Preparation of Deuterium Labeled Compounds by Pd/C-Al-DO Facilitated Selective H-D Exchange Reactions.

The chemo/regioselective H-D exchange of amino acids and synthetic building blocks by an environmentally benign Pd/C-Al-DO catalytic system is described. Due to the importance of isotope labeled compounds in medicinal chemistry and structural biology, notably their use as improved drug candidates and biological probes, the efficient and selective deuteration methods are of great interest. The approach is based on selective H-D exchange reactions where the deuterium source is simple DO.

Methyl Cation Affinities of Canonical Organic Functional Groups.

Methyl cation affinities are calculated for the canonical nucleophilic functional groups in organic chemistry. These methyl cation affinities, calculated with a solvation model (MCA*), give an emprical correlation with the term from the Mayr equation under aprotic conditions when they are scaled to the Mayr reference cation (4-MeOCH)CH (Mayr = 0). Highly reactive anionic nucleophiles were found to give a separate correlation, while some ylides and phosphorus compounds were determined to give a poor correlation.

Methyl Anion Affinities of the Canonical Organic Functional Groups.

Calculated methyl anion affinities are known to correlate with experimentally determined Mayr parameters for individual organic functional group classes but not between neutral and cationic organic electrophiles. We demonstrate that methyl anion affinities calculated with a solvation model (MAA*) give a linear correlation with Mayr parameters for a broad range of functional groups. Methyl anion affinities (MAA*), plotted on the log scale of Mayr , provide insights into the full range of electrophilicity of organic functional groups.

Direct Alkylation of 1-Azabicyclo[1.1.0]butanes.

The facile synthesis of functionalized azetidines has been an ongoing challenge. Here, we report a general method to directly alkylate 1-azabicyclo[1.1.