Organic chemistry

Polymer chemistry

Heteroatom

Ring (chemistry)

Palladium

Composite number

Catalysis

Carbon fibers

Composite material

Chemistry

Materials science

Reinforced carbon–carbon

Nature Chemistry

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)-catalysed 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. Traditionally, strong-bond activation by transition metals has been achieved through an oxidative addition pathway. Now, a redox-neutral palladium(ii)-catalysed β-elimination strategy has been shown to activate alkyl C–O, N, C, F and S bonds to give an alkene that can be trapped with various nucleophiles. This functional group metathesis allows upgrading of amino acid derivatives and ring-opening of saturated heterocycles.

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