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

Abstract

AbstractThe highly efficient synthesis of all-carbon tetrasubstituted olefins has been a challenge for decades, especially of multi-aryl-substituted olefins which are 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, in which a series of triarylated tetrasubstituted olefins were obtained in moderate yields. Because a weak chelation effect is generally difficult to support such a thorough trifold Heck arylation, and β-trans-selective alkenyl C–H activation cannot be achieved via a twisted endo-metallocyclic intermediate, the key to success is the compatibility between several mechanisms, including Heck reaction, C–H activation and E/Z-isomerization. Here, the judicious selection of a flexible-alkyl-chain-tethered carbonyl group seems to be critical, as it provides a proper chelation effect that not only assists 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 a native directing group (i.e., aldehyde, ketone and ester) and aryl iodides.