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.