Two-, three- and four-component coupling to form isoquinolones based on directed metalation

Benzamides undergo ortho-metalation with magnesiate bases to allow trapping with propargylic chlorides. Cyclization provides isoquinolones in a one-pot operation. Benzamides can be formed in situ from aryl Grignard reagents and isocyanates. Moreover, electrophilic trapping after cyclization introduces further complexity. Alternative cyclization conditions provide the isomeric aza-isocoumarins.