In vitro and In silico Studies on the Base Effect in Palladium‐Catalyzed Direct Arylation

Abstract

AbstractPalladium‐catalyzed direct‐arylation (DAr) has shown promise in synthesizing conjugated molecules and polymers. Herein, palladium‐catalyzed DAr reactions of 2‐bromo‐3‐alkyl‐thiophene in the presence of distinct bases including pivalate, acetate, carbonate, and hydroxide, are performed in vitro and in silico. The entire pathways comprising oxidative addition (OA), concerted metalation‐deprotonation (CMD), and reductive elimination (RE) are investigated theoretically, indicating that the rate‐determining step varies with the base. Natural bond orbital analysis on the CMD transition states reveals that the classical Lewis pair and frustrated Lewis pair play important roles in the base‐coordinated CMD and the base‐assisted CMD, respectively. Multivariate regression analysis between the calculated CMD activation barrier and the orbital interactions yields a model equation, which is employed to further elucidate the characters of Lewis acid and Lewis base in the CMD. Overall, the computational results from the present study are in agreement with the experimental reaction yields and constitute the interpretation of the working principles for the DAr catalytic system, shedding light on further optimization and advance.