Iridium-Catalyzed Asymmetric Cascade Allylation/Retro-Claisen Reaction

An enantiomerically enriched 3-hydroxymethyl pentenal unit is one of the key structural cores in plenty of natural products and drug candidates with significant biological activities. However, very few synthetic methodologies for the facile construction of the related skeletons have been reported to date. Herein, an elegant iridium-catalyzed asymmetric cascade allylation/retro-Claisen reaction of readily available beta-diketones with VEC was successfully developed, and a wide range of functionalized chiral 3-hydroxymethyl pentenal derivatives could be prepared in good yields with excellent enantioselectivities. Various 1,3-diketones and functionalized ketones containing different electron-withdrawing groups on the beta-position were well tolerated as outstanding partners with high reactivity and excellent regio-/chemo-/enantioselectivity. The synthetic utility of product chiral 3-hydroxymethyl pentenal derivatives was well shown through gram-scale transformation, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. Moreover, this elegant protocol demonstrated synthetic applications in the concise synthesis of synthetically useful chiral building block (S)-Taniguchi lactone and the formal synthesis of natural product cytisine. A rational reaction pathway was proposed based on the experimental results and control experiments.

Automated summary

This study successfully developed an elegant synthetic method for the efficient and enantioselective construction of a range of functionalized chiral 3-hydroxymethyl pentenal derivatives. The synthesized products exhibited broad synthetic utility, including transformations, hydrogenation, cyclopropanation, hydroboration, and olefin metathesis. The method also demonstrated synthetic applications in the concise synthesis of a useful chiral building block and the formal synthesis of a natural product.