10062 J. Am. Chem. Soc., Vol. 119, No. 42, 1997
Katz et al.
J ) 8.2 Hz, 4H), 7.33 (d, J ) 8.1 Hz, 4H), 4.34 (dd, J ) 8.1 and 4.0
Hz, 2H), 3.55 (m, 2H), 3.26 (m, 2H), 2.43 (s, 6H), 2.19 (m, 2H), 2.05
(m, 4H), 1.78 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 167.19, 143.97,
134.83, 129.89, 127.53, 61.07, 48.63, 30.43, 24.70, 21.57.
immediately turned red. The solution was filtered, washed twice with
saturated aqueous NaHCO3, dried (MgSO4), and filtered again. After
the solvent had been stripped, chromatography (eluting with 5% THF
in toluene), followed by drying in Vacuo at 25 °C, gave 1.09 g (94%)
1
of pure helicene (+)-11c, a noncrystalline solid. The H NMR and
This anhydride (1.34 g, 2.71 mmol) was dissolved in 2 mL of hot
DMF, and after the solution had cooled to 0 °C, TMEDA (0.30 g, 2.59
mmol), helicenebisquinone 11c (0.20 g, 0.32 mmol), and Zn powder
(0.632 g, 9.7 mmol) were added sequentially and the mixture was stirred
at 0 °C for 4.5 h. After precipitates had been filtered through Celite
(washing with THF), Et3N (0.5 mL) and H2O (0.5 mL) were added to
the filtrate. The solution was diluted with CHCl3 (ca. 50 mL), washed
with 1 M aqueous NaOH (3X, back extracting twice with CHCl3), 1
M HCl, H2O (3×), and finally brine, dried (MgSO4), and stripped. The
residue was dissolved in 4 mL of hot acetone, loaded onto a
chromatography column (1.5 in. × 14 in.), and eluted with hexane-
CH2Cl2-acetone (5:4:1). The diastereomer that eluted first was (-)-
14 (0.250 g, 95%), followed by (+)-14 (0.245 g, 93%). Both were
yellow solids. A similar experiment starting with 2.00 g of 11c gave
2.49 g of (-)-14 (95%) and 2.50 g of (+)-14 (95%). These were
isolated by loading 1.0-1.5 g portions of the crude product dissolved
in 8 mL of warm acetone onto 2.25 in. × 14 in. columns and eluting
as above.
13C NMR spectra were identical to those of the racemic material. [R]D
) +2249 (c 0.0105, CH3CN). UV-vis (CH3CN, c ) 1.66 × 10-5 M)
λ
max (nm) (log ꢀ) 300 (4.5), 282 (4.3), 248 (4.7). CD (c ) 1.66 × 10-5
M, CH3CN) nm ([θ]) 352 (-4.9 × 106), 297 (3.8 × 106), 260 (-2.6
× 106), 226 (5.1 × 106), 214 (-1.7 × 106). The same reaction
conditions applied to the other diastereomer, (-)-14, gave pure (-)-1.
[R]D ) -2247 (c ) 0.110 g/L, CH3CN). UV-vis (CH3CN, c ) 1.66
× 10-5 M) λmax (nm) (log ꢀ) 300 (4.5), 282 (4.3), 249 (4.7). CD (c )
1.66 × 10-5 M, CH3CN), nm ([θ]), 351 (4.7 × 106), 296 (-3.8 ×
106), 259 (2.4 × 106), 226 (-5.8 × 106), 213 (1.5 × 106).
1,4,13,16-Tetrahydro-1,4,13,16-tetraoxo-6,11-bis[1-(2-butoxy-
ethoxy)ethenyl]-3,14-bis[1-[2-hydroxymethyl)pyrrolidinyl]][6]-
helicene (15). Helicenebisquinone 11c (4 g, 6.5 mmol) was added to
a solution of (S)-2-(hydroxymethyl)pyrrolidine20 (3.26 g, 32.2 mmol)
and Cu(OAc)2‚H2O (6.69 g, 33.5 mmol) in 32 mL of CHCl3 plus 32
mL of MeOH, and the solution was refluxed under O2 for 20 h.
Dilution with CHCl3 (150 mL), washing with 1 M HCl, 30% aqueous
NH3 (3×), and H2O, drying (MgSO4), and stripping gave 5.78 g of
crude 15 as a solid. Chromatography (2.25 in. × 6.5 in., eluting with
15% EtOH in CHCl3) gave 2.10 g of (+)-15 (Rf 0.33) and 2.21 g of
(-)-15 (Rf 0.42), an 82% yield. (+)-15: 1H NMR (400 MHz, CDCl3)
δ 8.16 (d, J ) 8.4, 2H), 7.90 (d, J ) 8.8 Hz, 2H), 6.59 (br s, 2H), 5.31
(s, 2H), 4.14 (m, 1H), 3.96 (m, 2H), 3.84 (m, 1H), 3.35 - 3.77 (m, J
) 14H), 3.26 (m, 2H), 2.61 (m, 2H), 1.85 (m, 4H), 1.65 (pentet, J )
7.4 Hz, 4H), 1.45 (sextet, 8.0 Hz, 4H), 1.76-1.40 (m, 10H), 0.99 (t, J
) 7.2 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 183.40, 181.79, 180.74,
158.76, 151.05, 135.60, 131.81, 130.90, 127.66, 127.49, 126.92, 126.33,
121.95, 102.17, 100.89, 71.48, 68.76, 65.33, 62.45, 50.43, 31.69, 28.30,
21.10, 29.29, 13.93. IR (CDCl3) 3628, 3450, 2962, 2936, 2874, 1667,
1611, 1592, 1554, 1511, 1480, 1456, 1409, 1381, 1349, 1287, 1232,
1211, 1440, 1086, 1040, 1016 cm-1; MS (EI) m/z 819 (MH+), 787,
590.; HRMS calcd for C48H55N2O10 819.3857, found 819.3825. [R]D
) +4071 (c 0.0206, CHCl3). UV-vis (CH3CN, c ) 1.25 × 10-5 M)
To recover excess N-tosyl-L-proline, the 1 M NaOH layers above
were washed with CHCl3, acidified with concentrated HCl, and
extracted with CHCl3 (3×). Washing with H2O and brine, drying
(MgSO4), stripping (after some benzene had been added), and drying
in Vacuo, first at 100 °C and then at ca. 130 °C, recovered 87% of
practically pure N-tosyl-L-proline.
(+)-14: 1H NMR (400 MHz, CDCl3) δ 8.68 (d, J ) 8.4 Hz, 2H),
8.31 (d, J ) 8.4 Hz, 2H), 7.86 (d, J ) 8.0 Hz, 4H), 7.46 (s, 2H), 7.38
(d, J ) 8.0 Hz, 4H), 7.19 (d, J ) 8.0 Hz, 4H), 7.0 (d, J ) 8.4 Hz, 4H),
6.69 (d, 8.0 Hz, 2H), 6.27 (d, 8.4 Hz, 2H), 4.65 (m, 4H), 4.56 (m, 2H),
3.99 (m, 4H), 3.65 (t, J ) 6.4 Hz, 6H), 3.25 (m, 2H), 3.10 (m, 4H),
2.96 (m, 2H), 2.47 (s, 6H), 2.28 (s, 6H), 2.25 (m, 2H), 2.16 (m, 2H),
1.87-1.51 (m, 14 H), 1.40 (sextet, J ) 7.6 Hz, 4H), 0.92 (t, J ) 7.2
Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 171.41, 169.27, 154.11, 143.96,
143.84, 142.94, 142.61, 135.89, 134.99, 131.86, 129.95 (two peaks),
129.13 (two peaks), 127.75, 127.68, 127.55 (two peaks), 127.20 (two
peaks), 126.86, 125.95, 124.88, 120.58, 120.43, 118.02, 115.94, 97.66,
71.40, 69.25, 68.65, 60.45, 59.48, 48.67, 47.76, 32.00, 31.21, 30.62,
25.02, 24.08, 21.57, 21.39, 19.38, 13.98; IR (CDCl3) 2961, 2933, 2874,
1770, 1619, 1608, 1528, 1511, 1495, 1460, 1446, 1342, 1292, 1262,
1198, 1164, 1132, 1095, 1024, 842, 816, 589 cm-1; MS (EI) m/z 1630
(MH+), 1476, 1378, 1127, 876, 625; HRMS Calcd for C86H93N4O20S4
1629.5270, found 1629.5256.
λmax (nm) (log ꢀ) 407 (4.0), 330 (4.5), 297 (4.6). CD (CH3CN, c ) 1.25
× 10-5 M), nm ([θ]), 268 (8.3 × 106), 306 (-5.3 × 106), 330 (-7.8
× 106), 409 (5.7 × 106), 452 (4.0 × 106). (-)-15: 1H NMR (400
MHz, CDCl3) δ 8.36 (d, J ) 8.7 Hz, 2H), 7.89 (d, J ) 8.7 Hz, 2H),
7.46 (br s, 2H), 5.33 (br s, 2H), 4.53 (m, 2H), 4.41 (m, 2H), 3.97 (t, J
) 4.6 Hz, 4H), 3.63 (t, J ) 6.6 Hz, 4H), 3.50 (m, 2H), 3.31 (m, 8H),
1.96 (m, 8H), 1.66 (quintet, 6.6 Hz, 4H), 1.44 (sextet, 7.2 Hz, 4H),
0.96 (t, J ) 7.4 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 181.57, 180.18,
157.46, 151.28, 135.54, 131.46, 130.16, 126.54 (two peaks), 126.22,
126.04, 122.07, 101.20, 100.08, 71.25, 68.87, 67.59, 61.96, 60.10, 52.20,
31.65, 26.46, 23.86, 19.30, 13.94. IR (CDCl3) 3307, 2961, 2935, 2875,
1669, 1593, 1558, 1512, 1482, 1466, 1430, 1410, 1364, 1342, 1240,
1233, 1211, 1088, 1048, 1008 cm-1; MS (EI) m/z 819 (MH+), 789,
590. HRMS calcd for C48H55N2O10 819.3857, found 819.3854. [R]D
) -3738 (c 0.0215, CHCl3); UV-vis (CH3CN, c ) 6.26 × 10-5 M)
(-)-14: 1H NMR (400 MHz, CDCl3) δ 8.51 (d, J ) 8.4 Hz, 2H),
8.00 (d, J ) 8.4 Hz, 2H), 7.88 (d, J ) 8.0 Hz, 4H), 7.71 (d, 8.4 Hz,
4H), 7.60 (s, 2H), 7.45 (d, J ) 8.0 Hz, 4H), 7.32 (d, J ) 8.4 Hz, 4H),
6.94 (d, J ) 8.4 Hz, 2H), 6.27 (d, J ) 8.4 Hz, 2H), 4.80 (dd, J ) 8.4
and 4.8 Hz, 2H), 4.52 (t, J ) 4.4 Hz, 4H), 3.88 (m, 4H), 3.53 (m, 2H),
3.48 (t, J ) 6.4 Hz, 4H), 3.36 (m, 4H), 3.17 (m, 2H), 3.00 (q, 8.8 Hz,
2H), 2.44 (s, 6H), 2.42 (s, 6H), 2.37 (s, 4H), 2.18 (m, 2H), 1.87 (septet,
J ) 6.8 Hz, 2H), 1.52 (pentet, J ) 6.8 Hz, 4H), 1.35 (m, 8H), 1.16 (m,
2H), 0.89 (t, J ) 7.6 Hz, 6H); 13C NMR (75 MHz, CDCl3) δ 171.01,
169.37, 154.00, 143.84, 143.62, 143.54, 143.21, 135.58, 135.08, 131.16,
129.85 (two peaks), 129.80 (two peaks), 129.97 , 127.72 (two peaks),
127.49 (two peaks), 127.08, 126.43, 126.12, 124.66, 121.06, 120.37,
118.78, 116.36, 98.00, 70.88, 69.17, 68.64, 60.71, 58.66, 48.64, 47.85,
31.92, 31.42, 29.70, 25.08, 23.91, 21.48 (two peaks), 19.32, 13.95; IR
(CDCl3) 2961, 2933, 2874, 1769, 1619, 1609, 1527, 1511, 1461, 1446,
λ
max (nm) (log ꢀ) 409 (4.0), 324 (4.5), 299 (4.6). CD (CH3CN, c ) 1.21
× 10-5 M), nm ([θ]), 270 (-8.8 × 106), 302 (4.9 × 106), 333 (9.1 ×
106), 415 (-6.5 × 106), 443 (-5.0 × 106).
Addition of L-Prolinol to (-)-11c. A mixture of (-)-11c (4 mg, 7
µmol), L-prolinol (9 mg, 90 µmol) and Cu(OAc)2 (7 mg, 40 µmol) in
1 mL of 1:1 MeOH-CHCl3 open to the air was refluxed for 12 h.
Dilution with CH2Cl2, aqueous workup, solvent removal, and trituration
with hexane left a red solid. Chromatography (eluting with 15% EtOH
1351, 1341, 1293, 1199, 1163, 1133, 1095, 1013, 842, 816, 589 cm-1
;
1
MS (EI) m/z 1630 (MH+), 1476, 1378, 1127, 876, 625; HRMS Calcd
in CHCl3) gave (-)-15c (5 mg, 94%), whose H NMR spectrum was
identical to that recorded above.
for C86H93N4O20S4 1629.5270, found 1629.5230.
Recovery of Nonracemic Helicenes 11c from Tetraesters 14. The
diastereomerically pure helicenebisquinone (+)-14 (3.04 g, 1.87 mmol)
as a solid (washed in with THF) was added in portions to a stirred
mixture of LiAlH4 (849 mg, 22.4 mmol) in 18.7 mL of THF at 0 °C.
The mixture was refluxed for 3 h, cooled to 0 °C, and while still under
a N2 atmosphere, slowly quenched, while being stirred, with saturated
aqueous NH4Cl (ca. 1 mL), 1 M HCl (ca. 10 mL, added slowly), and
finally more 1 M HCl (100 mL). The bright yellow solution obtained
by extraction with ethyl acetate (3×), washing with water (1×), and
drying (MgSO4), when treated with chloranil (1.15 g, 4.47 mmol)
Adduct of 11c and Pyrrolidine. A mixture prepared by adding
pyrrolidine (0.24 mL, 0.20 g, 2.8 mmol) to a solution of 11c (50 mg,
81 mmol) and Cu(OAc)2 (0.20 g, 1.22 mmol) in 6 mL of 1:1 MeOH-
CH2Cl2 was refluxed for 1 h while open to the air. After the solvent
had been stripped, the residue triturated with hexane, and a solution in
CH2Cl2 filtered, chromatography (0.5 in. × 3 in., eluting with 25%
acetone in CH2Cl2) gave an adduct, seemingly 15 without the
hydroxymethyl groups (56 mg, 92%), a red-orange solid, mp 208-
212 °C. The 1H NMR integrals in the region of quinone proton
resonance imply this to be >95% one isomer. 1H NMR δ 8.38 (d, J