Abstract: The possibility of performing designed transition-metal catalyzed reactions in biological and living contexts can open unprecedented opportunities to interrogate and interfere with biology. However, the task is far from obvious, in part because of the presumed incompatibly between organometallic chemistry and complex aqueous environments.  Nonetheless, in the past decade there has been a steady progress in this research area, and several transition-metal (TM)-catalyzed bioorthogonal and biocompatible reactions have been developed. These reactions encompass a wide range of mechanistic profiles, which are very different from those used by natural metalloenzymes. Herein we present a summary of the latest progress in the field of TM-catalyzed bioorthogonal reactions, with a special focus on those triggered by activation of multiple carbon-carbon bonds.

Abstract: Pd(0) catalysts featuring phosphorous-based monodentate ligands can detour the reactivity of carbonyl-tethered alkylidenecyclopropanes (ACPs) from standard (3+2) cycloadditions towards tandem cycloisomerization / cross-coupling processes. This new reactivity lies on the formation of key π-allyl oxapalladacyclic intermediates, which are subsequently trapped with external nucleophilic partners, instead of undergoing canonical C-O reductive eliminations. Importantly, the use of imine-tethered ACP’s is also feasible. Therefore, the method provides a straightforward and stereoselective entry to a wide variety of highly functionalized cyclic alcohols and amines.