Three-component domino aza-Morita-Baylis-Hillman reaction under green conditions

Abstract

The synthesis of α-methylene-β-amino compounds using a novel highly atomeconomic, one-pot, three-component reaction was studied and optimised. The reaction, which is known as the aza-Morita-Baylis-Hillman reaction, can be performed using a three-component strategy between aldehydes, amines, and electron-deficient alkenes. This variation has only been studied few times and the currently available procedures require the use of expensive and non-sustainable, acidic metal-based catalysts. In the quest towards a ‘greener’ multicomponent procedure, the reaction was studied in both the two-component and three-component formats to understand the catalytic requirements. An acid-cocatalyst approach was tested using a variety of heterogeneous acidic catalysts including those synthesised in the lab and others found in the market. Heterogeneous sulfonic acid-based ion exchange Amberlyst-15 beads were found to work outstandingly in catalysing the three-component reaction concertedly with the base catalyst DABCO. This combination provided improved yields and selectivity without the requirement of previously utilised metallic catalysts. Furthermore, the catalyst is non-polluting, readily available, and cheap. Minimal solvent use, room temperature conditions and near stoichiometric amounts of reactants further extend the sustainability the developed procedure. The protocol has been applied successfully for various aldehyde substrates, tolerating both electron-poor and electron-rich aryl aldehydes and various Michael acceptors yielding moderate to good yields. This chemistry was however unsuccessfully applied towards the use of other amine components. Attempts have also been made to immobilise the nucleophilic base catalysts onto a solid support to form a completely heterogeneous catalyst. Novel bifunctional DABCO immobilised on Amberlyst-15 catalysts was amongst the catalysts synthesised. These completely heterogeneous catalysts were however unsuccessful in catalysing the aza- MBH reaction indicating that the mechanism may require the base component to be homogeneous.