{Reference Type}: Journal Article
{Title}: Type I [4σ+4π] versus [4σ+4π-1] Cycloaddition To Access Medium-Sized Carbocycles and Discovery of a Liver X Receptor β-Selective Ligand.
{Author}: Jiang C;Hu L;Shen S;Zhang J;Wang X;Ma D;Lu G;Xu T;
{Journal}: Angew Chem Int Ed Engl
{Volume}: 63
{Issue}: 28
{Year}: 2024 Jul 8
{Factor}: 16.823
{DOI}: 10.1002/anie.202405838
{Abstract}: Transition-metal-catalyzed [4+4] cycloaddition leading to cyclooctanoids has centered on dimerization between 1,3-diene-type substrates. Herein, we describe a [4σ+4π-1] and [4σ+4π] cycloaddition strategy to access 7/8-membered fused carbocycles through rhodium-catalyzed coupling between the 4σ-donor (benzocyclobutenones) and pendant diene (4π) motifs. The two pathways can be controlled by adjusting the solvated CO concentration. A broad range (>40 examples) of 5-6-7 and 5-6-8 polyfused carbocycles was obtained in good yields (up to 90 %). DFT calculations, kinetic monitoring and 13C-labeling experiments were carried out, suggesting a plausible mechanism. Notably, one 5-6-7 tricycle was found to be a very rare, potent, and selective ligand for the liver X receptor β (KD=0.64 μM), which is a potential therapeutic target for cholesterol-metabolism-related fatal diseases.