ACCEPTED MANUSCRIPT
7
Na2SO4 and concentrated under reduced pressure. Purification
by column chromatography using 9:1 hexanes/EtOAc as eluent
gave a separable 1:1 mixture of 16a:16b as colourless solids.
1214, 746; δH (400 MHz, CDCl3): 7.35-7.27 (5H, m, PhH),
5.06 (1H, t, J = 4.8 Hz, H-4), 4.53 (2H, dd, J = 29.3, 12.1 Hz,
CH2Ph), 4.28 (1H, d, J = 4.5 Hz, H-3), 4.25-4.19 (1H, m, H-9),
3.56 (1H, dd, J = 9.9, 5.4 Hz, H-10), 3.48 (1H, dd, J = 9.8, 5.8
Hz, H-10), 2.51 (1H, d, J = 14.2 Hz, H-5), 2.18-1.99 (5H, m,
H-5, H-7, H-8), 1.92-1.84 (1H, m, H-7),1.27 (3H, s, CH3), 1.21
(3H, s, CH3); δC (100 MHz, CDCl3): 178.8 (C=O, C-1), 138.6
(C, Ph), 128.3 (2 × CH, Ph), 127.6 (2 × CH, Ph), 127.4 (CH,
Ph), 115.7 (C, C-6), 87.3 (CH, C-9), 85.3 (CH, C-4), 79.7 (CH,
C-3), 73.5 (CH2, C-10), 73.3 (CH2, CH2Ph), 44.6 (C, C-2), 41.7
(CH2, C-5), 36.0 (CH2, C-7), 27.9 (CH2, C-8), 24.6 (CH3), 18.3
(CH3). HRMS (ESI): calcd. for C19H25O5: 333.1697, found:
333.1694.
Data for 16a; (0.05 g, 38%), Rf: 0.36 (60% hexanes/EtOAc);
20
[α]D -37.5 (c 1.0, CHCl3); mp: 60-64 °C; vmax (film)/cm-1:
3440, 2930, 1762, 1457, 1086; δH (400 MHz, CDCl3): 7.36-
7.26 (5H, m, PhH), 4.54 (2H, s, CH2Ph), 4.54-4.50 (1H, m, H-
4), 4.18-4.12 (1H, m, H-9), 4.04-4.02 (2H, m, H-6, H-3), 3.99
(1H, d, J = 2.9 Hz, OH), 3.52 (1H, dd, J = 10.0, 3.6 Hz, H-10),
3.38 (1H, dd, J = 10.1, 5.7 Hz, H-10), 2.17-2.04 (3H, m, H-5,
H-7), 1.98-1.89 (1H, m, H-8), 1.87-1.78 (1H, m, H-8), 1.74-
1.64 (1H, m, H-7), 1.28 (3H, s, CH3), 1.26 (3H, s, CH3); δC
(100 MHz, CDCl3): 181.1 (C=O, C-1), 137.5 (C, Ph), 128.4 (2
× CH, Ph), 128.1 (2 × CH, Ph), 127.8 (CH, Ph), 80.4 (CH, C-
4), 78.8 (CH, C-9), 76.5 (CH, C-6), 76.5 (CH, C-3), 73.5 (CH2,
CH2Ph), 71.8 (CH, C-10), 45.0 (C, C-2), 34.9 (CH2, C-5), 32.1
(CH2, C-7), 27.4 (CH2, C-8), 23.2 (CH3), 17.9 (CH3). HRMS
(ESI): calcd. for C19H26KO5: 373.1412, found: 373.1407.
4.1.13 (2S,3a'S,5S,6a'S)-5-((benzyloxy)methyl)-6',6'-
dimethyltetrahydro-3H,3'H-spiro[furan-2,2'-furo[3,2-b]furan]-
5'(3a'H)-one 15a and (2R,3a'S,5S,6a'S)-5-((benzyloxy)methyl)-
6',6'-dimethyltetrahydro-3H,3'H-spiro[furan-2,2'-furo[3,2-
b]furan]-5'(3a'H)-one 15b
Data for 16b; (0.05 g, 38%), Rf: 0.25 (60% hexanes/EtOAc);
A solution of lactone 16a (0.03 g, 0.09 mmol) in CH2Cl2 (0.1
mL) was added to a stirring solution of PhI(OAc)2 (0.06 g, 0.18
mmol) and I2 (0.05 g, 0.21 mmol) in hexane (0.2 mL). N2 gas
was bubbled through the solution for 5 min and the reaction
was then irradiated with a 75 W desk lamp for 1 h. The
solution was diluted with Et2O (0.2 mL) and saturated aq.
Na2S2O3 (0.1 mL) was added, the mixture was extracted with
Et2O (3 × 1 mL), dried over Na2SO4 and concentrated under
reduced pressure. Purification on deactivated silica using 9:1 to
3:2 hexanes/EtOAc gave a colourless oil.
20
[α]D -18.0 (c 0.3, CHCl3); mp: 59-65 °C; vmax (film)/cm-1:
3441, 2929, 1763, 1466, 1095; δH (400 MHz, CDCl3): 7.36-
7.26 (5H, m, PhH), 4.71-4.66 (1H, H-4), 4.55 (2H, s, CH2Ph),
4.26-4.19 (2H, m, H-6, H-9), 3.92 (1H, t, J = 3.6 Hz, H-3),
3.61 (1H, d, J = 3.6 Hz, OH), 3.46 (2H, d, J = 4.9, H-10), 2.31-
2.24 (1H, m, H-5), 2.14-2.02 (3H, m, H-5, H-8), 1.79-1.63
(2H, m, H-7), 1.26 (6H, s, 2 × CH3); δC (100 MHz, CDCl3):
180.8 (C=O, C-1), 138.1(C, Ph), 128.4 (2 × CH, Ph), 127.6 (2
× CH, Ph), 127.6 (CH, Ph), 78.3 (CH, C-9), 77.8 (CH, C-4),
76.5 (CH, C-3), 75.4 (CH, C-6), 73.4 (CH2, CH2Ph), 72.6
(CH2, C-10), 45.2 (C, C-2), 31.8 (CH2, C-5), 30.4 (CH2, C-7),
28.5 (CH2, C-8), 23.3 (CH3), 17.9 (CH3). HRMS (ESI): calcd.
for C19H26NaO5: 357.1672, found: 357.1675.
Data for 15b; (0.007 g, 25%), Rf: 0.69 (50% hexanes/EtOAc);
20
[α]D -41.5 (c 0.4, CHCl3); vmax (film)/cm-1: 2933, 1776, 1138,
1089,1052; δH (400 MHz, CDCl3): 7.36-7.26 (5H, m, PhH),
5.00 (1H, ddd, J = 6.3, 3.9, 1.5 Hz, H-4), 4.58 (2H, s, CH2Ph),
4.34-4.27 (1H, m, H-9), 4.24 (1H, d, J = 3.7 Hz, H-3), 3.49
(1H, dd, J = 9.9, 7.7 Hz, H-10), 3.42 (1H, dd, J = 9.9, 4.0 Hz,
H-10), 2.57 (1H, dd, J = 15.0, 6.4 Hz, H-5), 2.34 (1H, dd, J =
15.0, 1.4 Hz, H-5), 2.10-1.90 (3H, m, H-7, H-8), 1.81-1.70
(1H, m, H-8), 1.19 (6H, s, 2 × CH3); δC (100 MHz, CDCl3):
180.8 (C=O, C-1), 138.2 (C, Ph), 128.4 (2 × CH, Ph), 127.8 (2
× CH, Ph), 127.6 (CH, Ph), 115.7 (C, C-6), 85.1 (CH, C-9),
80.3 (CH, C-4), 79.0 (CH, C-3), 74.2 (CH2, C-10), 73.2 (CH2,
CH2Ph), 44.3 (C, C-2), 41.5 (CH2, C-5), 36.1 (CH2, C-7), 27.3
(CH2, C-8), 23.0 (CH3), 17.9 (CH3). HRMS (ESI): calcd. for
C19H24NaO5: 355.1516, found: 355.1516.
4.1.12 2R,3a'R,5S,6a'R)-5-((benzyloxy)methyl)-6',6'-
dimethyltetrahydro-3H,3'H-spiro[furan-2,2'-furo[3,2-b]furan]-
5'(3a'H)-one 8a and (2S,3a'R,5S,6a'R)-5-((benzyloxy)methyl)-
6',6'-dimethyltetrahydro-3H,3'H-spiro[furan-2,2'-furo[3,2-
b]furan]-5'(3a'H)-one 8b
A solution of lactone 9a (0.02 g, 0.06 mmol) in CH2Cl2 (0.1
mL) was added to a stirring solution of PhI(OAc)2 (0.04 g, 0.12
mmol) and I2 (0.04 g, 0.14 mmol) in hexane (0.2 mL). N2 gas
was bubbled through the solution for 5 min and the reaction
was then irradiated with a 75 W desk lamp for 1 h. The
solution was diluted with Et2O (0.2 mL) and saturated aq.
Na2S2O3 (0.1 mL) was added, the mixture was extracted with
Et2O (3 × 1 mL), dried over Na2SO4 and concentrated under
reduced pressure. Purification on deactivated silica using 9:1 to
3:2 hexanes/EtOAc gave colourless oils.
Data for 15a; (0.007 g, 25%), Rf: 0.57 (50% hexanes/EtOAc);
20
[α]D -20.4 (c 0.25, CHCl3); vmax (film)/cm-1: 2936, 1774,
1120, 1105; δH (400 MHz, CDCl3): 7.36-7.26 (5H, m, PhH),
5.10 (1H, t, J = 5.2 Hz, H-4), 4.53 (2H, s, CH2Ph), 4.35 (1H, d,
J = 5.0 Hz, H-3), 4.29-4.25 (1H, m, H-9), 3.52-3.42 (2H, m, H-
10), 2.47 (1H, d, J = 14.1 Hz, H-5), 2.15-2.01 (4H, m, H-5, H-
7, H-8), 1.84-1.80 (1H, m, H-8), 1.26 (3H, s, CH3), 1.22 (3H, s,
CH3); δC (100 MHz, CDCl3): 180.8 (C=O, C-1), 138.5 (C, Ph),
128.3 (2 × CH, Ph), 127.6 (2 × CH, Ph), 127.5 (CH, Ph), 115.7
(C, C-6), 86.9 (CH, C-3), 79.9 (CH, C-4), 78.6 (CH, C-9), 73.3
(CH2, CH2Ph), 72.1 (CH2, C-10), 44.3 (C, C-2), 41.4 (CH2, C-
5), 34.2 (CH2, C-7), 26.7 (CH2, C-8), 25.2 (CH3), 18.4 (CH3).
HRMS (ESI): calcd. for C19H24KO5: 371.1255, found:
371.1268.
Data for 8b; (0.005 g, 25%), Rf: 0.69 (50% hexanes/EtOAc);
20
[α]D +42.0 (c 0.26, CHCl3); vmax (film)/cm-1: 2930, 1776,
1050, 754; δH (400 MHz, CDCl3): 7.36-7.7 (5H, m, PhH), 5.02
(1H, ddd, J = 6.4, 3.7, 1.6 Hz, H-4), 4.56 (2H, dd, J = 12.2, 9.0
Hz, CH2Ph), 4.32 (1H, d, J = 3.8 Hz, H-3), 4.30-4.26 (1H, m,
H-9), 3.48-3.41 (2H, m, H-10), 2.58 (1H, dd, J = 15.0, 6.5 Hz,
H-5), 2.36 (1H, dd, J = 15.1, 1.5 Hz, H-5), 2.17-1.96 (4H, m,
H-7, H-8), 1.74-1.66 (1H, m, H-8), 1.26 (3H, s, CH3), 1.22
(3H, s, CH3); δC (100 MHz, CDCl3): 175.0 (C=O, C-1), 138.2
(C, Ph), 128.4 (3 × CH, Ph), 127.6 (2 × CH, Ph), 116.0 (C, C-
6), 85.3 (CH, C-9), 80.5 (CH, C-4), 77.7 (CH, C-3), 73.4 (CH2,
C-10), 72.4 (CH2, CH2Ph), 44.4 (C, C-2), 41.9 (CH2, C-5), 35.2
(CH2, C-7), 26.8 (CH2, C-8), 23.0 (CH3), 18.0 (CH3). HRMS
(ESI): calcd. for C19H24NaO5: 355.1516, found: 355.1528.
4.1.14 (2R,3a'S,5S,6a'S)-5-(hydroxymethyl)-6',6'-
dimethyltetrahydro-3H,3'H-spiro[furan-2,2'-furo[3,2-b]furan]-
5'(3a'H)-one 23
A solution of spiroacetal 15a (6.0 mg, 0.018 mmol) was
stirred in EtOAc (0.5 mL) over 10% Pd/C (0.01 g) under H2
overnight. The mixture was filtered through a plug of Celite®
Data for 8a; (0.005 g, 25%), Rf: 0.56 (50% hexanes: EtOAc);
20
[α]D -2.9 (c 0.17 in CHCl3); vmax (film)/cm-1: 2926, 1773,