Reaction Outcome Critically Dependent on the Method of Workup: An Example from the Synthesis of 1-Isoquinolones.

A striking dependence on the method of workup has been found for annulation of benzonitriles ArC≡N to -methyl 2-toluamide (), facilitated by -BuLi (2 equiv): quenching the reaction by a slow addition water produced the expected 1-isoquinolones ; by contrast, slow pouring of the reaction mixture water afforded the cyclic aminals (retaining the NMe group of the original toluamide). The mechanism of the two processes is discussed in terms of the actual H concentration in the workup. Both and were then converted into the corresponding 1-chloroisoquinolines , coupling of which, mediated by (PhP)NiCl/Zn, afforded bis-isoquinolines .