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

Abstract

While catalytic asymmetric alkynylation reaction has been extensively studied, existing examples predominantly focus on the construction of 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 diversity of products with challenging remote alkyne-tethered 1,4-central chirality. Mechanistic studies demonstrate that the initial desymmetrisative deprotonation of 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 in whole process. This strategy can be extended to kinetic transformation of racemic terminal alkynes successfully. Such a stepwise asymmetric deprotonation and alkynylation strategy facilitated by a single chiral catalyst provides a robust platform for diastereo- and enantioselective construction of products having challenging rectilinear 1,4-central chirality.