Experimental section
was heated at reflux for 3 h with azeotropic removal of water using
a Dean–Stark trap. The mixture was cooled to room temperature
and concentrated in vacuo. The residue was then purified by flash
column chromatography (silica gel, hexanes : EtOAc) to afford the
Chemical reagents were purchased from commercial suppliers
and used without further purification, unless otherwise noted.
Solvents were analytical grade or were purified by standard
procedures prior to use. Yields were calculated for material judged
homogeneous by thin layer chromatography and nuclear magnetic
4
desired compound 6a as a colourless oil (397 mg, 80% yield).
-1
IR (film): nmax/cm 3059, 3028, 2960, 2928, 1652, 1630, 1028.
1
H NMR (CDCl
3
, 300 MHz, Me Si): d = 7.36–7.28 (m, 4H, Ar–
4
1
resonance ( H NMR). All reactions were monitored by thin
H), 7.23–7.17 (m, 1H, Ar–H), 6.02 (dd, J = 5.7, 2.3 Hz, 1H, 2-H),
layer chromatography (TLC) performed on silica gel 60 F254 pre-
coated aluminium sheets, visualized by a 254 nm UV lamp, and
stained with an ethanolic solution of 4-anisaldehyde. Glassware
for reactions was oven-dried at 125 C and cooled under a
dry atmosphere prior to use. Column flash chromatography was
performed using silica gel 60 (230–400 mesh). Melting points
5
3
.94 (dd, J = 5.6, 2.0 Hz, 1H, 3-H), 4.04 (q, J = 2.1 Hz, 1H, 1-H),
.15 (q, J = 1.7 Hz, 1H, 8b-H), 2.26 (d, J = 1.6 Hz, 2H, 5-H), 2.25
(
3
s, 2H, 7-H), 1.57 (s, 3H, 3a-CH
3
), 1.101 (s, 3H, 6-CH
3
), 1.097 (s,
◦
13
H, 6-CH
3
). C NMR (CDCl
3
, 75 MHz): d = 194.4 (s, C-8), 173.4
(
s, C-4a), 143.5 (s, Ar), 137.2 (d, C-2), 133.4 (d, C-3), 128.4 (2 ¥
d, Ar), 127.1 (2 ¥ d, Ar), 126.3 (d, C-4¢), 115.4 (s, C-8a), 104.4
s, C-3a), 56.84 (d, C-1), 56.80 (d, C-8b), 51.0 (t, C-7), 37.8 (t,
C-5), 33.8 (s, C-6), 28.5 (q, C6-CH ), 28.4 (q, C6-CH ), 25.2 (q,
C3a–CH ). HRMS: m/z calcd. for C20
found 295.1690.
(
m.p.) were taken on an electrothermal melting point apparatus
(
and are uncorrected. Nuclear magnetic resonance spectra were
acquired at 300 MHz for H and 75 MHz for C using CDCl
as solvent. 2D 900 ms NOESY experiments were collected
on a Bruker Avance DMX-500 NMR instrument operating at
3
3
1
13
+
3
H
O (M + H ) 295.1693,
3
23
2
1
5
00.13 MHz for H. Chemical shifts for proton nuclear magnetic
1
Preparation of 9a-methyl-7-phenyl-7,9a-dihydro-6H,6bH-cyclo-
penta[4,5]furo[3,2-c]chromen-6-one (6b
resonance ( H NMR) spectra are reported in parts per million
relative to the signal of tetramethylsilane at 0 ppm (internal
standard) and coupling constants (J) are reported in hertz (Hz).
4
)
A mixture of 4-hydroxy-coumarin (289 mg, 1.75 mmol), 2-
methyl-5-phenyl-penta-2,4-dienal (300 mg, 1.75 mmol), piperidine
1
3
Chemical shifts for carbon nuclear magnetic resonance ( C NMR)
spectra are reported in parts per million relative to the center line
(0.023 mL, 0.24 mmol) and acetic acid (0.047 mL, 0.82 mmol) in
of the CDCl triplet at 76.9 ppm. The following abbreviations
3
toluene (18.0 mL) was heated at reflux for 4 h with azeotropic
removal of water using a Dean–Stark trap. The mixture was
cooled to room temperature and concentrated in vacuo. The
residue was then purified by flash column chromatography (silica
are used to explain the multiplicities: s = singlet, d = doublet, t =
triplet, q = quartet, quint = quintet, m = multiplet, pent = pentet,
hex = hexet, br = broad. IR spectra were obtained using an FT-
IR spectrometer and only partial spectral data are listed. High
resolution mass spectra (HRMS) were recorded at the University
of California Riverside Mass Spectrometry Facility.
gel, hexanes : EtOAc) to afford the desired compound 6b
4
as a
colourless to pale yellow solid (255 mg, 46% yield). Mp: 151.5–
◦
-1
1
2
3
52.5 C (from hexanes : chloroform). IR (KBr): nmax/cm 3056,
1
980, 2924, 1713, 1645, 1497, 1406, 1067. H NMR (CDCl
00 MHz, Me Si): d = 7.65 (dd, J = 7.8, 1.6 Hz, 1H, 1-H), 7.54 (td,
3
,
2
-Methyl-5-phenyl-penta-2,4-dienal
4
J = 7.9, 1.4 Hz, 1H, 3-H), 7.39–7.32 (m, 5H, 4-H, 2¢-H, 3¢-H, 5¢-H,
6¢-H), 7.29–7.22 (m, 2H, 4¢-H, 2-H), 6.12 (dd, J = 5.6, 2.2 Hz, 1H,
To a stirred solution of cinnamaldehyde (1.0 mL, 7.8 mmol), and
propionaldehyde (0.6 mL, 7.8 mmol) in ethanol (7.8 mL) at 0 C
◦
8
-H), 6.07 (dd, J = 5.6, 1.8 Hz, 1H, 9-H), 4.28 (q, J = 1.9 Hz,
H, 7-H), 3.48 (d, J = 1.8 Hz, 1H, 6b-H), 1.74 (s, 3H, 9a-CH ).
, 75 MHz): d = 163.9 (s, C-10a), 160.4 (s, C-6),
54.8 (s, C-4a), 142.7 (s, C-1¢), 137.7 (d, C-8), 133.2 (d, C-9), 132.1
was added NaOH (10% w/v aq., 0.33 mL). The resulting mixture
was warmed to room temperature and stirred for 3 days. Then
HCl (0.6 N, 0.65 mL) was added. Ethanol was evaporated under
reduced pressure and the resulting crude mixture was extracted
with ethyl acetate (3 ¥ 5 mL). The combined organic layers were
1
3
1
3
C NMR (CDCl
3
1
(
(
d, C-3), 128.6 (2 ¥ d, C-3¢, C-5¢), 127.2 (2 ¥ d, C-2¢, C-6¢), 126.7
d, C-4¢), 123.6 (d, C-2), 122.9 (d, C-1), 116.8 (d, C-4), 112.9 (s,
washed with brine (20 mL), dried (Na
2
SO ) and concentrated in
4
C-10b), 106.5 (s, C-9a), 105.6 (s, C-6a), 57.4 (d, C-6b), 56.6 (d,
C-7), 25.3 (q, C-9a-CH ). HRMS: m/z calcd. for C21 (M +
H ) 317.1172, found 317.1178.
vacuo. Flash column chromatography (silica gel, hexanes : ethyl
3
H
17
O
3
acetate, 9.7 : 0.3) afforded aldehyde as a pale yellow solid (729 mg,
+
◦
-1
5
3
3
4% yield). Mp: 53.5–54.5 C. IR (KBr): nmax/cm 3060, 3036,
1
001, 2982, 2921, 2826, 1667, 1616, 1591. H NMR (CDCl
3
,
00 MHz, Me
4
Si): d = 9.44 (s, 1H), 7.49–7.45 (m, 2H), 7.36–7.25
General experimental procedures for RDC measurements and gel
preparation
(
(
m, 3H), 7.15 (dd, J = 15.9, 10.6 Hz, 1H), 6.92–6.86 (m, 2H), 1.89
13
d, J = 0.9 Hz, 3H) C NMR (CDCl
3
, 75 MHz): d = 194.3 (d),
NMR experiments were collected on a Bruker Avance DMX-500
1
1
48.3 (d), 140.7 (d), 137.2 (s), 135.6 (s), 128.9 (d), 128.4 (2 ¥ d),
1
NMR instrument operating at 500.13 MHz for H, 125.77 MHz
27.0 (2 ¥ d), 122.9 (d), 9.1 (q). HRMS: m/z calcd. for C12
H
12ONa
1
3
2
+
for C and 76.73 MHz for H, equipped with a broad band
(
M + Na ) 195.0780, found 195.0774.
inverse (BBI) probe with only Z gradients and a 2H-TX board
2
1
2
to perform H and H 3D gradshimming, and H NMR ex-
Preparation of 3a,6,6-trimethyl-1-phenyl-1,3a,5,6,7,8b-hexahydro-
H-benzo[b]cyclopenta[d]furan-8-one (6a
2
1
periments. H 1D, H 1D, HSQC experiments were collected
using standard pulse programs from the Bruker software library.
The monomer, methyl methacrylate (MMA, 99%, Aldrich) was
purified prior to the experiments by passing the neat liquid
through a short column filled with basic alumina in order to
8
4
)
A mixture of dimedone (250 mg, 1.69 mmol), 2-methyl-5-phenyl-
penta-2,4-dienal (290 mg, 1.69 mmol), piperidine (0.022 mL, 0.23
mmol) and acetic acid (0.045 mL, 0.78 mmol) in toluene (15.0 mL)
This journal is © The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 3170–3175 | 3173