Enantioselective Alkyne Conjugate Addition Enabled by Readily Tuned AtropisomericP,N-Ligands

By the nature of its structure, the 5-membered chiral biaryl heterocyclic scaffold represents a departure from 6-membered P,N-ligands that facilitates tuning and enables ligand evolution to address issues of selectivity and reactivity. In this vein, the Cu-catalyzed enantioselective conjugate alkynylation of Meldrum's acid acceptors is reported using Me-StackPhos. Enabled by this new ligand, the reaction tolerates a wide range of alkynes furnishing the products in high yields and excellent enantioselectivity. The transformation provides access to highly useful chiral β-alkynyl Meldrum's acid building blocks as demonstrated by an efficient enantioselective synthesis of the preclinical agent OPC 51803.