Aqueous tantalum polyoxometalate reactivity with peroxide.

Peroxide ligation of aqueous metal-oxo clusters provides rich speciation and structural diversity, radiation sensitivity for manipulation with light, and both broadens and shifts pH-range stability. Here we demonstrate peroxide ligation of the polyoxometalate (POM) [Ta6O19]8-. We study in detail solution speciation of the peroxide-substituted cluster, and benchmark it to the peroxide-ligated niobate analogue, [Nb6O10(OH)3(O2)6]5-, whose solid-state structure has been reported. Raman and electrospray ionization mass spectroscopy do not detect any significant differences between the two analogues. However, small and wide-angle and total X-ray scattering strongly indicate that peroxide promotes linking of the hexameric tantalate clusters, rather than terminating and capping the clusters, as observed for the niobate analogue. We used computational studies to identify Raman peak positions, determine the energetics of exchange of oxo-ligands for peroxo-ligands, and provide models to help explain the X-ray scattering data. Understanding the solution speciation of peroxide-substituted polyoxotantalates is an important step towards its use in solution processed thin film materials, as well as developing new Ta-POM chemistry.

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products.

The guanidine functional group, displayed most prominently in the amino acid arginine, one of the fundamental building blocks of life, is an important structural element found in many complex natural products and pharmaceuticals. Owing to the continual discovery of new guanidine-containing natural products and designed small molecules, rapid and efficient guanidinylation methods are of keen interest to synthetic and medicinal organic chemists. Because the nucleophilicity and basicity of guanidines can affect subsequent chemical transformations, traditional, indirect guanidinylation is typically pursued. Indirect methods commonly employ multiple protection steps involving a latent amine precursor, such as an azide, phthalimide, or carbamate. By circumventing these circuitous methods and employing a direct guanidinylation reaction early in the synthetic sequence, it was possible to forge the linear terminal guanidine containing backbone of clavatadine A to realize a short and streamlined synthesis of this potent factor XIa inhibitor. In practice, guanidine hydrochloride is elaborated with a carefully constructed protecting array that is optimized to survive the synthetic steps to come. In the preparation of clavatadine A, direct guanidinylation of a commercially available diamine eliminated two unnecessary steps from its synthesis. Coupled with the wide variety of known guanidine protecting groups, direct guanidinylation evinces a succinct and efficient practicality inherent to methods that find a home in a synthetic chemist's toolbox.