The δ C-H amination of unactivated, secondary C-H bonds to form a broad range of functionalized pyrrolidines has been developed via a triiodide (I3−)-mediated strategy. By in situ (i) oxidation of sodium iodide and (ii) sequestration of the transiently generated iodine (I2) as I3−, this approach precludes undesired I2− mediated decomposition that can otherwise limit synthetic utility to only weak C-H bonds. The mechanism of this triiodide-mediated cyclization of unbiased, secondary C-H bonds, via thermal or photolytic initiation, is supported by NMR and UV-Vis spectroscopic data and intercepted intermediates.

After the identification of the influence of serotonergic receptors in ameliorating the negative symptoms associated with schizophrenia, atypical antipsychotics were developed by incorporating dopamine and serotonin antagonism. Risperidone, sold under the trade name Risperdal, was the second atypical antipsychotic developed following clozapine but quickly became a first-line treatment for acute and chronic schizophrenia because of its preferential side effect profile. Despite initial Food and Drug Administration approval 25 years ago, risperidone continues to be a fundamental treatment for schizophrenia, bipolar I disorder, and autism-related irritability. It is on the World Health Organization's List of Essential Medicines for its balance of efficacy, safety, tolerability, and cost-effectiveness. In this review, we highlight the history and importance of risperidone as an atypical antipsychotic, in addition to its chemical synthesis, manufacturing, drug metabolism and pharmacokinetics, pharmacology, structure-activity relationship, indications, and adverse effects.

The Cδ−H amination of unactivated, secondary C−H bonds to form a broad range of functionalized pyrrolidines has been developed by a triiodide (I3−)‐mediated strategy. By in situ 1) oxidation of sodium iodide and 2) sequestration of the transiently generated iodine (I2) as I3−, this approach precludes undesired I2‐mediated decomposition which can otherwise limit synthetic utility to only weak C(sp3)−H bonds. The mechanism of this triiodide‐mediated cyclization of unbiased, secondary C(sp3)−H bonds, by either thermal or photolytic initiation, is supported by NMR and UV/Vis data, as well as intercepted intermediates.

N-Alkyl substituted chlorotetrazines were coupled with various boronic acids under Suzuki conditions in high yield at room temperature, giving a mild and straightforward synthetic route toward diverse unsymmetrical 1,2,4,5-tetrazines, a rare heteroarene. This chemistry not only expands the known substrate scope of tetrazine cross-coupling reactions but also allows for the synthesis of novel, tetrazine-containing biologically active molecules with improved DMPK properties.

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