Copper(I)-Catalyzed Ligand-Promoted Multicomponent Reactions of

Publication Date (Web): September 14, 2017. Copyright © 2017 American Chemical Society. *E-mail: [email protected]., *E-mail: [email protected]...
0 downloads 0 Views 1MB Size
Download PDF
Article Cite This: J. Org. Chem. 2017, 82, 10866-10874

pubs.acs.org/joc

Copper(I)-Catalyzed Ligand-Promoted Multicomponent Reactions of Isocyanides, Selenium, Amines, and Iodoarenes: Access to Highly Functionalized Carbamimidoselenoates Huan Liu,† Yi Fang,† Ling Yin,†,‡ Shun-Yi Wang,*,† and Shun-Jun Ji*,† †

Key Laboratory of Organic Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and Materials Science & Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou, 215123, P. R. China ‡ Department of Chemistry and Chemical Engineering, Jining University, Qufu, 273155, P. R. China S Supporting Information *

ABSTRACT: A new and facile approach toward highly functionalized carbamimidoseleknoates was developed through the copper(I)-catalyzed ligand-promoted four-component reaction of isocyanides, selenium, amines, and aryl iodides. The reaction constructed a range of organoselenium compounds containing an isoselenourea skeleton with potential bioactivity directly from selenium powder. The simplicity of method and broad diversity of substrates also highlight this work.

■

INTRODUCTION Organoselenium chemistry has attracted increasing attention since selenium-containing compounds exhibit great diversity and wide applications in drug candidates, bioactive materials, and functional organic materials.1−4 Furthermore, organoselenium compounds containing an isoselenourea skeleton have shown antitumor and antibacterium activities (Scheme 1).5 However, the reported approaches to the synthesis of

handled reagent. In 2007, Kambe reported the copper-catalyzed reactions of 2-halidephenyl isocyanides, selenium powder, and amines to furnish 2-amine-benzoselenazoles bearing isoselenourea skeletons.10 To the best of our knowledge, the intermolecular reaction between isocyanides, selenium powder, amines, and iodoarenes to construct acyclic isoselenoureas has not been reported. Herein, we demonstrate a novel approach toward acyclic isoselenoureas by the in situ generated copper(I)-complex-catalyzed four-component reaction of isocyanides, selenium powder, amines, and aryl iodides under mild conditions (Scheme 2). 1,10-Phenanthroline is a crucial ligand for the success of this multicomponent reaction.

Scheme 1. Bioactive Compounds Containing an Isoselenourea Skeleton

■

RESULTS AND DISCUSSION Initially, we investigated the one-pot reaction of 1-isocyano-3nitrobenzene 1a, elemental selenium 2, diethylamine 3a, and iodobenzene 4a in tetrahydrofuran catalyzed by CuI under ligand-free conditions. Unfortunately, no desired product was observed (Table 1, entry 1). It is worth noting that the desired product 5a was observed in 48% isolated yield when 10 mol % 1,10-Phen was added to the reaction system (Table 1, entry 2). The structure of 5a was confirmed by 1H NMR, 13C NMR, and IR spectroscopy. Moreover, density functional theory calculation results showed that the (Z)-configuration of 5a is more stable than the (E)-configuration (see Supporting Information p S5). Encouraged by this result, we screened a range of different ligands and found that 1,10-Phen served as an optimal ligand. It is noteworthy that no desired product was obtained when other ligands were applied (Table 1, entries 3−5). Next, different copper salts, including Cu(I) and Cu(II) salts, were

isoselenourea derivatives from easily handled materials under mild conditions are still rare. Therefore, development of an efficient approach for the synthesis of organic useful organoselenium compounds bearing an isoselenourea skeleton is of great significance. It is well-known that alkylation reactions of selenoureas with alkyl sulfates6 or alkyl halides7 are two general methods for the synthesis of organoselenium compounds containing an isoselenourea skeleton. However, applications of these methodologies in the pharmaceutical industry are limited because selenoureas are usually unavailable, unstable, and toxic.8 In recent years, the reactions for the construction of isoselenourea skeleton involving isocyanides and selenium powder have gained increasing attention.9 In comparison to selenourea, selenium powder is commercially available, stable, and easily © 2017 American Chemical Society

Received: July 4, 2017 Published: September 14, 2017 10866

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry Scheme 2. Copper-Catalyzed Cross-Coupling Reaction for the Construction of Acyclic Isoselenoureas

Table 1. Optimization of the Reaction Conditionsa

entry

ligandd

[Cu]

solvent

yield %b

1 2 3 4 5 6 7 8 9 10 11 12 13 14e,f 15e,f,g

 1,10-phen bpy PPh3 dppe 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen 1,10-phen

CuI CuI CuI CuI CuI CuBr CuOAc CuCl2 Cu(OTf)2 CuI CuI CuI CuI CuI CuI

THF THF THF THF THF THF THF THF THF CH3CN DMF DMSO MTBE THF THF

0 52 (48)c 0 0 0 35 24 39 36 30 11 7 32 78c 83c

With the optimal reaction conditions in hand, the substrate scope of isocyanides 1 was investigated (Scheme 3). The reactions of aryl isocyanides with electron-withdrawing groups proceeded smoothly to afford the desired products in moderate to good yields. Substrates bearing strong electron-withdrawing groups, such as nitro (5a and 5b), cyano (5c), and amido (5d), gave better results, affording the corresponding products in 67%−82% yields. The copper catalysis also accommodated electron-withdrawing acetyl (5e), ester (5f), and bromo (5g) substituents, which showed slightly lower efficiency of the transformations. When employing chloro substituent 1h as the substrate, we could afford the expected product 5h in 71% yield. Disappointedly, aryl isocyanides bearing electrondonating groups, such as 1-isocyano-4-methoxybenzene (1i), 2,6-xylyl isocyanide (1j), and alkyl isocyanides (1k, 1l, and 1m), failed to lead to the desired products. Next, the substrate scope of this multicomponent coupling reaction was further expanded to a range of amines. A number of secondary amines including aliphatic amines and aromatic amines were subjected to the reactions, and all the reactions proceeded smoothly to afford the corresponding products in moderate to good yields (Scheme 4). When dipropylamine (6b), dibutylamine (6c), and dibenzylamine (6d) were submitted to the reaction, we could afford the expected products in 52%−70% yields. Methylamine derivatives could also be tolerated in the reaction, giving the desired products 6e and 6f in 21% and 64% yields, respectively. This result indicated that the electronic effect greatly impacted the efficiency of the reaction. To our delight, fluoxetine, an antidepressant medicine, could be transformed to the product 6g in 25% yield. Annular aliphatic secondary amines, such as morpholine (6h) and tert-butyl piperazine-1-carboxylate (6i), were subjected to the reactions to furnish the expected products in 46% and 47% yields, respectively. It was notable that aromatic secondary amines (3k, 3l, and 3m) were proven to be suitable candidates for the reaction, leading to the desired carbamimidoselenoates (6k, 6l, and 6m) in 49%−68% yields. Unfortunately, no desired products were detected when nbutylamine and aniline were employed in this reaction (6j and 6n). It was gratifying that the reaction of functionalized amine containing a bioactive skeleton of epiandrosterone successively afforded the desired product 6o in 37% yield. Finally, we further investigated the substrate scope of the aryl iodides under the optimized conditions (Scheme 5). To our delight, a series of aryl iodides could participate in this multicomponent reaction to give the corresponding products in 53%−81% yields. Aryl iodides bearing electron-withdrawing groups 4b−4h resulted in the desired products 7b−7h in 65%− 79% yields. When electron-donating groups, such as methoxy (7i), methyl (7j, 7k, and 7l), were submitted to the reaction, the desired products were afforded in 53%−72% yields.

a All reactions were performed with 1a (0.15 mmol), 2 (0.225 mmol), 3a (0.225 mmol), 4a (0.30 mmol), [Cu] (0.015 mmol), ligand (0.015 mmol), and Cs2CO3 (0.30 mmol) in solvent (2 mL) at 55 °C for 12 h unless otherwise noted. bYields were determined by LC-MS analysis using biphenyl as an internal standard. cIsolated yields. d1,10-Phen = 1,10-Phenanthroline. bpy = 2,2′-Dipyridyl. e0.0225 mmol of 1,10-Phen was used. fReaction performed at 70 °C. g1.0 mL of THF was used.

employed, but no better result was observed (Table 1, entries 6−9). Subsequently, the effect of different solvents was tested, and the result showed that other solvents such as acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide, and tert-butyl methyl ether proved to be ineffective for this transformation (Table 1, entries 10−13). In addition, further screening of the bases and reaction temperatures showed that conducting the reaction at 70 °C in the presence of Cs2CO3 gave the better results and the isolated yield of the target product increased to 56% (see Supporting Information p S3). Furthermore, we investigated the effects of the ratio of 1,10-Phen to CuI on the yield of 5a. It should be noted that a 0.05 equiv excess of 1,10Phen increased the yield of 5a from 48% to 78% (Table 1, entry 14). By further increasing the concetration of the reaction, 5a was obtained in 83% yield (Table 1, entry 15). The optimal conditions were affirmed as follows: 1a (0.15 mmol, 1.0 equiv), 2 (0.225 mmol, 1.5 equiv), 3a (0.225 mmol, 1.5 equiv), 4a (0.3 mmol, 2.0 equiv) in THF (1 mL) at 70 °C catalyzed by 0.015 mmol of CuI in the presence of 0.0225 mmol of 1,10Phenanthroline and 0.30 mmol of Cs2CO3 under an air atmosphere for 12 h. 10867

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry Scheme 3. Substrate Scope of Isocyanides 1a,b

a All reactions were performed with 1a (0.30 mmol), 2 (0.45 mmol), 3a (0.45 mmol), 4a (0.60 mmol), CuI (0.03 mmol), 1,10-Phen (0.045 mmol), and Cs2CO3 (0.60 mmol) in THF (2 mL) at 55 °C under air for 12 h unless otherwise noted. bIsolated yields.

■

CONCLUSION In summary, we have developed a copper(I)-catalyzed fourcomponent reaction for the synthesis of highly functionalized carbamimidoselenoates. Commercially available, stable, and easily handled elemental selenium powder is an ideal selenium source. This method provides a portable tool for the direct construction of organoselenium compounds bearing an acyclic isoselenourea skeleton with potential biological and medicinal activities under mild conditions.

Moreover, heteroaryl iodides such as 3-iodopyridine and 3iodothiophene could also lead to the expected products (7m and 7n) in 81% and 66% yields, respectively. Unfortunately, bromobenzene failed to result in the corresponding product under the optimal reaction conditions. To understand the reaction mechanism, we conducted two controlled experiments. First, we prepared 1,1-diethyl-3-(3nitrophenyl)selenourea 8a in situ by the one-pot reaction of 1isocyano-3-nitrobenzene 1a (0.30 mmol), elemental selenium 2 (0.45 mmol), and diethylamine 3a (0.45 mmol) in THF (2 mL) at ambient temperature in the presence of Cs2CO3 (0.60 mmol). We then investigated the reaction of 8a generated in situ with iodobenzene under standard conditions, and 5a can be isolated in 66% yield (Scheme 6, eq 1). The result of the onepot two-step reaction indicated that 8a was a crucial intermediate in this multicomponent reaction. It is wellknown that isocyanides could react with secondary amines catalyzed by copper to produce a range of formimidamide derivatives.11 Therefore, we also investigated the reaction of 9a, Se powder, and iodobenzene under standard conditions. However, the reaction could not occur at all, which ruled out the possibility of 9a as a reaction intermediate (Scheme 6, eq 2). On the basis of the above experiment results and previous literatures,12,13 we propose a plausible reaction pathway involving the SNAr mechanism in Scheme 7. Initially, 1isocyano-3-nitrobenzene 1a reacts with elemental selenium 2 and diethylamine 3a to generate selenoate 8a, followed by ligand exchange with copper(I) complex A to give the intermediate B. Oxidative addition of the intermediate B with iodobenzene affords the intermediate C. Subsequently reductive elimination of C furnishes the desired product 5a and regenerates copper(I) complex A.

■

EXPERIMENTAL SECTION

General Experimental Information. Unless otherwise noted, all commercially available compounds were used as provided without further purification. Solvents for chromatography were analytical grade and used without further purification. Tetrahydrofuran was purchased from Shanghai Lingfeng Chemical Reagent Co., Ltd. Analytical thinlayer chromatography (TLC) was performed on silica gel, visualized by irradiation with UV light. For column chromatography, 300−400 mesh silica gel was used. 1H NMR and 13C NMR were recorded on a BRUKER 400 MHz spectrometer in CDCl3. Chemical shifts (δ) were reported referenced to an internal tetramethylsilane standard or the CDCl3 residual peak (δ 7.26) for 1H NMR. Chemical shifts of 13C NMR are reported relative to CDCl3 (δ 77.16). Data are reported in the following order: chemical shift (δ) in ppm; multiplicities are indicated s (singlet), bs (broad singlet), d (doublet), t (triplet), m (multiplet); coupling constants (J) are in hertz (Hz). Melting points were measured on an electrothermal digital melting point apparatus and were uncorrected. IR spectra were recorded on a BRUKER VERTEX 70 spectrophotometer and are reported in terms of frequency of absorption (cm−1). HRMS spectra were obtained by using a BRUKER MICROTOF-Q III instrument with an ESI source. General Procedure for the Synthesis of 5a. In a 15 mL reaction tube, 3-nitrophenyl isocyanide 1a (0.3 mmol, 1.0 equiv), selenium powder 2 (0.45 mmol, 1.5 equiv), CuI (0.03 mmol), 1,10phenanthroline (0.045 mmol), diethylamine 3a (0.45 mmol, 1.5 equiv), and iodobenzene 4a (0.6 mmol, 2.0 equiv) were dissolved in 2 10868

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry Scheme 4. Substrate Scope of the Amines 3a,b

a All reactions were performed with 1a (0.30 mmol), 2 (0.45 mmol), 3a (0.45 mmol), a (0.60 mmol), CuI (0.03 mmol), 1,10-Phen (0.045 mmol), and Cs2CO3 (0.60 mmol) in THF (2 mL) at 55 °C under air for 12 h unless otherwise noted. bIsolated yields. cN.D. = Not detected d0.6 mmol scale. e0.2 mmol scale

mL of THF. The system was stirred in an oil bath at 70 °C under air. After 12 h, it was removed from the oil bath. The reaction mixture was charged with silica gel and concentrated. The residue was purified by 60−70 g 300−400 mesh silica gel column chromatography (eluent: Petroleum ether/EtOAc) to obtain the desired product 5a as a yellow oil liquid. Phenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (5a). Following the general procedure, using 50/1 petroleum ether/ EtOAc as the eluant afforded a yellow oil liquid (91.0 mg, 81% yield). IR 2972, 2931, 1585, 1519, 1343, 1221, 1112, 845, 735, 679 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.61 (dd, J = 8.2, 1.3 Hz, 1H), 7.32 (t, J = 2.2 Hz, 1H), 7.12−7.00 (m, 6H), 6.88 (dd, J = 7.9, 1.1 Hz, 1H), 3.63 (q, J = 7.0 Hz, 4H), 1.23 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.8, 150.3, 148.2, 133.8, 129.0, 128.7, 128.5, 128.4, 127.4, 117.6, 115.9, 77.5, 77.2, 76.8, 45.5, 13.9 ppm. HRMS (ESI) m/z calculated for C17H20N3O2Se [M + H]+, 378.0721; found, 378.0717. Phenyl (Z)-N,N-Diethyl-N′-(4-nitrophenyl)carbamimidoselenoate (5b). Following the general procedure, using 50/1 petroleum ether/ EtOAc as the eluant afforded a yellow solid (90.4 mg, 80% yield). Mp: 57.3−59.0 °C. IR 2967, 2926, 1558, 1490, 1316, 1223, 1095, 868, 853, 737 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.87−7.78 (m, 2H), 7.18− 7.08 (m, 3H), 7.04−6.98 (m, 2H), 6.61−6.53 (m, 2H), 3.63 (q, J = 7.0

Hz, 4H), 1.23 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 156.9, 150.3, 141.4, 134.3, 129.0, 128.2, 127.7, 124.1, 122.1, 77.5, 77.2, 76.8, 45.6, 13.9 ppm. HRMS (ESI) m/z calculated for C17H20N3O2Se [M + H]+, 378.0721; found, 378.0728. Phenyl (Z)-N′-(4-Cyanophenyl)-N,N-diethylcarbamimidoselenoate (5c). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a pale yellow solid (90.4 mg, 80% yield). Mp: 57.8−59.5 °C. IR 2973, 2934, 2214, 1556, 1357, 1225, 1107, 856, 740, 689 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.24−7.19 (m, 2H), 7.16−7.09 (m, 3H), 7.04 (dd, J = 8.1, 6.9 Hz, 2H), 6.62−6.54 (m, 2H), 3.61 (q, J = 7.0 Hz, 4H), 1.21 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 2973, 2934, 2214, 1556, 1357, 1225, 1107, 856, 740, 689 ppm. HRMS (ESI) m/z calculated for C18H20N3Se [M + H]+, 358.0822; found, 358.0842. Phenyl (Z)-N′-(4-(Diethylcarbamoyl)phenyl)-N,N-diethylcarbamimidoselenoate (5d). Following the general procedure, using 10/1 petroleum ether/EtOAc as the eluant afforded a pale yellow solid (86.7 mg, 67% yield). Mp: 82.4−84.3 °C. IR 2961, 2926, 1611, 1580, 1221, 1067, 867, 736, 685 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.22 (dt, J = 6.6, 1.7 Hz, 2H), 7.15−7.06 (m, 5H), 6.65− 6.59 (m, 2H), 3.59 (q, J = 7.0 Hz, 8H), 1.17 (t, J = 7.0 Hz, 12H) ppm. 13 C NMR (100 MHz, CDCl3) δ 171.3, 151.3, 148.0, 132.7, 129.6, 10869

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry Scheme 5. Substrate Scope of the Aryl Iodides 4a,b

a

All reactions were performed with 1a (0.30 mmol), 2 (0.45 mmol), 3a (0.45 mmol), 4a (0.60 mmol), CuI (0.03 mmol), 1,10-Phen (0.045 mmol), and Cs2CO3 (0.60 mmol) in THF (2 mL) at 55 °C under air for 12 h unless otherwise noted. bIsolated yields. cRun for 15 h. dRun for 14 h.

Scheme 6. Investigation of the Reaction Mechanism

Ethyl (Z)-4-(((Diethylamino)(phenylselanyl)methylene)amino)benzoate (5f). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a pale yellow oil liquid (40.0 mg, 33% yield). IR 2975, 2931, 1707, 1571, 1267, 1222, 1163, 1096, 869, 736, 688 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.77−7.70 (m, 2H), 7.20−7.03 (m, 5H), 6.66−6.59 (m, 2H), 4.31 (q, J = 7.1 Hz, 2H), 3.58 (q, J = 7.0 Hz, 4H), 1.35 (t, J = 7.1 Hz, 3H), 1.16 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 167.0, 155.3, 148.7, 133.4, 130.0, 129.1, 129.0, 127.2, 123.2, 122.0, 77.5, 77.2, 76.8, 60.4, 45.2, 14.5, 13.7 ppm. HRMS (ESI) m/z calculated for C20H25N2O2Se [M + H]+, 405.1081; found, 405.1090. Phenyl (Z)-N′-(4-Bromophenyl)-N,N-diethylcarbamimidoselenoate (5g). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (65.1 mg, 53% yield). IR 2970, 2929, 1595, 1573, 1220, 1104, 1068,

129.0, 128.4, 126.5, 126.2, 121.5, 77.0, 76.6, 76.3, 44.6, 13.2 ppm. HRMS (ESI) m/z calculated for C22H30N3OSe [M + H]+, 432.1554; found, 432.1544. Phenyl (Z)-N′-(4-Acetylphenyl)-N,N-diethylcarbamimidoselenoate (5e). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (49.3 mg, 44% yield). IR 2971, 2930, 1671, 1565, 1356, 1267, 1221, 1105, 866, 736 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.67−7.62 (m, 2H), 7.20−7.11 (m, 3H), 7.08−7.02 (m, 2H), 6.66−6.61 (m, 2H), 3.60 (q, J = 7.0 Hz, 4H), 2.50 (s, 3H), 1.18 (t, J = 7.1 Hz, 6H) ppm. 13 C NMR (100 MHz, CDCl3) δ 196.9, 155.0, 148.3, 133.0, 130.0, 128.5, 128.4, 126.7, 121.6, 76.9, 76.6, 76.3, 44.8, 25.9, 13.2 ppm. HRMS (ESI) m/z calculated for C19H23N2OSe [M + H]+, 375.0976; found, 375.1006. 10870

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry

= 8.2, 2.3, 1.0 Hz, 1H), 7.40−7.30 (m, 7H), 7.29−7.26 (m, 4H), 7.14− 7.06 (m, 4H), 7.03−6.98 (m, 2H), 6.92 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 4.81 (s, 4H) ppm. 13C NMR (100 MHz, CDCl3) δ 152.8, 151.4, 148.2, 137.5, 134.3, 129.1, 128.8, 128.5, 128.4, 128.0, 127.8, 127.8, 127.6, 117.5, 116.4, 77.5, 77.2, 76.8, 53.3 ppm. HRMS (ESI) m/z calculated for C27H24N3O2Se [M + H]+, 502.1034; found, 502.1049. Phenyl (Z)-N-Allyl-N-methyl-N′-(3-nitrophenyl)carbamimidoselenoate (6e). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (90.6 mg, 70% yield). IR 2961, 2920, 1586, 1519, 1344, 1187, 1064, 819, 736, 681 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.66 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.36 (t, J = 2.2 Hz, 1H), 7.15−7.03 (m, 6H), 6.92 (dd, J = 7.9, 1.1 Hz, 1H), 5.81 (ddt, J = 16.2, 10.8, 5.5 Hz, 1H), 5.27− 5.21 (m, 2H), 4.26 (dt, J = 5.5, 1.5 Hz, 2H), 3.14 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 152.1, 151.7, 148.3, 134.0, 133.3, 129.1, 128.7, 128.6, 128.3, 127.7, 117.6, 117.5, 116.4, 77.5, 77.2, 76.8, 55.6, 38.3 ppm. HRMS (ESI) m/z calculated for C17H18N3O2Se [M + H]+, 376.0564; found, 376.0577. Phenyl (Z)-N-(2-Cyanoethyl)-N-methyl-N′-(3-nitrophenyl)carbamimidoselenoate (6f). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (74.5 mg, 64% yield). Mp: 115.2−116.4 °C. IR 2969, 2923, 1596, 1514, 1345, 1257, 1068, 738, 689, 677 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.70 (d, J = 8.0 Hz, 1H), 7.36 (d, J = 2.4 Hz, 1H), 7.13 (dq, J = 27.4, 7.6, 7.0 Hz, 6H), 6.94 (d, J = 7.8 Hz, 1H), 3.89 (t, J = 6.6 Hz, 2H), 3.28 (s, 3H), 2.75 (t, J = 6.6 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3) δ 150.7, 150.5, 147.7, 133.2, 128.8, 128.3, 127.9, 127.4, 127.3, 117.7, 116.8, 116.3, 77.0, 76.7, 76.4, 47.8, 39.3, 15.6 ppm. HRMS (ESI) m/z calculated for C17H17N4O2Se [M + H]+, 389.0517; found, 389.0503. Phenyl (Z)-N-Methyl-N′-(3-nitrophenyl)-N-(4-phenyl-4-(4(trifluoromethyl)phenoxy)butyl)carbamimidoselenoate (6g). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (46.8 mg, 25% yield). Mp: 29.8− 30.4 °C. IR 2988, 2972, 2902, 1589, 1522, 1394, 1345, 1250, 1066, 737 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 8.2, 2.2 Hz, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.37−7.27 (m, 6H), 7.13−6.98 (m, 6H), 6.89 (d, J = 8.4 Hz, 2H), 6.76 (d, J = 7.8 Hz, 1H), 5.21 (dd, J = 8.8, 4.0 Hz, 1H), 3.91 (dt, J = 14.7, 7.5 Hz, 1H), 3.77 (ddd, J = 13.8, 8.4, 5.0 Hz, 1H), 3.17 (s, 3H), 2.27 (dddd, J = 24.9, 10.5, 8.0, 3.2 Hz, 2H) ppm. 13 C NMR (100 MHz, CDCl3) δ 160.4, 151.6, 151.5, 148.2, 140.6, 133.8, 129.2, 129.0, 128.6, 128.4, 128.2, 127.7, 127.0, 126.9, 126.9, 126.8, 125.7, 117.4, 116.4, 115.8, 78.1, 77.5, 77.2, 76.8, 49.7, 39.0, 37.0, 29.8 ppm. HRMS (ESI) m/z calculated for C30H27F3N3O3Se [M + H]+, 614.1170; found, 614.1185. Phenyl (Z)-N-(3-Nitrophenyl)morpholine-4-carbimidoselenoate (6h). Following the general procedure, using 15/1 petroleum ether/ EtOAc as the eluant afforded a pale yellow solid (54.2 mg, 46% yield). Mp: 57.8−59.5 °C. IR 2972, 2856, 1587, 1524, 1347, 1197, 1120, 1022, 739, 684 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.76 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.47 (t, J = 2.1 Hz, 1H), 7.23 (ddd, J = 8.0, 4.9, 3.2 Hz, 3H), 7.15 (dqt, J = 8.7, 6.3, 1.8 Hz, 3H), 6.99 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 3.71 (dd, J = 5.7, 3.8 Hz, 4H), 3.60 (dd, J = 5.7, 3.8 Hz, 4H) ppm. 13C NMR (100 MHz, CDCl3) δ 153.2, 151.5, 148.4, 133.9, 129.4, 128.9, 128.5, 128.4, 127.9, 117.3, 117.1, 77.5, 77.2, 76.8, 66.6, 49.4 ppm. HRMS (ESI) m/z calculated for C17H17N3NaO3Se [M + Na]+, 414.0333; found, 414.0318. tert-Butyl (Z)-4-(((3-Nitrophenyl)imino)(phenylselanyl)methyl)piperazine-1-carboxylate (6i). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (69.7 mg, 47% yield). IR 2975, 2927, 1693, 1589, 1522, 1346, 1160, 997, 738, 681 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.76 (dd, J = 8.2, 1.3 Hz, 1H), 7.48 (t, J = 2.2 Hz, 1H), 7.28−7.09 (m, 6H), 6.99 (dd, J = 7.9, 1.1 Hz, 1H), 3.71−3.64 (m, 4H), 3.38−3.30 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3) δ 154.6, 153.0, 151.5, 148.4, 133.9, 129.4, 128.9, 128.5, 128.4, 128.0, 117.3, 117.2, 80.3, 77.5, 77.2, 76.8, 48.7, 28.5 ppm. HRMS (ESI) m/z calculated for C22H26N4NaO4Se [M + Na]+, 513.1017; found, 513.1029. Phenyl (Z)-N-(3-Nitrophenyl)-3,4-dihydroquinoline-1(2H)carbimidoselenoate (6k). Following the general procedure, using

Scheme 7. Plausible Mechanism

863, 735, 688 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.22−7.06 (m, 7H), 6.52−6.41 (m, 2H), 3.56 (q, J = 7.0 Hz, 4H), 1.14 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 149.7, 148.3, 132.8, 130.5, 128.9, 128.5, 126.6, 123.6, 114.0, 77.0, 76.6, 76.3, 44.6, 13.2 ppm. HRMS (ESI) m/z calculated for C17H20BrN2Se [M + H]+, 410.9975; found, 410.9979. Phenyl (Z)-N′-(4-Chlorophenyl)-N,N-diethylcarbamimidoselenoate (5h). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a pale yellow solid (78.4 mg, 71% yield). Mp: 44.8−46.3 °C. IR 2973, 2929, 1595, 1571, 1220, 1105, 861, 731, 682 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.22− 7.07 (m, 5H), 7.00−6.95 (m, 2H), 6.56−6.48 (m, 2H), 3.56 (q, J = 7.1 Hz, 4H), 1.15 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 149.8, 148.9, 133.3, 129.5, 129.0, 128.1, 127.1, 126.9, 123.6, 77.5, 77.2, 76.8, 45.2, 13.7 ppm. HRMS (ESI) m/z calculated for C17H20ClN2Se [M + H]+, 367.0480; found, 367.0492. Phenyl (Z)-N′-(3-Nitrophenyl)-N,N-dipropylcarbamimidoselenoate (6b). Following the general procedure, using 50/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (79.6 mg, 66% yield). IR 2963, 2931, 1585, 1520, 1344, 1207, 1118, 820, 735, 680 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 8.2, 2.3 Hz, 1H), 7.28 (t, J = 2.2 Hz, 1H), 7.11−7.03 (m, 4H), 7.00 (dd, J = 8.1, 6.4 Hz, 2H), 6.86 (dd, J = 7.8, 1.1 Hz, 1H), 3.58−3.48 (m, 4H), 1.74−1.65 (m, 4H), 0.94 (t, J = 7.4 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.8, 151.0, 148.2, 133.9, 128.9, 128.6, 128.5, 128.3, 127.4, 117.5, 115.8, 77.5, 77.2, 76.8, 53.0, 21.9, 11.4 ppm. HRMS (ESI) m/z calculated for C19H24N3O2Se [M + H]+, 406.1034; found, 406.1044. Phenyl (Z)-N,N-Dibutyl-N′-(3-nitrophenyl)carbamimidoselenoate (6c). Following the general procedure, using 50/1 petroleum ether/ EtOAc as the eluant afforded a yellow oil liquid (90.6 mg, 70% yield). IR 2958, 2929, 1580, 1520, 1345, 1185, 1120, 822, 735, 680 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.60 (dd, J = 8.1, 2.3 Hz, 1H), 7.29 (d, J = 1.8 Hz, 1H), 7.14−6.96 (m, 6H), 6.87 (dd, J = 7.8, 2.0 Hz, 1H), 3.56 (t, J = 7.7 Hz, 4H), 1.64 (p, J = 7.4 Hz, 4H), 1.35 (h, J = 7.4 Hz, 4H), 0.96 (t, J = 7.4 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.9, 150.9, 148.2, 133.9, 128.9, 128.6, 128.3, 127.4, 117.5, 115.8, 77.5, 77.2, 76.8, 51.0, 30.8, 20.2, 14.0 ppm. HRMS (ESI) m/z calculated for C21H28N3O2Se [M + H]+, 434.1347; found, 434.1353. Phenyl (Z)-N,N-Dibenzyl-N′-(3-nitrophenyl)carbamimidoselenoate (6d). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (77.9 mg, 52% yield). Mp: 67.2−67.8 °C. IR 2927, 1568, 1518, 1346, 1171, 1075, 823, 736, 697 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.65 (ddd, J 10871

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry

(m, 1H), 7.15 (t, J = 8.1 Hz, 1H), 6.96 (dd, J = 8.0, 2.1 Hz, 1H), 3.67 (q, J = 7.0 Hz, 4H), 1.28 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.8, 148.9, 148.1, 147.3, 134.0, 132.8, 129.9, 128.7, 128.5, 127.3, 126.0, 117.3, 116.8, 77.5, 77.2, 76.8, 45.5, 13.9 ppm. HRMS (ESI) m/z calculated for C17H19N4O4Se [M + H]+, 423.0572; found, 423.0565. Methyl (Z)-2-((N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoyl)selanyl)benzoate (7d). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a orange solid (102.3 mg, 79% yield). Mp: 65.1−67.0 °C. IR 2970, 2930, 1576, 1520, 1344, 1257, 1223, 1114, 737, 681 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.80 (dd, J = 7.8, 1.7 Hz, 1H), 7.65 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.50− 7.45 (m, 2H), 7.36 (td, J = 7.7, 1.6 Hz, 1H), 7.20−7.16 (m, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.92 (ddd, J = 7.9, 2.2, 1.0 Hz, 1H), 3.83 (s, 3H), 3.67 (q, J = 7.0 Hz, 4H), 1.26 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 166.8, 152.4, 150.3, 148.1, 135.2, 132.8, 131.8, 131.2, 129.0, 128.9, 128.4, 126.1, 117.3, 116.4, 77.5, 77.2, 76.8, 52.4, 45.2, 13.9 ppm. HRMS (ESI) m/z calculated for C19H22N3O4Se [M + H]+, 436.0776; found, 436.0783. 4-Cyanophenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7e). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (78.7 mg, 65% yield). Mp: 125.2−126.4 °C. IR 2972, 2928, 2224, 1581, 1517, 1349, 1217, 1081, 743, 677 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.67 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.47 (t, J = 2.2 Hz, 1H), 7.36− 7.31 (m, 2H), 7.28−7.23 (m, 2H), 7.10 (t, J = 8.0 Hz, 1H), 6.83 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 3.65 (q, J = 7.0 Hz, 4H), 1.26 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.4, 148.2, 147.9, 135.9, 133.1, 132.1, 129.0, 128.6, 118.2, 117.2, 116.4, 110.7, 77.5, 77.2, 76.8, 45.7, 13.9 ppm. HRMS (ESI) m/z calculated for C18H19N4O2Se [M + H]+, 403.0673; found, 403.0677. 4-Chlorophenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7f). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (81.5 mg, 66% yield). Mp: 92.3−94.1 °C. IR 3312, 2976, 1595, 1344, 1258, 1113, 1094, 1021 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.66 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.38 (t, J = 2.2 Hz, 1H), 7.10 (t, J = 8.1 Hz, 1H), 7.04−6.98 (m, 4H), 6.84 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 3.63 (q, J = 7.0 Hz, 4H), 1.24 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ151.6, 149.9, 148.2, 135.2, 133.9, 129.1, 128.7, 128.5, 126.6, 117.3, 116.0, 77.5, 77.2, 76.8, 45.6, 14.0 ppm. HRMS (ESI) m/z calculated for C17H19ClN3O2Se [M + H]+, 412.0331; found, 412.0326. 4-Fluorophenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7g). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (81.4 mg, 69% yield). Mp: 66.5−68.3 °C. IR 2982, 2932, 1579, 1518, 1344, 1218, 1114, 825, 741, 678 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.64 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.39 (t, J = 2.2 Hz, 1H), 7.11−7.04 (m, 3H), 6.82 (ddd, J = 8.0, 2.1, 1.0 Hz, 1H), 6.75−6.69 (m, 2H), 3.63 (q, J = 7.1 Hz, 4H), 1.23 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 163.6, 161.2, 151.6, 150.5, 148.3, 136.2, 136.1, 128.7, 128.5, 123.0, 122.9, 117.1, 116.3, 116.1, 115.9, 77.5, 77.2, 76.8, 45.5, 13.9 ppm. HRMS (ESI) m/z calculated for C17H19FN3O2Se [M + H]+, 396.0627; found, 396.0631. 4-(Trifluoromethyl)phenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7h). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (91.1 mg, 68% yield). Mp: 93.2−95.0 °C. IR 2978, 2932, 1561, 1519, 1320, 1116, 1076,828, 741, 677 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.64 (dd, J = 8.1, 1.3 Hz, 1H), 7.41 (t, J = 2.2 Hz, 1H), 7.26 (q, J = 8.4 Hz, 4H), 7.06 (t, J = 8.0 Hz, 1H), 6.82 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 3.65 (q, J = 7.1 Hz, 4H), 1.26 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.5, 148.9, 148.2, 133.6, 133.5, 129.7, 129.4, 128.8, 128.5, 125.7, 125.6, 125.6, 125.5, 125.2, 122.5, 117.3, 116.2, 77.5, 77.2, 76.8, 45.7, 13.9 ppm. HRMS (ESI) m/z calculated for C18H19F3N3O2Se [M + H]+, 446.0595; found, 446.0588. 4-Methoxyphenyl (Z)-N,N-Diethyl-N ′-(3-nitrophenyl)carbamimidoselenoate (7i). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (87.2 mg, 72% yield). Mp: 51.2−52.2 °C. IR 2973, 2933, 1586, 1517,

20/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (89.3 mg, 68% yield). IR 2946, 2881, 1590, 1568, 1522, 1347, 1192, 736, 679 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.85 (dd, J = 8.2, 1.3 Hz, 1H), 7.68 (t, J = 2.2 Hz, 1H), 7.44 (d, J = 6.9 Hz, 1H), 7.35 (t, J = 8.0 Hz, 1H), 7.19−6.94 (m, 8H), 6.85 (d, J = 7.1 Hz, 1H), 3.86 (t, J = 6.6 Hz, 2H), 2.34 (t, J = 6.5 Hz, 2H), 1.88 (p, J = 6.5 Hz, 2H) ppm. 13 C NMR (100 MHz, CDCl3) δ 153.6, 151.4, 148.5, 140.2, 135.0, 132.0, 129.2, 128.7, 128.1, 128.0, 128.0, 127.8, 125.8, 124.0, 124.0, 117.7, 116.9, 77.5, 77.2, 76.8, 48.8, 26.6, 24.1. HRMS (ESI) m/z calculated for C22H20N3O2Se [M + H]+, 438.0721; found, 438.0700. Phenyl (Z)-N-Methyl-N′-(3-nitrophenyl)-N-phenylcarbamimidoselenoate (6l). Following the general procedure, using 20/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (179.6 mg, 73% yield). Mp: 66.7−68.2 °C. IR 3513, 3336, 2972, 1598, 1335, 1073 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.68 (dd, J = 7.9, 2.1 Hz, 1H), 7.51 (t, J = 2.2 Hz, 1H), 7.31−7.21 (m, 3H), 7.18−7.13 (m, 3H), 7.06−6.90 (m, 6H), 3.45 (s, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.9, 151.1, 148.2, 145.7, 134.6, 129.1, 128.6, 128.6, 128.3, 127.6, 127.5, 127.0, 117.2, 116.7, 77.5, 77.2, 76.8, 41.8 ppm. HRMS (ESI) m/ z calculated for C20H18N3O2Se [M + H]+, 412.0564; found, 412.0554. Phenyl (Z)-N-Ethyl-N′-(3-nitrophenyl)-N-(o-tolyl)carbamimidoselenoate (6m). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (64.3 mg, 49% yield). Mp: 96.1−98.0 °C. IR 3340, 2965, 1594, 1240, 1135, 1076 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.57 (ddd, J = 8.1, 2.3, 1.0 Hz, 1H), 7.39 (t, J = 2.2 Hz, 1H), 7.29 (d, J = 4.5 Hz, 2H), 7.22 (dt, J = 8.9, 4.3 Hz, 1H), 7.15 (d, J = 7.2 Hz, 1H), 7.06 (t, J = 8.0 Hz, 1H), 7.01−6.95 (m, 4H), 6.93−6.88 (m, 2H), 4.20 (s, 1H), 3.54 (s, 1H), 2.39 (s, 3H), 1.25 (t, J = 7.1 Hz, 3H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.0, 150.9, 148.2, 142.4, 137.2, 134.9, 131.3, 130.1, 128.7, 128.5, 128.5, 128.3, 128.2, 127.6, 126.8, 117.3, 116.1, 77.5, 77.2, 76.8, 47.3, 18.3, 12.8 ppm. HRMS (ESI) m/z calculated for C22H22N3O2Se [M + H]+, 440.0877; found, 440.0891. (3R,5R,8S,9R,10R,13R,14R)-10,13-Dimethyl-17-oxohexadecahydro-1H-cyclopenta[a]phenanthren-3-yl 3-(methyl((Z)-((3-nitrophenyl)imino)(phenylselanyl)methyl)amino)propanoate (6o). Following the general procedure, using 10/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (49.7 mg, 37% yield). Mp: 46.8− 48.5 °C. IR 2988, 2972, 1733, 1589, 1522, 1394, 1345, 1250, 1066, 737 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.67 (dd, J = 8.2, 1.3 Hz, 1H), 7.36 (t, J = 2.1 Hz, 1H), 7.16−7.04 (m, 6H), 6.92 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 4.73 (td, J = 11.4, 5.7 Hz, 1H), 3.91 (t, J = 7.0 Hz, 2H), 3.19 (s, 3H), 2.66 (t, J = 7.0 Hz, 2H), 2.47−2.40 (m, 1H), 2.10−2.04 (m, 1H), 1.96−1.90 (m, 1H), 1.82−1.73 (m, 4H), 1.64 (ddd, J = 12.4, 6.2, 3.6 Hz, 2H), 1.54 (dd, J = 10.8, 4.7 Hz, 2H), 1.39−1.22 (m, 9H), 1.08−0.96 (m, 2H), 0.86 (s, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 171.2, 151.6, 151.3, 148.3, 133.8, 129.2, 128.6, 128.6, 128.3, 127.7, 117.5, 116.5, 77.5, 77.2, 76.8, 74.1, 54.4, 51.4, 48.8, 47.9, 44.7, 39.4, 36.8, 35.9, 35.7, 35.1, 34.1, 33.2, 31.6, 30.9, 29.8, 28.4, 27.5, 21.9, 20.6, 13.9, 12.3 ppm. HRMS (ESI) m/z calculated for C36H46N3O5Se [M + H]+, 680.2603; found, 680.2590. 4-Nitrophenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7b). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (96.9 mg, 77% yield). Mp: 113.2−114.8 °C. IR 2960, 2927, 1583, 1513, 1347, 1114, 1081, 842, 740, 677 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.92−7.85 (m, 2H), 7.65 (dd, J = 8.2, 2.3 Hz, 1H), 7.43 (t, J = 2.2 Hz, 1H), 7.30 (d, J = 8.8 Hz, 2H), 7.08 (t, J = 8.0 Hz, 1H), 6.88−6.81 (m, 1H), 3.64 (q, J = 7.1 Hz, 4H), 1.25 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.4, 148.2, 147.5, 146.7, 138.6, 132.8, 129.0, 128.7, 123.7, 117.2, 116.5, 77.5, 77.2, 76.8, 45.8, 13.9 ppm. HRMS (ESI) m/z calculated for C17H19N4O4Se [M + H]+, 423.0572; found, 423.0576. 2-Nitrophenyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7c). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (95.3 mg, 75% yield). Mp: 83.8−85.6 °C. IR 2973, 2902, 1583, 1518, 1339, 1219, 1075, 728, 680 cm−1. 1H NMR (400 MHz, CDCl3) δ 8.02 (dd, J = 8.3, 1.5 Hz, 1H), 7.68 (dd, J = 7.9, 2.1 Hz, 1H), 7.62 (dd, J = 8.1, 1.3 Hz, 1H), 7.50 (td, J = 7.7, 1.5 Hz, 1H), 7.41−7.36 (m, 1H), 7.32−7.28 10872

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

The Journal of Organic Chemistry

■

1340, 1248, 1221, 812, 740, 674 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.61 (dd, J = 8.2, 1.3 Hz, 1H), 7.25 (t, J = 2.2 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 7.01−6.94 (m, 2H), 6.88 (dd, J = 7.9, 1.1 Hz, 1H), 6.57− 6.50 (m, 2H), 3.70 (s, 3H), 3.62 (q, J = 7.0 Hz, 4H), 1.23 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 159.5, 151.8, 151.4, 148.2, 136.1, 128.4, 128.3, 118.3, 117.4, 115.8, 114.7, 77.5, 77.2, 76.8, 55.3, 45.4, 14.0 ppm. HRMS (ESI) m/z calculated for C18H22N3O3Se [M + H]+, 408.0826; found, 408.0820. o-Tolyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7j). Following the general procedure, using 30/1 petroleum ether/ EtOAc as the eluant afforded a yellow solid (63.9 mg, 55% yield). Mp: 49.4−50.6 °C. IR 2968, 2927, 1570, 1515, 1336, 1223, 1112, 1075, 739, 677 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.56 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.28 (t, J = 2.2 Hz, 1H), 7.10 (dd, J = 7.7, 1.4 Hz, 1H), 7.05−6.91 (m, 3H), 6.85−6.77 (m, 2H), 3.65 (q, J = 7.0 Hz, 4H), 2.16 (s, 3H), 1.25 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.8, 150.0, 148.1, 140.3, 135.2, 129.9, 129.4, 128.3, 128.2, 128.1, 126.4, 116.9, 115.9, 77.5, 77.2, 76.8, 45.5, 22.6, 14.0 ppm. HRMS (ESI) m/z calculated for C18H22N3O2Se [M + H]+, 392.0877; found, 392.0886. m-Tolyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate(7k). Following the general procedure, using 30/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (70.6 mg, 60% yield). IR 2971, 2930, 1583, 1520, 1343, 1121, 1111, 740, 679 cm−1. 1 H NMR (400 MHz, CDCl3) δ 7.61 (dd, J = 8.1, 1.3 Hz, 1H), 7.28 (t, J = 2.2 Hz, 1H), 7.09 (t, J = 8.0 Hz, 1H), 6.97−6.83 (m, 5H), 3.64 (q, J = 7.0 Hz, 4H), 2.15 (s, 3H), 1.24 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.8, 150.6, 148.1, 138.8, 134.6, 131.1, 128.8, 128.6, 128.4, 128.2, 128.0, 117.7, 115.8, 77.5, 77.2, 76.8, 45.5, 21.1, 13.9 ppm. HRMS (ESI) m/z calculated for C18H22N3O2Se [M + H]+, 392.0877; found, 392.0883. p-Tolyl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7l). Following the general procedure, using 30/1 petroleum ether/ EtOAc as the eluant afforded an orange solid (61.6 mg, 53% yield). Mp: 64.2−65.9 °C. IR 2972, 2930, 1581, 1516, 1341, 1221, 1074, 804, 740, 678 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.62 (ddd, J = 8.2, 2.3, 1.0 Hz, 1H), 7.22 (t, J = 2.2 Hz, 1H), 7.10 (t, J = 8.0 Hz, 1H), 6.98− 6.94 (m, 2H), 6.90 (ddd, J = 7.9, 2.1, 1.0 Hz, 1H), 6.81 (d, J = 7.8 Hz, 2H), 3.63 (q, J = 7.0 Hz, 4H), 2.19 (s, 3H), 1.23 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.9, 150.9, 148.2, 137.8, 134.2, 129.8, 128.4, 128.3, 124.7, 117.7, 115.9, 77.5, 77.2, 76.8, 45.5, 21.0, 14.0 ppm. HRMS (ESI) m/z calculated for C18H22N3O2Se [M + H]+, 392.0877; found, 392.0884. Pyridin-3-yl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7m). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a yellow solid (87.2 mg, 77% yield). Mp: 44.6−46.3 °C. IR 2962, 2928, 1580, 1519, 1343, 1223, 1076, 843, 740, 680 cm−1. 1H NMR (400 MHz, CDCl3) δ 8.30 (q, J = 1.9 Hz, 2H), 7.65 (dd, J = 8.2, 1.3 Hz, 1H), 7.42−7.35 (m, 2H), 7.10 (t, J = 8.0 Hz, 1H), 6.95 (dd, J = 7.9, 4.8 Hz, 1H), 6.84 (dd, J = 7.9, 1.1 Hz, 1H), 3.66 (q, J = 7.0 Hz, 4H), 1.27 (t, J = 7.0 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 153.6, 151.3, 149.0, 148.4, 148.2, 141.0, 128.8, 128.7, 126.1, 123.9, 117.2, 116.4, 77.5, 77.2, 76.8, 45.8, 14.0 ppm. HRMS (ESI) m/z calculated for C16H19N4O2Se [M + H]+, 379.0673; found, 379.0679. Thiophen-3-yl (Z)-N,N-Diethyl-N′-(3-nitrophenyl)carbamimidoselenoate (7n). Following the general procedure, using 15/1 petroleum ether/EtOAc as the eluant afforded a yellow oil liquid (75.9 mg, 66% yield). IR 2965, 2921, 1584, 1519, 1343, 1220, 769, 740, 678 cm−1. 1H NMR (400 MHz, CDCl3) δ 7.66 (dd, J = 8.2, 1.3 Hz, 1H), 7.38 (t, J = 2.2 Hz, 1H), 7.14 (t, J = 8.0 Hz, 1H), 7.05 (dd, J = 5.0, 2.9 Hz, 1H), 6.90 (dd, J = 7.9, 1.1 Hz, 1H), 6.83 (dd, J = 3.0, 1.3 Hz, 1H), 6.71 (dd, J = 4.9, 1.2 Hz, 1H), 3.63 (q, J = 7.1 Hz, 4H), 1.23 (t, J = 7.1 Hz, 6H) ppm. 13C NMR (100 MHz, CDCl3) δ 151.6, 149.9, 148.3, 132.5, 129.0, 128.4, 128.3, 125.9, 120.4, 117.0, 116.0, 77.5, 77.2, 76.8, 45.5, 13.9 ppm. HRMS (ESI) m/z calculated for C15H18N3O2SSe [M + H]+, 384.0285; found, 384.0277.

Article

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01663. The copies of 1H and 13C NMR spectra of the products (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Shun-Yi Wang: 0000-0002-8985-8753 Shun-Jun Ji: 0000-0002-4299-3528 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We gratefully acknowledge the National Natural Science Foundation of China (21772137, 21542015, 21672157), the Major Basic Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions (No. 16KJA150002), the Ph.D. Programs Foundation of Ministry of Education of China (2013201130004), PAPD, and Soochow University for financial support, and State and Local Joint Engineering Laboratory for Novel Functional Polymeric Materials.

■

REFERENCES

(1) (a) Nicolaou, K. C.; Winssinger, N.; Hughes, R.; Smethurst, C.; Cho, S. Y. Angew. Chem., Int. Ed. 2000, 39, 1084. (b) Okamoto, K.; Nishibayashi, Y.; Uemura, S.; Toshimitsu, A. Angew. Chem., Int. Ed. 2005, 44, 3588. (c) Khokhar, S. S.; Wirth, T. Angew. Chem., Int. Ed. 2004, 43, 631. (d) Trenner, J.; Depken, T.; Weber, C.; Breder, A. Angew. Chem., Int. Ed. 2013, 52, 8952. (e) Guo, R.; Huang, J.; Huang, H.; Zhao, X. Org. Lett. 2016, 18, 504. (2) (a) Mugesh, G.; du Mont, W.; Sies, H. Chem. Rev. 2001, 101, 2125. (b) Nogueira, C. W.; Zeni, G.; Rocha, J. B. T. Chem. Rev. 2004, 104, 6255. (c) Sarma, B. K.; Mugesh, G. J. Am. Chem. Soc. 2005, 127, 11477. (d) Bhabak, K. P.; Mugesh, G. Chem. - Eur. J. 2007, 13, 4594. (e) Bhabak, K. P.; Mugesh, G. Acc. Chem. Res. 2010, 43, 1408. (f) Manjare, S.; Kim, T. Y.; Churchill, D. G. Acc. Chem. Res. 2014, 47, 2985. (g) Li, T. Y.; Yi, Y.; Xu, H. P. Huaxue Xuebao 2014, 72, 1079. (3) (a) Reich, H. J.; Jasperse, C. P. J. Am. Chem. Soc. 1987, 109, 5549. (b) Back, T. G.; Dyck, B. P. J. Am. Chem. Soc. 1997, 119, 2079. (c) Jacob, C.; Giles, G. I.; Giles, N. M.; Sies, H. Angew. Chem., Int. Ed. 2003, 42, 4742. (4) (a) Muller, A.; Cadenas, E.; Graf, P.; Sies, H. Biochem. Pharmacol. 1984, 33, 3235. (b) Parnham, M.; Sies, H. Expert Opin. Invest. Drugs 2000, 9, 607. (5) (a) Ibáñez, E.; Plano, D.; Font, M.; Calvo, A.; Prior, C.; Palop, J. A.; Sanmartín, C. Eur. J. Med. Chem. 2011, 46, 265. (b) Terazawa, R.; Garud, D. R.; Hamada, N.; Fujita, Y.; Itoh, T.; Nozawa, Y.; Nakane, K.; Deguchi, T.; Koketsu, M.; Ito, M. Bioorg. Med. Chem. 2010, 18, 7001. (c) Levshin, I. B.; Tsurkan, A. A.; Rudzit, É. A.; Neshchadim, G. N. Pharm. Chem. J. 1981, 15, 242. (6) Wolfrom, M. L.; Rice, F. A. H. J. Am. Chem. Soc. 1947, 69, 1833. (7) (a) Chu, S.; Mautner, H. G. J. Org. Chem. 1962, 27, 2899. (b) Comrie, A. M.; Dingwall, D.; Stenlake, J. B. J. Pharm. Pharmacol. 1964, 16, 268. (c) Warner, J. S.; Page, T. F., Jr. J. Org. Chem. 1966, 31, 606. (d) Hideg, K.; Sár, C. P.; Hankovszky, O. H.; Jerkovich, G. Synthesis 1991, 1991, 616. (e) Kálai, T.; Bárácz, N. M.; Jerkovich, G.; Hankovszky, O. H.; Hideg, K. Synthesis 1995, 1995, 1278. (f) Kálai, T.; Balog, M.; Jekö, J.; Hideg, K. Synthesis 1999, 1999, 973. (g) Plano, D.; 10873

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874

Article

The Journal of Organic Chemistry Sanmartin, C.; Moreno, E.; Prior, C.; Calvo, A.; Palop, J. A. Bioorg. Med. Chem. Lett. 2007, 17, 6853. (8) (a) Zhou, Y.; Denk, M. K. Tetrahedron Lett. 2003, 44, 1295. (b) Koketsu, M. Synth. Commun. 2002, 32, 3075. (9) (a) Fang, Y.; Wang, S. Y.; Shen, X. B.; Ji, S. J. Org. Chem. Front. 2015, 2, 1338. (b) Maeda, H.; Matsuya, T.; Kambe, N.; Sonoda, N. Tetrahedron 1997, 53, 12159. (c) Fang, Y.; Zhu, Z. L.; Xu, P.; Wang, S. Y.; Ji, S. J. Green Chem. 2017, 19, 1613. (10) Fujiwara, S. I.; Asanuma, Y.; Shin-ike, T.; Kambe, N. J. Org. Chem. 2007, 72, 8087. (11) Saegusa, T.; Ito, Y.; Kobayashi, S.; Hirota, K.; Yoshioka, H. Tetrahedron Lett. 1966, 7, 6121. (12) (a) Maeda, H.; Matsuya, T.; Kambe, N.; Sonoda, N.; Fujiwara, S.; Shin-ike, T. Tetrahedron 1997, 53, 12159. (b) Asanuma, Y.; Fujiwara, S.; Shin-ike, T.; Kambe, N. J. Org. Chem. 2004, 69, 4845. (13) (a) Xiao, F. X.; Chen, S. Q.; Li, C.; Huang, H. W.; Deng, G. J. Adv. Synth. Catal. 2016, 358, 3881. (b) Yan, K.; Yang, D. S.; Wei, W.; Lu, S. L.; Li, G. Q.; Zhao, C. X.; Zhang, Q. Y.; Wang, H. Org. Chem. Front. 2016, 3, 66.

10874

DOI: 10.1021/acs.joc.7b01663 J. Org. Chem. 2017, 82, 10866−10874