Chiral Quaternary Stereocenters via Rh(I)-Catalyzed [2+2+2] Cycloaddition

Significance

Using a preformed [Rh(cod){(S)-xylyl-BINAP}]BF₄ catalyst, a tethered diyne and a cyclic exo-α,β-unsaturated ester or ketone can undergo a formal [2+2+2] cycloaddition to afford chiral spirocyclic dienes with excellent levels of enantio- and regioselectivity and yield. This approach was extended to the synthesis of dienes with chiral tertiary and quaternary stereocenters by employing acrylates and a [Rh(cod){(S)-H₈-BINAP}]BF₄ catalyst. Generally, the loading of the exo-alkene coupling partner is much lower than previously reported intermolecular ene-diyne cyclizations, however, heteroatom-tethered diynes require a large excess of exo-alkene to prevent diyne homocoupling.