Triple cross-electrophile coupling enabled by palladium/norbornene cooperative catalysis.

Abstract

Cross-electrophile coupling (XEC) is a powerful strategy for forming C-C bonds in synthetic organic chemistry. While XEC reactions between two electrophiles are well established, those involving three distinct electrophiles have remained underdeveloped. Herein, we report an intriguing formal triple XEC enabled by palladium/norbornene cooperative catalysis. Readily available aryl iodides, alkyl/aryl bromides, and propargyl esters are used as the distinct electrophilic coupling partners, leading to the synthesis of a diverse array of tetrasubstituted allenes. In particular, the challenging asymmetric formal triple XEC has also been realized through palladium/chiral norbornene cooperative catalysis, which uses the sterically hindered 2,6-disubstituted aryl bromides as the arylating reagents to prepare tetrasubstituted allenes bearing an axially chiral biaryl unit. Density functional theory calculations reveal that the selection of propargyl esters as electrophilic terminating reagents is key to the success of this reaction because it enables a thermodynamically favored pathway for reaction termination involving alkyne insertion followed by β-O elimination.