Regiodivergent Construction of Medium-Sized Heterocycles from Vinylethylene Carbonates and Allylidenemalononitriles
Medium-sized heterocycles exist in a broad spectrum of biologically active natural products and medicinally important synthetic compounds. The construction of medium-sized rings remains challenging, particularly the assembly of different ring sizes from the same type of substrates. Here we report palladium-catalyzed, regiodivergent [5+4] and [5+2] annulations of vinylethylene carbonates and allylidenemalononitriles. We describe the production of over 50 examples of nine- and seven-membered heterocycles in high isolated yields and excellent regioselectivities. We demonstrate the synthetic utility of this approach by converting a nine-membered ring product to an interesting polycyclic caged molecule via a [2+2] transannulation. Mechanistic studies suggest that the [5+2] annulation proceeds through a palladium-catalyzed ring-opening/re-cyclization from the [5+4] adducts.