Synthesis of Cyclodextrin Ketoesters and Epoxidation of Alkenes
171.89 (C=O), 139.66, 139.34, 139.28, 139.21, 139.15, 138.86, (CH2=), 100.79, 99.88, 98.17, 98.01, 97.63, 97.25, 97.08 (C-1),
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138.65, 138.56, 138.47, 138.31, 138.28, 138.20, 138.13, 137.79,
137.73, 136.90, 136.67 (Cipso), 128.69, 128.47, 128.40, 128.37,
128.33, 128.28, 128.22, 128.18, 128.08, 128.05, 127.98, 127.93,
127.86, 127.76, 127.69, 127.65, 127.60, 127.57, 127.37, 127.25,
83.53, 81.88, 81.50, 81.36, 81.17, 81.03, 80.93, 80.80, 80.53, 80.37,
80.12, 79.43, 79.27, 79.09, 78.95, 78.40, 78.37, 78.06, 77.37, 76.63,
76.59, 76.56, 76.20, 76.04, 74.29, 74.19, 74.00, 73.44, 73.41, 73.37,
73.28, 72.83, 72.80, 72.63, 72.57, 72.45, 72.23, 71.75, 71.58, 71.45,
127.10, 127.02, 127.00, 126.95, 126.81, 126.53, 126.47 (CHPh), 70.92, 70.59, 70.09, 69.66, 69.38, 68.92, 68.62, 68.45, 64.26, 63.50
100.79, 100.18, 98.84, 97.90, 97.24, 96.17, 95.76 (C-1), 83.23, 82.37,
81.07, 80.44, 80.24, 79.74, 79.22, 78.16, 77.73, 76.53, 76.25, 75.61,
74.55, 74.15, 73.37, 73.13, 72.93, 72.73, 72.66, 72.59, 71.29, 70.74,
70.57, 70.44, 69.38, 68.95, 60.46 (CH2, CH) ppm. MS: calcd. for
C175H180KO37 2912.1840, found 2912.9507.
(CH, CH2) ppm. MS: calcd. for C179H184NaO37 2948.2413, found
2948.5800.
6A,6D-Di-O-propan-2-on-1,3-diyl Hexadeca-O-benzyl-α-cyclodex-
trin-6A,6D-dicarboxylate (9): To a solution of compound 7 (820 mg,
0.33 mmol) in a mixture of acetone/water (9:1, 50 mL) was added
NMO (N-methylmorpholine N-oxide) (133 mg, 3 equiv.) and a
solution of osmium tetroxide 2.5% in butanol (412 μL). The reac-
tion mixture was stirred for ca. 12 h and a solution of sodium thio-
sulfate (10% in water) was added. The mixture was extracted with
AcOEt (3×50 mL), and the organic layer was dried with MgSO4.
Evaporation of the solvent gave the corresponding diol as a white
foam. The diol was dissolved in CH2Cl2 (5 mL), and 1.5 g of
NaIO4/SiO2 (2.54 g NaIO4/10 g SiO2, 5 equiv.) was added. After
stirring for 3 h, the suspension was filtered through Celite. Evapo-
ration of the solvent and flash chromatography (eluent: pentane/
AcOEt, 5:2) gave 0.67 g (82%, 2 steps) of compound 9 as a white
6A,6D-Di-O-prop(2-methylene)-1,3-diyl Hexadeca-O-benzyl-α-cyclo-
dextrin-6A,6D-dicarboxylate (7): To a solution of diacid 5 (1.11 g,
0.45 mmol) in dry DMF (30 mL) was added Cs2CO3 (592 mg,
4 equiv.). After stirring for 30 min at room temperature, 3-chloro-
2-chloromethylpropene (58 μL, 1.1 equiv.) was added, and the reac-
tion mixture was stirred for ca. 12 h at room temperature. The reac-
tion was quenched by the addition of water (30 mL) and AcOEt
(50 mL), and then the organic phase was washed with water
(4×30 mL), dried with MgSO4 and concentrated. The remaining
oil was purified by column chromatography on silica gel (eluent:
pentane/AcOEt, 5:1.5), which resulted in 0.91 g (80%) of com-
1
1
pound 7 as a white foam. [α]D +30.0 (c = 1.2, CHCl3). H NMR
foam. [α]D +36.2 (c = 1.1, CHCl3). H NMR (400 MHz, CDCl3):
(400 MHz, CDCl3): δ = 7.60–6.90 (m, 80 H, CHPh), 5.73 (d, 2 H,
δ = 7.30–6.80 (m, 80 H, CHPh), 5.61 (d, 2 H, J = 4.0 Hz, 1-H),
J = 4.0 Hz, 1-H), 5.61 (d, 2 H, J = 10.8 Hz, H-CHPh), 5.22 (d, 2 5.45 (d, 2 H, J = 10.4 Hz, H-CHPh), 5.07 (d, 2 H, J = 10.4 Hz, H-
H, J = 10.4 Hz, H-CHPh), 5.04 (d, 4 H, J = 11.2 Hz, CH2), 4.96–
4.71 (m, 13 H), 4.69–4.05 (m, 43 H), 4.02–3.94 (m, 5 H), 3.90–3.77
(m, 5 H), 3.72–3.63 (m, 5 H), 3.49 (d, 3 H, J = 9.2 Hz), 3.26 (td, 3
H, J = 3.1 Hz, J = 9.4 Hz) ppm. 13C NMR (100 MHz, CDCl3): δ
= 168.11 (C=O), 139.62, 139.41, 139.34, 138.87, 138.65, 138.48,
137.85, 137.79 (C=, Cipso), 128.43, 128.38, 128.36, 128.13, 128.10,
128.02, 127.97, 127.90, 127.84, 127.79, 127.66, 127.53, 127.34,
127.02, 126.89, 126.79, 126.12 (CHPh), 121.53 (CH2=), 99.11, 98.88,
98.28 (C-1), 81.85, 81.50, 81.27, 80.51, 79.73, 78.80, 78.35, 76.75,
76.53, 76.04, 73.83, 73.68, 73.48, 73.45, 72.75, 72.50, 71.79, 71.31,
69.81, 69.62, 69.05, 64.22 (CH, CH2) ppm. MS: calcd. for
CHPh), 4.89 (d, 2 H, J = 10.4 Hz, H-CHPh), 4.77–4.59 (m, 13 H),
4.53–3.94 (m, 50 H), 3.79 (dd, 3 H, J = 4.4 Hz, J = 9.2 Hz), 3.72–
3.59 (m, 6 H), 3.54 (dd, 3 H, J = 4.0 Hz, J = 9.6 Hz), 3.43 (t, 5 H,
J = 10.0 Hz), 3.32–3.24 (m, 5 H) ppm. 13C NMR (100 MHz,
CDCl3): δ = 198.48, 167.72 (C=O), 139.53, 139.31, 139.80, 138.60,
138.42, 137.75, 137.59 (Cipso), 128.50, 128.41, 128.18, 128.12,
128.08, 128.07, 128.02, 127.80, 127.73, 127.60, 127.37, 127.31,
127.11, 126.96, 126.87, 126.14 (CHPh), 98.89, 98.49 (C-1), 82.22,
81.24, 80.95, 80.50, 79.65, 78.85, 78.21, 76.72, 76.38, 76.01, 73.88,
73.66, 73.46, 72.80, 72.65, 71.90, 71.48, 69.83, 69.72, 68.89, 66.59
(CH, CH2) ppm. MS: calcd. for C151H154NaO33 2518.0269, found
2518.0715.
C152H156NaO32 2516.0477, found 2516.0084.
6A,6D-Di-O-prop(2-methylene)-1,3-diyl Nonadeca-O-benzyl-β-cyclo-
dextrin-6A,6D-dicarboxylate (8): To a solution of diacid 6 (900 mg,
0.31 mmol) in dry DMF (20 mL) was added Cs2CO3 (410 mg,
4 equiv.). After stirring for 30 min at room temperature, 3-chloro-
2-chloromethyl propene (40 μL, 1.1 equiv.) was added, and the re-
action mixture was stirred for ca. 12 h at room temperature. The
reaction was quenched by the addition of water (30 mL) and Ac-
OEt (50 mL), and then the organic phase was washed with water
(4×30 mL), dried with MgSO4 and concentrated. The remaining
oil was purified by column chromatography on silica gel (eluent:
pentane/AcOEt, 5:1), which resulted in 0.63 g (69%) of compound
8 as a white foam. [α]D +37.6 (c = 1.3, CHCl3). 1H NMR
(400 MHz, CDCl3): δ = 7.30–6.82 (m, 95 H, CHPh), 5.83 (d, 1 H,
J = 4.0 Hz, 1-H), 5.63 (d, 1 H, J = 4.0 Hz, 1-H), 5.41 (t, 2 H, J =
6A,6D-Di-O-propan-2-on-1,3-diyl
Nonadeca-O-benzyl-β-cyclodex-
solution of compound
trin-6A,6D-dicarboxylate (10): To
a
8
(763 mg, 0.26 mmol) in a mixture of acetone/water (9:1, 40 mL)
was added NMO (106 mg, 3 equiv.) and a solution of osmium te-
troxide 2.5% in butanol (327 μL). The reaction mixture was stirred
for ca. 12 h, and a solution of sodium thiosulfate (10% in water)
was added. The mixture was extracted with AcOEt (3×50 mL),
and the organic layer was dried with MgSO4. Evaporation of the
solvent gave the corresponding diol as a white foam. The diol was
dissolved in CH2Cl2 (5 mL), and 1.3 g of NaIO4/SiO2 (2.54 g
NaIO4/10 g SiO2, 5 equiv.) was added. After stirring for 3 h, the
suspension was filtered through Celite. Evaporation of the solvent
and flash chromatography (eluent: pentane/AcOEt, 5:2) gave 0.60 g
(79%, 2 steps) of compound 10 as a white foam. [α]D +41.1 (c =
9.8 Hz), 5.25–5.16 (m, 3 H), 5.01 (d, 2 H, J = 10.8 Hz, H-CHPh), 1.2, CHCl3). 1H NMR (400 MHz, CDCl3): δ = 7.30–6.70 (m, 95
4.97 (d, 1 H, J = 3.2 Hz, 1-H), 4.91–4.76 (m, 6 H), 4.74–4.09 (m, H, CHPh), 5.73 (d, 1 H, J = 4.0 Hz, 1-H), 5.43 (d, 1 H, J = 11.2 Hz,
40 H), 4.09–3.99 (m, 5 H), 3.98–3.66 (m, 33 H), 3.62 (d, 1 H, J = H-CHPh), 5.39 (d, 1 H, J = 3.6 Hz, 1-H), 5.27 (d, 1 H, J = 10.0 Hz,
10.4 Hz), 3.58–3.41 (m, 6 H), 3.40–3.30 (m, 6 H), 3.26 (dd, 1 H, J
CH2), 5.17–4.95 (m, 7 H), 4.90–4.34 (m, 62 H), 4.32–3.65 (m, 27
= 3.4 Hz, J = 9.8 Hz), 3.19 (d, 1 H, J = 10.8 Hz) ppm. 13C NMR
H), 3.63–3.19 (m, 21 H) ppm. 13C NMR (100 MHz, CDCl3): δ =
(100 MHz, CDCl3): δ = 168.70, 168.25 (C=O), 139.75, 139.71, 196.95, 168.46, 166.98 (C=O), 139.62, 139.43, 139.31, 138.95,
139.46, 139.33, 139.27, 138.99, 138.71, 138.65, 138.60, 138.54,
138.37, 138.20, 138.17, 138.01, 137.95, 137.75, 137.72, 137.66,
137.03 (C=, Cipso), 128.51, 128.44, 128.40, 128.35, 128.29, 128.25,
128.22, 128.11, 128.05, 128.00, 127.96, 127.89, 127.83, 127.80,
127.76, 127.69, 127.60, 127.57, 127.44, 127.37, 127.18, 127.11,
127.05, 126.95, 126.89, 126.61, 126.53, 126.37 (CHPh), 121.43
138.85, 138.71, 138.63, 138.37, 138.28, 138.23, 137.90, 137.86,
137.73, 137.70, 137.52 (Cipso), 128.66, 128.43, 128.40, 128.36,
128.29, 128.22, 128.20, 128.17, 128.11, 127.99, 127.94, 127.92,
127.88, 127.85, 127.81, 127.73, 127.69, 127.63, 127.50, 127.47,
127.28, 127.25, 127.18, 126.93, 126.44 (CHPh), 99.58, 99.24, 99.14,
98.40, 97.68, 97.59, 97.05 (C-1), 83.01, 82.18, 81.92, 81.37, 81.15,
Eur. J. Org. Chem. 2005, 2734–2739
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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