Nitrogen heterocycles are prevalent components of small-molecule drugs, residing in 59% of FDA approved pharmaceuticals in 2012. Within this class of compounds, six-membered heteroaromatics, such as pyridines, quinolines, pyrimidines, pyrazines, and pyridazines are especially common. Given their abundance in pharmaceuticals and agrochemistry, as well as the challenges associated with selectively transforming these moieties, direct methods to selectively functionalize nitrogen heteroaromatics grow increasingly important. A method has been developed in our laboratory to selectively install triphenylphosphonium salts at the 4-position of pyridines and diazines with excellent regioselectivity. Using these N-heterocyclic phosphonium salts, a broadly applicable protocol for deuteration and tritiation of pyridines, diazines, and pharmaceuticals has been developed. This process is operationally simple and installs the isotopes in high yields and, in general, with exclusive regioselectivity. Additionally, a new means to construct bisheterobiaryls directly from pyridine C-H bonds and heterocyclic phosphonium salts via a single-electron pathway has been accomplished.<br/>

Selective functionalization of nitrogen heteroaromatics via heterocyclic phosphonium salts

2019 Spring National Meeting

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