Tertiary enamines of acetoacetic ester, obtained with morpholine and piperidine, add to 2-R1-3-nitro-2Н-chromenes (R1 = CF3, CCl3, Ph) via the vinylogue β-methyl group and give the respective cis,trans-2,3,4-trisubstituted chromans, the stereoconfiguration of which was established by X-ray structural analysis. Acidic hydrolysis of these compounds was accompanied by decarboxylation and produced 4-acetonyl-3-nitrochromans with retention of configuration.
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2H-Chromene and its derivatives belong to an important class of oxygen-containing heterocyclic compounds, which are common in plants and show various types of biological activity.1 The presence of electron-withdrawing substituents in the pyran fragment of these molecules increases the reactivity of С(3)=С(4) bond with regard to nucleophiles, and for this reason 2Н-chromenes are valuable substrates for the preparation of more complex heterocycles. Of particular synthetic value are 3-nitro-2H-chromenes, featuring a double bond conjugated with a nitro group.2 The introduction of a trihalomethyl group at position 2 of nitrochromene system further increases the reactivity of double bond in pyran ring and offers rich synthetic possibilities for interactions of 3-nitro-2-trihalomethyl-2Н-chromenes3 with various C-, N-, S-nucleophiles, which have been studied in detail.4 However, their reactions with pushpull enamines remain little known. Only one study5 describes the reactions of 2-aryl-3-nitro-2Н-chromenes with methyl β-methylaminocrotonate, leading to mixtures consisting of product from nucleophilic addition at the С-4 atom of chromene and the respective chromeno[3,4-b]-pyrrole formed by its further Grob cyclization.
Recently we studied the reactions of 2-trifluoromethyland 2-trichloromethyl-3-nitro-2Н-chromenes 1 with enamines of acetoacetic ester, acetylacetone, and benzoylacetone,6 , 7 and showed that the regio- and stereochemistry of the addition products changed in the direction from primary and secondary enamines (obtained from ammonia, methylamine, and benzylamine) to tertiary enamines (obtained from morpholine and piperidine). While in the first case the reaction involved the most nucleophilic α-carbon atom of enamine and led to the formation of chromans 2 as trans,trans diastereomers with Z-configuration of double bond, tertiary enamines added via their β-Me vinylogous group and gave cis,trans-chromans 3 with E-configuration of double bond (preliminary report,6 Scheme 1).
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Due to the rare occurrence of the latter direction involving methyl group of enamine, usually observed only in the series of highly electrophilic ketones and imines,8 we undertook a more detailed study of the reaction between 3-nitro-2Н-chromenes and tertiary enamines, based on acetoacetic ester. In the current work, we present complete data about the interaction of 2-substituted 3-nitro-2Н-chromenes with ethyl β-morpholino- and β-piperidinocrotonates, as well as conversion of the obtained addition products to 4-acetonylchromans under the conditions of acidic hydrolysis.
We established that 2-trifluoromethyl-, 2-trichloromethyl-, and 2-phenyl-3-nitro-2Н-chromenes 1a–h smoothly reacted with acetoacetic ester enamines 4a,b in a minimum amount of acetonitrile (0.2–0.4 ml for 1.0 mmol of reagent) over 1–2 days at room temperature, and gave ethyl 3-morpholino(piperidino)-4-(3-nitrochroman-4-yl)-2-butenoates 5a–l in 14–79% yields after recrystallization from a 2:1 hexane–dichloromethane system. The lowest yields of adducts 5e,f,j,k (14–41%) were obtained from chromenes 1d,g containing an electron-donating МеО group at position 6 (Scheme 2, Table 1).
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The structure of the obtained compounds was established from elemental analysis, IR spectroscopy, 1Н and 19F NMR spectroscopy, and X-ray structural analysis. The addition reaction occurred at the С-4 atom of chromene via the vinylogous β-Me group without elimination of nitrous acid fragments, and compounds 5a–l were formed only as the cis,trans diastereomers (3 J Н2,Н3 ≈ 3 J Н3,Н4 ≈ 1.5 Hz, ct-isomer)9 with E-configuration of the double bond. The stereoconfiguration of 2,3,4-trisubstituted chromans 5a–l was confirmed by monocrystal X-ray structural analysis of compounds 5b,i (Fig. 1 and 2). The CF3 group was observed in 19F NMR spectra of trifluoromethylated chromans 5a–f in CDCl3 as a doublet at 86.7 ppm (J = 6.0 Hz). We should note that an analogous reaction between conjugated nitroalkenes and enamines of β-dicarbonyl compounds was previously described only for the example of α-(trichloroethylidene)nitroalkanes.10
The molecular structure of compound ct- 5b with atoms represented by thermal vibration ellipsoids of 50% probability.
The molecular structure of compound ct- 5i with atoms represented by thermal vibration ellipsoids of 50% probability.
We have recently shown7 that adducts 3 (R = Me) during refluxing in methanol in the presence of hydrochloric acid either underwent hydrolysis to the respective chroman β-diketones 7 (R1 = CCl3) or cyclized to chromenopyridines 8 (R1 = CF3) (Scheme 3). For this reason, we were interested in studying the behavior of addition products 5a–l under analogous conditions. We found that the ester group hydrolysis in ct-chromans 5a–l upon heating for 6 h in 70% ethanol or methanol in the presence of a catalytic amount of hydrochloric acid was accompanied by decarboxylation and gave the acetonyl derivatives 6a–l with the same pyran ring configuration (3 J Н2,Н3 ≈ 3 J Н3,Н4 ≈ 2.0 Hz, ct-isomer)9 in 16–91% yields (Scheme 3, Table 1). The lowest yields (16–19%) were observed in the case of 4-acetonylchroman 6e, obtained by hydrolysis of adducts 5e,f with the MeO group at position 6.
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We previously obtained compounds 6a,h by tandem condensation of о-hydroxybenzylideneacetone with (E)-1-nitro-3,3,3-trifluoro(trichloro)propenes.6 However, the reaction in this case was less stereoselective and chromans 6a,h were formed as a mixture of two diastereomers (ct:tt = 80:20 in the case of compound 6а and tc:tt = 72:28 in the case of compound 6h). A whole series of cis,trans-4-acetonyl-2-aryl-3-nitrochromans, including chroman 6l, was recently synthesized by direct addition of acetone to 2-aryl-3-nitro-2Н-chromenes in the presence of pyrrolidine and benzoic acid.11
It should be noted that performing the hydrolysis in ethanol in the case of CCl3-adducts 5i–k led to a partial or complete epimerization at the С-3 atom linked to the NO2 group, therefore the expected chromans ct-6i,j were accompanied by their isomers tc- 6i,j, of which the isomer tc- 6j was isolated as pure compound in 65% yield (3 J Н2,Н3 ≈ 3 J Н3,Н4 ≈ 5.5 Hz, tc-isomer).9 Apparently, the main factor determining the stereoconfiguration of products 5 and 6 is the preferred trans configuration of substituents at positions 2 and 4 of the chroman system (Scheme 4).
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The cis,trans configuration of chromans 5, identified from the analysis of NMR coupling constants, was confirmed by monocrystal X-ray structural study of compounds 5b,i. The structure of diastereomer ct- 5b is presented in Figure 1, showing that the methylene and nitro groups occupy axial positions, while the trifluoromethyl group takes an equatorial position, corresponding to the assigned configuration of diastereomer ct- 5b. The pyran ring had a conformation of slightly twisted half-chair, explained by steric interactions between its bulky substituents. The C(4)–C(3)–C(2)–C(1) and С(5)–C(4)–C(3)–N(2) torsion angles were −177.8(2) and 80.8(2)°, respectively, while the angle formed by С(6)–С(5)–С(4) plane and methylene group was 74.0(3)°. The same conformation of heterocycle was also found in the structurally related chroman 5i, containing a trichloromethyl group instead of trifluoromethyl group (Fig. 2).
The aminoenone fragment was practically planar in both cases, explained by delocalization of the lone electron pair of nitrogen atom with the ester carbonyl group. For example, the N(1)–C(13)–C(12)–C(11) torsion angle in chroman 5b was equal to −174.9(2)°, while the analogous angle in chroman 5i was smaller by only 3.6°. The angles between benzene and aminoenone fragment planes in molecules of compounds 5b,i were respectively 172.0(2)° (i.e., these fragments were nearly coplanar) and 134.0(2)° (i.e., the presence of relatively bulky trichloromethyl group forced a rotation of aminoenone fragment with respect to the chroman system).
Thus, reactions of 2-substituted 3-nitro-2Н-chromenes with tertiary enaminoesters obtained from cyclic amines produced cis,trans-3-amino-4-(3-nitrochroman-4-yl)-2-butenoates, which gave 4-acetonylchromans upon acidic hydrolysis. The described polyfunctional products are promising intermediates for the synthesis of more complex heterocyclic compounds, including molecules with trifluoroand trichloromethyl groups.
Experimental
IR spectra were recorded on a PerkinElmer Spectrum BX-II instrument using an ATR accessory for compounds 5e, 6d, 6e, tc -6j and in KBr for the rest of the compounds. 1Н and 19F NMR spectra were acquired on a Bruker DRX-400 spectrometer (400 and 376 MHz, respectively), 13C NMR spectra were acquired on a Bruker Avance-500 spectrometer (126 MHz) in CDCl3, internal standards were TMS and C6F6 (−162.9 ppm). Elemental analysis was performed on an automated PE 2400 analyzer. Melting points were determined on an SMP40 apparatus. 3-Nitro-2Н-chromenes 1 were obtained according to a published procedure.3
Preparation of chromans 5a–l (General method). A mixture of the appropriate chromene 1 (1.0 mmol) and ethyl (E)-3-piperidinocrotonate (4a) (0.20 g, 1.0 mmol) or ethyl (E)-3-morpholinocrotonate (4b) (1.0 mmol) in anhydrous acetonitrile (0.4 ml) was heated at 50°C until dissolution (1–2 min) and maintained for 1–2 days at ~20°C. The precipitate that formed was filtered off and recrystallized from a 1:2 mixture of hexane–dichloromethane.
Ethyl ( E )-3-morpholino-4-[(2 S * ,3 R * ,4 S * )-3-nitro-2-(trifluoromethyl)chroman-4-yl]but-2-enoate (5a). Yield 79%. White powder. Mp 174–175°C (decomp.). IR spectrum, ν, cm−1: 1677, 1585, 1557, 1495, 1481, 1449, 1394, 1379. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.79 (1H, dd, J = 15.3, J = 4.4, 4'-CH aHb); 3.22 (2H, dt, J = 12.8, J = 4.9) and 3.33 (2H, dt, J = 12.8, J = 4.9, N(CH2)2); 3.39 (1H, dd, J = 12.2, J = 4.4, 4-CH); 3.76 (4H, t, J = 4.9, O(CH2)2); 4.05 (1H, dq, J = 10.9, J = 7.1) and 4.12 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.18 (1H, dd, J = 15.3, J = 12.2, 4'-CHa H b); 5.06 (1H, s, 2'-CH); 5.15 (1H, br. s, 3-CH); 5.20 (1H, qd, J = 6.0, J = 1.4, 2-CH); 7.06 (1H, td, J = 7.5, J = 1.2, H-6); 7.07 (1H, dd, J = 8.2, J = 1.2, H-8); 7.17 (1H, d, J = 7.7, H-5); 7.26 (1H, ddd, J = 8.2, J = 7.3, J = 1.5, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 14.3; 32.6; 38.4; 47.4; 59.7, 66.3; 70.6 (q, J = 34.1, C-2); 77.4, 94.2; 117.6; 120.8; 122.2 (q, J = 280.7, CF3); 122.9; 128.3; 128.8; 152.0; 159.2; 168.4 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 86.7 (d, J = 6.0, CF3). Found, %: С 54.12; Н 5.11; N 6.34. C20H23F3N2O6. Calculated, %: С 54.05; Н 5.22; N 6.30.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-bromo-3-nitro-2-(trifluoromethyl) chroman-4-yl]-3-(1-piperidinyl)but-2-enoate (5b). Yield 76%. White powder. Mp 154–155°C (decomp.). IR spectrum, ν, cm−1: 1666, 1583, 1559, 1478, 1448, 1411, 1395, 1378. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 1.56–1.72 (6H, m, 3CH2); 2.75 (1H, dd, J = 15.5, J = 4.5, 4′-CH aHb); 3.27–3.40 (5H, m, N(CH2)2, 4-CH); 4.02 (1H, dq, J = 10.9, J = 7.1) and 4.09 (1H, dq, J =10.9, J = 7.1, OCH2); 4.25 (1H, br. t, J = 14.0, 4′-CHa H b); 5.00 (1H, s, 2′-CH); 5.11 (1H, br. s, 3-CH); 5.27 (1H, qd, J = 6.0, J = 1.3, 2-CH); 6.95 (1H, d, J = 8.8, H-8); 7.30 (1H, d, J = 2.3, H-5); 7.35 (1H, dd, J = 8.8, J = 2.3, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 14.4; 24.3; 25.6; 32.6; 38.2; 48.5; 59.4; 70.7 (q, J = 34.4, C-2); 91.8; 114.9; 119.3; 122.1 (q, J = 280.9, CF3); 123.4; 131.0; 131.7; 151.2; 158.4; 169.0 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 86.7 (d, J = 6.0, CF3). Found, %: С 48.49; Н 4.58; N 5.43. C21H24BrF3N2O5. Calculated, %: С 48.38; Н 4.64; N 5.37.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-bromo-3-nitro-2-(trifluoromethyl) chroman-4-yl]-3-morpholinobut-2-enoate (5с). Yield 67%. Colorless prisms. Mp 169–170°C (decomp.). IR spectrum, ν, cm−1: 1673, 1582, 1561, 1482, 1450, 1413, 1371. 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.77 (1H, dd, J = 15.2, J = 4.6, 4′-CH aHb); 3.21 (2H, dt, J = 12.8, J = 4.9) and 3.30 (2H, dt, J = 12.8, J = 4.9, N(CH2)2); 3.36 (1H, dd, J = 12.2, J = 4.6, 4-CH); 3.76 (4H, t, J = 4.9, O(CH2)2); 4.03 (1H, dq, J = 10.9, J = 7.1) and 4.12 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.15 (1H, br. t, J = 13.3, 4′-CHa H b); 5.07 (1H, s, 2′-CH); 5.12 (1H, br. s, 3-CH); 5.21 (1H, qd, J = 6.0, J = 1.4, 2-CH); 6.96 (1H, d, J = 8.8, H-8); 7.27 (1H, d, J = 2.3, H-5); 7.36 (1H, dd, J = 8.8, J = 2.3, H-7). 1H NMR spectrum (C6D6), δ, ppm (J, Hz): 1.06 (3H, t, J = 7.1, CH3); 2.19 (2H, dt, J = 12.8, J = 4.9, N(CH aHb)2); 2.34 (2H, dt, J = 12.8, J = 4.9, N(CHa H b)2); 3.03 (4H, t, J = 4.9, O(CH2)2); 3.15 (1H, dd, J = 12.1, J = 4.6, 4-CH); 3.79 (1H, br. s, 4′-CHa H b); 3.96 (1H, dq, J = 10.9, J = 7.1) and 4.04 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.78 (1H, s, 2′-CH); 5.31 (1H, br. s, 3-CH); 5.41 (1H, br. q, J = 6.1, 2-CH); 6.56 (1H, d, J = 8.8, H-8); 6.94 (1H, dd, J = 8.8, J = 2.3, H-7); 7.13 (1H, d, J = 2.3, H-5); the signal of the 4'-CH aHb proton is masked at about 2.19 ppm. 13C NMR spectrum (CDCl3), δ, ppm (J, Hz): 14.3; 32.4; 38.2; 47.5; 59.8; 66.3; 70.7 (q, J = 34.4, C-2); 94.6; 115.0; 119.4; 122.1 (q, J = 280.9, CF3); 123.0; 131.0; 131.9; 151.2; 158.8; 168.5 (C=O). 19F NMR spectrum (CDCl3), δ, ppm (J, Hz): 86.7 (d, J = 6.0, CF3). 19F NMR spectrum (C6D6), δ, ppm (J, Hz): 88.0 (d, J = 6.1, CF3). Found, %: С 45.99; Н 4.22; N 5.36. C20H22BrF3N2O6. Calculated, %: С 45.90; Н 4.24; N 5.35.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-3,6-dinitro-2-(trifluoromethyl)-chroman-4-yl]-3-(1-piperidinyl)but-2-enoate (5d). Yield 49%. Light-yellow powder. Mp 142–143°C (decomp.). IR spectrum, ν, cm−1: 1673, 1600, 1555, 1527, 1484, 1445,1382, 1349. 1H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t, J = 7.1, СН3); 1.60–1.75 (6H, m, 3CH2); 2.90 (1H, br. d, J = 15.0, 4′-CH aHb); 3.30–3.40 (4H, m, N(CH2)2); 3.44 (1H, dd, J = 12.1, J = 4.9, 4-CH); 4.00 (1H, dq, J = 10.9, J = 7.1) and 4.08 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.14–4.27 (1H, m, 4'-CHa H b); 5.02 (1H, s, 2′-CH); 5.17 (1H, br. s, 3-CH); 5.47 (1H, br. q, J = 6.0, 2-CH); 7.18 (1H, d, J = 9.0, H-8); 8.12 (1H, d, J = 2.5, H-5); 8.17 (1H, dd, J = 9.0, J = 2.5, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 14.4; 24.3; 25.6; 32.5; 38.4; 48.6; 59.5; 71.0 (q, J = 34.8, C-2); 92.2; 118.3; 121.9 (q, J = 280.9, CF3); 122.0; 124.5; 124.9; 142.9; 156.9; 157.9; 169.1 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 86.7 (d, J = 5.9, CF3). Found, %: С 51.75; Н 4.99; N 8.55. C21H24F3N3O7. Calculated, %: С 51.75; Н 4.96; N 8.62.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-methoxy-3-nitro-2-(trifluoromethyl) chroman-4-yl]-3-(1-piperidinyl)but-2-enoate (5e). Yield 37%. White powder. Mp 147–148°C (decomp.). IR spectrum, ν, cm−1: 1668, 1575, 1556, 1488, 1447, 1429, 1395, 1371. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 1.52−1.72 (6H, m, 3CH2); 2.70–2.82 (1Н, m, 4′-CH aHb); 3.27−3.41 (5H, m, N(CH2)2, 4-CH); 3.80 (3H, s, СН3O); 4.02 (1H, dq, J = 10.8, J = 7.1) and 4.09 (1H, dq,J = 10.8, J = 7.1, OCH2); 4.27 (1H, br. t, J = 13.4, 4′-CHa H b); 5.00 (1H, s, 2′-CH); 5.11 (1H, br. s, 3-CH); 5.21 (1H, br. q, J = 6.0, 2-CH); 6.73 (1H, d, J = 2.8, H-5); 6.82 (1H, dd, J = 9.0, J = 2.8, H-7); 6.99 (1H, d, J = 9.0, H-8). 13C NMR spectrum, δ, ppm (J, Hz): 14.4; 24.4; 25.5; 32.8; 38.6; 48.4; 55.8; 59.3; 71.8 (q, J = 34.2, C-2); 91.5; 113.6; 113.9; 118.1; 122.1; 122.3 (q, J = 280.6, CF3); 124.5; 146.1; 154.9; 158.9; 169.0 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 86.7 (d, J = 6.0, CF3). Found, %: С 55.64; Н 5.81; N 5.95. C22H27F3N2O6. Calculated, %: С 55.93; Н 5.76; N 5.93.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-methoxy-3-nitro-2-(trifluoromethyl) chroman-4-yl]-3-morpholinobut-2-enoate (5f). Yield 41%. White powder. Mp 145–146°C (decomp.). IR spectrum, ν, cm−1: 1687, 1675, 1581, 1558, 1500, 1450, 1374. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.79 (1H, dd, J = 15.0, J = 4.5, 4'-CH aHb); 3.21 (2H, dt, J = 13.0, J = 4.9) and 3.31 (2H, dt, J = 13.0, J = 4.9, N(CH2)2); 3.36 (1H, dd, J = 12.2, J = 4.5, 4-CH); 3.75 (4H, t, J = 4.9, O(CH2)2); 3.80 (3H, s, СН3O); 4.04 (1H, dq, J = 10.9, J = 7.1) and 4.11 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.17 (1H, br. t, J = 13.4, 4′-CHa H b); 5.06 (1H, s, 2′-CH); 5.11 (1H, br. s, 3-CH); 5.13 (1H, br. q, J = 6.0, 2-CH); 6.69 (1H, d, J = 2.8, H-5); 6.83 (1H, dd, J = 9.0, J = 2.8, H-7); 7.00 (1H, d, J = 9.0, H-8). 13C NMR spectrum, δ, ppm (J, Hz): 14.3; 32.5; 38.6; 47.4; 55.8; 59.6; 66.3; 70.8 (q, J = 34.1, C-2); 77.4; 94.3; 113.7; 113.9; 118.2; 121.7; 122.3 (q, J = 280.7, CF3); 146.0; 155.0; 159.2; 168.4 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 86.7 (d, J = 6.0 Hz, CF3). Found, %: С 53.10; Н 5.19; N 5.88. C21H25F3N2O7. Calculated, %: С 53.16; Н 5.31; N 5.90.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-3-nitro-2-(trichloromethyl)-chroman-4-yl]-3-(1-piperidinyl)but-2-enoate (5g). Yield 54%. White powder. Mp 171–172°C (decomp.). IR spectrum, ν, cm−1: 1678, 1588, 1554, 1488, 1456, 1397, 1377. 1H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t, J = 7.1, СН3); 1.54–1.72 (6H, m, 3CH2); 2.84 (1H, dd, J = 15.4, J = 4.5, 4'-CH aHb); 3.26–3.42 (5H, m, N(CH2)2, 4-CH); 4.04 (1H, dq, J = 10.9, J = 7.1) and 4.08 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.45 (1H, br. t, J = 13.6, 4′-CHa H b); 5.02 (1H, s, 2′-CH); 5.26 (1H, s, 2-CH); 5.57 (1H, s, 3-CH); 7.06 (1H, t, J = 7.6, H-6); 7.12 (1H, d, J = 8.1, H-8); 7.22 (1H, d, J = 7.6, H-5); 7.26 (1H, t, J = 7.5, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 14.5; 24.4; 25.6; 32.6; 39.9; 48.5; 59.3; 59.4; 78.3; 80.1; 91.9; 96.0; 117.4; 121.2; 122.6; 128.5; 152.7; 159.2; 168.9 (C=O). Found, %: С 51.19; Н 5.08; N 5.67. C21H25Cl3N2O5. Calculated, %: С 51.29; Н 5.12; N 5.70.
Ethyl ( E )-3-morpholino-4-[(2 S * ,3 R * ,4 S * )-3-nitro-2-(trichloromethyl)chroman-4-yl]but-2-enoate (5h). Yield 41%. White powder. Mp 190–191°C (decomp.). IR spectrum, ν, cm−1: 1680, 1588, 1553, 1489, 1455, 1397, 1378. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.91 (1H, dd, J = 15.4, J = 4.5, 4′-CHaHb); 3.20 (2H, dt, J = 12.8, J = 4.9) and 3.29 (2H, dt, J = 12.8, J = 4.9, N(CH2)2); 3.40 (1H, dd, J = 11.9, J = 5.5, 4-CH); 3.68–3.75 (4H, m, O(CH2)2); 4.06 (1H, dq, J = 10.9, J = 7.1) and 4.11 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.32 (1H, br. t, J = 13.7, 4′-CHaHb); 5.08 (1H, s, 2′-CH); 5.17 (1H, br. d, J = 0.7, 2-CH); 5.60 (1H, br. s, 3-CH); 7.06 (1H, t, J = 7.6, H-6); 7.13 (1H, d, J = 8.1, H-8); 7.19 (1H, d, J = 7.6, H-5); 7.28 (1H, t, J = 7.8, H-7). Found, %: С 48.55; Н 4.58; N 5.63. C20H23Cl3N2O6. Calculated, %: С 48.65; Н 4.70; N 5.67.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-bromo-3-nitro-2-(trichloromethyl) chroman-4-yl]-3-morpholinobut-2-enoate (5i). Yield 56%. Colorless prisms. Mp 209–210°C (decomp.). IR spectrum, ν, cm−1: 1673, 1583, 1556, 1480, 1449, 1400, 1354. 1H NMR spectrum (CDCl3), δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.85 (1H, dd, J = 15.2, J = 5.4, 4′-CH aHb); 3.19 (2H, dt, J = 12.8, J = 4.9) and 3.27 (2H, dt, J = 12.8, J = 4.8, N(CH2)2); 3.36 (1H, dd, J = 11.6, J = 5.4, 4-CH); 3.73 (4H, t, J = 4.8, O(CH2)2); 4.06 (1H, dq, J = 10.9, J = 7.1) and 4.10 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.31 (1H, br. t, J = 13.4, 4′-CHa H b); 5.08 (1H, s, 2′-CH); 5.18 (1H, d, J = 1.4, 2-CH); 5.56 (1H, br. s, 3-CH); 7.03 (1H, d, J = 8.8, H-8); 7.28 (1H, d, J = 2.2, H-5); 7.38 (1H, dd, J = 8.8, J = 2.2, H-7). 1H NMR spectrum (C6D6), δ, ppm (J, Hz): 1.05 (3H, t, J = 7.1, СН3); 2.21–2.38 (5H, m, 4′-CH aHb, N(CH)2); 3.07 (4H, t, J = 4.8, O(CH2)2); 3.12 (1H, dd, J = 11.4, J = 5.9, 4-CH); 3.96–4.08 (3H, m, 4′-CHa H b, OCH2); 4.86 (1H, s, 2′-CH); 5.43 (1H, d, J = 1.0, 2-CH); 5.76 (1H, br. s, 3-CH); 6.69 (1H, d, J = 8.8, H-8); 6.96 (1H, dd, J = 8.8, J = 2.2, H-7); 7.11 (1H, d, J = 2.2, H-5). Found, %: С 41.78; Н 3.74; N 4.95. C20H22BrCl3N2O6. Calculated, %: С 41.95; Н 3.87; N 4.89.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-methoxy-3-nitro-2-(trichloromethyl) chroman-4-yl]-3-(1-piperidinyl)but-2-enoate (5j). Yield 26%. White powder. Mp 172–173°C (decomp.). IR spectrum, ν, cm−1: 1673, 1579, 1555, 1497, 1456, 1421, 1380. 1H NMR spectrum, δ, ppm (J, Hz): 1.23 (3H, t, J = 7.1, СН3); 1.54–1.72 (6H, m, 3CH2); 2.83 (1H, dd, J = 15.4, J = 4.5, 4′-CH aHb); 3.24–3.40 (5H, m, 4-CH, N(CH2)2); 3.81 (3H, s, CH3O); 4.04 (1H, dq, J = 10.9, J = 7.1) and 4.07 (1H, dq, J = 10.9, J = 7.1, OCH2); 4.45 (1H, br. t, J = 13.4, 4′-CHa H b); 5.02 (1H, s, 2′-CH); 5.19 (1H, s, 2-CH), 5.54 (1H, s, 3-CH); 6.73 (1H, d, J = 2.8, H-5); 6.84 (1H, dd, J = 8.9, J = 2.8, H-7); 7.06 (1H, d, J = 8.9, H-8). 13C NMR spectrum, δ, ppm: 14.5; 24.3; 25.6; 32.5; 40.1; 44.5; 48.5; 55.8; 59.3; 78.2; 80.3; 92.0; 96.0; 113.6; 118.0; 122.0; 146.7; 154.8; 159.2; 168.8 (C=O). Found, %: С 50.43; Н 5.51; N 5.63. C22H27Cl3N2O6. Calculated, %: С 50.64; Н 5.22; N 5.37.
Ethyl ( E )-4-[(2 S * ,3 R * ,4 S * )-6-methoxy-3-nitro-2-(trichloromethyl) chroman-4-yl]-3-morpholinobut-2-enoate (5k). Yield 14%. White powder. Mp 180–181°C (decomp.). IR spectrum, ν, cm−1: 1679, 1578, 1554, 1498, 1448, 1397, 1354. 1H NMR spectrum, δ, ppm (J, Hz): 1.24 (3H, t, J = 7.1, СН3); 2.89 (1H, dd, J = 15.5, J = 5.2, 4'-CH aHb); 3.19 (2H, dt, J = 12.9, J = 4.9) and 3.27 (2H, dt, J = 12.9, J = 4.9, N(CH2)2); 3.36 (1H, dd, J = 11.7, J = 5.2, 4-CH); 3.72 (4H, t, J = 4.9, O(CH2)2); 3.80 (3H, s, СН3O); 4.06 (1H, dq, J = 10.7, J = 7.1) and 4.09 (1H, dq, J = 10.7, J = 7.1, OCH2); 4.31 (1H, br. t, J = 13.6, 4'-CH a H b); 5.07 (1H, s, 2'-CH); 5.10 (1H, s, 2-CH); 5.56 (1H, s, 3-CH); 6.70 (1H, d, J = 2.9, H-5); 6.85 (1H, dd, J = 9.0, J = 2.9, H-7); 7.07 (1H, d, J = 9.0, H-8). 13C NMR spectrum, δ, ppm: 14.4; 32.2; 40.2; 47.6; 55.9; 59.6; 66.3; 78.2; 80.4; 94.8; 96.0; 113.6; 113.9; 118.1; 121.7; 146.8; 154.9; 159.5; 168.2 (C=O). Found, %: С 47.94; Н 4.83; N 5.30. C21H25Cl3N2O7. Calculated, %: С 48.15; Н 4.81; N 5.35.
Ethyl ( E )-3-morpholino-4-[(2 S * ,3 R * ,4 S * )-3-nitro-2-phenylchroman-4-yl]but-2-enoate (5l). Yield 63%. White powder. Mp 178–179°C (decomp.). IR spectrum, ν, cm−1: 1685, 1584, 1549, 1489, 1451, 1391, 1377. 1H NMR spectrum, δ, ppm (J, Hz): 1.31 (3H, t, J = 7.1, СН3); 2.83 (1H, dd, J = 15.3, J = 4.0, 4'-CH a Hb); 3.20 (2H, dt, J = 12.8, J = 5.0) and 3.36 (2H, dt, J = 12.8, J = 5.0, N(CH2)2); 3.45 (1H, dd, J = 12.3, J = 4.0, 4-CH); 3.68–3.78 (4H, m, O(CH2)2); 4.15 (1H, dq, J = 10.8, J = 7.1) and 4.20 (1H, dq, J = 10.8, J = 7.1, OCH2); 4.43 (1H, dd, J = 15.3, J = 12.3, 4'-CHa H b); 5.06 (1H, d, J = 1.9, 2-CH); 5.07 (1H, s, 2'-CH); 5.78 (1H, d, J = 1.9, 3-CH); 7.03 (1H, t, J = 7.6, H-6); 7.06 (1H, d, J = 8.4, H-8); 7.20–7.27 (2H, m, H-5, H-7); 7.34–7.53 (5H, m, Н Ph). 13C NMR spectrum, δ, ppm: 14.5; 32.9; 38.1; 47.4; 59.5; 66.3; 72.9; 85.5; 94.0; 117.7; 121.4; 121.8; 125.9; 128.1; 128.4; 128.5; 128.6; 136.2; 153.9; 160.2; 168.6 (C=O). Found, %: С 66.42; Н 6.34; N 6.24. C25H28N2O6. Calculated, %: С 66.36; Н 6.24; N 6.19.
Preparation of 4-acetonylchromans 6a–l (General method). A mixture of the appropriate chroman 5a–l (1.0 mmol), H2O (1.0 ml), EtOH or MeOH (3.0 ml), and conc. HCl (0.4 ml) was stirred and refluxed for 6 h. The mixture was then cooled to room temperature, the precipitate was filtered off, washed with water (2×1 ml), dried, and recrystallized from a 1:1 mixture of hexane and dichloromethane, yielding compounds 6a–l as white powders.
1-[(2 S * ,3 R * ,4 S * )-3-Nitro-2-(trifluoromethyl)chroman-4-yl]propan-2-one ( ct -6a). Yield 44% (EtOH). Mp 109–110°C. IR spectrum, ν, cm−1: 1719, 1585, 1564, 1490, 1375. 1H NMR spectrum, δ, ppm (J, Hz): 2.23 (3H, s, СН3); 2.80 (1H, dd, J = 18.8, J = 9.7) and 3.05 (1H, dd, J = 18.8, J = 3.8, CH2); 3.97 (1H, br. d, J = 8.8, 4-CH); 4.52 (1H, qd, J = 5.9, J = 2.2, 2-CH); 5.16 (1H, t, J = 2.0, 3-CH); 7.02 (1H, dd, J = 8.3, J = 1.0, H-8); 7.06 (1H, td, J = 7.3, J = 1.0, H-6); 7.13 (1H, dd, J = 7.7, J = 1.3, H-5); 7.24 (1H, td, J = 7.6, J = 1.3, H-7). 19F NMR spectrum, δ, ppm (J, Hz): 87.0 (d, J = 5.9, CF3). Found, %: С 51.62; Н 4.03; N 4.49. C13H12F3NO4. Calculated, %: С 51.49; Н 3.99; N 4.62.
1-[(2 S * ,3 R * ,4 S * )-6-Bromo-3-nitro-2-(trifluoromethyl)-chroman-4-yl]propan-2-one ( ct -6c). Yield 65% (EtOH), 63% (MeOH). Mp 135–136°C. IR spectrum, ν, cm−1: 1715, 1563, 1481, 1409, 1368. 1H NMR spectrum, δ, ppm (J, Hz): 2.25 (3H, s, СН3); 2.80 (1H, dd, J = 19.0, J = 9.5) and 3.04 (1H, dd, J = 19.0, J = 3.5, CH2); 3.94 (1H, br. d, J = 8.8, 4-CH); 4.51 (1H, qd, J = 5.8, J = 2.0, 2-CH); 5.15 (1H, t, J = 1.5, 3-CH); 6.92 (1H, d, J = 8.8, H-8); 7.27 (1H, d, J = 2.3, H-5); 7.35 (1H, dd, J = 8.8, J = 2.3, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 30.1; 33.3; 49.3; 70.7 (q, J = 34.6, C-2); 78.4; 115.6; 119.1; 121.8 (q, J = 281.5, CF3); 123.0; 131.1; 131.8; 150.8; 203.7 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 87.0 (d, J = 5.8, CF3). Found, %: С 40.76; Н 2.80; N 3.67. C13H11BrF3NO4. Calculated, %: С 40.86; Н 2.90; N 3.67.
1-[(2 S * ,3 R * ,4 S * )-3,6-Dinitro-2-(trifluoromethyl)-chroman-4-yl]propan-2-one ( ct -6d). Yield 38% (MeOH). Mp 166–167°C. IR spectrum, ν, cm−1: 1720, 1588, 1560, 1521, 1486, 1434, 1409, 1352. 1H NMR spectrum, δ, ppm (J, Hz): 2.27 (3H, s, СН3); 2.90 (1H, dd, J = 19.1, J = 9.5) and 3.11 (1H, dd, J = 19.1, J = 3.6, CH2); 4.03 (1H, br. d, J = 9.0, 4-CH); 4.68 (1H, qd, J = 5.8, J = 2.0, 2-CH); 5.26 (1H, t, J = 1.8, 3-CH); 7.17 (1H, d, J = 9.0, H-8); 8.13 (1H, d, J = 1.8, H-5); 8.16 (1H, dd, J = 9.0, J = 1.8, H-7). 13C NMR spectrum, δ, ppm (J, Hz): 30.1; 33.5; 48.8; 71.0 (q, J = 35.0, C-2); 77.9; 118.2; 121.6 (q, J = 281.6, CF3); 121.9; 124.6; 124.7; 143.4; 156.3; 203.4 (C=O). 19F NMR spectrum, δ, ppm (J, Hz): 87.1 (d, J = 5.8, CF3). Found, %: С 45.06; Н 3.00; N 7.80. C13H11F3N2O6. Calculated, %: С 44.84; Н 3.18; N 8.04.
1-[(2 S * ,3 R * ,4 S * )-6-Methoxy-3-nitro-2-(trifluoromethyl)-chroman-4-yl]propan-2-one ( ct -6e) was extracted from the reaction mixture with chloroform (2×1 ml), dried over Na2SO4, and purified by column chromatography (eluent – chloroform). The solvents were removed at reduced pressure and the residue was recrystallized from a 1:1 mixture of hexane–dichloromethane. Yield 19% (from 5e in MeOH), 16% (from 5f in MeOH). Mp 88–89°C. IR spectrum, ν, cm−1: 1711, 1566, 1495, 1444, 1423, 1412, 1400, 1365, 1348. 1H NMR spectrum, δ, ppm (J, Hz): 2.23 (3H, s, СН3); 2.79 (1H, dd, J = 18.8, J = 9.3) and 3.06 (1H, dd, J = 18.8, J = 3.8, CH2); 3.77 (3H, s, MeO); 3.94 (1H, br. d, J = 7.8, 4-CH); 4.47 (1H, qd, J = 5.9, J = 1.5, 2-CH); 5.11 (1H, br. t, J = 1.5, 3-CH); 6.63 (1H, d, J = 2.6, H-5); 6.80 (1H, dd, J = 9.0, J = 2.6, H-7); 6.95 (1H, d, J = 9.0, H-8). 13C NMR spectrum, δ, ppm (J, Hz): 30.2; 33.8; 49.6; 55.7; 70.8 (q, J = 34.3, C-2); 78.9; 112.9; 114.7; 118.1; 121.5; 122.0 (q, J = 281.4, CF3); 145.6; 155.4; 204.1 (C=O). 19F NMR spectrum, δ, ppm: 87.0 (d, J = 5.9, CF3). Found, %: С 50.40; Н 3.93; N 4.05. C14H14F3NO5. Calculated, %: С 50.46; Н 4.23; N 4.20.
1-[(2 S * ,3 R * ,4 S * )-3-Nitro-2-(trichloromethyl)chroman-4-yl]propan-2-one ( ct -6h). Yield 56% (EtOH). Mp 79–80°C (hexane). IR spectrum, ν, cm−1: 1717, 1591, 1559, 1487, 1371. 1H NMR spectrum, δ, ppm (J, Hz): 2.25 (3H, s, CH3); 2.78 (1H, dd, J = 18.8, J = 9.8) and 3.06 (1H, dd, J = 18.8, J = 3.8, CH2); 3.96 (1H, br. dd, J = 9.8, J = 3.5, 4-CH); 4.46 (1H, br. s, 2-CH); 5.56 (1H, s, 3-CH), 7.04–7.18 (3H, m, Н Ar), 7.24–7.30 (1H, m, Н Ar). Found, %: С 44.31; Н 3.23; N 3.72. C13H12Cl3NO4. Calculated, %: С 44.28; Н 3.43; N 3.97.
1-[(2 S * ,3 R * ,4 S * )-6-Bromo-3-nitro-2-(trichloromethyl)-chroman-4-yl]propan-2-one ( ct -6i). Yield 47% (MeOH). Mp 183−184°C. IR spectrum, ν, cm−1: 1715, 1561, 1483, 1408, 1365. 1H NMR spectrum, δ, ppm (J, Hz): 2.26 (3H, s, СН3); 2.78 (1H, dd, J = 19.0, J = 9.8) and 3.04 (1H, dd, J = 19.0, J = 3.7, CH2); 3.93 (1H, dd, J = 9.8, J = 3.7, 4-CH); 4.45 (1H, s, 2-CH); 5.54 (1H, s, 3-CH); 7.00 (1H, d, J = 8.8, H-8); 7.29 (1H, d, J = 2.0, H-5); 7.37 (1H, dd, J = 8.8, J = 2.0, H-7). 13C NMR spectrum, δ, ppm: 30.2; 35.2; 50.1; 79.1; 80.7; 95.2; 115.4; 119.0; 123.1; 131.1; 131.7; 151.8; 203.6 (C=O). Hydrolysis of compound 5i in ethanol at 60°C gave a mixture of ct- and tc-isomers in 84:16 ratio and 77% total yield. 1H NMR spectrum, δ, ppm (J, Hz): tc-6i (16%): 2.22 (3H, s, CH3); 2.82 (1H, dd, J = 18.3, J = 7.0) and 2.98 (1H, dd, J = 18.3, J = 6.9, CH2); 4.12 (1H, q, J = 6.0, 4-CH); 5.36 (1H, d, J = 5.3, 2-CH); 5.48 (1H, t, J = 5.5, 3-CH); 7.01 (1H, d, J = 8.8, H-8); 7.30 (1H, d, J = 2.3, H-5); 7.41 (1H, dd, J = 8.8, J = 2.3, H-7). Found, %: С 36.07; Н 2.39; N 3.20. C13H11BrCl3NO4. Calculated, %: С 36.19; Н 2.57; N 3.25.
1-[(2 S * ,3 R * ,4 S * )-6-Methoxy-3-nitro-2-(trichloromethyl)-chroman-4-yl]propan-2-one ( ct -6j). Yield 91% (from 5j in MeOH), 85% (from 5k in MeOH). Mp 165–166°C. 1H NMR spectrum, δ, ppm (J, Hz): 2.25 (3H, s, СН3); 2.79 (1H, dd, J = 18.8, J = 9.7) and 3.06 (1H, dd, J = 18.8, J = 3.8, CH2); 3.78 (3H, s, СН3O); 3.93 (1H, dd, J = 9.7, J = 3.7, 4-CH); 4.42 (1H, s, 2-CH); 5.51 (1H, s, 3-CH); 6.64 (1H, d, J = 2.8, H-5); 6.83 (1H, dd, J = 9.0, J = 2.8, H-7); 7.04 (1H, d, J = 9.0, H-8). 13C NMR spectrum, δ, ppm: 30.2; 35.7; 50.3; 55.7; 79.6; 80.9; 95.5, 112.9; 114.7; 118.0; 121.5; 146.6; 155.3; 204.0 (C=O). Hydrolysis of compound 5j in EtOH at 60°C gave a mixture of ct- and tc-isomers in 89:11 ratio and 68% total yield. Found, %: С 43.95; Н 3.48; N 3.60. C14H14Cl3NO5. Calculated, %: С 43.95; Н 3.69; N 3.66.
1-[(2 S * ,3 S * ,4 S * )-6-Methoxy-3-nitro-2-(trichloromethyl)-chroman-4-yl]propan-2-one ( tc -6j). Yield 65% (from 5k in EtOH). Mp 86–87°C. IR spectrum, ν, cm−1: 1714, 1560, 1499, 1409, 1369. 1H NMR spectrum, δ, ppm (J, Hz): 2.19 (3H, s, СН3); 2.82 (1H, dd, J = 18.3, J = 7.1, CHH); 2.97 (1H, dd, J = 18.3, J = 6.9, CHH); 3.78 (3H, s, СН3O); 4.11 (1H, q, J = 6.0, 4-CH); 5.34 (1H, d, J = 5.8, 2-CH); 5.42 (1H, t, J = 5.4, 3-CH); 6.70 (1H, d, J = 2.8, H-5); 6.80 (1H, dd, J = 9.0, J = 2.8, H-7); 7.04 (1H, d, J = 9.0, H-8).
1-[(2 S * ,3 R * ,4 S * )-3-Nitro-2-phenylchroman-4-yl]-propan-2-one ( ct -6l). Yield 82% (EtOH). Mp 185–186°C (mp 170.5–171.5°С).11 IR spectrum, ν, cm−1: 1710, 1587, 1545, 1490, 1371. 1H NMR spectrum, δ, ppm (J, Hz): 2.27 (3H, s, СН3); 2.92 (1H, dd, J = 18.4, J = 9.8) and 3.13 (1H, dd, J = 18.4, J = 4.0, CH2); 3.98 (1H, dd, J = 9.8, J = 4.0, 4-CH); 5.04 (1H, t, J = 2.0, 3-CH); 5.26 (1H, d, J = 2.1, 2-CH); 7.00–7.06 (2H, m, H-6,8); 7.17 (1H, dd, J = 8.3, J = 1.4, H-5); 7.23 (1H, ddd, J = 8.7, J = 7.3, J = 1.4, H-7); 7.35–7.45 (5H, m, H Ph). Found, %: С 69.40; Н 5.50; N 4.42. C18H17NO4. Calculated, %: С 69.44; Н 5.50; N 4.50.
X-Ray structural study of chromans 5b,i was performed at 20°C temperature on an Xcalibur S diffractometer with a CCD-detector according to standard method (МоKα-radiation, graphite monochromator, ω-scanning, 2θmax 52°). Compound 5b. The crystals of compound 5b (C21H24BrF3N2O5, M 523.31) were monoclinic; a 11.3487(10), b 8.7553(7), c 22.362(2) Å; β 95.612(7)°; V 2211.3(3) Å3; Z 4; space group P2(1)/n; d calc 1.345 g·cm−3; μ 1.923 cm−1; F(000) 1064. A total of 18370 reflections were collected, including 5168 independent, and 1874 reflections were used for refinement (I > 2σ(I)). The final probability factor values: R 1 0.0392, wR 2 0.0530, GOF 1.001 (Δρmin/Δρmax = 0.436/–0.436 e·Å−3).
Compound 5i. Crystals of compound 5i (C20H22BrCl3N2O6, M 572.66) were monoclinic; a 12.0862 (11), b 12.0044(7), c 17.4391(16) Å; β 106.161(8)°; V 2430.2(3) Å3; Z 4; space group P2(1)/n; d calc 1.565 g·cm−3; μ 2.059 cm−1; F(000) 1160. A total of 22261 reflections were collected, including 7908 independent, and 2997 reflections were used for refinement (I > 2σ(I)). The final probability factor values: R 1 0.0334, wR 2 0.0512, GOF 1.008 (Δρmin/Δρmax = 0.585/–0.560 e·Å−3).
The structures of compounds 5b,i were solved by direct method, using the SHELX97 software suite.12 All nonhydrogen atoms were refined independently in anisotropic approximation, while hydrogen atoms were placed in geometrically calculated positions and included in refinement according to the "rider" model with dependent thermal parameters. The complete X-ray structural data sets for compounds 5b,i were deposited at the Cambridge Crystallographic Data Center (deposits CCDC 1046820 and CCDC 915041, respectively).
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The results of this work were obtained within the framework of fulfilling the State Assignment of the Ministry of Education and Science of Russia, with partial financial support from the Russian Foundation for Basic Research (project No. 14-03-00179).
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Translated from Khimiya Geterotsiklicheskikh Soedinenii, 2015, 51(5), 440–446
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Korotaev, V.Y., Kutyashev, I.B., Barkov, A.Y. et al. Stereoselective addition of ethyl 3-morpholino(piperidino)-crotonates to 2-trihalomethyl-3-nitro-2H-chromenes. Synthesis of 4-acetonyl-3-nitrochromans. Chem Heterocycl Comp 51, 440–446 (2015). https://doi.org/10.1007/s10593-015-1718-1
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DOI: https://doi.org/10.1007/s10593-015-1718-1