Selectfluor-Mediated Chlorination and Fluorination of Arenes: Late-Stage Functionalization of APIs and Its Biological Effects.

By using active pharmaceutical ingredients (APIs) previously recovered from expired drugs, it is shown that Selectfluor can act as a reagent for operationally simple late-stage fluorination and chlorination of electron-rich arenes under mild reaction conditions. As shown in mechanistic experiments, aromatic fluorination thereby competes with chlorine-for-fluorine exchange on Selectfluor and subsequent aromatic chlorination, whereat the chloride ions may either be provided by the hydrochloride salt of the respective API or by triethylammonium chloride. Biological testing of the fluorinated or chlorinated APIs at adrenergic, dopaminergic, muscarinergic, opioid or serotoninergic receptors demonstrated that improved binding affinities can be achieved via this straightforward strategy.

pH-Dependent Conformational Switching of Amide Bonds─from Full trans to Full cis and Vice Versa.

Strategies enabling the pH-dependent conformational switching of amide bonds from trans to cis, and vice versa, are yet limited in the sense that, in a suitable pH range, one rotamer may be stabilized to a large extent while the complementary pH range only leads to a mixture of isomers. By exploiting the effects of steric demand and the interaction of the amide carbonyl with a positive charge, we herein present the first examples for reversible pH-dependent switching from full trans to full cis.

Visible Light Promoted, Catalyst-Free Radical Carbohydroxylation and Carboetherification under Mild Biomimetic Conditions.

Metal and catalyst-free carbohydroxylations and carboetherifications at room temperature have been achieved by a combination of beneficial factors including high aryl diazonium concentration and visible light irradiation. The acceleration of the reaction by visible light irradiation is particularly remarkable against the background that neither the aryldiazonium salt nor the alkene show absorptions in the respective range of wavelength. These observations point to weak charge transfer interactions between diazonium salt and alkene, which are nevertheless able to considerably influence the reaction course. As highly promising perspective, many more aryldiazonium-based radical arylations might benefit from simple light irradiation without requiring a photocatalyst or particular additive.

Aryl Radical Selectivity in Biphasic Systems.

Aryl radicals generated in the aqueous phase of biphasic mixtures have-regardless of a comparably low polarity- a strong preference to react with aromatic substrates in the aqueous phase and not to undergo phase-transfer into a lipophilic phase, independent from the presence of a surfactant. These results represent an important prerequisite toward future studies in biological systems, which typically consist of various compartments of either hydrophilic or lipophilic character.