SUPPORTING INFORMATION

for

NBS-Mediated Synthesis of β-Keto Sulfones from Benzyl Alcohols and Sodium Arenesulfinates

Madithedu Muneeswara, Nallappan Sundaravelu and Govindasamy Sekar*

Department of Chemistry, Indian Institute of Technology Madras, Chennai,

Tamil Nadu-600 036, India

gsekar@iitm.ac.in

Table of contents

Experimental section 2 General procedure for synthesis of secondary benzyl alcohols 2 General procedure for the synthesis of β-keto sulfones 2 Physical and spectral data of all compounds 3 Reference 10 1H and 13C spectra for all compounds 11

1

1.0 Experimental section

1.1 General information

The N-haloimides were purchased from Avra Synthesis Pvt. Ltd. Aldehydes and aryl bromides were purchased from Sigma-Aldrich, Alfa Aesar, and Spectrochem Pvt. Ltd. Solvents used for extraction and column chromatography were laboratory grade and used as received. Reaction solvents used were received from Fischer Scientific, India Pvt. Ltd. and Spectrochem Pvt.Ltd. Thin layer chromatography was performed on Merck silica gel (60 F254 pre-coated plates 0.25 mm), and the developed plates were visualized by UV fluorescence quenching. Silica gel (100–200 mesh) for column chromatography was purchased from Avra Synthesis Pvt. Ltd. The 1H and 13C NMR spectroscopic data were recorded with a Bruker 400 or 500 MHz instrument. Chemical shifts for the 1H NMR spectra are reported relative to residual CHCl3 (δ=7.26 ppm) or DMSO-d6 (δ=2.50 ppm). 13C NMR are reported relative to CDCl3

(δ=77.00 ppm) or DMSO-d6 (δ=39.52 ppm). FTIR spectra were recorded on a JASCO spectrometer and are reported in wavenumbers (cm–1). High resolution mass spectra (HR-MS) were recorded on Q-ToF Micro mass spectrometer and 6545 Accurate-Mass Q-ToF LC/MS instrument.

1.2 General procedure for synthesis of secondary benzyl alcohols 11

An oven dried round-bottom flask was charged with magnesium (1.2 equiv.), applied high vacuum three times and back filled with nitrogen. Then a small piece iodine (I2) and solvent dry THF 5 mL was added under N2 atmosphere. Solution of aryl bromide (1.0 equiv. 3 mmol) in 5 mL of dry THF was dropped slowly to the round bottom flask and stirred at room temperature for 30 min under N2 atmosphere. After the formation of Grignard reagent, the reaction mixture was cooled to 0 oC and then corresponding aldehyde 1.5 equiv. was added dropwise. The reaction mixture was stirred for 1-2 h. Progress of the reaction was monitored by TLC. After consumption of reactants, the reaction mixture was quenched with sat. NH4Cl solution and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was washed with sat. NaCl solution and dried over anhydrous Na2SO4. The organic layer was concentrated under vacuum, and the crude mixture was purified by silica gel column chromatography (hexanes/ethyl acetate) to afford pure secondary benzyl alcohols 1.

1.3 General procedure for the synthesis of β-keto sulfones 5

2

An oven dried reaction tube containing secondary benzyl alcohol 1 (0.7 mmol) was charged with NBS 2a (2.0 equiv.) under open atmosphere and allowed to stir for a few min. at room temperature. 1 mL of THF was added after the generation of brown color gas (bromine), which resulted in a reddish brown color mixture, then reaction tube was closed with glass stopper. The formation of α-bromo ketone 3 was monitored by TLC and the fadeout of reddish brown color was observed in 10-15 min. Then, DMSO was added to the reaction mixture and followed by the addition of 1.1 equiv. p-toluenesulfinate. After the reaction was allowed to stir for 50 min-1.5 h at room temperature (see the time given in Table 2 for the respective examples). After complete consumption of reactants (progress of the reaction was monitored by TLC), the reaction mixture was washed with 10 mL of sat. NaHCO3 solution and extracted using ethyl acetate (3 x 20 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel (hexanes:ethyl acetate = 8:2) to give pure β-keto sulfone 5.

1-Phenyl-2-tosylproan-1-one 5a

94% yield (189 mg), white solid, mp = 102-104 °C (lit.28 101-102 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.55 (d, J = 7.0 Hz, 3H), 2.43 (s, 3H), 5.15 (q, J = 7.0 Hz, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.47 (t, J = 7.5 Hz, 2H), 7.60 (tt, J = 7.5, 1.0 Hz, 1H), 7.65 (d, J = 8.5 Hz, 2H), 7.97 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.2, 21.7, 64.9, 128.7, 129.2, 129.5, 129.8, 133.0, 134.0, 136.2, 145.3, 192.6; FTIR (KBr): 3063, 2945, 1679, 1587, 1447, 1310, 1142, 942, 809, 739 cm -1; HRMS (m/z): [M+NH4]+ calcd. for C16H20NSO3: 306.1163; found: 306.1161.

1-(4-Methyl)phenyl-2-tosylpropan-1-one 5b

92% yield (195 mg), white solid, mp = 104-106 °C; Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.54 (d, J = 7.0 Hz, 3H), 2.42 (s, 3H), 2.43 (s, 3H), 5.12 (q, J = 7.0 Hz, 1H), 7.27 (d, J = 9.0 Hz, 2H), 7.30 (d, J = 8.5 Hz, 2H), 7.65 (d, J = 8.5 Hz, 2H), 7.88 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.2, 21.7, 21.7, 64.9, 129.3, 129.4, 129.5, 129.8, 133.0, 133.8, 145.2, 145.2, 192.1; FTIR (KBr): 3042, 2941, 1679, 1450, 1313, 1146, 935, 812, 756 cm -1; HRMS (m/z): [M+Na]+ calcd. for C17H18SO3Na: 325.0874; found: 325.0885.

1-(4-Chloro)phenyl-2-tosylpropan-1-one 5d

81% yield (183 mg), white solid, mp = 142-144 °C; Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.54 (d, J = 7.0 Hz, 3H), 2.44 (s, 3H), 5.09 (q, J = 7.0 Hz, 1H), 7.32 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.5 Hz, 2H), 7.63 (d, J = 8.5 Hz, 2H),

3

7.93 (d, J = 9.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.1, 21.7, 65.1, 129.1, 129.6, 129.8, 130.6, 132.7, 134.6, 140.7, 145.5, 191.4; FTIR (KBr): 2997, 2934, 1682, 1583, 1489, 1313, 1146, 942, 820, 770 cm -1; HRMS (m/z): [M+K]+ calcd. for C16H15ClSO3K: 361.0067; found: 361.0069.

1,2-Diphenyl-2-tosylethan-1-one 5i

61% yield (150 mg), white solid, mp = 147-149 °C (lit.2 145-146°C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.41 (s, 3H), 6.12 (s, 1H), 7.21 (d, J = 8.0 Hz, 2H), 7.29-7.31 (m, 2H), 7.33-7.35 (m, 3H), 7.41 (t, J = 7.6 Hz, 2H), 7.50-7.55 (m, 3H), 7.87 (d, J = 8.0Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.7, 76.1, 128.6, 128.7, 128.8, 128.8, 129.0, 129.6, 130.3, 130.4, 133.8, 134.0, 136.0, 145.0, 190.8; FTIR (KBr): 3061, 2986, 1679, 1592, 1496, 1450, 1313, 1146, 994, 809, 735 cm-1; HRMS (m/z): [M+H]+ calcd. for C21H19SO3: 351.1054; found: 351.1047.

1-Phenyl-2-tosylpentan-1-one 5k

85% yield (188 mg), white solid, mp = 90-92 °C (lit.2 89-90 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 0.85 (t, J = 7.6 Hz, 3H), 1.24 (sext, J = 7.6 Hz, 2H), 1.96-2.11 (m, 2H), 2.43 (s, 3H), 5.07 (dd, J = 6.4, 4.0 Hz, 1H), 7.30 (d, J = 7.6 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.58-7.65 (m, 3H), 7.96 (d, J = 7.6 Hz, 2H);13C NMR (100 MHz, CDCl3): δ 13.8, 20.3, 21.7, 30.4, 69.0, 128.8, 129.0, 129.5, 129.8, 133.4, 133.9, 137.3, 145.3, 192.8; FTIR (KBr): 3061, 2962, 1679, 1544, 1450, 1313, 1142, 994, 816, 749 cm-1; HRMS (m/z): [M+Na]+ calcd. for C18H20SO3Na: 339.1030; found: 339.0989.

1-Phenyl-2-tosylethan-1-one 5l

81% yield (156 mg), white solid, mp = 106-108 °C (lit.27 105-107 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.44 (s, 3H), 4.72 (s, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.47 (t, J = 7.4 Hz, 2H), 7.61 (t, J = 7.4 Hz, 1H), 7.76 (d, J = 8.0 Hz, 2H), 7.94 (d, J = 8.0 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 21.7, 63.6, 128.6, 128.8, 129.3, 129.8, 134.3, 135.8, 135.8, 145.3, 188.1; FTIR (KBr): 2980, 1689, 1602, 1433, 1317, 1148, 893, 724 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H15SO3: 275.0741; found: 275.0741.

1-(4-Methyl)phenyl-2-tosylethan-1-one 5m

4

84% yield (170 mg), white solid, mp = 102-104 °C (lit.24a 104-105 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.42 (s, 3H), 2.44 (s, 3H), 4.68 (s, 2H), 7.27 (d, J = 8.8 Hz, 2H), 7.33 (d, J = 8.0 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H), 7.84 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.7, 21.8, 63.5, 128.6, 129.5, 129.5, 129.8, 133.3, 135.7, 145.3, 145.5, 187.6; FTIR (KBr): 3057, 2945, 1679, 1489, 1440, 1321, 1146, 998, 897, 773 cm -1; HRMS (m/z): [M+H]+ calcd. for C16H17SO3: 289.0898; found: 289.0897.

1-(4-Chloro)phenyl-2-tosylethan-1-one 5n

79% yield (171 mg), white solid, mp = 166-168 °C (lit.28 167-168 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H), 4.68 (s, 2H), 7.34 (d, J = 8.0 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.74 (d, J = 8.0 Hz, 2H), 7.89 (d, J = 8.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.7, 63.7, 128.5, 129.2, 129.9, 130.8, 134.0, 135.5, 141.1, 145.5, 187.0; FTIR (KBr): 3001, 2948, 1675, 1583, 1486, 1317, 1146, 844, 773 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H14ClSO3: 309.0352; found: 309.0350.

1-(4-Bromo)phenyl-2-tosylethan-1-one 5o

70% yield (173 mg), white solid, mp = 145-147 °C (lit.27 142-144 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.45 (s, 3H), 4.67 (s, 2H), 7.33 (d, J = 6.8 Hz, 2H), 7.63 (d, J = 6.8 Hz, 2H), 7.74 (d, J = 6.4 Hz, 2H), 7.81 (d, J = 6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.7, 63.8, 128.5, 129.9, 129.9, 130.8, 132.2, 134.5, 135.6, 145.5, 187.2; FTIR (KBr): 3004, 1679, 1535, 1517, 1307, 1145, 820, 743 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H14BrSO3: 352.9847; found: 352.9827.

1-Phenyl-2-(phenylsulfonyl)propan-1-one 5p

75% yield (144 mg), white solid, mp = 83-85 °C (lit.28 85-86 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.57 (d, J = 6.5 Hz, 3H), 5.17 (q, J = 7.0 Hz, 1H), 7.48 (t, J = 7.5 Hz, 2H), 7.52 (t, J = 8.0 Hz, 2H), 7.61 (t, J = 7.5 Hz, 1H), 7.65 (t, J = 7.0 Hz, 1H), 7.79 (d, J = 7.0 Hz, 2H), 7.97 (d, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.2, 65.0, 128.8, 128.9, 129.1, 129.8, 134.1, 134.2, 136.0, 136.2, 192.5; FTIR (KBr): 3063, 2990, 1682, 1591, 1450, 1310, 1142, 945, 740 cm -1; HRMS (m/z): [M+H]+ calcd. for C15H15SO3: 275.0741; found: 275.0745.

1-(4-Methyl)phenyl-2-(phenylsulfonyl)propan-1-one 5q

71% yield (143 mg), white solid, mp = 102-104 °C (lit.28 103-104 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 1.56 (d, J = 6.8 Hz, 3H), 2.42 (s, 3H), 5.15 (q, J = 6.8 Hz, 1H), 7.27 (d, J = 8.4 Hz, 2H), 7.52 (t, J = 7.6 Hz, 2H), 7.65 (t,

5

J = 7.6 Hz, 1H), 7.78 (d, J = 7.6 Hz, 2H), 7.87 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 13.2, 21.7, 64.8, 128.8, 129.3, 129.5, 129.8, 133.7, 134.1, 136.0, 145.3, 191.9; FTIR (KBr): 3057, 2983, 1675, 1444, 1310, 1139, 942, 825, 743 cm -1; HRMS (m/z): [M+H]+ calcd. for C16H17SO3: 289.0898; found: 289.0894.

1-(4-Chloro)phenyl-2-(phenylsulfonyl)propan-1-one 5r

65% yield (141 mg), white solid, mp = 146-148 °C (lit.28 148-150 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.55 (d, J = 7.0 Hz, 3H), 5.10 (q, J = 7.0 Hz, 1H), 7.45 (d, J = 8.5 Hz, 2H), 7.53 (t, J = 8.0 Hz, 2H), 7.65-7.68 (m, 1H), 7.76 (d, J = 7.0 Hz, 2H), 7.93 (d, J = 8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.1, 65.0, 128.9, 129.1, 129.7, 130.6, 134.3, 134.5, 135.8, 140.8, 191.3; FTIR (KBr): 3071, 2983, 1675, 1583, 1478, 1307, 1142, 942, 840, 767 cm -1; HRMS (m/z): [M+H]+ calcd. for C15H14ClSO3: 309.0352; found: 309.0351.

1-(3-Fluoro)phenyl-2-(phenylsulfonyl)propan-1-one 5s

51% yield (104 mg), white solid, mp = 108-110 °C (lit.28 110-112 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 1.56 (d, J = 7.0 Hz, 3H), 5.10 (q, J = 7.0 Hz, 1H), 7.28-7.32 (m, 1H), 7.44-7.48 (m, 1H), 7.53 (t, J = 8.0 Hz, 2H), 7.62-7.67 (m, 2H), 7.76-7.79 (m, 3H); 13C NMR (125 MHz, CDCl3): δ 13.1, 65.3, 115.7 (d, 22.8 Hz), 121.1 (d, 21.5 Hz), 125.0 (d, 3 Hz), 128.9, 129.7, 130.4 (d, 7.5 Hz), 134.3, 135.9, 138.3 (d, 6.4 Hz), 162.8 (d, 247.3 Hz), 191.4; FTIR (KBr): 3063, 2994, 1692, 1591, 1482, 1433, 1317, 1156, 884, 717 cm-1; HRMS (m/z): [M+NH4]+ calcd. for C15H17NFSO3: 310.0913; found: 310.0912.

1-Phenyl-2-(phenylsulfonyl)pentan-1-one 5t

79% yield (167 mg), white solid, mp = 82-84 °C; Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (500 MHz, CDCl3): δ 0.85 (t, J = 7.5 Hz, 3H), 1.26 (sext, J = 7.5 Hz, 2H), 2.00-2.12 (m, 2H), 5.08 (dd, J = 6.0, 4.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 2H), 7.51 (t, J = 7.5 Hz, 2H), 7.59 (t, J = 8.0 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.78 (d, J = 7.0 Hz, 2H), 7.95 (d, J = 7.5 Hz, 2H); 13C NMR (125 MHz, CDCl3): δ 13.7, 20.3, 30.3, 69.8, 128.8, 128.8, 128.9, 129.8, 134.0, 134.1, 136.5, 137.2, 192.6; FTIR (KBr): 3061, 2948, 1679, 1598, 1447, 1321, 1146, 848, 747 cm-1; HRMS (m/z): [M+H]+ calcd. for C17H19SO3: 303.1054; found: 303.1047.

1-(4-Methyl)phenyl-2-(phenylsulfonyl)ethan-1-one 5u

6

79% yield (152 mg), white solid, mp = 122-124 °C; Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.42 (s, 3H), 4.71 (s, 2H), 7.27 (d, J = 7.6 Hz, 2H), 7.54 (t, J = 7.8 Hz, 2H), 7.66 (t, J = 7.2 Hz, 1H), 7.83 (d, J = 8.0 Hz, 2H), 7.89 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 21.7, 63.4, 128.5, 129.1, 129.4, 129.5, 133.3, 134.1, 138.8, 145.6, 187.4; FTIR (KBr): 3063, 2945, 1686, 1591, 1440, 1310, 1148, 889, 743 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H15SO3: 275.0741; found: 275.0733.

1-(4-Chloro)phenyl-2-(phenylsulfonyl)ethan-1-one 5v

62% yield (128 mg), white solid, mp = 132-134 °C; Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 4.70 (s, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.56 (t, J = 7.6 Hz, 2H), 7.68 (t, J = 7.6 Hz, 1H), 7.87-7.90 (m, 4H); 13C NMR (100 MHz, CDCl3): δ 63.6, 128.5, 129.2, 129.3, 130.7, 134.0, 134.4, 138.5, 141.2, 186.8; FTIR (KBr): 2948, 2894, 1679, 1583, 1482, 1310, 1146, 977, 829, 675 cm-1; HRMS (m/z): [M+NH4]+ calcd. for C14H15NClSO3: 312.0461; found: 312.0444.

2-((4-Methoxyphenyl)sulfonyl)-1-phenylpropan-1-one 5w

77% yield (164 mg), colorless liquid, Rf = 0.5 (in 25% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 1.55 (d, J = 6.8 Hz, 3H), 3.86 (s, 3H), 5.15 (q, J = 6.8 Hz, 1H), 6.96 (d, J = 8.8 Hz, 2H), 7.47 (t, J = 7.6 Hz, 2H), 7.60 (t, J = 7.6 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 13.2, 55.6, 65.0, 114.0, 127.3, 128.7, 129.1, 132.0, 134.0, 136.2, 164.1, 192.8; FTIR (neat): 2952, 2889, 1672, 1588, 1486, 1315, 1148, 962, 836 cm -1; HRMS (m/z): [M+H]+ calcd. for C16H17SO4: 305.0847; found: 305.0840.

2-((4-(Tert-butyl)phenyl)sulfonyl)-1-phenylpropan-1-one 5x

81% yield (187mg), colorless liquid, Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 1.31, (s, 9H), 1.57 (d, J = 6.8 Hz, 3H), 5.16 (q, J = 6.8 Hz, 1H), 7.43 (t, J = 7.6 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.56 (t, J = 7.2 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.97 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 12.8, 30.9, 35.2, 64.7, 125.8, 128.6, 129.0, 129.5, 133.2, 133.8, 136.2, 158.0, 192.5; FTIR (neat): 3053, 2950, 2890, 1670, 1598, 1487, 1320, 1144, 850, 756 cm-1; HRMS (m/z): [M+H]+ calcd. for C19H23SO3: 331.1367; found: 331.1362.

2-((4-Chlorophenyl)sulfonyl)-1-phenylpropan-1-one 5y

85% yield (183 mg), white solid, mp = 113-118 °C (lit.28 120-121 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): 1.57 (d, J = 6.8 Hz, 3H), 5.17 (q, J = 6.8 Hz, 1H), 7.44-7.54 (m, 4H), 7.63 (t, J = 6.8 Hz, 1H), 7.71 (d, J = 8.4 Hz, 2H), 7.97

7

(d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 13.3, 65.0, 128.8, 129.1, 129.1, 129.2, 131.3, 134.3, 136.0, 141.2, 192.4; FTIR (KBr): 2956, 2892, 1683, 1578, 1488, 1324, 1138, 976, 839, 687 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H14ClSO3: 309.0352; found: 309.0342.

2-((4-Bromophenyl)sulfonyl)-1-phenylpropan-1-one 5z

80% yield (197 mg), white solid, mp = 150-152 °C (lit.28 149-151 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): 1.57 (d, J = 6.8 Hz, 3H), 5.17 (q, J = 6.8 Hz, 1H), 7.45-7.66 (m, 6H), 7.66-7.75 (m, 1H), 7.96 (d, J = 8.0 Hz, 2H); 13C NMR (100 MHz, CDCl3): δ 13.3, 65.0, 128.8, 129.1, 129.8, 131.4, 132.2, 134.3, 134.8, 136.0, 192.4; FTIR (KBr): 2959, 2896, 1686, 1581, 1480, 1318, 1148, 982, 842, 678 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H14BrSO3: 352.9847; found: 352.9832.

General procedure for the gram scale reaction 5a

7.5 mmol (1 g) of 1-phenylpropanol 1a was added to an oven dried round-bottom flask and reacted with 15 mmol (2.67 g) of NBS 2a, stir for a few min. at room temperature under open atmosphere. After the generation of brown color gas (bromine), 10 mL of THF was added, which resulted in a reddish brown color mixture, then closed with stopper. α-Bromo ketone 3a formation was monitored by thin-layer chromatography and the fadeout of reddish brown color was observed in 10 min. To which 10 mL of DMSO solvent was added and followed by the addition of (8.25 mmol) p-toluenesulfinate. After the reaction was allowed for 1 h at room temperature (progress of the reaction was monitored by TLC). The reaction mixture was washed with 50 mL of sat. NaHCO3 solution and extracted using ethyl acetate (3 x 50 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude residue was purified by column chromatography on silica gel (hexanes:ethyl acetate = 8:2) to give pure β-keto sulfone 5a in 92% (1.45 g) yield.

Procedure for the synthesis of 1-phenyl-2-tosylpropan-1-ol 63

To an oven dried round bottom flask containing magnetic stir bar and 5a (1 mmol) in 3 mL of methanol, was added NaBH4 (2.0 equiv.) in portion wise and allowed to stir at 0 oC for 1 h. After the reaction completion, the reaction mixture was washed with sat. NH4Cl solution and extracted with ethyl acetate (3 x 20 mL). The combined organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (hexanes: ethyl acetate = 8:2) to give 1-phenyl-2-tosylpropan-1-ol 6 in 90% yield (261 mg). White solid, mp = 94-96 °C (lit.[32b] 95-100 °C); Rf = 0.4 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, DMSO-d6): δ 0.88 (d, J = 7.2 Hz, 3H), 2.41 (s, 3H), 3.63 (qt, J = 7.2 Hz, 1H), 4.82(dd, J

8

= 7.6, 4.4 Hz, 1H), 5.54 (d, J = 4.4 Hz, 1H), 7.26-7.32 (m, 5H), 7.42 (d, J = 8.0 Hz, 2H), 7.78 (d, J = 8.4 Hz, 2H); 13C NMR (100 MHz, DMSO-d6): δ 10.8, 21.1, 64.7, 72.5, 127.3, 127.7, 128.1, 128.3, 129.4, 137.6, 141.9, 143.7; FTIR (KBr): 3498, 3051, 1596, 1495, 1444, 1312, 1137, 890, 729 cm-1; HRMS (m/z): [M+NH4]+ calcd. for C16H22NSO3: 308.1320; found: 308.1315.

Procedure for the synthesis of 2-bromo-1-phenyl-2-tosylethan-1-one 74

To a stirred solution of β-keto sulfone 5l (1 mmol) in water (10 mL) and acetic acid (0.5 mL) was added KBr (1.1 mmol) followed by H2O2 (8 mmol 30%). The reaction mixture was further stirred at room temperature for 6 h. Then diluted with water (10 mL), extracted into ethyl acetate (3 × 20 mL). The combined organic extract was dried over anhydrous Na2SO4 and evaporated under reduced pressure. The crude product was purified by column chromatography on silica gel (hexanes: ethyl acetate = 8:2) to give 7 in 62% yield (219 mg). White solid, mp = 148-150 °C (lit.[33b] 150-152 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.46 (s, 3H), 6.23 (s, 1H), 7.37 (d, J = 8.0 Hz, 2H), 7.51 (t, J = 8.0 Hz, 2H), 7.65 (t, J = 7.6 Hz, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 7.6 Hz, 2H); 13C NMR (100 MHz, DMSO-d6): δ 21.2, 60.6, 128.9, 129.5, 129.7, 130.1, 132.6, 134.1, 134.8, 146.0, 187.3; FTIR (KBr): 3059, 2988, 2926, 1672, 1588, 1498, 1447, 1302, 1146, 949, 878, 734, 694 cm -1; HRMS (m/z): [M+NH4]+ calcd. for C15H17NSO3Br: 370.0112; found: 370.0106.

Procedure for the synthesis of 1-phenyl-2-tosylethan-1-one oxime 85

A suspension of hydroxylamine hydrochloride (1.5 mmol), and NaOAc (1.5 mmol) in EtOH (2 mL) and water (3ml) was stirred at room temperature for 30 min. To this solution, 5l (1 mmol) was added and the reaction mixture was reflux for 1 h. After the completion of reaction, the reaction mass was cooled to rt. After cooling, the precipitate was filtered using Buchner funnel, and the crude product was washed with cold water and dried under vacuum. The obtained crude was purified by column chromatography with hexane:ethyl acetate (8:2) as eluent to obtain 8 in 83% yield (240 mg). White solid, mp = 198-200 °C (lit.[34c] 201-202 °C); Rf = 0.5 (in 30% ethyl acetate: hexanes); 1H NMR (400 MHz, DMSO-d6): δ 2.37 (s, 3H), 4.90 (s, 2H), 7.30-7.40 (m, 5H), 7.60-7.70 (m, 4H), 11.77 (s, 1H); 13C NMR (100 MHz, DMSO-d6):δ 21.1, 51.5, 126.4, 127.9, 128.2, 128.9, 129.5, 134.6, 136.9, 144.4, 145.7; FTIR (KBr): 3275, 3043, 2914, 1675, 1647, 1620, 1584, 1463, 1309, 1137, 953, 812, 679 cm-1; HRMS (m/z): [M+H]+ calcd. for C15H16NSO3: 290.0850; found: 290.0849.

Procedure for the synthesis of (E)-1,3-diphenyl-2-tosylprop-2-en-1-one 96

9

A mixture of 5l (1.0 mmol), benzaldehyde (1.0 mmol), piperidine (0.1 mmol), and acetic acid (0.1 mmol) in benzene (4 mL) was heated at reflux for 1 h with azeotropic removal of water using a Dean-Stark trap. The mixture was cooled to room temperature and concentrated in vacuum. The residue was purified by flash chromatography on silica gel (hexanes: ethyl acetate = 9.5:0.5) to give 9 in 85% yield (308 mg). White solid, mp = 142-144 °C (lit.[35] 142.4-142.5 °C); Rf = 0.5 (in 20% ethyl acetate: hexanes); 1H NMR (400 MHz, CDCl3): δ 2.31 (s, 3H), 7.05-7.11 (m, 2H), 7.11-7.15 (m, 1H), 7.16-7.25 (m, 6H), 7.39 (t, J = 7.6 Hz, 1H), 7.70 (d, J = 8.0 Hz, 2H), 7.82 (d, J = 7.6 Hz, 2H), 7.99 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 21.4, 128.4, 128.6, 128.7, 129.6, 130.0, 130.8, 131.2, 134.2, 135.3, 136.5, 139.7, 140.8, 144.6, 192.1; FTIR (KBr): 3066, 2918, 1666, 1596, 1490, 1451, 1306, 1149, 890, 734, 657 cm -1; HRMS (m/z): [M+H]+ calcd. for C22H19SO3: 363.1054; found: 363.1040.

Reference

1. a) Grignard Reagents: New Developments, ed. H. G. Richey, Jr., John Wiley & Sons Inc., New York, 2000; b) Zong, H.; Huang, H.; Liu, J.; Bian, G.; Song, L. J. Org. Chem. 2012, 77, 4645-4652.

2. Inomata, K.; Sasaoka, S.; Kobayashi, T.; Tanaka, Y.; Igarashi, S.; Ohtani, T.; Kinoshita, H.; Kotake, H. Bull. Chem. Soc. Jpn. 1987, 60, 1767-1779.

3. a) Lin, Y.-S.; Kuo, Y.-C.; Kuei, C.-H.; Chang, M.-Y. Tetrahedron 2017, 73, 1275-1282; b) b) Field, L.; McFarland, J. W. J. Am. Chem. Soc. 1953, 75, 5582-5586.

4. a) Suryakiran, N.; Srinivasulu, M.; Venkateswarlu, Y. J. Sulfur Chem. 2007, 28, 345-350; b) Chen, W.; Liu, X.; Chen, E.; Chen, B.; Shao, J.; Yu, Y. Org. Chem. Front. 2017, 4, 1162-1166.

5. a) Yang, X.; Liu, S.; Yu, S.; Kong, L.; Lan, Y.; Li, X. Org. Lett. 2018, 20, 2698-2701; b) Liu, N.; Yin, P.; Chen, Y.; Deng, Y.; He, L. Eur. J. Org. Chem. 2012, 2711-2714; c) Wang, B.; Tang, L.; Liu, L.; Li, Y.; Yang, Y.; Wang, Z. Green Chem. 2017, 19, 5794−5799.

6. Cao, W.; Ding, W.; Chen, J.; Chen, Y.; Zang, Q.; Chen, G. Synth. Commun. 2004, 34, 1599-1608.

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500 MHz 1H-NMR spectra of 5a in CDCl3

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125 MHz 13C-NMR spectra of 5a in CDCl3

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500 MHz 1H-NMR spectra of 5b in CDCl3

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125 MHz 13C-NMR spectra of 5b in CDCl3

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500 MHz 1H-NMR spectra of 5c in CDCl3

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125 MHz 13C-NMR spectra of 5c in CDCl3

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500 MHz 1H-NMR spectra of 5d in CDCl3

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125 MHz 13C-NMR spectra of 5d in CDCl3

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500 Mz 1H-NMR spectra of 5f in CDCl3

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125 MHz 13C-NMR spectra of 5f in CDCl3

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500 MHz 1H-NMR spectra of 5g in CDCl3

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125 MHz 13C-NMR spectra of 5g in CDCl3

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400 MHz 1H-NMR spectra of 5i in CDCl3

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100 MHz 13C-NMR spectra of 5i in CDCl3

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400 MHz 1H-NMR spectra of 5k in CDCl3

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100 MHz 13C-NMR spectra of 5k in CDCl3

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400 MHz 1H-NMR spectra of 5l in CDCl3

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125 MHz 13C-NMR spectra of 5l in CDCl3

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400 MHz 1H-NMR spectra of 5m in CDCl3

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100 MHz 13C-NMR spectra of 5m in CDCl3

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400 MHYz 1H-NMR spectra of 5n in CDCl3

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100 MHz 13C-NMR spectra of 5n in CDCl3

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400 MHz 1H-NMR spectra of 5o in CDCl3

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100 MHz 13C-NMR spectra of 5o in CDCl3

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500 MHz 1H-NMR spectra of 5p in CDCl3

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125 MHz 13C-NMR spectra of 5p in CDCl3

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400 MHz 1H-NMR spectra of 5q in CDCl3

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100 MHz 13C-NMR spectra of 5q in CDCl3

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500 MHz 1H-NMR spectra of 5r in CDCl3

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125 MHz 13C-NMR spectra of 5r in CDCl3

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500 MHz 1H-NMR spectra of 5s in CDCl3

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125 MHz 13C-NMR spectra of 5s in CDCl3

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500 MHz 1H-NMR spectra of 5t in CDCl3

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125 MHz 13C-NMR spectra of 5t in CDCl3

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400 MHz 1H-NMR spectra of 5u in CDCl3

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100 MHz 13C-NMR spectra of 5u in CDCl3

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400 MHz 1H-NMR spectra of 5v in CDCl3

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100 MHz 13C-NMR spectra of 5v in CDCl3

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400 MHz 1H-NMR spectra of 5w in CDCl3

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100 MHz 13C-NMR spectra of 5w in CDCl3

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400 MHz 1H-NMR spectra of 5x in CDCl3

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100 MHz 13C-NMR spectra of 5x in CDCl3

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400 MHz 1H-NMR spectra of 5y in CDCl3

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100 MHz 13C-NMR spectra of 5y in CDCl3

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400 MHz 1H-NMR spectra of 5z in CDCl3

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100 MHz 13C-NMR spectra of 5z in CDCl3

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400 MHz 1H-NMR spectra of 6 in DMSO-d6

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100 MHz 13C-NMR spectra of 6 in DMSO-d6

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400 MHz 1H-NMR spectra of 7 in CDCl3

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100 MHz 13C-NMR spectra of 7 in DMSO-d6

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400 MHz 1H-NMR spectra of 8 in DMSO-d6

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100 MHz 13C-NMR spectra of 8 in DMSO-d6

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400 MHz 1H-NMR spectra of 9 in CDCl3

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100 MHz 13C-NMR spectra of 9 in CDCl3

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