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), K 3 PO 4 (as a base), and Ag 2 CO 3 (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 K 3 PO 4 and in the absence of additive Ag 2 CO 3, 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 Ag 2 CO 3 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.