Alkyl-alkynyl cross coupling reactions have been extensively studied in the construction of alkylated acetylenes due their wide applicability in the synthesis of natural products and biologically active molecules. There are two major pathways to perform alkyl-alkynyl cross-coupling reactions; (i) cross-coupling of alkylmetal reagents with haloalkynes and (ii) alkylation of metal acetylides with primary alkyl halides. However, poor yields, limited substrate scope, tedious reaction conditions, use of expensive metal catalysts and less tolerance towards the reactive functional groups such as esters or nitriles or imides limit their laboratory application. On the other hand, alkylzirconocenes are unique class of alkylating reagents unlike traditional organometallic reagents because of their high functional group tolerance and their regioselective generation from alkenes. In the recent years, researchers utilized these reagents in cross-coupling reactions via transmetalation, for the effective synthesis of functionalized alkanes. Herein, we developed a simple strategy for the generation of terminal alkylzirconocenes using Schwartz’s reagent on alkenes followed by transmetalation and cross-coupling with alkynyl bromides under copper catalysis. Reaction has a broad scope, a range of functionalized bromoalkynes and alkylzirconium reagents, resulted in generally good yields of the desired internal alkynes. The ‘ligandless’ and ‘base free’ conditions make this methodology more attractive from the standpoints of atom economy and ease of purification. Substrate scope and mechanism details of the reaction will be discussed during the meet.

Transmetalation of alkylzirconocenes: Copper-catalyzed alkyl–alkynyl cross-coupling with bromoalkynes

253rd National Meeting (2017)

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