Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and

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Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and Arenethiols with Molecular Oxygen as the Sole Oxidant Changliu Wang, Zhenming Zhang, Yongliang Tu, Ying Li, Jiale Wu, and Junfeng Zhao J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02926 • Publication Date (Web): 16 Jan 2018 Downloaded from http://pubs.acs.org on January 16, 2018

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The Journal of Organic Chemistry

Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and Arenethiols with Molecular Oxygen as the Sole Oxidant ** Changliu Wang, Zhenming Zhang, Yongliang Tu, Ying Li, Jiale Wu, Junfeng Zhao** Key Laboratory of Chemical Biology of Jiangxi Province, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, 330022, P. R. China Supporting Information ABSTRACT: A highly efficient palladium-catalyzed oxidative cross-coupling of arylhydrazines and arenethiols with molecular oxygen as the sole oxidant to afford unsymmetrical diaryl sulfides has been developed. The only by-products are nitrogen and water. A broad range of functional groups, even the reactive iodides are tolerated and thus offering opportunity for further functionalization.

Transition metal-catalyzed oxidative cross-coupling reactions have emerged as powerful and general tools for carboncarbon and carbon-heteroatom bonds formation during the past decade.1 However, among these reactions, the formation of carbon-sulfur bond via oxidative cross-coupling of thiols has attracted less attention2 due to the homo coupling of thiols under the oxidative reaction conditions.3 In addition, diaryl sulfides are of great importance as building block in biologically active molecules,4 pharmaceutical,5 and natural products.6 As a consequence, their syntheses have attracted considerable attention.7 Recently, transition metal-catalyzed traditional cross-coupling reactions have been developed to construct sp2 C-S bond.8 Although significant advances have been made along these lines, the development of efficient synthetic methodologies for diaryl sulfides via palladium-catalyzed oxidative cross-coupling still remains a challenging topic. The palladium-catalyzed cross-coupling reaction of aryl thiols with different electrophiles represents one of the most straightforward tools to afford a variety of unsymmetrical diaryl sulfides (Scheme 1, eq 1).9 These classic methods for carbon-sulfur bond formation involve an addition-elimination mechanism by using Pd(0) as catalyst. However, these methods are usually limited in substrate scope and require harsh reaction conditions.10 Compared with Pd(0) catalyzed reactions carried out under inert atmosphere, Pd(II) catalyzed coupling reactions are relatively easy to handle.11 Recently, Pd(II)-catalyzed decarboxylative cross-coupling reaction of benzoic acids with thiols or disulfides using Ag or Cu salts as oxidant to afford diaryl sulfides derivatives is reported (Scheme 1, eq 2).12 Herein, we disclosed a novel and efficient Pd(II)-catalyzed oxidative cross-coupling reaction of arylhydrazines with aryl thiols using O2 as the sole oxidant to give unsymmetrical diaryl sulfides (Scheme 1, eq 3). Arylhydrazines have evolved into environmentally friendly arylation agents for the palladium-catalyzed oxidative crosscoupling reactions because the only side products are water and nitrogen.13 Our group is interested in C-N bond cleavage of arylhydrazines and reported the palladium catalyzed oxidative carbonylation of arylhydrazines with alkynes, phenols and

amines.14 Based on these works, we envisioned that aryl thiols could also react with arylhydrazines to afford the Scheme 1. Synthetic strategies for diaryl sulfides via palladium-catalyzed cross-coupling of arenethiols

corresponding diaryl sulfides through palladium-catalyzed oxidative cross-coupling. With this proposal in mind, we started from testing different palladium catalysts in the oxidative coupling of phenylhydrazine 1a and 4-methoxybenzenethiol 2a with 10 mol % of PPh3, 2 equiv of Na2CO3 in dimethyl sulfoxide (DMSO) at 100 oC for 12 h under balloon pressure of O2 (Table 1). Preliminary screening revealed that Pd(OAc)2 was most effective for this transformation (Table 1, entries 16). Further exploration of ligands disclosed that the ligand is crucial and PCy3 gave the best yield (Table 1, entries 7-12). Base also played an important role in this reaction and Na2CO3 was identified to be the best one among others (Table 1, entries 13-17). In addition, toluene demonstrated a beneficial effect on this reaction (Table 1, entries 18-20). Decrease of reaction temperature has a deleterious effect on the reaction efficiency (Table 1, entry 21). As expected, there is no reaction at all when the experiment was performed under N2 atmosphere (Table 1, entry 23).

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The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Table 1. Optimization of the Reaction Conditionsa

entry catalyst

ligand

Scheme 2. Substrate Scope of Arylhydrazinesa

base

solvent

yield (%)b

1

PdCl2(PPh3)2 PPh3

Na2CO3

DMSO

52

2

PdCl2(dppf)

PPh3

Na2CO3

DMSO

51

3

Pd(PPh3)4

PPh3

Na2CO3

DMSO

58

4

Pd2(dba)3

PPh3

Na2CO3

DMSO

43

5

Pd(TFA)2

PPh3

Na2CO3

DMSO

53

6

Pd(OAc)2

PPh3

Na2CO3

DMSO

70

7

Pd(OAc)2

P(o-Tol)3

Na2CO3

DMSO

27

8

Pd(OAc)2

PCy3

Na2CO3

DMSO

77

9

Pd(OAc)2

P(2-furyl)3 Na2CO3

DMSO

47

10

Pd(OAc)2

Binap

Na2CO3

DMSO

53

11

Pd(OAc)2

1,10-Phen

Na2CO3

DMSO

64

12

Pd(OAc)2

--

Na2CO3

DMSO

trace

13

Pd(OAc)2

PCy3

Cs2CO3

DMSO

73

14

Pd(OAc)2

PCy3

K2CO3

DMSO

75

15

Pd(OAc)2

PCy3

NaOH

DMSO

27

16

Pd(OAc)2

PCy3

Et3N

DMSO

38

17

Pd(OAc)2

PCy3

DBU

DMSO

30

18

Pd(OAc)2

PCy3

Na2CO3

PhMe

82

19

Pd(OAc)2

PCy3

Na2CO3

DMF

46

Next, the palladium-catalyzed oxidative cross-coupling reactions of (4-nitrophenyl)hydrazine hydrochloride (1n) with a variety of aryl thiols were also examined and the results are summarized in Scheme 3. Aryl thiols with a series of electrondonating groups, such as 4-methyl, 4-ethyl, 4-t-butyl, 3methoxy and 3,5-dimethyl, could convert to the corresponding products (3nb-3ng) in good to high yields. Interestingly, the

20

Pd(OAc)2

PCy3

Na2CO3

CF3Ph

67

Scheme 3. Substrate Scope of Arenethiolsa

Pd(OAc)2

PCy3

Na2CO3

PhMe

60

Pd(OAc)2

PCy3

Na2CO3

PhMe

25

Pd(OAc)2

PCy3

Na2CO3

PhMe

trace

21 22 23

c d e

a Reaction conditions: 1 (0.4 mmol), 2a (0.2 mmol), Pd(OAc)2 (5 mol%), PCy3 (10 mol%), Na2CO3 (0.4 mmol), PhMe (2.0 mL) under O2 balloon at 100 oC for 12 h.

a

Reaction condition: 1a (0.4 mmol), 2a (0.2 mmol), base (0.4 mmol), Pd catalyst (5 mol %), ligand (10 mol %), solvent (2.0 mL) at 100 oC for 12 h, with a O2 balloon. bIsolated yield. c60 oC. dUnder air. eUnder N2.

With the optimized reaction conditions in hand (Table 1, entry 18), we explored the scope of this oxidative crosscoupling reaction between various arylhydrazines and 4methoxybenzenethiol. As shown in Scheme 2, a broad range of arylhydrazines with ortho, meta, or para alkyl substituents reacted equally well with 4-methoxybenzenethiol 2a to afford the corresponding products (3ba-3fa) in 77-84% yields. Even the steric demanding dimethyl substituents were tolerated to furnish the desired products (3ga and 3ha) in high yields. It should be noted that the reaction could be conducted in the presence of halogen substituents (3ia-3la) and the carbonhalogen bonds, which are reactive under conventional palladium catalyzed cross-coupling conditions, were intact. Moreover, diaryl sulfides containing strong electron-withdrawing (3na) substituent could also be prepared by using this method. In addition, (4-(trifluoromethoxy)phenyl)hydrazine and naphthalen-2-ylhydrazine could afford the coupling products (3ma and 3oa) in high yields. Disappointingly, no target products were obtained when heterocyclic hydrazines were used.

a Reaction conditions: 1n (0.4 mmol), 2 (0.2 mmol), Pd(OAc)2 (5 mol%), PCy3 (10 mol%), Na2CO3 (0.4 mmol), PhMe (2.0 mL) under O2 balloon at 100 oC for 12 h.

halogen substituents such as -Cl, and -Br, could be tolerated in this reaction and afforded the diaryl sulfides products (3nh and 3ni) in 79% and 83% yields, respectively, and thus offering an advantage for further manipulation by conventional


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The Journal of Organic Chemistry coupling reaction. Then, (4-(trifluoromethoxy)phenyl)hydrazine and naphthalen-2-ylhydrazine were also converted to the coupling products (3nj and 3nk) in good yields. However, no reaction occurred when 4-nitrobenzenethiol (3nl) was employed as substrate. Scheme 4. Synthetic Application

ger (Scheme 5, eq 3). All of these experiments indicating that a radical pathway was not likely to be involved in this reaction. A possible reaction mechanism for the palladium-catalyzed oxidative cross-coupling reaction of arylhydrazines with arenethiols was proposed in Scheme 6. Aryl palladium species A was initially produced by the oxidative C-N bond cleavage of arylhydrazine with Pd(OAc)2 under O2.13a On the other hand, arenethiols reacted with base to yield the benzenethiolate intermediate B. Then, the active palladium species C might be formed through transmetallation of species A with intermediate B. Finally, reductive elimination affords the coupling product D and regenerated the Pd catalyst to close the catalytic cycle. Scheme 6. Proposed Reaction Mechanism

The potential application of this oxidative cross-coupling reaction was illustrated in Scheme 4. The diaryl sulfide 3ka could be prepared efficiently from the palladium-catalyzed cross-coupling of 1k and 2a (Scheme 4, path a). Interestingly, the cross-coupling of 2l and 1p could also offer the same diaryl sulfide 3ka in good yield (Scheme 4, path b). Such feature will be remarkably useful when one coupling partner is expensive or not available. Furthermore, product 3ka could efficiently undergo Hiyama reaction and Suzuki reaction to afford the corresponding coupling product 6a in 77% and 85% yields, respectively (Scheme 4, path c and d). Scheme 5. Control Experiments

■ CONCLUSIONS In summary, we have developed the first palladium-catalyzed oxidative cross-coupling of arylhydrazines and aryl thiols with O2 as the sole oxidant to afford diaryl sulfides in good to high yields. A variety of functional groups including halide substituents which are reactive under conventional transition metal catalyzed cross coupling reaction conditions are tolerated. This method provides a highly efficient approach to unsymmetrical diaryl sulfides.

■ EXPERIMENTAL SECTION

To probe whether a transition metal-free radical pathway was involved in this reaction mechanism,15 several experiments were performed in Scheme 5. When 1a was treated with 2a in the absence of Pd catalyst, only small amount of the desired product 3aa was obtained (Scheme 5, eq 1). A significant lower yield of 3aa was observed when disulfide 4a was used under the standard conditions (Scheme 5, eq 2). Furthermore, control experiment with 2,2,6,6-tetramethyl-1piperidinyloxy (TEMPO) demonstrated that the reaction efficiency was kept intact in the presence of as the radical scaven-

All reactions were carried out in oven-dried glassware. All arylhydrazine hydrochloride and arenethiols were obtained from commercial sources and used without further purification. All the reactions were monitored by thin-layer chromatography (TLC); products were purified by using silica gel column chromatography. 1H/13C NMR spectra were recorded on Bruker avance 400 MHz and Bruker AMX 400 MHz spectrometer at 400/100 MHz, respectively, in CDCl3. unless otherwise stated, using either TMS or the undeuterated solvent residual signal as the reference. Chemical shifts are given in ppm and are measured relative to CDCl3 as an internal standard. Mass spectra were obtained by the electrospray ionization time-of-flight (ESI-TOF) mass spectrometry. Flash column chromatography purification of compounds was carried out by gradient elution using ethyl acetate (EA) in light petroleum ether (PE).

General procedure for the Preparation of unsymmetrical diaryl sulfides: Arylhydrazine hydrochloride (0.4 mmol, 2.0 equiv), Pd(OAc)2 (1.1 mg, 0.01 mmol, 5 mol %), PCy3



(5.6 mg, 0.02 mmol 10 mol %), and Na2CO3 (42.4 mg, 0.4 mmol, 2.0 equiv) were combined in an oven-dried Schlenk tube equipped with a stir bar. After the addition of all the solid reagent, the balloon filled with O2 was connected to the Schlenk tube via a syringe. The Schlenk tube was heated at 100°C for 12 h. After the reaction was completed (monitored by TLC), the contents were cooled to room temperature and then the balloon gas was released. The solvent was removed under reduced pressure to give crude products, which were purified by column chromatography (inner diameter: 3.0 cm and length: 30 cm) over silica gel (PE/ EA) to afford pure products. (4-Methoxyphenyl)(phenyl)sulfane (3aa).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3aa as a pale yellow oil (35.4 mg, 82%); Rf = 0.40 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2945, 2834, 1588, 1487, 1245, 1023, 826 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.8 Hz, 2H), 7.31−7.01 (m, 5H), 6.89 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 159.9, 138.6, 135.3, 128.9, 128.3, 125.8, 124.4, 115.0, 55.4. (4-Methoxyphenyl)(p-tolyl)sulfane (3ba).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ba as a colorless oil (35.4 mg, 77%); Rf = 0.60 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2936, 2839, 1593, 1497, 1244, 1032, 826 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.46−7.29 (m, 2H), 7.23−7.14 (m, 1H), 7.14−7.03 (m, 2H), 7.00 (d, J = 7.6, 1H), 6.95−6.82 (m, 2H), 3.82 (s, 3H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.6, 137.2, 137.0, 134.5, 130.2, 129.2, 126.5, 126.2, 124.0, 115.01, 55.4, 20.3. (4-Methoxyphenyl)(m-tolyl)sulfane (3ca).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ca as a colorless oil (38.7 mg, 79%); Rf = 0.45 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2925, 2834, 1588, 1497, 1250, 1028, 826 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.48−7.34 (m, 2H), 7.13 (t, J = 7.7 Hz, 1H), 7.03 (s, 1H), 6.97 (t, J = 6.7 Hz, 2H), 6.92−6.85 (m, 2H), 3.83 (s, 3H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8, 138.8, 138.2, 135.1, 129.1, 128.8, 126.8, 125.6, 124.7, 115.0, 55.4, 21.3. (4-Methoxyphenyl)(o-tolyl)sulfane (3da).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3da as a colorless oil (41.2 mg, 84%); Rf = 0.50 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 3011, 2920, 1593, 1492, 1244, 1028, 805 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.9 Hz, 2H), 7.14 (d, J = 8.2 Hz, 2H), 7.07 (d, J = 8.1 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.5, 136.2, 134.3, 134.3, 129.8, 129.4, 125.7, 114.9, 55.4, 21.0. (4-Ethylphenyl)(4-methoxyphenyl)sulfane (3ea). Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ea as a colorless oil (41.2 mg, 84%); Rf = 0.60 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2965, 2839, 1593, 1492, 1245, 1032, 832 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.36 (d, J = 8.8 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 7.08 (d, J = 8.2 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 3.79 (s, 3H), 2.59 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.5, 142.5, 134.7, 134.5, 129.3, 128.6, 125.6, 114.9, 55.4, 28.4, 15.5. HRMS (ESI-TOF): calcd for C15H17OS [M + H]+: 245.0995, found: 245.0992 (4-(tert-Butyl)phenyl)(4-methoxyphenyl)sulfane (3fa).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3fa as a colorless oil (44.6 mg, 82%); Rf = 0.60 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2965, 2899, 1593, 1492, 1250, 1032, 821 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.39 (d, J = 8.9 Hz, 2H), 7.26 (d, J = 8.6 Hz, 2H), 7.13 (d, J = 8.6 Hz, 2H), 6.87 (d, J = 8.9 Hz, 2H), 3.80 (s, 3H), 1.28 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 159.6, 149.2, 134.8, 134.7, 128.6, 126.0, 125.2, 114.9, 55.4, 34.4, 31.3. (3,4-Dimethylphenyl)(4-methoxyphenyl)sulfane (3ga). Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ga as a colorless oil (39.1 mg, 80%); Rf = 0.45 (PE/EA = 50:1, v/v) ; IR (KBr) ν̃ 2940, 2834, 1587, 1497, 1239, 1033, 826 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J = 8.8 Hz, 2H), 7.16−6.94 (m, 3H), 6.88 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H) , 2.23 (s, 3H) , 2.21 (s, 3H);

13

C NMR (100 MHz, CDCl3) δ 159.4, 137.4, 135.0, 134.4, 134.2, 130.8, 130.3, 127.1, 126.0, 114.9, 55.4, 19.7, 19.3; HRMS (ESITOF): calcd for C15H17OS [M + H]+: 245.0995, found: 245.0992. (3,5-Dimethylphenyl)(4-methoxyphenyl)sulfane (3ha).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ha as a colorless oil (37.6 mg, 77%); Rf = 0.50 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 2925, 2834, 1593, 1497, 1250, 1038, 832 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.52−7.32 (m, 2H), 6.97−6.87 (m, 2H), 6.84 (s, 2H), 6.81 (d, J = 0.5 Hz, 1H), 3.83 (s, 3H), 2.25 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 159.7, 138.6, 137.8, 135.0, 127.9, 126.3, 124.9, 114.9, 55.4, 21.2. (4-Fluorophenyl)(4-methoxyphenyl)sulfane (3ia).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ia as a colorless oil (33.2 mg, 71%); Rf = 0.60 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 2940, 2834, 1588, 1493, 1420, 1033, 826; 1H NMR (400 MHz, CDCl3) δ 7.35 (d, J = 8.8 Hz, 2H), 7.23−7.16 (m, 2H), 6.99−6.91 (m, 2H), 6.87 (d, J = 8.8 Hz, 2H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.6 (d, JCF = 245.9 Hz), 159.7, 134.5, 133.1 (d, JCF = 3.3 Hz), 131.1 (d, JCF = 8.0 Hz), 125.3, 116.1 (d, JCF = 22.0 Hz), 115.0, 55.4. (4-Chlorophenyl)(4-methoxyphenyl)sulfane (3ja).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ja as a colorless oil (37.0 mg, 74%); Rf = 0.60 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 3096, 2965, 1593, 1502, 1330, 1083, 851 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.40 (d, J = 8.8 Hz, 2H), 7.19 (d, J = 8.7 Hz, 2H), 7.08 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 160.1, 137.4, 135.5, 131.7, 129.4, 129.0, 123.9, 115.2, 55.4. (4-Bromophenyl)(4-methoxyphenyl)sulfane (3ka).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ka as a yellow oil (43.6 mg, 74%); Rf = 0.55 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 3091, 2960, 1593, 1502, 1335, 1084, 851 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.41 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 7.01 (d, J = 8.6 Hz, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.83 (s, 3H); 13 C NMR (100 MHz, CDCl3) δ 160.1, 138.2, 135.6, 131.9, 129.5, 123.6, 119.4, 115.2, 55.4. (4-Iodophenyl)(4-methoxyphenyl)sulfane (3la).18 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3la as a colorless oil (56.3 mg, 77%); Rf = 0.60 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 2936, 2830, 1593, 1492, 1250, 1033, 852 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.52 (d, J = 8.5 Hz, 2H), 7.41 (d, J = 8.8 Hz, 2H), 6.89 (dd, J1 = 14.7, J2 = 8.7 Hz, 4H), 3.83 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.2, 139.2, 137.8, 135.8, 129.6, 123.3, 115.2, 90.2, 55.4. (4-Methoxyphenyl)(4-(trifluoromethoxy)phenyl)sulfane (3ma).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ma as a colorless oil (48.0 mg, 80%); Rf = 0.60 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 2940, 2834, 1588, 1493, 1255, 1033, 832; 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 8.8 Hz, 2H), 7.18−7.10 (m, 2H), 7.11−7.00 (m, 2H), 6.91 (d, J = 8.8 Hz, 2H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.2, 147.2, 137.7, 135.7, 129.1, 123.6, 121.5 (JCF = 256.0), 119.2, 115.2, 55.4. (4-Methoxyphenyl)(4-nitrophenyl)sulfane (3na).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3na as a yellow solid (39.2 mg, 74%); Rf = 0.60 (PE/EA = 50:1, v/v); mp 62−63 oC; IR (KBr) ν̃ 2930, 2834, 1593, 1497, 1240, 1023, 751 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 9.0 Hz, 2H), 7.48 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 6.99 (d, J = 8.8 Hz, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 161.1, 150.0, 145.1, 137.1, 125.6, 124.0, 120.2, 115.7, 55.5. (4-Methoxyphenyl)(naphthalen-2-yl)sulfane (3oa).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3oa as a white solid (41.9 mg, 80%); Rf = 0.40 (PE/EA = 50:1, v/v); mp 67−69 oC; IR (KBr) ν̃ 2930, 2834, 1593, 1493, 1239, 1023, 826 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.80−7.74 (m, 1H), 7.74−7.64 (m, 2H), 7.61 (d, J = 1.3 Hz, 1H), 7.51−7.37 (m, 4H),


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The Journal of Organic Chemistry 7.31−7.30 (m, 1H), 6.99−6.88 (m, 2H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9, 135.9, 135.2, 133.8, 131.8, 128.5, 127.7, 127.2, 126.8, 126.5, 126.5, 125.6, 124.5, 115.1, 55.4. (4-Nitrophenyl)(phenyl)sulfane (3nb).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nb as a yellow solid (37.9 mg, 82%); mp 55−56 oC; Rf = 0.40 (PE/EA = 50:1, v/v); IR (KBr) ν̃ 3057, 2925, 1568, 1512, 1336, 1078, 847 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.06 (d, J = 9.0 Hz, 2H), 7.55−7.53 (m, 2H), 7.46−7.45 (m, 3H), 7.18 (d, J = 9.0 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 148.5, 145.4, 134.7, 130.6, 130.0, 129.7, 126.8, 124.0. (4-Nitrophenyl)(p-tolyl)sulfane (3nc).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nc as a yellow solid (40.2 mg, 82%); Rf = 0.50 (PE/EA = 50:1, v/v); mp 79−81 oC; IR (KBr) ν̃ 3445, 2920, 1578, 1508, 1341, 1084, 806 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 9.0 Hz, 2H), 7.43 (d, J = 8.1 Hz, 2H), 7.26 (d, J = 7.7 Hz, 2H), 7.13 (d, J = 9.0 Hz, 2H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 149.3, 145.2, 140.2, 135.1, 130.9, 126.6, 126.2, 124.0, 21.3. (4-Ethylphenyl)(4-nitrophenyl)sulfane (3nd).18 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nd as a yellow solid (41.4 mg, 80%); Rf = 0.40 (PE/EA = 50:1, v/v); mp 87−88 o C; IR (KBr) ν̃ 3090, 2950, 1580, 1505, 1351, 1077, 850 cm-1; 1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 9.0 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.21 (d, J = 8.3 Hz, 2H), 7.06 (d, J = 9.1 Hz, 2H), 2.63 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H); 13C NMR (100MHz, CDCl3) δ 148.3, 145.4, 144.2, 134.1, 128.6, 125.8, 125.2, 123.0, 27.6, 14.2. (4-(tert-Butyl)phenyl)(4-nitrophenyl)sulfane (3ne).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ne as a colorless solid (43.1 mg, 75%); Rf = 0.40 (PE/EA = 50:1, v/v); mp 65−66 oC; IR (KBr) ν̃ 3097, 2945, 1578, 1508, 1331, 1078, 841 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.05 (d, J = 8.9 Hz, 2H), 7.47 (s, 4H), 7.16 (d, J = 9.0 Hz, 2H), 1.36 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 153.3, 149.1, 145.2, 134.7, 127.1, 126.7, 126.4, 124.0, 34.9, 31.2. (3-Methoxyphenyl)(4-nitrophenyl)sulfane (3nf).16 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nf as a yellow solid (43.3 mg, 83%); Rf = 0.45 (PE/ EA = 50:1, v/v); mp 78−80 o C; IR (KBr) ν̃ 3445, 2961, 1583, 1502, 1331, 1078, 857 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 9.0 Hz, 2H), 7.36 (t, J = 8.0 Hz, 1H), 7.21 (d, J = 9.0 Hz, 2H), 7.12 (d, J = 7.7 Hz, 1H), 7.09−7.04 (m, 1H), 7.02−6.93 (m, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 160.6, 148.2, 145.5, 131.6, 130.8, 126.9, 126.7, 124.1, 119.6, 115.6, 55.5. (3,5-Dimethylphenyl)(4-nitrophenyl)sulfane (3ng).19 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ng as a yellow solid (39.9 mg, 77%); Rf = 0.5 (PE/ EA = 50:1, v/v); mp 98−100 oC; IR (KBr) ν̃ 2930, 2829, 1593, 1493, 1245, 1028, 745 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.04 (d, J = 9.0 Hz, 2H), 7.17 (s, 1H), 7.15 (d, J = 2.1 Hz, 3H), 7.08 (s, 1H), 2.34 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 149.1, 145.3, 139.8, 132.4, 131.5, 129.7, 126.6, 124.0, 21.2. (4-Chlorophenyl)(3-nitrophenyl)sulfane (3nh).20 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nh as a yellow solid (41.9 mg, 79%); Rf = 0.40 (PE/EA = 50:1, v/v); mp 87−88 oC; IR (KBr) ν̃ 2930, 2830, 1588, 1487, 1245, 1028, 741 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.8 Hz, 2H), 7.47 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 7.19 (d, J = 8.9 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 147.5, 145.7, 136.1, 135.8, 130.3, 129.3, 127.1, 124.2. (4-Bromophenyl)(3-nitrophenyl)sulfane (3ni).20 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3ni as a yellow solid (51.1 mg, 83%); Rf =0.45 (PE/EA = 50:1, v/v); mp 92−93 o C; IR (KBr) ν̃ 3097, 2945, 1578, 1508, 1331, 1078, 841 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.08 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H), 7.39 (d, J = 8.3 Hz, 2H), 7.20 (d, J = 8.7 Hz, 2H);

13

C NMR (100 MHz, CDCl3) δ 147.3, 145.7, 135.9, 133.2, 132.5, 130.0, 127.2, 124.2. (4-Nitrophenyl)(4-(trifluoromethoxy)phenyl)sulfane (3nj).17 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nj as a yellow solid (50.8 mg, 80%); Rf =0.40 (PE/EA = 50:1, v/v); mp 84−86 oC; IR (KBr) ν̃ 2940, 2834, 1588, 1493, 1255, 1033, 832; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 7.6 Hz, 2H), 7.49 (d, J = 7.3 Hz, 2H), 7.22 (d, J = 7.9 Hz, 2H), 7.14 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 150.1, 147.2, 145.8, 136.0, 129.4, 127.2, 124.2, 122.2, 120.4 (JCF = 257). Naphthalen-1-yl(4-nitrophenyl)sulfane (3nk).21 Purification by chromatography (PE/EA = 100:1, v/v) afforded 3nk as a red solid (40.5 mg, 72%); Rf =0.40 (PE/EA = 50:1, v/v); mp 84−86 oC; IR (KBr) ν̃ 3445, 3091, 1572, 1497, 1331, 1084, 766 cm-1; 1H NMR (400 MHz, CDCl3) δ 8.13 (d, J = 8.0 Hz, 1H), 7.93−7.75 (m, 5H), 7.42 (d, J = 7.4, 3H), 6.98−6.81 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 148.5, 145.2, 135.8, 134.6, 134.2, 131.5, 129.0, 127.8, 127.0, 126.8, 126.1, 126.0, 125.5, 124.0. [1,1'-Biphenyl]-4-yl(4-methoxyphenyl)sulfane (6a).22 Purification by chromatography (PE/EA = 100:1, v/v) afforded 6a as a white solid (40.5 mg, 72%); Rf = 0.30 (PE/EA = 50:1, v/v); mp 137−138 oC; 1H NMR (400 MHz, CDCl3) δ 7.45 (d, J = 7.2 Hz, 2H), 7.37 (dd, J1 = 8.6, J2 = 4.0 Hz, 4H), 7.32 (t, J = 7.6 Hz, 2H), 7.23−7.25 (m, 1H), 7.14 (d, J = 8.5 Hz, 2H), 6.83 (d, J = 8.8 Hz, 2H), 3.73 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.9, 139.4, 137.7, 136.7, 134.4, 127.8, 127.5, 126.6, 126.2, 125.8, 123.16, 114.0, 54.4.

■ ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at http://pubs.acs.org. Copies of 1H and 13C NMR spectra for all compounds

■ AUTHOR INFORMATION Corresponding Author *E-mail: [email protected]

ORCID Junfeng Zhao: 0000-0003-4843-4871 Notes The authors declare no competing financial interests.

■ ACKNOWLEDGMENT This work was supported by the National Natural Science Foundation of China (21462023, 21762021) and the Natural Science Foundation of Jiangxi Province (20143ACB20007, 20153BCB 23018, 20161BAB213069).

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Palladium-Catalyzed Oxidative Cross-Coupling of Arylhydrazines and

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