J. Pꢂrez Sestelo, L. A. Sarandeses et al.
as a clear liquid. [a]D =À3.4 (c=0.8 in MeOH); 1H NMR (300 MHz,
CDCl3, 258C): d=1.50 (d, J=7.0 Hz, 3H), 2.38 (s, 3H), 2.57 (s, 3H),
4.91 ppm (q, J=7.0 Hz, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=14.0
(CH3), 17.6 (CH3), 30.1 (CH3), 79.3 (CH), 124.7 (C), 170.2 (C), 177.6 (C),
195.1 ppm (C); IR (ATR): n˜ =2928, 2255, 1750, 1688, 1632 cmÀ1; MS
(FAB, NPOE): m/z (%): 155 (16) [M++H], 140 (100), 111 (21) [M+
ÀC2H3O]; HRMS (FAB, NPOE): m/z: calcd for C8H11O3: 155.0703 [M+
+H]; found: 155.0702.
ÀC2H3O2], 96 (100); HRMS (EI): m/z: calcd for C9H12O3F3S: 257.0432
[M+ÀC2H3O2]; found: 257.0454.
Methyl 2-[(1S,6R)-1,6-dimethyl-2-(trifluoromethylsulfonyloxy)cyclohex-
2-enyl]-acetate (17): To a solution of 16 (160 mg, 0.506 mmol) in DMF
(10 mL), was added MeI (63 mL, 1.01 mmol) and K2CO3 (0.140 g,
1.01 mmol). After stirring overnight at RT, water (10 mL) was added and
extracted with Et2O (3ꢄ15 mL). The combined organic phase was
washed with brine (20 mL), dried, filtered and concentrated to reduced
pressure, to give an oil which was purified by column chromatography
(20% Et2O/hexanes) to afford 17 (160 mg, 0.62 mmol, 95%) as a color-
less oil. [a]2D0 =+2.1 (c=0.40 in MeOH); 1H NMR (300 MHz, CDCl3,
258C): d=0.97 (d, J=6.9 Hz, 3H), 1.08 (s, 3H), 1.47–1.63 (m, 2H), 2.02–
2.14 (m, 1H), 2.17–2.23 (m, 2H), 2.47 (d, J=15.1 Hz, 1H), 2.60 (d, J=
15.1 Hz, 1H), 3.66 (s, 3H), 5.79 (t, J=4.1 Hz, 1H); 13C NMR (75 MHz,
CDCl3, 258C): d=15.5 (CH3), 19.6 (CH3), 23.2 (CH2), 25.9 (CH2), 35.3
(CH), 40.2 (CH2), 41.1 (C), 51.4 (CH3), 116.7 (CH), 120.4 (C), 153.2 (C),
170.9 (C); IR (ATR): n˜ =2928, 2854, 2359, 2208, 2172, 2085, 2018, 1971,
1943 cmÀ1; MS (EI): m/z (%): 257 (4) [M+ÀC3H5O2], 149 (100); HRMS
(EI): m/z: calcd for C9H12O3F3S: 257.0446 [M+ÀC3H5O2]; found:
257.0454.
Ethyl 2-[(1S,6R,Z)-1,6-dimethyl-3-[[methyl
oxocyclohexyl]acetate (14): To cold solution of LDA (0.68 mL,
1.41 mmol) in THF (10 mL) at À788C, solution of 13 (0.312 g,
ACHTUNGTNER(NUNG phenyl)amino]methylene]-2-
a
a
1.28 mmol) in THF (5 mL) was added dropwise. After 20 min stirring,
ethyl bromoacetate (0.50 mL, 4.48 mmol) was added via syringe over a
10 min period and the reaction mixture was slowly allowed to reach RT.
The solvent was evaporated under reduced pressure and the residue was
partitioned between saturated NaHCO3 (15 mL), H2O (15 mL) and Et2O
(15 mL). The aqueous phase was extracted and the combined organic ex-
tracts were washed with brine (25 mL), dried, filtered and concentrated
in vacuo. The residue was purified by column chromatography (50%
Et2O/hexanes) to give 14 (251 mg, 0.760 mmol, 60%) as an orange oil.
1H NMR (300 MHz, CDCl3, 258C): d=0.90 (d, J=6.9 Hz, 3H), 1.02 (s,
3H), 1.25 (t, J=7.3 Hz, 3H), 1.42–1.53 (m, 2H), 2.05–2.25 (m, 3H), 2.40
(d, J=16.6 Hz, 1H), 3.14 (d, J=16.6 Hz, 1H), 3.42 (s, 3H), 4.05–4.17 (m,
2H), 7.03–7.10 (m, 3H), 7.29–7.34 (m, 2H), 7.54 ppm (s, 1H); 13C NMR
(75 MHz, CDCl3, 258C): d=14.2 (CH3), 16.3 (CH3), 19.7 (CH3), 26.6
(CH2), 27.6 (CH2), 34.2 (CH3), 41.7 (CH2), 42.3 (CH), 48.1 (C), 59.9
(CH2), 111.2 (C), 120.9 (CH), 123.6 (CH), 128.8 (CH), 145.4 (CH), 146.1
(C), 172.1 (C), 203.2 ppm (C); IR (ATR): n˜ =3383, 2961, 2927, 2324,
1730, 1652, 1598 cmÀ1; MS (EI): m/z (%): 330 (3) [M++1], 329 (16) [M+
], 284 (13) [M+ÀC2H5O], 242 (19) [M+ÀC4H7O2]; HRMS (EI): m/z:
calcd for C20H27NO3: 329.1985 [M+]; found: 329.1986.
Methyl 2-[(1S,6R)-1,2,6-trimethylcyclohex-2-enyl]acetate (18): To a cold
solution of InCl3 (44 mg, 0.20 mmol) in THF (5 mL) at À788C, a solution
of MeLi in Et2O (0.39 mL, 1.6m, 0.61 mmol) was slowly added via syringe
for a 15 min period. The reaction mixture was allowed to reach RT and a
solution of 17 (135 mg, 0.41 mmol) and [PdACTHNUGTRNEG(UN PPh3)2Cl2] (29 mg,
0.04 mmol) in THF (6 mL) was added via cannula. The resulting mixture
was heated at reflux overnight, cooled, the solvent removed in the evapo-
rator at reduced pressure. The residue was dissolved in Et2O (20 mL)
and the organic phase successively washed with satd. NH4Cl (20 mL),
satd. NaHCO3 (20 mL) and brine (20 mL), dried, filtered and concentrat-
ed to give an oil which was purified by column chromatography (10%
Et2O/hexanes) to afford 18 (74 mg, 0.38 mmol, 93%) as an oil. [a]D25
=
(3aS,4R,7aR)-Hexahydro-7a-hydroxy-3a,4-dimethylbenzofuran-2(3H)-
one (15): A solution of 14 (248 mg, 3.34 mmol) in HCl (10 mL, 10%) was
heated at reflux for 45 minutes. The mixture was cooled and extracted
with Et2O (3ꢄ10 mL). The organic layer was concentrated at reduced
volume and treated with a solution of NaOH (10 mL, 2n) at reflux for
1 h. The mixture was cooled, acidified with HCl (10%) and extracted
with Et2O (3ꢄ15 mL). The combined organic phase was washed with
brine (20 mL), dried, filtered and concentrated in vacuo. Purification by
column chromatography (50% Et2O/hexanes) afforded 15 (122 mg,
0.66 mmol, 88%) as a white solid. M.p. 107–1088C; [a]2D5 =À24.8 (c=0.5
in MeOH); 1H NMR (300 MHz, CDCl3, 258C): d=0.89 (d, J=6.6 Hz,
3H), 1.06 (s, 3H), 1.10–1.26 (m, 2H), 1.37–1.57 (m, 2H), 1.64–1.75 (m,
2H), 2.03–2.08 (m, 1H), 2.36 (d, J=16.6 Hz, 1H), 2.66 ppm (d, J=
16.6 Hz, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=11.6 (CH3), 16.4
(CH3), 21.8 (CH2), 29.0 (CH2), 32.4 (CH2), 37.3 (CH), 41.2 (CH2), 46.1
(C), 108.2 (C), 176.9 ppm (C); IR (ATR): n˜ =3333, 2960, 2948, 2872,
+30 (c=0.5 in MeOH); 1H NMR (300 MHz, CDCl3, 258C): d=0.92 (d,
J=6.8 Hz, 3H), 0.97 (s, 3H), 1.36–1.49 (m, 1H), 1.52–1.61 (m, 1H), 1.71
(s, 3H), 1.84–2.02 (m, 3H), 2.43 (d, J=14.3 Hz, 1H), 2.52 (d, J=14.3 Hz,
1H), 3.64 (s, 3H), 5.42 ppm (brs, 1H); 13C NMR (75 MHz, CDCl3,
258C): d=15.9 (CH3), 19.4 (CH3), 20.9 (CH3), 24.5 (CH2), 26.8 (CH2),
34.5 (CH), 40.5 (C), 41.7 (CH2), 51.1 (CH3), 123.5 (CH), 138.3 (C),
172.4 ppm (C); IR (ATR): n˜ =2923, 1734, 1435, 1377, 1316, 1281 cmÀ1
;
MS (EI): m/z (%): 196 (8) [M+], 123 (55) [M+ÀC3H5O2], 122 (100);
HRMS (EI): m/z: calcd for C12H20O2: 196.1458 [M+]; found: 196.1450.
2-[(1S,6R)-1,2,6-Trimethylcyclohex-2-enyl]ethanol (19): To a solution of
18 (216 mg, 1.10 mmol) in THF (12 mL) at 08C, a solution of LiAlH4 in
THF (3.3 mL, 1m, 3.30 mmol) was added via syringe. After 3 h, the sol-
vent was removed and the residue was dissolved in Et2O (15 mL) and the
resulting organic phase was washed with HCl (10 mL, 5%), and brine
(20 mL), dried, filtered and concentrated. The residue was purified by
column chromatography (40% Et2O/hexanes) to afford 19 (161 mg,
0.96 mmol, 87%) as an oil. [a]2D5 =+36.3 (c=0.44 in MeOH); 1H NMR
(300 MHz, CDCl3, 258C): d=0.89 (s, 3H), 0.91 (d, J=6.8 Hz, 3H), 1.26–
1.30 (m, 1H), 1.38–1.47 (m, 2H), 1.67 (broad s, 3H), 1.75 (t, J=7.6 Hz,
2H), 1.91–1.98 (m, 2H), 3.45–3.55 (m, 1H), 3.60–3.68 (m, 1H), 5.43 ppm
(brs, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=16.0 (CH3), 19.3 (CH3),
21.0 (CH3), 25.4 (CH2), 26.9 (CH2), 34.2 (CH), 39.1 (CH2), 39.6 (C), 59.9
(CH2), 124.2 (CH), 139.4 ppm (C); IR (ATR): n˜ =3312, 2960, 2920, 2876,
2857, 2837, 1453, 1437, 1377 cmÀ1; MS (EI): m/z (%): 169 (4) [M++1],
168 (4) [M+], 123 (100) [M+ÀC2H5O]; HRMS (EI): m/z: calcd for
C11H20O: 168.1509 [M+]; found: 168.1505.
1737, 1724 cmÀ1 MS (EI): m/z (%): 184 (2) [M+], 125 (62) [M+
;
ÀC2H3O2], 96 (100); HRMS (EI): m/z: calcd for C10H16O3: 184.1094 [M+
]; found: 184.1094.
2-[(1S,2R)-1,2-Dimethyl-6-oxocyclohexyl]acetic acid (16): To a cold solu-
tion of LDA (2.52 mL, 4.20 mmol) in THF (6 mL) at À408C, a solution
of 15 (352 mg, 1.91 mmol) in THF (8 mL) was added. After 30 min, a so-
lution of PhNTf2 (0.75 g, 2.10 mmol) in THF (5 mL) was added dropwise
via syringe and allowed to reach RT in a 6 h period. The reaction was
quenched with few drops of MeOH and added over NH4Cl (20 mL, satd.
sol.). The aqueous layer was extracted with Et2O (3ꢄ20 mL), and the
combined organic extracts were washed with brine (25 mL), dried, fil-
tered and concentrated in vacuo. The residue was purified by column
chromatography (40% Et2O/hexanes) to afford 16 (523 mg, 2.03 mmol,
87%) as an oil. [a]2D5 =+36.7 (c=0.45 in MeOH); 1H NMR (300 MHz,
CDCl3, 258C): d=1.00 (d, J=7.1 Hz, 3H), 1.12 (s, 3H), 1.47–1.70 (m,
2H), 2.06–2.26 (m, 3H), 2.51 (d, J=15.2 Hz, 1H), 2.66 (d, J=15.2 Hz,
1H), 5.81 ppm (t, J=4.0 Hz, 1H); 13C NMR (75 MHz, CDCl3, 258C): d=
15.4 (CH3), 19.6 (CH3), 23.1 (CH2), 25.8 (CH2), 35.3 (CH), 40.1 (CH2),
41.0 (C), 117.1 (CH), 120.5 (C), 152.7 (C), 175.8 ppm (C); IR (ATR): n˜ =
3387, 2931, 2873, 2358, 1756, 1709 cmÀ1; MS (EI): m/z (%): 257 (12) [M+
AHCTUNGTERG(NNUN 5R,6S)-6-(2-Iodoethyl)-1,5,6-trimethylcyclohex-1-ene (5): To a solution
of 19 (154 mg, 0.915 mmol) in dry THF (15 mL) at RT, PPh3 (288 mg,
1.10 mmol), imidazole (125 mg, 1.83 mmol) and I2 (279 mg, 1.10 mmol)
were successively added. After 45 min, the reaction mixture was poured
in a separating funnel with Na2S2O3 (10 mL, satd. sol.). The aqueous
layer was extracted with Et2O (3ꢄ20 mL), and the combined organic
phase was washed with brine (20 mL), dried, filtered and concentrated to
give a residue which was purified by column chromatography (hexanes),
to afford 5 (247 mg, 0.89 mmol, 97%) as a colorless oil. [a]D =À3.4 (c=
0.8 in MeOH); 1H NMR (300 MHz, CDCl3, 258C): d=0.87 (s, 3H), 0.89
914
ꢃ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 910 – 916