193944-65-9

Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

Methods of preparing a fluorinated aryl or heteroaryl substrate by combining a quaternary ammonium cyanide and an aryl or heteroaryl substrate substituted with at least one chloro, bromo, sulfonyl, or nitro group to thereby provide a mixture, and combining the mixture with hexafluorobenzene to thereby provide the fluorinated substrate.

A range of (2,2':6',2''-terpyridine)platinum(II) complexes are shown to possess antiprotozoal activity in vitro against Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, the causative organisms of tropical diseases leishmaniasis and trypanosomiasis. The best compounds caused 100% and 78% inhibition of growth of the intracellular amastigote forms of L. donovani and T. cruzi, respectively, at a concentration of 1 μM and 100% inhibition of growth of the bloodstream trypomastigote forms of T. brucei at a concentration of 0.03 μM. The results obtained with complexes in which the fourth ligand to platinum(II) is capable of being substituted with a substitution inert hydroxyethanethiolate complex are compared. The amine complexes show high antiprotozoal activity suggesting that the trans influence of the 2,2':6',2''-terpyridine ligand has a profound effect on the ease of displacement of the fourth ligand in (2,2':6',2''- terpyridine)platinum(II) complexes, although nonbonded interaction between the amine ligand and the 6 and 6'' hydrogens probably also weakens the ligation to Pt(II).