C. P. Rosa et al. / Tetrahedron 63 (2007) 6529–6534
6533
added in three portions. The reaction mixture was cooled to
0 ꢂC after 3 h (white needle crystals formed), at which point
2 M HCl was added until the pH of the solution was approxi-
mately 3. The addition of aqueous HCl caused the solution to
become cloudy. The reaction mixture was then extracted
with three 50 mL portions of 1:1 EtOAc–Hex solution.
The combined extracts were washed with three 100 mL por-
tions of water and with 100 mL of brine. The organic layers
were combined, washed with brine, dried, filtered, and con-
centrated in vacuo. The residue was purified by column chro-
matography (50% EtOAc in hexanes) to afford 3.34 g (87%)
of (6E,10E)-11-((4-hydroxy-2-methoxyphenoxy)methyl)-
3,7-dimethyldodeca-2,6,10-trienal (S3, see Supplementary
data) as a 5:1 (E/Z) mixture with respect to the D2-double
bond (by NMR). All characterization data reported refer to
this mixture. Rf 0.43 (50% EtOAc in hexanes); IR: 3384,
the temperature rose to 150 ꢂC after less than 30 min. The
solution color changed from colorless to light brown over
the course of the heating. The solution was concentrated in
vacuo and purified via column chromatography (10% EtOAc
in hexanes) to afford 85.5 mg (95%) of 20 as a white solid,
mp 115 ꢂC. Rf 0.24 (10% EtOAc in hexanes); IR: 3522,
1
2923, 2852, 2484, 1613 cmꢁ1; H NMR (400 MHz) d 6.36
(s, 1H), 6.26 (d, J¼9.6 Hz, 1H), 5.49 (d, J¼9.6 Hz, 1H),
5.29 (s, 1H), 5.29 (t, J¼7.2 Hz, 1H), 4.70 (t, J¼8 Hz, 1H),
3.88 (s, 3H), 3.69 (d, J¼16 Hz, 1H), 3.06 (d, J¼16 Hz,
1H), 2.03 (m, 8H), 1.74 (s, 3H), 1.54 (s, 3H), 1.42 (s, 3H);
13C NMR (125 MHz) d 146.5, 146.2, 137.4, 132.7, 132.5,
127.5, 126.4, 123.8, 121.7, 121.0, 115.1, 98.3, 77.6, 55.9,
39.8, 37.9, 33.3, 27.0, 24.7, 22.5, 17.0, 14.4; HRMS (EI+)
m/z calcd for C22H28O3: 340.2041; found: 340.2038.
1
2918, 2886, 1671, 1509, 1198 cmꢁ1; H NMR (400 MHz)
5.4. Acetic acid (7E,11Z)-4-acetoxy-7,11,15-trimethyl-
19-oxa-tricyclo[13.3.1.0]nonadeca-1,3,5(18),7,11,16-
hexaen-3-yl ester (21)
d 9.94 (d, J¼8.3 Hz, 1H), 9.84 (d, J¼8.3 Hz, 0.2H), 6.74–
6.62 (m, 2.6H), 6.49–6.41 (m, 1.3H), 6.33–6.26 (m, 1.1H),
5.88 (d, J¼8.2 Hz, 1.3H), 5.41 (t, J¼6.8 Hz, 1.3H), 5.03 (t,
J¼6.4 Hz, 1.1H), 4.37 (s, 0.2H), 4.33 (s, 2.2H), 3.75 (s,
3.7H), 3.66 (s, 0.3H), 2.55 (t, J¼7.4 Hz, 0.4H), 2.31 (s,
0.4H), 2.26–2.05 (m, 10.7H), 2.00–1.92 (m, 3.5H), 1.69
(s, 3.3H), 1.65 (s, 0.5H); 13C NMR (125 MHz) d 191.8,
191.7, 165.2, 165.1, 151, 150.6, 141.8, 136.8, 136.0,
131.4, 131.3, 128.4, 128.3, 128.1, 128.0, 127.2, 127.1,
122.6, 122.2, 116.2, 116.0, 105.9, 100.7, 76.3, 76.2, 55.8,
55.6, 40.5, 40.2, 38.9, 33.8, 32.5, 26.9, 26.0, 25.6, 25.5,
17.6, 17.4, 15.8, 14.2, 13.8, 13.7; HRMS (EI+) m/z calcd
for C25H30O4: 358.21441; found: 358.2138.
To a solution of 20 (38.8 mg, 0.114 mmol) in 3:1 acetoni-
trile–H2O (9 mL) was added a solution of ammonium ceriu-
m(IV) nitrate (188.9 mg, 0.345 mmol) in H2O (2.5 mL) over
1 min at 0 ꢂC. The solution color changed from colorless to
dark orange. After 15 min the reaction was warmed to rt and
0.25 M aqueous Na2S2O4 (2.5 mL) was added. The solution
immediately turned light yellow. The reaction mixture
was then extracted with three 10 mL portions of EtOAc, to
which DMAP (16.7 mg, 0.137 mmol) and Ac2O (0.1 mL,
1.06 mmol) were added. After 1.5 h, the mixture was dried,
filtered, and concentrated in vacuo. The product was purified
via column chromatography (10% EtOAc in hexanes) to af-
ford 18.5 mg (40%) of 21 as a colorless oil. Rf 0.58 (30%
To a solution of (6E,10E)-11-((4-hydroxy-2-methoxy-
phenoxy)methyl)-3,7-dimethyldodeca-2,6,10-trienal (S3,
20.0 mg, 0.0558 mmol) in toluene (4 mL) were added phe-
nylboronic acid (14.0 mg, 0.0837 mmol) and acetic acid
(0.400 mL). The reaction mixture was then fitted with
a Dean–Stark apparatus and heated under reflux for 3 h.
The mixture was cooled to room temperature, diluted with
CH2Cl2, washed with water, saturated NaHCO3, and brine,
dried over MgSO4, and concentrated in vacuo. The product
was purified by column chromatography (10% EtOAc in
hexanes, CAM) to afford 4.9 mg (26%) of smenochromene
D (11) as a clear oil. Rf 0.26 (10% EtOAc in hexanes); IR:
EtOAc in hexanes); IR: 2977, 2931, 2853, 1774, 1209 cmꢁ1
;
1H NMR (400 MHz) d 6.57 (s, 1H), 6.20 (d, J¼10 Hz, 1H),
5.54 (d, J¼10 Hz, 1H), 5.18 (t, J¼6.9 Hz, 1H), 4.67 (t,
J¼6.7 Hz, 1H), 3.20 (d, J¼16 Hz, 1H), 3.07 (d, J¼16 Hz,
1H), 2.26 (s, 3H), 2.23 (s, 3H), 2.21–2.09 (m, 3H), 2.09–1.82
(m, 4H), 1.80–1.69 (m, 1H), 1.63 (s, 3H), 1.48 (s, 3H), 1.37 (s,
3H); 13C NMR (125 MHz) d 168.68, 168.05, 151.42, 141.87,
134.29, 132.726, 131.50, 129.11, 128.87, 127.35, 125.42,
120.96, 119.85, 109.60, 78.34, 39.56, 39.22, 34.59, 27.54,
24.69, 22.57, 20.70, 20.30, 16.95, 14.44; HRMS (EI+) m/z
calcd for C25H30O5: 410.2093; found: 410.2090.
1
3394, 2921, 2852, 1616, 1505 cmꢁ1; H NMR d 6.52 (s,
1H), 6.31 (d, J¼12.8 Hz, 1H), 6.29 (s, 1H), 5.31 (d,
J¼12.8 Hz, 1H), 4.93 (t, J¼7.2 Hz, 1H), 4.82 (t, J¼8 Hz,
1H), 4.52 (d, J¼15.2 Hz, 1H), 4.14 (d, J¼15.2 Hz, 1H),
3.76 (s, 3H), 2.09 (m, 4H), 1.77 (m, 2H), 1.69 (s, 3H),
1.58 (m, 2H), 1.47 (s, 3H), 1.36 (s, 3H); 13C NMR
d 153.4, 150.3, 139.3, 132.0, 131.8, 129.8, 126.6, 125.8,
123.5, 119.1, 113.3, 99.9, 80.3, 79.0, 55.6, 41.4, 38.9,
30.2, 24.6, 23.1, 14.4, 14.1; HRMS (EI+) m/z calcd for
C22H28O3: 340.2038; found: 340.2033.
5.5. Smenochromene B (9)
To a solution of 21 (4.5 mg, 0.011 mmol) dissolved in
MeOH (1 mL) was added 0.01 M NaOMe in MeOH
(0.5 mL). The solution color changed from colorless to
dark orange/red. After 1 h the solution was concentrated in
vacuo, without exposing the reddish substrate to air. The resi-
due was then dissolved in 1 mL of DMF, and 45 mg of CsF
was added. The solution then darkened to black, at which
point 0.1 M CH2BrCl in DMF (0.1 mL) was added. The
stirred solution was heated to 115 ꢂC for 16 h under N2.
The mixture was quenched with 30 mL of H2O, extracted
with three 10 mL portions of Et2O, dried, filtered, and con-
centrated in vacuo. The product was purified via column
chromatography (5% EtOAc in hexanes) to afford 0.8 mg
(18%) of smenochromene B as a colorless oil. Rf 0.34 (5%
EtOAc in hexanes); IR: 2921, 1620, 1462, 942 cmꢁ1; see
the table for comparison of carbon and hydrogen NMR
5.3. (7E,11Z)-3-Methoxy-7,11,15-trimethyl-19-oxa-
tricyclo[13.3.1.0]nonadeca-1,3,5(18),7,11,16-hexaen-4-
ol (20)
A solution of smenochromene D (11, 90.5 mg, 0.266 mmol)
in o-dichlorobenzene (10 mL) was degassed by bubbling
N2 for 10 min. The vial was sealed and heated via
microwave irradiation while stirring for 3.5 h. Heating to
a maximum temperature of 163 ꢂC required 1 h, although