Organic & Biomolecular Chemistry
Paper
[α]2D2 −24.3° (c 0.57, CHCl3);
(1R,2S,3R)-1,2-Dimethyl-3-(prop-1-en-2-yl)cyclopentanol (6).
1H NMR, COSY (400 MHz, CDCl3) δ (ppm) 4.79–4.77 (m, Methyl xanthogenate 5 (6.00 g, 23.0 mmol) and AIBN (378 mg,
2
3
1H, H-1′), 4.76–4.73 (m, 1H, H-1′), 3.90 (dd, J = 11.4 Hz, J = 2.30 mmol, 0.10 eq.) were dissolved in deoxygenated toluene
2
3
3.2 Hz, 1H, H-7), 3.71 (dd, J = 11.4 Hz, J = 5.1 Hz, 1H, H-7), (500 mL) under argon atmosphere. nBu3SnH (12.2 mL,
3
3
2.86 (dt, J = 10.8 Hz, J = 8.7 Hz, 1H, H-3), 1.98–1.88 (m, 1H, 46.1 mmol, 2 eq.) was added at room temperature. Sub-
H-4), 1.80–1.71 (m, 2H, H-5), 1.70 (s, 3H, H-3′), 1.64–1.59 (m, sequently the mixture was heated to reflux for 15 minutes and
1H, H-2), 1.54–1.49 (m, 1H, H-4), 1.39 (s, 3H, H-10); 13C NMR, the reaction mixture rapidly turned dark. The solvent was
HSQC, HMBC (100.6 MHz, CDCl3) δ (ppm) 146.9 (C-2′), 110.7 removed in vacuo and the residue was purified by flash column
(C-1′), 81.6 (C-1), 60.9 (C-7), 52.6 (C-2), 46.9 (C-3), 41.7 (C-5), chromatography (cyclohexane–ethyl acetate, 8 : 1) to afford the
28.5 (C-6), 28.0 (C-4), 19.3 (C-3′).
title compound (2.56 g, 16.6 mmol, 72%) as a colorless oil.
(1R,2R,3S)-2-(hydroxymethyl)-3-isopropyl-1-methylcyclo- The material contained 13% (NMR) of the saturated analogue
pentanol (reduced side product)
but was used without further purification for the next step.
Rf 0.24 (silica gel, cyclohexane–ethyl acetate, 8 : 1).
[α]2D2 −13.8° (c = 1.00, CHCl3);
1H NMR, COSY (400 MHz, CDCl3) δ (ppm) 3.85 (dd, 2J =
3
2
3
11.4 Hz, J = 3.0 Hz, 1H, H-7), 3.71 (dd, J = 11.3 Hz, J = 6.4
Hz, 1H, H-7), 1.84 (m, 1H, H-3), 1.83–1.75 (m, 1H, H-4),
1H NMR, COSY (400 MHz, CDCl3) δ (ppm) 4.73–4.71 (m,
1.72–1.65 (m, 2H, H-5), 1.65–1.58 (m, 1H, H-2′), 1.52–1.46 (m, 2H, H-1′), 2.43 (dt, 3J = 11.3 Hz, 3J = 8.9 Hz, 1H, H-3), 1.92 (ddt,
1H, H-2), 1.35 (s, 3H, H-6), 1.34–1.29 (m, 1H, H-4), 0.93 (d, 3J = 2J = 12.7 Hz, J = 8.9 Hz, J = 7.5 Hz, 1H, H-4), 1.79–1.72 (m,
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3
6.8 Hz, 3H, H-1′), 0.84 (d, 3J = 6.7 Hz, 3H, H-3′); 13C NMR, 2H, H-5), 1.69 (t, 4J = 1.1 Hz, 3H, H-3Ä′), 1.55–1.49 (m, 1H, H-2),
3
HSQC, HMBC (100.6 MHz, CDCl3) δ (ppm) 82.1 (C-1), 62.5 1.49–1.42 (m, 1H, H-4), 1.28 (s, 3H, H-6), 0.86 (d, J = 6.8 Hz,
(C-7), 52.3 (C-2), 45.4 (C-3), 41.3 (C-5), 31.0 (C-2′), 28.9 (C-6), 3H, H-7); 13C NMR, HSQC, HMBC (100.6 MHz, CDCl3) δ (ppm)
25.1 (C-4), 21.6 (C-1′), 18.6 (C-3′).
147.1 (C-2′), 110.3 (C-1′), 80.3 (C-1), 52.7 (C-3), 47.0 (C-2), 40.0
(C-5), 27.5 (C-4), 26.6 (C-6), 19.0 (C-3′), 10.6 (C-7).
The data are in accordance with the literature.22
O-[(1R,2R,5R)(2-Hydroxy-2-methyl-5-(prop-1-en-2-yl)cyclo-
The data are in accordance with the literature.22
pentyl)methyl]S-methylcarbonodithioate (5). Compound
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1-((1R,2S,3R)-3-Hydroxy-2,3-dimethylcyclopentyl)ethanone
(7.00 g, 41.1 mmol, containing 10% of the reduced byproduct (7). Olefin 6 (1.00 g, 6.49 mmol) and K2OsO4·2H2O (47.9 mg,
4a) and CS2 (9.94 mL, 165 mmol, 4.00 eq.) was dissolved in 0.130 mmol, 2 mol%) were dissolved in THF (100 mL), H2O
t
THF (300 mL). NaH (1.97 g, 49.3 mmol, 1.20 eq., 60% dis- (33 mL) and BuOH (10 mL) under stirring at room tempera-
persion in mineral oil) was suspended in THF (200 mL), ture. Solid NaIO4 (13.9 g, 64.9 mmol, 10 eq.) was added within
combined with the alcohol solution at 0 °C and the mixture 5 minutes in two portions. The reaction mixture was filtered
was stirred at this temperature for 30 min. The reaction after 16 h, diluted with H2O (50 mL) and extracted with EtOAc
mixture was allowed to warm up to room temperature and was (200 mL). The separated aqueous layer was extracted twice
stirred for another 60 min while its color changed from yellow- with EtOAc (100 mL each). The combined organic layers were
ish to brown. Iodomethane (20.6 mL, 329 mmol, 8.00 eq.) was washed with cold saturated aqueous Na2S2O3 solution
added slowly (CAUTION!) and stirring was continued for (150 mL), dried over anhydrous MgSO4 and filtered. The
15 min. The mixture was diluted with MTBE (200 mL) and solvent was removed in vacuo and the residue was purified by
washed two times with brine (250 mL). The organic layer was flash column chromatography (cyclohexane–ethyl acetate, 3 : 1)
dried over anhydrous MgSO4 and filtered. The solvent was to afford the title compound (474 mg, 3.04 mmol, 47%) as a
removed in vacuo and the residue was purified by flash column light yellowish oil which became a waxy solid at room
chromatography (cyclohexane–ethyl acetate, 10 : 1) to afford temperature.
8.80 g (33.8 mmol, 82%) of the title compound as a yellowish
oil. The material still contained the saturated analogue but
was used without further purification for the next step.
Rf 0.25 (silica gel, cyclohexane–ethyl acetate, 10 : 1).
IR (ATR) νmax/cm−1 3456, 2959, 2872, 1643, 1455, 1375,
1216, 1054, 965, 890;
Rf 0.16 (silica gel, cyclohexane–ethyl acetate, 3 : 1).
IR (ATR) νmax/cm−1 3438, 2971, 2933, 2874, 1694, 1454,
1426, 1370, 1350, 1204, 1024, 567;
[α]2D2 −52.0° (c = 1.00, CHCl3);
1H NMR, COSY (400 MHz, CDCl3) δ (ppm) 2.83 (td, 3J = 10.4
3
Hz, J = 6.9 Hz, 1H, H-1), 2.17 (s, 3H, COCH3), 2.16–2.11 (m,
[α]2D2 −13.4° (c 0.53, CHCl3);
1H, H-5), 1.92 (dq, 3J = 10.3 Hz, 3J = 6.8 Hz, 1H, H-2), 1.83–1.71
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1H NMR, COSY (400 MHz, CDCl3) δ (ppm) 4.83 (dd, J = 11.2 (m, 2H, H-4), 1.71–1.61 (m, 1H, H-5), 1.28 (s, 3H, H-6), 0.96 (d,
3
Hz, J = 8.7 Hz, 1H, H-7), 4.80–4.78 (m, 1H, H-1′), 4.77–4.74 (m, 3J = 6.8 Hz, 3H, H-7); 13C NMR, HSQC, HMBC (100.6 MHz,
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1H, H-1′), 4.65 (dd, J = 11.2 Hz, J = 4.4 Hz, 1H, H-7), 2.66–2.58 CDCl3) δ (ppm) 211.4 (CO), 80.7 (C-3), 57.7 (C-1), 46.0 (C-2),
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(m, 1H, H-5), 2.56 (s, 3H, SCH3), 2.13 (ddd, J = 11.1 Hz, J = 8.4 40.0 (C-4), 29.9 (COCH3), 25.7 (C-5), 25.7 (C-6), 11.6 (C-7);
3
Hz, J = 4.4 Hz, 1H, H-1), 2.02–1.92 (m, 1H, H-4), 1.84–1.76 (m,
2H, H-3), 1.74 (s, 3H, H-3′), 1.58–1.51 (m, 1H, H-4), 1.41 (s, 3H, [M]+. No ionization could be achieved in ESI-HRMS.
H-6); 13C NMR, HSQC, HMBC (100.6 MHz, CDCl3) δ (ppm) 216.0
(1R,2S,3R)-3-(2-Hydroxy-6-methylhept-5-en-2-yl)-1,2-dimethyl-
(CvS), 146.0 (C-2′), 111.3 (C-1′), 79.7 (C-2), 73.0 (C-7), 50.5 (C-1), cyclopentanol, cyclonerodiol (1). Lithium wire (50.0 mg,
FD-MS: m/z calculated for [C9H16O2]+: 156.12, found: 156.27
49.0 (C-5), 41.3 (C-3), 28.2 (C-6), 28.1 (C-4), 19.0 (SCH3).
The data are in accordance with the literature.22
7.00 mmol, 11.0 eq.) was freshly cut and added to meticulously
deoxygenated diethyl ether. A portion (25 drops) of homo-
This journal is © The Royal Society of Chemistry 2014
Org. Biomol. Chem., 2014, 12, 9707–9715 | 9713