Gold-catalyzed highly enantioselective cycloadditions of 1,6-enynes and 1,6-diynes assisted by remote hydrogen bonding interaction

Gold(I)-catalyzed highly enantioselective [4 + 2] cycloadditions of 1,6-enynes were achieved by utilizing chiral bifunctional P,N ligand. A wide range of 1,6-enynes were converted to enantioenriched 5-6-6-fused tricyclic compounds under mild reaction condition (up to 99% ee). This chiral gold(I) complex was also employed in the first desymmetric cycloadditions of 1,6-diynes bearing single ester group at the tether (up to 93% ee), where 5-<i>exo</i>-<i>dig</i> pathway predominates over 6-<i>endo</i>-<i>dig</i> pathway. DFT calculations and control experiments were performed to rationalize the origin of precise stereocontrol. It implies that hydrogen bonding interaction between the ester group of substrates and the secondary amine of the chiral P,N ligands plays a pivotal role in the control of enantioselectivity. The utilities of the current reaction were demonstrated by scale-up experiment and derivatizations.