The Journal of Organic Chemistry
Article
Hz, 1H, one of CH OR), 3.82 (dd, J = 13.0, 1.2 Hz, 1H, one of
1H, one of OCH C), 4.13 (dd, J = 12.2, 2.5 Hz, 1H, one of
2
2
CH OR), 2.09 (s, 3H, OAc), 0.91 (s, 9H, C(CH ) ), 0.140 (s, 3H,
CH OR), 4.06 (ddt, J = 12.7, 5.2, 1.4 Hz, 1H, one of OCH C), 3.93
2
3
3
2
2
13
SiCH ), 0.136 (s, 3H, SiCH ); C NMR (CDCl , 125 MHz) δ 170.7,
(app s, 1H, CHOH), 3.79 (dt, J = 12.2, 1.3 Hz, 1H, one of CH OR),
3
3
3
2
2.00 (d, J = 8.9 Hz, 1H, OH); 13C NMR (CDCl , 125 MHz) δ 134.19,
1
1
1
33.2 (C5), 123.2 (C4), 87.9 (C6), 63.5 (C3), 61.2 (C2), 25.7, 21.1,
3
8.1, −5.3, −4.5; IR (film) 2955, 2931, 2858, 1739, 1372, 1237, 1109,
129.22 (C4), 128.47 (C5), 117.56, 92.31 (C6), 68.5, 64.30 (C2),
−1
+
031, 960, 870, 838 cm ; HRMS-ESI (m/z) calcd for C H O SiNa
61.54 (C3); IR (film) 3398, 2922, 1399, 1319, 1260, 1188, 1099, 1077,
13
24
4
+
−1
25
[
M + Na] 295.1342, found 295.1345, Δ = 1.0 ppm.
Preparation of (±)-6-Hydroxy-3,6-dihydro-2H-pyran-3-yl Methyl
Carbonate, cis- and trans-10g. To a solution of trans-10a (0.096 g,
.33 mmol, 1.0 equiv) in acetonitrile (8 mL), at room temperature,
1033, 964, 930, 833 cm ; [α]D = +68.3 (c = 0.5, CHCl ); HRMS-
3
+
+
ESI (m/z) calcd for C H O Na [M + Na] 179.0684, found
8
12
3
1
79.0688, Δ = 2.2 ppm.
Preparation of (3S,6S)-6-allyloxy-3,6-dihydro-2H-pyran-3-ol, cis-
0
was added HF·pyridine (0.240 mL, 0.266 g, 13.3 mmol, 40 equiv). The
reaction was stirred overnight before being quenched with saturated
aqueous sodium bicarbonate, extracted with EtOAc, dried over
10k. Using the general procedure for acetate saponification, (3S,6R)-6-
allyloxy-3,6-dihydro-2H-pyran-3-acetate (0.016 g, 0.081 mmol, 1.0
equiv), MeOH (2.5 mL), and K CO (0.056 g, 0.40 mmol, 5.0 equiv)
2
3
MgSO , filtered and concentrated in vacuo. The crude product was
4
were added to the reaction. The title compound was obtained as a
1
purified by silica gel chromatography (50% EtOAc/petroleum ether).
The desired product was isolated as a clear oil composed of a ca. 3:1
mixture of trans- and cis-diastereomers, respectively. (0.018 g, 31%
clear colorless oil (0.004 g, 32% yield): H NMR (CDCl , 500 MHz) δ
3
6
1
.04 (m, 1H, HC), 5.95 (m, 1H, HC), 5.80 (dt, J = 10.3, 2.0 Hz,
H, HC), 5.31 (m, 1H, one of CH ), 5.21 (m, 1H, one of
2
yield). R = 0.23 (40% EtOAc/petroleum ether). Characterization data
f
CH ), 4.98 (m, 1H, CHOAllyl), 4.28 (m, 1H, one of OCH C), 4.25
2
2
1
for trans-10g: H NMR (CDCl , 500 MHz) δ 6.14 (m, 1H, HC),
3
(m, 1H, CHOH), 4.07 (dd, J = 12.7, 6.3 Hz, 1H, one of OCH C),
2
6
.10 (dd, J = 10.1, 2.6 Hz, 1H, HC), 5.42 (dd, J = 4.8, 2.5 Hz, 1H,
3
.82 (dd, J = 11.0, 5.3 Hz, 1H, one of CH OR), 3.72 (dd, J = 11.0, 8.0
2
CHOH), 4.84 (ddd, J = 4.6, 3.0, 1.6 Hz, 1H, CHCO Me), 4.28 (dd, J
13
2
Hz, 1H, one of CH OR), 1.56 (br. s, 1H, OH); C NMR (CDCl3,
2
=
13.1, 2.9 Hz, 1H, one of CH OR), 3.95 (m, 1H, one of CH OR),
2
2
125 MHz) δ 134.2, 133.0, 127.8, 117.5, 93.7, 69.2, 63.8, 63.2; IR (film)
13
3.80 (s, 3H, OCO CH ), 2.77 (d, J = 4.2 Hz, 1H, OH); C NMR
−1
25
2
3
3397, 2919, 1395, 1276, 1261, 1186, 1032, 935, 884 cm ; [α]D =
(
(
(
CDCl , 125 MHz) δ 155.3, 132.0 (C5), 124.5 (C4), 87.7 (C6), 66.5
C3), 61.1 (C2), 55.0. Characterization data for cis-10g: H NMR
+
3
+34.7 (c = 0.19, CHCl ); HRMS-ESI (m/z) calcd for C H O Na [M
3 8 12 3
1
+
+
Na] 179.0684, found 179.0681, Δ = 1.7 ppm.
Preparation of Benzyl cis-(±)-6-[(tert-Butyldimethylsilyl)oxy]-3,6-
CDCl , 500 MHz) δ 6.04 (dd, J = 10.3, 2.8 Hz, 1H, HC), 5.96 (dt,
3
J = 10.3, 1.8 Hz, 1H, HC), 5.33 (m, 1H, CHOH), 5.10 (dddt, J =
dihydro-2H-pyran-3-yl Carbonate, 10m. To a solution of cis-(±)-6-
[(tert-butyldimethylsilyl)oxy]-3,6-dihydro-2H-pyran-3-ol (0.753 g,
3.27 mmol, 1.0 equiv) in 32 mL of freshly distilled CH Cl was
6
.6, 5.0, 3.1, 1.7 Hz, 1H, CHOCO Me), 3.95 (m, 2H, CH OR), 3.80
2
2
13
(
s, 3H, OCO CH ), 2.90 (d, J = 6.4 Hz, 1H, OH); C NMR (CDCl3,
2 3
2
2
1
6
1
25 MHz) δ 155.3, 131.0 (C5), 127.9 (C4), 89.3 (C6), 68.0 (C3),
1.0 (C2), 54.9. Combined data: IR (film) 3413, 2959, 2925, 1740,
added DMAP (0.499 g, 4.08 mmol, 1.25 equiv), followed by benzyl
chloroformate (0.582 mL, 0.696 g, 4.08 mmol, 1.25 equiv). The
reaction was stirred overnight at room temperature before
concentration in vacuo and purification by flash column chromatog-
raphy (silica gel, 5% EtOAc/petroleum ether). The desired product
−1
443, 1252, 1061, 975, 937 cm ; HRMS-ESI (m/z) calcd for
+
+
C H O Na [M + Na] 197.0426, found 197.0422, Δ = 2.0 ppm.
These data match those previously obtained.
7
10
5
17
General Procedure for the Saponification of 3,6-Dihydro-
was isolated as a clear colorless oil (0.604 g, 51% yield). R = 0.26 (5%
f
2
H-pyran-3-yl Acetates. Preparation of (3S,6R)- and (3S,6S)-6-
1
EtOAc/petroleum ether): H NMR (CDCl , 500 MHz) δ 7.40−7.32
3
Isopropoxy-3,6-dihydro-2H-pyran-3-ol, cis- and trans-10j. To a
solution of (3S,6S)- and (3S,6R)-6-isopropoxy-3,6-dihydro-2H-pyran-
(
complex m, 5H, ArH), 5.92 (ddt, J = 10.3, 2.2, 1.0 Hz, 1H, HC),
5
5
1
3
.84 (dt, J = 10.3, 2.0 Hz, 1H, HC), 5.27 (app s, 1H, CHOTBS),
3-yl acetate (10h, 0.047 g, 0.232 mmol, 1.0 equiv, 3.4:1 ratio of trans-
.18−5.16 (complex m, 2H, OCH Ph), 5.14 (tdd, J = 5.6, 2.8, 1.3 Hz,
2
1
0h:cis-10h) in methanol (2.5 mL) was added K CO (0.160 g, 1.16
2
3
H, CHOCO Bn), 3.91 (dd, J = 11.1, 7.9 Hz, 1H, one of CH OR),
2
2
mmol, 5.0 equiv). The reaction mixture was stirred at room
.87 (ddd, J = 11.2, 5.8, 1.0 Hz, 1H, one of CH OR), 0.90 (s, 9H,
SiC(CH ) ), 0.12 (s, 3H, SiCH ), 0.12 (s, 3H, SiCH ); C NMR
2
temperature for 3 h before being quenched with H O and extracted
2
13
3
3
3
3
twice with EtOAc. The combined organic layers were dried over
(
CDCl , 125 MHz) δ 154.6, 135.0, 132.2 (C5), 128.6, 128.6, 128.3,
3
MgSO , filtered, and concentrated in vacuo. The title compounds were
4
1
26.4 (C4), 89.2 (C6), 69.8, 68.5 (C3), 60.0 (C2), 25.7, 18.0, −4.4,
isolated together as a clear colorless oil. Characterization data for trans-
1
−5.2; IR (film) 2954, 2930, 2857, 1742, 1384, 1246, 1099, 1034, 867,
8
1
0j: H NMR (CDCl , 500 MHz) δ 6.11 (dd, J = 10.0, 5.3 Hz, 1H,
3
−1
+
37, 779 cm ; HRMS-ESI (m/z) calcd for C H O SiNa [M +
19 28 5
HC), 5.85 (dd, J = 10.0, 3.1 Hz, 1H, HC), 5.04 (d, J = 3.0 Hz,
+
Na] 387.1604, found 387.1602; Δ = 0.5 ppm.
1
H, CHOiPr), 4.14 (dd, J = 12.3, 2.6 Hz, 1H, one of CH OR), 3.98
2
Preparation of 4-[[cis-(±)-6-[(tert-Butyldimethylsilyl)oxy]-3,6-di-
hydro-2H-pyran-3-yl]oxy]-6-methyl-2H-pyran-2-one, 10n. A reac-
tion vessel was charged with 4-hydroxy-6-methyl-α-pyrone (0.040 g,
(
m, 1H, OCH(Me) ), 3.81 (app s, 1H, CHOH), 3.77 (app d, J = 12.3
2
Hz, 1H, one of CH OR), 2.11 (br. s, 1H, OH), 1.23 (d, J = 6.4 Hz,
2
13
3
H, CH ), 1.17 (d, J = 6.1 Hz, 3H, CH ); C NMR (CDCl , 125
3
3
3
0
.315 mmol, 1.0 equiv) and Pd(PPh ) (0.0037 g, 0.0032 mmol, 1 mol
3 4
MHz) δ 129.07 (C5), 128.95 (C4), 91.31 (C6), 69.82, 64.11 (C2),
1
%), evacuated, and backfilled with argon. Toluene (6 mL, degassed by
sparging with argon for approximately 20 min) was added to the
reaction vessel, followed by the substrate, cis-(±)-6-[(tert-
butyldimethylsilyl)oxy]-3,6-dihydro-2H-pyran-3-yl methyl carbonate
6
1.63 (C3), 23.53, 21.82. Characterization data for cis-10j: H NMR
(
CDCl , 500 MHz) δ 6.00 (m, 1H, HC), 5.74 (dt, J = 10.2, 2.1 Hz,
3
1
3
1
H, HC), 5.01 (app s, 1H, CHOiPr), 4.22 (app s, 1H, CHOH),
.98 (m, 1H, OCH(Me) ), 3.79−3.69 (m, 2H, CH OR), 1.84 (br. s,
2
2
(0.091 g, 0.315 mmol, 1.0 equiv). The reaction was stirred overnight
H, OH), 1.24 (d, J = 7.0 Hz, 3H, CH ), 1.17 (d, J = 6.1 Hz, 3H,
3
13
at room temperature before being concentrated in vacuo and purified
by flash column chromatography (silica gel, 30% EtOAc/petroleum
CH ); C NMR (CDCl , 125 MHz) δ 132.8 (C4), 128.4 (C5), 92.7
3
3
(
C6), 70.3, 63.6 (C2), 63.2 (C3), 23.6, 21.9. Characterization data
38
ether). The title compound was isolated as a yellow oil (0.009 g, 9%
match those reported previously.
1
yield): R = 0.20 (30% EtOAc/petroleum ether); H NMR (CDCl ,
Preparation of (3S,6R)-6-Allyloxy-3,6-dihydro-2H-pyran-3-ol,
trans-10k. Using the general procedure for acetate saponification,
f
3
500 MHz) δ 5.95 (app dt, J = 10.3, 0.9 Hz, 1H, HC), 5.89 (app dt, J
= 10.3, 1.9 Hz, 1H, HC), 5.77 (m, 1H, PyH), 5.41 (d, J = 2.1 Hz,
1H, CHOTBS), 5.30 (s, 1H, PyH), 4.79 (m, 1H, PyOCH), 3.95 (dd, J
(
3S,6S)-6-allyloxy-3,6-dihydro-2H-pyran-3-yl acetate (0.036 g, 0.18
mmol, 1.0 equiv), MeOH (2.5 mL) and K CO (0.124 g, 0.90 mmol,
2
3
5
.0 equiv) were added to the reaction. The title compound was
= 11.1, 8.0 Hz, 1H, one of CH OR), 3.88 (ddd, J = 11.1, 5.4, 0.9 Hz,
1H, one of CH OR), 2.20 (s, 3H, PyCH ), 0.91 (s, 9H, C(CH ),
0.13 (s, 6H, Si(CH ) ); C NMR (CDCl , 125 MHz) δ 169.2, 164.7,
3 2 3
2
1
obtained as a clear colorless oil (0.010 g, 36% yield): H NMR
2
3
)
3 3
13
(
CDCl , 500 MHz) δ 6.14 (ddt, J = 10.0, 5.3, 1.1 Hz, 1H, HC), 5.95
3
(
1
m, 1H, HC), 5.90 (dd, J = 10.0, 3.3 Hz, 1H, HC), 5.30 (ddd, J =
162.6, 132.7 (C5), 125.2 (C4), 100.6, 89.3 (C6), 88.4, 68.6 (C3), 59.8
7.2, 3.6, 2.0 Hz, 1H, one of CH ), 5.21 (m, 1H, one of CH ),
(C2), 25.7, 19.9, 18.0, −4.4, −5.3; IR (film) 2929, 2857, 1731, 1711,
2
2
−1
4
.99 (d, J = 3.1 Hz, 1H, CHOAllyl), 4.26 (ddt, J = 12.7, 5.2, 1.4 Hz,
1650, 1563, 1248, 1035, 838, 781 cm ; HRMS-ESI (m/z) calcd for
J
dx.doi.org/10.1021/jo500678k | J. Org. Chem. XXXX, XXX, XXX−XXX