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 18F labeled versions of the agents for subsequent use in positron emission tomography (PET) imaging. A homolog of the Alzheimer’s disease imaging agent Fallypride® was prepared using the methodology and additional analogs was identified.
Keywordsflow chemistry microfluidics fluorine positron emission tomography Sonogashira coupling
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