Hydrosulfonylation of Alkenes with Sulfonyl Chlorides under Visible Light Activation

Abstract Sulfonyl chlorides are inexpensive reactants extensively explored for functionalization, but never considered for radical hydrosulfonylation of alkenes. Herein, we report that tris(trimethylsilyl)silane is an ideal hydrogen atom donor enabling highly effective photoredox‐catalyzed hydrosulfonylation of electron‐deficient alkenes with sulfonyl chlorides. To increase the generality of this transformation, polarity‐reversal catalysis (PRC) was successfully implemented for alkenes bearing alkyl substituents. This late‐stage functionalization method tolerates a remarkably wide range of functional groups, is operationally simple, scalable, and allows access to building blocks which are important for medicinal chemistry and drug discovery.


NOTE:
 The amount of sulfonyl chloride can be reduced (< 2.5 equivalents) depending on the substitution pattern of the sulfone as well as the olefin used. The substrate scope described in the paper has been performed using 2.5 equivalents of sulfonyl chloride in order to promote higher yields for all substrates.
 The temperature of the reaction mixture could reach 35 °C depending on the distance of the vial to the kessil lights. Fluctuation of the temperature (from room temperature using a fan to 60 degrees in flow) didn't impact the outcome of the reaction.
 Desulfonylation has never been observed under our reaction conditions.    Figure S1: Quantitative 19 F NMR of the reaction mixture before and after irradiation with blue LEDs.
Previous reports showed that sulfinic acids can undergo Michael addition to electron-deficient alkenes. 17 Nevertheless, as shown above, the efficiency of this addition is dependent on the alkene.

Scale-up experiments
The scale-up experiments (in batch and in continuous flow) have been performed on the synthesis of compound 3am.

Scale-up experiment in batch
Scheme S1: Multigram synthesis of 3am in batch. 1.0 equiv) * was added to a 500 mL round bottom flask. To that solution was added 4-S15 fluorobenzenesulfonyl chloride (24.8 g, 127.4 mmol, 2.5 equiv) and fac-Ir(ppy)3 (167.6 mg, 0.25 mmol, 0.5 mol%). This suspension was transfered to the Radley 1L reactor, followed by the addition of (TMS)Si3H (31.4 mL, 101.9 mmol, 2.0 equiv) and MeCN (115 mL). The reactor was irradiated with two Kessil H150-Blue LED lights (34 W, 5 cm distance, see picture above) for 16 h at 30 °C. The reaction mixture was collected from the outlet and concentrated in vacuo. The crude was purified by flash column chromatography (silica, sample dry-loading with Celite ® , EtOAc in Heptane with 1% acetic acid, 0/100 to 100/0). The desired fractions were collected and concentrated in vacuo to give the desired hydrosulfonylated product 3am as mixture of diastereoisomers (89/11, cis/trans) and as an off-white solid (10.7 g, 41.5 mmol, 81%). Trituration with Et2O afforded exclusively the cis-diastereoisomer as a white solid (

trans-configuration:
No NOE interaction detected between Hα and Hβ.

cis-configuration:
NOE interaction detected between HA and HB.

trans-configuration:
No NOE interaction detected between HA and HB. 11. X-ray -Crystallographic Data for 6