The Journal of Organic Chemistry
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oils. Data for 38b: Rf 0.31 (10:1 n-hexane/AcOEt); [α]2D6 +7.1 (c 1.08,
133.4 (C), 135.5 (CH), 135.6 (CH), 175.9 (C); HRMS (ESI) m/z [M
+ Na]+ calcd for C30H39IO4SiNa 641.1560; found 641.1568.
CHCl3); IR (neat) 3071, 2932, 2859, 1732, 1456, 1427, 1227, 1113
1
cm−1; H NMR (500 MHz, CDCl3) δ 1.04 (d, J = 7.1 Hz, 3H), 1.05
Methyl [2R,2(1S),3R,5S]-5-(Hydroxymethyl)-3-methyl-2-(1-
methylcyclohex-2-en-1-yl)tetrahydrofuran-2-carboxylate (41).
NH4F (249 mg, 6.72 mmol) was added to a solution of TBDPS ether
38b (341 mg, 0.673 mmol) in MeOH/EtOH (5:2, 7 mL). After 24 h
of stirring, the mixture was partitioned between AcOEt (70 mL) and
H2O (15 mL), and the aqueous layer was extracted with AcOEt (70
mL). The combined organic extracts were washed with brine (20 mL)
and dried over anhydrous Na2SO4. Filtration and evaporation in vacuo
furnished the crude product (391 mg), which was purified by column
chromatography (silica gel 10 g, 2:1 n-hexane/AcOEt) to give alcohol
41 (170 mg, 94%) as a colorless oil. Rf 0.31 (3:1 n-hexane/AcOEt);
[α]2D2 +19.5 (c 1.17, CHCl3); IR (neat) 3442, 2937, 1732, 1456, 1227,
1101, 1051 cm−1; 1H NMR (500 MHz, CDCl3) δ 1.06 (d, J = 7.0 Hz,
3H), 1.20 (s, 3H), 1.52−1.71 (m, 4H), 1.81 (dt, J = 3.3, 12.5 Hz, 1H),
1.92−1.94 (m, 2H), 2.04 (ddd, J = 5.6, 9.0, 12.5 Hz, 1H), 2.55 (m,
1H), 3.47 (dd, J = 5.1, 11.6 Hz, 1H), 3.73 (s, 3H), 3.74 (dd, J = 3.4,
11.6 Hz, 1H), 4.32 (m, 1H), 5.75 (m, 1H), 5.84 (m, 1H); 13C NMR
(125.7 MHz, CDCl3) δ 18.0 (CH3), 19.2 (CH2), 23.2 (CH3), 24.8
(CH2), 31.1 (CH2), 36.5 (CH2), 37.0 (CH), 42.0 (C), 51.3 (CH3),
65.0 (CH2), 78.0 (CH), 94.1 (C), 127.8 (CH), 132.4 (CH), 173.2
(C); HRMS (ESI) m/z [M + Na]+ calcd for C15H24O4Na 291.1572;
found 291.1555.
(s, 9H), 1.08 (s, 3H), 1.49−1.62 (m, 4H), 1.80−1.89 (m, 3H), 2.16
(ddd, J = 5.0, 8.6, 13.5 Hz, 1H), 2.46 (m, 1H), 3.66 (dd, J = 4.3, 10.6
Hz, 1H), 3.69 (dd, J = 5.2, 10.6 Hz, 1H), 3.71 (s, 3H), 4.29 (m, 1H),
5.65 (m, 1H), 5.95 (m, 1H), 7.36−7.43 (m, 6H), 7.67 (m, 4H); 13C
NMR (125.7 MHz, CDCl3) δ 18.0 (CH3), 19.49 (C), 19.51 (CH2),
23.6 (CH3), 25.1 (CH2), 27.1 (CH3), 30.8 (CH2), 36.9 (CH), 37.3
(CH2), 42.1 (C), 51.4 (CH3), 66.0 (CH2), 78.3 (CH), 94.2 (C), 127.3
(CH), 127.87 (CH), 127.89 (CH), 129.8 (CH), 129.9 (CH), 133.0
(CH), 133.7 (C), 133.9 (C), 135.85 (CH), 135.90 (CH), 173.9 (C);
HRMS (ESI) m/z [M + Na]+ calcd for C31H42O4SiNa 529.2750;
found 529.2769.
Data for the [2S,2(1S),3R,5S] isomer 38a: Rf 0.28 (10:1 n-hexane/
AcOEt); [α]2D6 −14.2 (c 0.16, CHCl3); IR (neat) 3028, 2932, 2856,
1
1732, 1460, 1427, 1227, 1113 cm−1; H NMR (500 MHz, CDCl3) δ
1.056 (s, 9H), 1.063 (d, J = 6.7 Hz, 3H), 1.10 (s, 3H), 1.51−1.66 (m,
3H), 1.72 (dt, J = 3.4, 13.1 Hz, 1H), 1.86 (m, 1H), 1.90−1.93 (m,
2H), 2.20 (ddd, J = 7.0, 9.1, 12.2 Hz, 1H), 2.48 (m, 1H), 3.69 (dd, J =
3.8, 10.7 Hz, 1H), 3.71 (s, 3H), 3.80 (dd, J = 4.9, 10.7 Hz, 1H), 4.29
(m, 1H), 5.68 (dt, J = 10.0, 3.3 Hz, 1H), 5.76 (dd, J = 1.6, 10.0 Hz,
1H), 7.36−7.43 (m, 6H), 7.66−7.70 (m, 4H); 13C NMR (125.7 MHz,
CDCl3) δ 18.6 (CH3), 19.1 (CH2), 19.3 (CH), 23.3 (CH3), 24.9
(CH2), 26.8 (CH3), 31.3 (CH2), 36.8 (C), 37.4 (CH2), 42.5 (C), 51.2
(CH3), 65.2 (CH2), 78.4 (CH), 94.8 (C), 127.63 (CH), 127.65 (CH),
129.56 (CH), 129.61 (CH), 132.6 (CH), 133.5 (C), 133.6 (C), 135.6
(CH), 135.7 (CH), 173.4 (C); HRMS (ESI) m/z [M + Na]+ calcd for
C31H42O4SiNa 529.2750, found 529.2730.
Methyl [2R,2(1S),3R,5S]-5-(Iodomethyl)-3-methyl-2-(1-meth-
ylcyclohex-2-en-1-yl)tetrahydrofuran-2-carboxylate (42). Io-
dine (103 mg, 0.405 mmol) was added to a mixture of alcohol 41
(72.4 mg, 0.270 mmol), triphenylphosphine (106 mg, 0.405 mmol),
and imidazole (55.1 mg, 0.809 mmol) in toluene (2.7 mL). After 1 h
of stirring at 50 °C, the reaction was quenched with 1 M aqueous
Na2S2O3 (5 mL), and the resulting mixture was extracted with AcOEt
(2 × 30 mL). The combined organic extracts were washed with brine
(5 mL) and dried over anhydrous Na2SO4. Filtration and evaporation
in vacuo furnished the crude product (247 mg), which was purified by
column chromatography (silica gel 10 g, 20:1 n-hexane/AcOEt) to
give iodide 42 (96.3 mg, 94%) as a colorless oil. Rf 0.42 (10:1 n-
hexane/AcOEt); [α]2D0 −15.5 (c 1.20, CHCl3); IR (neat) 2936, 2876,
(1S,3S,5R,3a′S,4′S,7a′S)-3-[(tert-Butyldiphenylsilyl)-
oxymethyl]-4′-iodo-5,7a′-dimethyl-2,3′-dioxaspiro-
[cyclopentane-1,1′-hexahydroindan]-2′-one (39b). Iodine (453
mg, 1.78 mmol) was added to a solution of carboxylic acids 37a and
37b (797 mg, 1.62 mmol) in MeCN/saturated aqueous NaHCO3
(1:1, 20 mL) at 0 °C. After 90 min of stirring, the reaction was
quenched with 1 M aqueous Na2S2O3 (30 mL), and the resulting
mixture was extracted with AcOEt (2 × 100 mL). The combined
organic extracts were washed with brine (30 mL) and dried over
anhydrous Na2SO4. Filtration and evaporation in vacuo furnished the
crude product (977 mg), which was purified by flash column
chromatography (silica gel 70 g, 20:1 n-hexane/AcOEt) to give
isomer 39b (802 mg, 81%) as a white solid along with isomer 39a
(35.5 mg, 4%) as a colorless oil. Data for 39b: Rf 0.54 (5:1 n-hexane/
AcOEt); mp 139−140 °C (colorless prisms from n-hexane); [α]D25
+53.7 (c 1.08, CHCl3); IR (KBr) 3071, 2934, 2857, 1780, 1460, 1233,
1
1732, 1454, 1433, 1229, 1061 cm−1; H NMR (500 MHz, CDCl3) δ
1.04 (d, J = 6.7 Hz, 3H), 1.11 (s, 3H), 1.57−1.62 (m, 2H), 1.67 (m,
1H), 1.76 (ddd, J = 8.0, 8.8, 12.9 Hz, 1H), 1.82 (dt, J = 3.2, 12.5 Hz,
1H), 1.90−1.94 (m, 2H), 2.02 (ddd, J = 4.8, 8.7, 12.9 Hz, 1H), 2.52
(ddq, J = 8.7, 8.8, 6.7 Hz, 1H), 3.12 (dd, J = 8.4, 9.7 Hz, 1H), 3.29 (dd,
J = 4.4, 9.7 Hz, 1H), 3.72 (s, 3H), 4.35 (dddd, J = 4.4, 4.8, 8.0, 8.4 Hz,
1H), 5.59 (m, 1H), 5.91 (m, 1H); 13C NMR (125.7 MHz, CDCl3) δ
9.8 (CH2), 17.6 (CH3), 19.3 (CH2), 23.4 (CH3), 24.9 (CH2), 30.8
(CH2), 36.2 (CH2), 40.6 (CH), 41.8 (C), 51.3 (CH3), 77.5 (CH),
95.2 (C), 127.5 (CH), 132.3 (CH), 173.0 (C); HRMS (ESI) m/z [M
+ Na]+ calcd for C15H23IO3Na 401.0590; found 401.0587.
Methyl [2R,2(1S),3R]-2-(1-Methylcyclohex-2-en-1-yl)-3-
methyl-2-hydroxyhex-5-enoate (43). Activated zinc powder
(80.0 mg, 1.22 mmol) was added to a solution of iodide 42 (92.6
mg, 0.245 mmol) in AcOH (1.2 mL). After 1 h of stirring at 110 °C,
the suspension was filtered through a Celite pad, and the filtrate was
concentrated in vacuo. The residue was azeotropically dried with
toluene (3 × 5 mL) to furnish the crude product (127 mg), which was
purified by column chromatography (silica gel 5 g, 20:1 n-hexane/
AcOEt) to give diene 43 (51.3 mg, 83%) as a colorless oil. Rf 0.42
(10:1 n-hexane/AcOEt); [α]D23 +27.4 (c 1.06, CHCl3); IR (neat) 3510,
2938, 1720, 1639, 1437, 1229, 1153 cm−1; 1H NMR (500 MHz,
CDCl3) δ 0.77 (d, J = 6.7 Hz, 3H), 1.09 (s, 3H), 1.51−1.71 (m, 3H),
1.91−2.01 (m, 4H), 2.19 (m, 1H), 2.57 (m, 1H), 3.36 (s, 1H), 3.77 (s,
3H), 4.96−5.03 (m, 2H), 5.67 (m, 1H), 5.70−5.79 (m, 2H); 13C
NMR (125.7 MHz, CDCl3) δ 14.8 (CH3), 19.4 (CH2), 24.0 (CH3),
24.5 (CH2), 30.7 (CH2), 35.8 (CH2), 37.8 (CH), 41.9 (C), 52.4
(CH3), 83.9 (C), 115.9 (CH2), 126.5 (CH), 133.0 (CH), 137.5 (CH),
177.4 (C); HRMS (ESI) m/z [M + Na]+ calcd for C15H24O3Na
275.1623; found 275.1642.
1
1113, 970, 702 cm−1; H NMR (500 MHz, C6D6) δ 0.79 (m, 1H),
0.95−1.04 (m, 2H), 1.14 (d, J = 6.7 Hz, 3H), 1.16 (s, 9H), 1.28 (s,
3H), 1.33 (m, 1H), 1.48−1.60 (m, 2H), 1.83 (m, 1H), 1.93 (m, 1H),
2.10 (m, 1H), 3.51 (dd, J = 4.8, 10.7 Hz, 1H), 3.58 (dd, J = 4.7, 10.7
Hz, 1H), 4.19 (m, 1H), 4.28 (m, 1H), 4.72 (s, 1H), 7.25−7.26 (m,
6H), 7.75−7.79 (m, 4H); 13C NMR (125.7 MHz, C6D6) δ 15.9
(CH3), 17.4 (CH2), 17.8 (CH3), 19.4 (C), 23.5 (CH), 27.0 (CH3),
29.3 (CH2), 30.6 (CH2), 32.8 (CH), 36.7 (CH2), 43.9 (C), 66.0
(CH2), 77.7 (CH), 83.7 (CH), 91.4 (C), 128.11 (CH), 128.14 (CH),
128.3 (CH), 130.06 (CH), 130.10 (CH), 133.8 (C), 133.9 (C), 136.0
(CH), 172.0 (C); HRMS (ESI) m/z [M + Na]+ calcd for
C30H39IO4SiNa 641.1560; found 641.1549. Anal. Calcd for
C30H39IO4Si: C, 58.25; H, 6.35. Found: C, 58.17; H, 6.35.
Data for the (1R,3S,5R,3a′S,4′S,7a′S) isomer 39a: Rf 0.52 (5:1 n-
hexane/AcOEt); [α]2D7 +2.5 (c 1.19, CHCl3); IR (neat) 3071, 2932,
1
2859, 1782, 1456, 1236, 1113, 970, 702 cm−1; H NMR (500 MHz,
CDCl3) δ 1.06 (s, 9H), 1.10 (d, J = 7.1 Hz, 3H), 1.36 (s, 3H), 1.55−
1.63 (m, 3H), 1.75 (m, 1H), 1.88−2.00 (m, 3H), 2.15 (ddd, J = 4.7,
8.1, 12.5 Hz, 1H), 2.50 (m, 1H), 3.60 (dd, J = 4.0, 10.9 Hz, 1H), 3.70
(dd, J = 4.4, 10.9 Hz, 1H), 4.43 (m, 1H), 4.50 (d, J = 3.1 Hz, 1H), 4.62
(dt, J = 3.1, 3.3 Hz, 1H), 7.37−7.45 (m, 6H), 7.65−7.69 (m, 4H); 13C
NMR (125.7 MHz, CDCl3) δ 15.7 (CH3), 18.1 (CH2), 19.2 (C), 20.1
(CH3), 24.3 (CH), 26.8 (CH3), 30.0 (CH2), 31.2 (CH2), 35.3 (CH2),
35.5 (CH), 43.2 (C), 65.7 (CH2), 78.1 (CH), 83.5 (CH), 93.2 (C),
127.68 (CH), 127.72 (CH), 129.67 (CH), 129.74 (CH), 133.2 (C),
Methyl [2R,2(1S),3R,5S]-5-(Chloromethyl)-3-methyl-2-(1-
methylcyclohex-2-en-1-yl)tetrahydrofuran-2-carboxylate (44).
A mixture of alcohol 41 (170 mg, 0.632 mmol) and triphenylphos-
730
dx.doi.org/10.1021/jo402537u | J. Org. Chem. 2014, 79, 720−735