Research Projects

Asymmetric synthesis of substituted cyclohexane derivatives is crucial for the total synthesis of bioactive natural products and pharmaceutical drugs. Asymmetric aminocatalysis plays a significant role in the construction of chiral cyclohexane derivatives through multicomponent and cascade reactions. A novel methodology for asymmetric synthesis of chiral cyclohexane derivatives using cascade dual aminocatalysis via Mannich/Michael/intramolecular Michael reactions has been reported. However, substituted acetones like phenylacetone and diphenylacetone resulted in Michael addition followed by aldol condensation products. The reaction of azidoacetone or acetoacetates with α,β-unsaturated aldehydes using aminocatalysis yielded cyclohexanone derivatives with excellent enantioselectivity via Michael/aldol reaction. However, diarylacetones with α,β-unsaturated aldehydes produced Michael adducts with poor to moderate enantioselectivity. In situ kinetic resolution of the Michael adduct resulted in tetrasubstituted cyclohexanones with moderate enantioselectivity. The proposed methodology aims to study the reaction of diarylacetones with α,β-unsaturated aldehydes using dual aminocatalysis to obtain cyclohexane derivatives with higher enantioselectivity. The methodology can also be applied to the total synthesis of bioactive natural products, such as potent cannabinoid 10α-hydroxy-Δ8-tetrahydrocannabinol.