Palladium-Catalyzed Tsuji–Trost-Type Reactions in Bioorthogonal Chemistry: From Test Tubes to Living Systems

Abstract

The potential to conduct palladium-catalyzed Tsuji–Trost reactions in biological systems opens unprecedented opportunities to probe and manipulate cellular processes. However, implementing such transformations remains challenging due to the stringent requirements imposed by biocompatibility. To date, Tsuji–Trost allylation has not yet been successfully demonstrated in living cells, and in vivo applications remain unrealized, primarily due to the presumed incompatibility between traditional organic chemistry and the complex aqueous environments of biological systems. Nevertheless, significant progress has been made in this area over the past two decades. The successful execution of a Tsuji–Trost reaction in aqueous media requires careful consideration of several key factors, including the choice of catalyst, ligand, leaving group, and nucleophile, as well as the influence of water on reactivity and selectivity. In this review, we highlight the latest advancements in biocompatible palladium-catalyzed Tsuji–Trost-type reactions, with a particular focus on deprotection and allylation reactions conducted in aqueous environments and in living systems. Further development of in vivo Tsuji–Trost allylation is expected in the near future.

Graphical Abstract

This review explores recent advances in biocompatible Tsuji–Trost-type reactions, with emphasis on mechanistic insights and the transition from conventional benchtop protocols to biological applications.