Highly diastereodivergent green synthesis of cyclohexanones via double Michael addition of malononitrile to Dibenzalacetone

Abstract

The distinct biological activities of stereoisomers make diastereoselective synthesis a pivotal area in organic chemistry, especially following environmentally friendly practices. In this study, a novel green bis-Michael cycloaddition strategy was developed, adhering to multiple principles of green chemistry. Key highlights include using ethanol as the solvent, reaction conditions at room temperature, new cyclohexanone derivatives with good to excellent yield and diastereoselectivity, diastereodivergent, scalability, and simplified purification steps. Optimization studies involving various solvents, bases, and temperatures were conducted to establish the best reaction conditions. Furthermore, the versatility of this method was demonstrated with a range of electron-rich and electron-withdrawing substituents on DiBenzylideneAcetone (DBA) derivatives. Additionally, several transformations were performed to explore the conformations of the resulting products, employing 1D and 2D NMR techniques and mass spectrometry for detailed analysis.