LETTER
A Convergent Construction of Quaternary Centres and Polycyclic Structures
385
ClCH2CH2Cl (1.2 mL), was heated to reflux under an inert
atmosphere. After a few minutes of refluxing, solid lauroyl
NH4Cl and NaCl then dried over NaSO4. Concentration
under reduced pressure afforded a yellowish oil which was
purified by flash column chromatography in petroleum
ether–EtOAc (40% to 100%) to yield 17 as a colourless oil
(0.99 g, 70%). IR (film): 2937, 1707, 1458, 1257, 1036
cm–1. MS (IC, NH3) m/z = 264 [M + NH4]+, 247 [M + H]+.
1H NMR (400 MHz, CDCl3): δ (ppm) = 1.21 (s, 3 H, CH3C),
1.41 (ddd, 2JHH = 12.5 Hz, 3JHH = 8.6 Hz and 3JHH = 3.5 Hz,
1 H), 1.52–1.66 (m, 2 H), 2.00–2.08 (m, 3 H), 3.18 (dd,
2JHP = 21.6 Hz and 2JHH = 15.4 Hz, 1 H), 3.24 (dd,
peroxide (5 mol%) was added and heating was continued for
1.5 h. Another small amount of lauroyl peroxide (2 mol%)
was added followed by further similar lots every hour until
TLC indicated completion of the reaction (13 mol% in total).
After cooling to r.t., the solvent was removed under reduced
pressure and the residue purified by silica gel chromato-
graphy (EtOAc–petroleum ether, 5:95) to afford 7a as a
yellowish oil (180 mg; 70%). IR (film): 2957, 1751, 1715,
1367, 1218, 1051, 488 cm–1. 1H NMR (400 MHz, CDCl3): δ
(ppm) = 6.68 (dd, J1 = 5.1, J2 = 7.6 Hz, 1 H), 4.65 (q, J = 7.1
Hz, 2 H), 2.46 (s, 2 H), 2.20–2.04 (m, 8 H), 1.42 (t, J = 6.1
Hz, 3 H), 1.08 (s, 3 H), 1.07 (s, 3 H). 13C NMR (100 MHz,
CDCl3): δ (ppm) = 212.7, 207.5, 170.3, 78.3, 70.4, 53.0,
44.9, 32.8, 31.7, 27.5, 27.4, 28.0, 13.3. MS (IC, NH3): m/z =
324 [M + NH3]. Anal. Calcd for C13H22O4S2: C, 50.95; H,
7.24. Found: C, 50.92; H, 7.31. A solution of ketone 7a (100
mg; 0.4 mmol), p-TsOH (30 mg) and H2O (0.1 mL) in THF
(4 mL) was refluxed for 48 h. The reaction mixture was
cooled to r.t. and neutralised with a sat. solution of NaHCO3.
The organic layer was extracted with Et2O, washed with
brine, dried over Na2SO4, filtered, and the solvent removed
in vacuo. The residue was purified by silica gel
chromatography (elution by diethyl ether–pentane, 0.5:9.5)
to afford the known enone12 9a (39 mg, 82%). 1H NMR (400
MHz, CDCl3): δ (ppm) = 6.86 (dt, J1 = 4.1, J2 = 10.1 Hz, 1
H), 6.02 (dt, J1 = 2.0, J2 = 10.1 Hz, 1 H), 2.27 (s, 2 H), 2.24
(dd, J1 = 2.0, J2 = 4.1 Hz, 2 H), 1.04 (s, 6 H): 13C NMR (100
MHz; CDCl3): δ (ppm) = 199.7 (C=O), 148.1 (CH), 128.6
(CH), 51.4 (CH2), 39.5 (Cquat.), 29.3 (CH2), 28.9 (2 CH3). MS
(IC, NH3) m/z = 125 [M + H], 142 [M + NH4].
Methyl 1-Methyl-2-cyclohexenecarboxylate 16. To a
stirred solution of freshly distilled diisopropylamine (1.31
mL, 9.3 mmol, 1.4 equiv) in of THF (8 mL) maintained at
0 °C under argon were added dropwise n-BuLi (5.53 mL,
1.56 M in hexanes, 8.6 mmol, 1.3 equiv). After 15 min the
solution was cooled down to –78 °C and dry HMPA (1.50
mL, 8.6 mmol, 1.3 equiv) was added. The mixture was
stirred for 30 min at the same temperature and commercial
1-cyclohexenylmethyl-carboxylate (0.93 g, 6.6 mmol, 1.0
equiv) was then added followed after 10 min by (0.62 mL,
10.0 mmol, 1.5 equiv) of methyl iodide. The solution was
then allowed to warm to –5 °C over 2 h when a sat. aq
solution of NH4Cl was poured into the orange mixture. After
dilution with petroleum ether and washing with brine, the
organic layer was dried over NaSO4 and carefully
2JHP = 21.1 Hz and 2JHH = 15.4 Hz, 1 H), 3.78 (d, 3JHP = 2.1
Hz, 3 H), 3.81 (d, 3JHP = 2.1 Hz, 3 H), 5.66 (dt, 3JHH = 10.1
Hz and 4JHH = 2.1 Hz, 1 H), 5.90 (dt, 3JHH = 10.1 Hz and
3JHH = 3.7 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ (ppm)
= 18.8 (CH3), 23.9 (CH2), 24.5 (CH2), 31.4 (CH2), 35.9 (d,
1JCP = 136 Hz, 1 C, CH2P), 49.9 (Cquat.), 52.6 (CH3O), 129.2
(CH), 129.8 (CH), 205.3 (d, 1JCP = 7 Hz, 1 C, C=O).
O-Ethyl-S-[3-(1-methyl-cyclohex-2-enyl)-3-oxo-1-
phenyl-propyl] Dithiocarbonate 18a. To a suspension of
NaH (60% in mineral oil; 16 mg, 0.40 mmol) in THF (1 mL)
maintained at 0 °C under argon was added drop wise a
solution of 17 (82 mg, 0.33 mmol) in THF (0.5 mL). The
resulting mixture was stirred for 30 min before adding
benzaldehyde (41 µL, 0.40 mmol) slowly, leading rapidly to
a yellow solution. After 2 h at 0 °C, a TLC analysis showed
no more starting material. A sat. aq solution of NH4Cl was
poured into the flask and the mixture diluted with Et2O. The
organic layer was washed successively with sat.aq solutions
of NH4Cl and NaCl then dried over Na2SO4. Removal of
solvent under reduced pressure afforded crude 1-(1-methyl-
cyclohex-2-enyl)-1-oxo-3-phenyl-prop-2-ene as a yellow
oil. This compound was dissolved in a (3:2) mixture of
CH2Cl2 and HOAc (2.5 mL) and the solution was cooled
down to 0 °C. Commercial potassium O-ethyl xanthate (0.26
g, 1.64 mmol) was added portion-wise over 2 h, followed by
one more hour of stirring. After addition of water and
dilution with Et2O, the organic layer was washed
successively with H2O and brine and dried over Na2SO4.
After concentration in vacuo the resulting yellow oil was
submitted to flash column chromatography using petroleum
ether–EtOAc (5%) as eluent to give 18a as a viscous pale
yellow oil (81 mg, 71%) and as a (2:1) mixture of
diastereoisomers. IR (film): 3062, 3025, 2935, 2868, 1707,
1602, 1453, 1221, 1111, 1048 cm–1. MS (IC, NH3) m/z = 349
[M + H]+, 229 {M – [(SC(S)OEt] + H}+. 1H NMR (400 MHz,
CDCl3): δ (ppm) = 0.98 (s, 2 H, CH3C), 1.10 (s, 1 H, CH3C),
1.18–1.32 (m, 2 H), 1.35 (t, 3JHH = 7.1 Hz, 1.5 H,
concentrated in vacuo to give ester 16 as a yellow liquid,
which was used as such in the next step (0.98 g, crude yield:
96%). 1H NMR (400 MHz, CDCl3): δ (ppm) = 1.27 (s, 3 H,
CH3C), 1.45 (ddd, 2JHH = 13.1 Hz, 3JHH = 9.7 Hz and
3JHH = 3.4 Hz1 H), 1.56–1.71 (m, 2 H), 1.96–2.02 (m, 2 H),
2.13–2.19 (m, 1 H), 3.69 (s, 3 H, CH3O), 5.68 (dm,
CH3CH2O), 1.37 (t, 3JHH = 7.1 Hz, 1.5 H, CH3CH2O), 1.38–
1.43 (m, 1 H), 1.49–1.58 (m, 1 H,), 1.92–1.99 (m 4 H), 3.22
(d, 3JHH = 7.2 Hz, 2 H), 4.59 (q, 3JHH = 7.1 Hz, 2 H, CH2O),
5.28 (t, 3JHH = 7.2 Hz, 1 H, CH-Ph), 5.51 (dt, 3JHH = 10.1 Hz
and 4JHH = 1.9 Hz, 2/3 H), 5.60 (dt, 3JHH = 10.1 Hz and
4JHH = 1.9 Hz, 1/3 H), 5.78–5.84 (m, 1 H), 7.11 (d,
3JHH = 10.1 Hz, 1 H), 5.78 (dt, 3JHH = 10.1 Hz and 3JHH = 3.6
Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ (ppm) = 19.3
(CH3), 24.4 (CH2), 26.1 (CH2), 32.7 (CH2), 42.8 (Cquat.), 51.6
(CH3O), 127.6 (CH), 130.3 (CH), 177.2 (C=O).
3JHH = 15.7 Hz, 1 H), 7.18–7.31 (m, 3 H, Harom.), 7.34–7.36
(m, 2 H, Harom.). 13C NMR (100 MHz, CDCl3): δ (ppm) =
13.3 (CH3), 18.9 and 19.0 (CH2), 24.2 (CH3), 24.5 (CH2),
31.4 and 31.6 (CH2), 43.8 (Cquat.), 47.0 (CH2), 48.7 (CH),
69.6 (CH2), 127.3 (CH), 127.7 and 127.8 (CH), 128.2 (CH),
129.2 (CH), 129.5 (CH), 139.6 and 139.7 (Cquat. arom.), 209.8
and 209.9 (C=O), 212.0 (C=S).
O-Ethyl-S-(7a-methyl-1-oxo-3-phenyl-octahydro-inden-
4-yl) Dithiocarbonate 19a. A solution of 18a (81 mg, 0.23
mmol) in ClCH2CH2Cl (2.3 mL) was heated to reflux under
argon for 15 min then solid lauroyl peroxide (7 mg, 0.02
mmol) was added from the top of the condenser. The reflux
was continued for 7 h during which time a further four
smaller portions of peroxide were added every 90 min (total:
Dimethyl [2-(1-Methyl-cyclohex-2-enyl)-2-oxo-ethyl]-
phosphonate 17. n-BuLi (1.56 M in hexanes, 7.8 mL, 12.2
mmol, 2.1 equiv) was added at –78 °C under argon to a
stirred solution of commercial dimethyl methylphosphonate
(1.55 mL,14.3 mmol, 2.5 equiv) in THF (20 mL). After 30
min at –78 °C, ester 16 was added with a syringe over 10 min
and the mixture was stirred for 6 h at the same temperature.
At this point a sat. aq solution of NH4Cl was poured into the
flask and the mixture was diluted with EtOAc. The organic
layer was washed successively with sat. aq solutions of
Synlett 2003, No. 3, 382–386 ISSN 0936-5214 © Thieme Stuttgart · New York