Stereoselective Synthesis of Kalafungin Based on CuI-Catalyzed Tandem Reactions of Arylethynes Containing an Ortho-(1-Hydroxyethyl) Substituent with Alkyl Diazoacetates

An isochromene synthesis is developed utilizing a cascade reaction involving a CuI catalyzed coupling reaction between an alkyne and diazoacetate followed by allenoate isomerization and subsequent oxa-Michael addition. The cascade sequence was also demonstrated for the synthesis of naphthalenes. Furthermore, the methodology developed herein was applied toward a stereoselective synthesis of pyranonaphthoquinone kalafungin.

Automated summary

An isochromene synthesis method was developed using a cascade reaction involving a CuI catalyzed coupling reaction, allenoate isomerization, and subsequent oxa-Michael addition. The cascade sequence was also demonstrated for the synthesis of naphthalenes, and applied toward a stereoselective synthesis of pyranonaphthoquinone kalafungin.