Chelation-assisted multiple and relay C–H functionalization of unactivated aliphatic E-alkenes

Abstract

Olefinic C–H modification has been a highly sought-after objective to upgrade commodity molecules into densely functionalized compounds. Unactivated aliphatic E-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 E-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, via 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.