Gold-Catalyzed Desymmetric Lactonization of Alkynylmalonic Acids Enabled by Chiral Bifunctional P,N ligands
Bijin Lin1,2, Tilong Yang3, Dequan Zhang1
1Department of Chemistry, the Grubbs Institute, Medi-X Pingshan, Southern University of Science and Technology, Shenzhen, 518055, China.
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.
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