The Intramolecular Addition of Alkenyl Radicals to Furans
(52 mL), and then potassium fluoride (2.6 g) was added, followed (2-Bromocyclohex-2-enyl)acetaldehyde (16): A solution of 2-(2-
FULL PAPER
by water (2.2 mL). The mixture was stirred for 4 h. Potassium car-
bonate was then added to the reaction mixture, which was then
filtered. The filtrate was concentrated under reduced pressure and
the residue was subjected to flash column chromatography to af-
ford the title compound as a yellow oil (0.16 g, 50%). TLC: Rf ϭ
0.5 (40% PE/EtOAc). IR: ν˜max ϭ 2929, 1631, 1594, 1361, 1078
bromocyclohex-2-enyl)ethanol (15) (1.1 g, 5.5 mmol) in DCM
(5 mL) was added to a stirred solution of DessϪMartin periodin-
ane (3 g, 7.1 mmol) in DCM (30 mL). After 3 h of stirring, the
solution was poured into a separating funnel containing NaOH (1
, 30 mL) and diethyl ether (30 mL). The layers were separated and
the diethyl ether layer was washed with water (2 ϫ 30 mL) and
cmϪ1 1H NMR (CDCl3): δH ϭ 0.00 (s, 6 H), 0.93 (s, 9 H), brine (30 mL), dried over MgSO4, and then concentrated under
.
1.72Ϫ1.68 (m, 2 H), 2.00 (s, 3 H), 2.22Ϫ2.18 (m, 2 H), 2.42Ϫ2.38 reduced pressure. The residue was subjected to flash column chro-
(m, 2 H), 2.50 (t, J ϭ 7.6 Hz, 2 H), 4.84Ϫ4.80 (m, 3 H), 5.74 (m, matography to give the title compound as a colourless oil (0.92 g,
1 H), 6.29 (d, J ϭ 15.7 Hz, 1 H), 7.33 (d, J ϭ 15.7 Hz, 1 H) ppm.
82%). TLC: Rf ϭ 0.43 (75% PE/E). IR: ν˜max ϭ 2933, 28639, 1642,
13C NMR (75.5 MHz, CDCl3): δ ϭ 200.4, 153.2, 137.0, 135.7, 1448 cmϪ1
.
1H NMR(CDCl3): δH ϭ 1.59Ϫ1.51 (m, 4 H),
135.1, 126.3, 115.5, 78.1, 40.9, 37.4, 33.4, 28.7, 26.3, 18.5, 15.7,
2.14Ϫ2.10 (m, 2 H), 2.50 (dq, J ϭ 9.4, 2.16 Hz, 1Hb), 2.89 (dd,
J ϭ 3.3, 16.9 Hz, 1Ha), 2.94Ϫ2.90 (m, 1 H), 6.12 (dt, J ϭ 1.3,
Ϫ3.4, Ϫ4.2 ppm. GC-MS: m/z ϭ 263 ([Mϩ Ϫ tBu], 100%), 207
([Mϩ Ϫ (TBDMS-H)], 26%), 189. HRMS: calcd. for C15H23O2Si 4.0 Hz, 1 H), 9.82 (d, J ϭ 1.0 Hz, 1 H) ppm. 13C NMR (75.5 MHz,
m/z ϭ 263.1467; found: m/z ϭ 263.1458.
CDCl3): δ ϭ 201.8, 131.8, 126.3, 48.2, 37.4, 30.5, 28.0, 19.0 ppm.
GC-MS: m/z ϭ 204 ([Mϩ(81Br)], 11%), 202 ([Mϩ(79Br)], 8%), 103
([Mϩ(81Br) Ϫ CHO], 21%); 171 ([Mϩ(79Br) Ϫ CHO], 18%), 160
([Mϩ(81Br) Ϫ CH2CHO], 51%), 158 ([Mϩ(79Br) Ϫ CH2CHO],
51%), 123 ([Mϩ ϪBr], 78%).
tert-Butyl (2-Bromocyclohex-2-enyl)acetate (14): nBuLi (1.7 in
hexane, 1.55 mL, 15.2 mmol) was added dropwise to a solution of
iso-propylcyclohexylamine (2.14 g, 15.2 mmol) in DME (50 mL) at
Ϫ60 °C. The reaction mixture was stirred for 30 min, and then tert-
butyl acetate (1.8 g, 15.2 mmol) was added dropwise. After further
2-(2-Bromocyclohex-2-enyl)-1-(5-methylfuran-2-yl)ethanol
(17):
stirring for 15 min at 60 °C, a solution of 1,6-dibromocyclohexene nBuLi (6.3 mmol, 2.7 mL of 2.35 solution in hexane) was added
(13) (4 g, 18.2 mmol) in DME (15 mL) was added dropwise. The
suspension was warmed to ambient temperature and stirred for 4 h.
The reaction mixture was then poured into icecold 10% HCl
(75 mL) and extracted with diethyl ether (3 ϫ 60 mL). The com-
bined organic layers were washed with brine (60 mL), dried over
dropwise to a solution of 2-methylfuran (0.86 g, 10.5 mmol) in
THF (30 mL) cooled to Ϫ78 °C under a nitrogen atmosphere. The
solution was warmed to ambient temperature and stirred for 2 h
before being cooled to Ϫ78 °C. A solution of (2-bromocyclohex-2-
enyl)acetaldehyde (16) (1.7 g, 5.3 mmol) in THF (10 mL) was ad-
MgSO4, and filtered. The filtrate was concentrated under reduced ded slowly. The reaction mixture was warmed to ambient tempera-
pressure and the residue was subjected to flash column chromatog-
raphy. The title compound was afforded as a pale yellow oil (2.2 g,
ture and stirred for a further 3 h before being quenched with ice-
cold water (30 mL). The aqueous layer was washed with diethyl
ether (3 ϫ 25 mL) and the combined organic layers were washed
53%). TLC: Rf ϭ 0.6 (80% PE/E). IR: ν˜max ϭ 2933, 1719, 734, 650
1
cmϪ1. H NMR (CDCl3): δH ϭ 1.38 (s, 9 H), 1.58 (m, 4 H), 1.98 with brine (25 mL), dried over MgSO4, and filtered. The filtrate
(m, 2 H), 2.12Ϫ2.17 (dd, J ϭ 16.0, 11.0 Hz, 1Hb), 2.60 (m, 1Ha), was concentrated under reduced pressure. The residue was sub-
2.73Ϫ2.77 (dd, J ϭ 16.0, 3.3 Hz, 1 H), 6.01 (dt, J ϭ 4.1, 1.1 Hz, 1
H) ppm. 13C NMR (75.5 MHz, CDCl3): δ ϭ 171.9, 131.2, 126.7,
jected to flash column chromatography to afford the title com-
pound as a colourless oil (1.05 g, 70%). TLC: Rf ϭ 0.19 (88% PE/
80.8, 40.0, 39.9, 29.2, 28.5, 28.1, 18.7 ppm. GC-MS): m/z ϭ 276 EtOAc). IR: ν˜max ϭ 3463, 2931, 1738, 1447, 1246, 657 cmϪ1 1H
.
([Mϩ(81Br)], 4%), 274 ([Mϩ(79Br)], 4%), 261 ([Mϩ(81 Br) Ϫ Me], NMR (CDCl3): δH ϭ 1.54Ϫ1.45 (m, 4 H), 1.96Ϫ1.90 (m, 4 H),
27%), 259 ([Mϩ(79Br) Ϫ Me], 26%), 220 ([Mϩ(81Br) Ϫ tBu], 15%), 2.10 (s, 3 H), 2.89Ϫ2.83 (br., 1 H), 4.73 (t, J ϭ 6.7 Hz, 1 H), 5.84
218 ([Mϩ(79Br) Ϫ tBu], 16%), 203 ([Mϩ(81Br) Ϫ OtBu], 56%), 201 (d, J ϭ 3.9 Hz, 1 H), 6.03 (d, J ϭ 3.1 Hz, 1 H), 6.08 (d, J ϭ 3.1 Hz,
([Mϩ(79Br) Ϫ OtBu], 100%), 195. HRMS: calcd. for C8H1079BrO 1 H) ppm. 13C NMR (75.5 MHz, CDCl3): δH ϭ 154.0, 153.2, 131.8,
[M Ϫ OtBu] m/z ϭ 200.9910; found m/z ϭ 200.9926.
125.0, 109.6, 108.4, 66.9, 48.0, 31.7, 29.0, 22.3, 19.0, 14.8 ppm. GC-
MS: m/z ϭ 269 ([Mϩ(81Br) Ϫ OH], 73%), 267 ([Mϩ(79Br) Ϫ OH],
75%), 187 ([Mϩ Ϫ (BrϩOHϩH)], 100%). HRMS: calcd. for
C13H1679BrO m/z ϭ 267.0385; found m/z ϭ 267.0364.
2-(2-Bromocyclohex-2-enyl)ethanol (15): Lithium aluminum hydride
(0.9 g, 24 mmol) was placed in a nitrogen-flushed two-neck flask
equipped with a magnetic stirring bar. Dry diethyl ether (40 mL)
was slowly injected onto the solid stirring at 0 °C. A solution of [2-(2-Bromocyclohex-2-enyl)-1-(5-methylfuran-2-yl)ethoxy]-tert-
tert-butyl (2-bromocyclohex-2-enyl)acetate (14) (2.2 g, 8 mmol) in butyldimethylsilane (18): tert-Butyldimethylsilyl trifluoromethane-
diethyl ether (10 mL) was added dropwise. The cooling bath was sulfonate (0.8 g, 3.06 mmol) was added dropwise to a stirred solu-
then removed and the suspension was left overnight at ambient
temperature. When the reaction was complete by TLC, the flask
was cooled to 0 °C and potassium sodium tartrate was added
slowly to destroy excess lithium aluminum hydride. After filtration,
the filtrate was dried over MgSO4 and concentrated under reduced
pressure. Purification of the residue by flash column chromatogra-
tion of 2-(2-bromocyclohex-2-enyl)-1-(5-methylfuran-2-yl)ethanol
(17) (0.73 g, 2.55 mmol) and dry 2,6-lutidine (0.55 g, 5.1 mmol) in
DCM (3 mL) at Ϫ25 °C. The reaction mixture was stirred for 2 h
and then methanol (0.3 mL), DCM (20 mL) and water (25 mL)
were added. The mixture was extracted with DCM (3 ϫ 20 mL)
and the combined organic layers were washed with brine (20 mL),
phy afforded the title compound as a pale yellow oil (1.3 g, 80%). dried over MgSO4, and filtered. The filtrate was concentrated un-
TLC: Rf ϭ 0.22 (80% PE/E). IR: ν˜max ϭ 3340, 2924, 2855, 1644 der reduced pressure and the residue was subjected to flash column
cmϪ1 1H NMR (CDCl3): δH ϭ 1.63Ϫ1.52 (m, 1Hb), 1.75Ϫ1.65 chromatography to afford the title compound as a pale yellow oil
.
(m, 4 H), 1.86Ϫ1.80 (m, 1Ha), 2.12Ϫ2.04 (m, 3 H), 2.44Ϫ2.35 (br., (0.76 g, 75%). TLC: Rf ϭ 0.6 (88% PE/EtOAc). IR: ν˜max ϭ 2930,
1 H), 3.70Ϫ3.64 (m, 2 H), 6.08 (dt, J ϭ 1.2, J ϭ 4.0 Hz,1 H) ppm. 2856, 1618, 1254 cmϪ1. 1H NMR (CDCl3): δH ϭ 0.00 (s, 6 H), 0.81
13C NMR (75.5 MHz, CDCl3): δc ϭ 130.5, 127.7, 61.0, 39.7, 36.6,
32.2, 31.6, 18.6 ppm. GC-MS: m/z ϭ 188 ([Mϩ(81Br) Ϫ OH], 52%),
(s, 9 H), 1.64Ϫ1.53 (m, 6 H), 2.00Ϫ1.96 (m, 2 H), 2.19 (s, 3 H),
2.65Ϫ2.63 (br., 1 H), 4.73Ϫ4.69 (m, 1 H), 5.87Ϫ5.83 (m, 1 H), 6.03
186 ([Mϩ(79Br) Ϫ OH], 53%), 107 ([Mϩ Ϫ Br], 100%). HRMS: (d, J ϭ 3.1 Hz, 1 H), 6.14 (t, J ϭ 3.1 Hz,1 H) ppm. 13C NMR
calcd. for C8H1179Br m/z ϭ 186.0046; found m/z ϭ 186.0044.
(75.5 MHz, CDCl3): δC ϭ 152.0, 151.6, 131.1, 125.0, 109.0, 107.6,
Eur. J. Org. Chem. 2003, 1729Ϫ1732
2003 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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