C-H Alkenylation of Heteroarenes: Mechanism, Rate, and Selectivity Changes Enabled by Thioether Ligands.
Bradley J GorslineLong WangPeng RenBrad P CarrowPublished in: Journal of the American Chemical Society (2017)
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.
Keyphrases
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- electron transfer
- ms ms
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- liquid chromatography
- big data
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- simultaneous determination
- mass spectrometry
- drug induced
- dna binding
- gas chromatography mass spectrometry
- data analysis
- high resolution
- crystal structure
- case control
- high resolution mass spectrometry
- transition metal