Transition-Metal-Free Coupling Reaction of Dithiocarbamates with

Apr 25, 2018 - Zhang, H.; Bao, X.; Song, Y.; Qu, J.; Wang, B. Iodine-Catalysed Versatile ...... Chripkova, M.; Drutovic, D.; Pilatova, M.; Mikes, J.; ...
0 downloads 0 Views 843KB Size
Download PDF
Note Cite This: J. Org. Chem. 2018, 83, 5778−5783

pubs.acs.org/joc

Transition-Metal-Free Coupling Reaction of Dithiocarbamates with Indoles: C−S Bond Formation Azim Ziyaei Halimehjani,*,† Sahar Shokrgozar,‡ and Petr Beier*,‡ †

Faculty of Chemistry, Kharazmi University, P.O. Box 15719-14911, 49 Mofateh Street, Tehran 14911, Iran Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Flemingovo nám. 2, Prague 6, Prague 166 10, Czech Republic

‡

S Supporting Information *

ABSTRACT: A one-pot three-component route for the direct introduction of dithiocarbamates into indoles using a C−H sulfenylation strategy mediated by molecular iodine is disclosed. Various indole derivatives including 1-methylindole, 2methylindole, 3-methylindole, and 5-substituted indoles were applied successfully in this protocol to afford diverse indoledithiocarbamates containing the dithiocarbamate group on the position two or three in good to high yields. The reactions do not require transition metals or disulfiram but use an environmentally benign solvent and simple commercially available starting materials.

T

with disulfiram in the presence of a catalytic amount of iodine and FeF3 in dichloroethane at 80 °C (Scheme 1a).21 The chemistry and biological activities of indole-dithiocarbamates

he formation of C−S bonds is important in synthetic organic chemistry for the construction of various synthetic and natural biologically active compounds.1 Many reports exist for the direct C−H sulfenylation of indoles with thiols or disulfides. Various catalytic systems such as Pd/Al2O3/CuCl2,2 NBS,3 NCS,4 I2/DMSO,5 I2/air,6 NaOH/DMSO,7 K2CO3/ DMSO,8 I2/H2O2,9 I2/TBHP,10 (NH4)2S2O8,11 FeF3/I2,12 Nthioalkyl- and N-thioarylphthalimides/MgBr2,13 and CpCo(CO)I2/Cu(OAc)2/In(OTf)314 have been developed for the direct C−S bond formation via a C−H thiolation strategy. Notably, most of the reported methods are applicable for 3sulfenylation of indoles; however, 2-sulfenylation of indoles is rare.10,15 While numerous methods are available for the direct C−S bond formation via direct C−H sulfenylation of indoles with thiols and disulfides, a C−S bond formation through the direct introduction of dithiocarbamates into indoles has not been reported to date. The chemistry of dithiocarbamates is well-known for their widespread applications in agriculture,16 polymer chemistry,17 and coordination chemistry.18 Recently, dithiocarbamates have been used as intermediates in synthetic organic chemistry for the construction of biologically active compounds.19 Various heterocyclic compounds containing dithiocarbamate groups including chromone-dithiocarbamate, triazole-dithiocarbamates, benzodioxole-dithiocarbamates, benzimidazole-dithiocarbamates, indole-dithiocarbamates, and quinazolinone-dithiocarbamate have been introduced as potential anticancer agents.20 For this reason, methods of introduction of dithiocarbamate groups into heterocyclic compounds are useful in the design of novel biologically active compounds. Recently, Jiao et al. reported an efficient protocol for C−H sulfenylation of imidazohetecocycles © 2018 American Chemical Society

Scheme 1. Published and Proposed Introduction of Dithiocarbamates into Nitrogen Heterocyles

Received: January 23, 2018 Published: April 25, 2018 5778

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783

Note

The Journal of Organic Chemistry

iodine gave a similar result (Table 1, entry 3). However, increasing the reaction temperature to reflux afforded the product 2a in 45% isolated yield (Table 1, entry 6). Under these conditions, various solvents such as methanol, water, acetonitrile, DMF, toluene, THF, and petroleum ether were screened and afforded 2a, albeit in an unsatisfactory yield (Table 1, entries 7−13). In addition, a low yield (20%) of 2a was obtained under solvent-free conditions (Table 1, entry 14). We observed that by increasing the amount of iodine to 100 mol % in ethanol, the yield significantly improved to 65% (Table 1, entry 16). Attempts to improve the product yield by using iodine in the presence of various oxidants such as TBHP, H2O2, and DMSO gave unsatisfactory results (Table 1, entries 17−19). Furthermore, performing the reaction under conditions suitable for thiolation of indoles with thiols and disulfide by using NaOH/DMSO,7 K2CO3/DMSO,8 and NBS3 gave no product formation (Table 1, entries 20−22). In summary, stirring diethylamine (2 equiv) and CS2 (3 equiv) at room temperature for 10 min, followed by the addition of 1methylindole (1 equiv) and iodine (1 equiv), and stirring for 24 h at 60 °C was considered as that optimal reaction conditions. The scope of the reaction under the optimized reaction conditions was examined using various commercially available secondary amines and indoles. As shown in Table 2, all tested acyclic and cyclic secondary amines such as dimethylamine, diethylamine, dipropylamine, pyrrolidine, piperidine, azepane, and morpholine afforded the corresponding products 2 in high yields. Indole, 1-methylindole, 2-methylindole, 5-bromoindole, and 5-methoxyindole were applied successfully in this protocol to afford products containing the dithiocarbamate group substituted in the position three. The presence of an electron-withdrawing group on the carbon atom at the position five in the indole decreased the yield significantly (Table 2, compound 2p). Interestingly, by performing the reaction with 3-methylindole, the dithiocarbamate group was substituted on the carbon at the position two. It was also observed that primary amines were not suitable starting materials for this reaction and gave a mixture of isothiocyanate, starting materials, and other unidentified side products. A proposed mechanism for this transformation is depicted in Scheme 2. Initially, the reaction of an amine with CS2 provides the intermediate dithiocarbamic acid A, which reacts with molecular iodine to produce the intermediate B. The intermediate B may directly undergo an electrophilic substitution reaction with 1a to afford the intermediate D or react with another equiv of A to provide disulfiram C. Disulfiram C can furnish the intermediate B by the reaction with molecular iodine or HI. Finally, the removal of HI from D affords the product 2a. The proposed mechanism also explains why 1 equiv of iodine is needed for this transformation. A control experiment without using indole afforded the corresponding disulfiram C in a good yield. By using disulfiram in this protocol, a similar result was obtained in the presence of 0.5 equiv of iodine. For 3-substituted indoles, the reaction took place on the position two, via a similar mechanism. In conclusion, an efficient and environmentally benign protocol for the synthesis of indole-dithiocarbamates is reported for the first time via an iodine-mediated one-pot three-component reaction of secondary amines, CS2, and indoles. This metal-free method proceeds in an environmentally benign solvent and allows for an efficient introduction of the dithiocarbamate group by C−H sulfenylation of indoles at position two or three.

have been less investigated, presumably due to the lack of efficient procedures for their synthesis. Brassinin and isobrassinin are the most famous indole-dithiocarbamate compounds.22 Przheval’skii et al. reported the synthesis of S(indolyl-3) diethyl dithiocarmamates via Fischer indol synthesis (Scheme 1b).23 In addition, Krasovskiy et al. reported the synthesis of S-(indolyl-3) dimethyldithiocarbamate using metalated indole (Grignard reagent) and tetramethylthiuram disulfide (Scheme 1c).24 Due to a widespread application of indoles and dithiocarbamates and their importance in drug discovery, the development of elegant technologies enabling synthesis of compounds containing both the indole and the dithiocarbamate groups in a single structure is in high demand. For this purpose, a direct reaction of an amine, carbon disulfide, and an indole in the presence of iodine under transition-metal-free conditions was developed (Scheme 1d). C−H sulfenylation of indoles with dithiocarbamates was optimized using 1-methylindole, CS2, and diethylamine as a model reaction (Table 1). Initially, we observed that the reaction of diethylamine (2 equiv) with CS2 (3 equiv) in ethanol for 10 min, followed by the addition of 1-methylindole (0.5 mmol, 1 equiv) and iodine (25 mol %), with stirring for 24 h at room temperature afforded only a trace amount of 2a (Table 1, entry 1). Performing the same reaction with 50 mol % Table 1. Optimization of the Reaction Conditionsa

entry

catalyst (x mol %)

1 2 3 4 5 6 7 8 9 10 11 12 13

I2 I2 I2 I2 I2 I2 I2 I2 I2 I2 I2 I2 I2

(25) (25) (50) (50) (50) (50) (50) (50) (50) (50) (50) (50) (50)

14 15 16 17 18

I2 I2 I2 I2 I2

(50) (75) (100) (50) (50)

19 20

I2 (50) NaOH (200) K2CO3 (50) NBS (120)

21 22

oxidant (y mol %)

TBHP (100) DMSO (100) H2O2 (100) DMSO DMSO

time (h)/ temp (°C)

yield (%)

EtOH EtOH EtOH EtOH EtOH EtOH MeOH H2O CH3CN DMF toluene THF petroleum ether solvent-free EtOH EtOH EtOH EtOH

24/rt 3/reflux 24/rt 24/50 6/reflux 24/reflux 24/reflux 24/70 24/reflux 24/70 24/70 24/reflux 24/reflux

trace trace trace 20 35 45 30 trace 20 25 10 30 10

24/70 24/reflux 24/60 24/reflux 24/reflux

20 45 65 15 trace

EtOH DMSO

24/70 24/100

30 NRb

DMSO CH2Cl2

6/70 3/ice bath

NR trace

solvent

a

Reaction conditions: 1-methylindole (0.5 mmol), diethylamine (1 mmol), CS2 (1.5 mmol), catalyst (x mol %), oxidant (y mol %), solvent (3 mL). bNR = no reaction. 5779

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783

Note

The Journal of Organic Chemistry

PerkinElmer 2004 Series II CHN analyzer. High-resolution mass spectra (HRMS) were recorded on an Agilent 7890A gas chromatograph coupled with a Waters GCT Premier orthogonal acceleration time-of-flight detector using electron impact (EI) ionization. General Procedure for Synthesis of Indole-dithiocarbamates 2a− u. In a Schlenk flask under an Ar or a N2 atmosphere, EtOH (6 mL), a secondary amine (2 mmol, 2 equiv), and CS2 (3 mmol, 0.18 mL, 3 equiv) were added, respectively. After the mixture was stirred for 10 min at room temperature, an indole (1 mmol, 1 equiv) and I2 (1 mmol, 0.254 g, 1 equiv) were added, and the reaction mixture was further stirred at 60 °C for 24 h. An aqueous NaHSO3 solution was added, and the product was extracted into EtOAc (3 × 10 mL). The organic extracts were combined, washed with water (2 × 10 mL), dried with anhydrous Na2SO4 or MgSO4, and evaporated to give crude products. Chromatography on silica gel, eluting with EtOAc/ petroleum ether (1:15), afforded pure products. 1-Methyl-1H-indol-3-yl Diethylcarbamodithioate (2a): yellow solid; yield 181 mg (65%); mp 117−118 °C; IR (KBr) ν 1508, 1482, 1458, 1267, 1203, 740 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.63 (s, 1H, H−Ar), 7.52 (td, J = 8.2, 0.9 Hz, 1H, H−Ar), 7.35 (td, J = 7.8, 1.0 Hz, 1H, H−Ar), 7.21 (m, 1H, H−Ar), 7.10 (m, 1H, H−Ar), 3.97−3.88 (m, 4H), 3.84 (s, 3H), 1.37 (t, J = 7.0 Hz, 3H), 1.17 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (75 MHz, DMSO-d6) δ 196.3, 137.6, 137.0, 129.8, 121.8, 120.1, 118.7, 110.4, 99.1, 49.8, 46.9, 32.8, 12.8, 11.4 ppm. Anal. Calcd (%) for C14H18N2S2 (MW 278.44): C, 60.39; H, 6.52; N, 10.06. Found: C, 60.34; H, 6.24; N, 9.88. 1-Methyl-1H-indol-3-yl Pyrrolidine-1-carbodithioate (2b): cream solid; yield 218 mg (79%); mp 163−164 °C; IR (KBr) ν 1511, 1460, 1425, 1266, 1228, 1109, 1030, 959, 734 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.59 (s, 1H, H−Ar), 7.51 (dd, 1H, J = 8.3, 1.1 Hz, H− Ar), 7.39 (dd, 1H, J = 7.9, 1.1 Hz, H−Ar), 7.21 (m, 1H, H−Ar), 7.09 (m, 1H, H−Ar), 3.86−3.82 (m, 5H), 3.74 (t, 2H, J = 7.0 Hz), 2.13− 2.03 (m, 2H), 1.96−1.87 (m, 2H) ppm; 13C NMR (75 MHz, DMSOd6) δ 192.3, 137.4, 137.0, 129.7, 121.8, 120.1, 118.8, 110.5, 98.9, 55.4, 50.7, 32.9, 26.0, 23.8 ppm. Anal. Calcd (%) for C14H16N2S2 (MW 276.4): C, 60.83; H, 5.83; N, 10.13. Found: C, 60.95; H, 5.98; N, 10.50. 1-Methyl-1H-indol-3-yl Piperidine-1-carbodithioate (2c): cream solid; yield 162 mg (56%); mp 176−177 °C; IR (KBr) ν 2093, 1513, 1431, 1238, 1134, 1113, 1005, 968, 732 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.61 (s, 1H), 7.51 (d, 1H, J = 8.3 Hz, H−Ar), 7.36 (td, 1H, J = 7.1, 1.2 Hz, H−Ar), 7.21 (m, 1H, H−Ar), 7.10 (m, 1H, H− Ar), 4.17−4.98 (brs, 4H), 3.84 (s, 3H), 1.68−1.59 (brs, 6H) ppm; 13C NMR (75 MHz, DMSO-d6) δ 195.3, 137.6, 137.1, 129.8, 121.8, 120.1, 118.7, 110.4, 99.1, 53.1, 52.9, 32.8, 26.0, 25.3, 23.6 ppm. Anal. Calcd (%) for C15H18N2S2 (MW 290.4): C, 62.03; H, 6.25; N, 9.64. Found: C, 61.75; H, 6.36; N, 9.36. 1-Methyl-1H-indol-3-yl Morpholine-4-carbodithioate (2d): cream solid; yield 184 mg (63%); mp 176−177 °C; IR (KBr) ν 1509, 1462, 1427, 1372, 1342, 1116, 1005, 989, 737 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.63 (s, 1H), 7.52 (d, 1H, J = 8.2 Hz, H−Ar), 7.37 (d, 1H, J = 7.8 Hz, H−Ar), 7.25−7.19 (m, 1H, H−Ar), 7.10 (t, 1H, J = 7.4 Hz, H−Ar), 4.17 (brs, 4H), 3.85 (s, 3H), 3.72 (t, 4H, J = 7.8 Hz) ppm; 13 C NMR (75 MHz, DMSO-d6) δ 197.1, 137.6, 137.1, 129.7, 121.9, 120.2, 118.7, 110.5, 98.4, 65.7 (2C), 51.9, 51.1, 32.9 ppm. Anal. Calcd (%) for C14H16N2OS2 (MW 292.4): C, 57.50; H, 5.52; N, 9.58. Found: C, 57.38; H, 5.69; N, 9.40. 1-Methyl-1H-indol-3-yl Azepane-1-carbodithioate (2e): cream crystal; yield 198 mg (65%); mp 149−150 °C; IR (KBr) ν 2915, 1510, 1446, 1409, 1270, 1197, 1116, 945, 734 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.62 (s, 1H), 7.51 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 7.8 Hz, 1H), 7.21 (m, 1H, H−Ar), 7.10 (m, 1H, H−Ar), 4.10−4.06 (m, 4H), 3.84 (s, 3H), 1.96−1.88 (m, 2H), 1.79−1.71 (m, 2H), 1.59− 1.52 (m, 4H) ppm; 13C NMR (75 MHz, DMSO-d6) δ 196.1, 137.6, 137.1, 129.7, 121.8, 120.1, 118.7, 110.5, 99.2, 55.7, 52.7, 32.8, 27.1, 26.1, 25.9, 25.4 ppm. Anal. Calcd (%) for C16H20N2S2 (MW 304.47): C, 63.12; H, 6.62; N, 9.20. Found: C, 62.78; H, 6.64; N, 9.09. 2-Methyl-1H-indol-3-yl Diethylcarbamodithioate (2f): white yellow solid; yield 181 mg (65%); mp 119−120 °C; IR (KBr) ν 3232 (NH), 1490, 1454, 1416, 1267, 1203, 980, 747 cm−1; 1H NMR

Table 2. Diversity in the Synthesis of Indoledithiocarbamates 2

a

Isolated yield. Reaction conditions: amine (2 mmol), CS2 (3 mmol) indole (1 mmol), iodine (1 mmol), EtOH (6 mL), 24 h at 60 °C under N2 or Ar.

Scheme 2. Proposed Mechanism for C−H Functionalization of Indoles with Dithiocarbamates

■

EXPERIMENTAL SECTION

General. All chemicals and solvents were obtained from commercial sources and used as received. The 1H and 13C NMR spectra of products were recorded on Bruker AMX 300 and 400 MHz spectrometers referenced to internal Me4Si at 0.00 ppm. Reaction monitoring was carried out by thin-layer chromatography using TLC silica gel 60 F254 plates. IR spectra were recorded on an FTIR instrument using a film technique or KBr disc, and wave numbers are reported in cm−1. Elemental analyses were conducted with a 5780

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783

Note

The Journal of Organic Chemistry (300 MHz, DMSO-d6) δ 11.60 (s, 1H, N−H), 7.34 (m, 1H, H−Ar), 7.24 (m, 1H, H−Ar), 7.09−6.97 (m, 2H, H−Ar), 3.97−3.90 (m, 4H), 2.32 (s, 3H), 1.39 (t, 3H, J = 7.0 Hz), 1.17 (t, 3H, J = 6.9 Hz) ppm; 13 C NMR (75 MHz, DMSO-d6) δ 195.1, 143.9, 135.4, 130.3, 120.9, 119.7, 117.6, 111.1, 97.5, 49.7, 46.7, 12.8, 12.0, 11.4 ppm. Anal. Calcd (%) for C14H18N2S2 (MW 278.44): C, 60.39; H, 6.52; N, 10.06. Found: C, 60.54; H, 6.54; N, 9.98. 2-Methyl-1H-indol-3-yl Azepane-1-carbodithioate (2g): white yellow solid; yield 198 mg (65%); mp 79−80 °C; IR (KBr) ν 3228 (NH), 1453, 1417, 1363, 1291, 1202, 854, 746 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 11.60 (s, 1H, N−H), 7.32 (m, 1H, H−Ar), 7.24 (m, 1H, H−Ar), 7.07−6.93 (m, 2H, H−Ar), 4.12−4.06 (m, 4H), 2.32 (s, 3H), 1.98−1.90 (m, 2H), 1.79−1.71 (m, 2H), 1.62−1.45 (m, 4H) ppm; 13C NMR (75 MHz, DMSO-d6) δ 195.9, 143.9, 135.4, 130.3, 120.9, 119.7, 117.5, 111.1, 97.6, 55.8, 52.7, 27.1, 26.1, 25.8, 25.3, 11.9 ppm. Anal. Calcd (%) for C16H20N2S2 (MW 304.47): C, 63.12; H, 6.62; N, 9.20. Found: C, 62.79; H, 6.89; N, 8.90. 2-Methyl-1H-indol-3-yl Dimethylcarbamodithioate (2h): white solid; yield 188 mg (75%); mp 180−182 °C; IR (KBr) ν 3391 (NH), 3275 (NH), 1500, 1453, 1377, 1248, 1228, 1148, 973, 750 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.45 (s, 1H, N−H), 7.51 (m, 1H, H−Ar), 7.28 (m, 1H, H−Ar), 7.19−7.15 (m, 2H), 3.63 (s, 3H), 3.61 (s, 3H), 2.39 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3) δ 198.2, 143.2, 135.2, 130.3, 121.9, 120.8, 118.4, 111.0, 99.9, 46.1, 41.8, 12.4 ppm; HRMS calcd for C12H14N2NaS2 [M + Na]+ 273.0496, found 273.0491. 2-Methyl-1H-indol-3-yl Pyrrolidine-1-carbodithioate (2i): white solid; yield 190 mg (69%); mp 178−180 °C; IR (KBr) ν 3388 (NH), 3226 (NH), 1437, 1157, 1001, 951, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.48 (s, 1H, N−H), 7.53 (m, 1H, H−Ar), 7.29 (m, 1H, H− Ar), 7.18−7.14 (m, 2H), 4.00−3.95 (m, 4H), 2.42 (s, 3H), 2.22−2.17 (m, 2H), 2.06−2.02 (m, 2H) ppm; 13C NMR (101 MHz, CDCl3) δ 193.8, 143.1, 135.2, 130.3, 121.9, 120.8, 118.4, 111.1, 99.3, 55.5, 50.9, 26.5, 24.4, 12.5 ppm; HRMS calcd for C14H17N2S2 [M + H]+ 277.0833, found 277.0828. 2-Methyl-1H-indol-3-yl Dipropylcarbamodithioate (2j): viscous yellow oil; yield 230 mg (75%); IR (film) ν 3388 (NH), 3285 (NH), 2964, 2930, 2873, 1483, 1455, 1414, 1238, 988, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.41 (s, 1H, N−H), 7.49 (m, 1H, H−Ar), 7.29 (m, 1H, H−Ar), 7.17−7.15 (m, 2H, H−Ar), 3.97−3.88 (m, 4H), 2.40 (s, 3H), 2.02−1.94 (m, 2H), 1.88−1.80 (m, 2H), 1.11 (t, 3H, J = 7.4 Hz), 0.97 (t, 3H, J = 7.4 Hz) ppm; 13C NMR (101 MHz, CDCl3) δ 197.1, 143.2, 135.2, 130.4, 121.9, 120.7, 118.5, 111.0, 99.99, 57.5, 54.6, 21.2, 19.8, 12.5, 11.3, 11.2 ppm; HRMS calcd for C16H23N2S2 [M + H]+ 307.1303, found 307.1298. 2-Methyl-1H-indol-3-yl Dibenzylcarbamodithioate (2k): yellow solid; yield 298 mg (74%); mp 130−133 °C; IR (KBr) ν 3407 (NH), 2923, 1619, 1454, 1414, 1352, 1212, 1142, 957, 739, 698 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.39 (s, 1H, N−H), 7.55−7.19 (m, 14H, H−Ar), 5.39 (brs, 2H), 5.19 (brs, 2H), 2.48 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3) δ 200.6, 143.3, 135.8 (2C), 135.2, 130.3, 129.0, 128.9, 128.1, 127.9, 127.4, 127.3, 122.1, 120.9, 118.5, 111.0, 100.0, 57.0, 54.2, 12.6 ppm; HRMS calcd for C24H22N2NaS2 [M + H]+ 425.1122, found 425.1117. 1H-Indol-3-yl Pyrrolidine-1-carbodithioate (2l): yellow solid; yield 178 mg (68%); mp 162−165 °C; IR (film) ν 3393 (NH), 3257 (NH), 1437, 11559, 1000, 953, 741 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.74 (s, 1H, N−H), 7.63 (m, 1H, H−Ar), 7.37−7.32 (m, 2H, H−Ar), 7.25−7.19 (m, 2H, H−Ar), 4.02−3.93 (m, 4H), 2.23−2.16 (m, 2H), 2.08−2.01 (m, 2H) ppm; 13C NMR (101 MHz, CDCl3) δ 194.4, 136.2, 132.6, 129.2, 122.8, 120.9, 119.3, 112.0, 102.1, 55.6, 51.0, 26.5, 24.4 ppm; HRMS calcd for C13H14N2NaS2 [M + H]+ 285.0496, found 285.0492. 1H-Indol-3-yl Dimethylcarbamodithioate (2m): cream solid; yield 154 mg (65%); mp 181−183 °C; IR (KBr) ν 3402 (NH), 3326 (NH), 1505, 1457, 1411, 1371, 1252, 1239, 1147, 972, 738 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.66 (s, 1H, N−H), 7.60 (m, 1H, H−Ar), 7.39 (m, 1H, H−Ar), 7.35 (d, 1H, J = 2.7 Hz, H−Ar), 7.27−7.20 (m, 2H, H−Ar), 3.62 (s, 6H) ppm; 13C NMR (101 MHz, CDCl3) δ 198.8, 136.2, 132.6, 129.2, 122.9, 121.0, 119.3, 111.9, 102.8, 46.1, 41.9 ppm; HRMS calcd for C11H13N2S2 [M + H]+ 237.0520, found 237.0514.

1H-Indol-3-yl Azepane-1-carbodithioate (2n): white yellow solid; yield 160 mg (55%); mp 162−163 °C; IR (film) ν 3253 (NH), 2934, 1487, 1418, 1269, 1197, 735 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.64 (s, 1H, N−H), 7.60 (dd, J = 7.7, 1.4, 1H, H−Ar), 7.41−7.38 (m, 2H, H−Ar), 7.27−7.19 (m, 2H, H−Ar), 4.24 (t, 2H, J = 6.0 Hz), 4.16 (t, 2H, J = 6.2 Hz), 2.08−2.02 (m, 2H), 1.96−1.90 (m, 2H), 1.75− 1.67 (m, 4H) ppm; 13C NMR (101 MHz, CDCl3) δ 197.7, 136.2, 132.7, 129.3, 122.8, 121.0, 119.3, 111.9, 102.9, 56.5, 53.2, 27.8, 26.8, 26.7, 26.2 ppm; HRMS calcd for C15H19N2S2 [M + H]+ 291.0990, found 291.0984. 1H-Indol-3-yl Diethylcarbamodithioate (2o): cream solid; yield 172 mg (65%); mp 187−188 °C; IR (KBr) ν 3368 (NH), 1495, 1421, 1335, 1272, 1199, 974, 756 cm−1; 1H NMR (300 MHz, DMSO-d6) δ 11.66 (s, 1H, N−H), 7.6 (d, 1H, J = 2.7 Hz, H−Ar), 7.44 (d, 1H, J = 8.0 Hz, H−Ar), 7.34 (d, 1H, J = 7.7 Hz, H−Ar), 7.12 (m, 1H, H−Ar), 7.02 (m, 1H, H−Ar), 3.96−3.89 (m, 4H), 1.37 (t, 3H, J = 7.0 Hz), 1.17 (t, 3H, J = 7.1 Hz) ppm; 13C NMR (75 MHz, DMSO-d6) δ 195.5, 136.4, 134.1, 129.4, 121.7, 119.9, 118.5, 112.1, 100.2, 49.6, 46.7, 12.8, 11.4 ppm. Anal. Calcd (%) for C13H16N2S2 (MW 264.41): C, 59.05; H, 6.10; N, 10.59. Found: C, 58.88; H, 6.02; N, 10.37. 5-Bromo-1H-indol-3-yl Morpholine-4-carbodithioate (2p): white solid; yield 161 mg (45%); mp decomposed at >170 °C; IR (film) ν 3196 (NH), 3163 (NH), 2916, 2856, 1455, 1421, 1267, 1231, 1112, 1029 cm−1; 1H NMR (400 MHz, DMSO-d6 and CDCl3) δ 11.27 (s, 1H, N−H), 7.49 (m, 1H, H−Ar), 7.35−7.28 (m, 2H, H−Ar), 7.180 (m, 1H, H−Ar), 4.18 (brs, 4H), 3.76 (brs, 4H) ppm; 13C NMR (101 MHz, DMSO-d6 and CDCl3) δ 198.6, 135.5, 134.8, 131.3, 125.0, 121.5, 113.9, 113.8, 100.2, 66.2 (2C), 52.0, 50.9 ppm; HRMS calcd for C13H14BrN2OS2 [M + H]+ 356.9731, found 356.9727. 5-Methoxy-1H-indol-3-yl Pyrrolidine-1-carbodithioate (2q): white solid; yield 248 mg (85%); mp 134−137 °C; IR (KBr) ν 3365 (NH), 3241 (NH), 1622, 1584, 1485, 1437, 1288, 1206, 1169, 1037, 1004, 955 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.80 (s, 1H, N−H), 7.24− 7.19 (m, 2H, H−Ar), 7.05 (d, 1H, J = 2.4 Hz, H−Ar), 6.86 (dd, 1H, J = 8.8, 2.5 Hz, H−Ar), 4.00 (t, 2H, J = 7.0 Hz), 3.95 (t, 2H, J = 6.9 Hz), 3.88 (s, 3H), 2.23−2.16 (m, 2H), 2.08−2.01 (m, 2H) ppm; 13C NMR (101 MHz, CDCl3) δ 194.6, 155.1, 133.3, 131.3, 129.9, 113.2, 112.9, 101.2, 100.6, 55.8, 55.7, 51.0, 26.5, 24.4 ppm; HRMS calcd for C14H16N2NaOS2 [M + Na]+ 315.0602, found 315.0597. 5-Methoxy-1H-indol-3-yl Morpholine-4-carbodithioate (2r): cream solid; yield 203 mg (66%); mp 163−166 °C; IR (KBr) ν 3405 (NH), 3298 (NH), 1623, 1583, 1485, 1462, 1428, 1266, 1232, 1211, 1172, 1107, 1030, 990, 805 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.65 (s, 1H, N−H), 7.30−7.24 (m, 2H, H−Ar), 7.02 (dd, J = 3.0, 0.7 Hz, 1H, H−Ar), 6.90 (dd, 1H, J = 8.8, 2.5 Hz, H−Ar), 4.31(brs, 4H), 3.89−3.84 (m, 7H) ppm; 13C NMR (101 MHz, CDCl3) δ 199.2, 155.2, 133.4, 131.2, 130.0, 113.4, 112.8, 101.1, 100.8, 66.4 (2C), 55.8, 52.5, 51.3 ppm; HRMS calcd for C14H17N2O2S2 [M + H]+ 309.0731, found 309.0727. 3-Methyl-1H-indol-2-yl Pyrrolidine-1-carbodithioate (2s): white solid; yield 174 mg (63%); mp 163−165 °C; IR (KBr) ν 3423 (NH), 3301 (NH), 1628, 1442, 1332, 1159, 1002, 954 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.24 (s, 1H, N−H), 7.63 (m, 1H, H−Ar), 7.38 (td, 1H, J = 8.2, 1.0 Hz, H−Ar), 7.27 (m, 1H, H−Ar), 7.15 (m, 1H, H− Ar), 3.98−3.94 (m, 2H), 3.90−3.86 (m, 2H), 2.40 (s, 3H), 2.22−2.15 (m, 2H), 2.08−2.01 (m, 2H) ppm; 13C NMR (101 MHz, CDCl3) δ 191.1, 137.7, 128.3, 123.9, 121.9, 120.2, 119.8, 119.6, 111.2, 55.3, 51.3, 26.5, 24.4, 9.60 ppm; HRMS calcd for C14H16N2NaS2 [M + Na]+ 299.0653, found 299.0647. 3-Methyl-1H-indol-2-yl Morpholine-4-carbodithioate (2t): white solid; yield 205 mg (70%); mp 193−196 °C; IR (KBr) ν 3279 (NH), 1406, 1271, 1231, 1113, 1037, 991, 871, 746 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.19 (s, 1H, N−H), 7.65 (d, 1H, J = 8.0 Hz, H−Ar), 7.38 (d, 1H, J = 8.2 Hz, H−Ar), 7.31−7.27 (m, 1H, H−Ar), 7.17 (t, 1H, J = 7.5 Hz, H−Ar), 4.33−4.13 (brs, 4H), 3.85 (t, J = 5.0 Hz, 4H), 2.40 (s, 3H) ppm; 13C NMR (101 MHz, CDCl3) δ 195.7, 137.9, 128.3, 124.1, 122.6, 119.8, 119.7, 119.4, 111.2, 66.3, 66.2, 51.6, 51.3, 9.8 ppm; HRMS calcd for C14H17N2OS2 [M + H]+ 293.0782, found 293.0777. 3-Methyl-1H-indol-2-yl Azepane-1-carbodithioate (2u): yellow solid; yield 167 mg (55%); mp 131−134 °C; IR (KBr) ν 3395 5781

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783

Note

The Journal of Organic Chemistry

regioselective sulfenylation of indoles with thiols. Tetrahedron Lett. 2016, 57, 1912−1916. (6) Liu, X.; Cui, H.; Yang, D.; Dai, S.; Zhang, G.; Wei, W.; Wang, H. Iodine-catalyzed Direct Thiolation of Indoles with Thiols Leading to 3-Thioindoles Using Air as the Oxidant. Catal. Lett. 2016, 146, 1743− 1748. (7) Liu, Y.; Zhang, Y.; Hu, C.; Wan, J.-p.; Wen, C. Synthesis of 3sulfenylated indoles by a simple NaOH promoted sulfenylation reaction. RSC Adv. 2014, 4, 35528−35530. (8) Sang, P.; Chen, Z.; Zou, J.; Zhang, Y. K2CO3 promoted direct sulfenylation of indoles: a facile approach towards 3-sulfenylindoles. Green Chem. 2013, 15, 2096−2100. (9) Ji, X.-M.; Zhou, S.-J.; Chen, F.; Zhang, X.-G.; Tang, R.-Y. Direct Sulfenylation of Imidazoheterocycles with Disulfides in an Iodine− Hydrogen Peroxide System. Synthesis 2015, 47, 659−671. (10) Zhang, H.; Bao, X.; Song, Y.; Qu, J.; Wang, B. Iodine-Catalysed Versatile Sulfenylation of Indoles with Thiophenols: Controllable Synthesis of mono- and bis-Arylthioindoles. Tetrahedron 2015, 71, 8885−8891. (11) Prasad, C. D.; Kumar, S.; Sattar, M.; Adhikary, A.; Kumar, S. Metal free sulfenylation and bis-sulfenylation of indoles: persulfate mediated synthesis. Org. Biomol. Chem. 2013, 11, 8036−8040. (12) Fang, X.-L.; Tang, R.-Y.; Zhong, P.; Li, J.-H. Iron-Catalyzed Sulfenylation of Indoles with Disulfides Promoted by a Catalytic Amount of Iodine. Synthesis 2009, 4183−4189. (13) Tudge, M.; Tamiya, M.; Savarin, C.; Humphrey, G. R. Development of a Novel, Highly Efficient Halide-Catalyzed Sulfenylation of Indoles. Org. Lett. 2006, 8, 565−568. (14) Gensch, T.; Klauck, F. J. R.; Glorius, F. Cobalt-Catalyzed C-H Thiolation through Dehydrogenative Cross-Coupling. Angew. Chem., Int. Ed. 2016, 55, 11287−11291. (15) Li, Z.; Hong, J.; Zhou, X. An efficient and clean CuI-catalyzed chalcogenylation of aromatic azaheterocycles with dichalcogenides. Tetrahedron 2011, 67, 3690−3697. (16) (a) Len, C.; Boulogne-Merlot, A.-S.; Postel, D.; Ronco, G.; Villa, P.; Goubert, C.; Jeufrault, E.; Mathon, B.; Simon, H. Synthesis and antifungal activity of novel bis (dithiocarbamate) derivatives of glycerol. J. Agric. Food Chem. 1996, 44, 2856−2858. (b) Marinovich, M.; Viviani, B.; Capra, V.; Corsini, E.; Anselmi, L.; D’Agostino, G.; Nucci, A. D.; Binaglia, M.; Tonini, M.; Galli, C. L. Facilitation of Acetylcholine Signaling by the Dithiocarbamate Fungicide Propineb. Chem. Res. Toxicol. 2002, 15, 26−32. (c) Malik, A. K.; Rao, A. L. J. Spectrophotometric Determination of Ferbam [Iron(III) Dimethyl Dithiocarbamate] in Commercial Sample and Wheat Grains after Extraction of Its Bathophenanthroline Tetraphenylborate Complex into Molten Naphthalene. J. Agric. Food Chem. 2000, 48, 4044−4047. (d) Weissmahr, K. W.; Houghton, C. L.; Sedlak, D. L. Analysis of the Dithiocarbamate Fungicides Ziram, Maneb, and Zineb and the Flotation Agent Ethylxanthogenate by Ion-Pair Reversed-Phase HPLC. Anal. Chem. 1998, 70, 4800−4804. (17) Lai, J. T.; Shea, R. Controlled radical polymerization by carboxyl- and hydroxyl-terminated dithiocarbamates and xanthates. J. Polym. Sci., Part A: Polym. Chem. 2006, 44, 4298−4316. (18) (a) Fuhrmann, D.; Dietrich, S.; Krautscheid, H. Zinc Tin Chalcogenide Complexes and Their Evaluation as Molecular Precursors for Cu2ZnSnS4 (CZTS) and Cu2ZnSnSe4 (CZTSe). Inorg. Chem. 2017, 56, 13123−13131. (b) Morrison, C. E.; Wang, F.; Rath, N. P.; Wieliczka, B. M.; Loomis, R. A.; Buhro, W. E. Cadmium Bis(phenyldithiocarbamate) as a Nanocrystal Shell-Growth Precursor. Inorg. Chem. 2017, 56, 12920−12929. (19) (a) McMaster, C.; Bream, R. N.; Grainger, R. S. Radicalmediated reduction of the dithiocarbamate group under tin-free conditions. Org. Biomol. Chem. 2012, 10, 4752−4758. (b) Ziyaei Halimehjani, A.; Khoshdoun, M. Tandem Esterification/1,4-AdditionType Friedel-Crafts Alkylation Reactions of Phenols/Naphthols with Olefinic Thioazlactones: Access to Functionalized 1,2-Dihydrobenzo[f]chromen-3-ones and 3,4-Dihydrochromen-2-ones. J. Org. Chem. 2016, 81, 5699−5704. (c) Ziyaei Halimehjani, A.; Lotfi Nosood, Y. Synthesis of N, S - Heterocycles and Dithiocarbamates by the Reaction

(NH), 2930, 2852, 1617, 1445, 1415, 1352, 1268, 1165, 946, 738 cm−1; 1H NMR (400 MHz, CDCl3) δ 8.21 (s, 1H, N−H), 7.63 (m, 1H, H−Ar), 7.38 (td, 1H, J = 8.2, 1.0 Hz, H−Ar), 7.27 (m, 1H, H− Ar), 7.15 (m, 1H, H−Ar), 4.20 (t, J = 6.1 Hz, 2H), 4.07 (t, J = 6.0 Hz, 2H), 2.39 (s, 3H), 2.04−1.95 (m, 2H), 1.95−1.89 (m, 2H), 1.70−1.47 (m, 4H) ppm; 13C NMR (101 MHz, CDCl3) δ 194.7, 137.8, 128.4, 123.8, 122.1, 120.6, 119.8, 119.5, 111.2, 56.1, 53.5, 27.8, 26.7, 26.6, 26.1, 9.6 ppm; HRMS calcd for C16H20N2NaS2 [M + Na]+ 327.0966, found 327.0961.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b00206. Copies of 1H and 13C NMR spectra for all compounds (PDF)

■

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. Fax: +98 (21) 88820992. Tel: +98 (21) 88848949. *E-mail: [email protected] ORCID

Azim Ziyaei Halimehjani: 0000-0002-0348-8959 Petr Beier: 0000-0002-0888-7465 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We are grateful to the research council of Kharazmi University for supporting this work. This work was also supported by the Academy of Sciences of the Czech Republic (RVO 61388963).

■

REFERENCES

(1) (a) Nudelman, A. The Chemistry of Optically Active Sulfur Compounds; Gordon and Breach: New York, 1984. (b) SulphurContaining Drugs and Related Organic Compounds; Damani, L. A., Ed.; Wiley: New York, 1989. (c) Clayden, J.; MacLellan, P. Asymmetric synthesis of tertiary thiols and thioethers. Beilstein J. Org. Chem. 2011, 7, 582−595. (d) Chauhan, P.; Mahajan, S.; Enders, D. Organocatalytic carbon-sulfur bond-forming reactions. Chem. Rev. 2014, 114, 8807− 8864. (e) Dunbar, K. L.; Scharf, D. H.; Litomska, A.; Hertweck, C. Enzymatic Carbon-Sulfur Bond Formation in Natural Product Biosynthesis. Chem. Rev. 2017, 117, 5521−5577. (f) Kondo, T.; Mitsudo, T. Metal-Catalyzed Carbon−Sulfur Bond Formation. Chem. Rev. 2000, 100, 3205−3220. (2) Vasquez-Cespedes, S.; Ferry, A.; Candish, L.; Glorius, F. Heterogeneously Catalyzed Direct CH Thiolation of Heteroarenes. Angew. Chem., Int. Ed. 2015, 54, 5772−5776. (3) Huang, D.; Chen, J.; Dan, W.; Ding, J.; Liu, M.; Wu, H. A MetalFree Sulfenylation and Bromosulfenylation of Indoles: Controllable Synthesis of 3-Arylthioindoles and 2-Bromo-3-arylthioindoles. Adv. Synth. Catal. 2012, 354, 2123−2128. (4) Schlosser, K. M.; Krasutsky, A. P.; Hamilton, H. W.; Reed, J. E.; Sexton, K. A Highly Efficient Procedure for 3-Sulfenylation of Indole2-carboxylates. Org. Lett. 2004, 6, 819−821. (5) (a) Ge, W.; Wei, Y. Iodine-catalyzed oxidative system for 3sulfenylation of indoles with disulfides using DMSO as oxidant under ambient conditions in dimethyl carbonate. Green Chem. 2012, 14, 2066−2070. (b) Azeredo, J. B.; Godoi, M.; Martins, G. M.; Silveira, C. C.; Braga, A. L. A Solvent- and Metal-Free Synthesis of 3- Chacogenylindoles Employing DMSO/I2 as an Eco-friendly Catalytic Oxidation System. J. Org. Chem. 2014, 79, 4125−4130. (c) Yi, S.; Li, M.; Mo, W.; Hu, X.; Hu, B.; Sun, N.; Jin, L.; Shen, Z. Metal-free, iodine-catalyzed 5782

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783

Note

The Journal of Organic Chemistry of Dithiocarbamic Acids and S- Alkyl Dithiocarbamates with Nitroepoxides. Org. Lett. 2017, 19, 6748−6751. (d) Maddani, M.; Prabhu, K. R. A convenient method for the synthesis of substituted thioureas. Tetrahedron Lett. 2007, 48, 7151−7154. (e) Das, P.; Kumar, C. K.; Kumar, K. N.; Innus, M. D.; Iqbal, J.; Srinivas, N. Dithiocarbamate and CuO promoted one-pot synthesis of 2-(Nsubstituted)-aminobenzimidazoles and related heterocycles. Tetrahedron Lett. 2008, 49, 992−995. (f) Wong, R.; Dolman, S. J. Isothiocyanates from Tosyl Chloride Mediated Decomposition of in Situ Generated Dithiocarbamic Acid Salts. J. Org. Chem. 2007, 72, 3969−3971. (g) Guillaneuf, Y.; Couturier, J. L.; Gigmes, D.; Marque, S. R. A.; Tordo, P.; Bertin, D. Synthesis of highly labile SG1-based alkoxyamines under photochemical conditions. J. Org. Chem. 2008, 73, 4728−4731. (h) Ziyaei Halimehjani, A.; Dadras, A.; Ramezani, D. M.; Shamiri, E. V.; Hooshmand, S. E.; Hashemi, M. M. Synthesis of Dithiocarbamates by Markovnikov Addition Reaction in PEG and Their Application in Amidoalkylation of Naphthols and Indoles. J. Braz. Chem. Soc. 2015, 26, 1500−1508. (20) (a) Huang, W.; Ding, Y.; Miao, Y.; Liu, M. Z.; Li, Y.; Yang, G.-F. Synthesis and antitumor activity of novel dithiocarbamate substituted chromones. Eur. J. Med. Chem. 2009, 44, 3687−3696. (b) Zheng, Y.C.; Duan, Y.-C.; Ma, J.-L.; Xu, R.-M.; Zi, X.; Lv, W.-L.; Wang, M.-M.; Ye, X.-W.; Zhu, S.; Mobley, D.; Zhu, Y.-Y.; Wang, J.-W.; Li, J.-F.; Wang, Z.-R.; Zhao, W.; Liu, H.-M. Triazole−Dithiocarbamate Based Selective Lysine Specific Demethylase 1 (LSD1) Inactivators Inhibit Gastric Cancer Cell Growth, Invasion, and Migration. J. Med. Chem. 2013, 56, 8543−8560. (c) Altıntop, M. D.; Sever, B.; Ç iftçi, G. A.; Kucukoglu, K.; Kaplancıklı, Z. A. Synthesis and evaluation of new benzodioxole-based dithiocarbamate derivatives as potential anticancer agents and hCA-I and hCA-II inhibitors. Eur. J. Med. Chem. 2017, 125, 190−196. (d) Duan, Y.-C.; Ma, Y.-C.; Zhang, E.; Shi, X.-J.; Liu, H.-M. Design and synthesis of novel 1,2,3-triazole-dithiocarbamate hybrids as potential anticancer agents. Eur. J. Med. Chem. 2013, 62, 11−19. (e) Duan, Y.-C.; Zheng, Y.-C.; Li, X.-C.; Wang, M.-M.; Liu, H.-M. Design, synthesis and antiproliferative activity studies of novel 1,2,3triazole−dithiocarbamate−urea hybrids. Eur. J. Med. Chem. 2013, 64, 99−110. (f) Rani, P. J.; Thirumaran, S. Synthesis, characterization, cytotoxicity and antimicrobial studies on bis(N-furfuryl-N-(2phenylethyl)dithiocarbamato-S,S′)zinc(II) and its nitrogen donor adducts. Eur. J. Med. Chem. 2013, 62, 139−147. (g) Mohamed, G. G.; Ibrahim, N. A.; Attia, H. A. E. Synthesis and anti-fungicidal activity of some transition metal complexes with benzimidazole dithiocarbamate ligand. Spectrochim. Acta, Part A 2009, 72, 610−615. (h) Magedov, I. V.; Lefranc, F.; Frolova, L. V.; Banuls, L. M. Y.; Peretti, A. S.; Rogelj, S.; Mathieu, V.; Kiss, R.; Kornienko, A. Antiproliferative activity of 2,3-disubstituted indoles toward apoptosisresistant cancers cells. Bioorg. Med. Chem. Lett. 2013, 23, 3277−3282. (i) Cao, S.-L.; Feng, Y.-P.; Jiang, Y.-Y.; Liu, S.-Y.; Ding, G.-Y.; Li, R.-T. Synthesis and in vitro antitumor activity of 4(3H)-quinazolinone derivatives with dithiocarbamate side chains. Bioorg. Med. Chem. Lett. 2005, 15, 1915−1917. (21) Jiao, J.; Wei, L.; Ji, X.-M.; Hu, M.-L.; Tang, R.-Y. Direct Introduction of Dithiocarbamates onto Imidazoheterocy-cles under Mild Conditions. Adv. Synth. Catal. 2016, 358, 268−275. (22) Chripkova, M.; Drutovic, D.; Pilatova, M.; Mikes, J.; Budovska, M.; Vaskova, J.; Broggini, M.; Mirossay, L.; Mojzis, J. Brassinin and its derivatives as potential anticancer agents. Toxicol. In Vitro 2014, 28, 909−915. (23) Przheval’skii, N. M.; Magedov, I. V.; Drozd, V. N. New derivatives of indole. Synthesis of S-(indoyl-3) diethyl dithiocarbamates. Chem. Heterocycl. Compd. 1997, 33, 1475−1476. (24) Krasovskiy, A.; Gavryushin, A.; Knochel, P. A General Thiolation of Magnesium Organometallics Using Tetramethylthiuram Disulfide. Synlett 2005, 2691−2693.

5783

DOI: 10.1021/acs.joc.8b00206 J. Org. Chem. 2018, 83, 5778−5783