To investigate the optimal conditions for Larock macrocyclization, several different phosphine ligands were tested under heating conditions at 110 °C in PhMe with Pd(OAc)2 and DIPEA present (Scheme 2, Table ). Interestingly, when PPh3 was used, the desired compound 31, containing the highly strained atrop-Tyr-Trp linkage, was obtained with a low yield of 22% (Table , entry 1). It is worth noting that this reaction exhibited complete atroposelectivity in the formation of compound 31. Further exploration revealed that using the bulkier and electron-rich ligand PCy3 improved the yield to 51% (entry 2). However, the electron-poor ligand P(OMe)3 was not effective in this reaction (entry 3). Attempts were made to use bidentate ligands such as dppe and dppf, but they resulted in low yields (entries 4, 5). Since PCy3 provided relatively good results, Pd(tBu3P)2, which is a bulkier and electron-rich ligand, was used, but it was not very effective with a yield of 35% (entry 6). Interestingly, when tBu3P•HBF4 was used as a ligand, the yield improved to 59% (entry 7). This condition also proceeded well on an 18 g scale, and the desired compound 31 was synthesized with a yield of 45% (entry 8). Additionally, bases such as DBU, K2CO3, Cs2CO3, and NaOAc were investigated, but no results surpassing the best condition were obtained (entries 9-13). From this screening, it became clear that entry 7 is the best condi-The atropisomerism of compound 31 was determined to be in the Sa conformation by its NOESY spectrum (see the Supporting Information).