HETEROCYCLES

Paper | Special issue | Vol. 80, No. 1, 2010, pp. 289-302
Received, 21st February, 2009, Accepted, 31st March, 2009, Published online, 1st April, 2009.
DOI: 10.3987/COM-09-S(S)12

■ Regioselective Synthesis of 2,4-(Dioxobutyl)dihydroquinolines and -pyridines by Chloroformiate-Mediated Reaction of 1,3-Bis(Silyl Enol Ethers) with Quinolines and Pyridines

Uwe Albrecht, Anja Preuss, Andreas Schmidt, Christine Fischer, and Peter Langer*

Institute of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany

Abstract

2,4-(Dioxobutyl)dihydroquinolines and –pyridines were prepared by chloroformiate-mediated reaction of 1,3-bis(silyl enol ethers) with quinolines and pyridines.

INTRODUCTION
Quinoline, isoquinoline, and pyridine and their derivatives are of considerable pharmacological relevance and are present in various antibiotics1, 2, 3 and natural products.4, 5 Quinolinium- and isoquinolinium salts, generated by alkylation or acylation of quinoline and isoquinoline, represent important synthetic building blocks for the synthesis of such compounds.6 Quinolines have been functionalized by the Reissert reaction. The classic variant relies on the reaction of KCN in the presence of acylating agents. In a more recent variant TMSCN in the presence of a fluoride source is employed.3, 7, 8 The addition of Grignard reagents to quinoline was reported to give 1,2-dihydroquinolines.9 The ethyl chloroformiate mediated reaction of a quinoline with (trimethylsilylethinyl)magnesium chloride was used for the synthesis of endiyne-antibiotics.9 Addition reactions of zink-,10 tin-11,12 and titanium-organometallic reagents13 to quinoline derivatives have been reported. Palladino et al. reported the benzoyl chloride mediated addition of ethyl acetoacetate to quinoline to give 2,3-dihydroquinolines.14 The reaction of 4-silyloxyquinolinium triflates with enamines afforded 2-substituted 4-silyloxy-1,2-dihydroquinolines.15 The reaction of quinolinium salts with allylsilanes in the presence of AgOTf16 and ethyl trimethylsilylacetate17, 18 afforded regioisomeric mixtures of 2- and 4-substituted dihydroquinolines. Reddy et al. reported the synthesis of benzazepines by reaction of quinolinium- and isoquinolinium salts with diazoesters.19 Two-step cyclocondensations of 1,1-bis(trimethylsilyloxy)ketene acetals with quinoline and isoquinoline have been reported by Rudler20 and ourselves.21 Tropane derivatives were prepared by cyclization of 1,3-bis(silyl enol ethers)22 with bis(iminium) salts of 2,5-dimethoxypyrrolidines.23 Recently, the cyclocondensation of 1,3-bis(silyl enol ethers) with isoquinolines,24 quinoxalines25 and quinazolines was reported.26 Herein, we report a facile synthesis of 2,4-(dioxobutyl)dihydroquinolines and –pyridines by what are, to the best of our knowledge, the first condensation reactions of 1,3-bis(silyl enol ethers) with quinolines and pyridines.

RESULTS AND DISCUSSION
1,3-Bis(silyl enol ethers) 2 are available from the corresponding 1,3-dicarbonyl compounds in one or two steps.27 The reaction of quinoline (1) with 1,3-bis(silyl enol ether) 2a, in the presence of methyl chlorformate (3a), afforded 2,3-dihydroquinoline 4a (Scheme 1). The best yields were obtained when an excess of 2a and of 3a was employed. The reactions were carried out at 0 °C. The yields dropped when the reactions were carried out at −78 °C or at 20 °C. Notably, the yield dramatically decreased when benzyl rather than methyl chloroformiate was used (vide infra). A complex mixture was formed when 1.2 equiv.of benzenesulfonyl chloride or 4-nitrobenzoyl chloride were employed. The formation of 4a can be explained by formation of quinolinium salt A, regioselective attack of the terminal carbon atom of 2a onto carbon atom C-2 of the quinolinium salt to give intermediate B, and subsequent hydrolysis.

1,3-Bis(silyl enol ethers) 2a-e were prepared from methyl, ethyl, isopropyl, methoxyethyl and isobutyl acetoacetate, respectively (Scheme 2, Table 1).27 The reaction of 2a-d with quinoline, in the presence of methyl chloroformiate (3a), afforded 1,2-dihydroquinolines 4a-d in moderate to good yields. The reaction of 2a and 2b with 1, in the presence of benzyl chloroformiate (3b) rather than methyl chloroformiate (3a), afforded 2,3-dihydroquinolines 4e and 4f, however, in only low yield. The benzyl chloroformiate mediated reaction of quinoline with 2d and 2e afforded 1,2-dihydroquinolines 4g and 4h in moderate yields. The reaction of 1,3-bis(silyl enol ethers) 2f and 2g, prepared from acetylacetone and benzoylacetone, afforded 2,3-dihydroquinolines 4i and 4j in good yields, respectively.

The benzyl chloroformiate mediated reaction of 1,3-bis(silyl enol ethers) 2h and 2i, prepared from ethyl 3-oxohexanoate and ethyl 4-ethoxyacetoacetate, afforded 1,2-dihydroquinolines 4k and 4l, respectively. Reactions of substituted quinoline derivatives have not been studied. All reactions proceeded with excellent regioselectivity. The isolated products were regioisomerically pure (>98:2). The formation of the other regioisomers, formed by attack of the diene to carbon C-4 of the quinoline, was not observed.

The methyl chloroformiate mediated reaction of pyridine (5) with 1,3-bis(silyl enol ether) 2a, carried out following the procedure as developed for the analogous reactions of quinoline, afforded the unstable 1,4-dihydropyridine 6a in low yield (Scheme 3, Table 2). The formation of 6a can be explained by formation of pyridinium salt C, regioselective attack of the terminal carbon atom of 2a onto carbon atom C-4 of the pyridinium salt to give intermediate D, and subsequent hydrolysis. It is noteworthy that the same regioselectivity was previously observed for the ethyl chloroformiate mediated reaction of pyridine with simple silyl enol ethers.28 The reaction of 5 with 1,3-bis(silyl enol ethers) 2b and 2c, in the presence of 3a, afforded 1,4-dihydropyridines 6b and 6c, again, in low yields. In contrast to the corresponding reactions of quinoline, where the use of benzyl rather than methyl chloroformiate resulted in a decrease in yield, a considerably higher yield was obtained in the reaction of 1,3-bis(silyl enol ethers) 2a and 2b with pyridine when benzyl chloroformiate was employed (products 6d and 6e). The reaction of pyridine with 1,3-bis(silyl enol ether) 2f afforded 1,4-dihydropyridine 6f. The best yield was obtained when methyl chloroformiate was used as the activating agent. The employment of 4-picoline or 2,6-lutidine proved to be unsuccessful. All reactions proceeded with excellent regioselectivity. The isolated products were regioisomerically pure (>98:2). The formation of the other regioisomers, formed by attack of the diene to carbon C-2 of the pyridine, was not observed.

The different regioselectivities observed for the reactions of 1,3-bis(silyl enol ethers) 2 with quinoline and pyridine might be explained by the assumption that the attack of the diene onto carbon atom C-4 is more sterically hinderd than the attack to C-2. The fused benzene moiety might have a stronger steric influence than the carbamate moiety. In the case of pyridine, there is no steric hindrance associated with the attack of the diene to carbon atom C-4. On the other hand, the attack of the diene to carbon C-2 is hindered by the steric influence of the carbamate group. In addition, electronic reasons might play a role.
It is worth to be noted that, for pyridine, benzyl chloroformiate gave much better results than methyl chloroformiate. The opposite is true for quinoline. This might be explained by solubility reasons. In addition, the attack of the diene to carbon atom C-2 of the quinoline is more sterically hindered by the benzyl- than by the methyl-substituted carbamate moiety. This steric hindrance plays not a role in case of pyridine as the attack of the diene occurs at carbon C-4 of the pyridine moiety.

In conclusion, we reported the synthesis of 2,4-(dioxobutyl)dihydroquinolines and –pyridines by chloroformiate-mediated reaction of 1,3-bis(silyl enol ethers) with quinolines and pyridines.

EXPERIMENTAL
General. All solvents were dried by standard methods and all reactions were carried out under an inert atmosphere. For 1H and 13C NMR, the deuterated solvents indicated were used. Mass spectrometric data (MS) were obtained by electron ionization (70 eV), chemical ionization (CI, H2O) or electrospray ionization (ESI). For preparative scale chromatography, silica gel (60-200 mesh) was used. Melting points are uncorrected.

General procedure for the reaction of 1,3-bis(silyl enol ethers) with quinoline and pyridine. To a CH2Cl2 solution of quinoline or pyridine and of the 1,3-bis(silyl enol ether) was added the cloroformate at 0 °C. The solution was allowed to warm to 20 °C during 16 h and an aqueous solution of NH4Cl (20 mL, 1 M) was added. The organic and the aqueous layer were separated and the latter was extracted with CH2Cl2 (2 x 20 mL). The combined organic layers were dried (Na2SO4), filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography (silica gel, hexane/EtOAc = 5:1). Due to the hindered rotation of the carbon-nitrogen bond of the carbamate group, a doubling of some signals was observed in 1H and 13C NMR.

Ethyl 4-(1-N-methoxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4a). Starting with 1 (0.194 g, 1.5 mmol), 3a (0.161 g, 1.7 mmol) and 2a (0.822 g, 3.0 mmol), 4a was isolated as a yellow oil (0.237 g, 50%). 1H NMR (CDCl3, 300 MHz): δ = 1.22 (t, 3J = 7.0 Hz, 3 H, CH3), 2.70 (ddd, 3J = 18.0 Hz, 3J = 8.0 Hz, 3J = 6.0 Hz, 2 H, CH2), 3.41 (d, 3J = 8.0 Hz, 1 H, CH CH2), 3.70 (s, 3 H, CH3), 4.16 (q, 3J = 7.0 Hz, 2 H, CH2), 5.49 (ddd, 3J = 6.0 Hz, 1 H, CH), 6.14 (dd, 3Jcis = 10.0 Hz, 3J = 6.0 Hz, 1 H, CH), 6.49 (d, 3Jcis = 10.0 Hz, 1 H, CH), 7.08-7.10 (m, 2 H, CH), 7.21 -7.25 (m, 1 H, CH), 7.55 (d, 3J = 8.0 Hz, 1 H, CH). 13C NMR (75 MHz, CDCl3): δ = 14.1 (CH3), 46.6 (CH2), 48.8 (CH), 49.5 (CH2), 53.2 (CH3), 61.4 (CH2), 124.6, 124.6, 125.5, 126.4, 126.8, 127.8 (CH), 128.4, 133.9, 154.5, 166.8, 200.0 (C). MS (EI, 70 eV): m/z = 316 (M+, 84), 214 (16), 183 (57), 169 (51), 116 (100). Anal. Calcd for C17H19NO5: C, 64.34; H, 6.03; N, 4.41. Found: C, 64.07; H, 5.64; N, 3.93.

Methyl 4-(1-N-methoxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4b). Starting with 1 (2.0 mmol, 1.0 equiv.), CH2Cl2 (20 mL) 2b (4.0 mmol, 2.0 equiv.) and 3a (0.23 g, 2.4 mmol, 1.2 equiv.), 4b was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a yellow oil (0.33 g, 54%). 1H-NMR (300 MHz, CDCl3): δ = 2.62 - 2.80 (m, 2 H, CH2), 3.37 - 3.50 (m, 2 H, CH2, keto), 3.71, 3.73 (2 x s, 3 H, CH3, keto, enol) 3.78, 3.80 (2 x s, 3 H, CH3, keto, enol), 4.89 (s, 1 H, CH, enol), 5.49 (dt, 3J = 6.0 Hz, 1 H, CH), 6.14 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 6.49 (d, 3Jcis = 9.0 Hz, 1 H, CH), 7.08 - 7.11 (m, 2 H, CH), 7.21 - 7.24 (m, 1 H, CH), 7.55 (br d, 3J = 8.0 Hz, 1 H, CH), 11.97 (s, 1 H, OH, enol). 13C-NMR (CDCl3, 75 MHz): δ = 46.4 (CH2), 48.7 (CH3), 49.1 (CH2), 52.3 (CH3), 53.1 (CH), 124.5, 125.5, 125.6, 126.3 (CH), 126.7 (C), 127.7, 128.2 (CH), 133.8, 154.4, 167.1, 199.8 (C). UV-Vis (λ, log ε): 231.49 (4.6). IR (KBr): [ν]= 3033 (w), 3003 (w), 2956 (m), 1748 (s), 1714 (s), 1658 (m), 1604 (w), 1572 (w), 1528 (w), 1490 (s), 1440 (s). MS (EI, 70 eV): m/z (%) = 303 (M+, 1), 244 (6), 188 (100), 144 (48), 129 (12). Anal. Calcd for C16H17NO5: C, 63.36; H, 5.65; N, 4.62. Found: C, 63.30; H, 6.08; N, 4.79.

Isopropyl 4-(1-N-methoxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4c). Starting with 1 (0.129 g, 1.0 mmol), 3a (0.104 g, 1.1 mmol) and 2c, 4c was isolated as a yellow oil (0.283 g, 90%, keto/enol = 5:1). 1H NMR (CDCl3, 300 MHz): δ = 1.22 (d, 3J = 7.0 Hz, 6H, CH3), 2.62, 2.67, (d, 3J = 6.0 Hz, 1H, CH2, keto, enol), 2.73, 2.79 (d, 3J = 8.0 Hz, 1H, CH2, keto, enol), 3.30, 3.35 (s, 1H, CH2, keto, enol), 3.38, 3.44 (s, 1H, CH2, keto, enol), 3.78 (s, 3H, CH3), 5.02 (sep., 3J = 7.0 Hz, 1H, CH), 5.49 (ddd, 3J = 6.0 Hz, 3J = 6.0 Hz, 3J = 8.0 Hz, 1H, CH), 6.15 (dd, 3J = 10.0 Hz, 3J = 6.0 Hz, 1H, CH), 6.48 (d, 3J = 10.0 Hz, 1H, CH), 7.07 – 7.10 (m, 2H, CH), 7.20 – 7.26 (m, 1H, CH), 7.54 – 7. 56 (m, 1H, CH). 13C NMR (75 MHz, CDCl3): δ = 22.0 (CH3), 46.9 (CH2), 49.2 (CH), 50.2 (CH2), 53.6, 69.5, 125.0, 125.9, 126.1, 126.8 (CH), 127.2 (C), 128.2, 128.8 (CH), 134.0, 154.6, 166.3, 200.1 (C). IR (KBr): [ν]= 3443 (w), 3037 (w), 2983 (m), 2958 (m), 2856 (w), 1710 (s), 1645 (m), 1611 (w), 1577 (w), 1490 (s), 1442 (s) cm-1. UV-Vis (MeCN): λmax (lg ε) = 234.92 (4.43) nm. MS (EI, 70 eV): m/z = 331 (M+, 1), 272 (8), 188 (100), 144 (69), 129 (14). Anal. Calcd for C18H21NO5: C, 65.24; H, 6.39; N, 4.23. Found: C, 64.87; H, 6.74; N, 3.99.

Methoxyethyl 4-(1-N-methoxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4d). Starting with 1 (0.39 g, 3.0 mmol, 1.0 equiv.), 2c (1.83 g 6.0 mmol, 2.0 equiv.), 3a (0.34 g, 3.6 mmol, 1.2 equiv.) and CH2Cl2 (20 mL), 4d was isolated by chromatography (silica gel, hexane/EtOAc = 3:1 → 2:1) as a yellow oil (0.37 g, 36%). 1H-NMR (300 MHz, CDCl3): δ = 2.63 – 2.81 (m, 2 H, CH2), 3.26 – 3.62 (m, 7 H, CH2, CH2, CH3), 3.78, 3.79 (2 x s, 3 H, CH3), 4.25 – 4.29 (m, 2 H, CH2), 4.95 (s, 1 H, CH, enol), 5.49 (dt, 3J = 7.0 Hz, 1 H, CH), 6.14 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 6.49 (d, 3Jcis = 9.0 Hz, 1 H, CH), 7.07 – 7.10 (m, 2 H, CH), 7.21 – 7.26 (m, 1 H, CH), 7.55 (m, 1 H, CH), 11.95 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3): δ = 46.5 (CH2), 48.8 (CH3), 49.3 (CH2), 50.2 (CH3), 53.2 (CH), 64.2 (CH2), 70.1 (CH2), 124.6, 125.7, 126.3, 126.4 (CH), 126.9 (C), 127.8, 128.3 (CH), 133.9, 154.4, 166.8, 199.8 (C). UV-Vis (λ, log ε): 231.40 (4.5). IR (KBr): [ν]= 2955 (w), 2931 (w), 2894 (w), 1744 (s), 1656 (w), 1489 (m), 1441 (s). MS (EI, 70 eV): m/z (%) = 347 (M+, 1), 188 (100), 144 (51), 129 (22), 60 (16). Anal. Calcd for C18H21NO6: C, 62.24; H, 6.09; N, 4.03. Found: C, 61.98; H, 6.14; N 4.19.

Ethyl 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4e). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2a (1.098 g, 4.0 mmol, 2.0 equiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and CH2Cl2 (20 mL), 4e was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a yellow oil (0.109 g, 14%). 1H-NMR (300 MHz, CDCl3): δ = 1.20 - 1.31 (t, 3J = 7.0 Hz, 3 H, CH3), 2.68 - 2.75 (m, 2 H, CH2), 3.03 - 3.39 (m, 2 H, CH2, keto), 4.11 - 4.18 (q, 3J = 7.0 Hz, 2 H, CH2), 4.86 (s, 1 H, CH, enol), 5.17 - 5.32 (m, 2 H, CH2), 5.51 (dt, 3J = 6.0 Hz, 1 H, CH), 6.13 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 7.08 - 7.10 (m, 2 H, CH2), 7.20 - 7.23 (m, 1 H, CH), 7.31 - 7.38 (m, 5 H, CH), 7.56 (m, 1 H, CH), 12.04 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3): δ = 46.4 (CH2), 48.8 (CH3), 49.4 (CH2), 50.3 (CH), 61.3 (CH2), 67.9 (CH2), 124.6, 125.5, 126.4, 126.7 (CH), 127.7 (C), 127.9, 128.0, 128.0, 128.1, 128.3, 128.5 (CH), 133.8, 153.7, 166.7, 199.9 (C). IR (KBr): [ν]= 2983 (w), 1743 (s), 1652 (m), 1606 (w), 1491 (m), 1455 (m). UV-Vis (λ, log ε): 203.87 (4.6), 232.11 (4.5). MS (EI, 70 eV) m/z (%) = 393 (M+, 1), 264 (14), 220 (18), 129 (6), 91 (100). Anal. Calcd for C23H23NO5: C, 70.22; H, 5.89; N 3.56. Found: C, 70.10; H, 6.16; N, 3.51.

Methyl 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4f). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2b (1.04 g, 4.0 mmol, 2.0 equiv.), 3b (0.82 g, 50% solution in toluene, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 4f was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a yellow oil (0.18 g, 24%). 1H-NMR (300 MHz, CDCl3): δ = 2.68 - 2.74 (m, 2 H, CH2), 3.33 - 3.41 (m, 2 H, CH2, keto), 3.69, 3.72 (2 x s, 3 H, CH3, keto, enol), 4.88 (s, 1 H, CH, enol), 5.17 - 5.32 (m, 2 H, CH2), 5.54 (dt, 3J = 6.0 Hz, 1 H, CH), 6.13 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 6.49 (d, 3Jcis = 9.0 Hz, 1 H, CH) 7.08 - 7.10 (m, 2 H, CH), 7.19 - 7.24 (m, 1 H, CH), 7.32 - 7.37 (m, 5 H, CH), 7.55 (m, 1 H, CH), 11.97 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3): δ = 46.5 (CH2), 48.9 (CH3), 49.2 (CH2), 52.4 (CH), 68.0 (CH2), 124.7, 125.6, 125.8, 126.4 (CH), 126.8 (C), 127.8, 127.9, 128.1, 128.1, 128.2, 128.6 (CH), 133.9, 153.9, 167.2, 199.8 (C). IR (KBr): [ν]= 1747 (m), 1711 (s), 1657 (w), 1634 (w), 1491 (m), 1452 (m), 1441 (m). UV-Vis (λ, log ε): 206.69 (4.2), 235.66 (4.5). MS (EI, 70 eV): m/z (%) = 379 (M+, 3), 264 (59), 220 (67), 142 (36), 91 (100). Anal. Calcd for C22H21NO5: C, 69.65; H, 5.58; N, 3.69. Found: C, 69.31; H, 5.81; N, 3.64.

Methoxyethyl 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4g). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2d (1.22 g, 4.0 mmol, 2.0 equiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 4g was isolated by chromatography (silica gel, hexane/EtOAc = 4:1) as a yellow oil (0.327 g, 39%). 1H-NMR (300 MHz, CDCl3) δ = 2.69 - 2.75 (m, 2 H, CH2), 3.18 - 3.62 (m, 7 H, CH2, CH2, CH3), 4.23 - 4.32 (m, 2 H, CH2), 4.94 (s, 1 H, CH, enol), 5.16 - 5.32 (m, 2 H, CH2, keto, enol), 5.51 (dt, 3J = 6.0 Hz, 1 H, CH), 6.14 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 6.48 (d, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 7.08 - 7.10 (m, 2 H, CH), 7.20 - 7.22 (m, 1 H, CH), 7.31 - 7.36 (m, 5 H, CH), 7.55 (m, 1 H, CH), 11.91 (s, 1 H, OH). 13C-NMR (50 MHz, CDCl3): δ = 45.5 (CH2), 47.9 (CH3), 48.3 (CH2), 57.9 (CH3), 63.2 (CH), 66.3 (CH2), 66.8 (CH2), 69.1 (CH2), 123.6, 124.5, 125.4, 125.4 (CH), 126.6 (C), 126.9, 127.0, 127.2, 127.2, 127.6 (CH), 135.5, 152.5, 166.7, 199.8 (C). UV-Vis (λ, log ε): 232.18 (4.5). IR (KBr) [ν]= 3064 (w), 3038 (w), 2981 (m), 2956 (w), 2932 (w), 2892 (m), 1654 (m), 1606 (m) 1572 (w), 1491 (s), 1454 (s). MS (EI, 70 eV) : m/z (%) = 425 (M+, 1), 264 (10), 220 (17), 129 (10), 91 (100), 45 (10). Anal. Calcd for C24H25NO6: C, 68.07; H, 5.95; N, 3.31. Found: C, 67.86; H, 6.00; N, 3.38.

Isobutoxy 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-3-oxobutanoate (4h). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2e (1.21 g, 4.0 mmol, 2.0 equiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 4h was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a yellow oil (0.399 g, 47%). 1H-NMR (300 MHz, CDCl3) δ = 0.91 (d, 3J = 7.0 Hz, 6 H, CH3), 1.87 (tqq, 3J = 8.0 Hz, 1 H, CH), 2.61 - 2.80 (m, 2 H, CH2), 3.32 - 3.45 (m, 2 H, CH2, keto), 3.86 (d, 3J = 7.0 Hz, 2 H, CH2), 4.89 (s, 1 H, CH, enol), 5.16 - 5.31 (m, 2 H, CH2), 5.53 (dt, 3J = 7.0 Hz, 1 H, CH), 6.14 (dd, 3J = 6.0 Hz, 3Jcis = 9.0 Hz, 1 H, CH), 6.49 (d, 3Jcis = 9.0 Hz, 1 H, CH), 7.07 - 7.09 (m, 2 H, CH), 7.18 - 7.24 (m, 1 H, CH), 7.31 - 7.32 (m, 5 H, CH), 7.55 (m, 1 H, CH), 12.03 (s, 1 H, OH). 13C-NMR (50 MHz, CDCl3): δ = 46.7 (CH2), 49.0 (CH3), 49.5 (CH2), 50.5 (CH3), 68.0 (CH), 124.5, 125.6, 125.8, 126.4 (CH), 126.5 (C), 127.7, 127.9, 128.1, 128.1, 128.2, 128.4 (CH), 133.8, 153.7, 166.7, 199.9 (C). UV-Vis (λ, log ε): 325.69 (4.5). IR (KBr): [ν]= 2963 (m), 1741 (s), 1652 (w), 1491 (m), 1457 (w). MS (EI, 70 eV): m/z (%) = 423 (M+, 1), 264 (16), 220 (28), 212 (10), 91 (100). Anal. Calcd for C25H27NO5: C, 71.24; H, 6.46; N, 3.32. Found: C, 71.09; H, 7.07; N, 3.46.

1-(1-N-Methoxycarboyl-2-dihydroquinolyl)-2,4-dioxopentane (4i). Starting with 1 (0.194 g, 1.5 mmol), 3a (0.161 g, 1.7 mmol) and 2f (0.732 g, 3.0 mmol), 4i was isolated as a yellow oil (0.356 g, 83%, keto/enol = 2:1). 1H NMR (CDCl3, 300 MHz): δ = 1.95 (s, 3 H, CH3), 2.28, 2.31 (d, 3J = 7.0 Hz, 2 H, CH2), 3.70 (s, 3 H, CH3), 5.32 (s, 1 H, CH), 5.34 (dt, 3J = 7.0 Hz, 1 H, CH), 6.00 (dd, 3J = 7.0 Hz, 3Jcis = 10.0 Hz, 1 H, CH), 6.44 (d, 3Jcis = 10.0 Hz, 1 H, CH), 7.01 – 7.03 (m, 2 H, CH), 7.15 – 7.19 (m, 1 H, CH), 7.45 – 7.53 (m, 1 H, CH), 15.25 (br, 1 H, OH). 13C NMR (75 MHz, CDCl3): δ = 25.1 (CH3), 41.5 (CH2), 50.1 (CH), 53.1 (CH3), 57.8 (CH2, keto), 100.9 (CH, enol), 124.5, 124.6, 125.6, 126.4 (CH), 126.9 (C), 127.8, 128.2 (CH), 134.0 (C), 154.5, 189.2, 191.9 (CO). IR (KBr): [ν]= 3409 (w), 3068 (w), 3037 (w), 2975 (m), 2931 (w), 2862 (w), 1711 (s), 1623 (s), 1532 (m), 1490 (s), 1441 (s) cm-1. UV-Vis (MeCN): λmax (lg ε) = 230.71 (4.33) nm. MS (EI, 70 eV): m/z = 287 (M+, 2), 228 (4), 188 (100), 144 (69), 129 (20). Anal. Calcd for C16H17NO5: C, 66.89; H, 5.96; N, 4.88. Found: C, 67.09; H, 6.23; N, 5.25.

4-(1-N-Methoxycarboyl-2-dihydroquinolyl)-1,3-dioxo-1-phenylbutane (4j): Starting with 1 (0.194 g, 1.5 mmol), 3a (0.161 g, 1.7 mmol) and 2g (0.918 g, 3.0 mmol), 4j was isolated as a yellow oil (0.354 g, 68%, keto/enol > 98:2). 1H NMR (CDCl3, 300 MHz): δ = 3.02 (dt, 3J = 7.0 Hz, 2 H, CH2), 4.25 (s, 1 H, CH3), 6.03 (dt, 3J = 7.0 Hz, 1 H, CH), 6.58 (s, 1 H, CH), 6.61 (dd, 3J = 7.0 Hz, 3Jcis = 10.0 Hz, 1 H, CH), 7.03 (d, 3Jcis = 10.0 Hz, 1 H, CH), 7.60 – 7.62 (m, 2 H, CH), 7.72 – 7.77 (m, 1 H, CH), 7.90 – 8.14 (m, 4 H, CH), 8.33 – 8 35 (m, 2 H, CH), 16.53 (br. s, 1 H, OH). 13C NMR (CDCl3, 75 MHz): δ = 42.26 (CH2), 50.15 (CH), 53.07 (CH3), 97.03 (CH), 121.34, 124.50 (CH), 125.07 (C), 125.64, 126.40, 127.02, 127.79, 128.53, 128.59, 132.42 (CH), 134.00, 134.74, 154.48, 183.88, 191.74 (C). IR (KBr): [ν]= 3067 (w), 2955 (s), 2926 (s), 2857 (m), 1728 (s), 1668 (m), 1603 (s), 1573 (s), 1489 (s), 1443 (s) cm-1. UV-Vis (MeCN): λmax (lg ε) = 205.84 (4.06), 232.02 (4.07) nm. MS (EI, 70 eV): m/z = 349 (M+,2), 290 (7), 210 (6), 188 (100), 144 (77). HRMS (EI, 70 eV): Calcd for C21H19NO4: m/z = 188.0837; found: 188.0837 ± 2 ppm [M+].

Ethyl 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-4-ethyl-3-oxobutanoate (4k). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2h (1.21 g, 4.0 mmol, 2.0 Äquiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 4k was isolated by chromatography (silica gel, hexane/EtOAc = 10:1) as a yellow oil (0.237 g, 28%, mixture of diastereomers). 1H-NMR (300 MHz, CDCl3) δ = 0.79 – 0.89 (m, 3 H, CH3), 1.25 – 1.39 (m, 2 H, CH2), 3.34, 3.35 (2 x s, 3 H, CH3), 4.15 – 4.26 (m, 2 H, CH2), 4.90 (s, 1 H, CH, enol), 5.34 – 5.49 (m, 2 H, CH2), 6.10 – 6.12 (m, 1 H, CH), 6.57 – 6.64 (m, 1 H, CH), 7.09 – 7.18 (m, 1 H, CH), 7.27 – 7.31 (m, 1 H, CH), 7.38 – 7.52 (m, 5 H, CH), 8.01 – 8.11 (m, 1 H, CH), 12.25 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3) δ = 12.0 (CH3), 22.7 (CH2), 40.1 (CH3), 51.4 (CH2), 60.1 (CH), 68.1 (CH2), 121.7, 124.9, 126.1, 126.9 (CH), 127.6 (C), 128.0, 128.1, 128.3, 128.4, 128.4, 128.5, 128.5, 128.9 (CH), 135.5, 152.0, 166.5, 205.3 (C). IR (KBr): [ν]= 3067 (w), 3035 (w), 2968 (m), 2936 (m), 2878 (w), 1712 (s), 1652 (s), 1489 (s), 1457 (s). MS (EI, 70 eV): m/z (%) = 285 (24). UV (λ, log ε): 205.99 (4.3), 235.92 (4.2). Anal. Calcd for C25H27NO5: C, 71.24; H, 6.46; N, 3.32. Found: C, 71.14; H, 6.01; N, 3.09.

Ethyl 4-(1-N-benzyloxycarboyl-2-dihydroquinolyl)-4-ethyoxy-3-oxobutanoate (4l). Starting with 1 (0.26 g, 2.0 mmol, 1.0 equiv.), 2i (1.27 g, 4.0 mmol, 2.0 equiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 4l was isolated (silica gel, hexane/EtOAc = 10:1) as a yellow oil (0.400 g, 46%, mixture of diastereomers). 1H-NMR (300 MHz, CDCl3): δ = 0.95 – 1.05 (t, 3J = 7.0 Hz, 3 H, CH3), 1.23 – 1.35 (m, 2 H, CH2), 3.29 – 3.62 (m, 5 H, CH2, CH3), 4.14 – 4.19 (m, 2 H, CH2), 4.70 (s, 1 H, CH, enol), 5.28 – 5.38 (m, 2 H, CH2), 5.96 (q, 1 H, CH), 6.58 – 6.61 (m, 1 H, CH), 7.07 – 7.09 (m, 1 H, CH), 7.10 – 7.17 (m, 1 H, CH), 7.27 – 7.39 (m, 5 H, CH), 8.01 – 8.05 (m, 1 H, CH), 12.55 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3): δ = 13.9, 14.0, 14.7, 14.8 (CH3), 41.4, 41.5 (CH), 45.5, 45.7 (CH2), 46.4, 46.7 (CH2), 53.3 (CH), 61.1, 61.1 (CH2), 67.6, 67.7 (CH2), 84.9 (CH), 89.3 (CH), 97.6 (CH), 106.9 (CH), 122.8, 124.2, 124.6, 126.1, 126.5, 127.7, 127.8, 127.9, 128.0, 128.6, 128.9, 129.1 (CH), 135.7, 152.1, 166.9, 173.8, 203.5 (C). UV-Vis (λ, log ε): 204.32 (4.4), 236.88 (4.3). IR (KBr): [ν]= 3066 (w), 3035 (w), 2979 (m), 2936 (m), 2899 (w), 2877 (w), 1655 (s), 1499 (s), 1454 (m). MS (EI, 70 eV): m/z (%) = 438 (M+, 4), 262 (14), 220 (19), 91 (100), 29 (13). Anal. Calcd for C25H27NO6: C, 68.64; H, 6.22; N, 3.20. Found: C, 68.64; H, 6.22; N, 3.20.

Ethyl 4-(1-(N-methoxycarbonyl–4-dihydropyridyl)-3-oxobutanoate (6a). Starting with 5 (0.16 g, 2.0 mmol, 1.0 equiv.), 2a (1.09 g, 4.0 mmol, 2.0 equiv.), 3a (0.23 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 6a was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a red oil (0.115 g, 22%). 1H-NMR (300 MHz, CDCl3) δ = 1.33 (t, 3J = 7.0 Hz, 3 H, CH3), 2.66 (d, 3J = 7.0 Hz, 2 H, CH2), 3.42 - 3.52 (m, 3J = 8.0 Hz, 2 H, CH2, keto), 3.77, 3.79 ( 2 x s, 3 H, CH3), 4.16 - 4.23 (q, 3J = 7.0 Hz, 2 H, CH2), 4.84 - 4.87 (m, 1 H, CH), 5.03 (s, 1 H, CH, enol), 6.71 - 6.84 (m, 2 H, CH), 7.15 - 7.17 (m, 1 H, CH), 8.57 - 8.59 (m, 1 H, CH), 12.01 (s, 1 H, OH). Due to the instability of the compound, a 13C-NMR spectrum could not be obtained. UV-Vis (λ, log ε): 228.96 (4.1). IR (KBr): [ν]= 2984 (w), 2960 (w), 1722 (s), 1696 (s), 1654 (m), 1636 (m), 1445 (s). MS (EI, 70 eV): m/z (%) = 267 (M+, 7), 221 (31), 138 (93), 94 (40), 93 (100). Anal. Calcd for C13H17NO5: C, 58.42; H, 6.41; N, 5.24. Found: C, 58.77; H, 6.39; N, 5.36.

Methyl 4-(1-(N-methoxycarbonyl–4-dihydropyridyl)-3-oxobutanoate (6b). Starting with 5 (0.16 g, 2.0 mmol, 1.0 equiv.), CH2Cl2 (20 mL), 2b (4.0 mmol, 2.0 equiv.) and 3a (0.23 g, 2.4 mmol, 1.2 equiv.), 6b was isolated by chromatography (silica gel, hexane/EtOAc = 7:1 → 5:1) as a red oil (0.107 g, 21%). 1H-NMR (300 MHz, CDCl3): δ = 2.65 (d, 3J = 7.0 Hz, 2 H, CH2), 3.38 - 3.52 (m, 2 H, CH2, keto), 3.73, 3.74 (2 x s, 3 H, CH3, keto, enol), 3.80, 3.83 (2 x s, 3 H, CH3), 4.84 - 4.87 (m, 1 H, CH), 4.99 (s, 1 H, CH, enol), 6.72 - 6.83 (m, 2 H, CH), 7.15 - 7.17 (m, 1 H, CH), 8.57 - 8.59 (m, 1 H, CH), 12.02 (s, 1 H, OH). Due to the instability of the compound, a 13C-NMR spectrum could not be obtained. UV-Vis (λ, log ε): 229.41 (4.1). IR (KBr): [ν]= 2957 (w), 1695 (s), 1660 (w), 1634 (m), 1444 (s). MS (EI, 70 eV): m/z (%) = 253 (M+, 17), 252 (100), 178 (39), 150 (90), 101 (66). Anal. Calcd for C12H15NO5: C, 56.91; H, 5.97; N, 5.53. Found: C, 56.54; H, 5.34; N, 5.53.

Methoxyethyl 4-(1-(N-methoxycarbonyl–4-dihydropyridyl)-3-oxobutanoate (6c). Starting with 5 (0.316 g, 4.0 mmol), 3a (0.568 g, 6.0 mmol), and 2d (2.430 g, 8.0 mmol), 6c was isolated as a yellow oil (0.241 g, 20%, keto/enol = 5:1). 1H NMR (CDCl3, 300 MHz): δ = 2.50 (d, 3J = 7.0 Hz, 1 H, CH), 3.16 – 3.19 (m, 3 H, CH, CH2, keto, enol), 3.30 (s, 3 H, CH3, enol), 3.32 (s, 3 H, CH3, keto), 3.30-3.43 (m, 2 H, CH2, keto, enol), 3.58 (s, 3 H, CH3, enol), 3.60 (s, 3 H, CH3, keto), 4.07 – 4.10 (m, 2 H, CH2, keto, enol), 4.58-4.75 (m, 2 H, CH, keto), 4.86 (s, 1 H, CH, enol), 4.89 – 5.19 (m, 1 H, CH, enol), 5.39 – 5.81 (m, 1 H, CH, enol), 6.39 – 6.69 (m, 1 H, CH, keto), 11.81 (s, 1 H, OH, enol). 13C NMR (75 MHz, CDCl3): δ = 29.6, 30.2 (CH, keto, enol), 49.2, 49.5 (CH2, keto, enol), 51.2 (CH2, keto), 53.0, 53.1, 58.4, 58.5 (CH3, keto, enol), 63.8, 63.9, 69.9, 70.0 (CH2, keto, enol), 89.3 (CH, enol), 108.2, 108.7, 122.4, 122.6 (CH, keto, enol), 151.98, 150.99, 166.3, 166.5, 171.6, 200.2 (C, keto, enol).

Ethyl 4-(1-(N-benzyloxycarbonyl–4-dihydropyridyl)-3-oxobutanoate (6d). Starting with 5 (0.16 g, 2.0 mmol, 1.0 equiv.), 2a (1.09 g, 4.0 mmol, 2.0 equiv.), 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 6d was isolated by chromatography (silica gel, hexane/EtOAc = 10:1) as a red oil (0.453 g, 66%). 1H-NMR (300 MHz, CDCl3) δ = 1.28 (t, 3J = 7.0 Hz, 3 H, CH3), 2.65 (d, 3J = 7.0 Hz, 2 H, CH2), 3.41 (s, 1 H, CH), 3.47 (q, 3J = 9.0 Hz, 2 H, CH2), 4.16 - 4.23 (m, 2 H, CH2,), 4.83 - 4.90 (m, 1 H, CH), 5.19 - 5.27 (m, 2 H, CH2), 5.29 (s, 1 H, CH, enol), 5.90 - 5.96 (m, 1 H, CH), 6.76 - 6.86 (m, 2 H, CH), 7.30 - 7.38 (m, 5 H, CH). 13C-NMR (50 MHz, CDCl3): δ = 28.3 (CH), 49.9 (CH2), 51.7 (CH2), 61.5 (CH2), 68.2 (CH2), 124.8, 126.8 (CH), 127.4 (C), 127.9, 128.0, 128.1 (CH), 135.5, 166.8, 200.7 (C). IR (KBr) [ν]= 3466 (w), 3442 (w), 3065 (w), 3035 (w), 2983 (m), 2938 (w), 2905 (w), 1650 (m), 1638 (m), 1583 (w), 1498 (w), 1451 (m). MS (EI, 70 eV): m/z = 343 (M+, 2), 170 (14), 93 (24), 92 (16), 91 (100). Anal. Calcd for C19H21NO5: C, 66.46; H, 6.16; N, 4.08. Found: C, 65.40; H, 5.93; N, 3.98.

Methyl 4-(1-(N-benzyloxycarbonyl–4-dihydropyridyl)-3-oxobutanoate (6e). Starting with 5 (0.16 g, 2.0 mmol, 1.0 equiv.), 2b (1.04 g, 4.0 mmol, 2.0 equiv.) and 3b (0.41 g, 2.4 mmol, 1.2 equiv.), and 20 mL of CH2Cl2, 6e was isolated by chromatography (silica gel, hexane/EtOAc = 7:1) as a red oil (0.414 g, 63%). 1H-NMR (300 MHz, CDCl3): δ = 2.64 (d, 3J = 7 Hz, 2 H, CH2), 3.42 - 3.52 (m, 2 H, CH2, keto), 3.72, 3.73 (2 x s, 3 H, CH3, keto, enol), 4.82 - 4.92 (m, 1 H, CH), 5.19 - 5.26 (m, 2 H, CH2), 5.29 (s, 1 H, CH, enol), 5.90 - 5.95 (m, 1 H, CH), 6.68 - 6.86 (m, 2 H, CH), 7.30 - 7.41 (m, 5 H, CH), 12.01 (s, 1 H, OH). 13C-NMR (75 MHz, CDCl3): δ = 28.2 (CH), 49.2 (CH2), 51.5 (CH2), 52.3 (CH3), 68.1 (CH2), 124.9, 126.9 (CH), 127.5 (C), 128.1, 128.2, 128.6 (CH), 135.5, 167.3, 200.7 (C). UV-Vis (λ, log ε): 207.79 (4.0). IR (KBr): [ν]= 1746 (m), 1715 (s), 1651 (w), 1635 (w). MS (EI, 70 eV): m/z (%) = 329 (M+, 1), 214 (6), 170 (16), 92 (17), 91 (100). Anal. Calcd for C18H19NO5: C, 65.64; H, 5.81; N, 4.25. Found: C, 63.88; H, 5.24; N, 4.00.

1-(1-N-Methoxycarboyl-4-dihydropyridyl)-2,4-dioxopentane (6f). Starting with 5 (0.119 g, 1.5 mmol), 3a (0.213 g, 2.3 mmol), and 2f (0.732 g, 3.0 mmol), 6f was isolated as a yellow oil (0.126 g, 35%, keto/enol = 3:1). 1H NMR (CDCl3, 300 MHz): δ = 2.07 (s, 3 H, CH3), 2.36 (d, 3J = 7.0 Hz, 2 H, CH2), 3.43 (m, 1 H, CH), 3.57 (s, 2 H, CH2, keto), 3.77 (s, 3 H, CH3), 4.82 - 4.91 (m, 2 H, CH), 5.48 (s, 1 H, CH, enol), 6.68 – 6.85 (m, 2 H, CH), 15.43 (br, 1 H, OH). 13C NMR (75 MHz, CDCl3): δ = 25.0 (CH3), 30.1 (CH), 47.2 (CH2), 52.3 (CH2, keto), 53.3 (CH3), 100.9 (CH, enol), 108.5, 108.9, 123.2, 123.2 (CH, keto, enol), 151.7, 190.5, 191.7 (C). IR (KBr): [ν]= 3437 (w), 2958 (m), 2923 (w), 1725 (s), 1697 (s), 1630 (s), 1610 (s), 1444 (s), 1417 (m) cm-1. UV-Vis (MeCN): λmax (lg ε) = 228.52 (4.03) nm. MS (EI, 70 eV): m/z = 237 (M+, 10), 138 (100), 94 (62), 84 (32), 60 (14). Anal. Calcd for C12H15NO4: C, 60.75; H, 6.37; N, 5.90. Found: C, 61.09; H, 6.71; N, 5.52.

ACKNOWLEDGEMENTS
Financial support from the State of Mecklenburg-Vorpommern (scholarship for A. S.) is gratefully acknowledged.

References

1. R. B. Herbert, J. D. Philipson, M. F. Roberts, and M. H. Zenk, 'The Chemistry and Biology of Isoquinoline Alkaloids', Springer, Berlin, 1985.
2. H. Rimpler, 'Biogene Arzneistoffe', Deutscher Apotheker Verlag, Stuttgart, 1999.
3. N. D. Priestley, T. M. Smith, P. R. Shipley, and H. G. Floss, Bioorg. Med. Chem., 1996, 4, 1135. CrossRef
4. W. Steglich, B. Fugmann, and S. Lang-Fugmann, 'Römpp-Lexikon Naturstoffe' Georg Thieme Verlag, Stuttgart, New York, 1997.
5. W.-T. Chang, S.-S. Lee, F.-S. Chueh, and K. C. S. Liu, Phytochemistry, 1998, 48, 119. CrossRef
6. E. F. V. Scriven, 'Pyridines and their Benzo Derivatives: (ii) Reactivity at Ring Atoms', Vol. 2, Part 2A, Chapt. 2.05, ed. by A. J. Boulton and A. McKillop, in 'Comprehensive Heterocyclic Chemistry', ed. by A. R. Katritzky and C. W. Rees, Elsevier Science, Oxford, 1984, p. 165.
7. F. Diaba, C. Le Houerou, M. Grignon-Dubois, and P. Gerval, J. Org. Chem., 2000, 65, 907. CrossRef
8. M. Takamura, K. Funabashi, M. Kanai, and M. Shibasaki, J. Am. Chem. Soc., 2001, 123, 6801. CrossRef
9. J. J. Eisch and D. R. Comfort, J. Org. Chem., 1975, 40, 2288. CrossRef
10. M.-J. Wu, C.-F. Lin, H.-T. Chen, and T.-H. Duh, Bioorg. Med. Chem. Lett., 1996, 6, 2183. CrossRef
11. T. G. Dhar and C. Gluchowski, Tetrahedron Lett., 1994, 7, 989. CrossRef
12. R. Yamaguchi, M. Moriyasu, M. Yoshioka, and M. Kawanisi, J. Org. Chem., 1988, 53, 3507, and references cited therein. CrossRef
13. L.-L. Gundersen, F. Rise, and K. Undheim, Tetrahedron, 1992, 48, 5647. CrossRef
14. G. F. Palladino and W. E. McEwen, J. Org. Chem., 1978, 43, 2420. CrossRef
15. U. Beifuss and M. Taraschewski, J. Chem. Soc., Perkin Trans. 1, 1997, 2807. CrossRef
16. R. Yamaguchi, T. Nakayasu, B. Hatabo, T. Nagura, S. Kozima, and K. Fujita, Tetrahedron, 2001, 57, 109. CrossRef
17. F. Diaba, C. Le Houerou, M. Grignon-Dubois, and P. Gerval, J. Org. Chem., 2000, 65, 907. CrossRef
18. F. Diaba, C. Le Houerou, M. Grignon-Dubois, B. Rezzonico, and P. Gerval, Eur. J. Org. Chem., 2000, 2915. CrossRef
19. J. S. Yadav, B. V. S. Reddy, M. K. Gupta, A. Prabhakar, and B. Jagadeesh, Chem. Commun., 2004, 2124. CrossRef
20. H. Rudler, B. Denise, A. Parlier, and J.-C. Daran, Eur. J. Org. Chem., 2005, 3724. CrossRef
21. E. Ullah, S. Rotzoll, A. Schmidt, D. Michalik, and P. Langer, Tetrahedron Lett., 2005, 46, 8997. CrossRef
22. U. Albrecht, H. Armbrust, and P. Langer, Synlett, 2004, 143. CrossRef
23. P. Langer, Synthesis, 2002, 4, 441. CrossRef
24. A. Schmidt, J.-P. Gütlein, A. Preuss, U. Albrecht, H. Reinke, and P. Langer, Synlett, 2005, 2489. CrossRef
25. A. Schmidt, J.-P. Gütlein, and P. Langer, Tetrahedron Lett., 2007, 48, 2067. CrossRef
26. V. Karapetyan, S. Mkrtchyan, A. Schmidt, J.-P. Gütlein, A. Villinger, H. Reinke, H. Jiao, C. Fischer, and P. Langer, Org. Biomol. Chem., 2008, 2961. CrossRef
27. T.-H. Chan and P. Brownbridge, J. Am. Chem. Soc., 1980, 102, 3534; CrossRef G. A. Molander and K. O. Cameron, J. Am. Chem. Soc., 1993, 115, 830; CrossRef K. Krägeloh and G. Simchen, Synthesis, 1981, 30. CrossRef
28. K. Akiba, Y. Nishihara, and M. Wada, Tetrahedron Lett., 1983, 24, 5269. CrossRef