8
Tetrahedron
(3aR*,4S*,6aR*)-4-ethyldihydrofuro[3,4-b]furan-
(PE40−60 / EtOAc, gradient from 12:1 to 1:1) to give 30 as a
ACCEPTED MANUSCRIPT
2,6(3H,4H)-dione 33-min
yellowish solid (3.07 g, 8.66 mmol, 72% isolated as an
inseparable 2.3:1 mixture of diastereomers). Analysis is on the
mixture of diastereomers, Rf (PE40−60 / EtOAc, 8:1) = 0.2; m.p. =
70-72 °C; δH (500 MHz, CDCl3): 30-maj: 0.87 (t, 3 H, J = 7.1
Hz, CH2CH3), 1.25-1.43 (m, 12 H, 6 × CH2), 1.51 (s, 9 H,
OCCH3), 1.71-1.78 (m, 1 H, O=COCHCHH), 1.81-1.89 (m, 1 H,
O=COCHCHH), 2.58 (dd, 1 H, J = 18.3, 2.5 Hz, O=CCHHCH),
2.96 (dd, 1 H, J = 18.3, 9.5 Hz, O=CCHHCH), 3.05 (ddd, 1H, J =
9.3, 5.6, 2.4 Hz, O=CCHHCH), 4.27 (dt, 1 H, J = 7.6, 5.6 Hz,
O=COCHCHH); 30-min: 0.87 (t, 3 H, J = 7.1 Hz, CH2CH3),
1.25-1.43 (m, 12 H, 6 × CH2), 1.52 (s, 3 H, OCCH3), 1.71-1.78
(m, 1 H, O=COCHCHH), 1.81-1.89 (m, 1 H, O=COCHCHH),
2.68 (dd, 1 H, J = 18.3, 9.1 Hz, O=CCHHCH), 2.74 (dd, 1 H, J =
18.3, 9.8 Hz, O=CCHHCH), 3.40 (ddd, 1 H, J = 9.7, 9.1, 5.8 Hz,
O=CCHHCH), 4.74 (dt, 1 H, J = 8.6, 5.4 Hz, O=COCHCHH); δC
(125 MHz, CDCl3): 30-maj: 14.2 (CH3), 22.7 (CH2), 25.0 (CH2),
27.9 (CH3), 29.2 (CH2), 29.2 (CH2), 29.4 (CH2), 31.9 (CH2), 33.3
(CH2), 35.1 (CH2), 45.1 (CH), 85.8 (CH), 84.8 (C), 85.0 (C),
164.7 (C=O), 167.5 (C=O), 172.8 (C=O); 30-min: 14.2 (CH3),
22.7 (CH2), 25.7 (CH2), 28.0 (CH3), 28.0 (CH2), 29.2 (CH2), 29.3
(CH2), 29.4 (CH2), 31.1 (CH2), 31.8 (CH2), 44.3 (CH), 79.6 (CH),
85.4 (C), 86.0 (C), 163.9 (C=O), 168.5 (C=O), 172.4 (C=O); νmax
/ cm-1 2929m (C-H), 2957w (C-H), 1789s (C=O), 1759s (C=O);
m/z LRMS (ESI+): 377.2 ([M+Na]+, 100%) ; HRMS (ESI+) found
377.1931; C19H30O6Na [M+Na]+ requires 377.1935.
Using general procedure 5 with 17 (mixture of diastereomers,
3.95 g, 14.61 mmol), LiCl (2.17 g, 51.15 mmol) in DMSO (60.0
mL) and H2O (1.25 mL); EtOAc was used as the extraction
solvent and the residue was purified by FC (PE40−60 / EtOAc,
gradient from 3:1 to 1:1), to give 33 as a yellowish liquid (2.08
mg, 12.22 mmol, 80% isolated as an inseparable 2.03:1 mixture
of diastereomers). Analysis is on the mixture of diastereomers,
Rf (PE40−60 / EtOAc, 2:1) = 0.2; δH (500 MHz, CDCl3): 33-maj:
1.05 (t, 3 H, J = 7.5 Hz, CHHCH3), 1.79 (qdd, 1 H, J = 7.3, 5.9,
3.4 Hz, CHHCH3), 1.81 (dqd, 1 H, J = 10.5, 7.5, 4.7 Hz,
CHHCH3), 2.56 (dd, 1 H, J = 18.2, 4.1 Hz, O=CCHHCH), 2.95
(dd, 1 H, J = 18.2, 9.5 Hz, O=CCHHCH), 3.05 (m, 1 H,
O=CCHHCH), 4.30 (ddd, 1 H,
J = 6.9, 5.9, 4.8 Hz,
O=COCHCHHCH3), 5.01 (d, 1 H, J = 7.8 Hz, O=COCHC=O);
33-min: 1.07 (t, 3 H, J = 7.5 Hz, CHHCH3), 1.63 (dqd, 1 H, J =
10.9, 7.4, 6.1 Hz, CHHCH3), 1.89 (sept, 1 H, J = 7.4 Hz,
CHHCH3), 2.63 (dd, 1 H, J = 18.2, 9.5 Hz, O=CCHHCH), 2.64
(dd, 1 H, J = 18.2, 9.5 Hz, O=CCHHCH), 3.44-3.53 (m, 1 H,
O=CCHHCH), 4.55 (dt, 1 H, J = 8.3, 5.9 Hz, O=COCHCHH),
5.16 (d, 1 H, J = 8.4 Hz, O=COCHC=O); δC (125 MHz, CDCl3):
33-maj: 9.3 (CH3), 24.8 (CH2), 33.0 (CH2), 39.9 (CH), 77.1
(CH), 86.0 (CH), 169.9 (C=O), 173.6 (C=O); 33-min: 9.9 (CH3),
24.8 (CH2), 26.9 (CH2), 39.3 (CH), 77.1 (CH), 80.1 (CH), 170.5
(C=O), 173.7 (C=O); νmax / cm-1 2973w (C-H), 1777s (C=O),
1212m (C-O-C), 1150m (C-O-C), 1069m (C-O-C); m/z LRMS
(ESI+): 363.0 ([2M+Na]+, 40%); HRMS (ESI+) found 363.1050;
C16H20O8Na [2M+Na]+ requires 363.1050.
4.8.13. tert-Butyl (3aR*,4R*,6aR*)-4-decyl-2,6-
dioxotetrahydrofuro[3,4-b]furan-6a(6H)-
carboxylate 31-maj and tert-butyl
(3aR*,4S*,6aR*)-4-decyl-2,6-
dioxotetrahydrofuro[3,4-b]furan-6a(6H)-
carboxylate 31-min
4.8.15. (3aR*,4R*,6aR*)-4-Octyldihydrofuro[3,4-
b]furan-2,6(3H,4H)-dione 34-maj and
(3aR*,4S*,6aR*)-4-octyldihydrofuro[3,4-b]furan-
2,6(3H,4H)-dione 34-min
Using general procedure 4 with 16 (5.09 g, 11.56 mmol),
Mn(OAc)3•2H2O (9.30 g, 34.67 mmol) and KI (0.96 g, 5.78
mmol) in MeCN (77.0 mL) gave crude material that was purified
by FC (PE40−60 / EtOAc, gradient from 14:1 to 5:1) to give 31 as a
yellowish solid (3.28 g, 8.58 mmol, 74% isolated as an
inseparable 1.7:1 mixture of diastereomers). Analysis is on the
mixture of diastereomers, Rf (PE40−60 / EtOAc, 8:1) = 0.2; m.p. =
83-88 °C; δH (500 MHz, CDCl3): 31-maj: 0.88 (t, 3 H, J = 7.2
Hz, CH2CH3), 1.26-1.53 (m, 16 H, 8 × CH2), 1.53 (s, 9 H,
OCCH3), 1.71-1.78 (m, 1 H, O=COCHCHH), 1.83-1.91 (m, 1 H,
O=COCHCHH), 2.56 (dd, 1 H, J = 18.2, 2.3 Hz, O=CCHHCH),
2.96 (dd, 1 H, J = 18.2, 9.4 Hz, O=CCHHCH), 3.04 (ddd, 1 H, J
= 9.3, 5.9, 2.3 Hz, O=CCHHCH), 4.24 (dt, 1 H, J = 7.8, 5.7 Hz,
O=COCHCHH); 31-min: 0.88 (t, 3 H, J = 7.2 Hz, CH2CH3),
1.26-1.53 (m, 16 H, 8 × CH2), 1.54 (s, 9 H, OCCH3), 1.71-1.78
(m, 1 H, O=COCHCHH), 1.83-1.91 (m, 1 H, O=COCHCHH),
2.68 (dd, 1 H, J = 18.3, 9.2 Hz, O=CCHHCH), 2.74 (dd, 1 H, J =
18.3, 9.8 Hz, O=CCHHCH), 3.38 (td, 1 H, J = 9.5, 5.7 Hz,
O=CCHHCH), 4.75 (dt, 1 H, J = 8.8, 5.5 Hz, O=COCHCHH); δC
(125 MHz, CDCl3): 31-maj: 14.3 (CH3), 22.8 (CH2), 25.1 (CH2),
28.0 (CH3), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 29.7
(CH2), 32.0 (CH2), 33.3 (CH2), 35.2 (CH2), 45.3 (CH), 84.8 (CH),
84.9 (C), 85.9 (C), 164.7 (C=O), 167.3 (C=O), 172.6 (C=O); 31-
min: 14.3 (CH3), 22.8 (CH2), 25.7 (CH2), 27.8 (CH2), 28.0 (CH3),
28.0 (CH2), 29.4 (CH2), 29.4 (CH2), 29.5 (CH2), 29.6 (CH2), 31.2
(CH2), 32.0 (CH2), 44.4 (CH), 79.5 (CH), 85.4 (C), 86.1 (C),
164.0 (C=O), 168.4 (C=O), 172.2 (C=O); νmax / cm-1 2926m (C-
H), 2855w (C-H), 1789s (C=O), 1759m (C=O); m/z LRMS
(ESI+): 405.2 ([M+Na]+, 100%); HRMS (ESI+) found 405.2246;
C21H34O6Na [M+Na]+ requires 405.2248.
Using general procedure 5 with 30 (mixture of diastereomers,
350 mg, 0.99 mmol), LiCl (147 mg, 3.46 mmol) in DMSO (6.6
mL) and H2O (0.08 mL) gave 34 as brown oil (194 mg, 0.76
mmol, 77% isolated as a 2.23:1 inseparable mixture of
diastereomers). Analysis is on the mixture of diastereomers, Rf
(PE40−60 / EtOAc, 5:1) = 0.16, 0.22; δH (500 MHz, CDCl3): 34-
maj: 0.88 (t, 3 H, J = 7.1 Hz, CH2CH3), 1.25-1.84 (m, 14 H, 7 ×
CH2), 2.55 (dd, 1 H, J = 18.2, 4.1 Hz, O=CCHHCH), 2.94 (dd, 1
H, J = 18.2, 9.4 Hz, O=CCHHCH), 3.04 (dddd, 1 H, J = 9.4, 7.9,
4.9, 4.1 Hz, O=CCHHCH), 4.34 (dt, 1 H, J = 7.6, 5.2 Hz,
CHCHOC=O), 5.01 (d, 1 H, J = 7.9 Hz, O=COCHC=O); 34-
min: 0.88 (t, 3 H, J = 7.1 Hz, CH2CH3), 1.25-1.84 (m, 14 H, 7 ×
CH2), 2.63 (s apparent, 1 H, O=CCHHCH), 2.64 (s apparent, 1 H,
O=CCHHCH), 3.46 (tdd,
1 H, J = 9.6, 8.4, 5.7 Hz,
O=CCHHCH), 4.60 (dt, 1 H, J = 8.7, 5.7 Hz, CHCHOC=O), 5.16
(d, 1 H, J = 8.4 Hz, O=COCHC=O); δC (125 MHz, CDCl3): 34-
maj: 14.2 (CH3), 22.8 (CH2), 25.1 (CH2), 29.3 (CH2), 29.3 (CH2),
29.5 (CH2), 31.9 (CH2), 32.9 (CH2), 35.6 (CH2), 40.4 (CH), 77.1
(CH), 84.9 (CH), 169.9 (C=O), 173.6 (C=O); 34-min: 14.2
(CH3)), 22.8 (CH2), 25.6 (CH2), 27.0 (CH2), 29.3 (CH2), 29.3
(CH2), 29.4 (CH2), 31.6 (CH2), 31.9 (CH2), 39.6 (CH), 77.1 (CH),
78.8 (CH), 170.6 (C=O), 173.7 (C=O); νmax / cm-1 2925m (C-H),
2856w (C-H), 1781s (C=O), 1216w (C-O-C), 1150w (C-O-C);
m/z LRMS (ESI+): 531.4 ([2M+Na]+, 100%); HRMS (ESI+)
found 277.1412; C14H22O4Na [M+Na]+ requires 277.1410.
4.8.16. (3aR*,4R* 6aR)-4-Decyldihydrofuro[3,4-
b]furan-2,6(3H,4H)-dione 35-maj and
(3aR*,4S*,6aR*)-4-decyldihydrofuro[3,4-b]furan-
2,6(3H,4H)-dione 35-min
4.8.14. (3aR*,4R*,6aR*)-4-Ethyldihydrofuro[3,4-
b]furan-2,6(3H,4H)-dione 33-maj and
Using general procedure 5 with 31 (mixture of diastereomers,
3.28 g, 8.58 mmol), LiCl (1.27 g, 30.01 mmol) in DMSO (36.0
mL) and H2O (0.73 mL) gave 35 as a brown oil (2.33 g, 8.25