HETEROCYCLES

Paper | Regular issue | Vol. 83, No. 9, 2011, pp. 2001-2010
Received, 3rd May, 2011, Accepted, 30th June, 2011, Published online, 13th July, 2011.
DOI: 10.3987/COM-11-12246

■ Chemistry of Nitroenamines. Part 2. Synthesis of Saturated Pyrrolo-pyrimidines and -pyrazines

Pál Scheiber,* Gábor Tóth, Mihály V. Pilipecz, Támas R. Varga, and Péter Nemes

Department of Chemistry, School of Veterinary Medicine, Szent István University, H-1400 Budapest, P. O. Box 2, Hungary

Abstract

New saturated pyrrolo-pyrimidines and pyrrolo-pyrazines were synthesized from 2-nitromethylene-pyrrolidine. Additionally, some simple aminomethylated derivatives of Mannich type were prepared. The nitro compounds were reduced into diastereomeric amines, which were separated and characterized structurally.

INTRODUCTION
Due to their push pull electronic structure the nitroenamines1 can readily undergo chemical transformations providing a wide spectrum of various heterocycles. Thus in our preceding papers we have described the preparation of divers pyrrolizines2 and indolizidines3 starting from 2-nitromethylene-pyrrolidine (1). Enaminoesters, e.g. pyrrolidin-2-ylidene-acetic acid ethyl ester7 were also subjected to similar Mannich reactions, providing ester derivatives in moderate yields.
Although the thoroughly studied saxitoxin,4 an extremely toxic substance of marine organisms incorporates a pyrrolo-pyrimidine part in its tricyclic structure, simple pyrrolo-pyrimidines are less investigated. Based on the enhanced reactivity of the nitroenamines, in this paper we report the synthesis of some saturated pyrrolo-pyrimidines, along with some new pyrrolo-pyrazines, occurring as subunits in the molecules of some natural products, e.g. batzelladines5 and naseseazines.6

RESULTS AND DISCUSSION
Using the nitroenamine 1 as a C-H acid reactant several Mannich reactions were accomplished (Scheme 1). The reactions with various secondary amines in ethanol at room temperature led to formation of aminomethylated products in good yields (Table 1). Instead of formaldehyde and dimethylamine the Eschenmoser salt was also applied successfully.

As previously noted2 the high chemical shift (∼9 ppm) of the NH proton may indicate the Z arrangement of the double bond in 1. We confirmed this configuration by NOE experiments showing interaction between the olefinic =CH and 4-CH2 protons. In compounds 2-8 the δNH chemical shifts appeared also at ∼9 ppm proving the unchanged configuration.

Catalytic reduction of 2 gave the mixture of diastereomeric diamines 9 and 10 in comparable amounts. Noteworthy, that reductive removal of the dimethylamino group proceeded simultaneously. For the sake of clarity only the enantiomers (5R,5aR) and (5R,5aS) are shown in Scheme 2. In case of the nitroalkenes 3-8 no such removal of the amine component was observed. Upon treatment with diethyl oxalate at 60 oC the mixture of diamines 9 and 10 gave the pyrrolo-piperazine derivatives 11 and 12 (Scheme 2). Recrystallization led to a nearly pure substance containing the isomers 11 and 12 in a ratio ca. 97:3, respectively.

The stereochemistry of 11 and 12 was established by comprehensive one- and two-dimensional NMR methods using widely accepted strategies.8 The results are displayed in Figure 1.

Based on the significantly different 3J (H-1,H-8a) coupling constants 11 and 12 were identified unambiguously. The value of 10.5 Hz in 11 proves the antiperiplanar arrangement of H-1 and H-8a atoms, whereas the value of 4.5 Hz in 12 supports their gauche position.
The Mannich reactions of the nitroenamine 1 with primary amines gave the pyrrolo-pyrimidines 13-20 in good yields (Scheme 3, Table 2).

Reduction of 19 with Raney-Ni led to a mixture of diastereomers 21 and 22, with equatorial and axial C(4)-NH2 group, respectively, that was subjected column chromatography affording the pure isomers in a ratio 83:17 (Scheme 4).

The NMR signal assignments and the C(4) and C(4a) configurations were determined by 1H,13C, DEPT, 1H,1H-COSY, 1H,13C-HSQC, 1H,1H-NOESY and selective 1H-NOESY experiments in CDCl3. The conformation and the characteristic NMR correlations are depicted in Figure 2.

The H-4 signal at δ 2.74 ppm appeared with a ddd multiplicity. The measured J (H-4,H-4a) = 9.0 Hz and J (H-4,H-3β) = 11.0 Hz coupling constants are in accordance with their antiperiplanar arrangements, whereas the value of J (H-4,H-3α) = 4.3 Hz supports their gauche relation.
Hydrogenation of 19 with Pd/C catalyst led to formation of a mixture containing 23 predominantly and 24 in negligible amount. These diastereomers were not separated, the structure of 23 was proven by debenzylation of 21.
In conclusion we have demonstrated the synthetic usefulness of the nitroenamine 2 in preparation of various Mannich compounds. These primary products were reduced enabling us to prepare new pyrrolo-pyrazines and pyrrolo-pyrimidines.

EXPERIMENTAL
General. Commercially available (Aldrich, Alfa Aesar) reagents were used. Prior the use the solvents were redistilled. The reaction mixtures and the purity of the products were checked by analytical TLC performed on precoated Merck aluminum sheets (DC-Alufolien Kieselgel 60 F254). The spots were visualized by iodine vapor or Dragendorff reagent. Melting points were determined on a Büchi 20SchmP apparatus and are uncorrected. HRMS were determined with a Waters LCT Premier XE instrument. IR spectra were obtained with a Perkin-Elmer 1600 FT/IR instrument (KBr pellet or liquid film). NMR spectra were recorded at ambient temperature on a Varian UNITY spectrometer (300 MHz for 1H-spectra, 75 MHz for 13C spectra) and compounds 1, 11, 12, 19 and 21 on a Bruker Avance spectrometer (500 MHz and 125 MHz, resp.). Chemical shifts, given on the δ scale, were referenced to the solvent (CDCl3: δC = 77.0 and δH = 7.27; DMSO-d6: δC = 39.5 and δH = 2.50, resp.). In the 1D measurements (1H, 13C, DEPT-135), 64K data points were used for the FID. The pulse programs [gs-COSY, gs-HSQC, gs-HMBC, 1D NOESY (mixing time = 350 ms), 2D NOESY (mixing time = 400 ms)] were taken from the Bruker software library.
2-Nitromethylenepyrrolidine (1). The mixture of 2-methoxypyrroline (135.1 g, 1.36 mol) and nitromethane (166.1 g, 2.72 mol) was heated under reflux for 20 h. The red solution was concentrated to give a dark viscous residue which was purified by column chromatography using silica (100 g) and EtOAc - CH2Cl2 (1:1) eluent mixture. Evaporation furnished an orange solid, 90.2 g (51.8%); an analytical sample was obtained by recrystallization from ethyl acetate. Pale yellow crystals; mp 109-110 oC (lit.,9 108 oC). IR (KBr) νmax 3261 (NH), 1611, 1359 (NO2) cm-1; 1H NMR (CDCl3) δ 2.14 (2H, m), 2.72 (2H, t, J = 7.8 Hz), 3.73 (2H, t, J = 7.2 Hz), 6.63 (s, 1H), 9.20 (br, 1H); 13C NMR (CDCl3) δ 21.3, 31.3, 48.4, 106.7, 162.8.

General procedure for the preparation of compounds 2-8
A mixture of 128 mg (1.0 mmol) of 1, 150 mg (5 mmol) of paraformaldehyde and 1.0 mmol of a secondary amine in 6 mL EtOH was stirred at room temperature for 5 h. The crystalline product was either filtered off, or the reaction mixture was concentrated and the residue was crystallized. The products were purified by recrystallization using common alcohols. Yields and melting points are given in Table 1.
Dimethyl-(2-nitro-2-pyrrolidin-2-ylideneethyl)amine (2). Using dimethylamine hydrochloride (Scheme 1) 2.HCl was isolated. Mp 165 oC. The free base 2 was obtained by treatment with aqueous solution of potassium carbonate and subsequent extraction with dichloromethane. IR (KBr) νmax 3295 (NH), 1604, 1338 (NO2) cm-1; 1H-NMR (CDCl3) δ 2.07 (2H, m), 2.13 (6H, s), 2.88 (2H, t, J = 7.8 Hz), 3.27 (2H, s), 3.68 (2H, t, J = 7.2 Hz), 9.8 (1H, bs); 13C-NMR (CDCl3) δ 21.3, 32.1, 44.8, 48.6, 56.0, 115.8, 165.0; HRMS: calculated for C8H15N3O2 [MH]+ 186.1243, found 186.1242.
2.HI was obtained in reaction of 1 with equimolar amount of dimethyl methylene ammonium iodide (Eschenmoser salt) in EtOH at 20 oC for 4 h. White powderlike product (80%), recryst. from 95% EtOH, mp 200 oC.
Benzylmethyl-(2-nitro-2-pyrrolidin-2-ylideneethyl)amine (3). Pale yellow plates. IR (KBr) νmax 3304 (NH), 1606, 1350 (NO2) cm-1; 1H-NMR (CDCl3) δ 2.13 (2H, m), 2.18 (3H, s), 2.88 (2H, t, J = 7.8 Hz), 3.50 (2H, s), 3.50 (2H, s), 3.52 (2H, s), 3.73 (2H, t, J = 7.3 Hz), 7.10-7.30 (5H, m), 9.80 (1H, bs); 13C-NMR (CDCl3) δ 21.5, 32.0, 42.0, 48,7, 54.3, 61.8, 116.2, 126.9, 128.1, 128.9, 139.4, 165.4; HRMS: calculated for C14H19N3O2 [MH]+ 262.1556, found 262.1556.

[Methyl-(2-nitro-2-pyrrolidin-2-ylideneethyl)amino]acetic acid (4). White solid. IR (KBr) νmax 3264 (NH), 1630 (COOH), 1593, 1371 (NO2) cm-1; 1H-NMR (D2O) δ 2.04 (2H, m), 2.77 (3H, s), 2.91 (2H, t, J = 7.7 Hz), 3.59 (2H, s), 3.71 (2H, t, J = 7.4 Hz). 4.19 (2H, s); 13C-NMR (D2O) δ 23.3, 37.0, 44.0, 52.2, 53.4, 58.7, 60.6, 112.0, 171.3, 173.0; HRMS: calculated for C9H15N3O4 [MH]+ 230.1141, found 211.1155.
4-(2-Nitro-2-pyrrolidin-2-ylideneethyl)morpholine (5). Pale yellow crystals. IR (KBr) νmax 3321, 3280 (NH), 1611, 1345 (NO2) cm-1; 1H-NMR (CDCl3) δ 2.16 (2H, m), 2.38-2.45 (4H, m), 2.97 (2H, t, J = 7.9 Hz), 3.44 (2H, s), 3.58-3.65 (4H, m), 3.76 (2H, t, J = 7.3 Hz), 9.82 (1H, bs); 13C-NMR (CDCl3) δ 21.4, 32.2, 48.7, 53.0, 55.5, 67.0, 115.1, 165.1; HRMS: calculated for C10H17N3O3 [MH]+ 228.1348, found 228.1346.
1-(2-Nitro-2-pyrrolidin-2-ylideneethyl)piperidine (6). Yellowish white crystals. IR (KBr) νmax 3304 (NH), 1604, 1352 (NO2) cm-1; 1H-NMR (CDCl3) δ 1.30-1.60 (6H, m), 2.15 (2H, m), 2.30-2.46 (4H, m), 2.99 (2H, t, J = 7.9 Hz), 3.41 (2H, s), 3.76 (2H, t, J = 7.2 Hz), 9.80 (1H, bs); 13C-NMR (CDCl3) δ 21.5, 24.4, 26.1, 32.1, 48.7, 54.0, 55.8, 116.1, 165.3; HRMS: calculated for C11H19N3O2 [MH]+ 226.1556, found 226.1549.
2-Methyl-1-(2-nitro-2-pyrrolidin-2-ylideneethyl)piperidine (7). Yellowish white crystals. IR (KBr) νmax 3230 (NH), 1607, 1351 (NO2) cm-1; 1H-NMR (CDCl3) δ 1.05 (3H, d, J = 6.3 Hz), 1.10-1.60 (6H, m), 1,85-2.30 (4H, m), 2.50 - 3.35 (4H, m), 3.65-3.82 (3H, m), 9.91 (1H, bs); 13C-NMR (CDCl3) δ 18.3, 21.3, 23.5, 25.9, 32.1, 34.4, 48.6, 50.8, 51.1, 56.6, 116.1, 165.4; HRMS: calculated for C12H21N3O2 [MH]+ 240.1712, found 240.1701.
1-(2-Nitro-2-pyrrolidin-2-ylideneethyl)piperidine-4-carboxylic acid ethyl ester (8). Yellowish white crystals. IR (KBr) νmax 3334 (NH), 1720 (C=O), 1616, 1352 (NO2) cm-1; 1H-NMR (CDCl3) δ 1.23 (3H, t, J = 7.1 Hz), 1.55-2.33 (9H, m), 2.72-2.83 (2H, m), 2.98 (2H, t, J = 7.9 Hz), 3.44 (2H, s), 3.76 (2H, t, J = 7.3 Hz), 4.09 (2H, q, J = 7.1 Hz), 9.85 (1H, bs); 13C-NMR (CDCl3) δ 14.2, 21.4, 28.4, 32.1, 41.2, 48.7, 52.4, 55.3, 60.2, 115.7, 165.4, 175.3; HRMS: calculated for C14H23N3O4 [MH]+ 298.1767, found 298.1762.
1-Pyrrolidin-2-yl-ethylamines (9 and 10). 2 (0.37 g, 2.0 mmol) in 20 mL EtOH was hydrogenated at 25 oC under 0.8 MPa in presence of Pd/C catalyst for 3 h, followed by filtration and evaporation to yield a colourless oil (0.16 g, 70 %) as a mixture of 9 and 10. These diastereomers were not separated. IR (liquid film) νmax 3366 br (NH) cm-1; 1H-NMR (CDCl3) δ 1.03 and 1.08 (dublets, J = 6.0 Hz, 3H), 1.25-1.90 (4H, m), 2.40-3.00 (7H, m); 13C-NMR (CDCl3) two series of signals: δ 20.7, 26.0, 28.3, 46.4, 51.4, 65.7; and δ 20.9, 25.4, 26.8, 46.6, 50.2, 64.9.
Trans- and cis-1-Methyl-1-hexahydropyrrolo[1,2-a]pyrazine-3,4-dione (11 and 12). To a mixture of 9 and 10 (540 mg, 3.43 mmol) diethyl oxalate (502 mg, 3.43 mmol) was added. The reaction mixture was stirred at 60 oC for 3 h, and the white solid formed upon cooling was separated (230 mg, 40.0%). Recrystallization from isopropyl alcohol gave the trans diastereomer 11 containing about 3% of 12 (estimated by NMR signal intensities). IR (KBr) νmax 3430, 3200 (NH), 1689, 1678 (amide-I) cm-1; NMR data, Figure 1.

General procedure for the preparation of 13-20.
The solution of 1 (1.0 mmol), a primary amine (1.0 mmol) and 0.18 g of 35% formaline (2.0 mmol) in 5 mL MeOH was stirred at 25 oC for 4-6 h. After a complete reaction monitored by TLC, the solvent was evaporated in vacuo, and the residue was crystallized and/or recrystallized. Yields and melting points are given in Table 2.
2-Methyl-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (13). Pale yellow crystals. IR (KBr) νmax 1573, 1374 (NO2) cm-1; 1H NMR (CDCl3) δ 2.12 (2H, m), 2.44 (3H, s), 3.48 (2H, t, J = 7.5 Hz), 3.56 (2H, t, J = 7.3 Hz), 3.78 (2H, s), 4.02 (2H, s); 13C NMR (CDCl3) δ 20.3, 34.1, 41.4, 50.3, 52.4, 67.2, 113.7, 159.5; HRMS: calculated for C8H14N3O2 [MH]+ 184.1086, found 184.1091.
2-Isopropyl-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (14). Pale yellow crystals. IR (KBr) νmax 1575, 1349 (NO2) cm-1; 1H NMR (CDCl3): δ 1.12 (6H, d, J = 6.5 Hz), 2.10 (2H, m), 2.89 (1H, h, J = 6.5 Hz), 3.43 (2H, t, J = 7.7 Hz), 3.56 (2H, t, J = 7.4 Hz), 3.86 (2H, s), 4.10 (2H, s); 13C NMR (CDCl3) δ 20.3 (overlapped C-7 and CH3 signals), 34.2, 45.3, 51.2, 52.1, 63.0, 115.0, 160.6; HRMS: calculated for C10H18N3O2 [MH]+ 212.1399, found 212.1399.

2-tert-Butyl-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (15). Pale yellow crystals. IR (KBr) νmax 1588, 1363 (NO2) cm-1; 1H NMR (CDCl3) δ 1.18 (9H, s), 2.11 (2H, m), 3.43 (2H, t, J = 7.8 Hz), 3.58 (2H, t, J = 7.4 Hz), 3.85 (2H, s), 4.07 (2H, s); 13C NMR (CDCl3) δ 20.3, 26.9, 34.2, 43.0, 52.2, 54.1, 60.8, 116.1, 160.6; HRMS: calculated for C11H20N3O2 [MH]+ 226.1556, found 226.1559.
2-Cyclopropyl-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (16). Pale yellow crystals. IR (KBr) νmax 1575, 1365 (NO2) cm-1; 1H NMR (CDCl3): δ 0.5-0.6 (4H, m), 2.00 (1H, m), 2.13 (2H, m), 3.49 (2H, t, J = 7.8 Hz), 3.58 (2H, t, J = 7.4 Hz), 3.94 (2H, s), 4.15 (2H, s); 13C NMR (CDCl3) δ 20.3, 34.1, 41.4, 50.3, 52.4, 67.2, 113.7, 159.5; HRMS: calculated for C10H16N3O2 [MH]+ 210.1243, found 210.1249.
2-(4-Nitro-3,5,6,7-tetrahydropyrrolo[1,2-c]pyrimidin-2-yl)ethanol (17). Pale yellow crystals. IR (KBr) νmax 3384 (OH), 1577, 1367 (NO2) cm-1; 1H NMR (CDCl3) δ 2.09 (2H, m), 2.59 (1H, bs), 2.66 (2H, t, J = 5.1 Hz), 3.44 (2H, t, J = 7.8 Hz), 3.55 (2H, t, J = 7.2 Hz), 3.67 (2H, t, J = 5.1 Hz), 3.84 (2H, s), 4.15 (2H, s); 13C NMR (CDCl3) δ 20.1, 34.3, 48.1, 52.4, 55.0, 59.4, 66.2, 113.5, 160.3; HRMS: calculated for C9H15N3O3 [MH]+ 214.1192, found 214.1187.
2-(2-Methoxyethyl)-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (18). Pale yellow crystals. IR (KBr) νmax 1576, 1351 (NO2) cm-1; 1H NMR (CDCl3) δ 2.09 (2H, m), 2.70 (2H, t, J = 5.1 Hz), 3.34 (3H, s), 3.43 (2H, t, J = 7.8 Hz), 3.52 (2H, t, J = 5.1 Hz), 3.55 (2H, t, partly overlapped, J = 7.2 Hz), 3.86 (2H, s), 4.17 (2H, s); 13C NMR (CDCl3) δ 20.2, 34.2, 48.9, 52.3, 52.7, 58.9, 66.0, 71.0, 113.6, 160.1; HRMS: calculated for C10H17N3O3 [MH]+ 228.1358, found 228.1347.
2-Benzyl-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (19). Pale yellow crystals. IR (KBr) νmax 1579, 1371 (NO2) cm-1; 1H NMR (CDCl3) δ 2.10 (2H, m), 3.46 (2H, t, J = 7.5 Hz), 3.47 (2H, t, J = 7.5 Hz), 3.69 (2H, s), 3.93 (2H, s), 4.04 (2H, s), 7.25 - 7.35 (m, 5H); 13C NMR (CDCl3) δ 20.3, 34.2, 48.7, 52.2, 57.6, 64.5, 113.9, 127.7, 128.5, 128.8, 137.1, 160.1; HRMS: calculated for C14H18N3O2 [MH]+ 260.1399, found 260.1406.
2-[2-(3,4-dimethoxyphenyl)ethyl]-4-nitro-1,2,3,5,6,7-hexahydropyrrolo[1,2-c]pyrimidine (20). Pale yellow crystals. IR (KBr) νmax 1577, 1365 (NO2) cm-1; 1H NMR (CDCl3) δ 2.09 (2H, m), 2.69-2.83 (4H, m), 3.42-3.52 (4H, m), 3.84 (3H, s), 3.86 (3H, s), 3.96 (2H, s), 4.09 (2H, s), 6.69-6.81 (3H, m); 13C NMR (CDCl3) δ 20.2, 34.2, 34.4, 48.0, 52.3, 55.1, 55.9, 66.3, 111.4, 112.0, 113.8, 120.5, 132.0, 147.6, 149,0, 160.0; HRMS: calculated for C17H24N3O4 [MH]+ 334.1767, found 334.1763.
2-Benzyloctahydropyrrolo[1,2-c]pyrimidin-4-ylamine (21 and 22). The solution of 19 (1.30 g, 5.0 mmol) in EtOH (30 mL) was hydrogenated with Raney-Ni catalyst (1.1 g) under pressure (initial pressure 0.9 MPa) at 23 oC for 6 h. After removal of the catalyst the solvent was evaporated to yield a pale yellow oily residue (1.15 g, practically complete conversion). The crude product (1.10 g) was chromatographed using an eluent mixture (EtOAc - CH2Cl2 - isopropylamine, 40/10/3) to produce the diastereomer 21 (595 mg), white crystals, mp 63-64 oC, IR (KBr) νmax 3344, 3249, 3167 (NH), 1609, 1495 (C=C) cm-1; NMR data of 21: s. Figure 2. and diastereomer 22 (74 mg), as a pale yellow oil. IR (liquid film) νmax 3400 br (NH2) cm-1; 1H-NMR (CDCl3) δ 1.60-2.20 (9H, m), 2.37-2.44 (1H, m), 3.30-3.50 (3H, m), 3.47 (2H, s), 3.86 (1H, d), 7.20-7.40 (5H, m) 13C NMR (CDCl3) δ 21.0, 24.9, 46.9, 50.6, 59.6, 59.7, 66.8, 75.5, 126.9, 128.1, 128.7, 138.1.
Octahydropyrrolo[1,2-c]pyrimidin-4-ylamine (23 and 24). The solution of the nitro compound 19 (2.20 g, 8.5 mmol in 20 mL EtOH) was hydrogenated in presence of 10% Pd/C (1.45 g) at 0.8 MPa and 20 oC. As the hydrogen consumption ceased (about 3 h), the catalyst and the solvent was removed to yield a colorless oil (1.0 g, 83%), predominantly the diastereomer 23.
The solution of 21 (190 mg) in EtOH (15 mL) was hydrogenated in presence of 10% Pd/C catalyst (120 mg) at 0.8 MPa and 23 oC. As the hydrogen absorption ceased, the catalyst and the solvent were removed to furnish 23 as a colorless oil (115 mg, in quantitative yield). 1H-NMR (CDCl3) δ 1.35-1.7 (4H, m), 1.90-2.45 (8H, m), 2.85-2.95 (2H, m), 3.82 (1H, d); 13C NMR (CDCl3) δ 20.2, 28.2, 49.8, 52.7, 53.4, 66.8, 70.4; HRMS: calculated for C7H16N3 [MH]+ 142.1344, found 142.1336.
13C NMR signals of the minor component 24 (CDCl3) δ 22.7, 23.2, 40.2, 46.3, 52.9, 57.1, 68.3.

ACKNOWLEDGEMENTS
The PhD scholarship from Szent István University to M. V. P. is gratefully acknowledged. The authors’s thanks are due to Dr. L. Balázs for the HRMS measurements.

References

1. (a) S. Rajappa, Tetrahedron, 1981, 37, 1453; CrossRef (b) D. A. Efremov, V. V. Perekalin, E. S. Lipina, and V. M. Berestovitskaya, Nitroalkenes, John Wiley & Sons Ltd, 1994.
2. M. V. Pilipecz, Z. Mucsi, P. Nemes, and P. Scheiber, Heterocycles, 2007, 71, 1919. CrossRef
3. M. V. Pilipecz, T. R. Varga, Z. Mucsi, P. Scheiber, and P. Nemes, Tetrahedron, 2008, 65, 5545. CrossRef
4. J. J. Fleming, M. D. McReynolds, and J. Du Bois, J. Am. Chem. Soc., 2007, 129, 9964. CrossRef
5. H. Ming-Hua, J. Peng, D. C. Dunbar, R. F. Schinazi, A. G. de Castro Andrews, C. Cuevas, L. F. Garcia-Fernandez, M. Kelly, and M. T. Hamann, Tetrahedron, 2007, 63, 11179, and further references therein. CrossRef
6. R. Raju, A. M. Pigott, M. Conte, W. G. L. Aalbersberg, and K. Feussner, R. J. Capon, Org. Lett., 2009, 11, 3862. CrossRef
7. E. H. Bahaji, P. Tronche, J. Couqouelet, S. Harraga, J. Panouse-Perrin, and C. Rubat, Chem. Pharm. Bull., 1991, 39, 2126.
8. (a) E. Pretsch, G. Tóth, M. E. Munk, and M. Badertscher, In Spectra Interpretation and Structure Generation, Wiley-VCH, Weinheim, 2002; (b) H. Duddeck, W. Dietrich, and G. Tóth, Structure Elucidation by Modern NMR. A workbook, Springer-Steinkopff, Darmstadt, 1998.
9. Deutsche Offen., DE 1.695.594.