Photocatalytic C-S Bond Formation Using N-Thiophthalimide and N-Perthiophthalimide Derivatives

Unsymmetric disulfides are shown to be accessed directly from carboxylic acids or trifluoroborate salts by using N-perthiophthalimide derivatives (Harpp reagents) under photoredox catalysis. While this would appear to involve homolytic substitution of alkyl radicals on the Harpp reagents, the formation of the high-energy phthalimidyl radical renders this reaction prohibitively endergonic. Instead, computations and experiments suggest that the Harpp reagents are reduced in situ to form perthiyl radicals that dimerize to tetrasulfides (RSSSSR), which have previously been demonstrated to undergo radical substitution to give disulfides. Given these results, examples of previously reported radical sulfurations using N-thiophthalimide reagents under photoredox catalysis were investigated. Our results suggest that these reactions are likely to proceed via in situ formation of the corresponding disulfide as the sulfuration reagent rather than direct substitution on the N-thiophthalimide. The implications of these findings for the use of phthalimide (and related) derivatives in photoredox-catalyzed reactions are discussed.

Automated summary

Unsymmetric disulfides can be directly synthesized from carboxylic acids or trifluoroborate salts using N-perthiophthalimide derivatives (Harpp reagents) under photoredox catalysis. The Harpp reagents are reduced in situ to form perthiyl radicals, which then dimerize to tetrasulfides and ultimately lead to the formation of disulfides. Previous radical sulfurations with N-thiophthalimide reagents are likely to proceed through the formation of the corresponding disulfide as the sulfuration reagent.