We began our investigation into the utility of reagents Pinc and 2 in generating heterobiaryl linkages during a macrocyclization protocol with C-terminal 2-aminobenoic acid (anthranilic acid, or Ant)bearing linear peptide sequences. We recognized that typical head-to-tail cyclization at Ant residues are difficult as a result of unavoidable side reactions upon activation of the C-terminus carboxylate. We were keen to see whether our method would circumvent this reactivity and allow for efficient heterobiaryl forming macrocyclization at the Ant C-terminus. Linear Ant-containing peptide 3 and methylated Ant-containing peptide 4 were prepared via routine Fmoc SPPS employing mild Fmoc deprotection conditions (6 % piperazine in a 0.1 M 6-ClHOBt DMF solution for 2 x 10 min). Gratifyingly, linear peptides 3 and 4 smoothly underwent cyclization with Pinc and EtCHO in 1:1 DCE/MeCN (25 mM) at 50 o C to afford heterobiaryl containing cyclic peptides 7a (15 % yield) and 8a (18 % yield) respectively (Table -Entry 1 and 2). We found that the reaction of 3 and 4 with isocyanide reagent 2 did not result in desired peptides 7b and 8b (entry 2 and 4). Instead, in the case of linear peptide 4, a cyclic phosphorane intermediate (6b in Supporting information) was detected by LCMS. This suggested that the ylide intermediate produced by 2 is noticeably less nucleophilic than the imino-phosphorane intermediate afforded by 1. We concluded that the electron-rich carbonyl group of Ant-containing peptide sequences was not suitable for cyclization with 2. In stark contrast, we found that cyclization of analogous 3-aminobenzoic sequences 9 and 10 produced both oxadiazole-biaryl 11a (38 % yield) and 12a (25 % yield) as well as oxazole-biaryl 11b (35 % yield) and 12b (23 % yield) (Entry 5-8). No cyclic phosphorane was detected in either case. Finally, we tested the reaction on 4-aminobenzoic acid containing peptides 13. We recognized that this reaction was challenging as a result of the electron rich nature of the C-terminus carbonyl as well as the inflexible 4-aminobenzoic acid moiety. Indeed, under the standard reaction conditions no desired peptide was observed using both isocyanide reagents Pinc and 2. In both reactions, an enamine intermediate could be observed and isolated (see SI). We noticed that 13 was poorly soluble under our standard reaction conditions. The cyclization was thus conducted at 5 mM while heating to 60 o C with additional portions of Pinc and EtCHO added. This variation led to full conversion of peptide 13 and afforded the desired oxadiazole-biaryl 14a (18 % yield) (entry 9). Much like with the 2-aminobenzoic acid peptides, the reaction of 13 with isocyanide 2 failed; although, no cyclic phosphorane was detected in this instance (entry 10). Lastly, we tested the reaction on a more exotic substrate in form of the 4-amino-2-chlorobenzoic acid peptide 15. Cyclization of 15 proceeded smoothly with Pinc at 5 mM reaction dilution conditions to afford 16a (17 % yield) (entry 12). In all cases, the S-isomer was the major diastereomer generated.