Asymmetric Synthesis of Dihydropyranones from Ynones by Sequential Copper(I)-Catalysed Direct Aldol and Silver(I)-Catalysed Oxy-Michael Reactions

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.

DOI: 10.1002/anie.201109209


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