Exploration of copper-catalyzed Grignard cross-coupling between 3-halo-4-alkoxybenzoates and bromoisoprenoids

Abstract

Allylic functionality, often taking the form of terpenes, is a mainstay of marine natural products. The aryl-allyl connection is particularly common, appearing in several product classes derived from Callophycus serratus, many of which exhibit promising initial biological activities. In pursuit of several total syntheses, which leverage a copper-catalyzed Grignard cross-coupling between a 3-halo-4-alkoxybenzoate and geranylgeranyl bromide, we explored the effects of alkoxybenzoate and halogen substitutions on the coupling. By scrutinizing the constraints and influences of these protecting groups on cross-coupling success, we lay out the potential for downstream deprotection chemistry. Here, we present the results of this investigation, along with a theoretical basis for the observations.