-H1), 1.51 (sept, J = 6.6 Hz,
1 H, 7-H1), 1.60–1.80 (m, 2 H, 5-H2), 2.79 (AB system, J = 16.2 Hz,
(1.0 g, 3.6 mmol) was transformed to give 16a (1.05 g, 3.6 mmol,
quant.) as a colorless oil. Rf = 0.53 (PE/EtOAc, 20:1). [α]2D0 = –38.5
(c = 1.0, CHCl ). IR (CHCl ): ν = 2964, 1801, 1799, 1748 cm–1. 1H
˜
3
3
NMR (300 MHz, CDCl3): δ = 0.89 [s, 9 H, C(CH3)3], 1.58 (s, 3 H,
2 H, 3-H2), 10.5 (br. s, 2 H, 1-H1, 4-H1). 13C NMR (75 MHz, 13-H3), 1.68 (s, 3 H, 12-H3), 2.45 (d, J = 8.1 Hz, 2 H, 9-H2), 2.75
C3D6O): δ = 22.74 (C-9), 22.81 (C-8), 28.82 (C-7), 32.81 (C-6),
37.98 (C-5), 43.79 (C-3), 75.39 (C-2), 172.3 (C-4), 176.4 (C-1) ppm.
C9H16O5 (204.22): calcd. C 52.93, H 7.90; found C 52.76, H 7.86.
(s, 2 H, 6-H2), 3.59 (s, 3 H, OMe), 5.12 (s, 1 H, 2-H1), 5.12 (tt, J
= 8.1, 1.5 Hz, 1 H, 10-H1) ppm. 13C NMR (75 MHz, CDCl3): δ
= 17.90 (C-13), 23.49 [C(CH3)3], 25.85 (C-12), 32.46 (C-9), 34.06
[C(CH3)3], 39.62 (C-6), 51.79 (C-8), 80.60 (C-4), 108.2 (C-2), 137.6
(C-11), 115.7 (C-10), 168.7 (C-7), 173.8 (C-5) ppm. C15H24O5
(284.35): calcd. C 63.36, H 8.51; found C 63.45, H 8.59.
(2R)-2-Hydroxy-2-(4-methylpentyl)succinic Acid (13b): According
to General Procedure IV acetal 12b (1.54 g, 5.3 mmol) was cleaved
to give 13b (0.98 g, 4.5 mmol, 83%) of 13c as a solid. Rf = 0.25
(PE/EtOAc, 1:1). M.p. 90–91 °C (PE/EtOAc). [α]2D0 = –11.4 (c =
Methyl (2R,4R)-[2-tert-Butyl-4-(4-methylpent-2-enyl)-5-oxo-1,3-di-
oxolan-4-yl]acetate (16b): According to General Procedure I 10c
(1.02 g, 3.6 mmol) was transformed to give 16b (1.07 g, 3.6 mmol,
1.0, MeOH). IR (MeOH): ν = 3486, 2956 (br), 1706, 1461 cm–1.
˜
1H NMR (300 MHz, C3D6O): δ = 0.83 (s, 3 H, 10-H3), 0.85 (s, 3
H, 9-H3), 1.10–1.30 (m, 4 H, 5-H2, 6-H1), 1.40–1.70 (m, 3 H, 7-H2,
8-H1), 2.79 (AB system, J = 16.5 Hz, 2 H, 3-H2), 8.19 (br. s, 2 H,
1-H1, 4-H1) ppm. 13C NMR (C3D6O): δ = 21.69 (C-7), 22.72 (C-
10), 22.82 (C-9), 28.44 (C-8), 39.58 (C-6), 40.21 (C-5), 43.71 (C-3),
75.40 (C-2), 172.4 (C-4), 176.5 (C-1) ppm. C10H18O5 (218.24):
calcd. C 55.03, H 8.31; found C 54.89, H 7.99.
quant.) as an colorless oil. Rf = 0.59 (PE/EtOAc, 20:1). [α]2D0
=
–34.5 (c = 1.0, CHCl ). IR (CHCl ): ν = 2960, 1801, 1748,
˜
3
3
1
1485 cm–1. H NMR (300 MHz, CDCl3): δ = 0.85 [s, 9 H, C(CH3)
3], 0.63 (s, 3 H, 14-H3), 0.96 (s, 3 H, 13-H3), 2.25 (sept, J = 6.6 Hz,
1 H, 12-H1), 2.45 (d, J = 15.4 Hz, 2 H, 9-H2), 2.88 (s, 2 H, 6-H2),
3.63 (s, 3 H, OMe), 5.16 (s, 1 H, 2-H1), 5.32 (m, 1 H, 11-H1), 5.52
(dd, J = 15.4, 3.2 Hz, 1 H, 10-H1). 13C NMR (CDCl3): δ = 22.10
(C-14), 22.16 (C-13), 23.51 [C(CH3)3], 31.11 (C-12), 34.15
[C(CH3)3], 37.27 (C-9), 39.77 (C-6), 51.85 (C-8), 80.24 (C-4), 108.2
(C-2), 118.3 (C-10), 144.2 (C-11), 168.7 (C-7), 173.7 (C-5) ppm.
C16H26O5 (298.38): calcd. C 64.41, H 8.78; found C 64.36, H 8.87.
(2R)-2-Hydroxy-2-(2-methylpropyl)succinic Acid (13c): According
to General Procedure IV acetal 12c (1.39 g, 5.4 mmol) was cleaved
to give 13a (0.86 g, 4.5 mmol, 83 %) as a solid. Rf = 0.22 (PE/
EtOAc, 1:1). M.p. 105–106 °C (PE/EtOAc). [α]2D0 = –9.8 (c = 0.51,
MeOH). IR (MeOH): ν = 3544, 2960 (br), 1715, 1438 cm–1. 1H
˜
NMR (300 MHz, C3D6O): δ = 1.01 (d, J = 6.6 Hz, 3 H, 8-H3), 1.09
(d, J = 6.6 Hz, 3 H, 7-H3), 1.68 (ddd, J = 23.0, 14.0, 5.7 Hz, 2 H,
5-H1), 1.87 (sept, J = 6.6 Hz, 1 H, 6-H1), 2.79 (AB system, J =
16.5 Hz, 2 H, 3-H2), 10.5 (br. s, 2 H, 1-H1, 4-H1) ppm. 13C NMR
(75 MHz, C3D6O): δ = 23.95 (C-8), 24.64 (C-6), 24.73 (C-7), 44.29
(C-3), 48.29 (C-5), 75.51 (C-2), 172.4 (C-4), 176.8 (C-1) ppm.
C8H14O5 (190.20): calcd. C 50.52, H 7.42; found C 50.42, H 7.38.
Methyl (2R,4R)-[2-tert-Butyl-4-(3-methylbutyl)-5-oxo-1,3-dioxolan-
4-yl]acetate (17a): According to General Procedure III alkene 16a
(2.84 g, 10 mmol) was hydrogenated to afford 17a (2.72 g,
9.5 mmol, 95%) as an oil. Rf = 0.25 (PE/EtOAc, 10:1). [α]2D0
=
–18.6 (c = 1.0, CHCl ). IR (CHCl ): ν = 2959, 1801, 1749,
˜
3
3
1485 cm–1. H NMR (300 MHz, CDCl3): δ = 0.86 (s, 3 H, 13-H3)
0.88 (s, 3 H, 12-H3), 0.93 [s, 9 H, C(CH3)3], 1.15–1.40 (m, 2 H, 10-
H2), 1.52 (sept, J = 6.6 Hz, 1 H, 11-H1), 1.78 (tt, J = 8.7, 2.4 Hz,
2 H, 9-H2), 2.79 (s, 2 H, 6-H2), 3.64 (s, 3 H, 8-H3), 5.13 (s, 1 H, 2-
1
(2R)-2-Benzyl-2-hydroxysuccinic Acid (15a): According to General
Procedure IV acetal 14 (1.54 g, 5.4 mmol) was cleaved to give 15a
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 2965–2972