Direct Substitution of Arylalkynyl Carbinols Provides Access to Diverse Terminal Acetylene Building Blocks.

To develop next generation antifolates for the treatment of trimethoprim-resistant bacteria, synthetic methods were needed to prepare a diverse array of 3-aryl-propynes with various substitutions at the propargyl position. A direct route was sought whereby nucleophilic addition of acetylene to aryl carboxaldehydes would be followed by reduction or substitution of the resulting propargyl alcohol. The direct reduction, methylation, and dimethylation of these readily available alcohols provide efficient access to this uncommon functional array. In addition, an unusual silane exchange reaction was observed in the reduction of the propargylic alcohols.