We report a combined photocatalytic and hydrogen atom transfer (HAT) approach for the light-mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di-to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.

Straightforward and mild hexafluoroisopropanol (HFIP)-mediated, metal-free, three-component Friedel−Crafts approaches are reported for the synthesis of alkenyl and alkyl trifluoromethyl sulfides from arenes, (PhSO 2 ) 2 NSCF 3 , and alkynes or alkenes, respectively. The transformations proceed with high regio-and stereochemical control via the initial formation of cationic thiirenium and thiiranium intermediates, respectively, followed by Friedel−Crafts reactions with the arene. A mechanistically related three-component synthesis of alkenyl iodides from arenes, alkenes, and N-iodosuccinimide is also reported.

Unprotected, α,β-disubstituted tryptamines and phenethylamines are obtained by a one-pot, metal-free sequence that proceeds by the in situ formation of aziridinium salts followed by Friedel–Crafts reaction with electron-rich (hetero)arenes. Both steps are facilitated by hexafluoroisopropanol as the solvent. The one-pot sequence was effective for diversely substituted indoles and 1,3,5-trimethoxybenzene, for cyclic and acyclic alkenes, and proceeded in a stereospecific fashion for both (E)- and (Z)-1,2-disubstituted alkenes. Moreover, one-pot morpholine addition to an aziridinium salt provided a diamine.