γ-Pyronecarbaldehyde-Based Practical Asymmetric Catalytic Synthesis of Chiral 2,4-Dihydroxycarboxylic Acids and α-Hydroxy-γ-lactones

Biomass derived gamma-pyrone-2-carbaldehydes were proposed as robust heterocyclic platform for carrying out organocatalytic asymmetric cross-aldol reactions with various aldehydes and ketones in high yield with excellent diastereoselectivity and enantioselectivity. Origins of efficient stereoinduction were revealed by quantum-chemical calculations of four possible transition states. The products were converted to synthetically useful chiral 2,4-dihydroxy carboxylic acid derivatives via protection/deprotection and Ru-III-catalyzed oxidative fragmentation steps without racemization of stereogenic centers. The developed approach was applied for asymmetric synthesis of chiral pantolactones, valuable precursors of biologically active substances and natural products, and for synthesis of Dexpanthenol, a medication used for treating defects in the barrier function of skin.

Automated summary

Biomass derived gamma-pyrone-2-carbaldehydes were used as a robust platform for carrying out organocatalytic asymmetric cross-aldol reactions with high yield and excellent stereoinduction. The origins of efficient stereoinduction were revealed by quantum-chemical calculations, and the products were successfully converted to synthetically useful chiral compounds.