Reaction of benzocyclobutenoxides with nitriles: Synthesis of hypecumine and other 3-substituted isoquinolines

Abstract Treatment of benzocyclobuten-2-ols with MeLi affords o -tolualdehyde anions which in the presence of nitriles cyclize to 3-substituted isoquinolines. Examples include the synthesis of the alkaloid hypecumine from the precursors, 14 and 19 (1:1), in 50% yield.