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 Bronsted-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 invivo testing in MCF-7 cancer cells.