Imidoylation of organotellurium compounds with isonitriles has been investigated in conjunction with the radical-mediated C1 homologation reaction by using CO and isonitriles. Carbon-centered radicals generated photochemically or thermally from organotellurium compounds react with isonitriles in a group-transfer manner to give the corresponding imidoylated products. Organotellurium compounds have been found to serve as effective precursors of a wide variety of stabilized radicals, namely benzyl, alpha-alkoxy, alpha-amino, and acyl radicals, which take part in the imidoylation with high efficiency. The reactions are compatible with various functional groups, and can be carried out in various solvents including environmentally benign water. The reactivity of isonitriles has been compared with that of CO through competition experiments, and the results indicate that isonitriles are superior to CO as radical acceptors in reactions with stabilized radicals. The origin of the differences has been addressed in theoretical studies with density functional theory calculations using the B3LYP hybrid functional. The calculations suggest that both carbonylation and imidoylation proceed with low activation energies, and that there are virtually no differences in the kinetic sense. Instead, it indicates that thermodynamic effects, namely differences in the stability of the acyl and the imidoyl radicals, control the overall course of the reactions.

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A new thermal coupling reaction forms silyloxy imidoyl tellurides 2 from silyl tellurides 1, carbonyl compounds, and phenyl isocyanide [Eq. (1)]. A mechanism that involves the generation of the silyl radical from the silyl telluride and subsequent chemoselective coupling with carbonyl compounds and the isocyanide is proposed.

A series of compounds based on 7-{[4-(2-methylphenyl)piperidin-1-yl]methyl}-6,7,8,9-tetrahydro-5 H-cyclohepta[ b]pyridine-9-ol ( (-)-8b), a potent and selective opioid receptor-like 1 (ORL1) antagonist, was prepared and evaluated using structure-activity relationship studies with the aim of removing its affinity to human ether-a-go-go related gene (hERG) K (+) channel. From these studies, 10l was identified as an optimized structure with respect to ORL1 antagonist activity, and affinity to the hERG K (+)channel. Furthermore, 10l showed good in vivo antagonism with a wide therapeutic index in regards to adverse cardiovascular effects.