On the other hand, Baran et al. reported the total synthesis of tryptorubin A in 2020. In this synthesis, the highly strained Tyr-Trp linkage of tryptorubin A was synthesized via intramolecular Ullmann coupling using CuI. 12 Consequently, we investigated the construction of the highly strained atrop-Tyr-Trp linkage 11 by employing intramolecular Ullmann coupling on the cyclization precursor 10 using the conditions reported by Baran et al. (Figure , Table ). However, upon heating the cyclization precursor 10 with CuI (1.0 eq.) and K2CO3 (5.0 eq.) in dioxane at 100 °C for 12 hours, the target compound 11 was not obtained, and the byproduct oxindole 12 was observed instead (entry 1). In contrast, when L1 was used as the ligand, the desired compound 11 was obtained with an isolated yield of 13%, while the major byproduct was the dehalogenated compound 13 (entry 2). Similarly, using L2 as the ligand resulted in a 9% isolated yield of the target compound 11, but the dehalogenated compound 13 was still produced as a byproduct (entry 3). When L3 or L4 were used as ligands, the desired compound 11 was not obtained, and only the cyclization precursor 10 was recovered or the dehalogenated compound 13 was observed (entries 4 and 5). Further investigation of ligands revealed that neither L5 nor L6 produced the desired compound 11, and only the starting material was recovered (entries 6 and 7). Finally, when aminoquinoline L7 was used as a ligand, the target compound 11 was still not obtained, and the byproduct oxindole 12 was observed instead (entry 8). Various screenings of solvents and bases were also conducted, but none of them yielded the desired compound 11; only the starting material was recovered, or complex mixtures were produced (see the Supporting Information). From these results, it is evident that constructing the highly strained atrop-Tyr-Trp linkage in lapparbin (1) via intramolecular Ullmann coupling using CuI is challenging, probably due to the extreme strain in compound 11.