One-Pot Phosphonylation of Heteroaromatic Lithium Reagents: The Scope and Limitations of Its Use for the Synthesis of Heteroaromatic Phosphonates
Ewa Chmielewska,
Natalia Miodowska,
Błażej Dziuk,
Mateusz Psurski,
Paweł Kafarski
Affiliations
Ewa Chmielewska
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
Natalia Miodowska
Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland
Błażej Dziuk
Department of Inorganic and Structural Chemistry, Faculty of Chemistry, University of Opole, ul. Oleska 48, 45-052 Opole, Poland
Mateusz Psurski
Laboratory of Experimental Anticancer Therapy, Department of Experimental Oncology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland
Paweł Kafarski
Department of Chemistry, Faculty of Agriculture and Forestry, University of Warmia and Mazury, Plac Łódzki 4, 10-721 Olsztyn, Poland
A one-pot lithiation–phosphonylation procedure was elaborated as a method to prepare heteroaromatic phosphonic acids. It relied on the direct lithiation of heteroaromatics followed by phosphonylation with diethyl chlorophosphite and then oxidation with hydrogen peroxide. This protocol provided the desired phosphonates with satisfactory yields. This procedure also had some limitations in its dependence on the accessibility and stability of the lithiated heterocyclic compounds. The same procedure could be applied to phosphonylation of aromatic compounds, which do not undergo direct lithiation and thus require the use of their bromides as substrates. The obtained compounds showed weak antiproliferative activity when tested on three cancer cell lines.
