Aerobic Nickel-Catalyzed Hydroxysulfonylation of Alkenes Using

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The Journal of Organic Chemistry

Aerobic Nickel-catalyzed Hydroxysulfonylation of Alkenes Using Sodium Sulfinates Nobukazu Taniguchi* Department of Chemistry, Fukushima Medical University, Fukushima 960-1295, Japan [email protected]

Ar

1

R + Ar2SO2Na

R = H or Alkyl-

cat.Ni-TEEDA NH4PF6 AcOH, DMF, H2O, 60 °C, air

OH Ar1

R SO2Ar2

ABSTRACT. Nickel-catalyzed hydroxysulfonylation of alkenes was achieved using sodium sulfinates under air atmosphere. The procedure enabled the selective synthesis of βhydroxysulfones in good yields, and suppressed the formation of β-ketosulfones. On the contrary, sulfonylation of alkynes with sodium sulfonates afforded only β-ketosulfones.

Transition metal-catalyzed carbon−sulfur bond formation is an important methodology in organic synthesis. Numerous efficient reactions have been reported.1 Compounds produced using such methods have found widespread application as convenient reagents or intermediates. In the synthesis of these organosulfur compounds, oxidation of sulfides2 or sulfonylation using sulfonyl chlorides or its derivatives3,4 has been generally used to prepare sulfonyl compounds.

ACS Paragon Plus Environment

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However, these procedures are not well suited to the preparation of organosulfones bearing functional groups. For instance, direct oxidation of β-hydroxysulfides cannot give βhydroxysulfones because of the oxidation of the hydroxy-group. Addition of sodium sulfinates to alkenes is considered the most appropriate method to construct these compounds. Hydroxysulfonylation of styrene using sulfinic acids has recently been reported (Scheme 1).5 The procedure affords β-hydoroxysulfones in good yields (a); however, it requires excess sulfinic acids. Moreover, addition of PPh3 is often required for the reduction of peroxides. Similarly, reactions involving a strong oxidants such as CAN cannot produce hydroxysulfones because of the formation of alkenyl sulfones (b).6 A similar result has been observed in a coppercatalyzed reaction of sodium sulfinates with alkenes (c).7 Thus, a method for the convenient preparation of β-hydroxysulfones from alkenes is needed but has not yet been developed.

Scheme 1. Sulfonylation of alkenes (1) Sulfonylation of alkenes via oxidation of sulfinic acids

R

ArSO2H (2-10 equiv.) Py, O2(air) then PPh3

OH R

SO2Ar (a)

(2) Stoichiometric Sulfonylation of alkenes ArSO2Na, CAN, NaI R

R

SO2Ar

(b)

(3) Copper-catalyzed sulfonylation of alkenes ArSO2Na(1.1 equiv.), KI cat.CuX R air

R

SO2Ar (c)


2

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Copper-catalyzed sulfonylation of alkenes or alkynes with sodium sulfinates affords alkenyl sulfones with a trace amount of β-ketosulfones or β-hydroxysulfones as byproducts; however, the procedure cannot produce these additives as major products. These substituents are introduced through a radical process, and the origin of the hydroxy or keto groups is oxygen in air.5,8 Consequently, control of the reaction is generally troublesome.9 Solving this issue requires the use of reagents that promote both oxidation and reduction. One approach is to exploit the characteristics of transition metals that can transfer a single electron, and are easily oxidized or reduced by various materials or under certain conditions.10 Transition metal catalysts are expected to enable both the oxidation of sulfonyl anion and the reduction of peroxides (Scheme 2). Therefore, in this study, the transition metal-catalyzed hydroxysulfonylation of alkenes was investigated using transition metals other than copper. From various experiments, it was observed that a nickel-catalyzed reaction of alkenes with sodium sulfinates could produce the corresponding β-hydroxysulfones in excellent yields. Here, it will be described the methodology of this reaction.

Scheme 2. Strategy ArSO2Na Oxidation cat.M, air • ArSO2 R

• R

SO2Ar

• O2

O2 R

SO2Ar

OH

Reduction H+, cat.M

R

SO2Ar

As shown in Table 1, a nickel-catalyzed reaction using styrene with sodium 4-toluenesulfinate was initially surveyed to determine the suitable reaction conditions. When the reaction using


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NiBr2-bpy catalyst was conducted in DMF or AcOH, trace amounts of β-hydroxysulfones 2a and β-ketosulfones 3a were observed (entries 1 and 2). However, the targeted reaction was not promoted at all. When H2O was added to these solvents, 2a was obtained in in 23−30% yields (entries 3 and 4). However, a mixed solvent of DMF, AcOH and H2O produced unsatisfactory results (entry 5). Notably, use of N,N,N’,N’-tetraethyl ethylenediamine (TEEDA) instead of bpy furnished 2a in 51% yield (entry 6). Fortunately, when NH4PF6 was added, the yield of βhydroxysulfone 2a was improved to 88% and the formation of β-ketosulfone 3a was suppressed (entry 7). In contrast, other amine ligands did not promote the reaction satisfactorily, and diphenylphosphinoethane (dppe) as a ligand failed to give 2a as a product (entries 8−10). Other nickel catalysts were inferior to NiBr2 (entries 11−12). In the absence of the nickel catalyst, the reaction scarcely proceeded (entry 13).

Table 1. Investigation of suitable condition 4-MeC6H4SO2Na, NiX2-L (1:1, 10 mol%) Ph Solvent, 60 °C

1a

OH

O SO2C6H4Me-4 +

Ph

Ph

2a

SO2C6H4Me-4 3a

Entry

Ni-L

Solvent (mL)

2a(%)

2a/3ab

1

NiBr2-bpy

AcOH

-

80/20

2

DMF

-

91/9

3

AcOH/H2O (0.2/0.2)

23

91/9

4

DMF/H2O (0.2/0.2)

30

83/7

AcOH/DMF/H2O (0.1/0.3/0.2)

30

81/19

5

NiBr2-bpy

6

NiBr2-TEEDA

51

87/13

7c

NiBr2-TEEDA

88

95/5


4

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8c

NiBr2TMEDA

52

87/13

9c

NiBr2(EtNHCH2)2

62

87/13

10c

NiBr2-dppe

-

80/20

11

c

NiCl2-TEEDA

30

87/13

12

c

Ni(OAc)2TEEDA

10

78/22

None

16

83/17

13 a

Reaction conditions: A mixture of 1 (0.3 mmol), ArSO2Na (0.33 mmol) and NiX2-L (1:1, 5 mol%) in DMF (0.3 mL), H2O (0.2 mL) and AcOH (0.1 mL) was treated at 60 ºC. b Determined by 1H NMR analysis. cNH4PF6 (0.09 mmol) was added.

Numerous hydroxysulfonylations of alkenes were screened according to the aforementioned procedure (Table 2). When the mixture of terminal aryl alkenes with sodium arenesulfinates was treated with NiBr2-TEEDA catalyst in air, the corresponding β-hydroxysulfones 2 were obtained in excellent yields, along with a trace amount of β-ketosulfones 3 (entries 1−14). Not only terminal alkenes but also internal alkenes were used in the procedure (entries 15−18). Although these cases did not afford β-ketosulfones, regio-isomers were often obtained. NMR analysis revealed that these compounds were anti-adducts. Furthermore, reactions using trans- and cis-βmethylstyrenes gave the same products (entries 15 and 16). These reactions apparently proceeded via the same stable radical intermediate. On the contrary, use of 2-vinyl pyridine resulted in hydrosulfonylation (entry 19). The reaction involving 4-octene was hardly promoted (entry 20).

Table 2. Hyroxysulfonylation of alkenes


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ArSO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6

OH

R 1

R

DMF, AcOH, H2O, 60 °C air

Entry

OH O2 S

OH O2 S

2

O SO2Ar + R

SO2Ar 3

2

2

1

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(h)

2(%)

2/3b,c

18

88

95/5

36

80

91/9

36

70

91/9

36

76

100/0

36

75

95/5

18

70

95/5

18

71

91/9

18

68

100/0

18

62

91/91

18

65

83/17

2a

2b OMe

OH O2 S

3

2c Cl

OH O2 S

4

2d F

OH O2 S

5

OH O2 S

6

7

2e

2f

OH O2 S

2g

OH O2 S

2h

OH O2 S

2i

MeO

8 AcO

9 Cl

OH O2 S

10

2j

F


6

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11

12

OH O2 S

2k

OH O2 S

2l

36

65

91/9

36

74

95/5

18

62

91/9

18

73

-

18

75

86/14c

18

85

86/14c

36

67

94/6c

18

59

100/0

18

0f

-

18

0

-

Br OH O2 S

13

14

O2 S

HO

15d

OH O2 S

16e

OH O2 S

OH O2 S

17

OH O2 S

18

OH O2 S

19

2m

2n

2o

2o

2p

2q

2r

N

20

OH 2s O2S

a

Reaction conditions: A mixture of 1 (0.3 mmol), ArSO2Na (0.33 mmol), NH4PF6 (0.09 mmol) and NiBr2-TEEDA (1:1, 5 mol%) in DMF (0.3 mL), H2O (0.2 mL) and AcOH (0.1 mL) was treated at 60 ºC. bDetermined by 1H NMR analysis. cIn entries 15−17, the ratio of regio-isomers. d cis-β-Methylstyrene was used. etrans-β-Methylstyrene was used. fHydrosulfones were obtained in 52% yield.


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To elucidate the reaction mechanism, some experiments were then performed. A reaction in the absence of oxygen was examined (Scheme 3). When the mixture of styrene with sodium 4toluenesulfinate was treated under nitrogen atmosphere, the desired β-hydroxysulfone was not obtained. Similarly, in the presence of TEMPO as radical scavenger, the reaction did not proceed (Scheme 4). The necessity of water as a nucleophilic11 was also investigated (Scheme 5). The reaction in the absence of water afforded β-hydroxysulfone and β-ketosulfone in 56% and 12% yields, respectively. In addition, experiments involving H218O revealed that the

18

O isotope was not introduced as

the hydroxy oxygen atom (Scheme 6). These results indicate that sulfonylation is necessary for oxygen and that the hydroxyl group is introduced by the addition of oxygen. A plausible reaction mechanism deduced from these results is illustrated in Figure 1. In the first step, sodium sulfinate is oxidized by air in the presence of the nickel(II) catalyst.10b After the formation of the sulfonyl radical 5, a reaction with alkenes gives a radical intermediate 6. Sequentially, when 6 reacts with oxygen, an anion intermediate 7 is produced by the reduction of nickel(I) or a sulfonyl anion. Finally, 8 is reduced in the presence of a proton and affords βhydroxysulfones 2. Then, the produced sulfonyl radical 5 reacts with alkenes or is converted to sulfonyl anion 4 by nickel(I). Consequently, the catalytic process does not require a large excess of sodium sulfinates and phosphine as a reductant.

Scheme 3. Hydroxysulfonylation of styrene in the absence of oxygen


8

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4-MeC6H4SO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6 Ph DMF, AcOH, H2O, 60 °C under N2, 18 h

OH SO2C6H4Me-4

Ph

trace

Scheme 4. A reaction in the presence of TEMPO 4-MeC6H4SO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6, TEMPO (1 equiv.) Ph DMF, AcOH, H2O, 60 °C air, 18 h

OH SO2C6H4Me-4

Ph

Not observed

Scheme 5. A reaction in the absence of H2O 4-MeC6H4SO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6 Ph

DMF, AcOH, 60 °C, air, 18 h

OH Ph

SO2C6H4Me-4 + Ph 56%

O SO2C6H4Me-4 12%

Scheme 6. A reaction in the presence of H218O 4-MeC6H4SO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6 Ph 18

DMF, AcOH, H2 O, 60 °C, air, 18 h

18

OH SO2C6H4Me-4

Ph

Not obseved

Figure 1. A plausible reaction mechanism


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H 2O

NiIILn

II

Ni Ln

SO2Ar

Ar1 2

2

Ni Ln

Ar2SO2Na 4

I

OH

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O 2 , H+ NiILn

Ar2SO2• or NiIILn 5

• Ar2SO2 5

+ H 2O

Ar1

O2 Ar

1

Ar2SO2Na or NiILn

H+ 1

SO2Ar2

Ar1

8

•

SO2Ar2 6

• NiIILn or Ar2SO2

• O2 SO2Ar

1

NiILn or Ar2SO2Na Ar

2

O2

7

Attention was next focused on the selective synthesis of β-ketosulfones. As a first target, the reaction of styrene with sodium 4-toluenesulfinate under oxygen atmosphere was evaluated. Unfortunately, the expected oxosulfonylation did not ultimately proceed; the corresponding βhydroxysulfone was produced in 50% yield (Scheme 7). On the contrary, when alkynes were employed, a reaction of phenyl acetylene and 1-phenyl 1propyne gave the expected β-ketosulfone in 60% and 41% yields, respectively (Scheme 8).

Scheme 7. A reaction under oxygen atomsphere 4-MeC6H4SO2Na, NiBr2-TEEDA (1:1, 5 mol%) NH4PF6 Ph DMF, AcOH, H2O, 60 °C under O2, 18 h

OH

O Ph

SO2PhMe-4 + Ph trace

SO2PhMe-4 50 %

Scheme 8. Ketosulfonylation of alkynes


10

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4-MeC6H4SO2Na, NiBr2-bpy (1:1, 5 mol%) Ph

R 1

AcOH, H2O, 60 °C, air 18 h

O Ph

R SO2C6H4Me-4

3 R = H: 60% (3a) R = Me: 41% (3o)

In conclusion, nickel-catalyzed hydroxysulfonylation of alkenes was achieved using sodium sulfinates in air. The procedure enabled the selective synthesis of β-hydroxysulfones in good yields. Furthermore, the method enabled oxosulfonylation of alkynes with sodium sulfinates, affording β-ketosulfones.

Experimental Section General Procedure and Chemicals. All reactions were carried out in air. 1H and

13

C NMR

spectra were recorded at 270 and 67.5 MHz, respectively. Chemical shifts are reported in δ ppm referenced to an internal tetramethylsilane standard for 1H NMR and chloroform-d (δ 77.0) for 13

C NMR. Compounds 2a5a, 2f5a, 2i5a, 2j5a, 2k5a, 2n5a, 2o5a, 2p5a, 3a8 and 3o8 showed the

identical spectra reported in the literature. Typical procedure for nickel-catalyzed hydroxysulfonylation of alkenes: Synthesis of 2phenyl-1-(4-methylphenylsulfonyl)-ethane-2-ol (2a) (Table 2, entry 1) To a mixture of styrene (31.2 mg, 0.3 mmol), sodium 4-toluenesulfinate (58.8 mg, 0.33 mmol), and NH4PF6 (14.7 mg, 0.09 mmol), in DMF (0.3 mL), AcOH (0.1 mL) and H2O (0.2 mL) were added NiBr2 (3.2 mg, 0.015 mmol) and (Et2NCH2)2 (2.6 mg, 0.015 mmol), and the mixture was stirred at 60 °C for 18 h in air. After the residue was dissolved in Et2O, the solution was washed with H2O and saturated sodium chloride and dried over anhydrous magnesium sulfate.


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Chromatography on silica gel (60% diethyl ether / hexane) gave 2-phenyl-1-(4methylphenylsulfonyl)-ethane-2-ol 2a (72.8 mg, 88%): white solid. mp: 68.5−69.5 °C; 1H NMR (270 MHz, CDCl3) δ 7.83 (d, J = 8.2 Hz, 2H), 7.38 (d, J = 8.2 Hz, 2H), 7.31−7.26 (m, 5H), 5.24 (d, J = 9.9 Hz, 1H), 3.72 (brs, 1H), 3.47 (dd, J = 14.5 and 9.9 Hz, 1H), 3.31 (dd, J = 14.5 and 1.3 Hz, 1H), 2.46 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 145.2, 140.7, 136.1, 130.1, 128.7,

128.3, 127.9, 125.6, 68.4, 63.9, 21.6; IR (CHCl3) 3615, 1620, 1445, 1302, 1172 cm-1; Anal. Calcd for C15H16O3S: C, 65.19; H, 5.84. Found: C, 65.10; H, 5.86. 2-Phenyl-1-(4-methylphenylsulfonyl)-ethane-2-ol (2b): The title compound was obtained as colorless liquid (70.0 mg, 80%). 1H NMR (270 MHz, CDCl3) δ 7.88 (d, J = 8.9 Hz, 2H), 7.33−7.26 (m, 5H), 7.03 (d, J = 8.9 Hz, 2H), 5.24 (d, J = 9.6 Hz, 1H), 3.89 (s, 3H), 3.76 (brs, 1H), 3.47 (dd, J = 14.5 and 9.6 Hz, 1H), 3.31 (dd, J = 14.5 and 2.0 Hz, 1H);

13

C{1H} NMR (67.5

MHz, CDCl3) δ 164.0, 140.7, 130.2, 129.3, 128.7, 128.3, 125.6, 114.6, 68.5, 64.2, 55.7; IR (CHCl3) 3507, 1596, 1497, 1296, 1137 cm-1; Anal. Calcd for C15H16O4S: C, 61.62; H, 5.52. Found: C, 61.80; H, 5.37. 2-Phenyl-1-(4-chlorophenylsulfonyl)-ethane-2-ol (2c): The title compound was obtained as a white solid (62.1 mg, 70%). mp: 103.5 −105.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.87 (d, J = 8.9 Hz, 2H), 7.53 (d, J = 8.9 Hz, 2H), 7.31−7.26 (m, 5H), 5.27 (d, J = 9.7 Hz, 1H), 3.51 (dd, J = 14.5 and 9.7 Hz, 1H), 3.49 (brs, 1H), 3.33 (dd, J = 14.5 and 2.0 Hz, 1H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 140.8, 140.5, 137.8, 129.7, 129.5, 128.8, 128.4, 125.6, 68.5, 63.9; IR (CHCl3) 3517, 1582, 1477, 1313, 1149 cm-1; Anal. Calcd for C14H13ClO3S: C, 56.66; H, 4.42. Found: C, 56.87; H, 4.38.


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2-Phenyl-1-(4-fluorophenylsulfonyl)-ethane-2-ol (2d): The title compound was obtained as colorless liquid (63.8 mg, 76%). 1H NMR (270 MHz, CDCl3) δ 7.99−7.94 (m, 2H), 7.35−7.21 (m, 7H), 5.28 (d, J = 9.8 Hz, 1H), 3.51 (dd, J = 14.1 and 9.8 Hz, 1H), 3.49 (brs, 1H), 3.34 (dd, J = 14.1 and 2.0 Hz, 1H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 165.9 (d, 1J(C, F) = 256.9 Hz), 140.6, 135.3 (d, 4J(C, F) = 3.4 Hz), 131.0 (d, 3J(C, F) = 9.5 Hz), 128.8, 128.4, 125.6, 116.7 (d, 2J(C, F) = 21.0 Hz), 68.6, 64.1; IR (CHCl3) 3501, 1592, 1494, 1290, 1139 cm-1; Anal. Calcd for C14H13FO3S: C, 59.99; H, 4.67. Found: C, 60.27; H, 4.76. 2-Phenyl-1-phenylsulfonyl-ethane-2-ol (2e): The title compound was obtained as a white solid (59.0 mg, 75%). mp: 90.0−91.5 °C. 1H NMR (270 MHz, CDCl3) δ 7.96 (d, J = 8.2 Hz, 2H), 7.72−7.56 (m, 3H), 7.33−7.26 (m, 5H), 5.29 (dd, J = 9.0 and 2.0 Hz, 1H), 3.67 (d, J = 2.0 Hz, 1H), 3.51 (dd, J = 14.2 and 9.0 Hz, 1H), 3.34 (dd, J = 14.2 and 2.0 Hz, 1H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 140.6, 139.2, 134.1, 129.5, 128.8, 128.3, 127.9, 125.6, 68.4, 63.9; IR (CHCl3) 3619, 1621, 1447, 1307, 1147 cm-1; Anal. Calcd for C14H14O3S: C, 64.10; H, 5.38. Found: C, 64.20; H, 5.32. 2-(4-Methylphenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2f): The title compound was obtained as colorless liquid (61.1 mg, 70%).; 1H NMR (270 MHz, CDCl3) δ 7.82 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 5.20 (d, J = 9.7 Hz, 1H), 3.66 (brs, 1H), 3.47 (dd, J = 14.2 and 9.7 Hz, 1H), 3.29 (dd, J = 14.2 and 2.0 Hz, 1H), 2.46 (s, 3H), 2.30 (s, 3H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 145.1, 138.1, 137.7, 136.2, 130.0, 129.3, 127.9, 125.6, 68.3, 63.9, 21.6, 21.0; IR (CHCl3) 3502, 1597, 1515, 1313, 1133 cm-1; Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C, 65.91; H, 6.31.


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2-(4-Methoxyphenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2g): The title compound was obtained as colorless liquid (65.3 mg, 71%). 1H NMR (270 MHz, CDCl3) δ 7.82 (d, J = 8.4 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.20 (d, J = 8.9 Hz, 2H), 6.83 (d, J = 8.9 Hz, 2H), 5.19 (d, J = 9.9 and 1.8 Hz, 1H), 3.77 (s, 3H), 3.66 (brs, 1H), 3.47 (dd, J = 14.2 and 9.9 Hz, 1H), 3.29 (dd, J = 14.2 and 1.8 Hz, 1H), 2.46 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 159.5, 145.1, 136.2,

132.9, 130.0, 127.9, 126.9, 114.6, 68.1, 63.9, 55.2, 21.6; IR (CHCl3) 3506, 1598, 1514, 1302, 1137 cm-1; Anal. Calcd for C16H18O4S: C, 62.72; H, 5.92. Found: C, 62.92; H, 5.95. 2-(4-Acetoxyphenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2h): The title compound was obtained as a white solid (61.8 mg, 68%). mp: 102.7−104.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.84 (d, J = 8.1 Hz, 2H), 7.39 (d, J = 8.1 Hz, 2H), 7.32 (d, J = 8.1 Hz, 2H), 7.05 (d, J = 8.1 Hz, 2H), 5.26 (d, J = 10.4 Hz, 1H), 3.76 (brs, 1H), 3.45 (dd, J = 14.2 and 10.4 Hz, 1H), 3.30 (dd, J = 14.2 and 1.6 Hz, 1H), 2.47 (s, 3H), 2.28 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 169.4,

150.4, 145.4, 138.2, 136.0, 130.1, 127.9, 126.8, 121.9, 68.0, 63.9, 21.7, 21.1; IR (CHCl3) 3514, 1754, 1598, 1289, 1137 cm-1; Anal. Calcd for C17H18O5S: C, 61.06; H, 5.43. Found: C, 60.96; H, 5.41. 2-(4-Chlorophenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2i): The title compound was obtained as a white solid (57.3 mg, 62%). mp: 88.0−91.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.82 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.30−7.21 (m, 4H), 5.23 (d, J = 9.6 Hz, 1H), 3.81 (d, J = 2.0 Hz, 1H), 3.43 (dd, J = 14.2 and 9.6 Hz, 1H), 3.28 (dd, J = 14.4 and 2.0 Hz, 1H), 2.47 (s, 3H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 145.4, 139.1, 135.9, 134.0, 130.1, 128.9, 127.9, 127.0, 67.8, 63.8, 21.7; IR (CHCl3) 3513, 1598, 1493, 1303, 1137 cm-1; Anal. Calcd for C15H15ClO3S: C, 57.97; H, 4.86. Found: C, 57.86; H, 4.80.


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2-(4-Fluorophenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2j): The title compound was obtained as a white solid (57.3 mg, 65%). mp: 91.5−92.1 °C. 1H NMR (270 MHz, CDCl3) δ 7.83 (d, J = 8.3 Hz, 2H,), 7.39 (d, J = 8.3 Hz, 2H), 7.30−7.25 (m, 2H), 7.03−6.97 (m, 2H), 5.25 (d, J = 9.0 Hz, 1H), 3.81 (brs, 1H), 3.45 (dd, J = 14.5 and 9.0 Hz, 1H), 3.29 (dd, J = 14.5 and 2.0 Hz, 1H), 2.47 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 162.4 (d, 1J(C, F) = 245.0 Hz), 145.4,

136.4 (d, 4J(C, F) = 3.4 Hz), 135.9, 130.1, 128.0, 127.4 (d, 3J(C, F) = 8.1 Hz), 115.6 (d, 2J(C, F) = 21.6 Hz), 67.8, 63.9 (d, 5J(C, F) = 1.3 Hz), 21.7; IR (CHCl3) 3512, 1599, 1511, 1302, 1136 cm-1; Anal. Calcd for C15H15FO3S: C, 61.21; H, 5.14. Found: C, 61.33; H, 5.12. 2-(2-Methoxyphenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2k): The title compound was obtained as a white solid (57.0 mg, 65%). mp: 116.1-118.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.85 (d, J = 8.2 Hz, 2H), 7.48 (d, J = 7.2 Hz, 1H), 7.39 (d, J = 8.2 Hz, 2H), 7.25−7.14 (m, 2H), 7.08 (d, J = 7.2 Hz, 1H), 5.43 (d, J = 9.7 Hz, 1H), 3.68 (brs, 1H), 3.40 (dd, J = 14.5 and 9.7 Hz, 1H), 3.23 (dd, J = 14.5 and 1.6 Hz, 1H), 2.47 (s, 3H), 2.09 (s, 3H);

13

C{1H} NMR (67.5 MHz,

CDCl3) δ 145.3, 138.7, 136.0, 133.7, 130.5, 130.1, 128.0, 127.9, 126.6, 125.3, 65.0, 62.9, 21.7, 18.5; IR (CHCl3) 3515, 1598, 1460, 1312, 1139 cm-1; Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.23; H, 6.26. 2-(2-Bromophenyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2l): The title compound was obtained as a white solid (65.7 mg, 74%). mp: 105.0−106.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.90 (d, J = 8.6 Hz, 2H), 7.66 (d, J = 7.8 and 1.6 Hz, 1H), 7.44−7.32 (m, 4H), 7.13 (td, J = 7.8 and 1.6 Hz, 1H), 5.36 (d, J = 10.0 Hz, 1H), 4.05 (d, J = 1.6 Hz, 1H), 3.52 (dd, J = 14.5 and 1.3 Hz, 1H), 3.23 (dd, J = 14.5 and 10.0 Hz, 1H), 2.47 (s, 3H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 145.4, 139.3, 135.4, 132.6, 130.1, 129.6, 128.3, 128.0, 127.5, 120.8, 67.6, 61.8, 21.7; IR (CHCl3)


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3515, 1598, 1447, 1300, 1140 cm-1; Anal. Calcd for C15H15BrO3S: C, 50.71; H, 4.26. Found: C, 50.37; H, 4.17. 2-(2-Naphtyl)-1-(4-methylphenylsulfonyl)-ethane-2-ol (2m): The title compound was obtained as a white solid (60.7 mg, 62%). mp: 61.0−62.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.86−7.77 (m, 6H), 7.48−7.45 (m, 2H), 7.37−7.33 (m, 3H), 5.42 (d, J = 9.6 Hz, 1H), 3.83 (d, J = 1.8 Hz, 1H), 3.55 (dd, J = 14.3 and 9.6 Hz, 1H), 3.40 (dd, J = 14.3 and 1.8 Hz, 1H), 2.45 (s, 3H);

13

C{1H}

NMR (67.5 MHz, CDCl3) δ 145.3, 137.9, 136.1, 133.2, 133.1, 130.1, 128.7, 128.0, 127.9, 127.7, 126.4, 126.3, 124.8, 123.3, 68.6, 63.9, 21.7; IR (CHCl3) 3512, 1598, 1404, 1313, 1135 cm-1; Anal. Calcd for C19H18O3S: C, 69.91; H, 5.56. Found: C, 69.53; H, 5.52. 2-Phenyl-1-(4-methylphenylsulfonyl)-propan-2-ol (2n): The title compound was obtained as a white solid (61.0 mg, 73%). mp: 80.0−81.5 °C. 1H NMR (270 MHz, CDCl3) δ 7.49 (d, J = 8.2 Hz, 2H), 7.31−7.26 (m, 2H), 7.20−7.15 (m, 5H), 4.62 (brs, 1H), 3.70 (dd, J = 14.5 Hz, 1H), 3.58 (dd, J = 14.5 Hz, 1H), 2.38 (s, 3H), 1.70 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 144.5,

144.4, 137.3, 129.7, 128.2, 127.5, 127.1, 124.6, 73.1, 66.6, 30.7, 21.5; IR (CHCl3) 3506, 1598, 1495, 1312, 1157 cm-1; Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.07; H, 6.20. (1R*, 2S*)-1-Phenyl-2-(4-methylphenylsulfonyl)-propan-2-ol (2o): The title compound was obtained as colorless liquid (65.7 mg, 75%). 1H NMR (270 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.34−7.24 (m, 5H), 5.50 (brs, 1H), 3.33 (brs, 1H), 3.19 (dd, J = 7.2 and 1.3 Hz, 1H), 2.47 (s, 3H), 1.19 (d, J = 7.2 Hz, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ

145.2, 139.9, 134.3, 130.0, 128.7, 128.4, 127.6, 125.5, 69.2, 65.6, 21.6, 5.7; IR (CHCl3) 2526, 1597, 1452, 1301, 1143 cm-1; Anal. Calcd for C16H18O3S: C, 66.18; H, 6.25. Found: C, 66.43; H, 6.25.


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trans-2-(4-Methylphenylsulfonyl)tetralin-1-ol (2p): The title compound was obtained as a white solid (60.9 mg, 67%). mp: 120.7−122.5 °C. 1H NMR (270 MHz, CDCl3) δ 7.84 (d, J = 7.9 Hz, 2H), 7.60 (d, J = 7.5 Hz, 1H), 7.40 (d, J = 7.9 Hz, 2H), 7.27−7.14 (m, 2H), 7.02 (d, J = 7.2 Hz, 1H), 5.21 (d, J = 9.2 Hz, 1H), 4.19 (d, J = 2.0 Hz, 1H), 3.42−3.33 (m, 1H), 2.82−2.76 (m, 2H), 2.46 (s, 3H), 2.18−2.12 (m, 1H), 1.80−1.71 (m, 1H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 145.5, 135.8, 134.8, 133.4, 129.9, 129.2, 127.9, 127.6, 127.6, 126.8, 67.5, 66.9, 27.9, 22.9, 21.6; IR (CHCl3) 3523, 1598, 1493, 1290, 1141 cm-1; Anal. Calcd for C17H18O3S: C, 67.52; H, 6.00. Found: C, 67.17; H, 6.07. trans-2-(4-Methylphenylsulfonyl)-1H-inden-1-ol (2q): The title compound was obtained as a white solid (51.1 mg, 59%). mp: 135.0−136.3 °C. 1H NMR (270 MHz, CDCl3) δ 7.86 (d, J = 8.2 Hz, 2H), 7.40-7.36 (m, 3H), 7.29−7.22 (m, 2H), 7.15−7.12 (m, 1H), 5.75 (d, J = 6.6 Hz, 1H), 3.88−3.79 (m, 1H), 3.27 (dd, J = 16.0 and 8.9 Hz, 1H), 3.11 (dd, J = 16.0 and 8.9 Hz, 1H), 2.95 (brs, 1H), 2.46 (s, 3H);

13

C{1H} NMR (67.5 MHz, CDCl3) δ 145.2, 141.2, 137.7, 135.2, 130.1,

128.9, 128.5, 127.7, 124.5, 124.4, 75.5, 72.9, 31.7, 21.7; IR (CHCl3) 3616, 1598, 1423, 1286, 1146 cm-1; Anal. Calcd for C16H16O3S: C, 66.64; H, 5.59. Found: C, 66.24; H, 5.52. Typical procedure for nickel-catalyzed oxysulfonylation of alkynes: Synthesis of 1-phenyl2-(4-methylphenylsulfonyl)ethanone (3a) (Scheme 6) To a mixture of 1-phenylacetyrene (32.9 mg, 0.3 mmol), sodium 4-toluenesulfinate (58.8 mg, 0.33 mmol), and NH4PF6 (14.7 mg, 0.09 mmol), in AcOH (0.15 mL) and H2O (0.15 mL) were added NiBr2 (3.2 mg, 0.015 mmol) and bpy (2.3 mg, 0.015 mmol), and the mixture was stirred at 60 °C for 18 h in air using balloon. After the residue was dissolved in Et2O, the solution was washed with H2O and saturated sodium chloride and dried over anhydrous magnesium sulfate.


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Chromatography on silica gel (50% diethyl ether / hexane) gave 1-phenyl-2-(4methylphenylsulfonyl)ethanone 3a (49.2 mg, 60%): white solid. mp: 100.1−102.0 °C. 1H NMR (270 MHz, CDCl3) δ 7.95 (d, J = 7.2 Hz, 2H), 7.76 (d, J = 8.2 Hz, 2H), 7.61 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.2Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 4.71 (s, 2H), 2.44 (s, 3H); 13C{1H} NMR (67.5 MHz, CDCl3) δ 188.1, 145.4, 135.7, 135.7, 134.3, 129.8, 129.3, 128.8, 128.6, 63.6, 21.7; IR (CHCl3) 1681, 1598, 1327, 1155 cm-1; Anal. Calcd for C15H14O3S: C, 65.67; H, 5.14. Found: C, 65.76; H, 5.16. 1-Phenyl-2-(4-methylphenylsulfonyl)propanone (3o): The title compound was obtained as a white solid (35.4 mg, 41%). mp: 85.9−87.0 °C; 1H NMR (270 MHz, CDCl3) δ 7.98 (d, J = 7.2 Hz, 2H), 7.66 (d, J = 8.2 Hz, 2H), 7.60 (t, J = 7.2 Hz, 1H), 7.48 (t, J = 7.2Hz, 2H), 7.31 (d, J = 8.2 Hz, 2H), 5.15 (q, J = 6.9 Hz, 1H), 2.43 (s, 3H), 1.55 (dd, J = 6.9 Hz, 3H);

13

C{1H} NMR

(67.5 MHz, CDCl3) δ 192.5, 145.3, 136.2, 134.0, 132.9, 129.0, 129.5, 129.2, 128.7, 64.9, 21.7, 13.2; IR (CHCl3) 1682, 1597, 1449, 1326, 1149 cm-1; Anal. Calcd for C16H16O3S: C, 66.64; H, 5.59. Found: C, 66.30; H, 5.62.

Supporting Information. Copies of the 1H NMR and

13

C NMR Spectra are provided. This

material is available free of charge via the Internet at http://pubs.acs.org.

References 1 Selected reviews: (a) Metzner, P.; Thuillier, A. Sulfur Reagents in Organic Synthesis; Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W. Eds.; Academic Press: San Diego, 1994. (b)


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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


Paulmier, C. In Selenium Reagents and Intermediates in Organic Synthesis; Baldwin, J. E. Ed.; Organic Chemistry Series 4; Pergamon Press Ltd.: Oxford, 1986. (c) Wirth, T. Ed. Organoselenium Chemistry; Topics in Current Chemistry 208; Springer-Verlag; Heidelberg; 2000. (d) Ley, S. V.; Thomas, A. W. Angew. Chem. Int. Ed. 2003, 42, 5400–5449. (e) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205–3220. (f) Beletskaya, I. P.; Ananikov, V. P. Chem. Rev. 2011, 111, 1596–1636. (g) Partyka, D. V. Chem. Rev. 2011, 111, 1529–1595. (h) Allen, S. E.; Walvoord, R. R.; Padilla-Salinas, R.; Kozlowski, M. C. Chem. Rev. 2013, 113, 6234−6458. (i) Lee, C.; Liu, C.; Badsara, S. S. Chem. Asian J. 2014, 9, 706−722. (j) Shen, C.; Zhang, P.; Sun, Q.; Bai, S.; Andy Hor, T. S.; Liu, X. Chem. Soc. Rev. 2015, 44, 291−314. 2 (a) Uemura, S. Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press Ltd.: New York, 1991, Vol. 7, Chapter 6.2. (b) Backväll, J.-E.; Ericsson, A. J. Org. Chem. 1994, 59, 5850−5851. 3 Selected paper of sulfonylations: (a) Wang, S.-F.; Chuang, C.-P.; Lee, J.-H.; Liu, S.-T. Tetrahedron 1999, 55, 2273−2288. (b) Riggi, J. De, Surzur, J.-M.; Bertrand, M. P. Tetrahedron 1990, 46, 5285−5294. (c) Fang, J.-M.; Chen, M.-Y. Tetrahedron Lett. 1987, 28, 2853−2856. (d) Back, T. G.; Krishna, M. V. J. Org. Chem. 1987, 52, 4265−4269. (e) Wei, W.; Liu, X.; Yang, D.; Dong, R,; Cui, Y.; Yuan, F.; Wang, H. Tetrahedron Lett. 2015, 56, 1808−1811. 4 Selected paper of metal-mediated sulfonylations: (a) Truce, W. E.; Goralski, C. T. J. Org. Chem. 1971, 36, 2536−2538. (b) Sinnreich, J.; Asscher, M. J. Chem. Soc., Perkin Trans. I 1972, 1543−1545. (c) Kamigata, N.; Sawada, H.; Kobayashi, M. J. Org. Chem. 1983, 48, 3793−3796. (d) Beaulieu, C.; Guay, D.; Wang, Z.; Evans, D. A. Tetrahedron Lett. 2004, 45, 3233−3236. (e) Kar, A.; Sayyed, Iliyas, A.; Lo Wei, F.; Kaiser Hanns, M.; Tse, M. K. Org. Lett. 2007, 9,


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3405−3408. (f) Huang, F.; Batey, R. A. Tetrahedron 2007, 63, 7667−7672. (g) Taniguchi, T.; Idota, A.; Ishibashi, H.; Org. Biomol, Chem. 2011, 9, 3151−3153. 5 (a) Lu, Q.; Zhang, J.; Wei, F.; Qi, Y.; Wang, H.; Liu, Z.; Lei, A. Angew. Chem. Int. Ed. 2013, 52, 7156−7159. (b) Wei, W.; Liu, C.; Yang, D.; Wen, J.; You, J.; Suo, Y.; Wang, H. Chem. Comm. 2013, 49, 10239−10241. (c) Kariya, A.; Yamaguchi, T.; Nobuta, T.; Tada, N.; Miura, T.; Itho, A. RSC Advances 2014, 4, 13191−13194. 6 Nair, V.; Augustine, A.; Suja, T. D. Synthesis, 2000, 2259-2265. 7 (a) Taniguchi, N. Synlett 2011, 22, 1308−1312. (b) Taniguchi, N. Synlett 2012, 23, 1245−1249. (c) Taniguchi, N. Tetrahedron 2014, 70, 1984−1990. 8 Oxosulfonylation of alkynes: Handa, S.; Fennewald, J. C.; Lipshutz, B. H. Angew. Chem. Int. Ed. 2014, 53, 3432−3435. 9 Selected review: (a) Smadja, W. Synlett 1993, 1−26. (b) Porter, N. D.; Giese, B.; Curran, D. P. Acc. Chem. Res. 1991, 24, 296−304. 10 (a) Piera, J.; Backväll, J.-E. Angew. Chem. Int. Ed. 2008, 47, 3506−3523. (b) Kochi, J. K.; Organometallic Mechanisms And Catalysis; Academic Press: San Diego, 1978. 11 Jira, R. In Applied Homogeneous Catalysis with Organometallic Compounds, Cornils, B.; Herrmann, W. A. Eds.; Wiley-VCH: Weinheim, 2000; pp. 394–411.


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Aerobic Nickel-Catalyzed Hydroxysulfonylation of Alkenes Using

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