Asymmetric Synthesis of Chiral Aza-macrodiolides via Iridium-Catalyzed Cascade Allylation/Macrolactonization

Iridium-catalyzed cascade allylation/macrolactonization between vinylethylene carbonate (VEC) and isatoic anhydride derivatives was successfully developed, readily generating a wide range of C-2-symmetric chiral macrodiolides bearing 14-membered rings in moderate to good yields with excellent diastereoselectivities and enantioselectivities (generally 99% ee). Control experiments revealed that racemic VEC as the precursor of electrophilic iridium-pi-allyl species underwent kinetic resolution process. This expedient protocol features easily available substrates, excellent stereoselective control, and high step economy.

Automated summary

In this study, an iridium-catalyzed cascade allylation/macrolactonization reaction was developed, which efficiently synthesizes chiral macrodiolides with excellent diastereoselectivities and enantioselectivities. This method is characterized by readily available substrates, high stereoselective control, and efficient synthetic steps.