Activation of diverse carbon–heteroatom and carbon–carbon bonds via palladium(ii)-catalysed β-X elimination. Issue 11 (November 2018)

• Record Type: Journal Article
• Authors: Tran, Van; Gurak, John; Yang, Kin; Engle, Keary
• Is Part Of: Nature chemistry. Volume 10:Issue 11(2018)
• Page Start: 1126
• Page End: 1133
• Publication Date: 2018-11
• Subjects: Chemistry -- Periodicals; Chemistry, Physical and theoretical -- Periodicals; Bioorganic chemistry -- Periodicals; 540
• DOI: 10.1038/s41557-018-0110-z
• Languages: English
• ISSNs: 1755-4330

Abstract

Abstract 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(sp 3 ) 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(sp 3 )–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.