Three types of N(H)-nucleophiles, viz. hydrazine, acetyl hydrazide, and a set of hydrazones, were used to study the nucleophilic addition to the CN group of the 2-propanenitrilium closo-decaborate cluster (Ph₃PCH₂Ph)[B₁₀H₉NCEt], giving N-closo-decaborato amidrazones. A systematic mechanistic study of the nucleophilic addition is provided and included detailed synthetic, crystallographic, computational and kinetic work. As a result, two possible mechanisms have been proposed, which consist of firstly a consecutive incorporation of two Nu(H) nucleophiles, with the second responsible for a subsequent rapid proton exchange. The second possible mechanism assumes a pre-formation of a dinuclear [Nu(H)]₂ species which subsequently proceeds with the nucleophilic attack on the boron cluster. The activation parameters for hydrazones indicate a small dependence on bond formation [ΔH^‡ = 6.8–15 kJ mol⁻¹], but significantly negative entropies of activation [ΔS^‡ ranges from −139 to −164 J K⁻¹ mol⁻¹] with the latter contributing some 70–80% of the total Gibbs free energy of activation, ΔG^‡. In the X-ray structure of (Z)-(Ph₃PCH₂Ph)[B₁₀H₉N(H)C(Et)NHNCPh₂], very rare intramolecular non-covalent B–H⋯π(Ph) interactions were detected and studied by DFT calculations (M06-2x/6-311++G** level of theory) and topological analysis of the electron density distribution within the framework of Bader's theory (QTAIM method). The estimated strength of these non-covalent interactions is 0.8–1.4 kcal mol⁻¹.

Heterocyclic nonacetamide ligands are used as positron emission tomography (PET) imaging agents of the synaptic vesicle glycoprotein 2A (SV2A), with potential applications in the diagnosis of various neuropsychiatric diseases. To date, the main synthetic strategy to access these optically active compounds has involved the racemic synthesis of a late-stage intermediate followed by the separation of the enantiomers. Here, we describe the use of iminium organocatalysis for the asymmetric synthesis of SynVesT-1, an important PET imaging agent of SV2A. The key step involved the conjugate addition of nitromethane with a cinnamaldehyde in the presence of the Jørgensen-Hayashi catalyst using the Merck dual acid cocatalyst system. Pinnick-type oxidation and esterification of the adduct was then followed by chemoselective nitro group reduction and cyclization using nickel borate. N-Alkylation of the resulting lactam then completed the seven-step synthesis of SynVesT-1. This approach was amenable for the synthesis of an organotin analogue, which following copper(II)-mediated fluoro-destannylation allowed rapid access to [¹⁸F]SynVesT-1.

Fluorescent unnatural amino acids are important tools for peptide and biomolecular imaging, yet the development of new probes that combine strong emission with minimal structural perturbation remains a challenge. Herein, we report a versatile strategy for the diversification of tryptophan based on a stable and isolable C2-iodinated building block that is readily compatible with palladium-catalyzed cross-coupling reactions. This approach allows for the installation of alkynyl and aryl substituents at the C2 position, providing rapid access to a range of unnatural tryptophan derivatives and peptides in good to high yields. Photophysical studies revealed that aryl-substituted tryptophan analogues exhibit strong fluorescence, high quantum yields, and environment-sensitive emission. Strong fluorescence was retained upon incorporation into a tryptophan-containing dipeptide, highlighting the potential of these relatively small C2-substituted analogues as imaging probes for biomolecular imaging applications.