Head-tail carboboration of multisubstituted alkenes enabled by chain recognition

Precision in site-selective functionalization of molecules bearing multiple potentially reactive positions is a longstanding challenge in organic synthesis. Although migratory difunctionalization offers a powerful strategy for programmed functional group installation along carbon chains, its implementation with multisubstituted alkenes has been impeded by the increased complexity of site-selectivity. Here we report a head-tail carboboration of multisubstituted alkenes with exceptional site-selectivity, enabled by ligand steric exclusion in a nickel-catalysed chain-walking system. This catalytic system enables selective migratory transformations of tertiary alkyl-metal intermediates across a range of thermodynamically and kinetically accessible reaction site combinations. The importance of this study is evident in not only its capacity to efficiently couple structurally diverse carbon electrophiles with complex substrates, including natural terpenes, but also its contribution to streamlining the synthesis of natural products and materials.