The Journal of Organic Chemistry
Page 24 of 47
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0.71 mmol) as a colorless oil in 75% yield. Note: The minor (Z)ꢀisomer was detected by GC/MS analysis of
the crude (ca. 5.5% of the product) and was separated from the (E)ꢀisomer during the chromatographic
purification. TLC (SiO2): Rf = 0.48 (hexanes/EtOAc 95:5); [α]D25 = +27 (c 1.0, CHCl3); IR (ATR, cm−1): 2923,
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1716, 1648, 1457, 1386, 1221, 1143, 1040, 861; H NMR (250 MHz, CDCl3): δ 0.75 (s, 3H), 0.85 (s, 3H),
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0.87 (s, 3H), 1.27 (t, J = 7.1Hz, 3H), 1.69 (s, 3H), 0.79ꢀ1.74 (m, 9H), 2.16 (d, J = 1.3 Hz, 3H), 1.74ꢀ2.22 (m,
4H), 2.26ꢀ2.43 (m, 1H), 4.15 (q, J = 7.2 Hz, 2H), 5.40 (br. s, 1H), 5.66 (q, J = 1.0 Hz, 1H); 13C NMR (62.9
MHz, CDCl3): δ 13.5 (CH3), 14.3 (CH3), 18.7 (CH2), 18.9 (CH3), 21.8 (CH3), 22.1 (CH3), 23.8 (CH2), 25.3
(CH2), 32.9 (C), 33.1 (CH3), 36.8 (C), 39.1 (CH2), 42.2 (CH2), 43.4 (CH2), 50.1 (CH), 54.4 (CH), 59.4 (CH2),
115.5 (CH), 122.7 (CH), 134.7 (C), 160.3 (C), 166.8 (C); HRMS (ESI +): m/z calculated for C22H36O2Na+
[M+Na]+ 355.2608, found 355.2613.
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(E)-3-methyl-5-((1S,4aS,8aS)-2,5,5,8a-tetramethyl-1,4,4a,5,6,7,8,8a-octahydrona-phthalen-1-
yl)pent-2-enoic acid (16). Solid LiOH•H2O (298 mg, 12.2 mmol, 20 equiv) was added to a solution of ester
15 (203 mg, 0.610 mmol, 1 equiv) in a mixture of THF, iꢀPrOH and H2O (21 mL, 1:1:1). The reaction was
stirred at 60 °C for 20 h, then the volatiles were removed under reduced pressure. To the remaining
residue, EtOAc (30 mL) and HCl solution (1 M, 30 mL) were added. The organic phase was separated,
washed with brine (20 mL), dried over anhydrous MgSO4 and concentrated under reduced pressure. The
residue was subjected to flash chromatography (SiO2, hexanes/EtOAc 85:15) to give the carboxylic acid 16
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(141 mg, 0.463 mmol) as a white solid in 76% yield. TLC (SiO2): Rf = 0.46 (hexanes/EtOAc 75:25); [α]D
=
+34 (c 1.0, CHCl3); IR (ATR, cm−1): 3441 (broad), 2946 (broad), 2924, 2849, 1693, 1639, 1437, 1257,
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1173, 867; H NMR (250 MHz, CDCl3): δ 0.76 (s, 3H), 0.86 (s, 3H), 0.88 (s, 3H), 0.80ꢀ1.03 (m, 2H), 1.08ꢀ
1.73 (m, 7H), 1.70 (s, 3H), 2.19 (d, J = 1.1 Hz, 3H), 1.75ꢀ2.25 (m, 4H), 2.30ꢀ2.46 (m, 1H), 5.41 (br. s, 1H),
5.70 (q, J = 0.8 Hz, 1H), 11.46 (br. s, 1H); 13C NMR (62.9 MHz, CDCl3): δ 13.5 (CH3), 18.7 (CH2), 19.3
(CH3), 21.8 (CH3), 22.1 (CH3), 23.8 (CH2), 25.3 (CH2), 32.9 (C), 33.1 (CH3), 36.8 (C), 39.2 (CH2), 42.2
(CH2), 43.6 (CH2), 50.1 (CH), 54.4 (CH), 115.1 (CH), 122.8 (CH), 134.6 (C), 163.6 (C), 172.2 (C); HRMS
(ESI +): m/z calculated for C20H32O2Na+ [M+Na]+ 327.2295, found 327.2286.
(4aS,5S,8aS)-5-((E)-4-iodo-3-methylbut-3-en-1-yl)-1,1,4a,6-tetramethyl-1,2,3,4,4a,5,8,8a-
octahydronaphthalene (3). A flask was charged with carboxylic acid 16 (93.2 mg, 0.306 mmol, 1 equiv) and
CTAB (113 mg, 0.306 mmol, 1 equiv), the flask was purged with nitrogen, and dry acetonitrile (7 mL) was
added followed by NIS (138 mg, 0.612 mmol, 2 equiv). The reaction mixture was heated at 80 °C for 1 h
and, after cooling to room temperature, solvent was partially removed under reduced pressure to ~1 mL of
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