896
P. Skowronek and D. A. Lightner
Diethyl 3,30-di-tert-butyl-4,40-dimethyl-2,20-bipyrrole-5,50-dicarboxylate (5; C24H36N2O4)
To 2.51 g of iodopyrrole 4 (7.5 mmol) dissolved in 10 cm3 of dry xylene were added 2.86g of Cu powder
(45 mmol, 6 eq.), and the mixture was heated in a sealed tube at 140ꢀC for 2 days. After cooling, the Cu
was removed by filtration through celite, which was washed well with CHCl3. The organic filtrates were
washed with 25 cm3 of 1 M HCl and Na2S2O3, then H2O. After drying over anhydrous Na2SO4, the
solvents were removed, and the resulting solid was purified by radial chromatography using
CH3OH:CH2Cl2 ¼ 2:98 (v=v) as eluent and crystallized from CH2Cl2=n-hexane to give 450mg (1st
crop) þ 82mg (2nd crop) of 5. Yield: 528 mg (34%); mp: 291–2ꢀC (sealed capillary); UV (ethanol):
ꢂ
max(") ¼ 286 (34700), 250 (sh, ꢁ16400) nm; IR: ꢄꢀ¼ 3288, 2952, 1665, 1223, 1094cmÀ 1; 1H NMR:
ꢃ ¼ 1.20 (9H, s), 1.34 (3H, dd, J ¼ 6.85, 7.30 Hz), 2.53 (3H, CH3), 4.27 (1H, dq, J ¼ 10.96, 6.85 Hz), 4.32
(1H, dq, J ¼ 10.96, 7.30 Hz), 8.52 (1H, br) ppm; 13C NMR: ꢃ ¼ 13.46 (CH3CH2), 14.73 (C-4,40 CH3),
31.10 (tBu-CH3), 32.85 (tBu-C), 60.22 (CH2), 119.65, 123.88, 126.76, 1330.10, 161.62 (C¼O) ppm;
MS: m=z (%) ¼ 416 (Mþ ꢂ, 55), 345 (100), 299 (47), 253 (50), 225 (9), 155 (16), 147 (7), 57 (18).
Disobutyl 3,30-di-tert-butyl-4,40-dimethyl-2,20-bipyrrole-5,50-dicarboxylate (7; C30H48N2O4)
220 mg of bipyrrole 5 (0.529mmol) were suspended in 20cm3 of 95% ethanol and to this mixture was
added 180 mg (4.5mmol) of NaOH in 6 cm3 of H2O. The mixture was heated at reflux with stirring,
until the ester dissolved. After cooling, the reaction mixture was evaporated to dryness, and the residue
was dissolved in 20cm3 of H2O and acidified with conc HCl:H2O ¼ 1:1) to afford a white precipitate,
which was collected by filtration and dried to give diacid 6, which was used directly in the next step.
1
Yield: 185 mg (96%); decpt. 260ꢀC; H NMR (d6-DMSO): ꢃ ¼ 1.11 (9H, tBu-CH3), 2.42 (3H, CH3),
11.02 (H, s), 11.92 (1H, s) ppm; 13C NMR (d6-DMSO): ꢃ ¼ 13.57 (CH3), 30.86 (tBu-CH3), 32.56
(tBu-C), 119.16, 124.83, 124.98, 131.23, 163.05 (CO) ppm.
33.2mg of diacid 6 (0.0922 mmol) were suspended in 7 cm3 of CHCl3 to which 0.1 cm3 (>6 eq.)
of SOCl2 was then added. The stirred mixture was heated at reflux until it was clear. Then the reaction
mixture was evaporated, and the residue was dissolved in CHCl3 and re-evaporated. The residue was
dissolved in 3 cm3 of CH2Cl2, and 30 mm3 (ꢁ3 eq.) of (S)-(-)-2-methyl-1-butanol were added along
with ꢁ60 mm3 (ꢁ4 eq.) of triethylamine. The mixture was stirred for 1 h at room temperature, then the
solvent was evaporated and the residue redissolved in CH2Cl2. The CH2Cl2 solution was washed with
10% aq. HCl, then water, and it was dried over anhydrous Na2SO4. The solid, after evaporation, was
purified by radial chromatography on silica gel using CH2Cl2 as eluent to afford diester 7. Yield: 39 mg
(85%); mp: 209–210ꢀC; IR: ꢄꢀ¼ 3294, 2961, 1664, 1235, 1100 cmÀ 1; UV (ethanol): ꢂmax(") ¼ 285
(29000), 250 (sh, ꢁ15000) nm; 1H NMR: ꢃ ¼ 0.95 (6H, t, J ¼ 7.3 Hz), 0.976 (3H, d, J ¼ 6.8 Hz), 0.980
(3H, d, J ¼ 6.8 Hz), 1.21 (18H, s), 1.3 (2H, m), 1.5 (2H, m), 1.8 (2H, m), 2.55 (6H, s), 4.1 (4H, m), 9.55
(2H, br, NH) ppm; 13C NMR: ꢃ ¼ 11.50, 13.60, 16.83, 16.86, 26.39, 26.43, 31.11, 32.85, 34.55, 69.00,
119.74, 123.95, 126.47, 133.05, 161.93 ppm; MS: m=z (%) ¼ 501 (Mþ 1, 33), 500 (Mþ ꢂ, 100), 429
(37), 359 (53), 313 (22), 309 (34), 271 (16), 270 (13), 269 (29), 267 (38), 227 (12), 71 (18), 57 (49).
X-ray Structure and Solution
Crystals of bipyrrole 5 were grown from CH2Cl2=n-hexane. Suitable crystals were coated with epoxy
cement, mounted on a glass fiber and placed on a Siemens P4 diffractomer. Unit cell parameters were
determined by least squares analysis of 3614 reflections with 1591 independent ones (R(int) ¼ 0.0357).
The data were corrected for Lorentz and polarization effects. Crystal data are given in Table 1. Scat-
tering factors and corrections for anomalous dispersion were taken from a standard source [37].
Calculations were performed using Siemens SHELXTL PLUS, version 5.03, system of programs
refining on F2. The structure was solved by direct methods in the chiral space group, C2=c. The unit
cell contains an ordered array of the molecule with short N to O(1) #1 contacts. The handedness of the
molecule shown in Fig. 3 is therefore arbitrarily chosen.