G. Zhao, R. Tong / Tetrahedron xxx (xxxx) xxx
5
4.5.2. 6-Isopropoxy-2H-pyran-3(6H)-one (7). [29]
eq). The reaction mixture was stirred vigorously at rt for 1 h. Upon
completion (monitored by TLC), Ac2O (28.4 L, 0.3 mmol, 1.5 eq),
Et3N (223 L, 1.6 mmol, 8.0 eq) and styrene (229 L, 2.0 mmol, 10.0
Colorless oil, yield 56.7% for 3 steps. 1H NMR (400 MHz, CDCl3)
m
d
6.86 (dd, J ¼ 10.3, 3.4 Hz, 1H), 6.12 (d, J ¼ 10.3 Hz, 1H), 5.30 (d,
m
m
J ¼ 3.4 Hz, 1H), 4.48 (d, J ¼ 16.8 Hz, 1H), 4.12e3.99 (m, 2H), 1.27 (d,
eq) were added, and the resulting mixture was stirred overnight.
The mixture was quenched by addition of water, and the aqueous
phase was extracted with EtOAc. The combined organic fractions
were washed with saturated aqueous NH4Cl solution and brine,
dried over Na2SO4, filtered and concentrated under reduced pres-
sure. The residue was purified by flash chromatography (EtOAc/
hexane ¼ 1:5) to provide the title compound.
J ¼ 6.3 Hz, 3H), 1.22 (d, J ¼ 6.1 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d
195.1, 145.1, 127.8, 91.5, 71.2, 66.3, 23.4, 21.9.
4.5.3. 6-Benzyloxy-2H-pyran-3(6H)-one (8). [30]
Colorless oil, yield 68.9% for 3 steps 1H NMR-(400 MHz, CDCl3)
d
7.43e7.29 (m, 5H), 6.90 (dd, J ¼ 10.3, 3.4 Hz, 1H), 6.15 (d,
J ¼ 10.3 Hz, 1H), 5.29 (d, J ¼ 3.4 Hz, 1H), 4.86 (d, J ¼ 11.7 Hz, 1H), 4.67
(d, J ¼ 11.7 Hz, 1H), 4.49 (d, J ¼ 16.9 Hz, 1H), 4.12 (d, J ¼ 16.9 Hz, 1H).
6-endo-6-phenyl-8-oxabicyclo[3.2.1]oct-3-en-2-one (13). [41]
Colorless oil, yield 47.1% for 3 steps. 1H NMR (400 MHz, CDCl3)
13C NMR (100 MHz, CDCl3)
128.1, 92.2, 70.9, 66.5.
d
194.7, 144.4, 137.0, 128.8, 128.3, 128.3,
d
7.45e7.12 (m, 5H), 6.82 (dd, J ¼ 9.9, 4.4 Hz, 1H), 6.12 (dd, J ¼ 9.9,
1.4 Hz, 1H), 4.93 (dd, J ¼ 6.6, 4.4 Hz, 1H), 4.68 (dt, J ¼ 8.7, 1.7 Hz, 1H),
3.87 (dt, J ¼ 10.1, 6.9 Hz, 1H), 2.85 (ddd, J ¼ 13.6, 10.0, 8.6 Hz, 1H),
2.01 (ddd, J ¼ 13.6, 7.1, 1.9 Hz, 1H). 13C NMR (100 MHz, CDCl3)
4.5.4. 6-Butoxy-2H-pyran-3(6H)-one (9)
Colorless oil, yield 78.8% for 3 steps. FTIR: 2957.5, 2930.5, 2874.8,
1702.3, 1463.1, 1386.6, 1264.3, 1158.0, 1103.4, 1047.9, 851.9,
d 196.9, 151.7, 137.2, 128.7, 128.4, 127.5, 127.4, 82.0, 47.9, 31.1.
756.4 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
6.89 (dd, J ¼ 10.4, 3.3 Hz,
4.7. Synthesis of compound 14
1H), 6.12 (d, J ¼ 10.3 Hz, 1H), 5.19 (dd, J ¼ 3.3, 0.8 Hz, 1H), 4.45 (d,
J ¼ 16.8 Hz,1H), 4.09 (d, J ¼ 16.8 Hz,1H), 3.84 (dt, J ¼ 9.5, 6.7 Hz,1H),
3.57 (dt, J ¼ 9.5, 6.5 Hz, 1H), 1.69e1.55 (m, 2H), 1.48e1.34 (m, 2H),
An oven-dried 10 mL flask was charged with dry DMF (1 mL),
pre-hydrated silica gel (20 mg þ 3.6 mg H2O), furyl alcohol
(33.2 mg, 0.2 mmol, 1 eq), KBr (2.4 mg, 0.02 mmol, 0.1 eq), oxone
(86.1 mg, 0.28 mmol, 1.4 eq) and NaHCO3 (33.6 mg, 0.4 mmol, 2.0
eq). And the reaction mixture was stirred vigorously at rt for 6 h.
0.93 (t, J ¼ 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 194.9, 144.7,
127.8, 93.3, 69.4, 66.4, 31.8, 19.4, 13.9; HRMS (CI-TOF) m/z calcd. for
C9H15O3 [MþH]þ 171.1016, found 171.1029.
Upon completion (monitored by TLC), Ac2O (37.8 mL, 0.4 mmol, 2.0
4.5.5. 1-O-Methyl-2,3-O-isopropylidene-5-O-[3-oxo-3,6-dihydro-
2H-pyran-6-yl]-b-D-ribofuranose (10)
eq) and DABCO (179 mg, 1.6 mmol, 8.0 eq) were added, and the
resulting mixture was stirred for another 5 h. The mixture was
quenched by addition of water, and the aqueous phase was
extracted with EtOAc. The combined organic fractions were washed
with saturated aqueous NH4Cl solution and brine, dried over
Na2SO4, filtered and concentrated under reduced pressure. The
residue was purified by flash chromatography (EtOAc/hex-
ane ¼ 1:5) to provide the title compound.
dr 1.2:1, colorless oil, yield 60% for 3 steps. FTIR: 2985.4, 2938.2,
2837.4, 1701.6, 1461.2, 1379.2, 1266.3, 1206.4, 1160.5, 1099.0, 1046.6,
866.1 cmꢀ1
;
1H NMR (400 MHz, CDCl3)
d
6.89 (ddd, J ¼ 10.3, 3.3,
1.4 Hz, 1H), 6.14 (d, J ¼ 10.3 Hz, 1H), 5.25 (d, J ¼ 3.4 Hz, 0.45H), 5.22
(d, J ¼ 3.3 Hz, 0.55H), 4.98 (s, 1H), 4.69 (d, J ¼ 6.0 Hz, 0.55H), 4.65 (d,
J ¼ 6.0 Hz, 0.45H), 4.59 (dd, J ¼ 6.0, 3.9 Hz, 1H), 4.49 (d, J ¼ 3.6 Hz,
0.45H), 4.45 (d, J ¼ 3.7 Hz, 0.55H), 4.41e4.30 (m, 1H), 4.13 (d,
J ¼ 3.0 Hz, 0.55H), 4.09 (d, J ¼ 3.0 Hz, 0.45H), 3.87 (dd, J ¼ 10.2,
5.8 Hz, 0.55H), 3.79 (dd, J ¼ 10.1, 8.1 Hz, 0.45H), 3.62 (ddd, J ¼ 21.6,
10.1, 7.3 Hz, 1H), 3.33 (s, 3H), 1.48 (s, 3H), 1.32 (s, 3H). 13C NMR
(3aS,7R,8aS)-2,3,8,8a-tetrahydro-1H-3a,7-epoxyazulen-4(7H)-
one and (3aR,7S,8aR)-2,3,8,8a-tetrahydro-1H-3a,7-epoxyazulen-
4(7H)-one (14) [42]. Colorless oil, yield 63.6% for 3 steps. 1H NMR
(400 MHz, CDCl3)
d
7.13 (dd, J ¼ 9.7, 4.3 Hz, 1H), 5.97 (d, J ¼ 9.7 Hz,
(100 MHz, CDCl3)
d
194.6, 144.1, 144.1, 128.1, 112.7, 112.7, 109.6,
1H), 4.88 (dd, J ¼ 6.6, 4.3 Hz, 1H), 2.44e2.38 (m, 1H), 2.35e2.27 (m,
109.5, 93.8, 93.5, 85.3, 85.2, 85.2, 85.2, 82.1, 82.1, 70.3, 70.1, 66.5,
1H), 2.16 (dd, J ¼ 12.0, 8.9 Hz, 1H), 1.99e1.65 (m, 6H). 13C NMR
66.5, 55.2, 55.1, 26.6, 26.6, 25.2, 25.1. HRMS (CI-TOF) m/z calcd. for
(100 MHz, CDCl3)
30.0, 26.1.
d 197.6, 151.9, 126.2, 98.1, 76.1, 44.5, 36.7, 32.4,
C
14H24NO7 [MþNH4]þ 318.1547, found 318.1548.
4.5.6. 1,2:4,5-di-O-isopropylidene-3-O-[3-oxo-3,6-dihydro-2H-
pyran-6-yl]- -fructopyranose (11)
dr 1.2:1, colorless oil, yield 45% for 3 steps. FTIR: 2987.2, 2936.0,
2888.2, 1700.2, 1456.3, 1326.3, 1251.5, 1110.5, 1068.4, 996.3 cmꢀ1
1H NMR (400 MHz, CDCl3)
4.8. General procedure for the synthesis of compounds 15ce15i
b-D
An oven-dried 10 mL flask was charged with dry CH3CN (1 mL)
and DMF (0.1 mL), pre-hydrated silica gel (20 mg þ 3.6 mg H2O),
furfuryl alcohol (0.2 mmol,1.0 eq), KBr (9.52 mg, 0.08 mmol, 0.4 eq),
oxone (332 mg, 1.08 mmol, 5.4 eq) and NaHCO3 (45.3 mg,
0.54 mmol, 2.7 eq). Then, the reaction mixture was stirred vigor-
ously at rt. Upon completion (monitored by TLC), TEMPO (9.4 mg,
0.06 mmol, 0.3 eq) was added, and the resulting mixture was stir-
red for another 1e3 h. Then the residue was diluted by hexane and
poured onto silica gel and purified by flash chromatography
(EtOAc/hexane ¼ 1:1 to EtOAc) to provide the title compound.
;
d
6.96 (dd, J ¼ 10.4, 3.3 Hz, 0.55H), 6.91
(dd, J ¼ 10.3, 3.4 Hz, 0.45H), 6.18e6.08 (m, 1H), 5.75 (dd, J ¼ 3.3,
1.0 Hz, 0.55H), 5.36 (dd, J ¼ 3.4, 0.8 Hz, 0.45H), 4.77 (d, J ¼ 17.2 Hz,
0.45H), 4.47 (d, J ¼ 16.8 Hz, 0.55H), 4.35e4.28 (m, 1H), 4.24e4.19
(m, 1H), 4.19e4.13 (m, 1H), 4.14e4.05 (m, 2H), 4.05e3.96 (m, 2H),
3.89 (t, J ¼ 7.1 Hz, 1H), 1.55 (d, J ¼ 8.6 Hz, 3H), 1.49 (d, J ¼ 9.1 Hz, 3H),
1.41e1.33 (m, 6H). 13C NMR (100 MHz, CDCl3)
d 195.0, 194.5, 144.8,
143.6, 128.1, 127.6, 112.5, 112.0, 109.5, 109.4, 104.4, 104.3, 93.6, 93.5,
77.8, 75.9, 75.8, 75.5, 74.1, 73.8, 72.3, 72.2, 66.9, 66.8, 60.9, 60.4,
28.3, 27.8, 26.6, 26.6, 26.5, 26.3, 26.3, 26.2. HRMS (CI-TOF) m/z calcd.
for C17H28NO8 [MþNH4]þ 374.1809, found 374.1818.
4.8.1. 5-Hydroxy-6-(4-penten-1-yl)-2H-pyran-2-one (15c)
Colorless oil, yield 65.7% for 2 steps. FTIR: 3377.6, 2934.0, 2875.2,
1771.9, 1722.7, 1629.5, 1446.0, 1389.2, 1173.2, 1081.3, 1015.6,
4.6. Synthesis of compound (13)
911.8 cmꢀ1; 1H NMR (400 MHz, MeOD)
d
7.39 (d, J ¼ 9.7 Hz,1H), 6.13
(d, J ¼ 9.7 Hz, 1H), 5.83 (ddt, J ¼ 17.0, 10.2, 6.7 Hz, 1H), 5.08e4.92 (m,
2H), 2.60 (t, J ¼ 7.5 Hz, 2H), 2.11 (q, J ¼ 7.1 Hz, 2H), 1.73 (p, J ¼ 7.4 Hz,
An oven-dried 10 mL flask was charged with dry DMF (1.0 mL),
pre-hydrated silica gel (20 mg þ 3.6 mg H2O), furyl alcohol
(19.6 mg, 0.2 mmol, 1.0 eq), KBr (2.4 mg, 0.02 mmol, 0.1 eq), oxone
(86.1 mg, 0.28 mmol, 1.4 eq) and NaHCO3 (33.6 mg, 0.4 mmol, 2.0
2H). 13C NMR (100 MHz, MeOD)
d 164.8, 151.4, 143.6, 139.1, 137.6,
115.6, 113.6, 34.2, 28.4, 27.3. HRMS (CI-TOF) m/z calcd. for C10H11O3
[M-H]þ 179.0703, found 179.0710.
Please cite this article as: G. Zhao, R. Tong, Silica gel enables Achmatowicz rearrangement with KBr/oxone under “anhydrous” condition for one-