Synthesis of Sulfur Perfluorophenyl Compounds Using a

Sep 12, 2017 - Synthesis of Sulfur Perfluorophenyl Compounds Using a ... Chiral Hypervalent Organoiodine-Catalyzed Enantioselective Oxidative ...
1 downloads 0 Views 754KB Size
Download PDF
Note pubs.acs.org/joc

Cite This: J. Org. Chem. 2017, 82, 11939-11945

Synthesis of Sulfur Perfluorophenyl Compounds Using a Pentafluorobenzenesulfonyl Hypervalent Iodonium Ylide Jiandong Wang,† Shichong Jia,‡ Kenta Okuyama,‡ Zhongyan Huang,† Etsuko Tokunaga,† Yuji Sumii,‡ and Norio Shibata*,†,‡ †

Department of Nanopharmaceutical Sciences, ‡Department of Life Science and Applied Chemistry, Nagoya Institute of Technology, Gokiso-cho, Showa-ku, Nagoya 466-8555, Japan S Supporting Information *

ABSTRACT: A novel pentafluorobenzenesulfonyl hypervalent iodonium ylide 3 was designed and synthesized as a useful tool for the preparation of sulfur pentafluorophenyl compounds containing a C6F5S or C6F5SO2 unit. Electrophilic pentafluorophenylthiolation of enamines, formal [3+2] cycloaddition reaction of nitriles and alkynes, and intramolecular SNAr cyclization were achieved using iodonium ylide 3. The fluoro-click reaction was also demonstrated using one of the products via an intermolecular SNAr reaction with heterocentered nucleophiles. “fluoro-click” reaction between a thiol-glycoside (2,3,4,6-tetraO-acetyl-1-thio-β-D-glucopyranose) and pentafluorostyrene in glycopolymers that tuned the active sites on the surface of pentafluorostyrene-containing nanoparticles.3a Moreover, the pentafluorophenylthio group is also applied in polymer modification and functionalization.3c−e Heeney and co-workers demonstrated that the pentafluorobenzene group is a useful end-group due to its ability to undergo rapid SNAr reactions induced by sulfur nucleophiles.3b In spite of the utility of C6F5S and C6F5SO2 scaffolds as mentioned above, less attention had been paid to the direct introduction of these groups.5 In this context, we have reported two novel reagents for the introduction of C6F5X moieties. First, we developed C6F5containing diaryl-λ3-iodanes 1 as electrophilic pentafluorophenylation reagents for enolates to provide C-C6F5 compounds.6 Second, pentafluorophenyl diethylaminosulfur difluoride (C6F5DAST, 2) was used for the pentafluorophenylthiolation of activated α-methylene ketones to furnish C-SC6F5 and CSC6F4-O type compounds.7 As a part of our research on this topic, we are interested in a novel reagent, pentafluorobenzenesulfonyl hypervalent iodonium ylide 3, for the preparation of various sulfur perfluorophenyl compounds (Figure 1). Aryliodonium ylides have proven to be excellent precursor of carbenes that react with a wide range of substrates.8 Metal carbenes, which have broad synthetic applications, such as cyclopropanation,9 cycloaddition,10 the C−H insert process,11 or reactions with nucleophiles,12 can be generated from aryliodonium ylides with metal complexes. We have recently developed electrophilic trifluoromethylthio13 and difluorome-

Recent advances in the field of organofluorine chemistry have greatly expanded organic chemists’ imagination for devising new synthetic routes toward the production of fluorinecontaining compounds, which have gained considerable interest in pharmaceutical and agrochemical drug development.1 Among them, pentafluorophenyl (C6F5), pentafluorophenylthio (C6F5S), and pentafluorobenzenesulfonyl (C6F5SO2) compounds have become extensive tools in biochemistry especially for the modification of peptides, polyproteins,2 and the functionalization of polymers in material science.3 Owing to the rigidity, lipophilicity, and strong electron-accepting property with a planar π system of perfluoroaromatic linkers,4 modifying biomolecules via the incorporation of C6F5, C6F5S, and C6F5SO2 moieties into a specific site has provided access to the study of structure−function relationships in macromolecules. Pentelute and co-workers reported cysteine perfluoroarylation via the SNAr approach of cysteine thiolate moieties in an unprotected peptide, which showed enhanced binding, cell permeability, and proteolytic stability compared to the corresponding unstapled analog.2a,g Subsequently, several strategies involving enzymatic click ligation (glutathione Stransferase catalyzed macrocyclization)2b,c and a four-aminoacid sequence (Phe-Cys-Pro-Phe) as the “π-clamp” to control the reactivity of the thiol residue in the cysteine site in peptides, were provided to tune selectivity in the cysteine SNAr modification process to construct a pentafluorophenylthio linkage. Recently, Derda and co-workers noted that a decafluoro-diphenylsulfone containing C6F5SO2 moiety served as a SNAr electrophile toward Cys-residues in peptides for the rapid biocompatible macrocyclization of peptides.2e Subsequently, Pentelute and co-workers reported lysine N-arylation via SNAr reactions between amine residues in lysine of peptides and the decafluoro-diphenylsulfone framework. Within the field of material science, Schubert and co-workers revealed a thiol © 2017 American Chemical Society

Special Issue: Hypervalent Iodine Reagents Received: July 30, 2017 Published: September 12, 2017 11939

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry

With the ylide 3 in hand, its utility for electrophilic pentafluorophenylthiolation of enamines 4 was examined, since enamines are versatile intermediates in organic synthesis.16 Under the optimized conditions of ylide 3 (2.0 equiv), CuCl (20 mol%) in 1,4-dioxane (0.2 M) at room temperature (rt) (70% 19F NMR yield, see Table S1, in SI), a series of enamines 4ai were employed to explore the substrate scope of pentafluorophenylthiolation (Scheme 3). N-Benzyl ketones

Figure 1. Reagents for the introduction of C6F5X units: diaryl iodonium salts 1 for pentafluorophenylation, C6F5-DAST 2 for pentafluorothiolation, and pentafluorobenzenesulfonyl hypervalent iodonium ylide 3 for the preparation of C6F5S and C6F5SO2 compounds (this work).

Scheme 3. Pentafluorophenylthiolation of Enamine 4a

14

thylthio reagents, trifluoromethanesulfonyl hypervalent iodonium ylide and difluoromethanesulfonyl hypervalent iodonium ylide. To further extend our aryliodonium ylide chemistry and the potential of C6F5S(O2) compounds, we disclose herein a novel reagent, pentafluorobenzenesulfonyl hypervalent iodonium ylide 3. This ylide 3 was designed based on trifluoromethylthio reagents13,14 and is easily synthesized in high yield. The ylide 3 shows dual utility, including as an electrophilic reagent for pentafluorophenylthiolation of enamines 4 and as a building block for the preparation of 5membered heterocycles 7 via a formal [3+2] cycloaddition reaction with nitriles and alkynes 6. Moreover, pharmaceutically attractive benzoxathinn (thiaflavan) skeleton 8 was also smoothly accessed from 3 in a single step via successive chlorination/intramolecular SNAr cyclization sequence. Compound 8 is a useful tool for the “fluoro-click” reaction with a variety of heterocentered nucleophiles 9 via the intermolecular SNAr reaction to furnish a wide variety of fluorinated thiaflavan derivatives 10 (Scheme 1).

a

Reaction of 4a−i (0.15 mmol) and 3 (0.3 mmol) with 20 mol% CuCl was carried out in 1,4-dioxane (0.1 M) at rt for 1 h. b19F NMR yield.

Scheme 1. Pentafluorobenzenesulfonyl Hypervalent Iodonium Ylide 3 and Its Utility for Pentafluorophenylthiolation, Formal [3+2] Cycloaddition, and Intra- and Intermolecular SNAr Reactions

4a,b and ester enamines 4c−e were nicely pentafluorophenylthiolated at their Csp2 position to provide corresponding C6F5S-products 5 in good yields. N-Aryl and N-alkyl substrates 4f−h were converted to the corresponding products 5f−h in 4960% yields. Additionally, 56% isolated yields were obtained for unprotected NH2 enamine 4i. While further potential of 3 for electrophilic pentafluorophenylthiolation reactions could be considered,17 we were next interested in the utility of 3 as a source of the SO2C6F5 unit. Since formal [3+2] cycloaddition using phenyliodonium ylides is a powerful methodology for the preparation of heterocycles.8 The reaction probably undergoes the 1,5electrocyclic ring closure of intermediate 1,3-dipoles, such as nitrile ylides derived from the combination of carbene species and nitriles.18 Thus, the copper-catalyzed formal [3+2] cycloaddition of iodonium ylide 3 was investigated. First, the formal [3+2] reaction of 3 with acetonitrile (MeCN, 6a) was investigated. After optimization of the reaction conditions (see Table SI-2, in SI), the combination of hypervalent iodonium ylide 3 (0.1 mmol) and MeCN (5.0 equiv) in the presence of copper acetate (CuOAc, 20 mmol%) in 1,2-dichloroethane (DCE, 0.1 M) at rt for 8 h, was chosen as the standard reaction condition (84% 19F NMR yield, Table S2, Scheme 4). The substrate scope was explored and a series of oxazoles 7 bearing a C6F5SO2 group at the C4 position were readily obtained. Alkyl nitriles 6a−e and aryl nitriles 6f,g afforded corresponding oxazoles 7a−g in 45% to 63% yields. It should be noted that the formal [3+2] reaction of 3 was extended to the synthesis of trisubstituted C6F5SO2-furan derivatives 7h by the reaction with aryl terminal alkyne 6h, although the conditions should be optimized to improve yield (Scheme 4).

Pentafluorobenzenesulfonyl hypervalent iodonium ylide 3 was easily prepared in high yield as follows. Silyl enol ether 11 reacted with pentafluorobenzenesulfonyl chloride (C6F5SO2Cl) in the presence of dichlorotris(triphenylphosphine)ruthenium(II) (Ru(PPh3)Cl2) in benzene at 110 °C overnight to furnish α-pentafluorobenzenesulfonyl phenyl ketone (12) in 74% yield. 15 The α-C 6 F 5 SO 2 -ketone 12 was treated with phenyliodine(III) diacetate (PIDA) in methanol (MeOH) to give desired ylide 3 in 90% yield (Scheme 2). Scheme 2. Preparation of Hypervalent Iodonium Ylide 3

11940

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry Scheme 4. Formal [3+2] Cycloaddition of 3 with Nitriles or Alkynes 6a

Scheme 5. (a) Construction of 4-Chloro Benzoxathiine 4,4Dioxide 8 from 3 via Chlorination/Intramolecular SNAr Cyclization and (b) Intermolecular SNAr Reaction of 8 with NuH 9, as the “Fluoro-Click” Reactiona

a

a Reaction conditions: 8 (0.1 mmol), NuH 9a,b (1.1 equiv) and Et3N (1.0 equiv) in MeCN (0.1 M) at 60 °C for 6−8 h. bK2CO3 (2.0 equiv) was used as the base and 9c (2.0 equiv) was used as nucleophile in DMF (0.1 M).

Reaction conditions: Iodonium ylide 3 (0.1 mmol), nitriles or alkynes 6 (5.0 equiv), and CuOAc (20 mol%) in DCE (0.1 M) at rt for 8 h. b19 F NMR yield.

Finally, the intramolecular SNAr cyclization reaction of iodonium ylide 3 to pharmaceutically attractive fluorinated benzoxathiin derivatives was conducted.19,20 The ylide 3 was treated with chlorotrimethylsilane (Me3SiCl, 2.0 equiv) in the presence of triethylamine (Et3N, 3.0 equiv) in DCE to smoothly generate 3-chlorotetrafluorobenzo[b][1,4]oxathiine 4,4-dioxide (8)21 in high yield of 96%. It is worth noting that the chloro atom was incorporated into the C3 position of the benzoxathiine 4,4-dioxide skeleton. The “fluoro-click” reaction of 8 was also performed. One of the fluorines in the benzene ring system was selectively replaced by secondary amines, such as morpholine (9a) and pyrrolidine (9b), to give the intermolecular SNAr products 10a,b in 80% and 50% yields, respectively, as single isomers (Scheme 5). Additionally, oxygen nucleophiles 9c were also introduced into the perfluorinated benzene ring of 8 to furnish 10c bearing two naphthalenol moieties in 55% yield. In conclusion, a novel pentafluorobenzenesulfonyl hypervalent iodonium ylide 3 was designed and synthesized as a useful tool for the preparation of sulfur pentafluorophenyl compounds containing a C6F5S or C6F5SO2 unit. This iodonium ylide 3 has been found to be an efficient electrophilic pentafluorophenylthiolation reagent for enamine ketones and enamino esters 4 under copper catalysis to provide the corresponding C6F5S products 5. The ylide 3 was also proved to be a useful building block for the preparation of C6F5SO2 group-containing aromatic heterocyclic skeletons 7, such as oxazoles and furan via formal [3+2] cycloaddition in the presence of a copper catalyst. It should be noted that in the presence of Me3SiCl, iodonium ylide 3 was smoothly converted into pharmaceutically attractive tetrafluoro-3-chloro thiaflavan derivative 8 via a successive chlorination/intramolecular SNAr cyclization sequence. Tetrafluoro thiaflavan 8 can be used for the “fluoro-click” reaction with a variety of heterocentered nucleophiles via an intermolecular SNAr reaction.

■

into reaction vessels though a rubber septum. All reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25 mm Merck silica gel (60-F254). The TLC plates were visualized with UV light and KMnO4 in water/heat. Column chromatography was carried out on columns packed with flash silica gel (60N spherical neutral size 40−50 μm). The 1H NMR (300 MHz), 19F NMR (659 or 282 MHz), 13C NMR (125 or 175 MHz) spectra for solution in CDCl3 were recorded on a Buruker Avance 500, a Varian Mercury 300 and Jeol 700 NMR spectrometers. Chemical shifts (δ) are expressed in ppm downfield from internal TMS (δ = 0.00) as an internal standard. Mass spectra were recorded on a SHIMADZU GCMS-QP5050A (EIMS) and SHIMAZU LCMS-2020 (ESI-MS). High-resolution mass spectrometry (HRMS) was recorded on a Waters Synapt G2 HDMS (ESI-MS) with a TOF analyzer. Solvents CH3CN, CH2Cl2, DMF, and NMP were dried and distilled before use. Preparation of Pentafluorobenzenesulfonyl Hypervalent Iodonium Ylide 3. (2-((Perfluorophenyl)sulfonyl)-1-phenyl-2-(phenyl-λ3-iodanylidene)ethan-1-one). The solution of 1-phenyl-2((pentafluorobenzene)sulfonyl)ethanone15 (418 mg, 1.2 mmol) and phenyl-λ3-iodanediyl diacetate (PIDA) (383 mg, 1.2 mmol) in MeOH (20 mL) was stirred for 2 h at 0 °C. Large amount of white precipitate was observed when dry hexane (30 mL) was added to the reaction mixture at the same temperature. Then the precipitate was filtered and washed with dry hexane (30 mL). After drying under vacuum overnight, the desired pentafluorobenzenesulfonyl hypervalent iodonium ylide 3 was obtained as a white solid (594 mg) in 90% yield without further purification. Mp: 131.3−132.5 °C; HRMS (ESI-TOF) calcd. for C20H10O3F5NaSI [(M+Na)+]: 574.9208 found 574.9201; 1H NMR (300 MHz, (CD3)2SO) δ 7.84 (d, J = 7.7 Hz, 2H), 7.56 (t, J = 7.3 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.42−7.25 (m, 5H); 19F NMR (282 MHz, (CD3)2SO) δ −136.84 (d, J = 18.6 Hz, 2F), −150.10 (t, J = 22.4 Hz, 1F), −161.30 (t, J = 20.8 Hz, 2F); 13C{1H} NMR (126 MHz, DMSO) δ 185.4, 143.4 (dm, J = 265.6 Hz), 142.2 (dm, J = 255.8 Hz), 139.8, 136.7 (dm, J = 252.3 Hz), 132.6, 130.8, 130.6, 129.3, 127.5, 127.2, 119.8 (m), 116.8. General Procedure A for Pentafluorophenylthiolation of Enamines. The pentafluorophenylsulfonyl hypervalent iodonium ylide 3 (0.3 mmol, 2.0 equiv) was added in one portion to the stirred solution of enamine 4 (0.15 mmol) in the presence of copper catalysis Cu(I)Cl (20 mol%) in dry 1,4-dioxane (1.5 mL) at room temperature. Then the reaction mixture was monitored by TLC and upon the completion of the reaction (about 1−2 h), it was filtered through a short plug of Celite to remove the copper salts and washed with Et2O.

EXPERIMENTAL SECTION

General Information. All reactions were performed in oven-dried glassware under positive pressure of nitrogen unless mentioned otherwise. Solvents were transferred via syringe and were introduced 11941

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry The filtrate was concentrated in vacuo. The crude mixture was purified through flash column chromatography on silica gel (hexane/EtOAc) to afford the desired product 5. (E)-3-(Benzylamino)-2-((perfluorophenyl)thio)-1-phenylbut-2-en1-one 5a. Following General Procedure A, (Z)-3-(benzylamino)-1phenylbut-2-en-1-one 4a (37.7 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 5a as yellow solid (40.8 mg) in 60% yield. Mp: 96.5− 97.1 °C; HRMS (ESI-TOF) calcd. for C23H16NOF5NaS [(M+Na)+]: 472.0765 found 472.0764; 1H NMR (300 MHz, CDCl3) δ 12.74 (s, 1H), 7.44−7.27 (m, 10H), 4.62 (d, J = 5.8 Hz, 2H), 2.53 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −137.04 (dd, J = 23.7, 7.5 Hz, 2F), −155.89 (t, J = 20.9 Hz, 1F), −161.93 (dt, J = 23.6, 7.6 Hz, 2F); 13 C{1H} NMR (126 MHz, CDCl3) δ 196.9, 172.1, 146.1 (dm, J = 246.1 Hz), 142.2, 139.9 (dm, J = 253.5 Hz), 137.4 (dm, J = 251.0 Hz), 136.2, 129.08, 129.05, 127.9, 127.4, 126.9, 113.4 (m), 93.4, 48.5, 18.1. (E)-2-((Perfluorophenyl)thio)-1-phenyl-3-((2-(trifluoromethyl)benzyl)amino)but-2-en-1-one 5b. Following General Procedure A, (Z)-1-phenyl-3-((2-(trifluoromethyl)benzyl)amino)but-2-en-1-one 4b (48.0 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 2 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 15/1) to give the desired product 5b as yellow solid (33.0 mg) in 43% yield. Mp: 132.5−133.2 °C; HRMS (ESI-TOF) calcd. for C24H15NOF8NaS [(M+Na)+]: 540.0639 found 540.0635; 1H NMR (300 MHz, CDCl3) δ 12.77 (s, 1H), 7.71 (d, J = 7.7 Hz, 1H), 7.60 (t, J = 7.6 Hz, 1H), 7.52−7.39 (m, 2H), 7.39−7.29 (m, 5H), 4.81 (d, J = 6.0 Hz, 2H), 2.50 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −60.45 (s, 3F), −137.16 (dd, J = 23.3, 7.1 Hz, 2F), −155.76 (t, J = 20.9 Hz, 1F), −161.88 (td, J = 23.2, 7.4 Hz, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 197.2, 172.3, 146.0 (dm, J = 246.2 Hz), 142.0, 140.0 (dm, J = 253.7 Hz), 137.3 (dm, J = 254.5 Hz), 135.12, 135.11, 132.73, 132.72, 129.2, 128.1, 128.0, 127.5, 126.9, 126.4 (q, J = 5.7 Hz), 113.3 (m), 94.1, 44.8 (q, J = 3.0 Hz), 17.9. Ethyl (E)-3-(Benzylamino)-2-((perfluorophenyl)thio)-3-phenyl acrylate 5c. Following General Procedure A, ethyl (Z)-3-(benzylamino)-3-phenyl acrylate 4c (40.1 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/1) to give the desired product 5c as white solid (36.1 mg) in 50% yield. Mp: 102.0 °C; HRMS (ESI-TOF) calcd. for C24H18NO2F5NaS [(M +Na)+]: 502.0871 found 502.0868; 1H NMR (300 MHz, CDCl3) δ 10.24 (s, 1H), 7.49−7.36 (m, 3H), 7.35−7.22 (m, 3H), 7.20−7.03 (m, 4H), 4.44−3.99 (m, 4H), 1.21 (t, J = 7.1 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −136.62 (dd, J = 23.7, 7.5 Hz, 2F), −157.13 (t, J = 20.8 Hz, 1F), −163.21 (td, J = 22.7, 7.5 Hz, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 170.2, 170.0, 146.2 (dm, J = 246.1 Hz), 139.8 (dm, J = 252.9 Hz), 137.8, 137.2 (dm, J = 251.9 Hz), 134.3, 129.2, 128.7, 128.3, 127.6, 127.5, 126.9, 113.9−112.8 (m), 83.2, 60.3, 49.3, 14.1. Methyl (E)-3-(Benzylamino)-2-((perfluorophenyl)thio)but-2enoate 5d. Following General Procedure A, methyl (Z)-3(benzylamino)but-2-enoate 4d (30.8 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 5c as white solid (30.3 mg) in 50% yield. Mp: 78.0−79.0 °C; HRMS (ESI-TOF) calcd. for C18H14NO2F5NaS [(M+Na)+]: 426.0558 found 426.0570; 1H NMR (300 MHz, CDCl3) δ 10.41 (s, 1H), 7.43−7.28 (m, 3H), 7.28−7.20 (m, 2H), 4.52 (d, J = 5.8 Hz, 2H), 3.67 (s, 3H), 2.51 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −136.92 (dd, J = 24.1, 7.8 Hz, 2F), −156.24 (t, J = 20.9 Hz, 1F), −162.64 (td, J = 23.2, 7.5 Hz, 2F); 13 C{1H} NMR (126 MHz, CDCl3) δ 171.0, 169.4, 146.7 (dm, J = 240.6 Hz), 140.3 (dm, J = 253.5 Hz), 137.4 (dm, J = 254.2 Hz), 137.2, 129.1, 127.9, 126.9, 113.0 (m), 81.9, 51.5, 48.2, 17.6. Methyl (E)-3-((4-Bromobenzyl)amino)-2-((perfluorophenyl)thio)but-2-enoate 5e. Following General Procedure A, methyl (Z)-3-((4-

bromobenzyl)amino)but-2-enoate 4e (42.6 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 5e as white solid (37.4 mg) in 52% yield. Mp: 135.6−136.4 °C; HRMS (ESI-TOF) calcd. for C18H13NO2F5NaSBr [(M+Na)+]: 503.9663 found 503.9671; 1H NMR (300 MHz, CDCl3) δ 10.39 (s, 1H), 7.49 (d, J = 8.4 Hz, 2H), 7.13 (d, J = 8.4 Hz, 2H), 4.47 (d, J = 6.0 Hz, 2H), 3.67 (s, 3H), 2.49 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −136.89 (dd, J = 23.8, 7.7 Hz, 2F), −156.03 (t, J = 20.9 Hz, 1F), −162.53 (td, J = 23.1, 7.5 Hz, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 170.8, 169.1, 146.7 (dm, J = 256.2 Hz), 140.3 (dm, J = 253.5 Hz), 137.5 (dm, J = 254.2 Hz), 136.3, 132.1, 128.5, 121.7, 112.9 (m), 82.5, 51.6, 47.6, 17.6. Methyl (E)-2-((Perfluorophenyl)thio)-3-(p-tolylamino)but-2enoate 5f. Following General Procedure A, methyl (Z)-3-(ptolylamino)but-2-enoate 4f (31.1 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/ 1) to give the desired product 5f as white solid (36.4 mg) in 60% yield. Mp: 114.9−115.9 °C; HRMS (ESI-TOF) calcd. for C18H14NO2F5NaS [(M+Na)+]: 426.0558 found 426.0559; 1H NMR (300 MHz, CDCl3) δ 11.55 (s, 1H), 7.17 (d, J = 7.9 Hz, 2H), 6.99 (d, J = 7.9 Hz, 2H), 3.71 (s, 3H), 2.42 (s, 3H), 2.36 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −136.61 (dd, J = 24.0, 7.7 Hz, 2F), −155.98 (t, J = 20.8 Hz, 1F), −162.35−-162.65 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 170.7, 167.6, 146.7 (dm, J = 240.5 Hz), 140.4 (dm, J = 253.6 Hz), 137.5 (dm, J = 257.7 Hz), 136.6, 135.8, 129.9, 125.8, 112.7 (m), 83.7, 51.7, 21.0, 19.1. Methyl (E)-3-((4-Bromophenyl)amino)-2-((perfluorophenyl)thio)but-2-enoate 5g. Following General Procedure A, methyl (Z)-3-((4bromophenyl)amino)but-2-enoate 4g (40.5 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/1) to give the desired product 5g as white solid (37.1 mg) in 53% yield. Mp: 136.6−137.5 °C; HRMS (ESI-TOF) calcd. for C17H11NO2F5NaSBr [(M+Na)+]: 489.9506 found 489.9492; 1H NMR (300 MHz, CDCl3) δ 11.59 (s, 1H), 7.50 (d, J = 8.3 Hz, 2H), 7.00 (d, J = 8.6 Hz, 2H), 3.72 (s, 3H), 2.45 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −136.41 (dd, J = 23.7, 7.2 Hz, 2F), −155.54 (t, J = 20.9 Hz, 1F), −162.31 (td, J = 23.6, 7.4 Hz, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 170.6, 166.7, 146.8 (dm, J = 245.8 Hz), 140.5 (dm, J = 264.2 Hz), 137.6, 137.5 (dm, J = 258.2 Hz), 132.4, 127.3, 120.0, 112.2 (m), 85.3, 51.8, 19.1. Methyl (E)-3-(Butylamino)-2-((perfluorophenyl)thio)but-2-enoate 5h. Following General Procedure A, methyl (Z)-3-(butylamino)but-2enoate 4h (25.7 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/1) to give the desired product 5h as white solid (27.1 mg) in 49% yield. Mp: 136.6− 137.5 °C; HRMS (ESI-TOF) calcd. for C15H16NO2F5NaS [(M +Na)+]: 392.0714 found 392.0711; 1H NMR (300 MHz, CDCl3) δ 10.06 (s, 1H), 3.65 (s, 3H), 3.40−3.21 (m, 2H), 2.49 (s, 3H), 1.74− 1.51 (m, 2H), 1.47−1.34 (m, 2H), 0.94 (t, J = 7.2 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −137.00 (dd, J = 24.0, 8.0 Hz, 2F), −156.47 (t, J = 20.9 Hz, 1F), −162.74 (td, J = 23.4, 7.9 Hz, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 171.0, 169.2, 146.7 (dm, J = 245.2 Hz), 140.2 (dm, J = 253.2 Hz), 137.4 (dm, J = 252.2 Hz), 113.3 (m), 80.5, 51.4, 44.2, 31.8, 20.0, 17.5, 13.7. (E)-3-Amino-2-((perfluorophenyl)thio)-1-phenylbut-2-en-1-one 5i. Following General Procedure A, (Z)-3-amino-1-phenylbut-2-en-1one 4i (24.2 mg, 0.15 mmol), CuCl (3.0 mg, 0.03 mmol) and hypervalent iodonium ylide 3 (165.7 mg, 0.3 mmol) in 1,4-dioxane (1.5 mL) were used at room temperature for 1 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 4/1) to give the desired product 5i as white solid (30.0 mg) in 56% yield. Mp: 192.2−193.1 °C; HRMS (ESI-TOF) calcd. for C16H10NOF5NaS [(M+Na)+]: 11942

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry 382.0295 found 382.0299; 1H NMR (300 MHz, CDCl3) δ 7.50−7.29 (m, 5H), 2.47 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −137.12 (dd, J = 23.4, 7.6 Hz, 2F), −156.08 (t, J = 20.9 Hz, 1F), −162.32 (dt, J = 23.0, 7.5 Hz, 2F); 13C{1H} NMR (126 MHz, (CD3)2SO) δ 195.9, 172.4, 145.8 (dm, J = 238.9 Hz), 142.9, 139.8 (dm, J = 250.0 Hz), 137.4 (dm, J = 254.0 Hz), 129.0, 127.7, 127.1, 113.8 (m), 91.1, 22.8. General Procedure B: Formal [3+2] Cycloaddition of Pentafluorobenzenesulfonyl Hypervalent Iodonium Ylide 3 with Nitriles or Alkynes 6. To a mixture of nitriles or alkynes 6 (1.0 equiv) and hypervalent iodonium ylide 3 (2.0 equiv) in DCE, catalyst CuOAc (20 mol%) was added under argon. Then the resulting mixture was allowed to stir over 8 h at room temperature. After the completion of the reaction monitored by TLC, the reaction mixtures were filtered through a short plug of Celite and washed with Et2O. The organic layer was washed with brine and concentrated in vacuo. The crude mixture was purified through flash column chromatography on silica gel (hexane/EtOAc) to afford the desired product 7. 2-Methyl-4-((perfluorophenyl)sulfonyl)-5-phenyloxazole 7a. Following General Procedure B, acetonitrile 6a (21 mg, 0.5 mmol), CuOAc (2.4 mg, 0.02 mmol) and hypervalent iodonium ylide 3 (55.2 mg, 0.1 mmol) in 1,2-dichloroethane (0.5 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 6/1) to give the desired product 7a as white solid (22.5 mg) in 58% yield. Mp 125.1−126.1 °C; HRMS (ESI-TOF) calcd. For C16H8F5NNaO3S [(M+Na)+]: 412.0037 found 412.0035; 1 H NMR (300 MHz, CDCl3) δ 7.93 (dd, J = 6.7, 3.1 Hz, 2H), 7.56− 7.44 (m, 3H), 2.52 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −133.47− −136.15 (m, 2F), −143.22− −143.72 (m, 1F), −157.05− −159.93 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 160.7, 153.9, 145.5 (dm, J = 258.1 Hz), 144.9 (dm, J = 263.5 Hz), 137.8 (dm, J = 262.7 Hz), 134.4, 131.2, 128.9, 128.7, 125.1, 115.8 (m, J = 13.9 Hz), 13.9. 2-Ethyl-4-((perfluorophenyl)sulfonyl)-5-phenyloxazole 7b. Following General Procedure B, propiononitrile 6b (55.1 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 6/1) to give the desired product 7b as white solid (40.3 mg) in 50% yield. Mp: 78.3−82.2 °C; HRMS (ESI-TOF) calcd. for C17H10F5NNaO3S [(M+Na)+]: 426.0194 found 426.0201; 1 H NMR (300 MHz, CDCl3) δ 8.08−7.72 (m, 2H), 7.67−7.34 (m, 3H), 2.84 (q, J = 7.6 Hz, 2H), 1.36 (t, J = 7.6 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −133.36− −136.48 (m, 2F), −142.65− −145.22 (m, 2F), −158.32− −158.77 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 164.9, 153.7, 145.5 (dm, J = 262.5 Hz), 144.9 (dm, J = 263.6 Hz), 137.8 (dm, J = 258.7 Hz), 134.2, 131.2, 128.9, 128.6, 125.2, 21.6, 10.8. 4-((Perfluorophenyl)sulfonyl)-5-phenyl-2-propyloxazole 7c. Following General Procedure B, butyronitrile 6c (69.1 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 7c as white solid (37 mg) in 44% yield. Mp: 88.8−89.9 °C; HRMS (ESI-TOF) calcd. for C18H12F5NNaO3S [(M+Na)+]: 440.0350 found 440.0363; 1H NMR (300 MHz, CDCl3) δ 7.94 (dt, J = 7.5, 3.6 Hz, 2H), 7.54−7.45 (m, 3H), 2.78 (t, J = 7.5 Hz, 2H), 1.80 (dq, J = 7.5, 7.5 Hz, 2H), 1.01 (t, J = 7.4 Hz, 3H); 19F NMR (282 MHz, CDCl3) δ −131.43− −137.38 (m, 2F), −139.82− −146.72 (m, 1F), −156.25− −161.66 (m, 2F); 13 C{1H} NMR (126 MHz, CDCl3) δ 164.0, 153.6, 145.5 (dm, J = 258.1 Hz), 144.9 (dm, J = 263.5 Hz), 137.8 (dm, J = 258.6 Hz), 134.2, 131.2, 128.8, 128.7, 125.2, 115.9 (m), 29.8, 20.2, 13.6. 2-Isopropyl-4-((perfluorophenyl)sulfonyl)-5-phenyloxazole 7d. Following General Procedure B, isobutyronitrile 6d (69.1 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 7d as white solid (47.8 mg) in 57% yield. Mp 102.7−104.4 °C; HRMS (ESI-TOF) calcd. for C18H12F5NNaO3S [(M+Na)+]: 440.0350 found 440.0364; 1 H NMR (300 MHz, CDCl3) δ 8.11−7.75 (m, 2H), 7.58−7.40 (m, 3H), 3.25−3.01 (m, 1H), 1.38 (s, 3H), 1.36 (s, 3H); 19F NMR (282

MHz, CDCl3) δ −134.65− −135.13 (m, 2F), −143.28− −143.66 (m, 1F), −158.11− −159.00 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 167.9, 153.5, 145.5 (dm, J = 266.8 Hz), 144.9 (dm, J = 263.4 Hz), 137.8 (dm, J = 258.5 Hz), 134.1, 131.2, 128.9, 128.6, 125.3, 115.9 (m), 28.5, 20.1. 2-Cyclohexyl-4-((perfluorophenyl)sulfonyl)-5-phenyloxazole 7e. Following General Procedure B, cyclohexanecarbonitrile 6e (109.2 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/1) to give the desired product 7e as white solid (52.7 mg) in 58% yield. Mp 100.2− 101.9 °C; HRMS (ESI-TOF) calcd. for C21H16F5NNaO3S [(M +Na)+]: 480.0663 found 480.0675; 1H NMR (300 MHz, CDCl3) δ 8.02−7.86 (m, 2H), 7.54−7.44 (m, 3H), 2.84 (tt, J = 11.4, 3.5 Hz, 1H), 2.06 (d, J = 12.8 Hz, 2H), 1.88−1.49 (m, 5H), 1.46−1.16 (m, 3H); 19F NMR (282 MHz, CDCl3) δ −134.05− −136.41 (m, 2F), −142.66− −144.95 (m, 1F), −158.34− −158.75 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 167.1, 153.2, 145.5 (dm, J = 275.0 Hz), 144.9 (dm, J = 263.2 Hz), 137.8 (dm, J = 253.0 Hz), 134.1, 131.1, 128.8, 128.6, 125.3, 115.9 (m), 37.4, 30.2, 25.5, 25.4. 4-((Perfluorophenyl)sulfonyl)-2,5-diphenyloxazole 7f. Following General Procedure B, benzonitrile 6f (103.1 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/ EtOAc, 9/1) to give the desired product 7f as white solid (57.0 mg) in 63% yield. Mp 167.5−168.2 °C; HRMS (ESI-TOF) calcd. for C21H10F5NNaO3S [(M+Na)+]: 474.0194 found 474.0193; 1H NMR (300 MHz, CDCl3) δ 8.19−7.90 (m, 4H), 7.69−7.36 (m, 6H); 19F NMR (282 MHz, CDCl3) δ −134.92− −135.54 (m, 2F), −143.35− −143.96 (m, 1F), −158.65− −159.16 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 160.3, 153.5, 145.6 (dm, J = 262.6 Hz), 144.9 (dm, J = 263.5 Hz), 137.8 (dm, J = 258.6 Hz), 135.7, 131.9, 131.4, 129.03, 128.96, 128.7, 126.9, 125.3, 125.1, 116.5−115.4 (m). 2-(3-Isodophenyl)-4-((perfluorophenyl)sulfonyl)-5-phenyloxazole 7g. Following General Procedure B, 3-iodobenzonitrile 6g (229.0 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 9/1) to give the desired product 7g as white solid (55.4 mg) in 48% yield. Mp 158.7−159.6 °C; HRMS (ESITOF) calcd. for C21H9F5INNaO3S [(M+Na)+]: 599.9160 found 599.9175; 1H NMR (300 MHz, CDCl3) δ 8.46−8.33 (m, 1H), 8.08− 7.96 (m, 3H), 7.91−7.80 (m, 1H), 7.63−7.53 (m, 3H), 7.32−7.16 (m, 1H); 19F NMR (282 MHz, CDCl3) δ −130.19− −137.41 (m, 2F), −142.04− −145.58 (m, 1F), −156.34− −161.12 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 158.6, 154.0, 145.4 (dm, J = 262.8 Hz), 145.1 (dm, J = 263.9 Hz), 140.8, 137.9 (dm, J = 259.2 Hz), 135.9, 135.5, 131.6, 130.6, 129.1, 128.8, 127.1, 126.1, 124.9, 115.8 (m), 94.3. 3-((Perfluorophenyl)sulfonyl)-2,5-diphenylfuran 7h. Following General Procedure B, ethynylbenzene 6h (104.1 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column chromatography on silica gel (hexane/EtOAc, 20/1) to give the desired product 7h as yellow solid (25.0 mg) in 27% yield. Mp 122.4−123.3 °C; HRMS (ESI-TOF) calcd. for C22H11F5NaO3S [(M+Na)+]: 473.0241 found 473.0229; 1H NMR (300 MHz, CDCl3) δ 7.98−7.88 (m, 2H), 7.77−7.70 (m, 2H), 7.50−7.34 (m, 6H), 7.21 (s, 1H); 19F NMR (282 MHz, CDCl3) δ −131.33− −131.62 (m, 2F), −139.75− −140.01 (m, 1F), −157.63− −157.94 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 155.2, 153.2, 145.0 (dm, J = 261.5 Hz), 144.5 (dm, J = 263.4 Hz), 137.7 (dm, J = 259.1 Hz), 130.7, 129.1, 129.0, 128.6, 128.5, 127.5, 125.5, 124.3, 117.2 (m), 106.7. 3-((Perfluorophenyl)sulfonyl)-2-phenyl-5-(p-tolyl)furan 7i. Following General Procedure B, 1-ethynyl-4-methylbenzene 6i (116.2 mg, 1.0 mmol), CuOAc (4.8 mg, 0.04 mmol) and hypervalent iodonium ylide 3 (110.4 mg, 0.2 mmol) in 1,2-dichloroethane (1.0 mL) were used at room temperature for 8 h. Isolated by column 11943

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry chromatography on silica gel (hexane/EtOAc, 30/1) to give the desired product 7i as yellow solid (14.6 mg) in 16% yield. Mp 121.3− 123.1 °C; HRMS (ESI-TOF) calcd. for C23H13F5NaO3S+ [(M+Na)+]: 487.0398 found 487.0409; 1H NMR (300 MHz, CDCl3) δ 7.99−7.85 (m, 2H), 7.62 (d, J = 8.0 Hz, 2H), 7.48−7.45 (m, 3H), 7.28−7.24 (m, 2H), 7.14 (s, 1H), 2.40 (s, 3H); 19F NMR (282 MHz, CDCl3) δ −135.13− −135.31 (m, 2F), −143.96− −144.16 (m, 1F), −158.38 − −158.60 (m, 2F); 13C{1H} NMR (126 MHz, CDCl3) δ 154.8, 153.5, 145.1 (dm, J = 261.3 Hz), 144.5 (dm, J = 263.4 Hz), 139.3, 137.7 (dm, J = 258.9 Hz), 130.6, 129.7, 128.6, 128.5, 127.6, 125.8, 125.4, 124.3, 117.5−117.2 (m), 105.9, 21.4. Procedure for the Preparation of Fluorinated Benzoxathiin Derivatives 8 via Intramolecular SNAr Cyclization Reactions. To a mixture of hypervalent iodonium ylide 3 (55.2 mg, 0.1 mmol) and triethylamine (30.3 mg, 0.3 mmol) in DCE (1.0 mL), fresh distilled TMSCl (21.7 mg, 0.02 mmol) was added in one portion under argon. Then the resulting solution was allowed to stir over 72 h at room temperature. After the completion of the reaction monitored by TLC, the crude product was purified by flash column chromatography on silica gel (hexane/EtOAc, 6/1) to afford the desired product 8 as colorless solid (35.1 mg) in 96% yield. 3-Chloro-5,6,7,8-tetrafluoro-2-phenylbenzo[b][1,4]oxathiine 4,4dioxide 8. Mp 153.2−154.9 °C; HRMS (ESI-TOF) calcd. for C14H5ClF4NaO3S [(M+Na)+]: 386.9476 found 386.9477; 1H NMR (300 MHz, CDCl3) δ 7.77 (d, J = 7.6 Hz, 2H), 7.67−7.49 (m, 3H); 19 F NMR (282 MHz, CDCl3) δ −137.74− −138.07 (m, 1F), −145.37 (td, J = 21.1, 5.6 Hz, 1F), −153.26 (dd, J = 20.0, 9.7 Hz, 1F), −155.52− −156.09 (m, 1F); 13C{1H} NMR (126 MHz, CDCl3) δ 153.4, 144.1 (dm, J = 258.0 Hz), 142.7 (dm, J = 262.2 Hz), 137.8 (dm, J = 258.8 Hz), 137.3 (dm, J = 259.7 Hz), 132.2, 129.1, 129.0, 128.8, 112.3, 111.7, 111.6. Procedure for the Preparation of Intermolecular SNAr Product 10a. To a stirred solution of 3-chloro-5,6,7,8-tetrafluoro-2phenylbenzo[b][1,4]oxathiine 4,4-dioxide 8 (36.4 mg, 0.1 mmol) and Et3N (10.1 mg, 0.1 mmol) in MeCN (1.0 mL), morpholine (9.6 mg, 0.11 mmol) was added at room temperature. Subsequently, the resulting mixture was allowed to stir at 60 °C for 8 h. The crude product was purified by flash column chromatography on silica gel (hexane/EtOAc, 6/1) to afford the intermolecular SNAr product 10a in 82% yield (37.6 mg) as white solid. Mp: 203.6−204.8 °C; HRMS (ESI-TOF) calcd. for C18H13ClF3NNaO4S [(M+Na)+]: 454.0098 found 454.0100; 1H NMR (300 MHz, CDCl3) δ 7.75 (dd, J = 8.0, 1.6 Hz, 2H), 7.62−7.45 (m, 3H), 3.87−3.77 (m, 4H), 3.47−3.36 (m, 4H); 19 F NMR (659 MHz) δ −140.54 (dd, J = 21.2, 9.0 Hz, 1F), −144.67 (s, 1F), −146.48 (d, J = 21.1 Hz, 1F); 13C{1H} NMR (126 MHz, CDCl3) δ 153.2, 143.3 (dm, J = 167.6 Hz), 141.3 (dm, J = 161.1 Hz), 140.3 (dm, J = 250.6 Hz), 136.8−135.6 (m), 134.3−133.4 (m), 131.9, 129.7, 129.1, 128.7, 111.8, 107.4 (d, J = 16.8 Hz), 67.1, 50.9 (t, J = 4.0 Hz). Procedure for the Preparation of Intermolecular SNAr Product 10b. To a stirred solution of 3-chloro-5,6,7,8-tetrafluoro-2phenylbenzo[b][1,4]oxathiine 4,4-dioxide 8 (36.4 mg, 0.1 mmol) and Et3N (10.1 mg, 0.1 mmol) in MeCN (1.0 mL), pyrrolidine (7.8 mg, 0.11 mmol) was added at room temperature. Subsequently, the resulting mixture was allowed to stir at 60 °C for 8 h. The crude product was purified by flash column chromatography on silica gel (hexane/EtOAc, 6/1) to afford the intermolecular SNAr product 10b in 50% yield (20.6 mg) as white solid. Mp: 163.3−164.6 °C; HRMS (ESI-TOF) calcd. For C18H13ClF3NNaO3S [(M+Na)+]: 438.0149 found 438.0151; 1H NMR (300 MHz, CDCl3) δ 7.82−7.69 (m, 2H), 7.59−7.45 (m, 3H), 3.83−3.49 (m, 4H), 2.01−1.92 (m, 4H); 19F NMR (282 MHz, CDCl3) δ −142.20 (dd, J = 20.0, 6.5 Hz, 1F), −151.39 (s, 1F), −151.68− −151.91 (m, 1F); 13C{1H} NMR (126 MHz, CDCl3) δ 153.0, 143.5 (dm, J = 253.1 Hz), 138.5 (dm, J = 247.0 Hz), 136.8−136.2 (m), 136.1 (dm, J = 244.4 Hz), 132.6 (td, J = 9.7, 3.1 Hz), 131.6, 130.0, 129.1, 128.6, 111.6, 101.5 (d, J = 17.3 Hz), 51.7 (t, J = 6.4 Hz), 25.8. Procedure for the Preparation of Intermolecular SNAr Product 10c. To a stirred solution of 3-chloro-5,6,7,8-tetrafluoro-2phenylbenzo[b][1,4]oxathiine 4,4-dioxide 8 (36.4 mg, 0.1 mmol) and

K2CO3 (27.6 mg, 0.2 mmol) in DMF (1.0 mL), naphthalen-1-ol (27.6 mg, 0.2 mmol) was added at room temperature. Subsequently, the resulting mixture was allowed to stir at 100 °C for 6 h. The crude product was purified by flash column chromatography on silica gel (hexane/EtOAc, 3/1) to afford the intermolecular SNAr product 10c in 55% yield (36.2 mg) as colorless oil. HRMS (ESI-TOF) calcd. for C34H19ClF2NaO5S [(M+Na)+]: 635.0502 found 635.0499; 1H NMR (700 MHz, CDCl3) δ 8.46 (dd, J = 8.4, 0.6 Hz, 1H), 8.37−8.25 (m, 1H), 7.89−7.83 (m, 2H), 7.80−7.76 (m, 2H), 7.63 (d, J = 8.3 Hz, 1H), 7.61 (d, J = 8.2 Hz, 1H), 7.59−7.49 (m, 7H), 7.34 (td, J = 8.0, 3.4 Hz, 2H), 6.86 (d, J = 7.7 Hz, 1H), 6.78 (d, J = 7.6 Hz, 1H); 19F NMR (659 MHz,) δ −138.04 (s, 1F), −144.52 (s, 1F); 13C{1H} NMR (126 MHz, CDCl3) δ 153.3, 152.83, 152.79, 145.8 (dm, J = 258.0 Hz), 141.9 (dm, J = 259.3 Hz), 138.1 (dd, J = 13.4, 12.3 Hz), 137.1 (dd, J = 11.4, 3.5 Hz), 136.5 (dd, J = 13.1, 4.9 Hz), 134.8, 134.7, 131.9, 129.6, 129.1, 128.7, 127.7, 127.5, 127.1, 126.9, 126.5, 126.4, 125.1, 125.0, 124.9, 124.8, 124.3, 123.9, 121.9, 121.4, 116.6, 112.5, 108.5, 108.3.

■

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01908. 1 H NMR, 19F NMR, and 13C NMR spectra for all new compounds (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*[email protected] ORCID

Norio Shibata: 0000-0002-3742-4064 Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS This research was partially supported by the Advanced Catalytic Transformation (ACT-C) from the JST Agency and JSPS KAKENHI Grant Number JP 16H01142 in Middle Molecular Strategy.

■

REFERENCES

(1) (a) Prakash, G. K. S.; Yudin, A. K. Chem. Rev. 1997, 97, 757. (b) Ma, J.-A.; Cahard, D. Chem. Rev. 2008, 108, PR1. (c) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (e) Campbell, M. G.; Ritter, T. Chem. Rev. 2015, 115, 612. (f) Champagne, P. A.; Desroches, J.; Hamel, J.-D.; Vandamme, M.; Paquin, J.-F. Chem. Rev. 2015, 115, 9073. (g) Charpentier, J.; Früh, N.; Togni, A. Chem. Rev. 2015, 115, 650. (h) Fustero, S.; Simón-Fuentes, A.; Barrio, P.; Haufe, G. Chem. Rev. 2015, 115, 871. (i) Huang, Y.-Y.; Yang, X.; Chen, Z.; Verpoort, F.; Shibata, N. Chem. - Eur. J. 2015, 21, 8664. (j) Liu, X.; Xu, C.; Wang, M.; Liu, Q. Chem. Rev. 2015, 115, 683. (k) Ni, C.; Hu, M.; Hu, J. Chem. Rev. 2015, 115, 765. (l) Xu, X.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115, 731. (m) Yang, X.; Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015, 115, 826. (2) (a) Spokoyny, A. M.; Zou, Y.; Ling, J. J.; Yu, H.; Lin, Y.-S.; Pentelute, B. L. J. Am. Chem. Soc. 2013, 135, 5946. (b) Zhang, C.; Spokoyny, A. M.; Zou, Y.; Simon, M. D.; Pentelute, B. L. Angew. Chem., Int. Ed. 2013, 52, 14001. (c) Zhang, C.; Dai, P.; Spokoyny, A. M.; Pentelute, B. L. Org. Lett. 2014, 16, 3652. (d) Dai, P.; Zhang, C.; Welborn, M.; Shepherd, J. J.; Zhu, T.; Van Voorhis, T.; Pentelute, B. L. ACS Cent. Sci. 2016, 2, 637. (e) Kalhor-Monfared, S.; Jafari, M. R.; Patterson, J. T.; Kitov, P. I.; Dwyer, J. J.; Nuss, J. M.; Derda, R. Chem. Sci. 2016, 7, 3785. (f) Lautrette, G.; Touti, F.; Lee, H. G.; Dai, P.; Pentelute, B. L. J. Am. Chem. Soc. 2016, 138, 8340. (g) Luhmann, T.; Mong, S. K.; Simon, M. D.; Meinel, L.; Pentelute, B. L. Org. Biomol. 11944

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945

Note

The Journal of Organic Chemistry Chem. 2016, 14, 3345. (h) Zhang, C.; Welborn, M.; Zhu, T.; Yang, N. J.; Santos, M. S.; Van Voorhis, T.; Pentelute, B. L. Nat. Chem. 2015, 8, 120. (3) (a) Becer, C. R.; Babiuch, K.; Pilz, D.; Hornig, S.; Heinze, T.; Gottschaldt, M.; Schubert, U. S. Macromolecules 2009, 42, 2387. (b) Boufflet, P.; Casey, A.; Xia, Y.; Stavrinou, P. N.; Heeney, M. Chem. Sci. 2017, 8, 2215. (c) Noy, J.-M.; Koldevitz, M.; Roth, P. J. Polym. Chem. 2015, 6, 436. (d) Qian, E. A.; Wixtrom, A. I.; Axtell, J. C.; Saebi, A.; Jung, D.; Rehak, P.; Han, Y.; Moully, E. H.; Mosallaei, D.; Chow, S.; Messina, M. S.; Wang, J. Y.; Royappa, A. T.; Rheingold, A. L.; Maynard, H. D.; Král, P.; Spokoyny, A. M. Nat. Chem. 2016, 9, 333. (e) Turgut, H.; Schmidt, A. C.; Wadhwani, P.; Welle, A.; Muller, R.; Delaittre, G. Polym. Chem. 2017, 8, 1288. (4) Meyer, E. A.; Castellano, R. K.; Diederich, F. Angew. Chem., Int. Ed. 2003, 42, 1210. (5) (a) Matsugi, M.; Murata, K.; Gotanda, K.; Nambu, H.; Anilkumar, G.; Matsumoto, K.; Kita, Y. J. Org. Chem. 2001, 66, 2434. (b) Matsugi, M.; Murata, K.; Nambu, H.; Kita, Y. Tetrahedron Lett. 2001, 42, 1077. (c) Ishimaru, T.; Ogawa, S.; Tokunaga, E.; Nakamura, S.; Shibata, N. J. Fluorine Chem. 2009, 130, 1049. (6) Matsuzaki, K.; Okuyama, K.; Tokunaga, E.; Shiro, M.; Shibata, N. ChemistryOpen 2014, 3, 233. (7) (a) Saidalimu, I.; Suzuki, S.; Wang, J.; Tokunaga, E.; Shibata, N. Org. Lett. 2017, 19, 1012. (b) Saidalimu, I.; Suzuki, S.; Tokunaga, E.; Shibata, N. Chem. Sci. 2016, 7, 2106. (8) (a) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299. (b) Yoshimura, A.; Zhdankin, V. V. Chem. Rev. 2016, 116, 3328−3435. (c) Müller, P. Acc. Chem. Res. 2004, 37, 243. (d) Jia, M.; Ma, S. Angew. Chem., Int. Ed. 2016, 55, 9134. (9) (a) Müller, P.; Ghanem, A. Org. Lett. 2004, 6, 4347. (b) Moreau, B.; Charette, A. B. J. Am. Chem. Soc. 2005, 127, 18014. (c) Deng, C.; Wang, L.-J.; Zhu, J.; Tang, Y. Angew. Chem., Int. Ed. 2012, 51, 11620. (d) Mo, S.; Li, X.; Xu, J. J. Org. Chem. 2014, 79, 9186. (10) (a) Asouti, A.; Hadjiarapoglou, L. P. Tetrahedron Lett. 1998, 39, 9073. (b) Gogonas, E. P.; Hadjiarapoglou, L. P. Tetrahedron Lett. 2000, 41, 9299. (c) Lee, Y. R.; Yoon, S. H.; Seo, Y.; Kim, B. S. Synthesis 2004, 2004, 2787. (d) Zhu, C.; Yoshimura, A.; Solntsev, P.; Ji, L.; Wei, Y.; Nemykin, V. N.; Zhdankin, V. V. Chem. Commun. 2012, 48, 10108. (11) Batsila, C.; Gogonas, E. P.; Kostakis, G.; Hadjiarapoglou, L. P. Org. Lett. 2003, 5, 1511. (12) Murphy, G. K.; West, F. G. Org. Lett. 2006, 8, 4359. (13) (a) Yang, Y.-D.; Azuma, A.; Tokunaga, E.; Yamasaki, M.; Shiro, M.; Shibata, N. J. Am. Chem. Soc. 2013, 135, 8782. (b) Arimori, S.; Takada, M.; Shibata, N. Dalton Trans. 2015, 44, 19456. (c) Arimori, S.; Takada, M.; Shibata, N. Org. Lett. 2015, 17, 1063. (d) Huang, Z.; Yang, Y.-D.; Tokunaga, E.; Shibata, N. Org. Lett. 2015, 17, 1094. (e) Huang, Z.; Yang, Y.-D.; Tokunaga, E.; Shibata, N. Asian J. Org. Chem. 2015, 4, 525. (14) Arimori, S.; Matsubara, O.; Takada, M.; Shiro, M.; Shibata, N. R. Soc. Open Sci. 2016, 3, 160102. (15) Kamigata, N.; Udodaira, K.; Shimizu, T. J. Chem. Soc., Perkin Trans. 1 1997, 1, 783. (16) (a) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Chem. Soc. Rev. 2012, 41, 4126. (b) Liu, X.; Cheng, R.; Zhao, F.; Zhang-Negrerie, D.; Du, Y.; Zhao, K. Org. Lett. 2012, 14, 5480. (c) Valenta, P.; Carroll, P. J.; Walsh, P. J. J. Am. Chem. Soc. 2010, 132, 14179. (d) Ogawa, S.; Iida, N.; Tokunaga, E.; Shiro, M.; Shibata, N. Chem. - Eur. J. 2010, 16, 7090. (e) Hsiao, Y.; Rivera, N. R.; Rosner, T.; Krska, S. W.; Njolito, E.; Wang, F.; Sun, Y.; Armstrong, J. D.; Grabowski, E. J. J.; Tillyer, R. D.; Spindler, F.; Malan, C. J. Am. Chem. Soc. 2004, 126, 9918. (f) Kubryk, M.; Hansen, K. B. Tetrahedron: Asymmetry 2006, 17, 205. (17) Reactivity of 3 is rather different from corresponding SCF3 and SCF2H reagents (see references 13 and 14), and electrophilic pentafluorophenylthiolation reactions of other nucleophiles, such as indoles, pyrroles, etc., by 3 are not successful under the same conditions. Further optimization should be required. (18) (a) Taylor, E. C.; Turchi, I. J. Chem. Rev. 1979, 79, 181. (b) Mloston, G.; Heimgartner, H. Curr. Org. Chem. 2011, 15, 675.

(19) (a) Buzzini, P.; Menichetti, S.; Pagliuca, C.; Branda, E.; Viglianisi, C.; Turchetti, B. Bioorg. Med. Chem. Lett. 2008, 18, 3731. (b) Lodovici, M.; Menichetti, S.; Viglianisi, C.; Caldini, S.; Giuliani, E. Bioorg. Med. Chem. Lett. 2006, 16, 1957. (c) Salum, L. B.; Polikarpov, I.; Andricopulo, A. D. J. Mol. Graphics Modell. 2007, 26, 434. (d) Sasaki, T.; Takahashi, T.; Nagase, T.; Mizutani, T.; Ito, S.; Mitobe, Y.; Miyamoto, Y.; Kanesaka, M.; Yoshimoto, R.; Takenaga, N.; Tokita, S.; Sato, N.; Tanaka, T. Bioorg. Med. Chem. Lett. 2009, 19, 4232. (e) Li, Y.; Doss, G. A.; Li, Y.; Chen, Q.; Tang, W.; Zhang, Z. Chem. Res. Toxicol. 2012, 25, 2368. (f) Zhuang, S.; Zhang, J.; Zhang, F.; Zhang, Z.; Wen, Y.; Liu, W. Bioorg. Med. Chem. Lett. 2011, 21, 7298. (g) Zhang, Z.; Chen, Q.; Li, Y.; Doss, G. A.; Dean, B. J.; Ngui, J. S.; Elipe, M. S.; Kim, S.; Wu, J. Y.; DiNinno, F.; Hammond, M. L.; Stearns, R. A.; Evans, D. C.; Baillie, T. A.; Tang, W. Chem. Res. Toxicol. 2005, 18, 675. (h) Kim, S.; Wu, J. Y.; Zhang, Z.; Tang, W.; Doss, G. A.; Dean, B. J.; DiNinno, F.; Hammond, M. L. Org. Lett. 2005, 7, 411. (i) Blizzard, T. A.; Morgan, J. D.; Chan, W.; Birzin, E. T.; Pai, L. − Y.; Hayes, E. C.; DaSilva, C. A.; Mosley, R. T.; Yang, Y. T.; Rohrer, S. P.; DiNinno, F.; Hammond, M. L. Bioorg. Med. Chem. Lett. 2005, 15, 5124. (j) Menichetti, S.; Nativi, C.; Sarri, P.; Viglianisi, C. J. Sulfur Chem. 2004, 25, 317. (k) Kim, S.; Wu, J. Y.; Birzin, E. T.; Frisch, K.; Chan, W.; Pai, L. − Y.; Yang, Y. T.; Mosley, R. T.; Fitzgerald, P. M. D.; Sharma, N.; Dahllund, J.; Thorsell, A. − G.; DiNinno, R.; Rohrer, S. P.; Schaeffer, J. M.; Hammond, M. L. J. Med. Chem. 2004, 47, 2171. (l) Bassoli, A.; Drew, M. G. B.; Hattotuwagama, C. K.; Merlini, L.; Morini, G.; Wilden, G. R. H. Quant. Struct.-Act. Relat. 2001, 20, 3. (m) Bassoli, A.; Merlini, L.; Morini, G.; Vedani, A. J. Chem. Soc., Perkin Trans. 2 1998, 2, 1449. (20) For the preparation of related fluorinated compounds, see (a) Domagala, Z.; Kolinski, R. A.; Wielgat, J. Roczniki Chemii 1976, 50, 993. (b) Cacioli, P.; Reiss, J. A. Aust. J. Chem. 1984, 37, 2537. (c) Yu, C.; Hu, G.; Zhang, C.; Wu, R.; Ye, H.; Yang, G.; Shi, X. J. Fluorine Chem. 2013, 153, 33. (21) The compound 8 is a sulfone derivative, while corresponding sulfide analogues are prepared by the use of C6F5-DAST 2, see 7a.

11945

DOI: 10.1021/acs.joc.7b01908 J. Org. Chem. 2017, 82, 11939−11945