IJOCInternational Journal of Organic Chemistry2161-4687Scientific Research Publishing10.4236/ijoc.2023.131003IJOC-123663ArticlesBiomedical&Life Sciences Chemistry&Materials Science Rhodium Catalyzed [2π + 2π + 2π]-Cycloaddition of Alkynyl-Ynamides and Carbon Disulfide to Indolo-Thiopyrane Thiones BenjaminDassonneville1FelixHinkel1HeinerDetert1*Department of Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany020220231301163917, January 202311, March 2023 14, March 2023© Copyright 2014 by authors and Scientific Research Publishing Inc. 2014This work is licensed under the Creative Commons Attribution International License (CC BY). http://creativecommons.org/licenses/by/4.0/

The synthesis of new indoloannulated thiopyranethiones is reported. The key-step is a rhodium-catalyzed [2 + 2 + 2]-cycloaddition of alkynyl-ynamides with carbon disulfide to close the pyrrole and the thiopyranethione rings simultaneously. A violet idolothiopyrane thione or a mixture of the violet and a red isomer result from [RhCl(C 8H 14) 2] 2/3BINAP catalyzed cycloadditions, the regiochemistry is controlled by the substitution pattern on the alkynyl-ynamide.

Cycloaddition Heterocycles Rhodium Sulfur Alkyne1. Introduction

Heteroannulated indoles like carbolines (1,2, Figure 1) form the core of a large group of alkaloids [1] [2] [3] [4] [5] . Many of these alkaloids possess pharmacological properties, ranging from antitumor to anxiolytic and anti-HIV activity [6] - [11] . Therefore, compounds based on these heterocyclic cores remain important targets for organic syntheses [12] - [17] . Classical methods for the synthesis of (hetero) annulated indoles are condensation reactions, e.g. Pictet-Spengler and Bischler-Napieralski. In recent times, highly successful Pd-catalyzed methods have been developed for the formation of the biaryl bond or closure of the pyrrole ring [18] - [26] . The comparably mild reaction conditions and the tolerance of a large scope of functional groups are advantages of this approach. The [2 + 2 + 2]-cycloaddition, found by Berthelot, has become a powerful tool for the synthesis of aromatics since the introduction of nickel catalysts by Reppe [27] [28] [29] . Transition-metal catalyzed [2 + 2 + 2]-cycloadditions receive continuously growing attention, with topical focusses like polycyclic systems and stereoselective arene formation [27] - [39] . The similar cocyclization of alkynes and nitriles is a highly effective route for the synthesis of pyridines [40] - [50] . Even annulated pyridines are accessible, either from tethered diynes or cyanoalkynes [51] - [67] . Modern catalytic systems for [2 + 2 + 2]-cycloadditions are typically based on cobalt, ruthenium and rhodium, other transition metals are emerging [68] - [75] . In some cases, Lewis acid catalysis effectively initiates cycloaddition [61] [76] . As part of a project focusing on condensed heterocycles, we used rhodium and ruthenium-based catalysts for the addition of nitriles to alkynyl-ynamides [77] - [86] . These metals catalyze the simultaneous construction of the pyrrole and the pyridine ring, thus forming β- and γ-carbolines 1,2 (Figure 1). The β/γ-ratio is strongly depending on the catalyst. This strategy has been successfully applied to the synthesis of alkaloids like lavendamycin [87] [88] [89] .

The [2 + 2 + 2]-co-cycloaddition methodology is not limited to alkynes with nitriles, cyclizations of alkynes with hetero-substituted nitriles, allenes, and even heterocumulenes have been performed [90] - [102] . Wakatzuki [103] reported the cobalt-catalyzed cocyclization of tolane and carbon disulfide to thiopyranthione 3 (Figure 1) already in 1973. This cycloaddition was followed by rare examples; Yamamoto applied Cp*RuCl(COD) as a catalyst for the cocyclization of 1,6-diynes 4 with CS2 and Tanaka introduced [RhCl(COD)]2/BINAP (Scheme 1) as a very efficient catalytic system for this route to thiopyranethiones 5 [104] [105] [106] .

[2 + 2 + 2]-Cocyclizations of tethered diynes and heterocumulenes to form annulated heterocycles appear only occasionally in the literature [101] [102] [104] [105] [106] [107] . Recently, we could show that rhodium catalyzes the addition of CS2 to an alkynyl-ynamide to form an indolothiopyrane thione, an unprecedented route to an almost unknown heterocyclic system [108] [109] . The intention of this communication is to extend the applicability of the [2 + 2 + 2]-cycloaddition approach with alkynyl-ynamides to the synthesis of indolo-annulated thiopyranethiones.

2. Results and Discussion2.1. Synthesis of o,N-Dialkynyl-N-Tosylanilides

The literature gives four independent routes to ynamides, direct oxidative alkyne-amide coupling, transfer of an activated alkyne to the amide, and stepwise construction of the ynamide [108] - [115] . While the alkynyliodonium routeoffers excellent yield, it is limited to certain substituents [111] [112] . The lengthy Brückner route [115] converts a formamide via dichlorovinyl-amide to a lithio- ynamide—beneficial for a one-pot Negishi coupling [111] . Most alkynylynamides 4b - 4e, 4g in this study were prepared via alkynyliodonium salts [116] according to the literature [84] [89] [117] . The new syntheses of alkynyl ynamides via Brückner route (4a, 4e), via Negishi coupling (4h, 4i), and the Sonogashira coupling to 4f are exemplified in Scheme 2.

2.2. [2 + 2 + 2]-Cycloadditions with Carbon Disulfide

Like the formation of carbazoles or carbolines in [2 + 2 + 2]-cycloadditions of o,N-dialkynyl-N-tosylanilides and alkynes or nitriles, a cycloaddition of carbon disulfide to the alkynyl-ynamide results in the synchronous formation of a pyrrole ring and an additional heterocycle, here, a thiopyranethione (Scheme 3).

As the orientation of the nitrile to the initially formed metallacyclopentadiene [104] [105] is decisive for the formation of β- and γ-carbolines, two different indolo-thiopyranthiones 7, 8 can result from the CS2 addition. Depending on the orientation of carbon disulfide in the addition step to the rhodacyclopentadiene, the thiopyrano[3,4-b]indole-3-thione 7 or its [4,3-b]-annulated isomer 8 results. We used o-propynyl-N-ethynyl-N-tosylanilide 4a (R1 = CH3, R2 = H) as a model system for the anticipated addition of CS2 to form indolothiopyrane thiones 7a and 8a and [Rh(COD)2]+ B F 4 − /BINAP, and Cp*RuCl(COD) as catalytic systems. These had been successfully applied in the synthesis of β- and γ-carbolines from alkynyl-ynamides [87] [88] [89] and of heterocumulenes with 1,6-diynes [104] [105] . Unfortunately, these catalysts gave no conversion (Table 1, entry 1, 2).

Recently, Rh(COD)Cl]2/2BINAP, a neutral complex, had been rewardingly applied by Tanaka [20] in cycloadditions of 1,6-diynes to give bicyclic dithiopyrones. Inspired by this work, we choose [RhCl(C8H14)2]2 with BINAP as ligand. The precatalyst was activated by hydrogenation and revealed a high activity: with 3.5 mol-% of [RhCl(C8H14)2]2 and 10 mol-% BINAP, cycloadduct 7a was formed in 84% yield within 3 h at 40˚C. Lowering the reaction temperature to 25˚C reduced the yield to 56%—even after a five-fold reaction time. A 95% yield of 8a was obtained when the addition was performed at 80 °C, but further increase of the temperature initiated side reactions. Lower yields were obtained upon reduction of the catalyst loading or use of other ligands, e.g. Xantphos (Table 1, entry 6 - 8).

The first successful experiment in this series (Table 1, entry 3) led to an apparently regiospecific formation the violet β-thio-γ-thione derivative 7a (R1 = CH3, R2 = H). The structure was confirmed by spectroscopic data and X-ray scattering [108] . However, in further experiments we observed a second product: according

Study of the [2 + 2 + 2]-cycloaddition of diyne 4a with CS<sub>2</sub> in dichloroethane
EntryCatalytic System [a]TtimeYield [b]
1[Rh(COD)2]+ B F 4 − /BINAP5 mol%/6 mol%80˚C6 h0% [c]
2Cp*RuCl(COD) 10 mol%80˚C6 h0%
3[RhCl(C8H14)2]2/3BINAP3.5 mol%/10 mol%40˚C3 h84%
4[RhCl(C8H14)2]2/3BINAP3.5 mol%/10 mol%25˚C15 h56%
5[RhCl(C8H14)2]2/3BINAP3.5 mol%/10 mol%80˚C3 h95%
6[RhCl(C8H14)2]2/3BINAP2 mol%/6 mol%80˚C6 h67%
7[RhCl(C8H14)2]2/Xantphos3.5 mol%/10 mol%80˚C6 h0%
8[RhCl(C8H14)2]2/dppf3.5 mol%/10 mol%80˚C6 h0%

As all reaction performed with 10 equiv. CS2 [a] activation of the Rh-precatalyst by hydrogenation [b] isolated yield of both isomers; [c] decomposition of starting material.

to 1H-NMR, this red component was formed in up to 3% but all attempts to isolate this side product failed due to decomposition. The successful cycloaddition to 7a prompted us to investigate the reaction more in detail; results are collected in Table 2. Variation of the substituent R1 on the alkynyl-ynamides has a strong impact on yield and regiochemistry. The violet compounds 7 are accompanied by 8, their red isomers (vide infra). Surprisingly, exchanging R1 = CH3 with the small hydrogen (entry 2) or with larger groups (entry 3 - 5) reduces the regioselectivity. The reaction with the non-substituted diyne led to both substituent-free thiopyranothiones 7b/8b (entry 2), as indicated by the violet and red spots observed on the TLC and the 1H NMR of the crude product. However, isolation of 7b failed due to decomposition during chromatography. Furthermore, while phenyl and butyl give almost equimolar amounts of both isomers, the voluminous TMS group hampers the reaction, inverts the 7/8 ratio to 1:2 and is split off to yield 7b/8b. Finally, the reactions with diynes having a substituted ynamide moiety 4g - 4i proceed with a surprisingly excellent regioselectivity, as only the violet thiopyranothiones 7g - 7i are obtained. This perfect selectivity resembles the regiochemistry of aminonitrile addition to diynes which was explained by sterical crowding [100] . This approach does not hold for alkynyl ynamides substituted on the phenylacetylene segment. Nearly all of these cycloadditions result in an excess of adduct 7—with the thiocarbonyl vicinal to the substituent!

[2 + 2 + 2]-cycloaddition of various diynes with CS<sub>2</sub>
EntryDiyneR1R2Isolated Yield [a]Ratio [b] 7/8
14aCH3H95%33/1
24bHH84% [c]3/1
34cn-BuH71%10/11
44dTMSH31% [c]1/2[d]
54ePhH92%5/4
64f4-Ph-PhH34%2/1
74gHPh68% [e]>99/1
84hH4-MeO-Ph36% [e]>99/1
94iHBenzofuranyl-221% [e]>99/1

[a] reactions performed with 10 equiv. CS2, 3.5 mol%/10 mol% of [RhCl(C8H14)2]2/3BINAP in DCE at 80˚C; activation of the Rh-precatalysts by hydrogenation; [b] determined by 1H-NMR of the crude product [c] 84% of product was isolated but was partially decomposed [d] proto-desilylation during reaction; [e] catalyst loading of 2.5 mol%/6 mol%.

Several of the cycloadditions above are accompanied by formation of small amounts of side products, FD-MS and some 1H-NMR signals indicate dimers formed via [2 + 2 + 2]-cycloaddition of diynes. On the other hand, benzofuranyl diyne 4i underwent an intramolecular cyclization to carbazole 9 (Scheme 4), probably via a dehydro Diels-Alder addition followed by a 1,5-H-shift. The mechanism follows Saá et al. who developed this route to new and successful access to benzo-annulated carbazoles [118] [119] .

Unfortunately, some of the thiopyranethiones, especially the violet isomers, are highly sensitive towards light and air, in several cases impeding the complete analytical and spectral characterization; aromatic substituents appear to be beneficial for stability.

2.3. Optical properties

Indolothiopyranethiones are deeply colored in solution and in the solid state; β- (8) and γ-thiono (7) derivatives are clearly distinguishable by their violet or red color. The absorption spectra of 7b and 8d without additional substituents on the thiopyrane ring are depicted in Figure 2. The intense color of these compound results from their absorption in the blue or green region of the visible spectrum. These maxima (535 nm resp. 474 nm) probably correspond to n ® π* transition of the thiocarbonyl group. Interestingly, the long-wavelength absorption maximum of related indolopyrones appear at λmax = 370 nm (“oxa-7”) and λmax = 309 nm (“oxa-8”), both about Δλ = 160 nm at shorter wavelengths [120] [121] . The length of the conjugation path from indole-N to carbonyl-O/-S appears

to be decisive for the red shift. Separated by huge energy differences (Δὔ = 12,954 cm−1 (7b); 5535 cm−1 (8b), the π* ® π* transitions occur in the UV (316 nm, 378 nm), with extinction coefficients about 6 - 7 times higher than of the n ® π* transitions. Donor-substitution on thiopyranethiones 7 shifts both transitions to lower energies (e.g. 7i: λmax = 391, 547 nm), the effect of substituents vicinal to the thiocarbonyl group are less pronounced than those in the α-position (7e: λmax = 313 nm, 535 nm, but 7g: λmax = 322 nm, 527 nm). Solvatochromism of both transitions of 7 and 8 is weak (Δλ ≤ 10 nm), but typically inverted, e.g. 7e: λmax in cyclohexane: 535 nm, 307 nm; in dichloromethane: 540 nm, 317 nm and in ethanol 535 nm, 313 nm.

3. Conclusion

The [2 + 2 + 2]-cycloaddition of alkynyl-ynamide to carbon disulfide catalyzed by Rhodium/Binap complexes is a short access to the unprecedented indolothiopyrane thione. Depending on the relative orientation, two different regioisomers are formed, a red β- and a violet γ-isomer. The formation of the violet isomers 7 is generally preferred, if the ynamide is substituted, nearly exclusively formation of the violet 7 occurs. The UV-vis spectra of the isomers differ not only in the long-wavelength absorption, even the π − π* transitions are separated by more than 6000 cm−1.

4. Experimental PartGeneral Information

All reactions were carried out under dry argon or nitrogen unless otherwise indicated. Commercially available reagents were used without further purification unless otherwise indicated; solvents and gases were dried by standard procedures. Yields refer to chromato-graphically and spectroscopically pure compounds unless otherwise stated. 1H and 13C NMR spectra: Bruker AC 300 (300 MHz), Bruker AV 400 (400 MHz), and Bruker ARX 400 (400 MHz), in CDCl3, CD3OD, and DMSO-d6. H and C signals were assigned on the basis of DEPT, COSY 45, HMQC, and HMBC experiments. Chemical shifts as δ values in ppm, coupling constants are given in Hz. Melting points: Büchi HWS SG 200; IR: JASCO 4100 FT-IR (ATR); FD-MS: Mat 95 (Finnigan); HR-ESI: Q-TOF-ULTIMA 3 with Lock Spray device (Waters-Micromass), NaICsI Standard as reference. UV-vis: Perkin-Elmer Lambda 16. Elemental analyses were carried out by using a Vario EL.

Starting materials: 4-methyl-N-(2(prop-1-ynyl)phenyl)benzenesulfonamide, N-(2-iodophenyl)-4-methyl-N-(trimethylsilylethynyl)-benzenesulfonamide,

4-methyl-N-(2(phenylethynyl)phenyl)-benzene-sulfonamide, and diynes 4b - 4d, 4g, 4h were prepared according to the literature. [14f, 15c, 27]

Negishi coupling on TMS-diynes: A freshly prepared LiHMDS solution (6.0 mL, 0.5M in THF, 1.5 equiv.) was added slowly to a cooled solution (−78˚C) of the diyne (2 mmol) in dry THF (10 mL) After stirring for 1 h, a solution of ZnBr2 (1.5 M in THF, 1.5 mL, 1.1 equiv.) was added via syringe and stirred for 20 min at 25˚C. The mixture was transferred via cannula to a solution of Pd2(dba)3*CHCl3 (103.5 mg, 0.1 mmol), PPh3 (104.9 mg, 0.4 mmol) and the haloarene in dry THF (4 mL) and stirred for 15 h. The solvent was removed, the residue portioned between CH2Cl2 and water (30 mL each) and the aqueous layer extracted with CH2Cl2 (3*20 mL). The combined organic layers were washed with 50 mL brine, dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography.

Desilylation of ynamides with TBAF to a solution of the silylated ynamide (1.0 mmol) in THF (20 mL) and two drops of water was added dropwise at 0˚C TBAF in THF (1M, 1.2 mL, 1.2 mmol). The solution was stirred at 0˚C. After completion of the reaction (TLC), EtOAc (20 mL) and brine (20 mL) were added. The aqueous layer was extracted twice with 20 mL of EtOAc. The combined organic layers were dried (MgSO4), filtered and concentrated. The crude product was purified by a column chromatography.

N-(2-(Prop-1-ynyl)phenyl)-N-tosylformamide Under N2 in a Schlenk tube, 4-methyl-N-(2(prop-1-inyl)phenyl)benzenesulfonamide (1.54 g, 5.4 mmol), formic acid (549 mg, 0.45 mL) and N,N-dimethylaminopyridine (7.3 mg, 0.11 mmol) in 10 mL toluene was stirred at 0˚C and N,N’-dicyclohexylcarbodiimide (DCC) (2.80 g, 13.6 mmol) was added. After 24 h at 25˚C, filtration through celite and chromatography (SiO2; petroleum ether: ethyl acetate = 2:1, Rf: 0.49) yielded 1.34 g (82%) of a colorless solid with m.p. = 103˚C. 1H-NMR (300 MHz, CDCl3): δ (ppm) = 1.69 (s, 3H’), 2.41 (s, 3H); 7.19 (t, 1 H, J = 5.2 Hz); 7.37 - 7.23 (m, 5H); 7.59 (d, 2H, J = 6.0 Hz); 9.23 (s, 1H); 13C-NMR (75 MHz, CDCl3): δ (ppm) = 4.35, 21.68, 75.20, 128.33, 128.45, 129.71, 129.77, 130.85, 132.45, 133.16, 134.95, 145.36, 160.31; IR (ATR): ν ˜ [cm−1] = 3263, 2917, 2091, 1707, 1595, 1595, 1485, 1364, 1170, 1080, 992, 812, 757; FD-MS: m/z (%) = 313.3 (100) [M+].

N-(2,2-Dichlorovinyl)-4-methyl-N-(2-(prop-1-ynyl)phenyl)benzenesulfonamide Tetrachloromethane (0.35 mL, 3.2 mmol) was added to a solution of N-(2-(prop-1-ynyl)phenyl)-N-tosylformamide (100 mg, 0.32 mmol) and triphenylphosphine (250 mg, 0.94 mmol) in dry toluene (1.5 mL). After 24 h at 110˚C, the solvent was removed and the residue purified via chromatography (SiO2; petroleum ether: ethyl acetate = 4:1, Rf: 0.39) to yield 108 mg (89%) of a yellowish oil. 1H-NMR (300 MHz, CDCl3): δ (ppm) = 1.74 (s, 3H), 2.41 (s, 3H), 7.02 (s, 1H), 7.15 (d, 1H, J = 7.8 Hz), 7.32 - 7.20 (m, 4H, 7.43 (d, 1H, J = 7.7 Hz); 7.51 (d, 2H, J = 8.3 Hz); 13C-NMR (100 MHz, CDCl3): δ (ppm) = 21.60, 29.68, 75.98, 91.96, 113.21, 126.07, 126.72, 127.90, 128.03, 128.34, 129.54, 131.92, 133.01, 135.29, 144.33; IR (ATR): ν ˜ (cm−1) = 2955, 2920, 2155, 1484, 1362, 1246, 1089, 1009, 840, 754; FD-MS: m/z (%) = 379.0 (100%, M+).

N-Ethinyl-4-methyl-N-(2-(prop-1-ynyl)phenyl)benzenesulfonamide 4a To N-(2,2-dichlorovinyl)-4-methyl-N-(2-(prop-1-inyl)phenyl)benzenesulfonamide

(68 mg, 0.18 mmol) in 1 mL dry THF at −78˚C was added butyl lithium (0.16 mL, 2.5M). Upon warming to −30˚C methanol (50 µL) was added, at 25˚C, petroleum ether (3 mL) and sat. NaHCO3 were added, the solvent stripped off to yield 55 mg (99%) of 4a. Analytical data were identical to the literature. [15a]

N-(2-(Phenylethinyl)phenyl)-N-tosylformamide Under N2 in a Schlenk tube, 4-methyl-N-(2(phenylethynyl)phenyl)-benzenesulfonamide (1.81 g, 5.4 mmol), formic acid (549 mg, 0.45 mL) and N,N-dimethylaminopyridine (7.3 mg, 0.11 mmol) in 10 mL toluene were stirred at 0˚C and N,N’-dicyclohexylcarbodiimide (2.80 g) was added. After 24 h at 25˚C, filtration through celite and chromatography (SiO2; petroleum ether: ethyl acetate = 2:1, Rf: 0.44) yielded 1.78 g (90%) of a colorless solid, m.p. = 109˚C. 1H-NMR (300 MHz, CDCl3): δ (ppm) = 2.23 (s, 3H), 7.07 (d, 2H, J = 8.0 Hz), 7.17 - 7.61 (m, 11H), 9.28 (s, 1H); 13C-NMR (75 MHz, CDCl3): δ (ppm) = 21.55, 75.65, 84.83, 113.78, 124.17, 128.15, 128.68, 129.17, 129.87, 131.13, 131.50, 131.52, 132.96, 133.01, 134.66, 145.45, 160.29, IR (ATR): (cm−1) = 3232, 2988, 1708, 1496, 1364, 1284, 1171, 1122, 1076, 1019, 906, 865, 756, 667; FD-MS: m/z (%) = 375.3 (100) [M+].

N-(2,2-Dichlorovinyl)-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide Tetrachloromethane (0.5 mL, 3.2 mmol) was added to a solution of N-(2-(phenylethynyl)phenyl)-N-tosylformamide (395 mg, 5 mmol) and triphenylphosphine (395 mg, 1.51 mmol) in dry toluene (3 mL). After 24 h at 110˚C, the solvent was removed and the residue purified via chromatography (SiO2; petroleum ether: ethyl acetate = 4:1, Rf: 0.34) to yield 95 mg (45 %) of a yellowish oil. 1H-NMR (300 MHz, CDCl3): δ (ppm) = 2.24 (s, 3H), 7.07 (d, 2H, J = 8.6 Hz), 7.15 (s, 1H), 7.25 (d, 2H, J = 8.4 Hz), 7.35 – 7.31 (m, 4H), 7.45 - 7.39 (m, 2H), 7.50 (d, 2H, J = 8.3 Hz, 7.57 (dd, 1H, J = 7.8, 1.4 Hz); 13C-NMR (75 MHz, CDCl3): δ (ppm) = 21.47, 85.37, 94.84, 115.03, 122.22, 122.50, 126.16, 127.72, 128.22, 128.32, 128.64, 128.79, 129.78, 131.30, 132.2, 132.98, 134.72, 138.66, 144.50; IR (ATR): ν ˜ (cm−1) = 3062, 2885, 2201, 1493, 1443, 1366, 1170, 1088, 912, 754; FD-MS: m/z (%) = 441.2 (100) [M+].

N-Ethynyl-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfonamide4e To N-(2,2-Dichlorovinyl)-4-methyl-N-(2-(phenylethynyl)phenyl)benzenesulfon­amide (80 mg, 0.18 mmol) in 1 mL dry THF at −78˚C was added butyl lithium (0.16 mL, 2.5M). Upon warming to −30˚C, methanol (50 µL) was added, at 25˚C, petroleum ether (3 mL) and sat. NaHCO3 were added, the solvent stripped off to yield 62 mg (92%) of 4a. Analytical data were identical to the literature [14f].

N-(2-(Biphenylyl-4-ethynyl)phenyl)-N-ethynyl-4-methylbenzenesulfon­amide4f: Pd(PPh3)2Cl2 (5 mol-%) and CuI (10 mol-%) were dissolved in THF/NEt3 (1:2, v:v) under N2 in a Schlenk tube, N-(2-iodophenyl)-4-methyl-N-(trimethylsilylethynyl)benzolsulfonamide (265 mg, 0.57 mmol) added and a solution of 4-biphenylylacetylene (131 mg, 0.734 mmol) in THF added dropwise. After stirring for 24 h at 80˚C, the solvent was evaporated and the crude product 4f-TMS was directly desilylated to yield 154 mg (0.35 mmol, 63%) 4f after chromatography. Rf = 0.28 (PE/EtOAc 40/10). 1H NMR (300 MHz, CDCl3, 25˚C): δ = 7.73 (d, J = 8.2 Hz, 2H, 2-H, 6-H Ts), 7.62 (d, J = 7.5 Hz, 2H), 7.37 - 7.57 (m, 11H), 7.13 (d, J = 8.1 Hz, 2H), 2.95 (s, CCH), 2.20 (s, 3H, CH3 Ts). 13C NMR (75 MHz, CDCl3, 25˚C): δ = 144.9 (C-4 Ts), 141.1 (Cq), 140.4 (Cq), 138.2 (Cq), 134.6 (Cq), 134.5 (Cq), 133.3 (CH), 132.0 (CH), 130.6 (CH), 129.9 (CH), 129.6 (CH), 129.2 (CH), 129.0 (CH), 128.4 (CH), 127.7 (CH), 127.0 (CH), 124.4 (CH), 122.8 (Cq), 121.7 (Cq), 95.3 (Cq), 88.4 (Cq), 85.5 (Cq), 59.1 (Cq), 21.5 (CH3). IR (neat, ATR) ν ˜ = 3297, 3034, 2130, 1489, 1392, 1169, 1089, 912, 763 cm−1. FD-MS: m/z (%) = 447.3 (100) [M+], 894.4 (22) [M2+].

2-(2-Trimethylsilylethynyl)-N-(2-(4-methoxyphenyl)ethynyl)-N-tosyl­benzenamine4h-TMS: Prepared according to the Negishi procedure from 4d

and 4-iodoanisole, yield = 83%, yellow oil, purified by column chromatography (SiO2, PE/EtOAc 95/5) Rf = 0.33 (PE/EtOAc 90/10). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 7.75 (d, 3J = 8.3 Hz, 2H, 2-H, 6-H, Ts), 7.52 (d, 3J = 5.7 Hz, 1H, 3-H), 7.32 (m, 7H, 3-H, 5-H Ts, 4-H, 5-H, 6-H An, 2-H, 6-H Ph), 6.80 (d, 3J = 8.9 Hz, 2H, 3-H, 5-H Ph), 3.78 (s, 3H, OCH3), 2.45 (s, 3H, CH3 Ts), 0.14 (9H, CH3 TMS). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 159.2 (Cq, C-4 Ph), 144.6 (Cq, C-4 Ts), 139.5 (Cq, C-1 An), 134.6 (Cq, C-1 Ts), 134.0 (CH, C-3), 133.0 (CH, C-2, C-6 Ph), 129.5 (CH, C-3, C-5 Ts), 129.1, 128.9, 128.6 (CH, C-4, C-5, C-6), 128.4 (CH, C-2, C-6 Ts), 122.8 (Cq, C-2), 114.9 (Cq, C-1 Ph), 113.7 (CH, C-3, C-5 Ph), 101.1 (Cq, C-C-TMS), 100.0 (Cq, C-C-TMS), 81.0 (Cq, C-C-Ph), 70.0 (Cq, C-C-Ph), 55.2 (OCH3), 21.6 (CH3, Ts), -0.4 (CH3, TMS). IR (neat, ATR) ν ˜ = 2958, 2837, 2238, 2157, 1600, 1567, 1508, 1486, 1444, 1366, 1291, 1245, 1173, 1089, 1032, 923, 830, 764, 706, 658 cm−1. FD-MS: m/z (%) = 473.4 (100) [M]+.

N-(2-Ethynylphenyl)-N-((4-methoxyphenyl)ethynyl)-4-methylbenzene­sulfonamide4h: According to the general procedure for desilylation of

TMS-diynes, 440 mg, 0.95 mmol) of 4h-TMS gave 310 mg (0.80 mmol, 86 %) of 6h as colorless solid. Rf= 0.39 (PE/EtOAc 40/10). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 7.71 (d, 3J = 8.1 Hz, 2H, 2-H, 6-H, Ts), 7.49 (d, 3J = 9.3 Hz, 1H, H-6 An), 7.23 - 7.34 (m, 7H), 6.77 (d, 2H, 3J = 8.7 Hz, 3-H, 5-H Ts), 3.75 (s, 3H, OCH3), 3.05 (s, 1H, CCH), 2.42 (s, 3H, CH3 Ts). IR (neat) ν ˜ = 2958, 2837, 2234, 2159, 1603, 1569, 1511, 1491, 1447, 1372, 1291, 1249, 1172, 1081, 1032, 923, 830, 764, 706, 658 cm−1.

2-(2-Trimethylsilylethynyl)-N-(2-(benzofuran-2-yl)ethynyl)-N-tosyl­benzenamine4i-TMS: Prepared according to the Negishi procedure from 4d

and 2-iodobenzofurane [115] , yield = 85%, yellow oil, purified by column chromatography (SiO2, PE/EtOAc 95/5), Rf = 0.58 (PE/EtOAc, 80/20). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 7.71 (d, 3J = 8.2 Hz, 2H, 2-H, 6-H Ts), 7.47 (m, 2H, 5-H Bf, 3-H An), 7.34 (m, 7H, 3-H, 5-H Ts, 4-H, 5-H, 6-H An, 6-H or 7-H, 8-H Bf), 7.23 (t, 3J = 6.9 Hz, 1H, 6-H or 7-H Bf), 6.91 (s, 1H, 3-H Bf), 2.46 (s, 3H, CH3 Ts), 0.19 (s, 9H, TMS). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 154.9 (Cq, C-9 Bf), 145.0 (Cq, C-4 Ts), 138.7, 138.6 (Cq, C-1 An and C-2 Bf), 134.6 (C, C-1 Ts), 134.5 (CH, C-3), 130.2 (CH, C-3, C-5 Ts), 129.6 (CH, C-2, C-6 Ts), 129.5, 128.9 (CH, C-4, C-5, C-6 sup.), 127.7 (Cq, C-4 Bf), 125.9 (CH, C-7 Bf), 123.4 (CH, C-6 Bf), 122.9 (Cq, C-2), 121.5 (CH, C-5 Bf), 113.0 (CH, C-8 Bf), 111.5 (CH, C-3Bf), 102.3 (Cq, C-C-TMS), 99.9 (Cq, C-C-TMS), 87.8 (Cq, C-C-Bf), 62.1 (Cq, C-C-Bf), 22.25 (CH3, Ts), 0.1 (CH3, TMS). IR (neat) ν ˜ = 3070, 2960, 2227, 2160, 1601, 1478, 1442, 1372, 1247, 1173, 1092, 844, 812, 753 cm−1. FD-MS: m/z (%) = 482.8 (100) [M]+.

2-Ethynyl-N-(2-(benzofuran-2-yl)ethynyl)-N-tosylbenzenamine4i Desilylation according to the general procedure from 4i-TMS, yield= 79%, white solid, m.p.: 127˚C, purified by column chromatography (SiO2, PE/EtOAc 90/10) Rf = 0.28. 1H NMR (400 MHz, CDCl3, 25˚C): δ = 7.76 (d, 3J = 8.3 Hz, 2H, 2-H, 6-H Ts), 7.54 (m, 3H), 7.36 (m, 7H), 7.23 (t, 3J = 7.2 Hz, 1H, Bf), 6.94 (s, 1H, Bf), 3.10 (s, 1H, CCH), 2.48 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 154.9 (Cq, Bf), 145.3 (Cq, C-4 Ts), 139.2 (Cq, C-1 An), 138.6 (C-2, Bf), 134.2 (CH, C-3 An), 134.0 (C, C-1 Ts), 129.8 (CH, C-3, C-5 Ts), 129.7, 129.3, 129.2 (CH, C-4, C-5, C-6 An), 128.6 (CH, C-2, C-6 Ts), 127.7 (Cq, Bf), 125.6 (CH, Bf), 123.1 (CH, Bf), 122.2 (Cq, C-2 An), 121.1 (CH, Bf), 113.0 (CH, Bf), 111.2 (CH, Bf), 87.6 (Cq, N-CC), 83.4 (CH, CCH), 78.5 (Cq, CCH), 61.6 (Cq, N-CC), 21.77 (CH3 Ts). IR (neat) ν ˜ = 3262, 2233, 1600, 1474, 1447, 1366, 1258, 1170, 1062, 923, 818, 754, 689 cm−1. FD-MS: m/z (%) = 411.1 (100) [M]+.

General procedure for [2 + 2 + 2]-cycloaddition of diynes with CS2

A degassed solution of BINAP (15.6 mg, 0.025 mmol, 10 mol%) and [RhCl(C8H14)2]2 (6.1 mg, 0.0087 mmol, 3.5 mol%) in CH2Cl2 (3.0 mL) was stirred in a Schlenk tube at 25˚C for 5 min under Ar and connected to a H2 reservoir for 30 min. The solvent was evaporated and the residue dissolved in dichloroethane (3.0 mL). A solution of the diyne (0.25 mmol) and CS2 (150 μL, 2.5 mmol) in DCE (7 mL) was added dropwise via syringe and the mixture was stirred at 80˚C. After completion of the reaction (TLC), the solvent was removed and the residue was purified by column chromatography.

4-Methyl-9-tosylthiopyrano[3,4-b]indole-3(9H)-thione7a: According to the general procedure 77.3 mg (0.25 mmol) of 4a gave 91.6 mg (0.237 mmol, 95%) of 7a as a violet solid with m. p. = 175˚C - 176˚C. Rf = 0.46 (Al2O3, PE/EtOAc 90/10). 1H NMR (400 MHz, CDCl3): δ = 8.55 (s, 1H, 1-H), 8.28 (d, 3J = 8.3 Hz, 1H, 8-H), 8.14 (d, 3J = 8.0, 1H, 5-H), 7.67 (“t”, 3J = 7.9 Hz, 1H, 7-H), 7.59 (d, 3J = 8.5 Hz, 2H, 2-H, 6-H Ts), 7.42 (“t”, 3J = 7.5 Hz, 1H, 6-H), 7.18 (d, 3J = 8.4 Hz, 2H, 3-H, 5-H Ts), 2.94 (s, 3H, 4-CH3 Ts), 2.33 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 197.6 (Cq, C=S), 146.0 (Cq, C-4 Ts), 142.2 (Cq, C-8a), 141.2 (Cq, C-9a), 134.3 (Cq, C-4), 134.2 (Cq, C-4a), 133.4 (Cq, C-1 Ts), 132.3 (CH, C-7), 130.1 (CH, C-3, C-5 Ts), 126.7 (CH, C-2, C-6 Ts), 126.6 (CH, C-5), 125.3 (CH, C-6), 125.3 (Cq, C-4b), 125.0 (CH, C-1), 115.3 (CH, C-8), 21.6 (CH3, Ts), 18.4 (4-CH3 Tp). IR (neat, ATR) ν ˜ = 2925, 1600, 1508, 1456, 1369, 1345, 1269, 1188, 1155, 1089, 1028, 936, 788, 743, 703, 668 cm−1. FD-MS: m/z (%) = 385.2 (100.0) [M]+. C19H15NO2S3 (385.52): calcd.: C 59.19, H 3.92, N 3.63, S 24.95; found: C 59.35, H 3.94, N 3.58, S 24.43. UV-Vis (CH2Cl2): λmax,1 = 529 nm, ε1 = 3927 cm2/mmol, λmax,2 = 312 nm, ε2 = 19,974 cm2/mmol.

Cycloaddition of CS2 to 4b (R1 = R2 = H) According to the general procedure, addition of CS2 to 4b (74.2 mg, 0.25 mmol) gave 15.9 mg (partially dec., 0.043 mmol, 17%) of 8b as a red solid together with 62.3 mg (partially dec., 0.168 mmol, 67%) of 7b as a violet solid.

8b: 5-Tosyl-thiopyrano[4,3-b]indole-3(5H)-thione, red solid with m.p.: 172˚C - 173˚C (dec.) Rf = 0.43 (SiO2, PE/CH2 Cl2/EtOAc 6/3/1). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.58 (s, 1H, 4-H), 8.22 (d, 3J = 8.4 Hz, 1H, 6-H), 8.15 (s, 1H, 1-H), 7.81 (d, 3J = 8.3 Hz, 2-H, 6-H Ts), 7.68 (d, 3J = 7.7 Hz, 1H, 9-H), 7.54 (“t”, 3J = 7.5 Hz, 1H, 7-H), 7.36 (“t”, 3J = 7.5 Hz, 1H, 8-H), 7.27 (d, 3J = 8.5 Hz, 3-H, 5-H Ts), 2.37 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 199.1 (Cq, C=S), 146.3 (Cq, C-4 Ts), 144.9 (Cq, C-4a), 139.8 (Cq, C-5a), 134.6 (CH, C-1), 134.0 (Cq, C-1 Ts), 130.4 (CH, C-7), 130.3 (CH, C-3, C-5 Ts), 127.0 (Cq, C-9b), 127.0 (CH, C-2, C-6 Ts), 125.3 (CH, C-8), 123.0 (CH, C-9), 122.9 (Cq, C-9a), 120.3 (CH, C-4), 115.3 (CH, C-6), 21.5 (CH3 Ts). IR (neat, ATR) ν ˜ = 1586, 1510, 1453, 1402, 1372, 1224, 1170, 1092, 987, 944, 866, 806, 752, 668 cm−1. FD-MS: m/z (%) = 371.2 (100) [M]+. HR-MS: [M + H]+ calcd: 372.0181; found 372.0189. UV-Vis (CH2Cl2): λmax,1 = 474 nm, ε1 = 3562 cm2/mmol, λmax,2 = 378 nm, ε2 = 27,770 cm2/mmol.

7b: 9-Tosyl-thiopyrano[3,4-b]indole-3(5H)-thione Violet solid, Rf = 0.43 (SiO2, PE/EtOAc 80/20). 1H NMR (300 MHz, CDCl3, 25˚C): δ = 8.49 (s, 1H, 1-H), 8.16 (d, J = 8.5 Hz, 1H, 8-H), 8.02 (s, 1H, 4-H), 7.80 (d, 1H, J = 7.7 Hz, 5-H), 7.69 (t, 1H, 7-H), 7.64 (d, 2H, J = 8.4 Hz, 2-H, 6-H Ts), 7.39 (t, J = 7.2 Hz, 6-H), 7.21 (d, J = 8.1 Hz, 2H, 3-H, 5-H Ts), 2.35 (s, 3H, CH3Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 197.9 (C=S), 146.3 (C-4 Ts), 142.5 (C-8a), 137.0 (C-4), 134.4 (C-9a), 133.7 (C-4a), 133.5 (C-1 Ts), 130.9 (C-7), 130.2 (C-3, C-5 Ts), 127.0 (C-2, C-6 Ts), 126.7 (C-6), 125.6 (C-4b), 122.9 (C-1), 115.5 (C-8), 21.67 (CH3 Ts). IR (neat, ATR) ν ˜ = 1589, 1515, 1451, 1372, 1224, 1171, 992, 957, 816, 767, 668 cm−1. FD-MS: m/z (%) = 371.2 (100) [M+]; UV-Vis (CH2Cl2): λmax,1 = 535 nm, ε1 = 5678 cm2/mmol, λmax,2 = 316 nm, ε2 = 33456 cm2/mmol.

Cycloaddition of the diyne 4c (R1 = n-Bu, R2 = H, 84 mg 0.24 mmol) and CS2 according to the general procedure gave 72.8 mg (0.17 mmol, 71%) of a mixture of 7c and 8c.

4-n-Butyl-9-tosyl-thiopyrano[3,4-b]indole-3(9H)-thione7c Violet solid, isolated by column chromatography (Al2O3, PE/EtOAc 90/10), Rf = 0.65 (SiO2, PE/EtOAc 80/20). Decomposition above 110˚C. 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.54 (s, 1H, 1-H), 8.30 (d, 3J = 8.4 Hz, 1H, 8-H), 7.99 (d, 3J = 7.8 Hz, 1H, 5-H), 7.67 (t, 3J = 8.4 Hz, 1H, 7-H), 7.60 (d, 3J = 8.4 Hz, 2H, 2-H, 6-H Ts), 7.43 (t, 3J = 8.2 Hz, 1H, 6-H), 7.19 (d, 3J = 8.2 Hz, 2H, 3-H, 5-H Ts), 2.34 (s, 3H, CH3 Ts), 1.69 (m, 2H, α-CH2), 1.57 (m, 2H, β-CH2), 1.25 (m, 2H, γ-CH2), 1.00 (t, 3J = 6.9 Hz, 3H, CH3 Bu). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 197.8 (C=S), 146.1 (C-4), 146.0 (C-4 Ts), 142.3 (C8a), 134.7 (C-9a), 133.8 (C-4a), 133.5 (C-1 Ts), 132.2 (C-7), 130.1 (C-3, C-5 Ts), 126.7 (C-2, C-6 Ts), 126.2 (C-5), 125.5 (C-6), 125.0 (C-4b), 124.6 (C-1), 115.5 (C-8), 30.4 (α-CH2 Bu), 27.5 (CH2 Bu), 23.1 (CH2 Bu), 21.7 (CH3 Ts), 13.9 (CH3 Bu). FD-MS: m/z (%) = 427.1 (100) [M+]. The product 8c was decomposed before all analyses were performed.

1-n-Butyl-5-tosyl-thiopyrano[4,3-b]indole-3(5H)-thione8c, red solid, decomposition above 100˚C. Isolated by column chromatography (Al2O3, PE/EtOAc 90/10), Rf= 0.48 (SiO2, PE/EtOAc 80/20). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.59 (s, 1H, 4-H), 8.32 (d, 3J = 8.4 Hz, 1H, 6-H), 7.80 (d, 3J = 8.6 Hz, 2H, 2-H, 6-H Ts), 7.73 (d, 3J = 8.0 Hz, 1H, 9-H), 7.54 (t, 3J = 8.4 Hz, 1H, 7-H), 7.39 (m, 1H, 8-H), 7.27 (d, 3J = 8.4 Hz, 2H, 3-H, 5-H Ts), 3.05 (t, 3J = 7.8 Hz, 2H, α-CH2), 2.37 (s, 3H, CH3 Ts), 1.74 (m, 2H, β-CH2), 1.50 (m, 2H, γ-CH2), 0.98 (t, 3J = 7.3 Hz, 3H, CH3 Bu). FD-MS: m/z (%) = 427.3 (100) [M]+. The product 9c was decomposed before all analyses were performed.

Cycloaddition of CS2 to4e (R1 = Ph, R2= H, 0.25 mmol) according to the general procedure, gave 103 mg (92 %) of a 5 /4 mixture of 7e and 8e. Separation by column chromatography (Al2O3, PE/CHCl3/EtOAc 7/2/1).

4-Phenyl-9-tosyl-thiopyrano[3,4-b]indole-3(9H)-thione7e: violet solid, m.p. = 167˚C - 168˚C, Rf = 0.54 (PE/EtOAc 80/20). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.61 (s, 1H, H-1), 8.16 (d, 3J = 8.5 Hz, 1H, H-8), 7.66 (d, 3J = 8.4 Hz, 2H, 2-H, 6-H Ts), 7.54 (m, 4H, 7-H Bz, 3-H, 5-H Ph), 7.24 (d, 3J = 8.5 Hz, 2H, 3-H, 5-H Ts), 7.14 (d, 3J = 7.7 Hz, 2H, 2-H, 6-H Ph), 6.94 (“t”, 3J = 8.7 Hz, 1H, 6-H), 6.11 (d, 3J = 8.2 Hz, 1H, 5-H), 2.38 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 197.8 (Cq, C-3), 146.1 (Cq, C-4 Ts), 143.6 (Cq, C-9a), 142.4 (Cq, C-8a), 136.6 (Cq, C-1 Ph), 134.8 (Cq, C-4), 134.6 (Cq, C-4a), 133.5 (Cq, C-1 Ts), 132.6 (CH, C-7), 130.1 (CH, C-3, C-5 Ts), 129.8 (CH, C-3, C-5 Ph), 128.8 (CH, C-4 Ph), 128.5 (CH, C-2, C-6 Ph), 126.7 (CH, C-2, C-6 Ts), 126.6 (CH, C-1), 126.2 (CH, C-5), 124.9 (CH, C-6), 124.2 (Cq, C-4b), 114.8 (CH, C-8), 21.6 (CH3 Ts). IR (neat, ATR): ν ˜ = 3084, 2988, 1594, 1513, 1447, 1375, 1342, 1282, 1251, 1167, 1159, 1092, 1041, 953, 899, 839, 809, 749, 695, 665 cm−1. FD-MS: m/z (%) = 447.2 (100) [M]+. HR-MS: [M + H]+ calcd.: 448.0494; found 448.0495. UV-Vis: (CH2Cl2): λmax,1 = 535 nm, ε1 = 4240 cm2/mmol, λ2 = 313 nm, ε2 = 21,099 cm2/mmol.

1-Phenyl-5-tosyl-thiopyrano[4,3-b]indole-3(5H)-thione8e: red solid, m.p. = 146˚C - 147˚C, Rf= 0.48 (Al2O3, PE/EtOAc 80/20). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.66 (s, 1H, 4-H), 8.26 (d, 3J = 8.4 Hz, 1H, 6-H), 7.86 (d, 3J = 8.4 Hz, 2H, 2-H, 6-H Ts), 7.56 (m, 3H, 3-H, 4-H, 5-H Ph), 7.42 (m, 3H, 7-H In, 2-H, 6-H Ph), 7.31 (d, 3J = 8.0 Hz, 2H, 3-H, 5-H Ts), 7.01 (t, 3J = 8.0 Hz, 1H, 8-H), 6.78 (d, 3J = 8.0 Hz, 1H, 9-H), 2.40 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 198.9 (Cq, C=S), 154.5 Cq, C-1), 146.3 (Cq, C-4 Ts), 145.9 (Cq, C-4a), 139.9 (Cq, C-5a), 134.0 (C, C-1 Ts), 133.2 (Cq, C-1 Ph), 130.8 (CH, C-4 Ph), 130.3 (CH, C-3, C-5 Ts), 129.93 (CH, C-7), 129.5 (CH, C-3, C-5 Ph), 128.5 (CH, C-2, C-6 Ph), 127.0 (CH, C-2, C-6 Ts), 124.8 (CH, C-8), 123.9 (Cq, C-9b), 122.8 (Cq, C-9a), 122.38 (CH, C-9), 121.4 (CH, C-4), 115.0 (CH, C-6), 21.7 (CH3 Ts). IR (neat, ATR): ν ˜ = 2973, 1583, 1519, 1456, 1363, 1176, 1155, 1086, 984, 942, 809, 746, 695, 671 cm−1. FD-MS: m/z (%) = 447.2 (100) [M]+. HR-MS: [M + H]+ calcd.: 448.0494; found 448.0513. UV-Vis: (CH2Cl2): λmax,1 = 497 nm, ε1 = 46,310 cm2/mmol, λmax,2 = 378 nm, ε2 = 23,841 cm2/mmol.

Cycloaddition of diyne4f (R1 = 4-biphenylyl, R2 = H) (134 mg, 0.3 mmol and CS2 according to the general procedure, gave 50 mg (34%) of a 2/1 mixture of 4-(biphenyl-4-yl)-9-tosylthiopyrano[3,4-b]indol-3(9H)-thione 7f and 1-(biphenyl4-yl)-5-tosylthiopyrano[4,3-b]indol-3(5H)-thione 8f. The violet isomer 7f decomposed very fast.

1-(Biphenyl-4-yl)-5-tosylthiopyrano[4,3-b]indol-3(5H)-thione 8f: Rf: 0.43 (petroleum ether/ethyl acetate/dichloromethane = 16/2/1). 1H NMR (400 MHz, CDCl3, 25˚C): δ = 8.67 (s, 1H, H-4), 8.27 (d, J = 8.5 Hz, 1H), 7.86 (d, J = 8.4 Hz, 2H, Ts), 7.78 (d, J = 7.2 Hz, 2H, Bp), 7.69 (d, J = 7.1 Hz, 2 H Bp), 7.42 - 7.53 (m, 6 H, Bp), 7.31 (d, J = 8.4 Hz, 2 H, Ts), 7.04 (t, J = 7.2 Hz, 1 H), 6.98 (t, J = 7.2 Hz, 1 Bp), 2.40 (s, 3H, CH3 Ts). 13C NMR (100 MHz, CDCl3, 25˚C): δ = 205.0 (C=S), 146.4 (C-4, C-1'Bp), 146.1 (C-4 Ts), 140.1 (C-9b), 139.5 (C-5a), 134.2 (C-1 Ts), 130.4 (C-7), 130.0 (C1), 129.1(C-3, C-5 Bp), 128.4 (C-3, C-5 Ts, C-4'Bp), 128.1 (C-2, C-6, C-3', C-5' Bp), 127.2 (C-2, C-6 Ts), 124.8 (C-8), 124.0 (C-9), 123.1 (C-4’ Bp), 122.5 (C9a), 121.5 (C-4), 115.1 (C-6), 21.8 (CH3 Ts), one signal missing due to superposition. IR (neat, ATR) ν ˜ = 3012, 1598, 1505, 1453, 1346, 1172, 1157, 1045, 952, 899, 767 cm−1. FD-MS: m/z (%) = 523.3 (100) [M+]. The product 7f decomposed before all analyses were performed.

Cycloaddition of CS2 to 4g (R1 = H, R2 = phenyl, 0.25 mmol) according to the general procedure, catalyst: 2.5 mol-% [RhCl(COD)]2, 5 mol-% 2,2'BINAP (11.2 mg, 0.018 mmol). Purification by column chromatography Rf: 0.46 (Al2O3, petroleum ether/ethyl acetate/chloroform = 8:1:1) gave 76 mg (68%) 4-phenyl-9-tosyl-thiopyrano[3,4-b]indole-3(9H)-thione as violet solid with m.p. = 175˚C - 176˚C. 1H NMR (CDCl3) δ ppm: 8.08 (d, J = 8.2 Hz, 1H), 7.75 (m, 2H), 7.70 (s, 1H), 7.63 (m, 2H), 7.54 (m, 3H), 7.37 (t, J = 7.2 Hz, 1H), 7.06 (d, J = 8.3 Hz), 6.97 (d, J = 8.3 Hz, 2H), 2.26 (s, 3H); 13C NMR (CDCl3) δ ppm: 201.0 (Cq), 149.8 (Cq), 145.4 (Cq), 144.8 (Cq), 141.6 (Cq), 135.7 (Cq), 133.6 (Cq), 132.9 (CH), 131.2 (Cq), 130.5 (CH), 129.3 (CH), 129.1 (CH), 128.3 (CH), 127.6 (CH), 127.2 (Cq), 127.1 (CH), 127.0 (CH), 122.4 (CH), 120.1 (CH), 21.6 (CH3); IR (neat, ATR) ν ˜ = 3042, 1600, 1516, 1486, 1453, 1372, 1207, 1167, 1110, 1047, 905, 818, 773, 662 cm−1; FD-MS: m/z (%) = 447.3 (100) [M+], 448.3 (38), 449.3 (7), 450.3 (3); UV-Vis (CH2Cl2): λmax1 = 527 nm, ε1 = 4895 cm2/mmol, λmax2 = 322 nm, ε2 = 22013 cm2/mmol.

Cycloaddition of CS2 to 4h (R1 = H, R2 = 4-anisyl, 0.3 mmol) according to the general procedure, catalyst: 3 mol-% [RhCl(COD)]2 (6.5 mg, 0.009 mmol), 6 mol-% 2,2'BINAP (11.2 mg, 0.018 mmol). Purification by column chromatography Rf: 0.22 (petroleum ether/ethyl acetate/DCM = 8:1:1) gave 51 mg (36%). 1-(4-Methoxyphenyl)-9-tosylthiopyrano[3,4-b]indol-3(9H)thione7h. the compound decomposes before melting. 1H-NMR (400 MHz, CDCl3): δ (ppm) = 2.26 (s, 3H), 3.90 (s, 3H), 6.97 (d, 2H, J = 8.1 Hz), 7.05 (d, 4H), 7.36 (t, 1H, J = 7.2 Hz), 7.59 - 7.65 (m, 2H), 7.66 (s, 1H, H4); 7.74 (d, 2H, H3‘‘, J = 8.9 Hz), 8.08 (d, 1H, J = 8.2 Hz); 13C-NMR (100 MHz, CDCl3): δ (ppm) = 21.59, 55.40, 114.63, 120.27, 122.40, 126.96, 127.03, 127.23, 127.50, 128.19, 129.93, 131.19, 132.72, 133.15, 141.97, 144.90, 145.37, 150.36, 161.50, 200.7; IR (CDCl3, ATR): ν ˜ (cm−1) = 2897, 1495, 1375, 1187, 1084, 925, 827, 827; FD-MS: m/z (%) = 477.2 (100) [M+]; UV-Vis (CH2Cl2): λmax1 = 538 nm, ε1 = 5990 cm2/mmol, λmax2 = 378 nm, ε2 = 40,456 cm2/mmol.

Cycloaddition of CS2 to6i (R1 = H, R2 = 2-benzofuranyl, 83 mg, 0.2 mmol) according to the general procedure, catalyst: [RhCl(COD)]2 3 mol-% (4.3 mg, 0.006 mmol), 6 mol-% 2,2'BINAP (7.5 mg, 0.012 mmol). Purification by column chromatography Rf: 0.25 (petroleum ether/ethyl acetate/DCM = 8:1:1) gave 21 mg (21%) 1-(Benzofuran-2-yl)-9-tosylthiopyrano[3,4-b]indole-3(9H)thione7i together with 7-tosyl-7H-benzofuro[2,3-b]carbazole 10 as by-product, the compound decomposes before melting. 1H-NMR: (400 MHz, CDCl3): δ (ppm) = 2.27 (s, 3H), 7.00 (d, 2H, J = 8.0 Hz), 7.17 (d, 2H, J = 8.4 Hz), 7.29 - 7.37 (m, 2H), 7.41 - 7.47 (m, 1H), 7.51 (s, 1H), 7.57 - 7.65 (m, 4H), 7.71 (d, 1H, J = 7.8 Hz), 8.08 (d, 1H, J = 8.4 Hz); 13C-NMR (100 MHz, CDCl3): δ (ppm) = 21.36, 110.33, 111.67, 119.72, 122.05, 122.20, 123.61, 126.71, 126.76, 126.82, 127.14, 127.55, 127.70, 129.12, 131.22, 132.62, 133.02, 136.41, 141.14, 144.72, 145.24, 148.59, 155.24, 199.59; IR (ATR): ν ˜ (cm−1) = 2892, 1608, 1537, 1512, 1368, 1177, 1109, 1046, 971, 890, 812, 755; FD-MS: m/z (%) = 487.2 (100) [M+]; UV-Vis (CH2Cl2): λmax1 = 547 nm, ε1 = 5358 cm2/mmol, λmax2 = 391 nm, ε2 = 33476 cm2/mmol.

7-Tosyl-7H-benzofuro[2,3-b]carbazole9 Rf: 0.30 (petroleum ether/ethyl acetate/DCM = 8:1:1); 1H-NMR (300 MHz, CDCl3): δ (ppm) = 2.23 (s, 3H), 7.07 (d, 2H, J = 8.5 Hz), 7.33 - 7.52 (m, 4H); 7.60 (d, 1H, J = 8.2 Hz), 7.72 (d, 2H, J = 8.4 Hz), 7.98 (t, 2H), 8.35 (d, 2H), 8.54 (s, 1H); IR (CDCl3, ATR): ν ˜ (cm−1) = 3279, 1489, 1370, 1170, 1125, 1124, 998, 809, 741; FD-MS: m/z (%) = 411.3 (100) [M+].

Acknowledgments

The authors are grateful to H. Kolshorn (Mainz) for discussions and NMR spectra and to B. Witulski (Caen) for initiating this project.

Conflicts of Interest

The authors declare no conflicts of interest regarding the publication of this paper.

Cite this paper

Dassonneville, B., Hinkel, F. and Detert, H. (2023) Rhodium Catalyzed [2π + 2π + 2π]-Cycloaddition of Alkynyl-Ynamides and Carbon Disulfide to Indolo-Thiopyrane Thiones. International Journal of Organic Chemistry, 13, 16-39. https://doi.org/10.4236/ijoc.2023.131003

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