Investigating chemical diversity: o-propargylphenols as key compounds in the divergent synthesis of 2-substituted benzofurans and chromenes†

Abstract

In this study, we explored and optimized a MW-enhanced divergent approach for the synthesis of 2-substituted benzofurans and chromenes, starting from seventeen substituted o-propargylphenols characterized by a monoaryl substitution on the propargylic sp³ carbon. Firstly, we developed a robust platform for the preparation of a library of o-propargylphenols. Under basic conditions, o-propargylphenols reacted regioselectively to yield benzofurans in yields ranging from 43% to 100%. Conversely, under cationic gold catalysis, we were able to obtain the corresponding 4H-chromenes, albeit in more variable yields (from 25% to 93%) and slightly lower regioselectively. We also proposed plausible mechanisms to explain the divergent outcomes observed. Our findings underscore the potential of diversity-oriented synthesis in the investigation of molecular complexity. Our neglected o-propargylphenols have proven to be versatile and strategic starting materials for accessing oxygen-containing heterocyclic scaffolds through intramolecular cyclization reactions.