Journal of the American Chemical Society
Journal of the American Chemical Society
5 years ago

C–H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands

C–H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands
Brad P. Carrow, Peng Ren, Bradley J. Gorsline, Long Wang
Thioether ancillary ligands have been identified that can greatly accelerate the C–H alkenylation of O-, S-, and N-heteroarenes. Kinetic data suggest thioether–Pd-catalyzed reactions can be as much as 800× faster than classic ligandless systems. Furthermore, mechanistic studies revealed C–H bond cleavage as the turnover-limiting step, and that rate acceleration upon thioether coordination is correlated to a change from a neutral to a cationic pathway for this key step. The formation of a cationic, low-coordinate catalytic intermediate in these reactions may also account for unusual catalyst-controlled site selectivity wherein C–H alkenylation of five-atom heteroarenes can occur under electronic control with thioether ligands even when this necessarily involves reaction at a more hindered C–H bond. The thioether effect also enables short reaction times under mild conditions for many O-, S-, and N-heteroarenes (55 examples), including examples of late-stage drug derivatization.

Publisher URL: http://dx.doi.org/10.1021/jacs.7b03887

DOI: 10.1021/jacs.7b03887

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