Nickel-Catalyzed C(sp<sup>3</sup>)–C(sp<sup>3</sup>) Cross-Electrophile Coupling of In Situ Generated NHP Esters with Unactivated Alkyl Bromides
Kai Kang, Daniel J. Weix
Abstract
The formation of C(sp3)–C(sp3) bonds by cross-coupling remains a challenge in synthesis. Here, we demonstrate a two-step, one-pot protocol for the in situ generation of N-hydroxyphthalimide esters and their nickel-catalyzed cross-electrophile coupling with unactivated alkyl bromides for the construction of 1°/1 ° C(sp3)–C(sp3) bonds. The conditions tolerate an array of functional groups, and mechanistic studies indicate that both substrates are converted to alkyl radicals during the reaction.
Topics & Concepts
ChemistryElectrophileAlkylCatalysisNickelIn situRadicalMedicinal chemistryCoupling (piping)Coupling reactionOrganic chemistryMechanical engineeringEngineeringCatalytic C–H Functionalization MethodsCatalytic Cross-Coupling ReactionsSulfur-Based Synthesis Techniques