Enantioselective Organocatalytic Synthesis of δ-Lactone-Fused 4-Chromanones

An organocatalytic enantioselective synthesis of delta-lactone-fused 4-chromanones was demonstrated using 1-(2-hydroxyaryl)-1,3-butanedione and alpha,beta-unsaturated aldehydes in the presence of the Jorgensen-Hayashi catalyst. The reaction proceeded through a Michael addition/cycloketalization/hemiacetalization sequence, and the resulting hemiacetals were oxidized into the corresponding lactone derivatives in a one-pot manner. The desired fusedO,O-ketal tricyclic lactone motifs containing three contiguous chiral centers were obtained in excellent chemical yields (up to 97%) and with high stereoselectivities (up to >20:1 dr and up to 95% ee).