208
A. N. Kumar et al. / Tetrahedron: Asymmetry 20 (2009) 205–209
2714, 1717 cmꢂ1; 1H NMR: d 1.46 (s, 3H), 1.49 (s, 3H), 1.62–1.72 (m,
2H), 2.55–2.71 (m, 1H), 2.84–2.95 (m, 1H), 4.19–4.28 (m, 2H), 7.21–
7.25 (m, 5H), 9.55 (s, 1H); 13C NMR: d 19.3, 30.3, 42.6, 69.3, 73.8, 99.0,
125.8, 126.1, 128.1, 129.3, 137.0, 200.9. Anal. Calcd for C14H18O3: C,
71.77; H, 7.74. Found: C, 71.96; H, 7.89.
½
a 2D2
ꢃ
¼ þ10:4 (c 1.18, CHCl3). IR: 3408, 1725 cmꢂ1
;
1H NMR: d
0.05 (s, 6H), 1.09 (s, 9H), 1.52–1.68 (m, 2H), 1.99 (s, 3H), 2.28 (br
s, 2H), 2.78–2.86 (m, 2H), 3.46–3.72 (m, 2H), 3.89–3.97 (m, 1H),
5.07–5.14 (m, 1H), 7.19 (br s, 5H); 13C NMR: d ꢂ5.3, 18.7, 20.8,
37.2, 40.9, 66.2, 68.0, 71.8, 126.3, 128.1, 129.2, 136.9, 171.6. Anal.
Calcd for C19H32O4Si: C, 64.73; H, 9.15. Found: C, 64.87; H, 9.27.
3.11. (3R,5R)-3-Hydroxy-5-phenylmethyldihydrofuran-2-one
(3R,5R)-1
3.15. (2R,4S)-1-(tert-Butyldimethylsilyloxy)-2,4-
isoproanedioxy-5-phenylpentane (2R,4S)-12
To a mixture of 9 (0.374 g, 1.6 mmol) in DMSO (1.6 mL) and a
solution of NaH2PO4 (52 mg) in water (0.6 mL) was dropwise
added NaClO2 (0.253 g, 2.24 mmol, 80% purity) in water (2.5 mL).
After stirring the reaction mixture at room temperature for 22 h,
it was acidified with aqueous 3 M HCl. The reaction mixture was
extracted with EtOAc, and the organic extract washed with water
and brine, and dried. Removal of the solvent in vacuo followed
by column chromatography (silica gel, 0–25% EtOAc/hexane) affor-
ded pure (R,R)-1. Yield: 0.135 g (44%); white solid; mp: 78–79 °C
A mixture of 11 (3.06 g, 15 mmol) and K2CO3 (4.15 g, 30 mmol) in
MeOH (25 mL) was stirred at room temperature for 6 h. The mixture
was filtered, concentrated in vacuo, and water was added after which
the mixture was extracted with EtOAc. The organic layer was washed
with water and brine, and dried. Removal of solvent in vacuo followed
by column chromatography of the residue (silica gel, 0–10% EtOAc/
hexane) afforded the corresponding alcohol. Yield: 1.04 g (91%).
A solution of the above-mentioned product (1.30 g, 3.0 mmol),
DMP (0.625 g, 6.0 mmol) and PPTS (0.075 g, 0.3 mmol) in CH2Cl2
(5 mL) was stirred at room temperature for 3 h. The reaction mixture
was diluted with Et2O, the organic layer was washed with 10% aque-
ous NaHCO3, water and brine, and dried. Removal of solvent in vacuo
followed by column chromatography (silica gel, 0–5% EtOAc/hex-
ane) of the residue afforded pure 12. Yield: 0.990 g (88%); colourless
(lit.3d mp: 80 °C); ½a 2D2
ꢃ
¼ þ38:6 (c 0.702, CHCl3) {lit.3d
½
a 2D5
ꢃ
¼ þ40
(c 0.3, CHCl3)}; IR: 3398, 1768 cmꢂ1 1H NMR: d 2.24–2.33 (m,
;
2H), 2.95 (d, J = 6.0 Hz, 2H), 3.35 (br s, 1H), 4.07 (t, J = 7.2 Hz,
1H), 4.85–4.91 (m, 1H), 7.17–7.31 (m, 5H); 13C NMR: d 34.4, 41.0,
67.0, 78.4, 127.1, 128.7, 129.5, 135.3, 177.7.
3.12. (3S,5S)-3-Hydroxy-5-phenylmethyldihydrofuran-2-one
(3S,5S)-1
oil; ½a 2D2
ꢃ
¼ þ7:5 (c 0.860, CHCl3). IR: 1484, 1383 cmꢂ1
;
1H NMR: d
0.05 (s, 6H), 1.08 (s, 9H), 1.26–1.32 (m, 1H), 1.40–1.71 (m containing
a s at d 1.43, 7H), 2.63–2.69 (m, 1H), 2.84–3.0 (m, 1H), 3.44–3.50 (m,
1H), 3.56–3.70 (m, 1H), 3.74–3.81 (m, 1H), 3.88–4.12 (m, 1H), 7.25–
7.41 (m, 5H); 13C NMR: d ꢂ5.4, 18.2, 23.8, 24.0, 33.1, 42.9, 66.8, 69.7,
72.9, 100.2, 126.3, 128.4, 129.4, 138.2. Anal. Calcd for C20H34O3Si: C,
68.52; H, 9.78. Found: C, 68.36; H, 9.60.
In analogy to the preparation of (3R,5R)-1 from (S)-3, (3S,5S)-1
was prepared from (R)-3 in six steps and 22% yield. White solid;
mp: 68 °C (lit.3b mp: 71–74 °C); ½a 2D2
¼ ꢂ36:4 (c 0.781, CHCl3)
ꢃ
{lit.3b
½
a 2D2
ꢃ
¼ ꢂ38:0 (c 0.3, CHCl3)}; IR: 3408, 1765 cmꢂ1
;
1H NMR:
d 2.22–2.35 (m, 2H), 2.68 (br s, 1H), 2.89 (d, J = 6.2 Hz, 2H), 3.95
(t, J = 7.2 Hz, 1H), 4.86–4.98 (m, 1H) and 7.17 (br s, 5H); 13C
NMR: d 34.7, 41.5, 66.8, 78.1, 127.3, 128.9, 135.5, 177.2.
3.16. (2R,4S)-2,4-Isopropanedioxy-5-phenylpentan-1-ol
(2R,4S)-13
3.13. (2R,4S)-4-Acetoxy-5-phenylpentane-1,2-diol (2R,4S)-10
As described for 8, compound 12 (0.700 g, 2.0 mmol) was desi-
lylated with Bu4NF (2.2 mL, 2.2 mmol, 1.0 M in THF) in THF (5 mL)
to furnish 13 after purification by column chromatography (silica
gel, 0–10% EtOAc/hexane). Yield: 0.396 g (84%); colourless oil;
A solution of (R)-4 (2.0 g, 10 mmol) in tert-BuOH/water (1:1,
25 mL) was added to a cooled (0 °C) and stirred suspension of AD
mix-b (14.0 g) in the same solvent (120 mL). The mixture was stir-
red at 0 °C for 14 h, treated with solid Na2SO3 (14.0 g), stirred for a
further 1 h at room temperature and extracted with CHCl3. The or-
ganic extract was washed with water and brine, and dried. Solvent
removal and column chromatography of the residue (silica gel, 0–
7% MeOH/CHCl3) afforded 10 as the sole product. Yield: 1.92 g
½
a 2D2
ꢃ
¼ þ5:2 (c 0.882, CHCl3); IR: 3431 cmꢂ1
;
1H NMR: d 1.22–
1.36 (m, 2H), 1.53 (s, 3H), 1.58 (s, 3H), 2.24 (broad s, 1H), 2.52–
2.75 (m, 2H), 3.43–3.47 (m, 2H), 3.78–3.93 (m, 2H), 7.20–7.26
(m, 5H); 13C NMR: d 23.7, 24.7, 38.6, 43.7, 69.4, 72.6, 75.3, 101.1,
126.1, 128.4, 129.2, 138.1. Anal. Calcd for C14H20O3: C, 71.16; H,
8.53. Found: C, 71.02; H, 8.65.
(81%); colourless oil; ½a D22
¼ þ14:8 (c 0.88, CHCl3). IR: 3442,
ꢃ
1734 cmꢂ1
;
1H NMR: d 1.56–1.72 (m, 2H), 2.01 (s, 3H), 2.63 (br s,
3.17. (2R,4S)-2,4-Isopropanedioxy-5-phenylpentanal (2R,4S)-14
2H), 2.87 (two overlapping d, J = 5.6 Hz, 2H), 3.46–3.72 (m, 2H),
4.08–4.18 (m, 1H), 5.21–5.27 (m, 1H), 7.19–7.34 (m, 5H); 13C
NMR: d 20.8, 37.2, 40.9, 66.2, 68.0, 71.8, 126.3, 128.1, 129.2,
136.9, 171.6. Anal. Calcd for C13H18O4: C, 65.53; H, 7.61. Found:
C, 65.38; H, 7.75.
Compound 13 (0.390 g, 1.65 mmol) was oxidized using oxalyl
chloride
(0.254 g,
1.92 mmol),
dimethylsulfoxide
(0.3 g,
3.84 mmol) and Et3N (0.910 g, 9 mmol) in CH2Cl2 (15 mL) to give
14 after work-up, as described for 9. Yield: 0.344 g (89%); colour-
less oil; ½a 2D2
ꢃ
¼ þ5:9 (c 1.04, CHCl3); IR: 2721, 1736 cmꢂ1
;
1H
3.14. (2R,4S)-1-(tert-Butyldimethylsilyloxy)-4-acetoxy 5-
phenylpentane-2-ol (2R,4S)-11
NMR: d 1.44–1.65 (m, containing two s at d 1.54 and d 1.62, 8H),
2.51–2.68 (m, 1H), 2.78–2.88 (m, 1H), 3.99–4.10 (m, 1H), 4.19–
4.24 (m, 1H), 7.32 (m, 5H), 9.52 (s, 1H); 13C NMR: d 23.6, 29.6,
44.7, 65.9, 71.0, 105.1, 126.4, 128.2, 129.3, 137.6, 202.3. Anal. Calcd
for C14H18O3: C, 71.77; H, 7.74. Found: C, 71.89; H, 7.91.
To
a
stirred and cooled (ꢂ30 °C) solution of 10 (1.20 g,
5.0 mmol), DMAP (catalytic) and Et3N (1.32 mL, 9.50 mmol) in
CH2Cl2 (25 mL) was added TBSCl (1.12 g, 7.50 mmol) in CH2Cl2
(25 mL). After stirring the mixture for 18 h at 0 °C, it was poured
into ice cold water and the organic layer was separated and the
aqueous portion was extracted with CHCl3. The combined organic
extracts were washed with aqueous saturated NH4Cl, water and
brine, and dried. Removal of solvent in vacuo followed by purifica-
tion with column chromatography (silica gel, 0–10% EtOAc/hex-
ane) afforded pure 11. Yield: 1.33 g (75%); colourless oil;
3.18. (3R,5S)-3-Hydroxy-5-phenylmethyldihydrofuran-2-one
(3R,5S)-1
Oxidation of 14 (0.340 g, 1.45 mmol) with NaClO2 (0.230 g,
2.0 mmol, 80% purity) and NaH2PO4 (50 mg) in DMSO (1.5 mL)
and water (3.5 mL) followed by acidic work-up and purification
furnished (3R,5S)-1. Yield: 0.116 g (42%); white solid; mp 99–