Diastereoselective Synthesis of Bicyclo[3.2.1]octanes via Catalyst-Free Cascade Michael/Henry Reaction with a Functionalized Vinylogous Nucleophile

A readily prepared and functionalized vinylogous nucleophile has been explored and utilized to construct bridged bicyclic compounds. The corresponding cascade Michael/Henry reaction occurred with relatively high reactivity under catalyst-free and mild conditions. A range of structurally distinct bicyclo[3.2.1]octanes were generated in 40-96% isolated yields with excellent diastereoselectivities (& GE;10:1 dr). Gram-scale synthesis was also demonstrated.