Direct Heterocycle C-H Alkenylation via Dual Catalysis Using a Palladacycle Precatalyst: Multifactor Optimization and Scope Exploration Enabled by High-Throughput Experimentation.

One of the major challenges in developing catalytic methods for C-C bond formation is the identification of generally applicable reaction conditions, particularly if multiple substrate structural classes are involved. Pd-catalyzed direct arylation reactions are powerful transformations that enable direct functionalization of C-H bonds; however, the corresponding direct alkenylation reactions, using vinyl (pseudo) halide electrophiles, are less well developed. Inspired by process development efforts toward , an investigational active pharmaceutical ingredient, we report that a Pd(II) palladacycle derived from tri--butylphosphine and Pd(OAc) is an effective single-component precatalyst for a variety of direct alkenylation reactions.