Direct Access to Quinazolines and Pyrimidines from Unprotected Indoles and Pyrroles through Nitrogen Atom Insertion
Julia C. Reisenbauer, Ann-Sophie K. Paschke, Jelena Krizic, Bence B. Botlik, Patrick Finkelstein, Bill Morandi
Abstract
Recent advances in single-atom insertion reactions have opened up new synthetic approaches for molecular diversification. Developing innovative strategies to directly transform biologically relevant molecules, without any prefunctionalization, is key to further expanding the scope and utility of such transformations. Herein, the direct access to quinazolines and pyrimidines from the corresponding unprotected 1 H -indoles and 1 H -pyrroles is reported, relying on the implementation of lithium bis(trimethylsilyl)amide (LiHMDS) as a novel nitrogen atom source in combination with commercially available hypervalent iodine reagents. Further application of this strategy in late-stage settings demonstrates its potential in lead structure diversification campaigns.