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,S-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.