Tetrabutylammonium Iodide–Promoted Thiolation of Oxindoles Using Sulfonyl Chlorides as Sulfenylation Reagents

3-Sulfanyloxindoles were synthesised by triphenylphosphine-mediated transition-metal-free thiolation of oxindoles using sulfonyl chlorides as sulfenylation reagents. The above reaction was promoted by iodide anions, which was ascribed to the in situ conversion of sulfenyl chlorides into the more reactive sulfenyl iodides. Moreover, the thiolation of 3-aryloxindoles was facilitated by bases. The use of a transition-metal-free protocol, readily available reagents, and mild reaction conditions make this protocol more practical for preparing 3-sulfanyloxindoles than traditional methods.


Discussion
Based on our previous work [21], a plausible reaction mechanism was proposed (Scheme 4), featuring the initial reduction of sulfonyl chloride 2 by PPh3 to sulfenyl chloride F via intermediates A-E. F is converted into sulfenyl iodide G in the presence of iodide anions. Finally, electrophilic thiolation of oxindoles 1 by G gives the corresponding oxindole thioethers.

General Methods and Material
All solvents were distilled prior to use. Unless otherwise noted, chemicals were used as received without further purification. For chromatography, 200−300 mesh silica gel was employed. 1 H-and 13 C-NMR spectra were recorded at 400 MHz and 100 MHz respectively. Chemical shifts are reported in ppm using tetramethylsilane as internal standard (see supplementary). HRMS was performed on an FTMS mass instrument. Melting points are reported as uncorrected.

Discussion
Based on our previous work [21], a plausible reaction mechanism was proposed (Scheme 4), featuring the initial reduction of sulfonyl chloride 2 by PPh 3 to sulfenyl chloride F via intermediates A-E. F is converted into sulfenyl iodide G in the presence of iodide anions. Finally, electrophilic thiolation of oxindoles 1 by G gives the corresponding oxindole thioethers.

Discussion
Based on our previous work [21], a plausible reaction mechanism was proposed (Scheme 4), featuring the initial reduction of sulfonyl chloride 2 by PPh3 to sulfenyl chloride F via intermediates A-E. F is converted into sulfenyl iodide G in the presence of iodide anions. Finally, electrophilic thiolation of oxindoles 1 by G gives the corresponding oxindole thioethers.

General Methods and Material
All solvents were distilled prior to use. Unless otherwise noted, chemicals were used as received without further purification. For chromatography, 200−300 mesh silica gel was employed. 1 H-and 13 C-NMR spectra were recorded at 400 MHz and 100 MHz respectively. Chemical shifts are reported in ppm using tetramethylsilane as internal standard (see supplementary). HRMS was performed on an FTMS mass instrument. Melting points are reported as uncorrected.

General Methods and Material
All solvents were distilled prior to use. Unless otherwise noted, chemicals were used as received without further purification. For chromatography, 200−300 mesh silica gel was employed. 1 H-and 13 C-NMR spectra were recorded at 400 MHz and 100 MHz respectively. Chemical shifts are reported in ppm using tetramethylsilane as internal standard (see supplementary). HRMS was performed on an FTMS mass instrument. Melting points are reported as uncorrected.

Synthesis of Oxindoles
1c-1i were synthesized according to the literature procedures [29]. 3-methylindolin-2-one (441 mg, 3 mmol) in acetonitrile (5 mL) was cooled to −15 • C. NBS (534 mg, 3 mmol) was added. After stirring for 1 h, the reaction was diluted with water (10 mL) and extracted with EtOAc (20 mL) for three times. The combined organic phase was washed with brine, dried over Na 2 SO 4 and concentrated under reduced pressure to give a residue which was purified by silica gel column chromatography to afford compound 1b (454 mg, 67%) as a white solid.

3-(p-Tolyl)indolin-2-one (4a)
Indoline-2,3-dione (1.47 g, 10 mmol) in THF (20 mL) was cooled to −15 • C. NaH (60%/mineral oil, 600 mg, 15 mmol) was added. After stirring for 30 min, p-tolylmagnesium bromide (1.0 M/THF, 10 mL, 10 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 1h. Then the reaction was quenched with NH4Cl (aq) (30 mL) and extracted with Et 2 O (50 mL) for three times. After stirring for 1 h, the reaction was diluted with water (10 mL) and extracted with EtOAc (20 mL) three times. The combined organic phase was washed with brine, dried over Na 2 SO 4 and concentrated under reduced pressure to give a residue, which was purified by silica gel column chromatography to afford compound 1b (454 mg, 67%) as a yellow solid.
Supplementary Materials: The following are available online, 1 H-NMR and 13 C-NMR of compound 3aa-3gb and 5aa-5ca.