Organic & Biomolecular Chemistry
Paper
(
R)-1-(Furan-2-yl)butan-2-yl acetate (12)
To furan (2.02 mL, 27.74 mmol) dissolved in THF (23 mL) at
°C was added n-BuLi (15.6 mL, 24.97 mmol) dropwise upon
ene)-Ts-DPEN (6.2 mg, 0.01 mmol), and the reaction was set to
reflux at 55 °C. After refluxing for 12 h, the orange solution
2 2
was diluted with water, extracted with CH Cl , washed with
0
brine and dried over Na SO . Purification by column chrom-
2
4
which a bright yellow color developed. After stirring for 1 h at
this temperature, (R)-(+)-butylene oxide (1.21 mL, 13.87 mmol)
was added and the reaction was slowly warmed to room temp-
erature. After stirring for 12 h, the deep red solution was
quenched with saturated NH
with brine and dried over Na
chromatography (10% EtOAc/hexanes) gave 1.69 g (87% yield)
of the resulting furan alcohol as a yellow oil.
To (R)-furan alcohol (868 mg, 6.19 mmol) dissolved in
CH Cl (21 mL) at 0 °C was added acetic anhydride (1.2 mL,
atography (10% to 20% EtOAc/hexanes) provided 261 mg (93%
yield) of alcohol 10 as a clear oil. This alcohol was obtained as
1
20
a single diastereomer by H NMR (ratio >20 : 1) [α]D +13.5
(
1
c 0.84, CHCl3); H NMR (500 MHz, CDCl ) δ: 6.10 (d, J =
3
4
Cl, extracted with EtOAc, washed
SO . Purification by column
3
6
1
1
.1 Hz, 1H), 5.97 (d, J = 3.1 Hz, 1H), 5.04 (m, 1H), 4.59 (q, J =
.8 Hz, 1H), 2.88–2.80 (m, 2H), 2.01 (s, 3H), 1.92 (d, J = 5.2 Hz,
H), 1.83–1.79 (m, 2H), 1.65–1.55 (m, 2H), 1.42 (m, 1H),
2
4
1
3
.31–1.30 (m, 5H), 0.93–0.86 (m, 6H); C NMR (125 MHz,
) δ: 170.7, 155.9, 151.3, 107.6, 106.7, 73.8, 68.0, 35.6,
2.6, 31.7, 26.8, 25.4, 22.7, 21.3, 14.2, 9.7; FT-IR (neat)
max = 3447, 2958, 2933, 2859, 1739, 1559, 1464, 1433, 1373,
CDCl
3
ν
3
2
2
1
3
2.4 mmol), Et N (1.3 mL, 9.3 mmol) and a few crystals of
DMAP. The reaction was allowed to warm to room temperature.
After 6 h, the reaction was quenched with saturated NaHCO3,
1
+
1
242, 1021, 964, 792 cm− ; LRMS-ESI (+) m/z 305.1 [M + Na] .
extracted with CH
2 2
Cl , washed with brine and dried over
(
R)-1-((2R,5S,6R)-5-Hydroxy-6-pentyltetrahydro-2H-pyran-2-yl)
Na SO . Purification by column chromatography (5% to 10%
2
4
butan-2-yl acetate (8)
EtOAc/hexanes) afforded 1.1 g (97% yield) of acetate 12 as a
2
0
1
To furanyl alcohol 10 (317 mg, 1.12 mmol) dissolved in THF
clear oil [α]D +19.6 (c 0.73, CHCl
3 3
); H NMR (500 MHz, CDCl )
(
8 mL) and H
2
O (2 mL) at 0 °C was added KBr (6.7 mg,
(47 mg, 0.56 mmol) and oxone (826 mg,
δ: 7.31 (dd, J = 1.9, 0.9 Hz, 1H), 6.28 (dd, J = 3.2, 1.9 Hz, 1H),
0
.06 mmol), NaHCO
3
6
2
.05 (dd, J = 3.2, 0.9 Hz, 1H), 5.04 (m, 1H), 2.87 (d, J = 6.3 Hz,
H), 2.02 (s, 3H), 1.65–1.55 (m, 2H), 0.92 (t, J = 7.5 Hz, 3H);
1
3
1.34 mmol) after which a light yellow color developed. After
stirring at 0 °C for 30 min, the reaction was quenched with
saturated NaHCO
C
NMR (125 MHz, CDCl ) δ: 170.7, 151.9, 141.5, 110.4, 107.0,
3
3
, extracted with EtOAc, washed with brine
7
3.8, 32.5, 26.7, 21.3, 9.7; FT-IR (neat) νmax = 2965, 2925, 2852,
−
1
and dried over Na SO . The resulting crude hemiacetal 9 was
2
4
1
738, 1507, 1461, 1436, 1376, 1239, 1012, 739 cm
.
used directly for the subsequent reaction.
To crude hemiacetal dissolved in CH Cl
was added Et SiH (0.89 mL, 5.6 mmol) and TFA (1.3 mL,
2
2
(10 mL) at −45 °C
(R)-1-(5-Hexanoylfuran-2-yl)butan-2-yl acetate (13)
3
Hexanoic acid (604 mg, 5.20 mmol) in an excess of thionyl
chloride was refluxed overnight. The thionyl chloride was
removed by distillation, strictly keeping the system under
argon. The remaining hexanoyl chloride was used immediately
for the subsequent reaction. To hexanoyl chloride (699 mg,
1
6.8 mmol) dropwise upon which a yellow color developed.
The reaction was stirred at this temperature for 3 h, then was
allowed to warm to room temperature. After stirring for 30 min
at 23 °C, the reaction was cooled to 0 °C and additional Et
3
SiH
·OEt
0.415 mL, 3.36 mmol). After stirring for 30 min at 0 °C, the
until the
effervescence ceased. The reaction was extracted with CH Cl
washed with brine and dried over Na SO . Purification by
(
(
0.895 mL, 5.6 mmol) was added followed by BF
3
2
5
.2 mmol) in CH
2 2 4
Cl (15 mL) at 0 °C was added SnCl (8.7 mL,
8
.7 mmol, 1 M in CH Cl ) dropwise. After stirring for 1 h at
2
2
reaction was quenched slowly with satd. NaHCO
3
this temperature, acetate 12 (789 mg, 4.33 mmol) dissolved in
CH Cl (5 mL) was added to the reaction mixture via cannula
and remained stirring at 0 °C. After 30 min, the red-brown
solution was quenched with ice, extracted with CH Cl
washed with brine and dried over Na SO . Purification by
column chromatography (10% to 20% EtOAc/hexanes) gave
2
2
,
2
2
2
4
column chromatography (10% to 30% EtOAc/hexanes) pro-
vided 151 mg (47% yield over two steps) of tetrahydropyran
derivative 8 as a clear oil. It was obtained as a single diastereo-
2
2
,
2
4
1
20
D
1
mer by H NMR analysis (>20 : 1) [α] +2.7 (c 0.49, CHCl
3
); H
) δ: 5.01 (m, 1H), 3.30–3.22 (m, 2H),
.95 (td, J = 9.0, 2.4 Hz, 1H), 2.06 (m, 1H), 2.03 (s, 3H), 1.79
m, 1H), 1.65–1.53 (m, 6H), 1.43–1.24 (m, 9H), 0.90–0.85 (m,
2
0
9
+
3
1
1
09 mg (75% yield) of furan derivative 13 as a clear oil; [α]
D
NMR (500 MHz, CDCl
2
(
3
1
3 3
16.2 (c 0.86, CHCl ); H NMR (500 MHz, CDCl ) δ: 7.07 (d, J =
.5 Hz, 1H), 6.21 (d, J = 3.5 Hz, 1H), 5.07 (quint, J = 6.4 Hz,
H), 2.99–2.91 (m, 2H), 2.74 (t, J = 7.9 Hz, 2H), 2.02 (s, 3H),
.72–1.66 (m, 2H), 1.65–1.59 (m, 2H), 1.34–1.31 (m, 4H), 0.92
13
6H); C NMR (125 MHz, CDCl
3
) δ: 170.7, 82.2, 74.1, 72.9, 70.9,
4
0.0, 33.3, 32.2, 32.1, 32.0, 31.8, 27.8, 25.0, 22.7, 21.3, 14.2, 9.5;
1
3
(
t, J = 7.4 Hz, 3H), 0.89 (t, J = 6.5 Hz, 3H); C NMR (125 MHz,
FT-IR (neat) νmax = 3451, 2929, 2859, 1739, 1718, 1461, 1436,
1
2
CDCl
3
) δ: 189.4, 170.6, 157.0, 152.1, 118.3, 109.9, 73.2, 38.4,
−1
373, 1242, 1080, 1056, 1024, 954 cm ; LRMS-ESI (+) m/z
3
2
2.8, 31.6, 26.9, 24.3, 22.6, 21.2, 14.0, 9.7; FT-IR (neat) νmax
=
.
+
87.1 [M + H] .
961, 2931, 2866, 1741, 1674, 1588, 1516, 1374, 1238, 1023 cm−
1
1-((2R,5S,6R)-5-((tert-Butyldimethylsilyl)oxy)-6-
(
R)-1-(5-((R)-1-Hydroxyhexyl)furan-2-yl)butan-2-yl acetate (10)
To furan derivative 13 (280 mg, 1 mmol) in CH Cl (5 mL) was To tetrahydropyran derivative 8 (141 mg, 0.49 mmol) dissolved
sequentially added Et N (1.0 mL, 7.5 mmol), formic acid in CH
pentyltetrahydro-2H-pyran-2-yl)butan-2-one (15)
2
2
3
2
Cl
2
(5 mL) at 0 °C was added 2,6-lutidine (0.23 mL,
(0.28 mL, 7.5 mmol) and Noyori catalyst, (R,R) RuCl(mesityl- 1.97 mmol) and TBSOTf (0.34 mL, 1.48 mmol) and the reac-
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