Abstract

Due to the linear coordination nature of gold(I) catalysts, achieving high enantiocontrol in asymmetric gold catalysis is a great challenge. To improve the enantiocontrol of gold catalysis, an ion-pairing strategy was therefore proposed. A series of bifunctional P,N ligands based on chiral spirocyclic and biaryl scaffolds were synthesized and applied in the gold(I)-catalyzed desymmetric lactonization of alkynylmalonic acids. A wide range of chiral lactones containing an α-position quaternary stereocenter were synthesized with high yields, excellent regioselectivity and enantioselectivity under mild reaction conditions. The synthetic utilities of the current reaction were demonstrated by gram scale synthesis and transformations of chiral lactones. The origin of enantioselectivity and the role of the alcohol additive were elucidated via control experiments and DFT calculations.

Reference:

1. Lin, B.; Yang, T.; Zhang, D.; Zhou, Y.; Wu, L.; Qiu, J.; Chen, G.-Q.; Che, C.-M.; Zhang, X. Angew. Chem., Int. Ed., 2022, 61, e202201739.