Asymmetric synthesis of chromanone lactones via vinylogous conjugate addition of butenolide to 2-ester chromones

Chiral chromanone lactones are a class of natural products with important biological activity. We report a direct diastereo- and enantioselective vinylogous conjugate addition of butenolide to 2-ester substituted chromones. The transformation proceeded well in the presence of as low as 1 mol% of a chiral N,N '-dioxide/Sc-III complex, 3 angstrom MS and a catalytic amount of hexafluoroisopropanol (HFIP). The scope of Michael acceptors includes a variety of substituted chromones at different positions, and the desired chromanone lactones upon reduction are afforded in good yield and diastereoselectivity, and excellent enantioselectivity (up to 99% ee). The strategy could be used in the concise synthesis of blennolide C and gonytolide A, C and G.

Automated summary

Chiral chromanone lactones are important natural products with significant biological activity. In this study, we developed a direct diastereo- and enantioselective vinylogous conjugate addition of butenolide to 2-ester substituted chromones. The reaction demonstrated good efficiency and selectivity, providing the desired products in high yield and excellent enantioselectivity.