Indium-Mediated Allenylation of Aldehydes
Typical Procedure for Ozonolysis (Method B): Synthesis of Com-
pounds 22, 23, and 28
Typical Procedure for Isopropylidine Cleavage of Allenes
(Method D): Synthesis of Compounds 26 and 27
1-O-Benzyl-4,5-O-isopropylidene-D-erythro-2-pentulose (22): Ozone
1-O-Benzyl-2-deoxy-2-C-ethenylidene-D-erythro-pentitol (26): To a
was bubbled through
a solution of compound 3a (145 mg,
suspension of compound 3a (34 mg, 0.117 mmol) in water/THF
(1:1, 2 mL) was added Amberlyst 15 (H+ form, 40 mg), and the
mixture was stirred at room temperature. After TLC monitoring
showed conversion of the starting material, the resin was removed
by filtration and washed with methanol, and the solvent was re-
moved under reduced pressure to yield compound 26 (28 mg; 97%).
0.5 mmol) in CH2Cl2 (25 mL) at –78 °C until the color of the mix-
ture turned blue. Dry air was bubbled through the solution until
the blue color disappeared. After addition of PPh3 (157 mg,
0.6 mmol), the mixture was allowed to reach room temperature by
stirring overnight. The solvent was removed under reduced pres-
sure, and the crude material was purified by flash chromatography
(hexane/ethyl acetate = 4:1) to yield compound 22 (133 mg; 95%).
[α]2D0 = –57.3 (c = 0.3, CH2Cl2).1H NMR (400 MHz, CDCl3): δ =
7.39–7.26 (m, 5 H, Ar-H), 4.62 (s, 2 H, CH2), 4.57 (d, 2J = 18.2 Hz,
1 H, CH2), 4.29 (d, 2J = 17.9 Hz, 1 H, CH2), 4.17 (dd, 2J = 6.7 Hz,
3J = 6.4 Hz, 1 H, CH2), 4.12–3.93 (m, 3 H, 2 CH, CH2), 3.29 (d,
3J = 5.8 Hz, 1 H, OH), 1.42 (s, 3 H, CH3), 1.33 (s, 3 H, CH3) ppm.
13C NMR (400 MHz, CDCl3): δ = 208.0 (C), 137.1 (C), 128.7 (2
CH), 128.3 (CH), 128.2 (2 CH), 110.4 (C), 76.2 (CH), 75.3 (CH),
73.7 (CH2), 73.6 (CH2), 67.1 (CH2), 26.7 (CH3), 25.2 (CH3) ppm.
[α]2D0 = +14.8 (c = 0.25, MeOH). H NMR (400 MHz, D2O): δ =
1
7.58–7.36 (m, 5 H, Ar-H), 5.12 (s, 2 H, CH2), 4.64 (s, 2 H, CH2),
4.27–4.13 (m, 3 H, CH, CH2), 3.89–3.77 (m, 2 H, CH2), 3.73–3.61
(m, 1 H, CH2) ppm. 13C NMR (400 MHz, D2O): δ = 207.0 (C),
137.1 (C), 128.8 (2 CH), 128.7 (2 CH), 128.4 (CH), 100.4 (C), 78.7
(CH2), 73.2 (CH), 71.8 (CH2), 70.5 (CH), 67.9 (CH2), 62.5 (CH2)
ppm. IR (film): ν = 3377, 2926, 1956, 1055, 745, 698 cm–1. HRMS
˜
(ESI): calcd. for C14H18O4Na [M + Na]+ 273.1103; found 273.1099.
(2R,3S)-4-Methylhexa-4,5-dien-1,2,3-triol (27): Method D was ap-
plied to compound 9a (46 mg, 0.25 mmol) for deprotection to yield
product 27 (35 mg, 98%). [α]2D0 = +25.9 (c = 0.35, MeOH). 1H
IR (film): ν = 3386, 2934, 1729, 1067, 739, 698 cm–1. HRMS (ESI):
˜
calcd. for C15H20O5Na [M + Na]+ 303.1208; found 303.1206.
3
NMR (400 MHz, D2O): δ = 4.88–4.80 (m, 2 H, CH2), 4.08 (dt, J
= 7.5 Hz, 5J = 1.4 Hz, 1 H, CH), 3.85 (dd, 2J = 11.7 Hz, 3J =
1-Deoxy-4,5-O-isopropylidene-D-erythro-2-pentulose
(23):
2.78 Hz, 1 H, CH2), 3.81–3.74 (m, 1 H, CH), 3.66 (dd, 2J =
Method B was applied to compound 9a (92 mg, 0.5 mmol) for
ozonolysis to yield product 23 (68 mg; 78%). [α]2D0 = –90.6 (c = 0.5,
CH2Cl2). 1H NMR (400 MHz, CDCl3): δ = 4.14–4.01 (m, 3 H, CH
CH2), 3.95–3.87 (m, 1 H, CH), 3.47 (d, 3J = 5.4 Hz, 1 H, OH), 2.3
(s, 3 H, CH3), 1.49 (s, 3 H, CH3), 1.35 (s, 3 H, CH3) ppm. 13C
NMR (400 MHz, CDCl3): δ = 209.1 (C), 110.4 (C), 77.6 (CH), 76.4
(CH), 67.5 (CH2), 27.7 (CH3), 26.8 (CH3), 25.4 (CH3) ppm. IR
3
5
11.7 Hz, J = 6.6 Hz, 1 H, CH2), 1.75 (t, J = 3.22 Hz, 3 H, CH3)
ppm. 13C NMR (600 MHz, D2O): δ = 206.9 (C), 98.5 (C), 76.0
(CH2), 73.4 (CH), 72.7 (CH), 63.0 (CH2), 14.0 (CH3) ppm. IR
(film): ν = 3317, 2926, 1961, 1035 cm–1. HRMS (ESI): calcd. for
˜
C7H12O3Na [M + Na]+ 167.0684; found 167.0680.
1-O-Benzyl-D-erythro-2-pentulose (28): Method C was applied to
compound 22 (39 mg, 0.139 mmol) for deprotection to yield prod-
uct 28 (27 mg; 81%), or compound 26 (25 mg, 0.1 mmol) was ozon-
ized in a mixture of MeOH/CH2Cl2 (9:1) according to method B
to yield product 28 (21.6 mg; 90%). Equilibrium of three com-
(film): ν = 3424, 2989, 1716, 1069 cm–1. HRMS (ESI): calcd. for
˜
C8H14O4Na [M + Na]+ 197.0790; found 197.0794.
4,5-O-Isopropylidene-D-erythro-2-pentulose (24): Pentulose deriva-
tive 22 (21 mg, 0.075 mmol) was dissolved in ethanol (2 mL) and
hydrogenated in the presence of 10% palladium-on-charcoal (1 mg)
with a balloon of hydrogen. The catalyst was removed by filtration,
and the solvent was removed under reduced pressure to yield com-
pound 24 (10 mg, 72%). [α]2D0 = –71.5 (c = 0.5, CH2Cl2). 1H NMR
pounds: α/β/open = 62:25:13. [α]2D0 = –20.7 (c = 2.25, MeOH). H
1
NMR (600 MHz, CD3COCD3+D2O, α-isomer): δ = 7.39–7.23 (m,
5 H, Ar-H), 4.65–4.46 (m, 2 H, CH2), 4.22–4.17 (m, 1 H, CH), 4.06
(d, 3J = 5.3 Hz, 1 H, CH), 3.92 (dd, 2J = 9.4 Hz, 3J = 5.3 Hz, 1 H,
2
3
(400 MHz, CDCl3): δ = 4.68 (dd, J = 20.1 Hz, J = 5.0 Hz, 1 H,
2
3
2
CH2), 3.78 (dd, J = 9.3 Hz, J = 3.6 Hz, 1 H, CH2), 3.52 (d, J =
10.6 Hz, 1 H, CH2), 3.44 (d, 2J = 10.2 Hz, 1 H, CH2) ppm. 1H
NMR (600 MHz, CD3COCD3+D2O, β-isomer): δ = 7.39–7.23 (m,
5 H, Ar-H), 4.65–4.46 (m, 2 H, CH2), 4.45–4.38 (m, 1 H, CH), 4.04
2
3
3
CH2), 4.40 (dd, J = 20.0 Hz, J = 3.5 Hz, 1 H, CH2), 4.24 (dd, J
= 7.7 Hz, 3J = 5.2 Hz, 1 H, CH), 4.14 (dd, 2J = 8.9 Hz, 3J = 6.3 Hz,
1 H, CH2), 4.07 (dd, 2J = 8.9 Hz, 3J = 5.0 Hz, 1 H, CH2), 3.99
3
3
3
3
(ddd, J = 7.8 Hz, J = 6.3 Hz, J = 5.1 Hz, 1 H, CH), 3.24 (d, J
2
3
3
(dd, J = 8.9 Hz, J = 6.3 Hz, 1 H, CH2), 3.97 (d, J = 5.3 Hz, 1
H, CH), 3.71 (d, J = 10.2 Hz, 1 H, CH2), 3.64 (dd, J = 8.9 Hz,
3
= 5.4 Hz, 1 H, OH), 3.05 (t, J = 4.9 Hz, 1 H, OH), 1.49 (s, 3 H,
2
2
CH3), 1.36 (s, 3 H, CH3) ppm. 13C NMR (400 MHz, CDCl3): δ =
2
1
3J = 4.7 Hz, 1 H, CH2), 3.58 (d, J = 10.2 Hz, 1 H, CH2) ppm. H
NMR (600 MHz, CD3COCD3+D2O, open isomer): δ = 7.71–7.55
(m, 2 H, Ar-H), 7.64–7.60 (m, 1 H, Ar-H), 7.57–7.51 (m, 2 H, Ar-
H), 4.65–4.46 (m, 4 H, 2 CH2), 4.23 (d, 3J = 5.7 Hz, 1 H, CH),
210.7 (C), 110.6 (C), 76.0 (CH), 75.4 (CH), 67.6 (CH2), 67.3 (CH2),
26.7 (CH ), 25.1 (CH ) ppm. IR (film): ν = 3411, 2925, 1726,
˜
3
3
1066 cm–1. HRMS (EI): calcd. for C7H11O6 [M – CH3]+ 175.0606;
found 175.0610.
2
3
3.89–3.84 (m, 1 H, CH), 3.66 (dd, J = 11.0 Hz, J = 5.3 Hz, 1 H,
CH2), 3.59 (dd, 2J = 11.2 Hz, 3J = 5.9 Hz, 1 H, CH2) ppm. 13C
NMR (600 MHz, CD3COCD3+D2O, α-isomer): δ = 139.3 (C),
129.0 (2 CH), 128.2 (2 CH), 128.1 (CH), 103.3 (C), 73.8 (CH2),
72.2 (CH2), 71.9 (CH2), 71.8 (CH), 71.2 (CH) ppm. 13C NMR
(600 MHz, CD3COCD3+D2O, β-isomer): δ = 139.2 (C), 128.5
(CH), 128.4 (2 CH), 128.1 (2 CH), 106.1 (C), 76.9 (CH), 74.0
(CH2), 72.3 (CH2), 71.9 (CH2), 71.6 (CH) ppm. 13C NMR
(600 MHz, CD3COCD3+D2O, open isomer): δ = 209.7 (C), 139.5
(C), 132.9 (2 CH), 132.6 (2 CH), 132.5 (CH), 77.0 (CH), 74.4
(CH2), 74.2 (CH), 73.3 (CH2), 62.9 (CH2) ppm. HRMS (ESI):
calcd. for C12H16O5Na [M + Na]+ 263.0895; found 263.0893.
Typical Procedure for Isopropylidine Cleavage of Ketoses
(Method C): Synthesis of Compounds 25, 28, and 29
D-erythro-2-Pentulose (25): To a suspension of 4,5-O-isopropylid-
ene-d-erythro-2-pentulose (24; 9 mg, 0.047 mmol) in water/THF
(1:1, 0.8 mL) was added Amberlyst 15 (H+ form, 6 mg), and the
mixture was stirred at room temperature. After TLC monitoring
showed conversion of the starting material, the pH of the solution
was adjusted to 7 by addition of 0.05 n NaOH. The resin was re-
moved by filtration and washed with water, and the solvent was
lyophilized. The crude product was purified by flash chromatog-
raphy over silica gel (ethyl acetate/MeOH = 8:1) to yield 25 (6.1 mg,
86%). Equilibrium of three compounds: α/β/open = 58:24:18.
[α]2D0 = –14.0 (c = 0.25, H2O). The spectroscopic data were identical
with those reported.[16]
1-Deoxy-
pound 23 (10 mg, 0.057 mmol) for deprotection to yield product 29
(7 mg; 91%). Equilibrium of three compounds: α/β/open
D-erythro-2-pentulose (29): Method C was applied to com-
=
Eur. J. Org. Chem. 2011, 1645–1651
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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