Lithium Enolate with a Lithium-Alkyne Interaction in the Enantioselective Construction of Quaternary Carbon Centers: Concise Synthesis of (+)-Goniomitine

Abstract

We report a method for direct enantioselective alkylation of 3-alkynoic and 2,3-alkendioic acids that form quaternary stereogenic centers, and application of this method to the total enantioselective synthesis of a complex alkaloid (+)-goniomitine. The methods were effective in the alkylation of both 3-alkynoic acids, 2,3-alkendioic acids substrates with a broad range of heterocyclic and functionalized alkyl group substituents. Accompanying crystallographic studies provide mechanistic insight into the structure of well-defined chiral aggregates, highlighting cation-π interactions between lithium and alkyne groups.

Keywords: Achiral Lithium Amides; Alkaloids; Alkylation Reactions; Alkynes; Molecular Recognition; Total Synthesis.