Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes

Abstract

Single electron reduction is more challenging for sulfamoyl chlorides than sulfonyl chlorides. However, sulfamoyl and sulfonyl chlorides can be easily activated by Cl-atom abstraction by a silyl radical with similar rates. This latter mode of activation was therefore selected to access aliphatic sulfonamides, applying a single-step hydrosulfamoylation using inexpensive olefins, tris­(trimethylsilyl)­silane, and photocatalyst Eosin Y. This late-stage functionalization protocol generates molecules as complex as sulfonamide-containing cyclobutyl-spirooxindoles for direct use in medicinal chemistry.

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

“…Illustrative example of a Cl atom abstraction strategy for the photocatalytic generation of sulfamoyl radicals from sulfamoyl chlorides: the radical chlorine abstraction for a Giese reaction reported by Gouverneur and co-workers [174].…”

“…To bypass the strong reductive conditions communally used for the activation of sulfamoyl chlorides to form the corresponding sulfamoyl radicals, Gouverneur and co-workers developed an efficient method based on chloride abstractions. They could successfully convert the sulfamoyl chlorides 44.1 to the alkyl sulfonamides 44.4 using eosin Y (OD13) as a photocatalyst and the supersilane 44.3 for a halogen abstraction (Scheme 44) [174]. Under visible-light irradiation, the excited state OD13* can oxidize the silane, generating, after deprotonation, a silyl radical, which can efficiently abstract the chlorine atom, resulting in the nucleophilic sulfamoyl radical.…”

Hydrosulfonylation of Alkenes with Sulfonyl Chlorides under Visible Light Activation

“…The excited state of fac ‐Ir(ppy) 3 is quenched by sulfonyl chloride 1 a , implying that a direct single‐electron reduction of the sulfonyl chloride, leading to the formation of sulfonyl radical anion is plausible. This reactivity profile contrasts with that of N , N ‐dimethylsulfamoyl chloride . Notably, (TMS) 3 SiH does not quench the excited state of fac ‐Ir(ppy) 3 , advocating against an initiation scenario whereby [Ir III *] could undergo single‐electron transfer with tris(trimethylsilyl)silane to generate the Si‐centered radical 12 upon loss of a proton…”

Stereoselective synthesis and applications of spirocyclic oxindoles

“…84 Gouverneur recently developed a silyl radical-mediated hydrosulfamoylation using sulfonyl chlorides and could effect a cascade spirocyclisation (Giese-type addition followed by aryl C-H transfer) from cyclobutene 15, albeit with only poor diastereoselectivity (Scheme 16). 85 [2 + 2]-Cycloaddition. A significant advance in spirocyclobutyl oxindole synthesis was made by Wang and successively by Jørgensen in 2014/2015 in the field of organocatalytic [2 + 2]cycloadditions of 3-ylideneoxindoles (Scheme 17).…”