Palladacycle

Palladacycle, as a class of metallacycles, refers to complexes containing at least one carbon-palladium bond. Palladacycles are invoked as intermediates in catalytic or palladium mediated reactions. They have been investigated as pre-catalysts for homogeneous catalysis and synthesis.

History of the palladacycle discovery
In the 1960s, Arthur C. Cope and Robert W. Siekman reported the cyclopalladation reaction between aromatic azobenzenes and palladium(II) dichloride. The potential of palladacycles as catalysts was highlighted by Herrmann's catalyst in 1990s. Derivatives of tris(o-tolyl)phosphine proved effective in Heck reactions.

Classes of palladacycles
There are two distinct types of palladacycle: four-electron donor (CY) and six-electron donor (YCY) complexes.

Neutral, cationic and anionic palladacycles
The palladacycles can be neutral, cationic, or anionic. Depending on the nature of the coordinating ligands, the neutral palladacycles can be monomers, dimers, or bis-cyclopalladated.

Palladacycles with various ring-sizes
Palladacycles with ring-sizes range from 3 to 10 have been synthesized and characterized,  whereas only 5-/6-membered ones are commonly used. Palladacycles of 3-/4-/>6-membered ring-sizes are usually unstable due to their ring strains.

Palladacycles with various donor groups
The palladacycles could also be classified by the donor atoms. For example, the Herrmann’s catalyst discussed before is a phosphine-derived palladacycle. Other types of palladacycles such as phosphite palladacycle, imine palladacycle, oxime palladacycle, CS-/CO-palladacycles are also effective in catalytic reactions. Palladacycles derived from 2-aminobiphenyl have been used in a variety of cross-coupling reactions.

Synthesis of palladacycles
Several methods are available for the preparation of palladacycles. A simple and direct method is C–H activation. The cyclopalladation of aromatic derivatives is usually considered to go through an electrophilic aromatic substitution pathway. The oxidative addition of aryl halides is another useful method. However, the accessibility of the aryl halides starting material is a major drawback.

Other types of reactions such as transmetalation and nucleopalladation also turned out to be effective methods in the synthesis of palladacycles.

Applications as precatalysts
Palladacycles are used as pre-catalysts, usually by the reductive elimination from palladium(II) to the catalytically active palladium(0). In the example of 2-aminobiphenyl palladacycles, a kinetically active 12-electrons Pd(0) species is formed, allowing for further oxidative addition with reactants. A series of 2-aminobiphenyl bearing various X and L groups were synthesized to better understand the electron/steric effect.

By employing palladacycles as pre-catalysts, high reactivity and selectivity have been achieved in Heck reaction[2] and a variety of cross-coupling reactions, such as Suzuki, Sonogashira, Stille, Buchwald–Hartwig reactions.

Total synthesis containing palladacycles have been demonstrated.

Other applications
Except their abilities in catalyzing organic reactions, palladacycles have also shown their potential in medicinal and biological chemistry after the success of cis-Pt(NH3)2Cl2 as an anticancer agent. Additionally, they can also be used in CO/SCN- sensing.