Science of Synthesis

Bernardi, L.; Ricci, A., Science of Synthesis: Multicomponent Reactions, (2014) 1, 153.

A tandem double Mannich reaction is observed when hydroxybenzaldehydes, pyrrole-2-carbaldehyde, or indole-3-carbaldehyde are reacted with acetone in ammonia solutions. The 6-aryl-2,2-dimethylpiperidin-4-ones ‌29‌ are obtained in moderate to good yields via the double activation of both aldehydes and ketones by ammonia (‌Scheme 32‌).[‌44‌] The absence of a proton in the aldehyde, either on the oxygen of the hydroxybenzaldehydes or the nitrogen of the pyrrole- and indolecarbaldehydes, drives the reaction toward the formation of the aldol instead of the Mannich product.

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References