Concerted metalation deprotonation

Concerted metalation-deprotonation (CMD) is a mechanistic pathway through which transition-metal catalyzed C–H activation reactions can take place.

[7] While there are a number of different possible mechanisms for C–H activation, a CMD pathway is common for high valent, late transition metals like PdII,[8] RhIII, IrIII, and RuII.

[2] Investigations into CMD paved the way for the development of many new C–H functionalization reactions, especially in the areas of direct arylation and alkylation by palladium and ruthenium.

[2] CMD begins with a high valent, late transition metal like PdII that may or may not be bound to a carboxylate anion.

[16] A notable example of a reaction that is catalyzed by ruthenium in which directed metalation occurs through CMD was reported by Igor Larossa and coworkers in 2018.

The ruthenium catalyst is functional group tolerant and enables the late stage synthesis of pharmaceutically relevant biaryls.

Mechanism of a CMD insertion into a C-H bond.
Mechanism of a CMD insertion into a C-H bond.
sp3 C–H activation by CMD mechanism from Keith Fagnou and co-workers in 2007
sp3 C–H activation by CMD mechanism from Keith Fagnou and co-workers in 2007
Example of directed arylation that occurs through concerted metalation deprotonation by Igor Larossa and coworkers in 2018
Example of directed arylation that occurs through concerted metalation deprotonation by Igor Larossa and coworkers in 2018