Turn left and turn right: recent advances in selectivity controlled carbonylation

Abstract

The quest for selectivity is a central theme in modern organic synthesis, aiming to construct complex molecules with precision and efficiency. Transition-metal-catalyzed carbonylation, which utilizes carbon monoxide as an ideal C1 building block, offers a powerful platform for this endeavor. However, the presence of multiple reactive sites or selectivities in a substrate often leads to a mixture of products, posing a significant challenge to synthetic utility. A paramount goal is to develop divergent synthetic methods where a single set of starting materials can be selectively converted into multiple, distinct products by subtle adjustments to the reaction conditions. This review summarizes key advances from 2018 to 2025 that demonstrate how selectivity in carbonylation can be effectively controlled not by the inherent reactivity of the substrate, but by the catalytic system itself. Strategic manipulation of key variables, especially ligand engineering, but also the choice of base, additives, and other conditions, allows precise steering of reaction pathways to turn “left” or “right”. These principles have been successfully applied across different substrate classes, including alkenes, alkynes, 1,3-enynes, alcohols, imines, oxime esters, and organohalides, enabling access to structurally diverse products from common starting materials which illustrates a general and tunable approach to divergent synthesis.