Traceless solid-phase synthesis of N-substituted 3,5-bis(substituted-idene)piperidin-4-one derivatives

A series of N-substituted 3,5-bis(substituted-idene)piperidin-4-ones have been prepared using solid-phase organic synthesis. The synthesis starts with a Michael addition with piperidin-4-one serving as the donor and REM resin as the acceptor. Various aldehydes were then utilized through a Knoevenagel condensation to afford the 3,5-bis(substituted-idene)piperidin-4-ones on the solid support. The final products were removed from the support and a second diversity position was introduced through a Hofmann elimination using different alkyl bromides.