Unlike the bornylamine scaffold above, resubmission of 5c to the reaction conditions gave a 26% yield of the diarylated compound 6c (Scheme 5), indicating that the monoarylated compound 5c can effectively form a reactive complex with palladium, perhaps because the picolinamide is less hindered than in 2e. In contrast to bornylamine above, arylation of the (1-methylcyclohexyl)methylamine scaffold with aryl bromides was ineffective. Furthermore, the arylation reaction with an aryl iodide could be suppressed by the addition of 30 mol% tetrabutylammonium bromide to the reaction mixture. It seems that the presence of bromide in the reaction mixture retards the C-H activation step, presumably by outcompeting acetate as a ligand on the intermediate palladium complex. This may also explain why only monoarylation of the bornylamine scaffolds is seen when aryl bromides are employed (Schemes 2 & 4) Conditions: 5 mol% Pd(OAc)2, 4 equiv. Combined isolated yield. Next we explored the effect of the eight different picolinamide directing groups on the flexible openchain scaffold 2-methylbut-1-ylamine (Table ). As anticipated, arylation of the methyl group occurs preferentially, followed by a second arylation on the ethyl group. Reaction of the unsubstituted amide 7a gives 72% yield of monoaryl product 8a and 21% of the diaryl compound 9a. Complete control over the formation of mono or diarylation products is more challenging in this case, but once again the 3methylpicolinamide gives the highest levels of selectivity yielding only 5% of diaryl compound 9b alongside a synthetically useful 73% yield of monoarylated compound 8b. Good selectivity was also observed with the 5-methyl (7d) and 5-methoxy (7h) derivatives which both also gave improved yields of the monoaryl derivatives 8d and 8h respectively. The 4-methylpicolinamide gave a poor overall yield as well as showing no selectivity in the arylation reaction with equal amounts of 8c and 9c being produced. In this latter reaction, it was possible to detect a third product 10c in which diarylation had taken place on the two methyl groups (Figure ). Trifluoromethyl picolinamides 7e and 7f gave high selectivity for the monoarylated products 8e and 8f but in only moderate yield. 4-Methoxypicolinamide 7g gave a similarly low overall yield but with high selectivity for monoarylation. Conditions: 5 mol% Pd(OAc)2, 4 equiv. CsOAc, 10 mol% CuBr2, 4 equiv.4-iodoanisole, t AmOH 1 M, 140 °C, 24 h. Combined isolated yield; yields of each product calculated by 1 H NMR shown in parentheses. Ratio of products 8:9 determined from crude 1 H NMR; it was not possible to accurately determine this ratio for all reactions. A mixture of two diarylated products was obtained including 10c (Figure ); see SI for further details. As a final example, we explored the arylation of substrates 11a/11b derived from isobutylamine, in which two equivalent methyl groups are present (Scheme 6). Switching from the unsubstituted picolinamide 11a to the 3-methylpicolinamide 11b led to a slightly increased selectivity for monoarylation (12b vs 13b), albeit with the diarylated compound being the major product in both cases. The overall arylation yield with the 3-methylpicolinamide was also slightly higher.