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

Abstrakt

A striking dependence on the method of workup has been found for annulation of benzonitriles ArC-N to N-methyl 2-toluamide (1), facilitated by n-BuLi (2 equiv): quenching the reaction by a slow addition of water produced the expected 1-isoquinolones 2; by contrast, slow pouring of the reaction mixture into water afforded the cyclic aminals 5 (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 2 and 5 were then converted into the corresponding 1-chloroisoquinolines 3, coupling of which, mediated by (Ph3P)2NiCl2/Zn, afforded bis-isoquinolines 4.

Klíčová slova

• chiral bipyridine N,N'-dioxides
• enantioselective allylation
• antitumor agents
• facile synthesis
• 2-amino-2'-diphenylphosphino-1,1'-binaphthyl map
• protoberberine alkaloids
• electrophilic additions
• palladium(II) complexes
• allylic substitution