A Synthesis of 4-(Hydroxymethyl)-1<i>H</i>-isochromen-1-one Analogs by Hydroxyl Oxetane Rearrangement in Protonic Acids

The synthesis of novel 4-hydroxymethyl isocoumarins through acid-promoted rearrangement of hydroxyl oxetane intermediates is reported. First, an oxetan-3-one <b>2</b> reacted with (hetero)aryl <b>1</b> through SN₂ reaction to yield the hydroxyl oxetane intermediate <b>3</b> and then <i>p</i>-TsOH or H₂SO₄ promoted the ring-opening and subsequent carboxylic acid trapping led to the dihydropyranone formation. Dehydration furnished the isocoumarin product. In one example, a terminal hydroxyl was converted to amide via tandem Ritter reaction when MeCN was the solvent. The synthesis is metal-free, and the products contain handles for further elaboration.