G. P. Mishra, B. V. Rao / Tetrahedron: Asymmetry 22 (2011) 812–817
815
mixture was filtered and the excess THF was evaporated under
4.4. (3aS,4S,6aR)-2,2-Dimethyl-5-(tetrahydro-pyran-2-
vacuum. To it, powdered activated Zn (200 mg, 2.91 mmol) was
added and further dried at reduced pressure for 20 min flushing
with nitrogen occasionally. Dry THF (7.5 mL) followed by dry
DMF (7.5 mL) were added to the reaction mixture, which was then
stirred for 30 min causing the colour to change from violet to
green. To it compound 7 (150 mg, 0.49 mmol) in THF (3 mL) was
added slowly. Stirring was continued for 8 h. When TLC showed
the absence of starting material, NiCl2 (40 mg, 0.29 mmol) was
added to the reaction mixture, stirred for 30 min and then iodo
compound 4 (259 mg, 0.97 mmol) in DMF (3 mL) was added to it.
The reaction mixture was allowed to stir for an additional 4 h, di-
luted with diethyl ether (50 mL), filtered through a scintered fun-
nel, concentrated and purified by column (ethylacetate/
hexane = 2:8) to afford a mixture of 8 and 9 (70 mg, 48%) in a 1:1
yloxymethyl)-4,6-dihydrocyclopenta[1,3]dioxol-4-ol 11
½
a 2D5
ꢂ
¼ þ3 (c 0.57, CHCl3),
m
max 3449, 2927, 2855, 1645.68, 1456,
1H
1378, 1208, 1152, 1118, 1073, 1029, 974, 8721, 812, 761 cmꢀ1
.
NMR: (200 MHz, CDCl3): 5.75 (s, 1H, –CH@C–), 4.97 (d, 1H, J = 5 Hz,
–CH–OH allylic), 4.78–4.59 (m, 2H, –O–CH–CH–O– allylic, –O–CH–
O anomeric), 4.51–4.28 (m, 2H, –O–CH–CH–O–, –CH(H)–OTHP),
4.05 (dd, 1H, J = 13.7, 5.9 Hz, –CH(H)–OTHP), 3.94–3.75 (m, 1H, –
CH(H)–O– of THP), 3.57–3.4 (m, 1H, –CH(H)–O– of THP), 2.59 (t,
1H, J = 9.4 Hz, –OH), 1.93–1.44 (m, 6H, –CH2–CH2–CH2–), 1.41 (s,
3H, –CH3), 1.38 (s, 3H, –CH3). 13C NMR (75 MHz, CDCl3): 19.9,
25.1, 25.2, 25.3, 31.1, 62.0, ⁄(63.0, 63.5), ⁄(73.9, 74.1), 77.4, 82.5,
⁄(98.0, 99.0), 112.5, ⁄(127.1, 127.2), 142.0. HRMS (ESIMS) m/z calcd
for C14H22O5Na 293.1376, found 293.1364. (⁄diastereomers be-
cause of the THP group).
ratio (by 1H NMR) as an yellow oil. ½a 2D5
¼ ꢀ10:6 (c 1.18, CHCl3),
ꢂ
IR (KBr) mmax 3446, 2926, 2854, 1741, 1647, 1458, 1377, 1255,
1215, 1163, 1119, 1029, 909, 871, 810 cmꢀ1 1H NMR: (300 MHz,
.
4.5. (3aR,6aR)-2,2-Dimethyl-5-((tetrahydro-2H-pyran-2-yloxy)
methyl)-3aH-cyclopenta[d][1,3]dioxol-4(6aH)-one 12
CDCl3): 6.09–5.95 (m, 1H, –CH2@CH), 5.43–5.19 (m, 4H, –CH@CH2,
–C@CH2), 4.70–4.56 (m, 2H, –O–CH–CH–O–, –CH–OH), 4.45–3.98
(m, 4H, –O–CH–CH–O–, –O–CH-O– anomeric, –CH2-OTHP), 3.89–
3.76 (m, 1H, –CH(H)–O– of THP), 3.57–3.44 (m, 1H, –CH(H)–O–
of THP), 2.74–2.42 (two br s, 1H, –OH), 1.88–1.46 (m, 6H, –CH2–
CH2–CH2–), 1.44 (s, 3H, –CH3), 1.39 (s, 3H, –CH3). 13C NMR
(75 MHz, CDCl3): ⁄(19.3, 19.5), ⁄{24.9, (24.9, 25.3), ⁄(25.4, 25.37)},
⁄{(27.2, 27.16), 27.8}, 30.5, ⁄{62.2, (62.4, 62.6)}, ⁄{(67.9, 68.2),
69.1}, ⁄{(70.9, 71.1), 72.5}, ⁄{78.8, (79.2, 79.17)}, ⁄{97.8, (98.0,
To a solution of 10 and 11 (0.327 g, 0.643 mmol) in DCM
(20 mL) were added powdered molecular sieves (4 Å) and then
pyridinium dichlorochromate (0.605 g, 1.6 mmol) at 0 °C. The reac-
tion mixture was stirred at rt for 5 h. After the completion of reac-
tion, the crude reaction mixture was filtered through Celite,
washed with water, dried over anhydrous Na2SO4 and concen-
trated at reduced pressure to give the crude product as a brownish
syrup. The syrup was purified on a column (ethylacetate/hex-
ane = 2:8) to give a single product 12 (0.318 g, 98%) as a liquid.
⁄
98.5)}, 108.7, 115.4, 117.0, 117.7, 119.3, 134.2, (144.4, 144.7).
(The extra peaks in 13C is because of the mixture of diastereo-
mers; the doubling of peaks is because of diastereomers due to
the stereogenic centre present in the THP functionality) HRMS
(LC–MS) m/z calcd for C16H26O5Na 321.1686, found 321.1677.
½
a 2D5
ꢂ
¼ ꢀ5 (c 0.850, CHCl3), IR (KBr) mmax 2931, 2856, 1725, 1458,
1377, 1248, 1204, 1130, 1099, 1036, 980, 915, 864, 814 cmꢀ1 1H
;
NMR: (300 MHz, CDCl3): 7.41 (d, 1H, J = 1.8 Hz, HC@C–), 5.18 (d,
1H, J = 5.5 Hz, –O–CH–CH–O– allylic), 4.64 (t, 1H, J = 2.9 Hz, –O–
CH–O– anomeric), 4.46 (d, 1H, J = 5.5 Hz, –O–CH–CH–O–), 4.4
(dd, 1H, J1 = 15.4, J2 = 1.8 Hz, –O–CH(H)–OTHP), 4.11 (dd, 1H,
4.2. (3aS,4R,6aR)-2,2-Dimethyl-5-(tetrahydro-pyran-2-yloxy
methyl)-di-hydro-cyclopenta[1,3]dioxol-4-ol 10 and
(3aS,4S,6aR)-2,2-dimethyl-5-(tetrahydro-pyran-2-yloxymethyl)-
4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 11
J1 = 15.4, J2 = 1.8 Hz, –O–CH(H)–OTHP), 3.86–3.75 (m, 1H,
–
CH(H)–O– of THP), 3.55–3.45 (m, 1H, –CH(H)–O– of THP), 1.90–
1.48 (m, 6H, –CH2–CH2–CH2–), 1.39 (s, 3H, –CH3), 1.39(s, 3H, –
CH3); 13C NMR (75 MHz, CDCl3): ⁄(19.27, 19.32), 25.3, ⁄(26.07,
26.12), 27.5, 30.4, ⁄(60.81, 60.87), ⁄(62.25, 62. 31), 76.6, 77.7,
98.8, 115.4, ⁄(114.4, 114.5), ⁄(153.2, 153.3), 201.4. HRMS (ESIMS)
m/z calcd for C14H20O5Na 291.1210, found 291.1208. (⁄diastereo-
mers because of the THP group).
To the diastereomeric mixture of compounds
8 and 9
(750 mg, 2.5 mmol) in anhydrous DCM (750 mL) under nitrogen
atmosphere, was added Grubbs’ second generation catalyst
(210 mg, 0.25 mmol) and the reaction mixture was allowed to
reflux for 6 h. After completion of the reaction, the reaction mix-
ture was evaporated at reduced pressure to give a crude residue,
which was purified by column (ethylacetate/hexane = 3:7) to
give the compounds 10 (170 mg, 41%) and 11 (157 mg, 40%) as
a yellow oil.
4.6. (3aS,4S,5R,6aR)-2,2-Dimethyl-5-((tetrahydro-2H-pyran-2-
yloxy)methyl)-tetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-ol 13
To compound 11 (0.1 g, 0.37 m mol) in dry methanol (5 mL), Pd/
C (10 wt %) was added and the mixture stirred for 2 h under a
hydrogen atmosphere. After the completion of the reaction, the
reaction mixture was filtered through Celite. The filtrate was con-
centrated to give compound 13 (0.099 g, 98%) as a thick syrup.
4.3. (3aS,4R,6aR)-2,2-Dimethyl-5-(tetrahydro-pyran-2-yloxy
methyl)-tetrahydrocyclopenta[1,3]dioxol-4-ol 10
½
a 2D5
ꢂ
¼ ꢀ35:8 (c 1.78, CHCl3), IR (KBr) mmax 3443, 2928, 2857,
1646, 1457, 1376, 1206, 1157, 1122, 1036, 904, 864 cmꢀ1., 1H
NMR: (200 MHz, CDCl3): 5.82 (d, 1H, J = 6.2 Hz, –CH@C–), 5.2 (br
s, 1H, –CH–OH allylic), 4.71–4.58 (m, 2H, –O–CH–CH–O– allylic,
–O–CH-O– anomeric), 4.51 (d, 1H, J = 5.9 Hz, –O–CH–CH–O–), 4.4
(d, 1H, J = 12.6 Hz, –CH(H)–O–), 4.15 (d, 1H, J = 12.6 Hz, –CH(H)–
O–), 3.93–3.76 (m, 1H, –CH(H)–O– of THP), 3.59–3.42 (m, 1H, –
CH(H)–O– of THP), 2.95–2.69 (br d, 1H, –OH), 1.96–1.37 (m, 6H,
–CH2–CH2–CH2–), 1.36 (s, 3H, –CH3), 1.32 (s, 3H, –CH3). 13C NMR
(75 MHz, CDCl3): ⁄(19.3, 19.6), 25.2, ⁄(25.60, 25.65), ⁄(27.3, 27.4),
⁄(30.4, 30.5), ⁄(62.3, 62.7), ⁄(64.9, 65.1), ⁄(80.8, 81.6), 83.4, ⁄(86.1,
86.2), ⁄(98.7, 99.0), 111.3, ⁄(130.2, 130.7), ⁄(144.3, 144.7). HRMS
(ESIMS) m/z calcd for C14H22O5Na 293.1376, found 293.1364. (⁄dia-
stereomers because of the THP group).
½
a 2D5
ꢂ
¼ ꢀ10:6 (c 0.175, CHCl3), IR (KBr) mmax 3446, 2933, 1705,
1646, 1457, 1379, 1262, 1206, 1159, 1121, 1058, 1027, 905, 898,
811 cmꢀ1 1H NMR: (200 MHz, CDCl3): 1H NMR: 4.66–4.54 (m,
;
2H, –O–CH-O– anomeric, –O–CH–CH–O–), 4.45 (dd, 1H, J1 = 6.8,
J2 = 5.3 Hz, –O–CH–CH–O–), 4.11–3.36 (m, 5H, –CH–OH, –CH2-
OTHP, –O–CH2–C– of THP), 2.26–2.13 (m, 1H, –CH-CHOTHP),
1.99–188 (m, 1H, –CH(H)– of cyclopentyl ring), 1.87–1.51 (m, 7H,
–CH(H)– of cyclopentyl ring, –CH2–CH2–CH2–), 1.52 (s, 3H, –CH3),
1.33 (s, 3H, –CH3); 13C NMR (75 MHz, CDCl3): 19.6, 24.2, 25.4,
26.1, 30.6, 31.8, ⁄(43.5, 44.0), 62.3, ⁄(66.5, 66.9), ⁄(70.6, 71.2),
79.3, 80.9, 99.0, 113.0. HRMS (ESIMS) m/z calcd for C14H24O5Na
295.1533, found 295.1521. (⁄diastereomers because of the THP
group).