Page 7 of 11
Organic & Biomolecular Chemistry
DOI: 10.1039/C6OB01447J
Hexane/EtOAc) to give the corresponding benzyl ether 26 (657
= 14.7, 8.6, 2.1 Hz, 1H), 1.89 (ddd, J = 14.7, 10.0, 4.6 Hz, 1H),
1
3
mg, 80%) as colorless liquid; R = 0.5 (10% EtOAcꢀhexane). 60 1.41–1.36 (d, J = 15.8 Hz, 6H), 1.16 (d, J = 7.0 Hz, 3H);
C
f
2
0
1
[
α]D = ꢀ63.7 (c 0.36, CHCl ); H NMR (500 MHz, CDCl ): δ
NMR (125 MHz, CDCl ): δ 137.7, 137.3, 128.3, 128.3, 128.0,
3
3
3
7
.35–7.26 (m, 10H), 4.77 (d, J = 11.6 Hz, 1H), 4.60–4.53 (q, J =
127.7, 127.6, 127.6, 109.3, 82.2, 81.2, 79.8, 75.4, 74.5, 73.5,
70.8, 70.0, 69.2, 42.4, 38.1, 35.8, 27.2, 26.8, 10.4; IR (neat):
3280, 3030, 2986, 2934, 1454, 1355, 1217, 1174, 1094, 910, 852,
5
0
5
0
5
0
5
0
5
0
5
11.2 Hz, 2H), 4.44 (d, J = 11.6 Hz, 1H), 4.17 (dd, J = 6.3, 2.0 Hz,
H), 4.12–4.08 (m, 1H), 3.88 (td, J = 8.4, 3.6 Hz, 1H), 3.80–3.76
1
ꢀ
1
+
(m, 1H), 3.57–3.50 (m, 2H), 2.46 (d, J = 2.0 Hz, 1H), 1.96 (m, 65 752 cm ; ESIꢀHRMS: m/z calcd for C H O NaS [M+Na]
28 36 7
1
6
H), 1.75–1.65 (m, 2H), 1.38 (s, 3H), 1.36 (s, 6H), 1.04 (d, J =
.9 Hz, 3H), 0.82 (s, 9H), 0.04 (s, 3H), 0.02 (s, 3H). C NMR
539.2074, found 539.2065.
13
1
1
2
2
3
3
4
4
5
5
(125 MHz, CDCl ): δ 137.9, 137.7, 128.2, 128.0, 127.5, 108.7,
(2S,3S,5R)-2-((Benzyloxy)methyl)-5-((2R,3S)-3-
(benzyloxy)pent-4-yn-2-yl)tetrahydrofuran-3-ol (28)
6.9, 25.8, 17.9, 9.6, ꢀ4.4, ꢀ4.6; IR (neat): 3305, 3031, 2984, 70 To the compound 12 (600 mg, 1.0 mmol) dissolved in MeOH (5
3
8
2
2
2.7, 80.1, 74.8, 74.3, 73.3, 70.5, 70.3, 69.2, 44.3, 37.9, 27.3,
ꢀ
1
931, 2858, 1456, 1371, 1254, 1096, 839, 776, 698 cm ; ESIꢀ
mL) was added pTsOH (8 mg) and the reaction was stirred at rt
for 12 h. The solvent was removed under reduced pressure and
diluted with water and EtOAc. The layers were separated and the
aqueous layer was extracted with EtOAc. The combine organic
75 extracts were washed with brine, dried over Na SO , and
concentrated under reduced pressure to provide diol (402 mg,
73%) as a colourless oil. To the diol obtained above (300 mg,
0.73 mmol) in THF (5 mL) was added drop wise at 0 C to the
+
HRMS: m/z calcd for C H O NaSi [M+Na] 575.3163, found
575.3155.
3
3
48
5
(2S,3R,4S)-4-(Benzyloxy)-1-((4S,5S)-5-((benzyloxy)methyl)-
2
4
2
,2-dimethyl-1,3-dioxolan-4-yl)-3-methylhex-5-yn-2-ol (27)
To a stirred solution of silyl ether 26 (600 mg, 1.0 mmol) in THF
(5 mL) was added tetrabutylammonium fluoride (1M solution in
THF, 1.25 mmol, 1mL). Then the solution was stirred at rt for 2
h. THF was removed by rotary evaporator and the crude mixture 80 oil, 0.81 mmol) in THF (5 mL) and the mixture was stirred at that
was purified by column chromatography (20% EtOAcꢀhexane)
without extractive workꢀup to give the title 27 (452 mg, 95%) as
colorless liquid. R = 0.5 (20% EtOAcꢀhexane). [α] = ꢀ57.3 (c
0
1
1
1
o
solution of sodium hydride (32 mg, 60% dispersion in mineral
temperature for 4 h. The solution was poured into waterꢀice
mixture and extracted with EtOAc. The organic phase was
combined, dried over anhydrous Na SO and concentrated. The
2
D
0
f
2
4
1
.36, CHCl ); H NMR (300 MHz, CDCl ): δ 7.40 – 7.28 (m,
residual oil was purified by column chromatography (30:70
3
3
0H), 4.84 (d, J = 11.5 Hz, 1H), 4.63–4.53 (m, 2H), 4.47 (d, J = 85 Hexane/EtOAc) to give the corresponding 28 (138 mg, 50%) as
1.5 Hz, 1H), 4.28 (dd, J = 4.2, 2.1 Hz, 1H), 4.14 (d, J = 9.5 Hz,
H), 4.03 (td, J = 8.4, 3.3 Hz, 1H), 3.92–3.85 (m, 1H), 3.62–3.52
2
0
white low melting solid. R = 0.5 (30% EtOAcꢀhexane). [α] = ꢀ
f D
1
55.5 (c 0.12, CHCl ); H NMR (500 MHz, CDCl ): δ 7.30ꢀ7.34
3
3
(m, 2H), 3.02 (s, 1H), 2.55 (d, J = 2.1 Hz, 1H), 1.91–1.79 (m,
H), 1.65–1.55 (m, 2H), 1.41 (d, J = 3.1 Hz, 6H), 1.12 (d, J = 7.0
(m, 10H), 4.82 (d, J = 11.8 Hz, 1H), 4.60–4.54 (m, 2H), 4.48 (dd,
J = 9.7, 7.1 Hz, 3H), 4.35 (td, J = 9.4, 5.6 Hz, 1H), 4.02 (dd, J =
1
1
3
Hz, 3H). C NMR (75 MHz, CDCl ): δ 137.8, 137.2, 128.3, 90 9.9, 4.6 Hz, 1H), 3.73 (ddd, J = 10.1, 5.4 Hz, 2H), 2.91 (s, 1H),
1
7
26.8, 8.1. IR (neat): 3287, 2985, 2927, 1724, 1454, 1374, 1218,
1
4
3
28.2, 127.8, 127.7, 127.5, 127.5, 127.3, 126.7, 108.7, 81.1, 79.8,
5.8, 75.4, 73.3, 72.5, 70.7, 70.4, 70.4, 64.9, 42.9, 38.3, 27.1,
2.45 (d, J = 2.0 Hz, 1H), 2.06 (dd, J = 13.2, 5.6 Hz, 1H), 1.89–
1.82 (m, 1H), 1.74 (ddd, J = 13.3, 10.1, 5.0 Hz, 1H), 1.04 (d, J =
13
7.0 Hz, 3H); C NMR (125 MHz, CDCl ): δ 138.1, 137.5, 128.4,
3
ꢀ
1
+
090, 772 cm ; ESIꢀHRMS: m/z calcd for C H O Na [M+Na]
128.1, 127.8, 127.7, 127.6, 127.3, 82.3, 79.7, 78.1, 74.0, 73.7,
95 73.6, 70.8, 69.0, 69.0, 44.1, 39.6, 9.9; IR (neat): 3446, 3289,
2
7
34
5
16.2292, found 416.2298.
2
973, 2922, 2869, 1496, 1454, 1374, 1339, 1207, 1066, 985, 739
ꢀ
1
+
(2S,3S,4S)-4-(Benzyloxy)-1-((4S,5S)-5-((benzyloxy)methyl)-
cm ; ESIꢀHRMS: m/z calcd for C H O Na [M+Na] 403.1879,
24 28 4
2,2-dimethyl-1,3-dioxolan-4-yl)-3-methylhex-5-yn-2-yl
methanesulfonate (12)
To the solution of alcohol 27 (400 mg, 0.91 mmol) in CH Cl (2 100 (2S,3S,5R)-2-((Benzyloxy)methyl)-5-((2R,3S)-3-
found 403.1872.
2
2
mL) was added Et N (0.17 mL. 1.26 mmol) followed by MsCl
(benzyloxy)pent-4-yn-2-yl)-3-methoxytetrahydrofuran (10)
To the solution of 28 (100 mg, 0.26 mmol) in THF (3 mL) at 0 °C
was added NaH (60% in oil, 16 mg, 0.40 mmol) and the
suspension stirred for 10 minutes. MeI (0.03 mL, 0.54 mmol) was
3
o
(0.8 mL, 1.0 mmol) at 0 C. The mixture was stirred for 1 h at rt
until the total consumption of the starting material occurred
monitored by TLC). Then, the reaction was quenched with a
(
saturated aqueous solution of NH Cl and extracted with CH Cl . 105 added dropwise and the reaction was warmed to room
The combined organic phase was washed with water, brine, dried
over anhydrous Na SO and concentrated. The residual oil was
purified by column chromatography (20:80 Hexane/EtOAc) to
give the product 12 (352 mg, 75%) as colorless liquid. R = 0.5
4
2
2
temperature. After one hour the reaction was quenched with
saturated aq NH Cl, partitioned between brine and EtOAc,
2
4
4
separated, and the aq. layer was extracted with EtOAc. The
combined organics were washed with brine, dried (Na SO ),
f
2
4
2
0
1
(20% EtOAcꢀhexane). [α]D = ꢀ32.4 (c 0.4, CHCl ); H NMR 110 filtered, and concentrated. The residue was purified by flash
3
(500 MHz, CDCl ): δ 7.38–7.26 (m, 10H), 5.06 (dt, J = 8.5, 4.2
chromatography (10:90, EtOAc/hexanes) to give the title product
3
2
0
Hz, 1H), 4.80 (d, J = 11.5 Hz, 1H), 4.55 (s, 2H), 4.43 (d, J = 11.5
Hz, 1H), 4.24 (dd, J = 5.4, 2.0 Hz, 1H), 3.93–3.89 (m, 1H), 3.80
10 (76 mg, 75%). R = 0.5 (10% EtOAcꢀhexane). [α] = ꢀ13.1 (c
f D
1
0.2, CHCl ); H NMR (400 MHz, CDCl ): δ 7.36–7.22 (m, 1H),
3
3
(
(
2
dt, J = 8.2, 5.0 Hz, 1H), 3.58 (dd, J = 10.2, 5.3 Hz, 1H), 3.51
dd, J = 10.1, 4.6 Hz, 1H), 2.97 (s, 1H), 2.97 (s, 3H), 2.55 (dd, J = 115 4.50 (d, J = 2.0 Hz, 1H), 4.47 (t, J = 2.6 Hz, 1H), 4.25–4.18 (m,
.0, 0.8 Hz, 1H), 2.34 (ddd, J = 7.0, 5.4, 4.0 Hz, 1H), 2.10 (ddd, J 1H), 4.10 (ddd, J = 6.6, 5.3, 4.0 Hz, 1H), 3.69 (dd, J = 10.1, 5.3
4.80 (d, J = 11.8 Hz, 1H), 4.61 (d, J = 12.1 Hz, 1H), 4.53 (s, 1H),
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7