Fluoroalkynylations of Aryl Halides under Continuous-Flow Homogeneous Catalysis

Continuous-flow methodologies have been applied to the synthesis of a number of fluorinated alkynyl arenes and heteroarenes. Through a series of optimizations reagent stoichiometry and reaction time were improved and substrate specificity was interrogated. Using optimized conditions under copper-free Sonogashira type couplings readily available arene building blocks were derivatized with fluoroalkynyl side chains in <10 min. Given the rapidity of the process and the enhanced purity profile of the products an immediate application of the work is in the development of F-18 labeled versions of the agents for subsequent use in positron emission tomography (PET) imaging. A homolog of the Alzheimer's disease imaging agent Fallypride (R) was prepared using the methodology and additional analogs was identified.