Synthesis of 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones

An efficient synthetic route to Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones has been developed. 3-Aryl-1-(3-bromo-5-chloro-2-hydroxyphenyl)-2-propen-1-one or 2-aryl-8-bromo-6-chlorochroman-4-one could be reacted under Mannich conditions yielding 2-aryl-8-bromo-6-chloro-3-methylenechroman-4-one, which was further converted to the target compound via an aza-Michael reaction followed by an SeO2 oxidation. This procedure represents a new method to introduce a primary aminomethyl group at the 3-position of a 2-arylchromone scaffold. The Cbz-protected 3-aminomethyl-2-aryl-8-bromo-6-chlorochromones can, e.g., be used in the synthesis of chromone-based beta-turn peptidomimetics.