The following set of conditions was identified based on these criteria after Step 1, initial optimizations (see SI), and used for the directing group informer library. [Cp*Ir(H2O)3SO4] was chosen as catalyst, allowing the reaction to be performed in absence of silver salts and insoluble additives, thus facilitating the use of liquid handling systems. Commercially available MozN3 (Moz = pmethoxybenzyloxycarbonyl) was selected as the nitrogen source, allowing for deprotection of the obtained carbamate under a number of conditions. Although the transformation was performed with a satisfactory outcome in a wide range of solvents (see SI), four were chosen for the informer library: 1,2-dichloroethane (DCE), which performed best in the initial study, cyclopentyl methyl ether (CPME) and EtOAc as greener solvent alternatives, and N-methyl-2-pyrrolidone (NMP) for its general good solubility of drug-like compounds and high boiling point. In step 2 (Figure ), the DG chemical space was probed. Out of the 48 substrates tested under the screening conditions, 16 DGs were shown to be productive for the C-N bond formation, with observed conversions ranging from 10 to >99% (Figure , for more details see SI). Given the variety of DGs tested this was an encouraging result. Although relatively low at the bottom end, we anticipated that the conversions could be improved by further optimization at a later stage. The following observations were made: DCE showed best performance throughout the scope, EtOAc and CPME had similar applicability, albeit in some cases with lower conversions. NMP performed well with heterocycles and carboxylic acids, however, was unproductive with the amide series. While the screening conditions allowed for the functionalization of a variety of substrates under a unified set of conditions, the HTE approach also facilitated rapid substrate-specific reaction optimization. Representative examples are discussed herein (for more studies see SI). In the catalyst loading study (Table ) we observed excellent conversions in all solvents with 10 mol% catalyst loading, following the informer library conditions. Performance at lower catalyst loadings was shown to be highly solvent dependent. The best results for both model substrates were obtained with DCE, with excellent conversions even at 4 mol% catalyst loading. The solvent effect varied between the model substrates, as the second best result for 2c was obtained in CPME, while for 2h this was in EtOAc, both at 6 mol% catalyst loading. The combined effect of catalyst and MozN3 loading on conversion was investigated next (Table ). A clear trend emerged from this study: while slight excess of MozN3 led to improved conversion, larger excess had a detrimental effect. This was most pronounced at lower catalyst loadings. Catalyst loading at 4 mol% and MozN3 (1.3 equiv) was chosen for scale-up. As formation of mono-and difunctionalization mixtures was observed for a number of compounds in the directing group informer library, tunable selectivity was investigated with 1-phenyl-1H-pyrazole (1e) as model system (Table ). Good monoselectivity was achieved at low catalyst and MozN3 loading. Conversely, enrichment of the difunctionalization product was achieved with increased catalyst and azide loadings. To confirm the performance of the catalytic system on a larger scale, a series of building blocks were functionalized and isolated (Scheme 1). The building block selection was based on positive hits from the directing group informer library (vide supra, Figure ). The effect of various substitution patterns on the functionalized system was investigated with the 2-phenylpyridine series. While the orthomethyl substituent was well tolerated in 1a, with increased substituent size in 1b a significant decrease in yield was observed (2b, 37%). The meta substituent in 1c was tolerated and yielded the anticipated product (2c) with complete regioselectivity. Importantly, the reaction could also be performed using CPME as solvent with maintained yield, albeit with increased catalyst loading (6 mol%). Functionalization of 2-phenylpyridine with high monoselectivity was achieved with decreased MozN3 loading (for optimization see SI), yielding compound 2d in 86 % yield. The monoselective functionalization observed with pyrazole 1e in the optimization study (Table ) translated well to the 0.5 mmol scale. Benzoxazole 2f was successfully obtained under modified conditions based on single substrate optimization results (see SI). The utility of the presented catalytic system beyond the formation of 5-membered iridacycles was demonstrated with the 2g-2i series, yielding the desired products via 6-membered iridacycle formation. The reaction of N-phenylpyrimidin-2-amine yielded a mixture of monoaminated 2g and diaminated 2g´, favoring the monofunctionalization product. In the indole series, both 2h and 2i were obtained with complete selectivity for the 7-position over the 2position, favoring 6-membered iridacycle formation. Importantly with 2h, the use of more environmentally benign EtOAc as solvent had no negative effect on yield. To our delight oxygencentered directing groups were also successfully utilized as demonstrated with the 2j -2m series.