Designing chemical systems for precision deuteration of medicinal building blocks.

Methods are lacking that can prepare deuterium-enriched building blocks, in the full range of deuterium substitution patterns at the isotopic purity levels demanded by pharmaceutical use. To that end, this work explores the regio- and stereoselective deuteration of tetrahydropyridine (THP), which is an attractive target for study due to the wide prevalence of piperidines in drugs. A series of d-d tetrahydropyridine isotopomers were synthesized by the stepwise treatment of a tungsten-complexed pyridinium salt with H/D and H/D.

Synthesis of 1-Azatriene Complexes of Tungsten: Metal-Promoted Ring-Opening of Dihydropyridine.

For nearly a century, chemists have explored how transition-metal complexes can affect the physical and chemical properties of linear conjugated polyenes and heteropolyenes. While much has been written about higher hapticity complexes (η-η), less is known about the chemistry of their η analogues. Herein, we describe a general method for synthesizing 5,6-η-(1-azatriene) tungsten complexes via a 6π-azaelectrocyclic dihydropyridine ring-opening that is promoted by the π-basic nature of {WTp(NO)(PMe)}.

The Tungsten-Promoted Synthesis of Piperidyl-Modified -Methylphenidate Derivatives.

Due to its efficacy as a dopamine receptor agonist, methylphenidate (MPH) is of interest as a potential therapeutic for cocaine addiction. While numerous derivatives of MPH have been investigated for their potential medicinal value, functionalization of the piperidine ring has not been explored. The pyridine borane ligand in WTp(NO)(PMe)(η-pyBH) is dearomatized by the metal and can be elaborated to the analogous η-mesylpyridinium complex.