Carbon-carbon bond cleavage of α-hydroxybenzylheteroarenes catalyzed by cyanide ion: Retro-benzoin condensation affords ketones and heteroarenes and benzyl migration affords benzylheteroarenes and arenecarbaldehydes

Abstract

4-(α-Benzylα-hydroxybenzyl)quinazoline (4a) underwent retro-benzoin condensation catalyzed by cyanide ion to give deoxybenzoin (2a) and quinazoline (5a). Similarly, several nitrogen-containing heteroarenes (4, 9, 12, 16-19) having an α-hydroxybenzyl group at the α-position of the nitrogen underwent retro-benzoin type condensation to afford kelones (2) and heteroarenes (5). However, similar reaction of pyrazolopyrimidines (13, 14, 15) having an α-benzyl-α-hydroxybelzyl group resulted in benzyl migration, giving benzylpyrazolopyrimidines (8) and arenecarbaldehydes (3). Tetrabutylammonium cyanide (11, Bu4NCN) was a more effective cyanide ion donor than KCN (10). The retro-benzoin condensation was applied to the synthesis of 2-substituted quinazolines (38) from 2-chloro-4- aroylquinazolines (34), using the aroyl group as a protecting and electron- withdrawing group.