Synthetic and Mechanistic Studies of a Versatile Heteroaryl Thioether Directing Group for Pd(II) Catalysis

A weakly coordinating monodentate heteroaryl thioether directing group has been developed for use in Pd­(II) catalysis to orchestrate key elementary steps in the catalytic cycle that require conformational flexibility in a manner that is difficult to accomplish with traditional strongly coordinating directing groups. This benzothiazole thioether, (BT)­S, directing group can be used to promote oxidative Heck reactivity of internal alkenes, providing a wide range of products in moderate to high yields. To demonstrate the broad applicability of this directing group, an arene C–H olefination method was also successfully developed. Reaction progress kinetic analysis provides insights into the role of the directing group in each reaction, which is supplemented with computational data for the oxidative Heck reaction. Furthermore, this (BT)S directing group can be transformed into a number of synthetically useful functional groups, including a sulfone for Julia olefination, allowing it to serve as a “masked olefin” directing group in synthetic planning. In order to demonstrate this synthetic utility, natural products (+)-salvianolic acid A and salvianolic acid F are formally synthesized using the (BT)­S-directed C–H olefination as the key step.