1470
L. V. White et al.
p-MBOH (42 mg, 0.30 mmol, 1.5 molar equiv.) in DMF (1 mL).
After stirring at 08C for 1 h, the reaction mixture was cooled to
ꢀ108C (ice–salt bath), and a solution of epoxide 5a (50 mg,
0.20 mmol) in DMF (1 mL) was then added dropwise. After a
further 1 h (at ꢀ108C), the resulting dark green reaction mixture
was treated, in one portion, with a chilled solution of H2O (1 mL)
in DMF (1 mL). After stirring for a further 0.25 h, the reaction
mixture was quenched by slow addition of NaHCO3 (10 mL of a
half-saturated aqueous solution). The ensuing mixture was
diluted with Et2O (20 mL), and the separated aqueous phase
extracted with Et2O (2 ꢁ 20 mL). The combined organic phases
were then dried (Na2SO4) before being concentrated under
reduced pressure. The residue thus obtained was subjected to
flash chromatography (silica, 1 : 3 - 1 : 1 v/v EtOAc/petroleum
spirit gradient elution), and concentration of the relevant frac-
tions (RF 0.25 in 1 : 1 v/v EtOAc/petroleum spirit) afforded a
clear, light yellow and rather unstable oil presumed to contain
compound 8a. On standing in the fridge, crystals began to form
from this oil and after 48 h, the material was triturated with
hexane (2 ꢁ 5 mL), and the solids retained after removal of the
solvent were dried under reduced pressure to afford bromoenone
3a (25 mg, 60 %) as a white, crystalline solid, mp 79.58C (dec.).
[a]D ꢀ29.28 (c 0.5 in CH3CN). nmax (KBr)/cmꢀ1 3372, 1698,
1601, 1383, 1297, 1110, 1072, 991, 848, 767, 614. dH (CDCl3,
400 MHz) 7.37 (dd, J 6.8, 2.5, 1H), 4.18 (d, J 10.9, 1H), 3.99 (m,
1H), 3.73 (br s, 1H), 2.96 (br s, 1H), 2.87 (dt, J 18.7, 4.0, 1H),
2.56 (dddd, J 18.7, 10.0, 2.6, 0.6, 1H). dC (CDCl3, 101 MHz)
192.0, 148.4, 120.6, 79.1, 71.4, 34.3. m/z (EI, 70 eV) 208 and
206 (both 8 %, Mþꢂ), 190 and 188 (both 18), 161 and 159 (both
22), 148 and 146 (47 and 49), 109 (100), 81 (96), 60 (86). m/z
(EI) 205.9582; Mþꢂ requires 205.9579.
Compound 8a: A magnetically stirred solution of diisopro-
pylamine (252 mL, 1.82 mmol) in dry THF (5 mL) maintained at
08C was treated with n-BuLi (1.14 mL of a 1.6 M solution in
hexane, 1.82 mmol). The resulting solution was stirred at 08C for
0.5 h then cooled at ꢀ108C and treated, dropwise, with a solution
of epoxide 5a (300 mg, 1.20 mmol) in THF (5 mL). After 1 h, the
yellow reaction mixture was treated, in one portion, with a
chilled solution of MOMBr (390 mL, 4.80 mmol) in THF (5 mL).
After a further 0.25 h, the reaction mixture was quenched by
slow addition of NaHCO3 (20 mL of a half-saturated aqueous
solution). The resulting mixture was diluted with Et2O (40 mL)
and the separated aqueous phase extracted with Et2O
(1 ꢁ 40 mL). The combined organic layers were dried (Na2SO4),
filtered, and concentrated under reduced pressure, and the
ensuing yellow oil was subjected to chromatography (silica,
1 : 4 v/v ethyl acetate/hexane elution) to afford, after concentra-
tion of the relevant fractions (RF 0.6), compound 8a (150 mg,
50 %) as a clear, colourless oil. [a]D ꢀ45.08 (c 1.0 in CHCl3).
nmax (KBr)/cmꢀ1 3400, 2990, 2848, 1686, 1586, 1454, 1385,
1299, 1217, 1133, 1067, 979, 951, 854, 828, 792, 719, 691. dH
(C6D6, 400 MHz) 5.70 (dd, J 10.0, 2.9, 1H), 5.17 (dm, J 10.0,
1H), 4.72 (d, J 12.9, 1H), 4.51 (br d, J 12.9, 1H), 1.81 (br s, 1H),
1.31 (s, 3H), 1.01 (s, 3H). dC (CDCl3, 101 MHz) 151.4, 128.6,
125.7, 115.9, 83.7, 79.9, 73.8, 26.5, 24.2. m/z (EI, 70 eV) 248
and 246 (both 30 %, Mþꢂ), 190 and 188 (both 33), 109 (34), 81
(100). m/z (EI) 245.9894; Mþꢂ requires 245.9892.
Concentration of fraction A (RF 0.6 in 1 : 1 v/v EtOAc/
petroleum spirit) afforded compound 9a (3.3 mg, 33 %) as a
clear, colourless oil. [a]D ꢀ168.58 (c 0.17 in CHCl3). nmax (KBr)/
cmꢀ1 3048, 2984, 1711, 1578, 1382, 1371, 1226, 1138, 1090,
1047, 864, 835, 791, 640. dH (C6D6, 400 MHz) 6.15 (dd, J 6.3,
2.4, 1H), 3.39 (d, J 10.8, 1H), 3.27 (app. td, J 10.8, 4.7, 1H), 1.86
(ddd, J 17.3, 6.3, 4.7, 1H), 1.57 (ddd, J 17.3, 9.9, 2.4, 1H), 1.24
(s, 6H). dC (C6D6, 101 MHz) 185.4, 144.1, 124.0, 112.2, 82.1,
74.7, 33.1, 27.0, 26.5. m/z (ESIþ) 271 and 269 (98 % and 100 %,
(M þ Na)þ). m/z (ESI) 268.9788; calcd for C9H1179BrNaO3
268.9784.
Concentration of fraction B (RF 0.1 in 1 : 1 v/v EtOAc/
petroleum spirit) afforded compound 3a (4.5 mg, 54 %) as a
white, crystalline solid that was identical, in all respects, to the
material obtained as described above.
Compound 5b: The commercially available cis-1,2-
dihydrocatechol 1b was converted into the previously
reported[8] epoxide 5b using essentially the same procedure as
described above for the conversion of 1a into 5a. By such
means the title compound was obtained in 87 % yield as
a white, crystalline solid, mp 59–608C. This material was
identical, in all respects, to an authentic sample.
Compound 3b: The transformation of epoxide 5b into
chloroenone 3b was conducted on a 50-mg scale under exactly
the same conditions as those used for the conversion of 5a into
3a. Compound 3b (25 mg, 63 %) was thereby obtained as a
white, crystalline solid, mp 84.68C (dec.). [a]D ꢀ42.28 (c 0.4 in
CHCl3). nmax (KBr)/cmꢀ1 3389, 1700, 1610, 1424, 1329, 1117,
1074, 999, 922, 856, 785, 626. dH (CDCl3, 400 MHz) 7.12 (m,
1H), 4.17 (d, J 10.8, 1H), 4.02–3.95 (complex m, 1H), 3.68 (br s,
1H), 2.90 (ddd, J 18.7, 6.8, 5.5, 1H), 2.90 (br s, 1H), 2.60 (ddd,
J 18.7, 10.0, 2.5, 1H). dC (CDCl3, 101 MHz) 191.8, 144.1, 130.1,
79.2, 71.5, 32.6. m/z (EI, 70 eV) 164 and 162 (8 % and 25 %,
M
þꢂ), 144 (29), 133 (45), 116 (75), 115 (68), 81 (63), 60 (100).
m/z (EI) 164.0055; Mþꢂ requires 164.0054.
X-Ray Crystallographic Studies
Crystallographic Data
Compound 3a: C6H7BrO3, M 207.02, monoclinic, space group
˚
C2, a 30.3600(15), b 5.0235(1), c 22.5219(11) A, b 124.000(8)8,
3
V 2847.7(3) A , Z 16, Dc 1.931 g cmꢀ3, T 150 K, 2ymax 1448,
˚
4536 unique data, R 0.019 (for 4469 reflections with I . 2.0s(I)),
wR 0.049 (all data), S 1.00.
Compound 7a: C19H20BrN3O6, M 466.29, orthorhombic,
˚
space group P212121, a 8.8590(1), b 10.8990(1), c 20.9314(1) A,
3
V 2021.02(3) A , Z 4, Dc 1.532 g cmꢀ3, T 150 K, 2ymax
˚
1448, 3965 unique data, R 0.022 (for 3911 reflections with
I . 2.0s(I)), wR 0.057 (all data), S 1.00.
Structure Determinations
Images were measured on an Agilent SuperNova CCD dif-
˚
fractometer (CuKa, mirror monochromator, l 1.54184 A) and
data were extracted using the CrysAlis package.[15] Structure
solution was by direct methods (SIR92).[16] The structures of
compounds 3a and 7a were refined using the CRYSTALS pro-
gram package.[17] Atomic coordinates, bond lengths and angles,
and displacement parameters have been deposited at the
Cambridge Crystallographic Data Centre (CCDC nos 1045882
and 1045883 for compounds 3a and 7a, respectively). These
Compound 9a: A solution of diene 8a (10 mg, 0.04 mmol) in
C6D6 (750 mL) was allowed to stand in an NMR tube for 48 h
then concentrated under reduced pressure. The resulting white
solid was subjected to flash chromatography (silica, 1 : 1 v/v
EtOAc/petroleum spirit - EtOAc gradient elution), thus
affording two fractions, A and B.