Direct functionalisation of chemically inert C(sp3)-H bonds provides a potent strategic approach for the synthesis of complex molecules by removing the need for prefunctionalisation. This in turn reduces the number of synthetic steps. Cross dehydrogenative coupling has emerged as a powerful tool in the last decade for the selective construction of C-C bonds from simple and abundant C-H bonds via tandem oxidation. However, challenges remain as typically a transition metal catalyst and/or sacrificial oxidant is required as an external driving force. By exploiting the reactivity of transient aryne intermediates, we have established a metal-free, redox-neutral approach to C(sp3)-C(sp3/sp2/sp) coupling via an intramolecular 1,5-hydride transfer onto an aryne intermediate. Mechanistic studies have provided support for a zwitterion intermediate which activates a pronucleophile. Subsequent recombination yields the α-C-H functionalised tertiary amines in moderate to excellent yields. A diverse range of pronucleophiles have been demonstrated to be amenable to this new approach to cross dehydrogenative coupling reactions which utilises aryne intermediates.

Intramolecular hydride transfer onto arynes: Transition metal-free C(sp3)-H functionalisation of amines

256th National Meeting (2018)

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