Abstract
An efficient transition-metal-free approach toward C–H bond activation by using molecular \(\hbox {I}_{2}\)-mediated \({ sp}^{3}\) C–H bond functionalization for the synthesis of indolizine derivatives via 1,3-dipolar cycloaddition reaction of nitrogen ylides with ynones is described.
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Introduction
Indolizines are important bridgehead nitrogen heterocycles which have received much attention due to their interesting molecular structures featuring \(10~\uppi \)-delocalized electrons [1]. Indolizine derivatives have potential pharmaceutical applications that have encouraged the design and synthesis of new analogues with increased pharmacological activities [1, 2]. Compounds containing the indolizine moiety have a wide range of biological activities, such as anticancer agents [3], calcium entry blockers [4], antimycobacterial agents [5], and HIV inhibitors [6]. Furthermore, substituted indolizines have been used extensively as versatile building blocks for the synthesis of dyes [7], biological markers [8, 9], and electroluminescent materials [10, 11] with enhanced electronic and photonic properties. Thus, efficient new approaches for the preparation of chemically and biologically relevant indolizines are of importance in chemical research.
Many substituted indolizines have been synthesized by conventional routes such as the Schmidt reaction [12], the Tschitschibabin reaction [13], 1,5-dipolar cyclizations [14, 15], and 1,3-dipolar cycloadditions of pyridinium methylides with electron-deficient alkynes or alkenes [16,17,18].
The pyridinium methylide may be prepared by two approaches: route (1) involves phenacyl bromide and pyridine [16], and route (2) requires an \(\hbox {I}_{2}\)-mediated C–H activation of acetophenone followed by reaction with pyridine (Scheme 1). The later method features a much broader scope on indolizine synthesis using pyridinium N-methylide derivatives.
Direct functionalization of relatively unreactive C–H bonds has become a major topic of research in organic synthesis. This methodology, based on atom- and step-economic principles, plays a crucial role in modern sustainable organic chemistry [19,20,21]. For this purpose, the functionalization of \({ sp}^{3}\) C–H bonds has received considerable attention in recent years [18].
Results and discussion
Recently, C–H activation reactions of acetophenone with various nucleophiles have emerged as a powerful tool in organic synthesis [22,23,24,25,26,27,28]. However, reactions involving the \({ sp}^{3}\) C–H bond have suffered inherent problems due to weak coordination. Recently, the metal-catalyzed C–H activation of alkyl-substituted azine N-oxides and N-iminopyridinium ylides has been reported [29, 30]. Several catalysts based on Pd, Cu, Ni, Ru, and Ir are particularly well known to serve this purpose. However, molecular iodine is a viable alternative and may be a promising catalyst for the synthesis of indolizine derivatives due to its high tolerance to air and moisture, low cost, and non-toxicity. Recently, the metal-free iodine-mediated C–H activation of alkyl azaarenes has been reported [31, 32]. Our group has also reported the synthesis of functionalized indolizines by 1,3-dipolar cycloaddition reaction of azomethine ylides via the iodine-mediated reaction of 2-methylquinoline with pyridines [33, 34]. In this paper, we report a direct C–H bond activation of acetophenone using iodine. To the best of our knowledge, formation of the indolizine skeleton using a 1,3-dipolar cycloaddition reaction of nitrogen ylides, generated in situ from iodine-promoted reaction of acetophenone and pyridine, with ynones has not been previously reported.
Initially, we studied the reaction between pyridinium ylide (6a), generated from acetophenone (1a) and pyridine (2), with 1,3-diphenyl-propynone (3a) using various organic bases. The resulting mixture was stirred for 3 h in different solvents. The reaction was carried out firstly by stirring the mixture of 3a and 6a in MeOH in the presence of \(\hbox {Et}_{3}\hbox {N}\) at \(60~{^{\circ }}\hbox {C}\) for 2 h where a yield of 10% of product 7a was obtained (Table 1, entry 1). The use of MeCN instead of MeOH and DMF as solvent led to an improved yield (Table 1, entry 3). Compound 7a was obtained in a higher yield (40%) in the presence of N,N-diisopropylethylamine (DIPEA) (Table 1, entry 4). These results encouraged us to further optimize the reaction conditions by increasing the amount of DIPEA. The conversion proceeded in 87% yield with two equivalents of DIPEA.
We then used the optimized conditions to prepare a series of functionalized indolizines from 3 and 6. The reactions proceeded smoothly providing the indolizine derivatives in moderate to good yields (Table 2).
The structures of compounds 7a–g were confirmed by \(^{1}\hbox {H}\) NMR, \(^{13}\hbox {C}\) NMR, and IR spectroscopy as well as mass spectrometry. The mass spectrum of 7c showed fragment ions at \(m/z = 77\) and 338, arising from loss of a phenyl moiety from the molecule. In the IR spectrum of 7c, absorption bands at 1609 (C\(=\)O) \(\hbox {cm}^{-1}\) were the most significant stretching frequencies. Observation of 29 distinct signals in the \(^{1}\hbox {H}\)-decoupled \(^{13}\hbox {C}\) NMR spectrum of 7c is in agreement with the proposed structure. The \(^{13}\hbox {C}\) NMR spectra of products 7a–g lack the ketone carbonyl signal.
To extend the scope of this transformation, we performed the reaction between isoquinoliniumylide 10 with ynone 3c (Scheme 2). This reaction led to the formation of (3-benzoyl-2-phenylpyrrolo[2,1-a]isoquinolin-1-yl)(o-tolyl)methanone (11) in 80% yield. Compound 11 was again fully characterized by its IR and NMR spectra. Unequivocal evidence for the structure of 11 was obtained from single-crystal X-ray analysis. The ORTEP diagram of 11 is shown in Fig. 1. The structure deduced from the crystallographic data and those of 7a–g were assumed to be analogous on account of their similar NMR spectra.
A mechanistic rationalization for the formation of product 7a is given in Scheme 3. Presumably, the initial event is activation of acetophenone by coordination to molecular iodine, which leads to intermediate 8a. This intermediate reacts with pyridine to afford 1-(2-oxo-2-phenylethyl)pyridinium iodide 9a which is then converted into nitrogen ylide 6a by DIPEA. The 1,3-dipolar cycloaddition reaction of ylide 6a with ynone 3a, followed by aromatization of the dihydropyrrole moiety of intermediate 10a, affords indolizine derivative 7a.
Conclusion
In summary, we have developed a transition-metal-free protocol toward C–H bond activation by using molecular \(\hbox {I}_{2}\)-promoted \({ sp}^{3}\) C–H bond functionalization of acetophenones for the synthesis of indolizine derivatives via 1,3-dipolar cycloaddition reaction of nitrogen ylides with ynones. The reactions perform well in the absence of any metal or ligand.
Experimental section
General remarks
All purchased solvents and chemicals were of analytical grade and used without further purification. Melting points and IR spectra of all compounds were measured on an Electrothermal 9100 apparatus and a Shimadzu IR-460 spectrometer, respectively. The \(^{1}\hbox {H}\) and \(^{13}\hbox {C}\) spectra were obtained with a Bruker DRX-500 AVANCE instrument using \(\hbox {CDCl}_{3}\) as applied solvent and TMS as internal standard at 500.1 and 125.7 MHz, respectively. The abbreviations used for NMR signals: s \(=\) singlet, d \(=\) doublet, t \(=\) triplet, and m \(=\) multiplet. Mass spectra were recorded on a Finnigan-MAT 8430 mass spectrometer operating at an ionization potential of 70 eV. Elemental analyses for C, H, and N were performed using a Heraeus CHN-O-Rapid Analyzer.
Typical experimental procedure for the synthesis of products 7 and 11
Ynones 3 were prepared from alkynes 4 (1 mmol) and acyl chlorides 5 (1 mmol), in the presence of \([\hbox {Pd}(\hbox {PPh}_{3})_{2}\hbox {Cl}_{2}]\) (14 mg, 0.02 mmol) and CuI (7 mg, 0.04 mmol) in MeCN (2 mL). A mixture of 1 (1 mmol), azaarene (2 mmol) and \(\hbox {I}_{2}\) (0.256 g, 1 mmol) in MeCN (3 mL) was warmed to \(60~{^{\circ }}\hbox {C}\) for 12 h. Then, a solution of DIPEA (0.258 g, 2 mmol) and 3 (2 mmol) in MeCN (2 mL) was added. The reaction mixture stirred at room temperature for 3 h, kept in a freezer for 5 h, the precipitate filtered, and recrystallized from n-hexane/AcOEt (1:5) to give product.
(2-Phenylindolizine-1,3-diyl)bis(phenylmethanone) (7a)
Yellow powder; yield: 0.31 g (78%); Mp: 183–185 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3058, 1609, 1602, 1494, 1457, 1384, 1225. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz,): \(\delta \) 9.72 (1H, d, \(J= 7.0\,\hbox {Hz}\)), 8.23 (1H, d, \(J= 8.9\,\hbox {Hz}\)), 7.47 (2H, d, \(J= 7.6\,\hbox {Hz}\)), 7.44 (1H, t, \(J= 7.0\,\hbox {Hz}\)), 7.40 (2H, d, \(J= 7.4\,\hbox {Hz}\)), 7.21 (1H, t, \(J = 7.2\,\hbox {Hz}\)), 7.15 (1H, t, \(J = 7.4\,\hbox {Hz}\)), 7.13 (1H, t, \(J = 7.4\,\hbox {Hz}\)), 7.07 (2H, t, \(J = 7.6\,\hbox {Hz}\)), 7.00 (2H, t, \(J = 7.6\,\hbox {Hz}\)), 6.89 (2H, d, \(J = 6.7\,\hbox {Hz}\)), 6.71–6.77 (3H, m). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz,): \(\delta \) 192.7 (C\(=\)O), 187.0 (C\(=\)O), 139.3 (C), 139.2 (C), 139.0 (C), 138.0 (C), 137.8 (C), 133.3 (CH), 131.5 (2CH), 130.7 (2CH), 130.5 (2CH), 129.4 (CH), 128.5 (CH), 127.5 (2CH), 127.2 (2CH), 127.0 (2CH), 125.8 (C), 120.8 (CH), 119.2 (CH), 118.8 (CH), 115.4 (CH), 114.2 (C). MS: m / z (%) = 401 (\(\hbox {M}^{+}\), 100), 324 (35), 296 (77), 219 (45), 114 (15), 105 (45), 77(55). Anal. Calcd. for \(\hbox {C}_{28}\hbox {H}_{19}\hbox {NO}_{2}\) (401.46): C, 83.77; H, 4.77; N, 3.49. Found: C, 83.45; H, 4.80; N, 3.52.
(3-Benzoyl-2-phenylindolizin-1-yl)(p-tolyl)methanone (7b)
Yellow powder; yield: 0.30 g (73%); Mp: 194–196 \({^{\circ }}\hbox {C}\). IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3056, 3105, 1608, 1495, 1457, 1384, 1226. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz): \(\delta 9.72\) (1H, d, \(J = 7.1\,\hbox {Hz}\)), 8.12 (1H, d, \(J = 8.9\,\hbox {Hz}\)), 7.48 (1H, t, \(J = 7.0\,\hbox {Hz}\)), 7.39–42 (4H, m), 7.20 (1H, t, \(J = 7.2\,\hbox {Hz}\)), 7.15 (1H, t, \(J = 7.4\,\hbox {Hz}\)), 7.09 (1H, t, \(J = 7.4\,\hbox {Hz}\)), 7.01 (2H, t, \(J = 7.6\,\hbox {Hz}\)), 6.9 (2H, t, \(J = 7.0\,\hbox {Hz}\)), 6.74–6.80 (3H, m), 6.52 (1H, d, \(J = 7.9\,\hbox {Hz}\)), 2.24 (3H, s). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta 192.5\) (C\(=\)O), 188.3 (C\(=\)O), 142.2 (C), 139.2 (C), 138.9 (C), 138.8 (C), 136.4 (C), 133.4 (C), 131.5 (2CH), 131.1 (CH), 130.2 (CH), 129.6 (2CH), 129.1 (2CH), 128.8 (2CH), 128.2 (CH), 127.5 (2CH), 127.0 (2CH), 126.6 (CH), 121.0 (C), 119.3 (CH), 115.1 (CH), 114.4 (C), 21.4 (Me). MS: m / z (%) = 415 (\(\hbox {M}^{+}\), 100), 338 (35), 296 (77), 191 (15), 119 (15), 105 (45), 77(55). Anal. Calcd. for \(\hbox {C}_{29}\hbox {H}_{21}\hbox {NO}_{2}\) (415.48): C, 83.83; H, 5.09; N, 3.37. Found: C, 83.68; H, 5.11; N, 3.40.
(3-Benzoyl-2-phenylindolizin-1-yl)(o-tolyl)methanone (7c)
Yellow powder; yield: 0.34 g (80%), Mp: 210–213 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3058, 2924, 1607, 1491, 1410, 1386, 1225. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz,): \(\delta ~9.69\) (1H, d, \(J = 7.1\,\hbox {Hz}\)), 8.39 (1H, d, \(J = 8.1\,\hbox {Hz}\)), 7.49 (1H, t, \(J = 6.9\,\hbox {Hz}\)), 7.36 (2H, d, \(J = 8.1\,\hbox {Hz}\)), 7.14 (2H, t, \(J = 7.4\,\hbox {Hz}\)), 6.97–7.02 (4H, m), 6.91 (1H, d, \(J = 7.5\,\hbox {Hz}\)), 6.83 (2H, d, \(J = 7.7\,\hbox {Hz}\)), 6.79 (1H, t, \(J = 7.4\,\hbox {Hz}\)), 6.68–6.75 (3H, m), 2.35 (3H, s). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta 194.8\) (C\(=\)O), 188.9 (C\(=\)O), 140.7 (C), 140.2 (C), 139.7 (C), 139.5 (C), 136.5 (C), 133.3 (C), 131.5 (2CH), 130.7 (CH), 130.0 (CH), 129.6 (2CH), 129.5 (CH), 128.3 (2CH), 127.8 (3CH), 127.2 (CH), 127.1 (2CH), 125.2 (CH), 122.2 (C), 120.0 (CH), 115.9 (CH), 115.2 (C), 20.2 (Me). MS: m / z (%) = 415 (\(\hbox {M}^{+}\), 100), 338 (45), 310 (5), 296 (63), 191 (10), 119 (15), 105 (35), 77(40). Anal. Calcd. for \(\hbox {C}_{29}\hbox {H}_{21}\hbox {NO}_{2}\) (415.48): C, 83.83; H, 5.09; N, 3.37. Found: C, 83.58; H, 5.12; N, 3.41.
(1-Benzoyl-2-phenylindolizin-3-yl)(4-bromophenyl)methanone (7d)
Yellow powder; yield: 0.36 g (75%), Mp: 212–214 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3057, 1611, 1492, 1385, 1225. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz,): \(\delta 9.71\) (1H, d, \(J = 7.0\,\hbox {Hz}\)), 8.19 (1H, d, \(J = 8.7\,\hbox {Hz}\)), 7.41–7.45(3H, m), 7.17–7.28 (3H, m), 7.02–7.12 (5H, m), 6.81–6.88 (3H, m), 6.72–6.76 (2H, m). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta 192.7\) (C\(=\)O), 187.0 (C\(=\)O), 139.3 (C), 139.2 (C), 139.0 (C), 138.0 (C), 137.8 (C), 133.3 (C), 131.5 (2CH), 130.7 (2CH), 130.5 (2CH), 129.4 (CH), 128.5 (CH), 127.5 (2CH), 127.2 (2CH), 127.0 (2CH), 125.8 (C), 120.8 (CH), 119.2 (CH), 118.8 (CH), 115.4 (CH), 114.2 (C). MS: m / z (%) = 480 (\(\hbox {M}^{+}\), 100), 402 (15), 374 (35), 296 (77), 219 (45), 182 (15), 105 (45), 77(55). Anal. Calcd. for \(\hbox {C}_{28}\hbox {H}_{18}\hbox {BrNO}_{2}\) (480.35): C, 70.01; H, 3.78; N, 2.92. Found: C, 70.36; H, 3.81; N, 2.96.
(3-(4-Bromobenzoyl)-2-phenylindolizin-1-yl)(p-tolyl)methanone (7e)
Yellow powder; yield: 0.37 g (75%), Mp: 209–211 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3050, 2924, 1605, 1493, 1389, 1386, 1225, 706. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz): \(\delta 9.75\) (1H, d, \(J = 7.0\,\hbox {Hz}\)), 8.12 (1H, d, \(J = 8.9\,\hbox {Hz}\)), 7.41 (1H, d, \(J = 8.4\,\hbox {Hz}\)), 7.19–7.23 (3H, m), 7.11–7.14 (4H, m), 6.89 (3H, t, \(J =8.4\,\hbox {Hz}\)), 6.81 (2H, t, \(J = 7.9\,\hbox {Hz}\)), 6.68 (1H, d, \(J = 7.9\,\hbox {Hz}\)), 6.61 (1H, d, \(J = 7.9\,\hbox {Hz}\)), 2.25 (3H, s). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta _{c} = 192.3\) (C\(=\)O), 186.9 (C\(=\)O), 142.3 (C), 139.1 (C), 138.9 (C), 138.1 (C), 136.2 (C), 133.2 (C), 131.5 (2CH), 130.7 (2CH), 130.5 (2CH), 129.6 (CH), 128.3 (2CH), 127.6 (CH), 127.2 (2CH), 126.9 (2CH), 126.1 (C), 125.7 (C), 120.7 (CH), 119.4 (CH), 115.2 (CH), 114.6 (C), 21.2 (Me). MS: m / z (%) = 494 (100), 416 (32), 374 (40), 310 (44), 296 (66), 182 (20), 119 (35), 77 (15). Anal. Calcd. for \(\hbox {C}_{29}\hbox {H}_{20}\hbox {BrNO}_{2}\) (494.38): C, 70.45; H, 4.08; N, 2.83. Found: C, 70.17; H, 4.11; N, 2.86.
(3-(4-Bromobenzoyl)-2-phenylindolizin-1-yl)(4-nitrophenyl)methanone (7f)
Yellow powder; yield: 0.45 g (87%), Mp: 218–220 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3068, 1594, 1519, 1487, 1408, 1343, 1221, 660. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz): \(\delta 9.73\) (1H, d, \(J = 7.0\,\hbox {Hz}\)), 8.49 (1H, d, \(J = 9.0\,\hbox {Hz}\)), 7.84 (2H, d, \(J = 8.6\,\hbox {Hz}\)), 7.59 (1H, t, \(J = 7.6\,\hbox {Hz}\)), 7.49 (2H, d, \(J = 8.6\,\hbox {Hz}\)), 7.20–7.23 (3H, m), 7.12 (2H, d, \(J = 8.3\,\hbox {Hz}\)), 6.85 (1H, t, \(J = 7.2\,\hbox {Hz}\)), 6.80 (2H, d, \(J = 7.0\,\hbox {Hz}\)), 6.74 (2H, t, \(J = 7.6\,\hbox {Hz}\)). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz,): \(\delta 191.0\) (C\(=\)O), 187.5 (C\(=\)O), 149.0 (C), 145.1 (C), 140.2 (C), 139.6 (C), 138.0 (C), 133.1 (C), 132.0 (2CH), 131.1 (4CH), 130.2 (2CH), 129.1 (CH), 128.4 (CH), 127.1 (CH), 127.9 (2CH), 126.6 (C), 122.9 (2CH), 121.6 (C), 119.8 (CH), 116.6 (CH), 113.5 (C). MS: m / z (%) = 525 (100), 447 (32), 374 (40), 341 (44), 296 (66), 182 (15), 150 (20), 77 (15). Anal. Calcd. for \(\hbox {C}_{28}\hbox {H}_{17}\hbox {BrN}_{2}\hbox {O}_{4}\) (525.35): C, 64.01; H, 3.26; N, 5.33. Found: C, 64.34; H, 3.24; N, 5.37.
(3-(4-Bromobenzoyl)-2-phenylindolizin-1-yl)(o-tolyl)methanone (7g)
Yellow powder; yield: 0.41 g (83%), Mp: 205–207 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3061, 2930, 1609, 1494, 1460, 1388, 1223, 651. \(^{1}\hbox {H}\) NMR (\(\hbox {CDCl}_{3}\), 500 MHz,): \(\delta \) 9.72 (1H, d, \(J = 7.0\,\hbox {Hz}\)), 8.39 (1H, d, \(J = 8.9\,\hbox {Hz}\)), 7.51 (1H, t, \(J = 7.6\,\hbox {Hz}\)), 7.14–7.20 (3H, m), 7.10 (2H, d, \(J = 7.5\,\hbox {Hz}\)), 7.01 (2H, t, \(J = 7.5\,\hbox {Hz}\)), 6.92 (1H, t, \(J = 7.6\,\hbox {Hz}\)), 6.78–6.85 (4H, m), 6.73 (2H, t, \(J = 7.5\,\hbox {Hz}\)), 2.34 (3H, s). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta 194.7\) (C\(=\)O), 187.5 (C\(=\)O), 140.6 (C), 140.4 (C), 139.9 (C), 138.4 (C), 136.5 (C), 133.1 (C), 131.5 (2CH), 131.2 (CH), 131.0 (2CH), 130.9 (2CH), 130.9 (CH), 130.8 (CH), 130.2 (CH), 129.5 (CH), 128.6 (CH), 128.4 (CH), 127.3 (2CH), 126.1 (C), 125.2 (C), 120.0 (CH), 116.1 (CH), 115.4 (C), 20.2 (Me). MS: m / z (%) = 494 (100), 416 (32), 374 (40), 310 (44), 296 (66), 182 (35), 119 (25), 77 (15). Anal. Calcd. for \(\hbox {C}_{29}\hbox {H}_{20}\hbox {BrNO}_{2}\) (494.38): C, 70.45; H, 4.08; N, 2.83. Found: C, 70.79; H, 4.06; N, 2.85.
(3-Benzoyl-2-phenylpyrrolo[2,1-a]isoquinolin-1-yl)(o-tolyl)methanone (11)
Yellow powder; yield: 0.37 g (80%), Mp: 215–217 \({^{\circ }}\hbox {C}\); IR \((\hbox {KBr, }\upnu _{\mathrm{max}}\,\hbox {cm}^{-1})\): 3059, 1616, 1513, 1451, 1386, 1210. \(^{1}\hbox {H}\) NMR (500 MHz, \(\hbox {CDCl}_{3}\)): \(\delta _{H} = 9.24\) (1H, d, \(J = 7.8\,\hbox {Hz}\)), 8.32 (1H, d, \(J = 8.3\,\hbox {Hz}\)), 7.74 (1H, d, \(J = 7.8\,\hbox {Hz}\)), 7.54 (1H, t, \(J = 7.2\,\hbox {Hz}\)), 7.40–7.48 (3H, m), 7.27 (1H, d, \(J = 8.3\,\hbox {Hz}\)), 7.19 (1H, d, \(J = 7.5\,\hbox {Hz}\)), 7.10–7.15 (2H, m), 6.99 (3H, t, \(J = 7.5\,\hbox {Hz}\)), 6.86–6.88 (3H, m), 6.73 (3H, t, \(J = 7.1\,\hbox {Hz}\)), 2.52 (3H, s). \(^{13}\hbox {C}\) NMR (\(\hbox {CDCl}_{3}\), 125.7 MHz): \(\delta 198.2\) (C\(=\)O), 188.2 (C\(=\)O), 139.2 (C), 139.0 (C), 138.6 (C), 136.5 (C), 133.4 (C), 132.1 (C), 131.5 (2CH), 131.2 (CH), 131.0 (2CH), 130.9 (2CH), 130.9 (C), 130.8 (CH), 130.2 (CH), 129.5 (CH), 128.6 (CH), 128.4 (CH), 127.8 (CH), 127.6 (2CH), 127.0 (2CH), 126.7 (CH), 125.2 (C), 124.5 (CH), 122.2 (C), 119.8 (C), 114.3 (CH), 21.3 (Me). MS: m / z (%) = 465 (100), 388 (32), 360 (40), 348 (44), 283 (66), 119 (25), 105 (20), 77 (15). Anal. Calcd. for \(\hbox {C}_{33}\hbox {H}_{23}\hbox {NO}_{2}\) (465.54): C, 85.14; H, 4.98; N, 3.01. Found: C, 85.54; H, 5.02; N, 3.04.
X-ray crystal structure determination of product 11
The X-ray diffraction measurements were carried out on STOE IPDS-2T diffractometers with graphite-monochromated \(\hbox {Mo}(\hbox {K}{\upalpha })\) radiation. All single crystals were mounted on a glass fiber and used for data collection. Colorless single crystals of compound 11 suitable for SC-XRD measurement were grown by slow evaporation of an ethyl acetate solution. The structure was solved by direct method and refined by full-matrix least-squares calculations based on \(\hbox {F}^{2}\) to final R1 \(=\) 0.0550 and wR2 (all data) \(=\) 0.1428, using SHELXL-2014 and WinGX-2013.3 programs [35, 36]. Compound 11 is crystallized as a triclinic crystal system and \(P-1\) space group. Two independent molecules with molecular formula of \(\hbox {C}_{33}\hbox {H}_{23}\hbox {NO}_{2}\) were found in the asymmetric unit, giving a total of \(Z = 2\) for the unit cell; \(a = 8.2382(16)\) Å, \(b = 12.088(2)\) Å, \(c = 14.289(3)\) Å, \(\alpha = 111.10(3){^{\circ }}\), \(\beta = 98.05(3){^{\circ }}\), \(\gamma = 103.08(3){^{\circ }}\), cell volume \(\hbox {V }= 1254.1(5){\AA }^{3}\), 3578 independent reflections, and max/min residual electron density [\(\hbox {e}\,{\AA }^{3}\)]: 0.18/\(-\)0.18. All non-hydrogen atoms were refined with anisotropic displacement parameters. Hydrogen atoms were placed in ideal positions and refined as riding atoms with relative isotropic displacement parameters. A view of the structure is depicted in Fig. 1. CCDC-1506730 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.
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Yavari, I., Sheykhahmadi, J., Naeimabadi, M. et al. Iodine-mediated \({ sp}^{3}\) C–H functionalization of methyl ketones: a one-pot synthesis of functionalized indolizines via the 1,3-dipolar cycloaddition reaction between pyridinium ylides and ynones. Mol Divers 21, 1–8 (2017). https://doi.org/10.1007/s11030-016-9720-9
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DOI: https://doi.org/10.1007/s11030-016-9720-9