Shi-Liang Shi, Motomu Kanai and Masakatsu Shibasaki Angew. Chem. Int. Ed.
Dihydropyranones are useful intermediates for the synthesis of natural products and natural product-like scaffolds. They are accessible asymmetrically through hetero-Diels-Alder reactions using Danishefsky’s diene and aldehydes as starting materials. Shibasaki and co-workers report a stereoselective sequential aldol – oxy-Michael process for the synthesis of chiral dihydropyranones with ynones as substrates.
Ynones can be synthesised form silyl-alkynes and acyl chlorides or by PCC oxidation of the corresponding alcohol, available over one step by either method. However, taking the Danishefsky’s diene approach requires preparing starting materials by a longer route – usually four-steps – involving organolithium reagents.
In Shibasaki’s approach, the intermediate aldol is synthesised using a catalytic amount of copper(I) and (R)-DTBM-Segphos as the chiral ligand. After aqueous work-up, AgOTf is added to the crude mixture and the desired dihydropyranone is obtained after microwave irradiation. The applicability and success of this process was demonstrated by the synthesis of a range of chiral dihydropyranones using aliphatic aromatic aldehydes and ynones.