Remote-Carbonyl-Directed Consecutive Arylation of Terminal Alkenes for the Synthesis of Tetrasubstituted Olefins

Abstract

The highly efficient synthesis of all-carbon tetrasubstituted olefins has been concerned for decades, especially for multi-aryl substituted olefins which widely used in functional organic materials and pharmaceuticals. This work presents a carbonyl-directed palladium-catalyzed consecutive arylation of terminal alkenes with aryl iodides under mild conditions, a series of triarylated tetrasubstituted olefins were obtained in moderate yields. Because a weak chelation effect is generally difficult to support such a thorough tri-fold Heck arylation, and the β-trans-selective alkenyl C–H activation cannot be achieved via a twisted endo-metallacyclic intermediate, thus, the key to success is the compatibility between several mechanisms, including Heck, C–H activation and E,Z-isomerization. Here, the judicious selection of a flexible-alkyl-chain-tethered carbonyl group seems to be critical, it provides a proper chelation effect that not only assists a distal alkenyl functionalization or isomerization, but also avoids byproducts caused by other possible β-H elimination or migration. The strategy developed herein greatly streamlines the preparation of the target molecules, and the protocol covers a range of readily available terminal alkenes bearing native directing groups (e.g., aldehyde, ketone and ester), and aryl iodides.