Chemists’ ability to synthesize structurally complex, high-value organic molecules from simple starting materials is limited by methods to selectively activate and functionalize strong alkyl C(sp3) covalent bonds. Recent activity has focused on the activation of abundant C–O, C–N and C–C bonds via a mechanistic paradigm of oxidative addition of a low-valent, electron-rich transition metal. This approach typically employs nickel(0), rhodium(I), ruthenium(0) and iron catalysts under conditions finely tuned for specific, electronically activated substrates, sometimes assisted by chelating functional groups or ring strain. By adopting a redox-neutral strategy involving palladium(II)-catalyzed C–H activation followed by β-heteroatom/carbon elimination, we describe here a catalytic method to activate alkyl C(sp3)–oxygen, nitrogen, carbon, fluorine and sulfur bonds with high regioselectivity. Directed hydrofunctionalization of the resultant palladium(II)-bound alkene leads to formal functional group metathesis. The method is applied to amino acid upgrading with complete regioselectivity and moderate to high retention of enantiomeric excess. Low-strain heterocycles undergo strong-bond activation and substitution, giving ring-opened products.

Activation of diverse carbon–heteroatom and carbon–carbon bonds via palladium(II)-catalyzed β-X elimination

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.