Whilst there are a large number of C-C bond forming reactions available for the construction of heterocycles a number of these protocols require the use of stoichiometric organometallic reagents. Since heterocycles are present in the vast majority of pharmaceutical agents the ability to forge these structures efficiently with a minimal amount of stoichiometric metallic waste is important. With this in mind we initiated a series of projects that focus on the use of [pi]-unsaturates to serve as surrogates to toxic, air and moisture sensitive nucleophilic organometallic reagents utilized in traditional C-C bond forming reactions. This has allowed us to develop catalytic couplings of vinyl azines to imines to form branched amines, to couplings of dimethylallene to isatin forming a tert-prenyl hydroxy oxindole and this neopentyl alcohol can be substituted with C-nucleophiles forming two contiguous quaternary all-carbon centers in our synthetic studies tert-prenyl indole alkaloid natural products. / text

Copper is an essential trace element for living organisms and has both known and additional suspected roles in human health and disease. The current understanding of copper metabolism is substantial but incomplete, particularly in regard to storage and exchange at the subcellular level, although available evidence indicates exchangeable intracellular copper is in the monovalent oxidation state. Selective fluorescent probes with sufficient sensitivity to detect Cu(I) availability at physiologically relevant levels and at subcellular resolution would be valuable tools for studying copper metabolism. As a contribution toward this goal, this work describes the development of Cu(I)-selective fluorescent probes with greatly improved aqueous solubility, contrast ratio, and fluorescence quantum yield. This work also describes the development of water-soluble, 1:1-binding chelators that form colorless, air-stable copper(I)-complexes. By acting as copper(I) buffering agents and affinity standards, these compounds can serve a complementary role to fluorescent probes in the study of copper biochemistry.