Taber and He
1150 (m), 1028 (m); 1H NMR (400 MHz, CDCl3) δ: 6.83-6.95
(m, 3H), 5.28 (m, 1H), 4.96 (d, J ) 23.6 Hz, 1H), 4.93 (d, J )
17.2 Hz, 1H), 4.16 (t, J ) 3.6 Hz, 1H), 3.97 (m, 4H), 3.88 (s,
3H), 3.86 (s, 3H), 3.08 (d, J ) 8.0 Hz, 1H), 1.65-2.50 (m, 8H);
13C NMR (CDCl3, 100 MHz) δ u: 148.6, 147.1, 137.2, 117.3,
108.7, 64.6, 64.1, 44.6, 41.6, 36.7, 30.5, 25.2; d: 134.3, 119.1,
110.8, 110.3, 74.3, 55.8, 55.7; HRMS calcd for C19H26O5 (M+)
334.1780, found 334.1774.
Tosylate (13). To a solution of diol 12 (major isomer, 133
mg, 0.478 mmol) in 5 mL of anhydrous CH2Cl2 was added
triethylamine (145 mg, 1.44 mmol) and tosyl chloride (91.2 mg,
0.478 mmol). After being stirred under N2 at ambient tem-
perature for 16 h, the reaction mixture was partitioned
between saturated aqueous Na2CO3 and CH2Cl2. The combined
organic extract was dried (Na2SO4) and concentrated. The
crude product was chromatographed to give 0.186 g of tosylate
13 (90% yield) as a clear oil. TLC Rf ) 0.34 (ether), [R]22D -11.4
(c 0.35, THF); IR (neat, cm-1): 3390 (b), 2938 (s), 1598 (s), 1464
(m), 1359 (s), 1252 (s), 1176 (s); 1H NMR (400 MHz, CDCl3) δ:
7.69 (d, J ) 8.0 Hz, 2H), 7.30 (d, J ) 8.0 Hz, 2H), 6.75 (br,
3H), 5.90 (dd, J ) 10.0 Hz, 1.2 Hz, 1H), 5.78 (d, J ) 10.0 Hz,
1H), 4.19 (br, 1H), 3.81-3.98 (m, 2H), 3.85 (s, 3H), 3.84 (s,
3H), 2.44 (s, 3H), 1.67-2.17 (m, 7H); 13C NMR (CDCl3, 100
MHz) δ u: 149.0, 147.7, 144.9, 137.8, 133.2, 67.8, 41.8, 40.9,
35.0, 28.8; d: 133.7, 132.5, 129.9, 127.9, 119.4, 111.1, 110.3,
67.0, 56.1, 56.0, 21.8; HRMS calcd for C23H28O6S (M+) 432.1607,
found 432.1605.
Enone (11). To a solution of alcohol 6d (0.90 g, 2.7 mmol)
in 10 mL of THF was added 10% aqueous HCl (4 mL). After
heating to reflux for 1 h, the reaction mixture was partitioned
between saturated aqueous Na2CO3 and CH2Cl2. The combined
CH2Cl2 extract was dried (Na2SO4) and concentrated in vacuo.
The residue was chromatographed to give 0.67 g of enone 11
(92% yield) as a colorless oil, TLC Rf ) 0.69 (PE/EtOAc, 1:1),
[R]22 -107.6 (c 0.8, THF); IR (neat, cm-1): 2935 (m), 1682
D
(s), 1639 (w), 1603 (w), 1518 (s), 1464 (m), 1255 (s), 1148 (m),
1027 (m); 1H NMR (400 MHz, CDCl3) δ: 7.07 (d, J ) 10.0 Hz,
1H), 6.86 (s, 3H), 6.17 (d, J ) 10.0 Hz, 1H), 5.56 (m, 1H), 5.11
(d, J ) 15.2 Hz, 1H), 5.08 (d, J ) 8.4 Hz, 1H), 3.88 (s, 3H),
3.87 (s, 3H), 2.15-2.73 (m, 6H); 13C NMR (CDCl3, 90 MHz) δ
u: 199.6, 149.1, 148.0, 135.4, 119.0, 46.3, 43.6, 36.1, 34.5; d:
155.3, 133.6, 129.5, 119.4, 111.1, 110.2, 56.1, 55.9; HRMS calcd
for C17H21O3 (M + H) 273.1491, found 273.1490.
(-)-Mesembrine (1). To a sealed thick-walled reaction
flask was added tosylate 13 (144 mg, 0.33 mmol), methylamine
(2.0 mL, 40% in water), and THF (4.0 mL). The reaction
mixture was heated at 65 °C for 1 h and then concentrated in
vacuo, and the residual oil was dissolved in CH2Cl2 (15 mL).
To this solution activated MnO2 (220 mg, 2.53 mmol) was
added, and the mixture was stirred at room temperature for
3 h. After filtration through a thin layer of Celite, the filtrate
was concentrated and the residue was chromatographed to
give 58.8 mg of (-)-mesembrine (61% yield) as a colorless oil.
Diol (12). To a solution of enone 11 (0.663 g, 2.43 mmol) in
HPLC-grade methanol (20 mL) was added an indicator amount
of Sudan III. After being purged with O2 at -78 °C for 2 min,
O3 was bubbled through the solution until the red color of
Sudan III disappeared. The reaction was purged with N2 for
5 min, and then CeCl3‚7H2O8 (1.00 g, 2.68 mmol) was added.
The reaction mixture was cooled with an ice-water bath, and
then NaBH4 (554 mg, 14.6 mmol) was added in three portions
over 5 min. After an additional 30 min, NaBH4 (92 mg, 2.43
mmol) was added followed by stirring for another 30 min. The
latter procedure was repeated once more. The reaction mixture
was partitioned between water and CH2Cl2. The combined
organic extract was dried (Na2SO4) and concentrated, and the
residue was chromatographed to give 0.474 g of diol 11 (4:1
mixture of two diasteromers, 73% yield) as a colorless oil. TLC
TLC Rf ) 0.21(wet ether), [R]22 -55.4 (c 0.54, MeOH); IR
D
(neat, cm-1): 2944 (m), 1716 (s), 1520 (s), 1454 (m), 1253 (s),
1148 (m), 1027 (m); 1H NMR (400 MHz, CDCl3) δ: 6.93 (dd, J
) 8.4, 2.4 Hz, 1H), 6.90 (d, J ) 2.0 Hz, 1H), 6.84 (d, J ) 8.4
Hz, 1H), 3.90 (s, 3H), 3.88 (s, 3H), 3.13-3.17 (m, 1H), 2.96 (t,
J ) 3.6 Hz, 1H), 2.61 (m, 2H), 2.35-2.46 (m, 2H), 2.33 (s, 3H),
2.04-2.26 (m, 5H); 13C NMR (CDCl3, 90 MHz) δ u: 211.5,
149.3, 147.8, 140.4, 55.1, 47.8, 40.8, 39.1, 36.4, 35.5; d: 118.2,
111.3, 110.3, 70.6, 56.2, 56.1, 40.3; HRMS calcd for C17H23-
NO3 (M+) 289.1678, found 289.1671.
Rf ) 0.18 (wet ether), [R]22 -23.5 (c 0.55, THF); IR (neat,
D
cm-1): 3390 (b), 2941 (s), 1715 (m), 1520 (s), 1260 (s), 1026
(s); 1H NMR (400 MHz, major isomer, CDCl3) δ: 6.78-6.82
(m, 3H), 5.86-5.95 (m, 2H), 4.21 (m, 1H), 3.86 (s, 3H), 3.85 (s,
3H), 3.47-3.58 (m, 2H), 1.62-2.07 (m, 7H); 13C NMR (CDCl3,
major isomer, 90 MHz) δ u: 148.8, 147.4, 139.1, 59.7, 45.0,
41.8, 35.0, 28.9; d: 134.9, 131.7, 119.4, 110.9, 110.5, 67.2, 56.1,
56.0; 1H NMR (400 MHz, minor isomer, CDCl3) δ: 6.80-6.82
(m, 3H), 5.60-6.06 (m, 2H), 4.13 (m, 1H), 3.87 (s, 3H), 3.85 (s,
3H), 3.55-3.65 (m, 2H), 1.62-2.10 (m, 7H); 13C NMR (CDCl3,
minor isomer, 90 MHz) δ u: 148.9, 147.5, 139.0, 59.7, 44.7,
41.9, 32.6, 28.5; d: 136.5, 130.0, 119.0, 111.1, 110.3, 64.6, 56.1,
56.0; HRMS calcd for C16H22O4Na (M + Na) 301.1416, found
301.1412.
Acknowledgment. We thank the NIH (GM60287)
for financial support of this study, and DSM for a gift
of Shi ketone. This work is dedicated to the memory of
Conrad J. Kowalski, a master of the science and art of
organic synthesis.
Supporting Information Available: General experimen-
tal details, characterization of the products from Table 1, and
spectra for all new compounds and for 1. This material is
JO0511039
7714 J. Org. Chem., Vol. 70, No. 19, 2005