Mechanism of copper-free Sonogashira reaction operates through palladium-palladium transmetallation

Abstract

The seminal contributions by Sonogashira, Cassar and Heck in mid 1970s on Pd/Cu- and Pd-catalysed (copper-free) coupling of acetylenes with aryl or vinyl halides have evolved in myriad applications. Despite the enormous success both in academia and in industry, however, critical mechanistic questions of this cross-coupling process remain unresolved. In this study, experimental evidence and computational support is provided for the mechanism of copper-free Sonogashira cross-coupling reaction. In contrast to the consensus monometallic mechanism, the revealed pathway proceeds through a tandem Pd/Pd cycle linked via a multistep transmetallation process. This cycle is virtually identical to the Pd/Cu tandem mechanism of copper co-catalysed Sonogashira cross-couplings, but the role of CuI is played by a set of PdII species. Phosphine dissociation from the square-planar reactants to form transient three-coordinate Pd species initiates transmetallation and represents the rate-determining step of the process.

A New Heterogeneous Catalyst Obtained via Supramolecular Decoration of Graphene with a Pd2+ Azamacrocyclic Complex

“…According to the proposed mechanism for the copper-free Sonogashira reaction [36], the partial reduction, occurring during the reaction, of Pd 2+ coordinated to H 2 L is not surprising and should be related to the formation of a Pd 0 complex as an intermediate species of the catalyzed process. This effect, which was insignificant in the case of MWCNT-(HL1)-Pd [20] is probably favored for the G-(H 2 L)-Pd catalyst due, as above said, to an elongated arrangement of the polyamine, facing the surface of G, which is adopted to optimize the stacking interactions, thus hampering the complexing ability of the polyamine to Pd 2+ , that is, the stability of the coordination of the polyamine to Pd(II).…”

Sonogashira Coupling (Cu/Amine‐Free) of ArBr/Cl in Aerobic Condition and N‐Benzylation of Aniline with Benzyl Alcohol Catalyzed by Complexes of Pd(II) with Sulfated/Selenated NHCs

“…These peaks support the formation of K and N as intermediates. Our mechanism prososal also has Pd−Pd transmetallation as proposed recently . The recyclabilty of 1 was tested for Sonogashira coupling.…”

Microwave-Assisted Palladium-Catalyzed Cross-Coupling Reactions: Generation of Carbon–Carbon Bond

“…It is worth mentioning that the mechanism of copper-free Sonogashira reaction was earlier proposed as a monometallic mechanism [47]. However, a catalytic cycle proceeds through a tandem Pd/Pd cycle comparable to the Pd/Cu tandem variant (Scheme 11) was quite recently revealed, supported by considerable experimental and computational scrutiny [48].…”