Organic Letters 2013-12-20

Modular isoquinoline synthesis using catalytic enolate arylation and in situ functionalization.

Ben S Pilgrim, Alice E Gatland, Charlie T McTernan, Panayiotis A Procopiou, Timothy J Donohoe

Index: Org. Lett. 15(24) , 6190-3, (2013)

Full Text: HTML

Abstract

A methyl ketone, an aryl bromide, an electrophile, and ammonium chloride were combined in a four-component, three-step, and one-pot coupling procedure to furnish substituted isoquinolines in overall yields of up to 80%. This protocol utilizes the palladium catalyzed α-arylation reaction of an enolate, followed by in situ trapping with an electrophile, and aromatization with ammonium chloride. tert-Butyl cyanoacetate participated in a similar protocol; after functionalization and decarboxylation, 3-amino-4-alkyl isoquinolines were prepared in high yield.