Diastereoselective and enantioselective construction of 1,4-nonadjacent alkyne-tethered products through CuI-promoted deprotonation and addition of terminal alkynes

Abstract

While catalytic asymmetric alkynylation reactions have been extensively studied, the existing examples predominantly focus on the construction of the stereogenic center at the addition site. Here, we disclose a chiral Cu^I complex-catalysed asymmetric alkynylation reaction of prochiral terminal diynes, which can furnish a diverse array of products with remote alkyne-tethered 1,4-central chirality that is challenging to achieve. Mechanistic studies demonstrate that the initial desymmetrising deprotonation of the terminal diynes mediated by a chiral π-acidic Cu^I complex plays a crucial role in governing the diastereoselectivity, while the nucleophilic alkynylation step determines the enantiocontrol of the whole process. This strategy could be successfully extended to the kinetic transformation of racemic terminal alkynes. This stepwise asymmetric deprotonation and alkynylation strategy facilitated by a single chiral catalyst provides a robust platform for diastereo- and enantioselective construction of products with challenging-to-achieve rectilinear 1,4-central chirality.