Synthesis of Phthalides and 3,4-Dihydroisocoumarins Using the Palladium-Catalyzed Intramolecular Benzannulation Strategy

A novel method for the synthesis of phthalides and 3,4-dihydroisocoumarins via the palladium-catalyzed <i>intramolecular</i> benzannulation of bis-enyne and enyne−diyne systems is described. Various kinds of substituted phthalides <b>9</b> and <b>17</b> and 3,4-dihydroisocoumarins <b>19</b> were synthesized from <b>8</b>, <b>16</b>, and <b>18</b>, respectively, in moderate to excellent yields. The benzannulation reaction proceeded chemoselectively to give the corresponding fused ring compounds <b>A</b> without the formation of the regioisomeric products <b>B</b> (eq 6). Furthermore, this methodology was applied to the synthesis of biologically active 3-<i>n</i>-butylphthalide <b>23</b>.