Chelation-assisted multiple and relay C–H functionalization of unactivated aliphatic <i>E</i> -alkenes

Olefinic C-H modification has been a highly sought-after objective to upgrade commodity molecules into densely functionalized compounds. Unactivated aliphatic <i>E</i>-alkenes of electronically and sterically unbiased properties are ubiquitous compounds, but they are challenging targets for alkenyl C-H functionalization due to low reactivity and selectivity issues. We report the first sequential and relay C-H functionalization of unactivated aliphatic <i>E</i>-alkenes using alkenes and alkynes to afford complex polyenes and polyeneynes. The dienes, obtained from olefinic C-H functionalization by alkyne hydroalkenylation, underwent upgrading and controllable C-H functionalization by a six- or seven-membered palladacycle. The method allows for a range of functionalizations such as oxidative alkenylation, hydroalkenylation and alkynylation, <i>via</i> five- to eight-membered cyclopalladation. The robustness of the protocols was demonstrated by the preparative scale, chemical derivation and intra-molecular reactions to produce 12- to 16-membered macrocycles. Mechanistic experiments combined with DFT calculations explained the reactivities and selectivities of various alkenyl C-H bonds.