Unveiling the Role of Base and Additive in the Ullmann-Type of Arene-Aryl C-C Coupling Reaction

The mechanism of Ullmann-type biaryl formation between benzo-[1,2-b:4,5-b′]dithiophene-1,1,5,5-tetraoxide (BDTT) and iodobenzene (ArI) was computationally studied in the presence of CuI, phenanthroline (Phen), K₃PO₄ (as a base), and Ag₂CO₃ (as an additive). It is shown that base and additive play critical roles in each step of the reaction, such as (a) the I-to-base exchange in complex (Phen)CuI, (b) substrate deprotonation via the acid-base mechanism, and (c) Ar-I activation and DBT-Ar coupling. It is shown that (a) the presence of sulfonyl oxygens in DBT is essential - it plays an anchoring role and brings substrate and base closer to each other. In the presence of K₃PO₄ and in the absence of additive Ag₂CO₃, the Ph-I activation and C-C coupling occurs via a Cu-mediated nucleophilic substitution mechanism and requires a significant free energy barrier. However, the addition of Ag₂CO₃ to the reaction mixture not only accelerates the DBT and PhI coupling by reducing the rate-limiting Ph-I activation barrier but also switches the mechanism of the reaction from a Cu-mediated nucleophilic substitution to a Ag(I)-promoted oxidative addition-reductive elimination. These findings are important for development of the next generation reaction conditions for Ullmann-type of coupling reactions.