For the past four years, a major focus of our research has been developing substrate-directed Heck- and Wacker-type alkene hydrofunctionalization and 1,2-difunctionalization reactions. In particular, we’ve previously found that alkenyl amides containing removable bi- and tridentate directing groups are highly effective substrates, owing to the ability of the directing group to facilitate regioselective addition of the first reaction partner and then subsequently form a stabilized palladacycle that can be intercepted with a proton, nucleophile, or electrophile. Based on these results, we became interested in identifying news weakly coordinating directing groups that can enable regioselective addition of a nucleophile and then allow a site-selective β-H elimination.
In a manuscript appearing online today in ACS Catalysis, we describe the discovery and development of the benzothiazole thioether, (BT)S, directing group for oxidative Heck and C–H activation reactions (click here). In a colossal 15-page-long (!!!) paper covering reaction development, mechanistic studies, and applications in total synthesis, Andrew, Kin, and Malkanthi, demonstrate the unique coordination properties of (BT)S and showcase its synthetic versatility . Congrats to the three Engle lab authors listed above, and huge thanks to our tireless collaborator Jason from the Scripps Research Automated Synthesis Facility for guidance on high-throughput experimentation, design of experiments, and kinetics! In case anyone missed it, a pre-print of this work was published on ChemRxiv back in early April (click here).