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K. Konuki, H. Nagai / Tetrahedron: Asymmetry 25 (2014) 1581–1589
(R)-14, 15.5 min for (S)-14; 1H NMR (CDCl3, 500 MHz) d 7.55 (dd,
J = 8.5, 2.5, 1H), 7.34 (d, J = 2.5, 1H), 6.97 (d, J = 8.5, 1H), 5.22–
5.19 (m, 1H), 3.97 (s, 3H), 3.95 (s, 3H), 2.99–2.88 (br m, 4H),
2.35–2.30 (m, 1H), 2.00–1.93 (m, 1H).
Next, EtOAc (5 mL, 5 v/w) was added to (R)-14 (1.0 g, 68.6% ee),
and heated until it dissolved. This solution was stirred overnight at
5 °C, and the precipitated crystals were filtered to furnish white
crystals (0.53 g, 61.8% ee, 53%): mp 87–90 °C. The mother liquor
was concentrated by an evaporator to provide a colorless oil
(0.38 g, 75.4% ee, 38%).
Next, MeOH (8 mL, 8 v/w) was added to (R)-14 (1.0 g, 68.6% ee),
and heated until it dissolved. This solution was stirred overnight at
room temperature, and the precipitated crystals were filtered to
furnish white crystals (0.85 g, 67.8% ee, 85%): mp 88–89 °C. The
mother liquor was concentrated by an evaporator to provide a col-
orless oil (0.12 g, 82.3% ee, 12%).
500 MHz) d 8.51 (s, 1H), 8.02–7.86 (m, 4H), 7.71–7.64 (m, 2H),
5.29–5.27 (m, 1H), 2.97–2.86 (br m, 4H), 2.35–2.32 (m, 1H),
1.99–1.93 (m, 1H).
Compound (R)-16 (1.0 g, 72.7% ee) was dissolved in EtOAc
(2 mL, 2 v/w) at room temperature. To this solution was added
dropwise hexane (4 mL, 4 v/w), and the mixture was stirred over-
night at room temperature. The precipitated crystals were filtered
and washed with hexane to furnish pale yellow crystals (0.52 g,
62.2% ee, 52%): mp 68–70 °C. The mother liquor was concentrated
by an evaporator to provide a pale yellow solid (0.35 g, 91.5% ee,
35%): mp 56–61 °C.
Compound (R)-16 (3.0 g, 72.7% ee) was dissolved in EtOAc
(6 mL, 2 v/w) at room temperature. To this solution was added
dropwise hexane (18 mL, 6 v/w), and the mixture was stirred over-
night at room temperature. The precipitated crystals were filtered
and washed with hexane to furnish pale yellow crystals (2.26 g,
65.7% ee, 75%): mp 64–66 °C; [
mother liquor was concentrated by an evaporator to provide a pale
yellow solid (0.44 g, 94.2% ee, 15%): mp 59–65 °C; [
20 = +13.5 (c
a]
20 = +10.6 (c 0.50, MeOH). The
D
4.2.13. (R)-3-[(1-Naphthalenesulfonyl)oxy]tetrahydrothiophene
15 (R)-15
a]
D
Using the same procedure as (R)-4, (R)-1 (2.0 g, 19.2 mmol) was
treated with DMAP (3.52 g, 28.8 mmol) and 1-naphthalenesulfonyl
chloride (5.21 g, 23.0 mmol), and gave crude (R)-15. The crude was
purified by silica gel chromatography (hexane/EtOAc 3:1–2:1,
stepwise) to yield (R)-15 (4.86 g, 72.4% ee, 86%) as a white solid:
0.50, MeOH). Reproducibility experiment: pale yellow crystals
(0.65 g, 66.5% ee, 65%): mp 67–70 °C, a pale yellow solid from the
mother liquor (0.28 g, 93.4% ee, 28%): mp 58–64 °C; [
(c 0.50, MeOH).
a]
20 = +13.6
D
Next, EtOAc (1.4 mL, 2 v/w) was added to (R)-16 (0.68 g, 72.7%
ee), and was heated until it dissolved. This solution was stirred
overnight at 0 °C, and the precipitated crystals were filtered to fur-
nish pale yellow crystals (0.23 g, 59.0% ee, 33%): mp 65–70 °C. The
mother liquor was concentrated by an evaporator to provide a pale
yellow solid (0.35 g, 84.9% ee, 51%): mp 61–62 °C.
mp 62–64 °C;
[a]
20 = +18.6 (c 0.50, MeOH); HPLC analysis:
D
Chiralpak AS-H column, mobile phase: hexane/2-PrOH = 90:10,
column temperature: 30 °C, flow rate: 1 mL/min, detection:
254 nm, tR = 19.6 min for (R)-15, 21.3 min for (S)-15; 1H NMR
(CDCl3, 500 MHz) d 8.59 (d, J = 8.5, 1H), 8.31 (d, J = 7.5, 1H), 8.15
(d, J = 8.5, 1H), 7.97 (d, J = 8.0, 1H), 7.72 (t, J = 8.5, 1H), 7.64 (t,
J = 7.0, 1H), 7.58 (t, J = 8.0, 1H), 5.19–5.16 (m, 1H), 2.90–2.80 (br,
4H), 2.25–2.19 (m, 1H), 1.89–1.82 (m, 1H).
4.2.15. (R)-3-[(5-(Dimethylamino)naphthalene-1-sulfonyl)oxy]
tetrahydrothiophene 17 (R)-17
Compound (R)-15 (1.0 g, 72.4% ee) was dissolved in EtOAc
(2 mL, 2 v/w) at room temperature. To this solution was added
dropwise hexane (4 mL, 4 v/w), and the mixture was stirred over-
night at room temperature. The precipitated crystals were filtered
and washed with hexane to furnish white crystals (0.52 g, 75.2% ee,
52%): mp 62–65 °C. The mother liquor was concentrated by an
evaporator to provide a white solid (0.38 g, 71.6% ee, 38%).
Compound (R)-15 (1.0 g, 72.4% ee) was dissolved in EtOAc
(2 mL, 2 v/w) at room temperature. To this solution was added
dropwise hexane (6 mL, 6 v/w), and the mixture was stirred over-
night at room temperature. The precipitated crystals were filtered
and washed with hexane to furnish white crystals (0.69 g, 73.7% ee,
Using the same procedure as (R)-4, (R)-1 (2.08 g, 20 mmol) was
treated with DMAP (3.66 g, 30 mmol) and 5-(dimethyl-
amino)naphthalene-1-sulfonyl chloride (6.74 g, 25 mmol), and
gave crude (R)-17. The crude was purified by silica gel chromatog-
raphy (hexane/EtOAc 9:1–5:1, stepwise) to yield (R)-17 (5.00 g,
71.4% ee, 74%) as
[a]
D
a light yellow solid: mp 100–104 °C;
20 = +16.7 (c 0.50, MeOH); HPLC analysis: Chiralcel OD column,
mobile phase: hexane/2-PrOH = 90:10, column temperature:
30 °C, flow rate: 1 mL/min, detection: 254 nm, tR = 7.7 min for
(R)-17, 8.4 min for (S)-17; 1H NMR (CDCl3, 500 MHz) d 8.61 (d,
J = 8.5, 1H), 8.29 (d, J = 7.5, 1H), 8.23 (d, J = 9.0, 1H), 7.60 (dd,
J = 8.0, 7.5, 1H), 7.55 (dd, J = 7.5, 7.5, 1H), 7.21 (d, J = 7.5, 1H),
5.18–5.15 (m, 1H), 2.94–2.85 (m, 3H), 2.90 (s, 3H), 2.89 (s, 3H),
2.82–2.78 (m, 1H), 2.26–2.21 (m, 1H), 1.90–1.83 (m, 1H).
69%): mp 64–66 °C; [a]
20 = +19.3 (c 0.50, MeOH). The mother
D
liquor was concentrated by an evaporator to provide a white solid
(0.28 g, 70.7% ee, 28%): mp 61–64 °C. Reproducibility experiment:
white crystals (0.64 g, 74.6% ee, 64%): mp 62–65 °C, a white solid
from the mother liquor (0.27 g, 70.6% ee, 27%).
EtOAc (2 mL, 2 v/w) was added to (R)-15 (1.0 g, 72.4% ee), and
heated until it dissolved. This solution was stirred overnight at
0 °C, and the precipitated crystals were filtered to furnish white
crystals (0.33 g, 74.6% ee, 33%): mp 63–66 °C. The mother liquor
was concentrated by an evaporator to provide a white solid
(0.58 g, 72.5% ee, 58%): mp 62–66 °C.
Compound (R)-17 (1.0 g, 71.4% ee) was dissolved in EtOAc
(10 mL, 10 v/w) at room temperature. To this solution was added
dropwise hexane (25 mL, 25 v/w), and the mixture was stirred
overnight at room temperature. The precipitated crystals were fil-
tered and washed with hexane to furnish light yellow crystals
(0.52 g, 84.9% ee, 52%): mp 104–106 °C; [a]
20 = +19.9 (c 0.50,
D
MeOH). The mother liquor was concentrated by an evaporator to
provide a yellow solid (0.44 g, 56.8% ee, 44%): mp 92–100 °C;
[a]
20 = +13.2 (c 0.50, MeOH).
D
4.2.14. (R)-3-[(2-Naphthalenesulfonyl)oxy]tetrahydrothiophene
16 (R)-16
4.2.16. (R)-3-[((+)-10-Camphorsulfonyl)oxy]tetrahydrothiophe-
ne 18 (R)-(+)-18
Using the same procedure as (R)-4, (R)-1 (5.0 g, 48.1 mmol) was
treated with DMAP (11.8 g, 96.2 mmol) and 2-naphthalenesulfonyl
chloride (16.4 g, 72.2 mmol), and gave crude (R)-16. The crude was
purified by silica gel chromatography (hexane/EtOAc 3:1) to yield
(R)-16 (8.22 g, 72.7% ee, 58%) as a pale yellow solid: HPLC analysis:
Chiralcel OJ column, mobile phase: hexane/2-PrOH = 60:40, col-
umn temperature: 30 °C, flow rate: 1 mL/min, detection: 254 nm,
tR = 12.8 min for (R)-16, 10.9 min for (S)-16; 1H NMR (CDCl3,
Using the same procedure as (R)-4, (R)-1 (2.0 g, 19.2 mmol) was
treated with DMAP (3.52 g, 28.8 mmol) and (+)-10-camphorsulfo-
nyl chloride (5.77 g, 23.0 mmol), and gave crude (R)-(+)-18
(6.36 g, 72% de, quant.) as a yellow solid: HPLC analysis: Chiralpak
AS-H column, mobile phase: hexane/2-PrOH = 80:20, column tem-
perature: 30 °C, flow rate: 1 mL/min, detection: 210 nm, tR = 20.9 -
min for (R)-(+)-18, 19.1 min for (S)-(+)-18; 1H NMR (CDCl3,
500 MHz) d 5.49–5.46 (m, 1H), 3.63 (d, J = 15.0, 1H), 3.17 (d,