Carbonylative Synthesis of 3-Substituted Thiochromenones via

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Cite This: J. Org. Chem. 2018, 83, 13612−13617

Carbonylative Synthesis of 3‑Substituted Thiochromenones via Rhodium-Catalyzed [3 + 2 + 1] Cyclization of Different Aromatic Sulfides, Alkynes, and Carbon Monoxide Fengxiang Zhu and Xiao-Feng Wu* Leibniz-Institut für Katalyse e.V., Universität Rostock, Albert-Einstein-Straße 29a, Rostock 18059, Germany

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S Supporting Information *

ABSTRACT: We have developed a rhodium-catalyzed carbonylative annulation methodology for the direct preparation of thiochromenones. With nonactivated aromatic sulfides and terminal alkynes as the substrates, the desired sulfur-containing six-membered heterocycles were prepared effectively via [3 + 2+1]-type annulation.

T

On the other hand, carbonylative transformations with transition metals as the catalysts have been broadly applied.7 Valuable chemicals can be prepared in a straightforward and atom economical was through carbonylative reactions. Notably, carbonylative procedures for the synthesis of thiochromones have been developed without surprise. By using 2-iodofluoroarenes and alkynes as the substrates, 2substituted thiochromones can be prepared in a one-pot twostep manner (Figure 1, eq c).8 Besides the advantages of these methods, drawbacks related to substrates accessibility and functional group compatibility still exist. The use of preactivated or highly functionalized compounds as the substrates will definitely generate wastes and increase the total costs. Hence, an ideal option will be the direct carbonylative [3 + 2+1] annulation of commercially available aromatic sulfides and alkynes (Scheme 1).

hiochromenones are important sulfur-containing heterocycles present in various naturally occurring products and biological active chemicals.1 Oxidized derivatives of thiochromenones have been used as cytomegalovirus protease inhibitors for humans2 as well as protecting groups for phosphate compounds.3 Considering their importance, different pathways have been established for their preparation.4 Nevertheless, the requirement of specific types of substrates and relatively harsh reaction conditions has limited their utilization. More recently, alternative procedures have been developed as well. For example, Sekar’s group developed a copper-catalyzed domino method for 2-arylthiochromanone preparation. The reaction proceeds through concomitant C−S bond formations using xanthate as the sulfur source (Figure 1, eq a).5 Matsubara and co-workers reported a nickel-catalyzed transformation between alkynes and thioisatins (Figure 1, eq b), and one molecule of CO was released from this system.6 However, challenges of the reported methodologies including limited functional group capacity and special substrate demands still need to be solved.

Scheme 1. Retrosynthetic Analysis: An Ideal Procedure

Under all of these backgrounds and based on our continued interest in carbonylative transformations,9 we report here our new results on rhodium-catalyzed carbonylative [3 + 2+1] cyclization of aromatic sulfides and alkynes. Initially, we chose diphenyl disulfide (1a) and phenylacetylene (2a) as the substrates to establish the catalytic system. [RhCl(COD)]2 has been used as the catalyst with DMF as the solvent (Table 1). To our delight, 3-phenyl-(4H)thiochromen-4-one (3aa) can be afforded with DTBP as the oxidant in 7% yield (Table 1, entry 1). Stimulated by this Received: September 5, 2018 Published: October 8, 2018

Figure 1. Selected procedures for thiochromones syntheses. © 2018 American Chemical Society

13612

DOI: 10.1021/acs.joc.8b02294 J. Org. Chem. 2018, 83, 13612−13617

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The Journal of Organic Chemistry Table 1. Establishing the Catalytic Systema

entry

oxidant

ligand

1 2 3 4 5 6 7 8 9 10c 11d 12d 13d 14d 15 16 17 18 19 20 21 22 23 24e 25f

DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP DTBP TBHP DCP BPO TBPB DCP DCP

PPh3 Xantphos DPEphos DPPF DPPP BuPad2 BINAP Phen. PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3 PPh3

Table 2. Rh-Catalyzed Thioflavone Synthesis: Testing of Diaryl Disulfidesa

additive

yield (%)b

AgOTf AgTFA AgBF4 AgSbF6 Bu4NCl Bu4NBr Bu4NI LiCl LiBr LiBr LiBr LiBr LiBr LiBr LiBr

7 43 25 29 24 14 16 13 9 21 15 9 17 13 46 45 46 41 48 25 61 48 30 65 73

a

Compound 1 (0.1 mmol equal to 0.2 mmol thiophenol), 2a (0.4 mmol), [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), DCP (0.4 mmol), LiBr (0.4 mol), CO (5 bar), 110 °C, DMA (2 mL), HFIP (0.2 mL), 24 h, isolated yield. bRegioselectivity ratio.

the annulation successfully. The corresponding thiochromenones were formed in good yields in general (Table 2, 3aa− 3ea). However, when m-substituted diaryl disulfide was applied, mixtures of two isomers were obtained (Table 2, 3fa−3ha). Then, different alkynes were tested under our standard conditions, and the corresponding products were isolated in moderate to good yields (Table 3, 3ab−3ak). 3-Ethynylthiophene and 3-phenyl-1-propyne can be transformed as well and gave the desired thiochromenones in 63% yield (Table 2, 3al and 3am). However, in the case of cyclohexylacetylene and 1-octyne, no desired products could be detected under our standard conditions. Internal alkynes and aryl alkenes such 2n and 2o were also tested, but unfortunately, the products 3an and 3ao could not be detected. Furthermore, thiophenols were tested with alkynes under our best conditions as well. To our delight, we found not only different thiophenols but also various alkynes can be transformed into the desired thiochromenones in good yields (Table, 4). On the basis of our previous work and literature,10 we know aromatic sulfides such as methylbenzenesulfinate, benzenesulfonyl chloride, and benzenesulfonohydrazide could be easily converted into the corresponding diaryl disulfides. On the basis of this idea and optimizations, we found that, by using benzenesulfonyl chlorides and benzenesulfonohydrazides as the substrates in the presence of 2 equiv of diethyl phosphate under our standard conditions, the desired thiochromenones can be formed successfully as well (Table 5). In general, good yields can be achieved with the tested substrates. Control experiments were performed as well for understanding the reaction pathway (Scheme 2). In the absence of

a

Compund 1a (0.1 mmol equal to 0.2 mmol thiophenol), 2a (0.4 mmol), [RhCl(COD)]2 (2.5 mol %), ligand (15 mol %), oxidant (0.4 mmol), 110 °C, DMF (2 mL), additive (0.4 mmol), 24 h, CO (5 bar). b GC yields using hexadecane as internal standard. cRhCl(PPh3)3 instead of [RhCl(COD)]2. dSilver salt (10 mol %). eDMA instead of DMF. fDMA and HFIP (0.2 mL) instead of DMF. DTBP, di-tertbutyl peroxide; DCP, dicumyl peroxide; BPO, benzoyl peroxide; TBPB, tert-butyl peroxybenzoate; DPEphos, (oxidi-2,1-phenylene)bis(diphenylphosphine); Xantphos, 4,5-bis(diphenylphosphino)-9,9dimethylxanthene; DPPF, 1,1′-ferrocenediyl-bis(diphenylphosphine); DPPP, 1,3-bis(diphenylphosphino)propane; BuPad2, butyldi-1-adamantylphosphine; BINAP, (2,2′-bis(diphenylphosphino)-1,1′-binaphthyl); Phen, 1,10-phenanthrolin.

exciting outcome, variations of the ligands were then performed (Table 1, entries 2−9). Improved yield can be obtained with PPh3 as the ligand (Table 1, entry 2), and 43% of thiochromenone was produced. Wilkinson’s catalyst RhCl(PPh3)3 was also screened but exhibited inefficient catalytic activity (Table 1, entry 10). Then, different additives were checked (Table 1, entries 11−19), and the yield was further increased to 48% when LiBr was added (Table 1, entry 19). The influences of the other peroxides were tested as well (Table 1, entries 20−23), and 61% yield can be achieved with DCP as the oxidant (Table 1, entry 21). Finally, DMA, NMP or HFIP as the solvent were also tested (Table 1, entries 24− 25), 73% of the product can be found when using DMA and HFIP as a mixed solvent (Table 1, entry 25). Subsequently, testing of diaryl disulfides 1 with phenylacetylene 2a was performed (Table 2). Various diaryl disulfides with electron-donating and -withdrawing groups underwent 13613

DOI: 10.1021/acs.joc.8b02294 J. Org. Chem. 2018, 83, 13612−13617

Note

The Journal of Organic Chemistry Table 3. Rh-Catalyzed Thioflavone Synthesis: Testing of Alkynesa

Table 4. Rh-Catalyzed Thioflavone Synthesis: Substrate Scope of Benzenethiols and Alkynesa

a Compound 1′ (0.2 mmol), 2 (0.4 mmol), [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), DTBP (0.8 mmol), Bu4NI (0.2 mol), CO (5 bar), 110 °C, DMA (2 mL), HFIP (0.2 mL), 24 h, GC yield using nhexadecane as internal standard.

the starting materials, the desired sulfur-containing heterocycles were prepared effectively.

■

a Compound 1a (0.1 mmol equal to 0.2 mmol thiophenol), 2 (0.4 mmol), [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), DCP (0.4 mmol), LiBr (0.4 mol), CO (5 bar), 110 °C, DMA (2 mL), HFIP (0.2 mL), 24 h, isolated yield.

EXPERIMENTAL SECTION

General Comments. NMR spectra were recorded on Bruker Avance 300 and Bruker ARX 400 spectrometers. Chemical shifts (ppm) are given relative to solvent: references for CDCl3 were 7.26 ppm (1H NMR) and 77.0 ppm (13C NMR). 13C NMR spectra were acquired on a broad band decoupled mode. Multiplets were assigned as s (singlet), d (doublet), t (triplet), dd (doublet of doublet), m (multiplet) and br s (broad singlet). All measurements were carried out at room temperature unless otherwise stated. Gas chromatography analysis was performed on an Agilent HP-5890 instrument with an FID detector and HP-5 capillary column (polydimethylsiloxane with 5% phenyl groups, 30 m, 0.32 mm i.d., 0.25 μm film thickness) using argon as carrier gas. The products were isolated from the reaction mixture by column chromatography on silica gel 60, 0.063− 0.2 mm, 70−230 mesh (Merck). All reactions were carried out under an Ar atmosphere. All of the reagents were purchased from SigmaAldrich or Alfa-Aesar chemical company. Because of the high toxicity of carbon monoxide, all of the reactions should be performed in an autoclave. The laboratory should well-equipped with a CO detector and alarm system. General Procedures. General Procedure A. A 4 mL screw-cap vial was charged with [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), alkyne (0.4 mmol), diphenyl disulfide (0.1 mmol) (benzenethiol) (0.2 mmol), dicumyl peroxide (0.4 mmol) (DCP) (0.8 mmol), LiBr (0.4 mol), DMA (2 mL), HFIP (0.2 mL), and an oven-dried stirring bar. The vial was closed by Teflon septum and phenolic cap and connected to the atmosphere with a needle. Then, the vial was fixed in an alloy plate and put into a Paar 4560 series autoclave (300 mL). At room temperature, the autoclave was flushed with carbon monoxide three times, and 5 bar of carbon monoxide was charged. The

DTBP, no thiochromenones could be obtained with benzenesulfonyl chloride and benzenesulfonohydrazide as substrates. Instead phenyl disulfide was isolated in 71 and 83% yields, respectively (Scheme 2, 1 and 2). In our model system, no product could be obtained when 2 equiv of radical scavengers (TEMPO, BHT, and 1,1-diphenylethylene) were added (Scheme 2, 3). We believe radical intermediates were involved during the reaction. A reaction pathway is proposed based on our understanding (Scheme 3). Initially, the thiophenol radical and RhII were produced in the presence of DCP via a single electron transfer process. Then, the addition of thiophenol radicals and terminal alkynes afforded vinyl radical C, which could be transformed to intermediate D through a SET process with RhII. Finally, the key intermediate seven-membered rhodium cycle complex E or E′ was formed after being reacted with CO followed by the reductive elimination to afford the desired product thiochromenone with the regeneration of RhI. In conclusion, a carbonylative procedure for the direct synthesis of thiochromenones has been developed. With rhodium as the catalyst and aromatic sulfides and alkynes as 13614

DOI: 10.1021/acs.joc.8b02294 J. Org. Chem. 2018, 83, 13612−13617

Note

The Journal of Organic Chemistry Table 5. Rh-Catalyzed Thioflavone Synthesis from Benzenesulfonyl Chloride and Benzenesulfonohydrazidea

Scheme 3. Plausible Reaction Mechanism

the vial was fixed in an alloy plate and put into a Paar 4560 series autoclave (300 mL). At room temperature, the autoclave was flushed with carbon monoxide three times, and 5 bar of carbon monoxide was charged. The autoclave was placed on a heating plate equipped with a magnetic stirring bar and an aluminum block. The reaction mixture was heated at 110 °C for 24 h. Afterward, the autoclave was cooled to room temperature, and the pressure was carefully released. The reaction solution was quenched with distilled water and extracted with ethyl acetate three times. The combined organic phases were washed with saturated NaCl solution and dried over Na2SO4. The crude product was purified by column chromatography (ethyl acetate/ pentane = 1:15) to give the pure product. Analytic Data. 3-Phenyl-4H-thiochromen-4-one (3aa)11 (33.8 mg, 71%). 1H NMR (400 MHz, chloroform-d) δ 8.56 (dt, J = 7.9, 1.2 Hz, 1H), 7.79 (s, 1H), 7.55−7.52 (m, 2H), 7.51−7.43 (m, 3H), 7.38− 7.26 (m, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 178.2, 137.5, 136.8, 136.8, 135.5, 132.8, 131.2, 129.5, 128.9, 128.3, 128.0, 127.78, 126.5. GC-MS (EI-70 eV): m/z (%) 238 (100), 136 (55), 108 (40). 6-Methyl-3-phenyl-4H-thiochromen-4-one (3ba)1 (36.8 mg, 73%). 1H NMR (300 MHz, chloroform-d) δ 8.48 (dp, J = 2.3, 0.8 Hz, 1H), 7.90 (s, 1H), 7.59−7.53 (m, 3H), 7.50−7.35 (m, 4H), 2.53 (s, 3H). 13 C{1H} NMR (75 MHz, CDCl3) δ 178.2, 138.1, 137.7, 136.6, 135.4, 133.8, 132.7, 132.6, 129.2, 128.9, 128.2, 127.9, 126.4, 21.4. GC-MS (EI, 70 eV): m/z (%) 252 (100), 150 (30), 121 (39). 6-Methoxy-3-phenyl-4H-thiochromen-4-one (3ca) (43.4 mg, 81%). 1H NMR (300 MHz, chloroform-d) δ 8.12 (d, J = 2.9 Hz, 1H), 7.93 (s, 1H), 7.62−7.37 (m, 6H), 7.28 (dd, J = 8.8, 2.9 Hz, 1H), 3.96 (s, 3H). 13 C{1H} NMR (75 MHz, CDCl3) δ 177.8, 159.6, 137.7, 135.7, 135.4, 134.2, 129.0, 128.8, 128.2, 127.9, 127.8, 121.8, 109.7, 55.7. GC-MS (EI, 70 eV): m/z (%) 268 (100), 123 (25). HRMS (EI): calcd for C16H12O2S [M]+ 268.0552, found 268.0550. 6-Fluoro-3-phenyl-4H-thiochromen-4-one (3da) (33.8 mg, 66%). 1H NMR (300 MHz, chloroform-d) δ 8.23 (ddd, J = 9.7, 2.9, 0.4 Hz, 1H), 7.83 (s, 1H), 7.55 (ddd, J = 8.8, 4.9, 0.5 Hz, 1H), 7.48−7.41 (m, 2H), 7.39−7.26 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.3, 162.2 (d, J = 249.75 Hz) 137.1, 135.9, 135.7, 134.7 (d, J = 6.82 Hz), 132.2 (d, J = 2.24 Hz), 128.9, 128.7 (d, J = 7.54 Hz), 128.3, 128.2, 120.2 (d, J = 24.33 Hz), 115.0 (d, J = 22.88 Hz). 19F NMR (282 MHz, CDCl3) δ −117.27. GC-MS (EI-70 eV): m/z (%) 256 (100), 154 (25), 126 (33). HRMS (EI): calcd for C15H9OFS [M]+ 256.0353, found 256.0354. 6-Chloro-3-phenyl-4H-thiochromen-4-one (3ea)11 (37.5 mg, 66%). 1 H NMR (300 MHz, chloroform-d) δ 8.54 (ddd, J = 1.6, 1.2, 0.5 Hz, 1H), 7.81 (s, 1H), 7.52−7.50 (m, 2H), 7.47−7.42 (m, 2H), 7.40− 7.30 (m, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.1, 137.0, 136.8, 135.4, 134.9, 134.4, 133.9, 131.7, 129.1, 128.9, 128.3, 128.3, 128.0. GC-MS (EI-70 eV): m/z (%) 272 (100), 170 (23), 142 (29), 102 (24).

a

Compound 1′ (0.2 mmol), 2 (0.4 mmol), [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), DTBP (0.8 mmol), Bu4NI (0.4 mol), diethyl phosphite (0.4 mmol), CO (5 bar), 110 °C, NMP (2 mL), HFIP (0.2 mL), 24 h, isolated yields.

Scheme 2. Control Experiments

autoclave was placed on a heating plate equipped with magnetic stirring bar and an aluminum block. The reaction mixture was allowed to be heated at 110 °C for 24 h. Afterward, the autoclave was cooled to room temperature, and the pressure was carefully released. The reaction solution was quenched with distilled water and extracted with ethyl acetate three times. The combined organic phases were washed with saturated NaCl solution and dried over Na2SO4. The crude product was purified by column chromatography (ethyl acetate/ pentane = 1:15) to give the pure product. General Procedure B. A 4 mL screw-cap vial was charged with [RhCl(COD)]2 (2.5 mol %), PPh3 (15 mol %), alkyne (0.4 mmol), benzenesulfonohydrazide or benzenesulfonyl chloride or methylbenzenesulfinate (0.2 mmol), DTBP (0.8 mmol), Bu4NI (0.4 mol), diethyl phosphite (0.4 mmol), NMP (2 mL), HFIP (0.2 mL), and an oven-dried stirring bar. The vial was closed by Teflon septum and phenolic cap and connected to the atmosphere with a needle. Then, 13615

DOI: 10.1021/acs.joc.8b02294 J. Org. Chem. 2018, 83, 13612−13617

Note

The Journal of Organic Chemistry 3-(p-Tolyl)-4H-thiochromen-4-one (3ab) (37.8 mg, 75%). 1H NMR (300 MHz, chloroform-d) δ 8.61−8.50 (m, 1H), 7.77 (s, 1H), 7.57− 7.41 (m, 3H), 7.40−7.30 (m, 2H), 7.22−7.10 (m, 2H), 2.31 (s, 3H). 13 C{1H} NMR (75 MHz, CDCl3) δ 178.3, 137.9, 136.8, 136.7, 134.9, 134.6, 132.8, 131.1, 129.5, 128.9, 128.8, 127.7, 126.5, 21.3. GC-MS (EI-70 eV): m/z (%) 252 (100), 136 (33), 115 (59), 108 (44). HRMS (EI): calcd for C16H12OS [M]+ 252.0603, found 252.0601. 3-(o-Tolyl)-4H-thiochromen-4-one (3ac) (31.8 mg, 63%). 1H NMR (300 MHz, chloroform-d) δ 8.70−8.60 (m, 1H), 7.79 (s, 1H), 7.73− 7.51 (m, 3H), 7.39−7.15 (m, 4H), 2.24 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 178.0, 138.1, 137.6, 137.1, 136.9, 135.9, 132.5, 131.2, 130.1, 129.8, 129.5, 128.3, 127.8, 126.6, 125.8, 20.0. GC-MS (EI-70 eV): m/z (%) 252 (45), 235 (100), 115 (69), 108 (39). HRMS (EI): calcd for C16H12OS [M]+ 252.0603, found 252.0604. 3-(2,4-Dimethylphenyl)-4H-thiochromen-4-one (3ad) (32.5 mg, 61%). 1H NMR (300 MHz, chloroform-d) δ 8.69−8.59 (m, 1H), 7.78 (s, 1H), 7.71−7.53 (m, 3H), 7.24−7.08 (m, 2H), 7.03 (dp, J = 2.0, 0.6 Hz, 1H), 2.36 (s, 3H), 2.19 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 178.1, 138.2, 137.4, 137.2, 135.7, 135.2, 133.7, 132.5, 131.2, 130.4, 129.9, 129.4, 129.0, 127.7, 126.6, 20.9, 19.5. GC-MS (EI-70 eV): m/z (%) 266 (60), 249 (100), 234 (29), 128 (35), 115 (34), 108 (41). HRMS (ESI): calcd for C17H15OS [M + H]+ 267.0844, found 267.0840. 3-(4-(tert-Butyl)phenyl)-4H-thiochromen-4-one (3ae) (43.5 mg, 74%). 1H NMR (300 MHz, chloroform-d) δ 8.61−8.51 (m, 1H), 7.79 (s, 1H), 7.56−7.44 (m, 3H), 7.43−7.35 (m, 4H), 1.28 (s, 9H). 13 C{1H} NMR (75 MHz, CDCl3) δ 178.4, 151.0, 136.8, 136.7, 134.9, 134.5, 132.8, 131.1, 129.5, 128.6, 127.7, 126.5, 125.3, 34.6, 31.3. GCMS (EI-70 eV): m/z (%) 294 (36), 279 (100), 136 (20), 115 (27), 108 (25). HRMS (ESI): calcd for C19H19OS [M + H]+ 295.1157, found 295.1154. 3-(4-Methoxyphenyl)-4H-thiochromen-4-one (3af) (41.8 mg, 78%). 1 H NMR (300 MHz, chloroform-d) δ 8.61−8.51 (m, 1H), 7.76 (s, 1H), 7.60−7.33 (m, 5H), 6.97−6.81 (m, 2H), 3.77 (s, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 178.4, 159.5, 136.8, 136.3, 134.4, 132.8, 131.1, 130.1, 129.9, 129.5, 127.7, 126.5, 113.7, 55.4. GC-MS (EI-70 eV): m/z (%) 268 (100), 136 (36), 117 (24), 108 (50), 89 (37), 63 (25). HRMS (ESI): calcd for C16H13O2S [M + H]+ 269.0637, found 269.0641. 3-(3-Fluorophenyl)-4H-thiochromen-4-one (3ag) (36.4 mg, 71%). 1H NMR (300 MHz, chloroform-d) δ 8.56 (ddd, J = 7.7, 1.0 Hz, 1H), 7.83 (s, 1H), 7.63−7.42 (m, 3H), 7.35−7.19 (m, 3H), 7.06−6.92 (m, 1H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.9, 162.6 (d, J = 245.85 Hz), 139.4 (d, J = 8.04 Hz), 136.6, 136.2, 135.5, 132.7, 131.4, 129.7 (d, J = 8.64 Hz), 129.5, 127.9, 126.5, 124.6 (d, J = 2.92 Hz), 116.1 (d, J = 22.56 Hz), 114.9 (d, J = 21.09 Hz). 19F NMR (282 MHz, CDCl3) δ −113.32. GC-MS (EI-70 eV): m/z (%) 256 (100), 136 (67), 120 (20), 108 (48). HRMS (EI): calcd for C15H9OFS [M]+ 256.0353, found 256.0349. 3-(4-Chlorophenyl)-4H-thiochromen-4-one (3ah) (37.5 mg, 69%). 1H NMR (300 MHz, chloroform-d) δ 8.65 (ddd, J = 7.8, 1.0 Hz, 1H), 7.91 (s, 1H), 7.69−7.56 (m, 3H), 7.54−7.39 (m, 4H). 13C{1H} NMR (75 MHz, CDCl3) δ 178.0, 136.7, 135.8, 135.7, 135.6, 134.0, 132.6, 131.4, 130.3, 129.5, 128.5, 127.9, 126.6. GC-MS (EI-70 eV): m/z (%) 272 (82), 136 (100), 108 (67). HRMS (EI): calcd for C15H9OClS [M]+ 272.0057, found 272.0055. 3-(3-Chlorophenyl)-4H-thiochromen-4-one (3ai) (39.7 mg, 73%). 1H NMR (300 MHz, chloroform-d) δ 8.61−8.51 (m, 1H), 7.83 (s, 1H), 7.64−7.43 (m, 4H), 7.43−7.20 (m, 3H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.9, 139.1, 136.6, 136.2, 135.4, 134.1, 132.7, 131.4, 129.5, 129.5, 129.0, 128.1, 127.9, 127.2, 126.6. GC-MS (EI-70 eV): m/z (%) 272 (100), 136 (75), 108 (48), 69 (24). HRMS (EI): calcd for C15H9OClS [M]+ 272.0057, found 272.0054. 3-(4-Bromophenyl)-4H-thiochromen-4-one (3aj) (36.1 mg, 57%). 1H NMR (300 MHz, chloroform-d) δ 8.64 (dt, J = 7.8, 1.2 Hz, 1H), 7.90 (s, 1H), 7.72−7.50 (m, 5H), 7.50−7.35 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.9, 136.7, 136.3, 135.8, 135.6, 132.6, 131.4, 130.6, 129.5, 127.9, 126.6, 122.3. GC-MS (EI-70 eV): m/z (%) 317 (100), 136 (85), 108 (61), 101 (27), 75 (29). HRMS (EI): calcd for

C15H9OBrS [M]+ 315.9552, found 315.9549. HRMS (EI): calcd for C15H9O81BrS [M]+ 317.9532, found 317.9534. 3-(4-(Trif luoromethyl)phenyl)-4H-thiochromen-4-one (3ak) (41.0 mg, 67%). 1H NMR (300 MHz, chloroform-d) δ 8.61−8.51 (m, 1H), 7.86 (s, 1H), 7.63−7.42 (m, 7H). 13C{1H} NMR (75 MHz, CDCl3) δ 177.9, 140.9, 136.7, 136.6, 135.4, 132.6, 131.5, 130.0 (q, J = 32.26 Hz), 129.5, 129.3, 128.1, 126.6, 125.2, 123.8 (q, J = 265.6 Hz). 19 F NMR (282 MHz, CDCl3) δ −62.57. GC-MS (EI, 70 eV): m/z (%) 306 (100), 237 (27), 151 (20), 136 (42), 108 (41), 69 (50). HRMS (EI): calcd for C16H9OF3S [M]+ 306.0321, found 306.0313. 3-(Thiophen-3-yl)-4H-thiochromen-4-one (3al) (30.7 mg, 63%). 1H NMR (300 MHz, chloroform-d) δ 8.63−8.53 (m, 1H), 7.97 (s, 1H), 7.85 (dd, J = 3.0, 1.4 Hz, 1H), 7.59−7.40 (m, 3H), 7.40−7.23 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 178.0, 136.9, 136.4, 134.1, 132.7, 131.2, 129.5, 127.7, 127.3, 126.5, 124.9, 124.3. GC-MS (EI-70 eV): m/z (%) 244 (100), 216 (39), 136 (61), 108 (99), 82 (27), 69 (50), 45 (33). HRMS (ESI): calcd for C13H9OS2 [M + H]+ 245.0096, found 245.0093. 3-Benzyl-4H-thiochromen-4-one (3am)12 (31.8 mg, 63%). 1H NMR (300 MHz, chloroform-d) δ 8.69−8.57 (m, 1H), 7.66−7.50 (m, 3H), 7.46−7.21 (m, 6H), 4.06−3.99 (m, 2H). 13C{1H} NMR (75 MHz, CDCl3) δ 179.0, 138.7, 137.2, 136.8, 134.1, 131.6, 131.0, 129.5, 129.1, 128.7, 127.5, 126.5, 126.5, 37.8. GC-MS (EI-70 eV): m/z (%) 252 (100), 235 (55), 115 (46), 108 (22), 89 (21).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.8b02294. NMR spectra (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Xiao-Feng Wu: 0000-0001-6622-3328 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank the Chinese Scholarship Council for financial Support. The analytic support of Dr. W. Baumann, Dr. C. Fisher, S. Buchholz, and S. Schareina is gratefully acknowledged. We also appreciate the general support from Professors Matthias Beller and Armin Börner in LIKAT.

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REFERENCES

(1) (a) Razdan, R. K.; Bruni, R. J.; Mehta, A. C.; Weinhardt, K. K.; Papanastassiou, Z. B. A New Class of Antimalarial Drugs: Derivatives of Benzothiopyrans. J. Med. Chem. 1978, 21, 643−649. (b) Nakazumi, H.; Ueyama, T.; Kitao, T. Synthesis and Antibacterial Activity of 2Phenyl-4H-benzo[b]thiopyran-4-ones (Thioflavones) and Related Compounds. J. Heterocycl. Chem. 1984, 21, 193−196. (c) Nakazumi, H.; Ueyama, T.; Kitao, T. Antimicrobial Activity of 3-(Substituted Methyl)-2-phenyl-4H-l-benzothiopyran-4-ones. J. Heterocycl. Chem. 1985, 22, 1593−1596. (d) Al Nakib, T.; Bezjak, V.; Meegan, M. J.; Chandy, R. Synthesis and Antifungal activity of some 3-Benzylidenechroman-4-ones, 3-Benzylidenethiochroman-4-ones and 2-Benzylidene-1-tetralones. Eur. J. Med. Chem. 1990, 25, 455−462. (e) Gotoda, S.; Takahashi, N.; Nakagawa, H.; Murakami, M.; Takechi, T.; Komura, T.; Uchida, T.; Takagi, Y. Synthesis and Fungicidal Activity Against Pyricularia Oryzae of 6-(1,2,4-Triazol-4-yl) chromone and −1-thiochromone Derivatives. Pestic. Sci. 1998, 52, 309−320. (f) Charris, J.; Dominguez, J.; Lobo, G.; Riggione, F. Synthesis of Some Thiochromone Derivatives and Activity Against Plasmodium 13616

DOI: 10.1021/acs.joc.8b02294 J. Org. Chem. 2018, 83, 13612−13617

Note

The Journal of Organic Chemistry Falciparum In-vitro. Pharm. Pharmacol. Commun. 1999, 5, 107−110. (g) Kataoka, T.; Watanabe, S.; Mori, E.; Kadomoto, R.; Tanimura, S.; Kohno, M. Synthesis and Structure Activity Relationships of Thioflavone Derivatives as Specific inhibitors of the ERK-MAP Kinase Signaling Pathway. Bioorg. Med. Chem. 2004, 12, 2397−2407. (2) Dhanak, D.; Keenan, R. M.; Burton, G.; Kaura, A.; Darcy, M. G.; Shah, D. H.; Ridgers, L. H.; Breen, A.; Lavery, P.; Tew, D. G.; West, A. Benzothiopyran-4-one based Reversible Inhibitors of the Human Cytomegalovirus (HCMV) Protease. Bioorg. Med. Chem. Lett. 1998, 8, 3677−3682. (3) (a) Kitani, S.; Sugawara, K.; Tsutsumi, K.; Morimoto, T.; Kakiuchi, K. Synthesis and Characterization of Thiochromone S,SDioxides as New Photolabile Protecting Groups. Chem. Commun. 2008, 2103−2105. (b) Zhang, Y.; Tanimoto, H.; Nishiyama, Y.; Morimoto, T.; Kakiuchi, K. Novel Photolabile Protecting Group for Phosphate Compounds. Synlett 2012, 23, 367−370. (c) Sugiura, R.; Kozaki, R.; Kitani, S.; Gosho, Y.; Tanimoto, H.; Nishiyama, Y.; Morimoto, T.; Kakiuchi, K. A Novel Thiochromone-type Photolabile Protecting Group for Carbonyl Compounds. Tetrahedron 2013, 69, 3984−3990. (4) (a) Bossert, F. Synthese von 1-Thiochromonen (Thiochromon(2′,3′: 3,2)-benzofurane). Tetrahedron Lett. 1968, 9, 4375−4376. (b) Angel, A. J.; Finefrock, A. E.; French, K. L.; Hurst, D. R.; Williams, A. R.; Rampey, M. E.; Studer-Martinez, S. L.; Beam, C. F. Preparation of N-aryl-4-oxo-4H-1-benzothiopyran-2-acetamides from Trilithiated Acetoacetanilides and Lithiated Methyl Thiosalicylate. Can. J. Chem. 1999, 77, 94−97. (c) Willy, B.; Müller, T. J. J. A Novel Consecutive Three-Component Coupling-Addition-SNAr (CASNAR) Synthesis of 4H-Thiochromen-4-ones. Synlett 2009, 2009, 1255− 1260. (d) Willy, B.; Frank, W.; Müller, T. J. J. Microwave-assisted Three-component Coupling-addition-SNAr (CASNAR) Sequences to Annelated 4H-thiopyran-4-ones. Org. Biomol. Chem. 2010, 8, 90−95. (e) Kobayashi, K.; Kobayashi, A.; Ezaki, K. A Convenient Synthesis of 2-Arylthiochromen-4-ones (Thioflavones) by Iodine-Mediated Cyclization of 3-Aryl-1-[2-(1,1-dimethylethylsulfanyl)phenyl]prop-2-en-1ones. Heterocycles 2012, 85, 1997−2004. (f) Yang, X.; Li, S.; Liu, H.; Jiang, Y.; Fu, H. Domino Reactions of 1-(2-alkoxyaryl)-3-akylprop-2yn-1-ones with Sodium Sulfide Leading to Thiochromen-4-one Derivatives. RSC Adv. 2012, 2, 6549−6554. (g) Li, M.; Cao, H.; Wang, Y.; Lv, X.-L.; Wen, L.-R. One-Pot Multicomponent Cascade Reaction of N,S-Ketene Acetal: Solvent-Free Synthesis of Imidazo[1,2-a]thiochromeno[3,2-e]pyridines. Org. Lett. 2012, 14, 3470− 3473. (h) Wen, L.-R.; Shi, Y.-J.; Liu, G.-Y.; Li, M. Modulating the Reactivity of Functionalized N,S-Ketene Acetal in MCR: Selective Synthesis of Tetrahydropyridines and Thiochromeno[2,3-b]pyridines via DABCO-Catalyzed Tandem Annulation. J. Org. Chem. 2012, 77, 4252−4260. (5) Sangeetha, S.; Muthupandi, P.; Sekar, G. Copper-Catalyzed Domino Synthesis of 2-Arylthiochromanones through Concomitant C−S Bond Formations Using Xanthate as Sulfur Source. Org. Lett. 2015, 17, 6006−6009. (6) Inami, T.; Kurahashi, T.; Matsubara, S. Nickel-Catalyzed Reaction of Thioisatins and Alkynes: A Facile Synthesis of Thiochromones. Org. Lett. 2014, 16, 5660−5662. (7) For selected recent reviews on the carbonylation reaction, see: (a) Wu, X.-F.; Neumann, H. Ruthenium and Rhodium-Catalyzed Carbonylation Reactions. ChemCatChem 2012, 4, 447−458. (b) Ryu, I. New Approaches in Radical Carbonylation Chemistry: Fluorous Applications and Designed Tandem Processes by Species-hybridization with Anions and Transition Metal Species. Chem. Rec. 2002, 2, 249−258. (c) Gabriele, B.; Mancuso, R.; Salerno, G. Oxidative Carbonylation as a Powerful Tool for the Direct Synthesis of Carbonylated Heterocycles. Eur. J. Org. Chem. 2012, 2012, 6825− 6839. (8) Shen, C.; Spannenberg, A.; Wu, X.-F. Palladium-Catalyzed Carbonylative Four-Component Synthesis of Thiochromenones: The Advantages of a Reagent Capsule. Angew. Chem., Int. Ed. 2016, 55, 5067−5070.

(9) (a) Zhu, F.; Li, Y.; Wang, Z.; Wu, X.-F. Iridium-Catalyzed Carbonylative Synthesis of Chromenones from Simple Phenols and Internal Alkynes at Atmospheric Pressure. Angew. Chem., Int. Ed. 2016, 55, 14151−14154. (b) Zhu, F.; Li, Y.; Wang, Z.; Wu, X.-F. Iridium-Catalyzed Carbonylative Synthesis of Halogen-Containing Quinolin-2(1H)-ones from Internal Alkynes and Simple Anilines. Adv. Synth. Catal. 2016, 358, 3350−3354. (c) Zhu, F.; Li, Y.; Wang, Z.; Wu, X.-F. Iridium-Catalyzed and Ligand-Controlled Carbonylative Synthesis of Flavones from Simple Phenols and Internal Alkynes. Chem. - Eur. J. 2017, 23, 3276−3279. (d) Li, X.; Li, X.; Jiao, N. RhCatalyzed Construction of Quinolin-2(1H)-ones via C-H Bond Activation of Simple Anilines with CO and Alkynes. J. Am. Chem. Soc. 2015, 137, 9246−9249. (10) (a) Li, Y.; Zhu, F.; Wang, Z.; Wu, X.-F. Synthesis of Thioethers and Thioesters with Alkyl Arylsulfinates as the Sulfenylation Agent under Metal-Free Conditions. Chem. - Asian J. 2016, 11, 3503−3507. (b) Zheng, Y.; Qing, F.-L.; Huang, Y.; Xu, X.-H. Tunable and Practical Synthesis of Thiosulfonates and Disulfides from Sulfonyl Chlorides in the Presence of Tetrabutylammonium Iodide. Adv. Synth. Catal. 2016, 358, 3477−3481. (c) Sun, J.; Wang, Y.; Pan, Y. Manganese Catalysed Sulfenylation of N-methyl amides with Arenesulfonyl Hydrazides. Org. Biomol. Chem. 2015, 13, 3878−3881. (11) Katekar, G. F.; Thomson, R. M. 1-Thioisoflavanones and related compounds. Aust. J. Chem. 1972, 25, 647−651. (12) Patonay, D.; Dinya, Z.; Lévai, A.; Molnár, M. Reactivity of αarylidene benzoheteracyclanone dibromides toward azide ion: an effective approach to 3-(α-substituted-benzyl)chromones and −1thiochromones. Tetrahedron 2001, 57, 2895−2907.

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