Employing C-H functionalization logic to access this unique connectivity, an 8-aminoquinoline(AQ)-directed Unfortunately, this reaction suffered from scalability issues above 100 mg. In accord with studies from the Reisman 24 and Boger 21 labs, pre-formed Pd(PtBu3)2 provided a glimmer of hope by allowing a slight reduction in Pd-loading (3.5 equivalents) and delivering 41% yield of 20´ along with a significant amount of the des-bromo byproduct. Since oxidative addition on 18 must be facile (as judged by extensive debromination), a combination of unfavorable steric interactions and strain likely hinder this cyclization. Traditionally, the Larock indole synthesis requires a hindered alkyl or silylterminated alkyne to provide the desired regiochemical outcome. It was reasoned that in this specific context, a triethylsilyl (TES) blocking group on 18 may actually be superfluous as the regiochemistry may be controlled by the conformation of the cyclization precursor. Gratifyingly, unprotected alkyne 19 engaged smoothly in Larock macrocyclization to deliver 20 in up to 60% yield, albeit using 1.9 equiv of Pd. Further optimization efforts were directed towards reducing the Pd loading to substoichiometric levels. Interstingly, the Pd loading could be reduced to 30 mol%, rendering the reaction catalytic, without detrimental impact to the yield. Ultimately the macrocyclization could be efficiently conducted on a gram-scale, furnishing 20 as a single atropisomer in 61% isolated yield. A small amount of byproducts with the same mass yet different polarity can be observed on LC, however appreciable amounts could not be isolated for characterization.