Acceleration of metallacycle-mediated alkyne–alkyne cross-coupling with TMSCl

Investigation of titanium-centered metallacycle-mediated cross-coupling between unsymmetrical internal alkynes has led to the discovery that TMSCl significantly accelerates the [Formula presented] bond forming event. We report a collection of results that compare the efficiency of this reaction employing Ti(Oi-Pr)₄/2n-BuLi in PhMe with and without TMSCl, demonstrating in every case that the presence of TMSCl has a profound impact on efficiency. While relevant in the context of developing this fundamental bond-forming process as an entry to more complex organometallic transformations, these modified reaction conditions allow coupling processes to be run at >10 times the concentrations previously possible [in 2.4 M n-BuLi (hexanes)], without the requirement of additional solvent. Finally, we demonstrate the effectiveness of these modified reaction conditions for the annulative cross-coupling between TMS-alkynes and 1,6-enynes leading to the formation of angularly substituted hydrindanes with, now well appreciated, high levels of regio- and stereoselection.