Catalytic Asymmetric [4+2]‐Cycloadditions Using Tropolones: Developments, Scope, Transformations, and Bioactivity

An organocatalyzed asymmetric [4+2]‐cycloaddition between tropolones and electron‐deficient dienophiles is presented. Complex and biologically interesting dihydrohomobarrelenone scaffolds are formed through a Diels–Alder reaction utilizing bifunctional Brønsted‐base catalysis, affording the corresponding bridged bicyclic cycloadducts in up to quantitative yields with good enantio‐ (up to 92 % ee) and diastereoselectivity (up to >20:1 d.r.). The synthetic value of the obtained products is explored by downstream transformations, including photoisomerizations, and their biological relevancy by in vivo testing in MCF‐7 cancer cells. Complex and biologically interesting dihydrohomobarrelenone scaffolds were synthesized through a Diels–Alder reaction between tropolones and electron‐deficient dienophiles, utilizing bifunctional Brønsted‐base catalysis. The synthetic value of the obtained products was explored by downstream transformations and biological relevancy by in vivo testing in MCF‐7 cancer cells.