With the key intermidiate 11 in hand, the construction of a unique Trp-Trp linkage by Larock macrocyclization was investigated (Table ). Initially, a variety of ligands were investigated using 0.4 eq. Pd(OAc)2, toluene as solvent, and 10 eq. DIPEA as base. Interestingly, it was found that the use of 0.8 eq. PPh3 as a monodentate ligand under heating at 110 °C for 12 h yielded the highly strained cyclic peptide 14 with atrop-Trp-Trp bond, albeit in trace amounts. (Table , entry 1). Next, Larock macrocyclization was attempted using 0.8 eq. PPh2Me, and the desired cyclized compound 14 was successfully as a single compound in 18% (entry 2). It is worth noting that the Larock macrocyclization of 11 proceeds with perfect atroposelectivity and regioselectivity. Furthermore, when PCy3, which is more electron-rich than PPh3, was used as a ligand, a slight yield improvement was observed and the Larock macrocyclization proceeded with a 20% isolated yield (entry 3). Bidentate ligands such as dppe and dppf were not effective for this macrocyclization (entries 4 and 5). On the other hand, Larock macrocyclization of indole skeleton into cyclic peptides and synthesis of complex alkaloids was reported by Reisman, Boger, Baran, and Sarlah group in their pioneering work. Based on these background studies, we performed this Larock macrocyclization using 0.4 eq. Pd(tBu3P)2. It was found that the yield was improved and the desired cyclized product 14 was obtained in an isolated yield of 38% (entry 6). This result indicates that bulky and electron-rich ligands are effective for this reaction. Further investigation of the reaction to improve the yield revealed that the use of 0.4 eq. Pd(OAc)2 and 0.8 eq. tBu3P•HBF4 was crucial for this reaction, and the atrop-Trp-Trp linkage was successfully constructed in 51% isolated yield (entry 7). The reaction was also found to proceed well at the gram scale, and compound 14 was well obtained at a larger scale (68%, entry 8). The reaction was then attempted using a different base. However, the yield of Et3N dropped to 26%, indicating that a bulky base is essential for this Larock macrocyclization (entry 9). Inorganic bases such as Na2CO3 and K2CO3 showed little progress in this macrocyclization due to solubility problems (entries 11 and 12). On the other hand, the effect of the solvent on the reaction was investigated, and the reaction hardly progressed with MeCN, and the isolated yield was 14% with PhMe/DMF = 1/1 (entries 13 and 14). In the case of PdCl2, the macrocyclization proceeded, but the isolated yield was 35% (entry 15). From these results, it is concluded that the most effective condition for the Larock macrocyclization is the use of Pd(OAc)2 and tBu3P•HBF4 at 110 °C in PhMe in the presence of DIPEA (entries 7 and 8).