Negishi or Suzuki–Miyaura Pd-Catalyzed Cross-Coupling Reaction: Which Reaction Mechanism is Ahead for the Formation of Well-Known Anticancer Drug Combretastatin A-4 Analogue?

In recent years, scientists have become increasingly interested in finding high-efficacy, low-toxicity anti-tumor compounds. Combretastatin A-4 (CA-4) is supposed to be one of the materials that has excellent anti-tumor properties. This study intends to develop a more acceptable pathway and cross-coupling mechanism to resolve the contest between Negishi and Suzuki–Miyaura cross-coupling to form a combretastatin analogue A-4 by using the CAM-B3LYP-D3 theory level with DEF2-SVP basis set in the presence of [Formula: see text],[Formula: see text]-dimethylformamide as a solvent. First, due to the experimental data for the formation of 4-methyl-[Formula: see text]-methoxybiphenyl in the Suzuki–Miyaura and Negishi reactions, two designated reactions were used to determine the 4-methyl-[Formula: see text]-methoxybiphenyl formation cycle. The mechanism for the progression of the regioselective compound 2-methoxy-5-(3-(3,4,5-trimethoxy phenyl) furan-2-yl) phenol via Suzuki–Miyaura and Negishi reactions can theoretically be reconciled with a more appropriate cross-coupling and pathway.