Double SO2 Insertion into 1,7-Diynes Leading to ... - ACS Publications

Feb 5, 2018 - Institute of Chemistry & BioMedical Sciences, Nanjing University, Nanjing 210093, P. R. China. §. Department of .... benzene-tethered 1...
3 downloads 0 Views 1MB Size
Download PDF
This is an open access article published under a Creative Commons Non-Commercial No Derivative Works (CC-BY-NC-ND) Attribution License, which permits copying and redistribution of the article, and creation of adaptations, all for non-commercial purposes.

Article Cite This: ACS Omega 2018, 3, 1482−1491

Double SO2 Insertion into 1,7-Diynes Leading to Functionalized Naphtho[1,2‑c]thiophene 2,2-dioxides Ai-Fang Wang,† Wen-Juan Hao,*,† Yi-Long Zhu,† Guigen Li,‡,§ Peng Zhou,‡ Shu-Jiang Tu,*,† and Bo Jiang*,† †

School of Chemistry & Materials Science, Jiangsu Normal University, Xuzhou 221116, P. R. China Institute of Chemistry & BioMedical Sciences, Nanjing University, Nanjing 210093, P. R. China § Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, Texas 79409-1061, United States ‡

S Supporting Information *

ABSTRACT: A novel metal-free double SO2 insertion/ multicomponent bicyclization cascade of benzene-linked 1,7diynes has been established by treatment with aryldiazonium tetrafluoroborates and DABCO−bis(sulfur dioxide) under redox-neutral conditions, providing a range of dual sulfonecontaining naphtho[1,2-c]thiophene 2,2-dioxides with generally high stereoselectivity. The reaction pathway is proposed to proceed through the sequence of arylsulfonyl-radical-induced 6-exo-dig/5-endo-trig bicyclization, H-abstraction, and diazotization.

■

INTRODUCTION Sulfone nucleus is a privileged structural component in a substantial number of natural products and bioactive substances.1 Among them, benzothiophene dioxides possessing a cyclic sulfonyl unit have drawn considerable attention owing to their unique physical and biological activities.2 For instance, benzothiophene dioxides have been found to behave as an absorbance and fluorescence switch.3 Specifically, some benzothiophene dioxides could serve as inhibitors of hepatitis C virus NS5B polymerase and carbonic anhydrase.4 Consequently, much effort has been made in developing general methods for the construction of benzothiophene dioxide frameworks. Most of the synthetic endeavors to assemble these compounds involve Rh-catalyzed [2 + 2 + 2] cycloadditions of alkynes,5 photochemical cyclization of o-tolualdehydes,6 catalytic Garratt−Braverman cyclization of dipropargyl sulfones,7 Rhcatalyzed C−H insertion of α-diazo-β-arylmethanesulfonyl esters,8 and Pd-catalyzed intramolecular arylations of enolates.9 Recently, Wu et al. reported the insertion of sulfur dioxide into 2alkynylaryldiazonium tetrafluoroborate10a or (2-alkynylaryl)boronic acids10b for forming benzothiophene dioxides. Despite these limited achievements, the development of facile and efficient protocols toward synthesizing new functionalized benzothiophene dioxides, starting from readily available substrates under mild conditions, is still highly desirable. On the other hand, the insertion of sulfur dioxide into molecular skeletons has proven to be a powerful tool for the collection of biologically interesting sulfone-containing structures like sulfones and sulfonamides in a convergent manner.11 Over the past few years, the pioneering work of the group of Willis12 has stimulated extensive studies on the insertion of sulfur © 2018 American Chemical Society

dioxide with nucleophiles (Nu) and electrophiles (E) for sulfone and sulfonamide syntheses by exploiting bench-stable solid DABCO·(SO2)2 (DABSO) as the source of sulfur dioxide (Scheme 1a).13 Later, Wu and co-workers reported a threecomponent reaction of aryldiazonium tetrafluoroborates, DABSO, and aryl propiolates to afford 3-sulfonated coumarins (Scheme 1b).14 Recently, our group has established a series of domino radical cyclizations for sulfone-containing multiple ring formations.15 For example, we employed benzene-linked alleneynes as starting materials to subject them to the reaction of Scheme 1. Profiles for S-Centered Radical Cyclization

Received: November 16, 2017 Accepted: January 23, 2018 Published: February 5, 2018 1482

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega aryldiazonium tetrafluoroborates and DABSO toward synthesizing sulfone-containing cyclobuta[a]naphthalen-4-ols.15a For this purpose, we considered preparing diyne-anchored starting material 116 by taking advantage of a methodology in which double SO2 insertion across its CC π system results in functionalized naphtho[1,2-c]thiophene 2,2-dioxide products. As expected, this transformation proceeded smoothly under redox-neutral conditions to directly form naphtho[1,2-c]thiophene 2,2-dioxides 4 with high diastereoselectivity (Scheme 1c). Interestingly, aryldiazonium salts play dual roles as an aryl radical donor as well as an azo source, which were trapped by DABSO and 1,7-diynes, thereby simultaneously installing both sulfonyl group and azo functionality into the molecular skeleton via radical addition. The present approach represents the first radical-triggered multicomponent dehydrobicyclization cascade of 1,7-diynes for the direct synthesis of these new naphtho[1,2c]thiophene 2,2-dioxides via double SO2 insertion in a one-pot manner without any additional oxidant. Herein, we elaborated this unprecedented radical dehydrobicyclization transformation.

Figure 1. Oak Ridge thermal ellipsoid plot drawing of 4a.

framework incorporating two SO2 and two PMP units, we then adjusted the substrate ratio to 1:2:3, and the reaction provided a slightly higher yield of 4a (27%, entry 2). The following careful screening of the substrate ratio (entries 3−6) showed that the substrate ratio 1:4:3 remarkably facilitated this reaction process and afforded a higher yield (43%). Subsequently, the effect of solvent on this transformation was investigated using various solvents such as dichloromethane (DCM), acetonitrile (CH3CN), 1,4-dioxane, N,N-dimethylformamide (DMF), toluene, and tetrahydrofuran (THF). The use of DCM remarkably decreased the yield to 29% (entry 7), whereas other attempted solvents completely suppressed the reaction process (entries 8− 12). Elevating the reaction temperature to 70 °C was not beneficial to the transformation, accessing 4a in a reduced yield (37%, entry 13). In contrast, a decrease of the reaction temperature could promote the conversion of 1,7-diyne 1a into product 4a as a higher yield (48%) was obtained with the reaction temperature being 50 °C (entry 14). Further lowering the reaction temperature to 40 °C showed no positive effect on the yield of 4a (entry 15). To our delight, use of 0.5 equiv of Et3N as a base promoter efficiently facilitated this double SO2 insertion, delivering product 4a in a higher yield (56%, entry 16). With these acceptable reaction conditions in hand, we then systematically studied the generality of this metal-free multicomponent dehydrobicyclization cascade toward synthesizing naphtho[1,2-c]thiophene 2,2-dioxides 4 by examining 1,7-diyne and aryldiazonium tetrafluoroborate components (Scheme 2). First, 1,7-diynes with different functional groups were evaluated in combination with p-methoxyphenyl (PMP) diazonium tetrafluoroborate (2a) and DABSO (3). Substituents bearing both electronically rich and poor properties at different positions of arylalkynyl (R1) moiety could be successfully engaged in this transformation, generating corresponding products 4a−h with 39−67% yields and high diastereoselectivity (6:1 to 20:1 dr). Functional groups like methyl (1b and 1c), ethyl (1d), t-butyl (1e), methoxy (1f), and chloride (1g) were tolerated with these optimal conditions, some of which needed to fine-tune the reaction temperatures. For instance, 1,7-diyne 1f carrying a methoxy group (R1) was subjected to the reaction of 2a with 3 at 30 °C, furnishing the desired product 4f in 62% yield, whereas the presence of slight electron-withdrawing chloro group seemed to lower the efficiency of this dehydrobicyclization reaction, as the corresponding product 4g was isolated in a decreased (39%) yield, although with a reaction temperature of 60 °C. Alternatively, 1,7-diyne 1h with a n-butyl group was proven to be a suitable reaction partner, enabling the radical-induced dehydrobicyclization process toward synthesizing naphtho[1,2c]thiophene 2,2-dioxide 4h with 56% yield and 6:1 dr. 1,7-Diynes 1 having either electron-donating (Me, 1i−j and MeO, 1k−m) or -withdrawing (Cl, 1n−r) substituents (R2) at the C4- or C5position of the internal arene ring readily participated in the current dehydrobicyclization cascades, enabling metal-free

■

RESULTS AND DISCUSSION Our initial investigation commenced with the treatment of benzene-tethered 1,7-diyne 1a with p-methoxyphenyl (PMP) diazonium tetrafluoroborate (2a) and DABSO (3) in 1:2:2.5 mole ratio at 60 °C under Ar conditions using 1,2-dichloroethane (DCE) as the reaction medium. The reaction proceeded to generate naphtho[1,2-c]thiophene 2,2-dioxide 4a bearing an unexpected azo group, albeit with a low 15% yield (Table 1, entry 1). Interestingly, the analysis of 1H NMR and X-ray diffraction of product 4a revealed that high diastereoselectivity in 20:1 dr was observed (Figure 1). This exciting result prompted us to undertake further investigations. Because of this molecular Table 1. Optimization of Reaction Conditionsa

entry

substrate ratio

solvent

t (°C)

yield (%)b

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16

1:2:2.5 (1a:2a:3) 1:2:3 (1a:2a:3) 1:2:4 (1a:2a:3) 1:3:3 (1a:2a:3) 1:3:4 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3) 1:4:3 (1a:2a:3)

DCE DCE DCE DCE DCE DCE DCM CH3CN 1,4-dioxane DMF toluene THF DCE DCE DCE DCE

60 60 60 60 60 60 60 60 60 60 60 60 70 50 40 50

15 27 NDc 19 trace 43 29 trace ND trace NRd NR 37 48 41 56e

a

Reaction conditions: 1a, 0.4 mmol; 2a, x equiv; DABSO, y equiv; solvent, 2.5 mL; under Ar conditions, 1.5 h. bIsolated yield based on 1a. cND, not detected. dNR, no reaction. eUse of Et3N, 0.5 equiv. 1483

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega Scheme 2. Substrate Scope for Forming Products 4a,b,c

normal product 4a (Scheme 3a). Among them, a TEMPO−PMP adduct was detected by liquid chromatography−mass spectromScheme 3. Control Experiments

etry (LC−MS) analysis, indicating that the reaction process might include in situ generation of aryl radicals. Treatment of 1a with 2a and DABSO under standard conditions resulted in 4a in 56% yield, together with anisole 5, 4-methoxybenzenesulfinic acid 6, 4-methoxybenzenesulfonyl fluoride 7, and sulfuryl difluoride (Scheme 3b), and byproducts 5, 6, and 7 were detected by LC−MS analysis. These results revealed that the in situ generation of aryl and arylsulfonyl radicals could abstract hydrogen atoms from 1,7-diynes to convert into the corresponding benzenes and arylsulfinic acids, and arylsulfonyl radicals act as a reduction reagent. As radical acceptors, aryldiazonium salts have previously been proven to be converted into radical cations of azo compounds via radical cross-coupling with radical species, which gain an electron to facilitate access to azo compounds through a single electron transfer (SET) process.17 For this reason, we believed that during this reaction process SO2 serves as another reduction reagent and is oxidized and trapped by the fluoride anion to access sulfuryl difluoride (Scheme 3b), but it is difficult to be detected as it is a gas. To support the above analysis and certify the redox pathway, potassium bromide (KBr) was subjected to the reaction of 1a with 2a and DABSO under standard conditions (Scheme 3c). As expected, both sulfuryl dibromide 8 and sulfuryl bromide 9 were observed by LC−MS analysis. Next, in the presence of naphthalen-1-ol, the reaction gave naphthalen-1-yl sulfurofluoridate 10 (observed by LC−MS, Scheme 3d). These results further supported the above analysis. Combining the aforementioned observations and previous reports,13,14 a reasonable mechanism is proposed in Scheme 4. The combination of aryldiazonium cations and DABSO is anticipated to give radical cation intermediates A, SO2, and aryl radicals by the homolytic cleavage of the N−S bond and a SET process.14,18 Then, aryl radicals are intercepted by SO2 to generate arylsulfonyl radicals. Subsequently, radical addition of aryl sulfonyl radicals into 1,7-diynes 1 gives intermediates B,19 followed by 6-exo-dig cyclization to vinyl radicals C,20 which are trapped by SO2 to sulfonyl radicals D. Sulfonyl radicals D triggered 5-endo-trig cyclization, giving intermediates E, which undergo SET and base-promoted deprotonation to yield intermediates G. A subsequent hydrogen atom transfer (Habstraction) between G and aryl/arylsulfonyl radicals yields benzenes/arylsulfinic acids and radical intermediates H, trapped by aryldiazonium cations via radical cross-coupling to afford radical cations I. Next, in the presence of tetrafluoroborate anions, intermediates I react with SO2 and/or aryl sulfonyl radicals via a redox process to give naphtho[1,2-c]thiophene 2,2-

a Reaction conditions: 1, 0.4 mmol; 2, 1.6 mmol; DABSO, 1.2 mmol; Et3N, 0.2 mmol; DCE, 2.5 mL; 50 oC, under Ar conditions, 1.5 h; isolated yields in brackets based on 1,7-diynes 1; dr value based on their 1H NMR analysis. bThe reaction was conducted at 30 oC. cThe reaction was conducted at 60 oC.

sulfonylation and diazotization to access functionalized naphtho[1,2-c]thiophene 2,2-dioxides 4i−r in 45−72% yields and 15:1 to 20:1 dr. The reaction can tolerate various aryldiazonium tetrafluoroborates 2b−e with both electron-rich groups (ethoxy 2b, dimethoxy 2c, and methyl 2d) at the para-position of arene ring and neutral (H, 2e) groups, leading to the formation of naphtho[1,2-c]thiophene 2,2-dioxides 4s−w with yields ranging from 43 to 62% and 10:1 to 15:1 dr. Unluckily, aryldiazonium tetrafluoroborate 2f having a chloro group was an ineffective partner, as the reaction failed to work under standard conditions (Scheme 2, 4x). Moreover, 1,7-diyne 1k possessing a methoxy group located at the C5-position of the internal arene ring was utilized to react with 2a and 3, and the corresponding product 4y was offered in 48% yield and 10:1 dr. Similarly, ester-protected 1,7-diyne still showed high reactivity, enabling its conversion into product 4z with 55% yield and 15:1 dr. In the case of 4a, its stereostructure was unequivocally confirmed by carrying out single-crystal X-ray diffraction (Figure 1). To gain more mechanistic insight into this transformation, several control experiments were performed. The presence of 3.0 equiv of 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or butylhydroxytoluene completely suppressed the generation of 1484

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

material. After filtration through a pad of Celite rinsing with Et2O, the residue was purified by chromatography on silica gel with petroleum ether/ethyl acetate as the eluent to afford compound I (90−100% yield). Under an Ar atmosphere, a mixture of compound I (5.0 mmol, 1.0 equiv), 3-bromoprop-1-yne (1.5 equiv), and zinc powder (4 equiv) in 60 mL of THF/DMF (1/1) was stirred at room temperature, and the reaction system was detected by TLC. After completion of the reaction, the residue was quenched with saturated NH4Cl solution, extracted with ethyl acetate, and dried on MgSO4. After removal of the solvent, the crude product was purified by column chromatography (EtOAc/hexanes, 1:10) to give compound II as a white solid (80−90% yield). To a solution of compound II (4.0 mmol, 1.0 equiv) in anhydrous THF (20 mL), NaH (2.0 equiv) was added dropwise at 0 °C. After stirring for 0.5 h, CH3I (1.2 equiv) was added and then the reaction mixture was stirred at room temperature. After the mixture was stirred overnight, the reaction mixture was quenched with saturated NH4Cl solution, extracted with ethyl acetate, and dried on MgSO4. After removal of the solvent, the crude product was purified by column chromatography (EtOAc/ hexanes, 1:100) to give compound 1 (oil, 80−95% yield). Synthesis of Compound 1s. To a solution of compound II (4.0 mmol, 1.0 equiv), pyridine (3.0 equiv), and 4dimethylaminopyridine (20 mol %) in anhydrous dichloromethane (15 mL) at 0 °C was slowly added Ac2O (2 equiv). The reaction mixture was stirred for 6 h, and then 20 mL of saturated aqueous sodium bicarbonate was added. The aqueous layer was extracted with dichloromethane, and the combined organic layer was dried over MgSO4 and concentrated in vacuo. Purification by flash chromatography delivered 1z (oil, 75−80% yield). 1-(1-Methoxybut-3-yn-1-yl)-2-(phenylethynyl)benzene (1a). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.68−7.63 (m, 3H), 7.61 (d, J = 1.2 Hz, 1H), 7.46−7.41 (m, 4H), 7.36−7.32 (m, 1H), 5.12−5.07 (m, 1H), 3.44 (s, 3H), 2.92−2.86 (m, 1H), 2.80−2.73 (m, 1H), 2.19−2.06 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 142.4, 132.2, 131.6, 128.8, 128.6(3), 128.6(6), 127.7, 125.7, 123.1, 122.0, 95.0, 86.9, 81.1, 79.5, 70.1, 57.5, 27.0. 1-(1-Methoxybut-3-yn-1-yl)-2-(p-tolylethynyl)benzene (1b). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.63−7.59 (m, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.46−7.41 (m, 1H), 7.36−7.31 (m, 1H), 7.23 (d, J = 8.0 Hz, 2H), 5.16−5.01 (m, 1H), 3.44 (s, 3H), 2.92−2.83 (m, 1H), 2.80−2.71 (m, 1H), 2.43 (s, 3H), 2.16−2.06 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 142.3, 138.7, 132.1, 131.5, 129.3, 128.6, 127.6, 125.7, 122.2, 120.1, 95.2, 86.2, 81.1, 79.5, 69.9, 57.5, 27.0, 21.6. 1-(1-Methoxybut-3-yn-1-yl)-2-(m-tolylethynyl)benzene (1c). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.57 (d, J = 8.0 Hz, 2H), 7.45−7.40 (m, 3H), 7.35−7.28 (m, 2H), 7.21 (d, J = 7.6 Hz, 1H), 5.05−5.01 (m, 1H), 3.41 (s, 3H), 2.88−2.81 (m, 1H), 2.74−2.67 (m, 1H), 2.41 (s, 3H), 2.10−2.02 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 142.2, 138.2, 132.1, 129.5, 128.6(4), 128.6(2), 128.4, 127.6, 125.6, 122.9, 122.0, 95.1, 86.4, 81.0, 79.4, 69.8, 57.5, 26.9, 21.3. 1-((4-Ethylphenyl)ethynyl)-2-(1-methoxybut-3-yn-1-yl)benzene (1d). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.53 (d, J = 8.0 Hz, 2H), 7.50−7.47 (m, 2H), 7.40−7.36 (m, 1H), 7.31−7.26 (m, 1H), 7.21 (d, J = 8.0 Hz, 2H), 5.00−4.96 (m, 1H), 3.37 (s, 3H), 2.83−2.76 (m, 1H), 2.71−2.67 (m, 2H), 2.67−2.61 (m, 1H), 2.04−2.00 (m, 1H), 1.26 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 145.0, 142.1, 132.0, 131.5, 128.5, 128.0, 127.5, 125.6, 122.1, 120.2, 95.1, 86.0, 81.0, 79.3, 69.7, 57.5, 28.9, 26.9, 15.4.

Scheme 4. Plausible Mechanism Pathway

dioxides J, sulfuryl difluorides, and aryl sulfonyl fluoride.15a Intermediates J are converted into final products 4 through 1,3-H transfer. In conclusion, we have discovered an unprecedented double SO2 insertion into benzene-linked 1,7-diynes under mild redoxneutral conditions, by which disulfone-containing naphtho[1,2c]thiophene 2,2-dioxides with a wide diversity in substituents were diastereoselectively synthesized through arylsulfonylradical-induced 6-exo-dig/5-endo-trig bicyclization. Notably, aryldiazonium salts play dual roles as the reaction initiator as well as the reaction terminator, installing the sulfonyl group and azo functionality into the molecular skeleton via radical addition. The reaction enabled direct construction of six new σ bond including C−S, C−C, and C−N bonds by combining aryldiazonium salts, DABSO, and C(sp3)-linked 1,7-diynes under catalyst-free conditions, providing an easy and metal-free protocol toward synthesizing a range of richly decorated naphtho[1,2-c]thiophene 2,2-dioxides. Further investigation on mechanistic insights and its applications will be conducted in due course.

■

EXPERIMENTAL SECTION General Procedure for the Synthesis of Compounds 1.

Under Ar conditions, a mixture of 2-bromobenzaldehyde (10.0 mmol), CuI (2 mol %), PdCl2(PPh3)2 (2 mol %), and Et3N (60 mL) as a solvent was stirred at 50 °C. Then, ethynylbenzene (1.05 equiv) was dropwise added into the reaction system. The resulting reaction mixture was stirred until thin-layer chromatography (TLC) indicated complete consumption of the starting 1485

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega 1-((4-(tert-Butyl)phenyl)ethynyl)-2-(1-methoxybut-3-yn-1yl)benzene (1e). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.61−7.49 (m, 4H), 7.47−7.36 (m, 3H), 7.35−7.29 (m, 1H), 5.09−4.94 (m, 1H), 3.39 (s, 3H), 2.86−2.77 (m, 1H), 2.73−2.64 (m, 1H), 2.08−2.01 (m, 1H), 1.37 (s, 9H). 13C NMR (100 MHz, CDCl3; δ, ppm) 151.9, 142.2, 132.0, 131.3, 128.5, 127.5, 125.6, 125.5, 122.1, 120.0, 95.0, 86.0, 81.0, 79.3, 69.7, 57.5, 34.8, 31.2, 26.9. 1-(1-Methoxybut-3-yn-1-yl)-2-((4-methoxyphenyl)ethynyl)benzene (1f). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.55−7.51 (m, 4H), 7.41−7.37 (m, 1H), 7.33−7.28 (m, 1H), 6.93 (d, J = 8.8 Hz, 2H), 5.02−4.98 (m, 1H), 3.87 (s, 3H), 3.39 (s, 3H), 2.85−2.79 (m, 1H), 2.71−2.64 (m, 1H), 2.06−2.03 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 159.8, 142.0, 133.0, 131.9, 128.3, 127.5, 125.5, 122.2, 115.1, 114.1, 94.9, 85.4, 81.1, 79.4, 69.7, 57.5, 55.4, 26.9. 1-((4-Chlorophenyl)ethynyl)-2-(1-methoxybut-3-yn-1-yl)benzene (1g). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.55 (d, J = 7.6 Hz, 2H), 7.53−7.50 (m, 2H), 7.45−7.41 (m, 1H), 7.39−7.36 (m, 2H), 7.34−7.30 (m, 1H), 4.98−4.95 (m, 1H), 3.39 (s, 3H), 2.83−2.77 (m, 1H), 2.71−2.65 (m, 1H), 2.05−2.04 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 141.3, 133.5, 131.7, 131.1, 127.9, 127.8, 126.6, 124.6, 120.5, 120.5, 92.6, 86.6, 79.9, 78.4, 68.8, 56.4, 25.9. 1-(Hex-1-yn-1-yl)-2-(1-methoxybut-3-yn-1-yl)benzene (1h). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.48 (d, J = 8.0 Hz, 1H), 7.41 (d, J = 7.6 Hz, 1H), 7.35−7.30 (m, 1H), 7.25− 7.20 (m, 1H), 4.92−4.87 (m, 1H), 3.34 (s, 3H), 2.75−2.69 (m, 1H), 2.63−2.56 (m, 1H), 2.50−2.46 (m, 2H), 2.03−2.00 (m, 1H), 1.68−1.61 (m, 2H), 1.58−1.50 (m, 2H), 0.99 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 142.0, 132.1, 127.8, 127.4, 125.4, 122.7, 96.0, 81.1, 79.2, 78.0, 69.5, 57.3, 30.8, 26.8, 22.1, 19.2, 13.6. 1-(1-Methoxybut-3-yn-1-yl)-4-methyl-2-(p-tolylethynyl)benzene (1i). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.51 (d, J = 8.0 Hz, 2H), 7.47 (d, J = 8.0 Hz, 1H), 7.41 (s, 1H), 7.25−7.21 (m, 3H), 5.04−5.00 (m, 1H), 3.41 (s, 3H), 2.87−2.80 (m, 1H), 2.75−2.68 (m, 1H), 2.43 (s, 3H), 2.40 (s, 3H), 2.08− 2.06 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 139.2, 138.6, 137.3, 132.5, 131.5, 129.5, 129.2, 125.6, 122.0, 120.1, 94.7, 86.3, 81.2, 79.2, 69.8, 57.4, 27.0, 21.6, 21.0. 2-((4-Chlorophenyl)ethynyl)-1-(1-methoxybut-3-yn-1-yl)4-methylbenzene (1j). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.52−7.48 (m, 2H), 7.43 (d, J = 8.0 Hz, 1H), 7.39−7.35 (m, 3H), 7.24 (d, J = 7.6 Hz, 1H), 4.95−4.91 (m, 1H), 3.37 (s, 3H), 2.80−2.73 (m, 1H), 2.70−2.63 (m, 1H), 2.38 (s, 3H), 2.06−2.01 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 139.3, 137.4, 134.5, 132.7, 132.6, 129.9, 128.8, 125.6, 121.6, 121.5, 93.2, 87.9, 81.0, 79.2, 69.7, 57.4, 27.0, 20.9. 4-Methoxy-2-(1-methoxybut-3-yn-1-yl)-1-(phenylethynyl)benzene (1k). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.56 (m, 2H), 7.49 (d, J = 8.4 Hz, 1H), 7.42−7.36 (m, 3H), 7.11 (d, J = 2.8 Hz, 1H), 6.88−6.84 (m, 1H), 4.99−4.95 (m, 1H), 3.88 (s, 3H), 3.41 (s, 3H), 2.85−2.79 (m, 1H), 2.70−2.63 (m, 1H), 2.10−2.04 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 160.1, 144.2, 133.5, 131.4, 128.4, 128.2, 123.4, 113.9, 113.7, 110.8, 93.5, 86.7, 80.9, 79.3, 69.8, 57.6, 55.4, 26.9. 4-Methoxy-2-(1-methoxybut-3-yn-1-yl)-1-(p-tolylethynyl)benzene (1l). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.50−7.42 (m, 3H), 7.19 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 2.8 Hz, 1H), 6.87−6.83 (m, 1H), 4.99−4.95 (m, 1H), 3.87 (s, 3H), 3.41 (s, 3H), 2.85−2.79 (m, 1H), 2.69−2.62 (m, 1H), 2.40 (s, 3H), 2.08−2.03 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm)

159.9, 144.1, 138.3, 133.4, 131.2, 129.2, 120.3, 114.2, 113.7, 110.8, 93.7, 86.0, 81.0, 79.3, 69.8, 57.6, 55.4, 26.8, 21.5. 1-((4-Chlorophenyl)ethynyl)-4-methoxy-2-(1-methoxybut3-yn-1-yl)benzene (1m). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.50−7.46 (m, 3H), 7.37−7.33 (m, 2H), 7.10 (d, J = 2.8 Hz, 1H), 6.88−6.84 (m, 1H), 4.95−4.91 (m, 1H), 3.88 (s, 3H), 3.40 (s, 3H), 2.83−2.76 (m, 1H), 2.69−2.61 (m, 1H), 2.07−2.04 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 160.3, 144.3, 134.1, 133.6, 132.5, 128.7, 121.9, 113.7, 113.6, 110.9, 92.4, 87.7, 80.9, 79.4, 69.8, 57.6, 55.4, 26.9. 4-Chloro-2-(1-methoxybut-3-yn-1-yl)-1-(phenylethynyl)benzene (1n). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.59−7.54 (m, 3H), 7.49 (d, J = 8.4 Hz, 1H), 7.42−7.38 (m, 3H), 7.31−7.29 (m, 1H), 4.96−4.92 (m, 1H), 3.41 (s, 3H), 2.84−2.77 (m, 1H), 2.71−2.64 (m, 1H), 2.08−2.04 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 144.2, 134.9, 133.3, 131.5, 128.8, 128.5, 127.9, 126.1, 122.7, 120.3, 95.7, 85.6, 80.4, 79.0, 70.1, 57.7, 26.7. 4-Chloro-2-(1-methoxybut-3-yn-1-yl)-1-(p-tolylethynyl)benzene (1o). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.54 (d, J = 2.0 Hz, 1H), 7.49−7.45 (m, 3H), 7.30−7.27 (m, 1H), 7.21 (d, J = 8.0 Hz, 2H), 4.97−4.92 (m, 1H), 3.40 (s, 3H), 2.84− 2.77 (m, 1H), 2.70−2.63 (m, 1H), 2.41 (s, 3H), 2.07−2.04 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 144.1, 139.0, 134.6, 133.2, 131.4, 129.3, 127.9, 126.0, 120.5, 119.6, 96.0, 85.0, 80.5, 79.0, 70.1, 57.7, 26.7, 21.6. 4-Chloro-1-((4-ethylphenyl)ethynyl)-2-(1-methoxybut-3yn-1-yl)benzene (1p). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.54 (d, J = 2.0 Hz, 1H), 7.51−7.46 (m, 3H), 7.30−7.27 (m, 1H), 7.24 (d, J = 8.0 Hz, 2H), 4.96−4.92 (m, 1H), 3.40 (s, 3H), 2.84−2.77 (m, 1H), 2.73−2.69 (m, 2H), 2.68−2.63 (m, 1H), 2.07−2.05 (m, 1H), 1.28 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 145.3, 144.1, 134.6, 133.2, 131.5, 128.1, 127.9, 126.0, 120.5, 119.8, 96.0, 85.0, 80.4, 79.0, 70.1, 57.7, 28.9, 26.7, 15.4. 1-((4-(tert-Butyl)phenyl)ethynyl)-4-chloro-2-(1-methoxybut-3-yn-1-yl)benzene (1q). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.55−7.49 (m, 3H), 7.47 (d, J = 8.4 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.30−7.27 (m, 1H), 4.96−4.92 (m, 1H), 3.40 (s, 3H), 2.83−2.76 (m, 1H), 2.70−2.62 (m, 1H), 2.06−2.05 (m, 1H), 1.36 (s, 9H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.2, 144.1, 134.6, 133.2, 131.3, 127.9, 126.0, 125.5, 120.5, 119.7, 95.9, 85.0, 80.4, 79.0, 70.1, 57.7, 34.9, 31.2, 26.6. 4-Chloro-2-(1-methoxybut-3-yn-1-yl)-1-((4methoxyphenyl)ethynyl)benzene (1r). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.56−7.49 (m, 3H), 7.46 (d, J = 8.4 Hz, 1H), 7.29−7.26 (m, 1H), 6.96−6.90 (m, 2H), 4.95−4.91 (m, 1H), 3.86 (s, 3H), 3.40 (s, 3H), 2.84−2.77 (m, 1H), 2.69−2.63 (m, 1H), 2.07−2.05 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 160.0, 143.9, 134.4, 133.1, 133.0, 127.9, 126.0, 120.7, 114.8, 114.2, 95.9, 84.4, 80.5, 79.1, 70.1, 57.7, 55.4, 26.7. 1-(2-(Phenylethynyl)phenyl)but-3-yn-1-yl acetate (1s). White oil; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.64−7.57 (m, 3H), 7.54 (d, J = 7.6 Hz, 1H), 7.42−7.38 (m, 4H), 7.36−7.32 (m, 1H), 6.51−6.47 (m, 1H), 3.03−2.97 (m, 1H), 2.92−2.85 (m, 1H), 2.20 (s, 3H), 2.05−2.03 (m, 1H). 13C NMR (100 MHz, CDCl3; δ, ppm) 169.9, 140.6, 132.3, 131.6, 128.6, 128.5, 128.4, 128.0, 125.8, 123.0, 121.4, 95.3, 86.4, 79.5, 71.7, 70.7, 25.3, 21.1. General Procedure for the Synthesis of Products 4. Example for the synthesis of 4a: To a 25 mL Schlenk tube under Ar conditions, 1-(1-methoxybut-3-yn-1-yl)-2-(phenylethynyl)benzene (1a, 0.4 mmol, 104 mg, 1.0 equiv), 1,4diazabicyclo[2.2.2]octane bis(sulfur dioxide) adduct (3, 1.2 1486

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

114.0, 69.2, 55.8, 55.5, 54.2, 28.9, 15.2. IR (film, ν, cm−1) 2965, 2839, 1594, 1577, 1496, 1332, 1260, 1145, 829. HR-MS (ESI) m/z calcd for C35H32N2NaO7S2 [M + Na]+ 679.1549, found 679.1552. (E)-1-(4-(tert-Butyl)phenyl)-5-methoxy-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4e, Major). 183 mg, 67%; red solid, mp 172−173 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.67−7.61 (m, 3H), 7.55−7.47 (m, 5H), 7.27−7.18 (m, 2H), 7.05 (d, J = 9.2 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 6.36 (s, 1H), 5.93 (s, 1H), 3.96 (s, 3H), 3.60 (s, 3H), 3.11 (s, 3H), 1.39 (s, 9H). 13C NMR (100 MHz, DMSO-d6; δ, ppm) 164.2, 163.7, 154.2, 148.3, 146.9, 138.6, 136.6, 136.0, 132.2, 131.7, 131.5, 130.2, 130.1, 128.9, 127.9, 127.2, 127.1, 127.0, 123.6, 114.9, 114.7, 76.7, 69.1, 56.4, 55.9, 55.1, 35.3, 31.4. IR (film, ν, cm−1) 2964, 2846, 1617, 1595, 1407, 1326, 1145, 838. HR-MS (ESI) m/z calcd for C37H36N2NaO7S2 [M + Na]+ 707.1862, found 707.1863. (E)-5-Methoxy-1-(4-methoxyphenyl)-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4f). 163 mg, 62%; red solid, mp 157−158 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.65−7.61 (m, 3H), 7.56 (d, J = 8.8 Hz, 2H), 7.52−7.47 (m, 1H), 7.23−7.18 (m, 1H), 7.07−7.02 (m, 5H), 6.59 (d, J = 8.8 Hz, 2H), 6.35 (s, 1H), 5.91 (s, 1H), 3.96 (s, 3H), 3.91 (s, 3H), 3.60 (s, 3H), 3.12 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.4, 161.7, 147.8, 147.1, 138.7, 135.7, 132.2, 132.0, 130.9, 130.7, 130.0, 128.4, 128.2, 127.6, 127.3, 126.0, 118.1, 115.0, 114.3, 114.0, 69.3, 55.8, 55.5, 55.4, 54.2. IR (film, ν, cm−1) 2933, 2842, 1600, 1578, 1499, 1322, 1257, 1146, 836. HR-MS (ESI) m/z calcd for C34H30N2NaO8S2 [M + Na]+ 681.1341, found 681.1342. (E)-1-(4-Chlorophenyl)-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)-3,5dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4g, Major). 103 mg, 39%; red solid, mp 181−182 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.83−7.78 (m, 2H), 7.67−7.61 (m, 3H), 7.59− 7.50 (m, 5H), 7.25−7.18 (m, 2H), 7.06 (d, J = 9.2 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 6.35 (s, 1H), 5.89 (s, 1H), 3.97 (s, 3H), 3.60 (s, 3H), 3.14 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.4, 163.6, 148.5, 147.0, 137.3, 137.2, 137.0, 135.9, 132.2, 131.9, 131.3, 130.8, 129.8, 129.5, 128.4, 127.9, 127.7, 127.2, 126.1, 124.8, 114.3, 114.0, 69.3, 55.8, 55.5, 54.5. IR (film, ν, cm−1) 2989, 2866, 1617, 1598, 1323, 1263, 1146, 835. HR-MS (ESI) m/z calcd for C33H27ClN2NaO7S2 [M + Na]+ 685.0846, found 685.0847. (E)-1-Butyl-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3((4-methoxyphenyl)sulfonyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4h, Major). 136 mg, 56%; red solid, mp 168−169 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80−7.74 (m, 2H), 7.71−7.66 (m, 2H), 7.60−7.54 (m, 3H), 7.06−7.01 (m, 2H), 6.98−6.78 (m, 1H), 6.57 (d, J = 8.8 Hz, 2H), 6.24 (s, 1H), 5.89 (s, 1H), 3.95 (s, 3H), 3.60 (s, 3H), 3.02 (s, 3H), 2.94−2.88 (m, 2H), 2.00−1.90 (m, 1H), 1.77−1.67 (m, 1H), 1.57−1.51 (m, 2H), 1.03 (d, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.3, 147.1, 147.0, 141.6, 135.8, 135.5, 132.2, 131.0, 130.8, 130.7, 128.9, 128.8, 127.7, 127.2, 127.0, 125.9, 114.5, 114.2, 113.9, 113.5, 69.2, 55.8, 55.4, 54.0, 30.5, 25.0, 23.1, 13.7. IR (film, ν, cm−1) 2940, 2870, 1596, 1577, 1499, 1336, 1256, 1140, 836. HR-MS (ESI) m/z calcd for C31H32N2NaO7S2 [M + Na]+ 631.1549, found 631.1552. (E)-5-Methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-8-methyl-1-(p-tolyl)-3,5-

mmol, 288 mg, 3.0 equiv), 4-methoxybenzenediazonium tetrafluoroborate (2a, 1.6 mmol, 355 mg, 4.0 equiv), triethylamine (0.2 mmol, 20 mg, 0.5 equiv), and 1,2-dichloroethane (2.5 mL) were successively added. Then, the tube was stirred at 50 °C for 1.5 h until complete consumption of 1a, as monitored by TLC analysis. After the reaction was completed, the reaction mixture was concentrated in vacuum and the resulting residue was purified by column chromatography on silica gel (eluent, petroleum ether/ethyl acetate = 3:1) to afford the desired product 4a as a red solid. (E)-5-Methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-1-phenyl-3,5-dihydronaphtho[1,2c]thiophene 2,2-dioxide (4a, Major). 141 mg, 56%; red solid, mp 153−154 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.71−7.46 (m, 9H), 7.19 (s, 2H), 7.06 (d, J = 8.4 Hz, 2H), 6.60 (d, J = 8.8 Hz, 2H), 6.36 (s, 1H), 5.92 (s, 1H), 3.97 (s, 3H), 3.60 (s, 3H), 3.12 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.5, 148.1, 147.0, 138.7, 136.5, 135.8, 132.3, 131.1, 130.7(4), 130.7(8), 130.5, 129.8, 129.4, 128.3, 128.1, 127.7, 127.2, 126.3, 126.1, 114.3, 114.0, 69.2, 55.8, 55.5, 54.2. IR (film, ν, cm−1) 2933, 2840, 1595, 1577, 1498, 1337, 1146, 838. HR-MS (ESI) m/z calcd for C33H28N2NaO7S2 [M + Na]+ 651.1236, found 651.1237. (E)-5-Methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-1-(p-tolyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4b, Major). 149 mg, 58%; red solid, mp 188−189 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.67−7.60 (m, 3H), 7.53−7.46 (m, 3H), 7.32 (d, J = 8.0 Hz, 2H), 7.25 (d, J = 8.0 Hz, 1H), 7.22−7.16 (m, 1H), 7.05 (d, J = 9.2 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 6.35 (s, 1H), 5.92 (s, 1H), 3.96 (s, 3H), 3.60 (s, 3H), 3.11 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.4, 147.9, 147.0, 141.2, 139.0, 136.1, 135.7, 132.2, 131.0, 130.7, 130.4, 130.2, 130.0, 128.3, 128.2, 127.7, 127.3, 126.0, 123.2, 114.3, 114.0, 69.2, 55.8, 55.5, 54.2, 21.6. IR (film, ν, cm−1) 2934, 2855, 1594, 1497, 1336, 1145, 831. HR-MS (ESI) m/z calcd for C34H30N2NaO7S2 [M + Na]+ 665.1392, found 665.1387. (E)-5-Methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-1-(m-tolyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4c, Major). 164 mg, 64%; red solid, mp 182−183 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80 (d, J = 8.8 Hz, 2H), 7.67−7.61 (m, 3H), 7.52−7.48 (m, 1H), 7.44−7.35 (m, 4H), 7.24−7.16 (m, 2H), 7.05 (d, J = 8.8 Hz, 2H), 6.60 (d, J = 9.2 Hz, 2H), 6.36 (s, 1H), 5.91 (s, 1H), 3.96 (s, 3H), 3.60 (s, 3H), 3.11 (s, 3H), 2.43 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.5, 148.0, 147.0, 139.3, 139.0, 136.3, 135.7, 132.2, 131.6, 131.1, 130.8, 130.6, 129.9, 129.3, 128.3, 128.2, 127.8, 127.6, 127.2, 126.2, 126.1, 114.3, 114.0, 69.2, 55.8, 55.5, 54.2, 21.4. IR (film, ν, cm−1) 2929, 2844, 1593, 1577, 1498, 1334, 1255, 1149, 838. HR-MS (ESI) m/z calcd for C34H30N2NaO7S2 [M + Na]+ 665.1392, found 665.1390. (E)-1-(4-Ethylphenyl)-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)-3,5dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4d, Major). 160 mg, 61%; red solid, mp 171−172 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.67−7.61 (m, 3H), 7.53−7.47 (m, 3H), 7.34 (d, J = 8.0 Hz, 2H), 7.26 (d, J = 7.6 Hz, 1H), 7.21−7.16 (m, 1H), 7.05 (d, J = 9.2 Hz, 2H), 6.59 (d, J = 8.8 Hz, 2H), 6.35 (s, 1H), 5.92 (s, 1H), 3.96 (s, 3H), 3.60 (s, 3H), 3.12 (s, 3H), 2.79−2.73 (m, 2H), 1.31 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.5, 147.9, 147.3, 147.0, 139.0, 136.1, 135.7, 132.2, 131.0, 130.7, 130.4, 130.0, 129.0, 128.3, 128.2, 127.7, 127.2, 127.1, 126.1, 123.4, 114.3, 1487

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

(s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.6, 161.9, 148.1, 147.0, 138.0, 137.0, 136.8, 135.3, 132.2, 132.0, 129.8, 129.3, 127.1, 126.1, 125.1, 120.2, 115.4, 114.7, 114.3, 114.0, 69.3, 55.8, 55.6, 55.5, 54.1. IR (film, ν, cm−1) 2948, 2938, 1596, 1577, 1497, 1332, 1257, 1148, 837. HR-MS (ESI) m/z calcd for C34H29ClN2NaO8S2 [M + Na]+ 715.0952, found 715.0957. (E)-7-Chloro-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3((4-methoxyphenyl)sulfonyl)-1-phenyl-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4n, Major). 119 mg, 45%; red solid, mp 177−178 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80 (d, J = 8.8 Hz, 2H), 7.66−7.62 (m, 3H), 7.61−7.52 (m, 5H), 7.18−7.12 (m, 2H), 7.06 (d, J = 8.8 Hz, 2H), 6.62 (d, J = 8.8 Hz, 2H), 6.34 (s, 1H), 5.87 (s, 1H), 3.97 (s, 3H), 3.61 (s, 3H), 3.14 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.4, 163.7, 147.8, 147.0, 139.1, 137.6, 137.2, 135.5, 132.2, 130.9, 130.6, 130.5, 129.5, 128.9, 128.7, 127.2, 126.6, 126.1(3), 126.1(7), 114.4, 114.1, 69.0, 55.8, 55.5, 54.6. IR (film, ν, cm−1) 2940, 1842, 1616, 1593, 1497, 1263, 1145, 837. HR-MS (ESI) m/z calcd for C33H27ClN2NaO7S2 [M + Na]+ 685.0846, found 685.0842. (E)-7-Chloro-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3((4-methoxyphenyl)sulfonyl)-1-(p-tolyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4o, Major). 130 mg, 48%; red solid, mp 225−226 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 8.43 (d, J = 2.0 Hz, 1H), 7.91 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 9.2 Hz, 3H), 7.36 (s, 1H), 7.32−7.22 (m, 3H), 7.11 (d, J = 8.8 Hz, 3H), 6.81 (d, J = 8.8 Hz, 3H), 6.30 (s, 1H), 4.24 (s, 3H), 3.98 (s, 3H), 3.84 (s, 3H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.6, 163.0, 153.5, 147.0, 140.1, 137.4, 134.4, 132.2, 131.9, 131.7, 131.0, 130.4, 129.8, 129.1, 128.7, 128.5, 127.9, 125.0, 124.9, 123.7, 119.1, 114.5, 114.1, 80.0, 69.1, 64.9, 55.8, 21.4. IR (film, ν, cm−1) 2960, 2835, 1637, 1616, 1593, 1500, 1338, 1257, 1145, 834. HR-MS (ESI) m/z calcd for C34H29ClN2NaO7S2 [M + Na]+ 699.1002, found 699.1003. (E)-7-Chloro-1-(4-ethylphenyl)-5-methoxy-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4p, Major). 152 mg, 55%; red solid, mp 177−178 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.79 (d, J = 9.2 Hz, 2H), 7.64 (d, J = 9.2 Hz, 3H), 7.51 (d, J = 8.0 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 7.23−7.15 (m, 2H), 7.05 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 9.2 Hz, 2H), 6.33 (s, 1H), 5.87 (s, 1H), 3.97 (s, 3H), 3.61 (s, 3H), 3.13 (s, 3H), 2.79− 2.73 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.6, 147.6, 147.5, 146.9, 139.4, 137.5, 137.1, 135.1, 132.2, 130.6, 130.3, 129.7, 129.1, 128.9, 128.7, 127.2, 126.8, 126.1, 123.1, 114.3, 114.0, 69.0, 55.8, 55.5, 54.5, 28.9, 15.2. IR (film, ν, cm−1) 2964, 2833, 1594, 1497, 1332, 1320, 1145, 1083, 832. HR-MS (ESI) m/z calcd for C35H31ClN2NaO7S2 [M + Na]+ 713.1159, found 713.1158. (E)-1-(4-(tert-Butyl)phenyl)-7-chloro-5-methoxy-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4q, Major). 155 mg, 54%; red solid, mp 166−167 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.80 (d, J = 9.2 Hz, 2H), 7.67−7.61 (m, 3H), 7.53 (s, 4H), 7.23−7.17 (m, 2H), 7.06 (d, J = 9.2 Hz, 2H), 6.62 (d, J = 9.2 Hz, 2H), 6.33 (s, 1H), 5.88 (s, 1H), 3.97 (s, 3H), 3.62 (s, 3H), 3.14 (s, 3H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.6, 154.5, 147.5, 147.0, 139.4, 137.5, 137.1, 135.1, 132.2, 130.6, 130.1, 129.7, 128.9, 128.7, 127.3, 126.8, 126.5, 126.1, 122.9, 114.3, 114.0, 69.0, 55.8, 55.5, 54.5, 35.0, 31.2. IR (film, ν, cm−1) 2953, 2841, 1595, 1501, 1458, 1336, 1263, 1145, 1083, 832. HR-MS (ESI) m/z calcd for C37H35ClN2NaO7S2 [M + Na]+ 741.1472, found 741.1471.

dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4i, Major). 165 mg, 63%; red solid, mp 166−167 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.78 (d, J = 8.8 Hz, 2H), 7.62 (d, J = 8.8 Hz, 2H), 7.54−7.48 (m, 3H), 7.32 (d, J = 8.0 Hz, 3H), 7.04 (d, J = 8.4 Hz, 3H), 6.61−6.55 (m, 2H), 6.34 (s, 1H), 5.87 (s, 1H), 3.95 (s, 3H), 3.58 (s, 3H), 3.09 (s, 3H), 2.47 (s, 3H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.4, 148.0, 147.0, 141.1, 138.7, 138.1, 136.3, 132.8, 132.2, 131.9, 130.5, 130.4, 130.1, 130.0, 128.2, 128.1, 127.2, 126.0, 123.3, 114.3, 114.0, 68.9, 55.8, 55.4, 53.9, 21.6, 21.2. IR (film, ν, cm−1) 2950, 2843, 1595, 1577, 1496, 1335, 1255, 1148, 847. HR-MS (ESI) m/z calcd for C35H32N2NaO7S2 [M + Na]+ 679.1549, found 679.1547. (E)-1-(4-Chlorophenyl)-5-methoxy-4-((4-methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)-8-methyl-3,5dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4j, Major). 127 mg, 47%; red solid, mp 180−181 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.78 (d, J = 8.8 Hz, 2H), 7.64−7.58 (m, 4H), 7.54−7.50 (m, 3H), 7.34−7.31 (m, 1H), 7.07−7.00 (m, 3H), 6.59 (d, J = 8.8 Hz, 2H), 6.34 (s, 1H), 5.84 (s, 1H), 3.96 (s, 3H), 3.59 (s, 3H), 3.11 (s, 3H), 2.18 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.6, 148.5, 147.0, 138.3, 137.2, 137.1, 133.0, 132.2, 132.1, 132.0, 130.6, 129.7, 128.1, 127.8, 127.1, 126.1, 125.0, 114.3, 114.0, 69.0, 55.8, 55.4, 54.3, 21.3. IR (film, ν, cm−1) 2991, 2927, 1597, 1576, 1496, 1335, 1264, 1146, 834. HRMS (ESI) m/z calcd for C34H29ClN2NaO7S2 [M + Na]+ 699.1002, found 699.1022. (E)-5,7-Dimethoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-1-phenyl-3,5-dihydronaphtho[1,2c]thiophene 2,2-dioxide (4k, Major). 179 mg, 68%; red solid, mp 171−172 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81 (d, J = 8.8 Hz, 2H), 7.65 (d, J = 9.2 Hz, 2H), 7.59−7.49 (m, 5H), 7.14−7.10 (m, 2H), 7.05 (d, J = 9.2 Hz, 2H), 6.73−6.70 (m, 1H), 6.61 (d, J = 9.2 Hz, 2H), 6.35 (s, 1H), 5.90 (s, 1H), 3.96 (s, 3H), 3.88 (s, 3H), 3.61 (s, 3H), 3.09 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.5, 161.7, 147.8, 147.0, 137.8, 136.7, 136.3, 132.2, 130.6, 130.5, 130.1, 129.4, 129.3, 127.3, 126.6, 126.0, 120.6, 115.1, 114.7, 114.3, 114.0, 69.2, 55.8, 55.5, 55.5, 53.8. IR (film, ν, cm−1) 2958, 2842, 1595, 1499, 1442, 1323, 1254, 1145, 1024, 833. HR-MS (ESI) m/z calcd for C34H30N2NaO8S2 [M + Na]+ 681.1341, found 681.1345. (E)-5,7-Dimethoxy-4-((4-methoxyphenyl)diazenyl)-3-((4methoxyphenyl)sulfonyl)-1-(p-tolyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4l, Major). 193 mg, 72%; red solid, mp 189−190 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.83−7.78 (m, 2H), 7.67−7.62 (m, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.31 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.8 Hz, 1H), 7.13 (d, J = 2.8 Hz, 1H), 7.05 (d, J = 9.2 Hz, 2H), 6.75−6.71 (m, 1H), 6.61 (d, J = 9.2 Hz, 2H), 6.34 (s, 1H), 5.90 (s, 1H), 3.96 (s, 3H), 3.88 (s, 3H), 3.61 (s, 3H), 3.09 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.4, 161.7, 147.6, 147.0, 140.9, 137.7, 137.0, 136.0, 132.2, 130.4, 130.2, 130.1, 129.3, 127.2, 126.0, 123.5, 120.7, 115.1, 114.7, 114.3, 114.0, 69.2, 55.8, 55.5(1), 55.5(8), 53.8, 21.6. IR (film, ν, cm−1) 2964, 2841, 1597, 1576, 1495, 1331, 1256, 1147, 1023, 836. HR-MS (ESI) m/z calcd for C35H32N2NaO8S2 [M + Na]+ 695.1498, found 695.1500. (E)-1-(4-Chlorophenyl)-5,7-dimethoxy-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4m, Major). 147 mg, 53%; red solid, mp 185−186 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.79 (d, J = 9.2 Hz, 2H), 7.63 (d, J = 8.8 Hz, 2H), 7.57−7.49 (m, 4H), 7.15−7.12 (m, 2H), 7.05 (d, J = 8.8 Hz, 2H), 6.78−6.74 (m, 1H), 6.60 (d, J = 9.2 Hz, 2H), 6.34 (s, 1H), 5.86 (s, 1H), 3.96 (s, 3H), 3.89 (s, 3H), 3.59 (s, 3H), 3.10 1488

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

Major). 129 mg, 49%; red solid, mp 184−185 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.70 (d, J = 8.4 Hz, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.57−7.50 (m, 4H), 7.36 (d, J = 8.0 Hz, 2H), 7.16−7.13 (m, 2H), 6.96 (d, J = 8.0 Hz, 2H), 6.79−6.75 (m, 1H), 6.37 (s, 1H), 5.86 (s, 1H), 3.90 (s, 3H), 3.11 (s, 3H), 2.51 (s, 3H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 161.9, 150.6, 148.1, 145.9, 143.7, 138.0, 137.1, 136.7, 135.7, 133.0, 132.0, 130.7, 129.9, 129.8(2), 129.8(8), 129.5, 129.3, 125.0, 123.9, 120.1, 115.4, 114.8, 69.3, 55.6, 54.2, 21.7, 21.5. IR (film, ν, cm−1) 2969, 2862, 1598, 1483, 1334, 1326, 1170, 1090, 827. HR-MS (ESI) m/z calcd for C34H29ClN2NaO6S2 [M + Na]+ 683.1053, found 683.1055. (E)-1-(4-Ethylphenyl)-5-methoxy-4-(phenyldiazenyl)-3(phenylsulfonyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4w, Major). 102 mg, 43%; red solid, mp 162−163 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.89−7.84 (m, 2H), 7.82− 7.78 (m, 2H), 7.64 (d, J = 7.6 Hz, 1H), 7.59−7.56 (m, 3H), 7.53−7.46 (m, 3H), 7.38−7.33 (m, 3H), 7.25−7.19 (m, 4H), 6.44 (s, 1H), 5.96 (s, 1H), 3.17 (s, 3H), 2.79−2.73 (m, 2H), 1.32 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 152.6, 148.3, 147.5, 139.6, 136.3, 136.0, 135.7, 134.5, 132.5, 131.2, 131.1, 130.7, 130.3, 130.1, 129.2, 129.0, 128.7, 128.3, 128.0, 127.8, 123.8, 123.2, 69.4, 54.5, 28.9, 15.2. IR (film, ν, cm−1) 2943, 2821, 1613, 1582, 1447, 1343, 1161, 1076, 776. HR-MS (ESI) m/z calcd for C33H28N2NaO5S2 [M + Na]+ 619.1337, found 619.1335. (E)-5,7-Dimethoxy-1-phenyl-4-(phenyldiazenyl)-3-(phenylsulfonyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4y, Major). 115 mg, 48%; red solid, mp 163−164 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.88−7.84 (m, 2H), 7.80 (d, J = 8.0 Hz, 2H), 7.60−7.56 (m, 3H), 7.55−7.49 (m, 5H), 7.41− 7.36 (m, 1H), 7.25−7.19 (m, 2H), 7.15 (d, J = 2.8 Hz, 1H), 7.08 (d, J = 8.8 Hz, 1H), 6.74−6.70 (m, 1H), 6.45 (s, 1H), 5.94 (s, 1H), 3.88 (s, 3H), 3.14 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 161.8, 152.6, 148.1, 137.8, 137.3, 136.3, 136.2, 134.5, 132.6, 131.4, 130.7, 130.5, 130.1, 129.4(1), 129.4(6), 129.2, 128.7, 126.4, 123.8, 123.6, 120.2, 115.2, 114.8, 69.3, 55.5, 54.1. IR (film, ν, cm−1) 3063, 2965, 1612, 1581, 1446, 1327, 1172, 1079, 780. HR-MS (ESI) m/z calcd for C32H26N2NaO6S2 [M + Na]+ 621.1130, found 621.1125. (E)-4-((4-Methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)-2,2-dioxido-1-phenyl-3,5-dihydronaphtho[1,2-c]thiophen-5-yl acetate (4z, Major). 144 mg, 55%; red solid, mp 178−179 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.83 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.58−7.51 (m, 4H), 7.49− 7.39 (m, 6H), 7.23−7.18 (m, 1H), 7.04−6.99 (m, 2H), 6.75 (d, J = 8.4 Hz, 1H), 6.55 (d, J = 8.8 Hz, 1H), 6.40 (s, 1H), 6.21 (s, 1H), 3.96 (s, 3H), 3.66 (s, 3H), 3.59 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 164.1, 163.7, 146.3, 143.8, 138.2, 136.9, 132.2, 131.8, 131.7, 130.8, 130.7, 130.5, 129.4, 129.2, 128.9, 128.6, 127.5, 127.3, 127.1, 126.2, 126.0, 114.5, 114.2, 114.0, 65.0, 55.8, 55.5(1), 55.5(7). IR (film, ν, cm−1) 2933, 2840, 1637, 1617, 1594, 1496, 1320, 1263, 1144, 835. HR-MS (ESI) m/z calcd for C34H28N2NaO8S2 [M + Na]+ 679.1185, found 679.1182.

(E)-7-Chloro-5-methoxy-1-(4-methoxyphenyl)-4-((4methoxyphenyl)diazenyl)-3-((4-methoxyphenyl)sulfonyl)3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4r, Major). 169 mg, 61%; red solid, mp 179−180 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.78 (d, J = 8.8 Hz, 2H), 7.65−7.60 (m, 3H), 7.56 (d, J = 8.8 Hz, 2H), 7.25 (d, J = 8.4 Hz, 1H), 7.21−7.17 (m, 1H), 7.07−7.02 (m, 4H), 6.60 (d, J = 8.8 Hz, 2H), 6.32 (s, 1H), 5.86 (s, 1H), 3.96 (s, 3H), 3.90 (s, 3H), 3.59 (s, 3H), 3.14 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 164.3, 163.6, 161.8, 147.4, 146.9, 139.1, 137.6, 137.0, 134.7, 132.2, 132.0, 130.6, 129.7, 128.8, 128.6, 127.2, 126.9, 126.1, 117.8, 115.1, 114.3, 114.0, 69.0, 55.8, 55.5, 54.6. IR (film, ν, cm−1) 2947, 2839, 1597, 1577, 1496, 1332, 1256, 1166, 837. HR-MS (ESI) m/z calcd for C34H29ClN2NaO8S2 [M + Na]+ 715.0952, found 715.0961. (E)-4-((4-Ethoxyphenyl)diazenyl)-3-((4-ethoxyphenyl)sulfonyl)-5-methoxy-1-phenyl-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4s, Major). 136 mg, 52%; red solid, mp 180−181 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.79 (d, J = 8.8 Hz, 2H), 7.65−7.59 (m, 5H), 7.56−7.47 (m, 4H), 7.22−7.15 (m, 2H), 7.03 (d, J = 8.8 Hz, 2H), 6.57 (d, J = 8.8 Hz, 2H), 6.36 (s, 1H), 5.92 (s, 1H), 4.22−4.16 (m, 2H), 3.86−3.79 (m, 1H), 3.70−3.62 (m, 1H), 3.12 (s, 3H), 1.52 (t, J = 7.0 Hz, 3H), 1.34 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 163.8, 163.0, 148.1, 146.9, 138.7, 136.5, 135.8, 132.2, 131.1, 130.7(1), 130.7(6), 130.6, 129.8, 129.4, 128.2(4), 128.2(8), 127.7, 126.9, 126.4, 126.1, 114.7, 114.5, 114.4, 69.2, 64.1, 63.9, 54.2, 14.7, 14.4. IR (film, ν, cm−1) 2978, 2933, 1593, 1574, 1494, 1321, 1254, 1145, 835. HR-MS (ESI) m/z calcd for C35H32N2NaO7S2 [M + Na]+ 679.1549, found 679.1554. (E)-4-((4-Ethoxyphenyl)diazenyl)-3-((4-ethoxyphenyl)sulfonyl)-5-methoxy-1-(p-tolyl)-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4t, Major). 153 mg, 57%; red solid, mp 184−185 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.81−7.76 (m, 2H), 7.65−7.59 (m, 3H), 7.51−7.46 (m, 3H), 7.34−7.31 (m, 2H), 7.26 (d, J = 7.2 Hz, 1H), 7.22−7.16 (m, 1H), 7.05−7.01 (m, 2H), 6.55−6.58 (m, 2H), 6.34 (s, 1H), 5.92 (s, 1H), 4.22−4.16 (m, 2H), 3.86−3.78 (m, 1H), 3.70−3.63 (m, 1H), 3.11 (s, 3H), 2.46 (s, 3H), 1.52 (t, J = 7.0 Hz, 3H), 1.35 (t, J = 7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 163.8, 162.9, 147.9, 146.9, 141.1, 140.0, 136.1, 135.7, 132.2, 131.0, 130.6, 130.4, 130.1, 129.9, 128.3, 128.2, 127.7, 126.9, 126.1, 123.3, 114.7, 114.4, 69.2, 64.1, 63.9, 54.1, 21.6, 14.7, 14.4. IR (film, ν, cm−1) 2981, 2931, 1599, 1574, 1494, 1322, 1254, 1146, 835. HR-MS (ESI) m/z calcd for C36H34N2NaO7S2 [M + Na]+ 693.1705, found 693.1708. (E)-4-((3,4-Dimethoxyphenyl)diazenyl)-3-((3,4dimethoxyphenyl)sulfonyl)-5-methoxy-1-(p-tolyl)-3,5dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4u, Major). 174 mg, 62%; red solid, mp 187−188 °C; 1H NMR (400 MHz, CDCl3; δ, ppm) 7.63−7.59 (m, 2H), 7.46−7.44 (m, 3H), 7.40 (d, J = 2.0 Hz, 1H), 7.32 (s, 1H), 7.30 (s, 1H), 7.25−7.16 (m, 3H), 7.04 (d, J = 8.4 Hz, 1H), 6.96 (d, J = 2.4 Hz, 1H), 6.51 (d, J = 8.8 Hz, 1H), 6.39 (s, 1H), 5.94 (s, 1H), 4.05 (s, 3H), 4.04 (s, 3H), 3.68 (s, 3H), 3.44 (s, 3H), 3.13 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3; δ, ppm) 154.0, 153.5, 149.7, 148.6, 148.0, 147.2, 141.3, 139.1, 135.9, 135.6, 131.0, 130.6, 130.3, 130.2, 130.0, 128.5, 128.4, 127.7, 126.9, 124.9, 123.1, 122.5, 111.8, 110.4, 110.2, 102.9, 69.2, 56.3, 56.2, 56.0, 55.8, 54.2, 21.6. IR (film, ν, cm−1) 2964, 2839, 1596, 1500, 1332, 1263, 1145, 1024, 832. HR-MS (ESI) m/z calcd for C36H34N2NaO9S2 [M + Na]+ 725.1603, found 725.1601. (E)-1-(4-Chlorophenyl)-5,7-dimethoxy-4-(p-tolyldiazenyl)3-tosyl-3,5-dihydronaphtho[1,2-c]thiophene 2,2-dioxide (4v,

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acsomega.7b01789. X-ray crystal data (CIF) for 4a (PDF) Crystallographic data (CIF) 1489

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

■

thiophene 1,1-dioxide sulfonamides. Bioorg. Med. Chem. Lett. 2005, 15, 4872−4876. (c) Villar, R.; Encio, I.; Migliaccio, M.; Gil, M. J.; MartinezMerino, V. Synthesis and cytotoxic activity of lipophilic sulphonamide derivatives of the benzo[b]thiophene 1,1-dioxide. Bioorg. Med. Chem. 2004, 12, 963−968. (5) (a) Grigg, R.; Scott, R.; Stevenson, P. Rhodium-catalysed [2 + 2 + 2] cycloadditions of acetylenes. J. Chem. Soc., Perkin Trans. 1 1988, 1357−1364. (b) Tahara, Y.-K.; Gake, M.; Matsubara, R.; Shibata, T. Catalytic [2 + 2 + 2] cycloaddition of benzothiophene dioxides with α,ω-diynes for the synthesis of condensed polycyclic compounds. Org. Lett. 2014, 16, 5980−5983. (6) (a) Charlton, J. L.; Durst, T. Photochemical synthesis of αoxygenated benzothiophenedioxides. Tetrahedron Lett. 1984, 25, 2663− 2666. (b) Charlton, J. L.; Koh, K. Substituent effects on the photochemistry of o-tolualdehydes. Tetrahedron Lett. 1988, 29, 5595− 5598. (7) (a) Zafrani, Y.; Gottlieb, H. E.; Sprecher, M.; Braverman, S. Sequential intermediates in the base-catalyzed conversion of bis(πconjugated propargyl) sulfones to 1,3-dihydrobenzo- and naphtho[c]thiophene-2,2-dioxides. J. Org. Chem. 2005, 70, 10166−10168. (b) Braverman, S.; Zafrani, Y.; Gottlieb, H. E. Base catalyzed rearrangement of π-conjugated sulfur and selenium bridged propargylic systems. Tetrahedron 2001, 57, 9177−9185. (c) Maji, M.; Mallick, D.; Mondal, S.; Anoop, A.; Bag, S. S.; Basak, A.; Jemmis, E. D. Selectivity in Garratt-Braverman cyclization: An experimental and computational study. Org. Lett. 2011, 13, 888−891. (d) Basak, A.; Das, S.; Mallick, D.; Jemmis, E. D. Which one is preferred: Myers-Saito cyclization of eneyne-allene or Garratt-Braverman cyclization of conjugated bisallenic sulfone? A theoretical and experimental study. J. Am. Chem. Soc. 2009, 131, 15695−15704. (e) Zafrani, Y.; Cherkinsky, M.; Gottlieb, H. E.; Braverman, S. A new approach to the synthesis of 2-vinylthiophenes and selenophenes; competition between free radical and anionic cycloaromatization of bridged di- and tetrapropargylic sulfides and selenides. Tetrahedron 2003, 59, 2641−2649. (f) Mukherjee, R.; Mondal, S.; Basak, A.; Mallick, D.; Jemmis, E. D. Reactivity of bispropargyl sulfones under basic conditions: Interplay between Garratt-Braverman and Schmittel/Myers-Saito cyclization pathway. Chem. - Asian J. 2012, 7, 957−965. (g) Mitra, T.; Das, J.; Maji, M.; Das, R.; Das, U. K.; Chattaraj, P. K.; Basak, A. A one-pot Garratt-Braverman cyclization and Scholl oxidation route to acene-helicene hybrids. RSC Adv. 2013, 3, 19844− 19848. (h) Ghosh, D.; Biswas, S.; Ghosh, K.; Basak, A. GarrattBraverman cyclization on basic alumina: a green protocol with improved selectivity. Tetrahedron Lett. 2014, 55, 3934−3937. (i) Das, J.; Bag, S. S.; Basak, A. Mechanistic studies on Garratt-Braverman cyclization: The diradical-cycloaddition puzzle. J. Org. Chem. 2016, 81, 4623−4632. (8) (a) Babu, S. D.; Hrytsak, M. D.; Durst, T. Intramolecular rhodium carbenoid insertions into aromatic C-H bonds. Preparation of 1,3dihydrothiophene 2,2-dioxides fused onto aromatic rings. Can. J. Chem. 1989, 67, 1071−1076. (b) Hrytsak, M.; Etkin, N.; Durst, T. Intramolecular rhodium carbenoid insertions into aromatic C-H bonds. Preparation of 1-carboalkoxy-1,3-dihydrobenzo[c]thiophene 2,2-dioxides. Tetrahedron Lett. 1986, 27, 5679−5682. (9) Ciufolini, M. A.; Qi, H. B.; Browne, M. E. Intramolecular arylations of soft enolates catalyzed by zerovalent palladium. J. Org. Chem. 1988, 53, 4149−4151. (10) (a) Luo, Y.; Pan, X.-L.; Chen, C.; Yao, L.-Q.; Wu, J. An unexpected reaction of 2-alkynylaryldiazonium tetrafluoroborate with sulfur dioxide. Chem. Commun. 2015, 51, 180−182. (b) Mao, R.-Y.; Zheng, D.-Q.; Xia, H.-G.; Wu, J. Copper(I)-catalyzed sulfonylation of (2-alkynylaryl)boronic acids with DABSO. Org. Chem. Front. 2016, 3, 693−696. (11) Emmett, E. J.; Willis, M. C. The development and application of sulfur dioxide surrogates in synthetic organic chemistry. Asian J. Org. Chem. 2015, 4, 602−611. (12) (a) Woolven, H.; González-Rodríguez, C.; Marco, I.; Thompson, A. L.; Willis, M. C. DABCO-Bis(sulfur dioxide), DABSO, as a convenient source of sulfur dioxide for organic synthesis: Utility in sulfonamide and sulfamide preparation. Org. Lett. 2011, 13, 4876−4878. (b) Deeming, A. S.; Russell, C. J.; Willis, M. C. Palladium(II)-catalyzed

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected] (W.-J.H.). *E-mail: [email protected] (S.-J.T.). *E-mail: [email protected] (B.J.). ORCID

Guigen Li: 0000-0002-9312-412X Bo Jiang: 0000-0003-3878-515X Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS We are grateful for financial support from the NSFC (Nos. 216020872 and 1472071), PAPD of Jiangsu Higher Education Institutions, the Outstanding Youth Fund of JSNU (YQ2015003), NSF of Jiangsu Province (BK20151163 and BK20160212), and the Qing Lan Project of Jiangsu Education Committee.

■

REFERENCES

(1) (a) Harrak, Y.; Casula, G.; Basset, J.; Rosell, G.; Plescia, S.; Raffa, D.; Cusimano, M. G.; Pouplana, R.; Pujol, M. D. Synthesis, antiinflammatory activity, and in vitro antitumor effect of a novel class of cyclooxygenase inhibitors: 4-(Aryloyl)phenyl methyl sulfones. J. Med. Chem. 2010, 53, 6560−6571. (b) Smith, D. A.; Jones, R. M. The sulfonamide group as a structural alert: a distorted story. Curr. Opin. Drug Discovery Dev. 2008, 11, 72−79. (c) Noutoshi, Y.; Ikeda, M.; Saito, T.; Osada, H.; Shirasu, K. Sulfonamides identified as plant immunepriming compounds in high-throughput chemical screening increase disease resistance in Arabidopsis thaliana. Front. Plant Sci. 2012, 3, No. 245. (d) Drews, J. Drug discovery: A historical perspective. Science 2000, 287, 1960−1963. (2) (a) Valente, C.; Guedes, R. C.; Moreia, R.; Iley, J.; Gut, J.; Rosenthal, P. J. Dipeptide vinyl sultams: Synthesis via the Wittig-Horner reaction and activity against papain, falcipain-2 and Plasmodium falciparum. Bioorg. Med. Chem. Lett. 2006, 16, 4115−4119. (b) Zhuang, L.; Wai, J. S.; Embrey, M. W.; Fisher, T. E.; Egbertson, M. S.; Payne, L. S.; Guare, J. P.; Vacca, J. P.; Hazuda, D. J.; Felock, P. J.; Wolfe, A. L.; Stilmock, K. A.; Witmer, M. V.; Moyer, G.; Schleif, W. A.; Gabryelski, L. J.; Leonard, Y. M.; Lynch, J. J.; Michelson, S. R.; Young, S. D. Design and synthesis of 8-hydroxy-[1,6]naphthyridines as novel inhibitors of HIV-1 integrase in vitro and in infected cells. J. Med. Chem. 2003, 46, 453−456. (c) Misu, Y.; Togo, H. Novel preparation of 2,1-benzothiazine derivatives from sulfonamides with [hydroxy(tosyloxy)iodo]arenes. Org. Biomol. Chem. 2003, 1, 1342−1346. (d) Ahn, K. H.; Kim, S. K.; Ham, C. Evaluation of chiral benzosultams as auxiliaries in asymmetric azidation reactions. Tetrahedron Lett. 1998, 39, 6321−6322. (e) Wells, G. J.; Tao, M.; Josef, K. A.; Bihovsky, R. 1,2-Benzothiazine 1,1-dioxide p2-p3 peptide mimetic aldehyde calpain I inhibitors. J. Med. Chem. 2001, 44, 3488−3503. (3) (a) Chen, S.; Yang, Y.; Wu, Y.; Tian, H.; Zhu, W. Multi-addressable photochromic terarylene containing benzo[b]thiophene-1,1-dioxide unit as ethene bridge: multifunctional molecular logic gates on unimolecular platform. J. Mater. Chem. 2012, 22, 5486−5494. (b) Chen, S.; Chen, L.-J.; Yang, H.-B.; Tian, H.; Zhu, W. Light-triggered reversible supramolecular transformations of multi-bisthienylethene hexagons. J. Am. Chem. Soc. 2012, 134, 13596−13599. (4) (a) Kim, S. H.; Tran, M. T.; Ruebsam, F.; Xiang, A. X.; Ayida, B.; McGuire, H.; Ellis, D.; Blazel, J.; Tran, C. V.; Murphy, D. E.; Webber, S. E.; Zhou, Y.; et al. Structure-based design, synthesis, and biological evaluation of 1,1-dioxoisothiazole and benzo[b]thiophene-1,1-dioxide derivatives as novel inhibitors of hepatitis C virus NS5B polymerase. Bioorg. Med. Chem. Lett. 2008, 18, 4181−4185. (b) Innocenti, A.; Villar, R.; Martinez-Merino, V.; Gil, M. J.; Scozzafava, A.; Vullo, D.; Supuran, C. T. Carbonic anhydrase inhibitors: inhibition of cytosolic/tumorassociated carbonic anhydrase isozymes I, II, and IX with benzo[b]1490

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491

Article

ACS Omega

(18) Eugène, F.; Langlois, B.; Laurent, E. N-Ethyldiisopropylamine and sulfur dioxide solutions. 2. Reactions with conjugate acceptors. J. Org. Chem. 1994, 59, 2599−2603. (19) (a) Yang, D.; Huang, B.; Wei, W.; Li, J.; Lin, G.; Liu, Y.; Ding, J.; Sun, P.; Wang, H. Visible-light initiated direct oxysulfonylation of alkenes with sulfinic acids leading to β-ketosulfones. Green Chem. 2016, 18, 5630−5634. (b) Wen, J.; Wei, W.; Xue, S.; Yang, D.; Lou, Y.; Gao, C.; Wang, H. Metal-Free oxidative spirocyclization of alkynes with sulfonylhydrazides leading to 3-sulfonated azaspiro[4,5]trienones. J. Org. Chem. 2015, 80, 4966−4972. (c) Wei, W.; Wen, J.; Yang, D.; Guo, M.; Wang, Y.; You, J.; Wang, H. Direct and metal-free arylsulfonylation of alkynes with sulfonylhydrazides for the construction of 3-sulfonated coumarins. Chem. Commun. 2015, 51, 768−771. (d) Wei, W.; Wen, J.; Yang, D.; Du, J.; You, J.; Wang, H. Catalyst-free direct arylsulfonylation of N-arylacrylamides with sulfinic acids: a convenient and efficient route to sulfonated oxindoles. Green Chem. 2014, 16, 2988−2991. (20) (a) Qiu, J.-K.; Jiang, B.; Zhu, Y.-L.; Hao, W.-J.; Wang, D.-C.; Sun, J.; Wei, P.; Tu, S.-J.; Li, G. Catalytic dual 1,1-H-abstraction/insertion for domino spirocyclizations. J. Am. Chem. Soc. 2015, 137, 8928−8931. (b) Jiang, B.; Li, J.; Pan, Y.-Y.; Hao, W.-J.; Li, G.; Tu, S.-J. Radicalenabled bicyclization cascades of oxygen-tethered 1,7-enynes leading to skeletally diverse polycyclic chromen-2-ones. Chin. J. Chem. 2017, 35, 323−334. (c) Li, J.; Zhang, W.-W.; Wei, X.-J.; Liu, F.; Hao, W.-J.; Wang, S.-L.; Li, G.; Tu, S.-J.; Jiang, B. Radical deaminative ipso-cyclization of 4methoxyanilines with 1,7-enynes for accessing spirocyclohexadienonecontaining cyclopenta[c]quinolin-4-ones. J. Org. Chem. 2017, 82, 6621− 6628. (d) Sun, J.; Qiu, J.-K.; Wu, Y.-N.; Hao, W.-J.; Guo, C.; Li, G.; Tu, S.-J.; Jiang, B. Silver-mediated radical C(sp3)-H biphosphinylation and nitration of β-alkynyl ketones for accessing functional isochromenes. Org. Lett. 2017, 19, 754−757.

synthesis of sulfinates from boronic acids and DABSO: A redox-neutral, phosphine-free transformation. Angew. Chem., Int. Ed. 2016, 55, 747− 750. (c) Lenstra, D. C.; Vedovato, V.; Flegeau, E. F.; Maydom, J.; Willis, M. C. One-pot sulfoxide synthesis exploiting a sulfinyl-dication equivalent generated from a DABSO/trimethylsilyl chloride sequence. Org. Lett. 2016, 18, 2086−2089. (d) Deeming, A. S.; Russell, C. J.; Willis, M. C. Combining organometallic reagents, the sulfur dioxide surrogate DABSO, and amines: A one-pot preparation of sulfonamides, amenable to array synthesis. Angew. Chem., Int. Ed. 2015, 54, 1168−1171. (e) Emmett, E. J.; Hayter, B. R.; Willis, M. C. Palladium-catalyzed synthesis of ammonium sulfinates from aryl halides and a sulfur dioxide surrogate: A gas- and reductant-free process. Angew. Chem., Int. Ed. 2014, 53, 10204−10208. (f) Emmett, E. J.; Hayter, B. R.; Willis, M. C. Palladium-catalyzed three-component diaryl sulfone synthesis exploiting the sulfur dioxide surrogate DABSO. Angew. Chem. 2013, 125, 12911−12915. (13) (a) Tsai, A. S.; Curto, J. M.; Rocke, B. N.; Dechert-Schmitt, A.-M. R.; Ingle, G. K.; Mascitti, V. One-step synthesis of sulfonamides from Ntosylhydrazones. Org. Lett. 2016, 18, 508−511. (b) Liu, T.; Zheng, D.; Ding, Y.; Fan, X.; Wu, J. Synthesis of β-keto sulfones by a catalyst-free reaction of aryldiazonium tetrafluoroborates, sulfur dioxide, and silyl enol ethers. Chem. - Asian J. 2017, 12, 465−469. (c) Xiang, Y.-C.; Kuang, Y.-Y.; Wu, J. Generation of β-halo vinylsulfones through a multicomponent reaction with insertion of sulfur dioxide. Chem. - Eur. J. 2017, 23, 6996−6999. (d) Zhou, K.; Xia, H.; Wu, J. Generation of benzosultams via radical process with the insertion of sulfur dioxide. Org. Chem. Front. 2017, 4, 1121−1124. (e) Waldmann, C.; Schober, O.; Haufe, G.; Kopka, K. A closer look at the bromine-lithium exchange with tert-butyllithium in an aryl sulfonamide synthesis. Org. Lett. 2013, 15, 2954−2957. (f) Wang, X.; Xue, L.-J.; Wang, Z.-Y. A copper-catalyzed three-component reaction of triethoxysilanes, sulfur dioxide, and hydrazines. Org. Lett. 2014, 16, 4056−4058. (g) Chen, C. C.; Waser, J. One-pot, three-component arylalkynyl sulfone synthesis. Org. Lett. 2015, 17, 736−739. (14) (a) Zheng, D.; Yu, J.; Wu, J. Generation of sulfonyl radicals from aryldiazonium tetrafluoroborates and sulfur dioxide: the synthesis of 3sulfonated coumarins. Angew. Chem., Int. Ed. 2016, 55, 11925−11929. (b) Qiu, G.; Zhou, K.; Gao, L.; Wu, J. Insertion of sulfur dioxide via a radical process: an efficient route to sulfonyl compounds. Org. Chem. Front. 2018, DOI: 10.1039/C7QO01073G. (15) (a) Liu, F.; Wang, J.-Y.; Zhou, P.; Li, G.; Hao, W.-J.; Tu, S.-J.; Jiang, B. Merging [2+2] cycloaddition with radical 1,4-addition: metalfree access to functionalized cyclobuta[a]naphthalen-4-ols. Angew. Chem., Int. Ed. 2017, 56, 15570−15574. (b) Huang, M.-H.; Zhu, Y.L.; Hao, W.-J.; Wang, A.-F.; Wang, D.-C.; Liu, F.; Wei, P.; Tu, S.-J.; Jiang, B. Visible-light photocatalytic bicyclization of 1,7-enynes toward functionalized sulfone-containing benzo[a]fluoren-5-ones. Adv. Synth. Catal. 2017, 359, 2229−2234. (c) Hao, W.-J.; Du, Y.; Wang, D.; Jiang, B.; Gao, Q.; Tu, S.-J.; Li, G. Catalytic diazosulfonylation of enynals toward diazoindenes via oxidative radical-triggered 5-exo-trig carbocyclizations. Org. Lett. 2016, 18, 1884−1887. (d) Zhu, Y.-L.; Jiang, B.; Hao, W.-J.; Wang, A.-F.; Qiu, J.-K.; Wei, P.; Wang, D.-C.; Li, G.; Tu, S.-J. A new cascade halosulfonylation of 1,7-enynes toward 3,4-dihydroquinolin-2(1H)-ones via sulfonyl radical-triggered addition/6-exo-dig cyclization. Chem. Commun. 2016, 52, 1907−1910. (e) Shen, Z.-J.; Wu, Y.-N.; He, C.-L.; He, L.; Hao, W.-J.; Wang, A.-F.; Tu, S.-J.; Jiang, B. Stereoselective synthesis of sulfonated 1-indenones via radical-triggered multi-component cyclization of β-alkynyl propenones. Chem. Commun. 2018, 54, 445−448. (16) Wang, A.-F.; Zhou, P.; Zhu, Y.-L.; Hao, W.-J.; Li, G.; Tu, S.-J.; Jiang, B. Metal-free benzannulation of 1,7-diynes toward unexpected 1aroyl-2-naphthaldehydes and their application in fused aza-heterocyclic synthesis. Chem. Commun. 2017, 53, 3369−3372. (17) Jiang, H.; Chen, Y.; Chen, B.; Xu, H.; Wan, W.; Deng, H.; Ma, K.; Wu, S.; Hao, J. Ag-initiated gem-difluoromethylenation of the nitrogen center of arenediazonium salts to gem-difluoromethylene azo compounds. Org. Lett. 2017, 19, 2406−2409. 1491

DOI: 10.1021/acsomega.7b01789 ACS Omega 2018, 3, 1482−1491