Cycloaddition reaction between oxazoles and arynes toward the preparation of functionalized isoquinolines

Isoquinoline core can be found in some bioactive natural products and synthetic drugs employed in the treatment of various diseases. Accordingly, the preparation of isoquinoline compounds have been explored through cycloaddition reactions between oxazoles and benzyne precursors, using relatively harsh reaction conditions, involving hazardous reagents and high temperatures, as well as Pb(OAc)4 as a strongly oxidizing reagent at low temperature. Therefore, we have decided to study the cycloaddition reaction between 4-aryloxazoles and 2-(trimethylsilyl)aryl triflates, well-established aryne precursors, employing mild reaction conditions, to produce cycloadducts in 56-75% yields, which have been converted to 3-aryl-4-hydroxyisoquinolines using trifluoroacetic acid in 79-92% yields.