Tf2O-mediated [4+2]-annulation of anthranils with 2-chloropyridines: enabling access to pyridoquinazolinones and euxylophoricine B

Abstract

We present an efficient approach for synthesizing pyridoquinazolinones in the presence of triflic anhydride utilizing anthranils and 2-chloropyridines as starting materials. In this process, Tf2O initially activates anthranils forming an electrophilic 1-((trifluoromethyl)sulfonyl)benzo[c]isoxazol-1-ium species. This species undergoes an in situ annulation reaction with 2-chloropyridines, resulting in therapeutically useful pyridoquinazolinones. The reaction is tolerant to various functional groups, allowing access to a wide range of substituted pyridoquinazolinones in good yields. Furthermore, the synthesis of euxylophoricine B, known to be an antitumor agent, was also achieved. © 2024 The Royal Society of Chemistry.