Direct sulfonylation of anilines mediated by visible light

Visible light photocatalysis allows the introduction of the sulfone functional group to anilines under mild reaction conditions, without the need for pre-functionalization.

. Photoredox apparatus.   After conducting a survey of literature reports for electrophilic aromatic sulfonylation reactions, three exemplar conditions 1 from the current state of the art were selected and applied to the methylsulfonylation of N,N-dimethyl-p-toluidine (Scheme S1). No trace of 1 was observed in all cases.
In some reactions thiosulfonates were isolated. To probe their possible role in the reaction S-methyl methanethiosulfonate was used in place of sodium methanesulfinate in the methanesulfonylation of N,N-dimethyl-p-toluidine following general procedure A (Scheme S2). The sulfonylation product was observed in only 6% NMR yield suggesting that thiosulfonates do not play a significant role.

Scheme S3. Radical trapping experiments.
A sulfonylation according to general procedure A was performed in the presence of 3 equivalents of TEMPO (Scheme S3) resulting in a much lower yield than would be otherwise expected (28% vs 85% without TEMPO) indicating that a mechanism involving radical intermediates is likely in operation. The same experiment instead utilizing 1,1-diphenylethene as a trapping agent resulted in the formation of aryl sulfone in only trace quantities. The known compound (2-methanesulfonyl-1phenylethenyl)benzene was observed in 12% NMR yield, indicating that sulfonyl radicals are likely formed under the reaction conditions. mechanism requiring oxidation of the aniline to the radical cation as electron-withdrawing groups will raise the oxidation potential.

2-Cyclobutylmethanesulfanylpyridine
2-Mercaptopyridine (278 mg, 2.50 mmol) in THF (2 mL) was added to a suspension of 60% NaH in mineral oil (300 mg, 3.00 mmol) in dry tetrahydrofuran (3 mL) at 0 °C. After stirring at this temperature for 30 mins bromomethylcyclobutane (0.14 mL, 3.00 mmol) was added. The mixture was allowed to warm to room temperature and stir overnight. A saturated NaHCO 3 solution (10 mL) was added and the mixture was extracted with ethyl acetate (3 x 10 mL). The combined organic extracts were dried (MgSO 4 ), filtered and the volatiles were removed under reduced pressure. Column chromatography on silica (0-20% ethyl acetate in petroleum ether), afforded the expected product as a pale yellow oil (260 mg, 1.45 mmol, 58%

2-Cyclobutylmethanesulfonylpyridine
Prepared according to a modified literature procedure. 2

Synthesis and Characterisation of Sulfonylation Products
In the following general procedures the solvent mixture was sparged with nitrogen for 10 mins prior to use. The reactions can be carried out in air but some N-dealkylation of the aniline substrate may be observed.
General procedure A: Table 2, aniline scope.

2-Methanesulfonyl-4-methoxy-N,N-dimethylaniline (15)
Prepared according to general procedure A. Following column chromatography on silica (0-60% ethyl acetate in petroleum ether), the material was redissolved in acetonitrile (1 mL) to which was added 2 M NaOH solution (1 mL). The mixture was stirred at room temperature for 3 h before extracting with ethyl acetate (3 x 1 mL). The combined organic extracts were dried (MgSO 4 ), filtered and the volatiles were removed under reduced pressure to afford the titled sulfone as a pale yellow, crystalline solid (