Understanding Precatalyst Activation in Cross-Coupling Reactions: Alcohol Facilitated Reduction from Pd(II) to Pd(0) in Precatalysts of the Type (η3-allyl)Pd(L)(Cl) and (η3-indenyl)Pd(L)(Cl)

Complexes of the type (η3-allyl)Pd(L)(Cl) (L = PR3 or NHC), have been used extensively as precatalysts for cross-coupling and related reactions, with systems containing substituents in the 1-position of the η3-allyl ligand, such as (η3-cinnamyl)Pd(L)(Cl), giving the highest activity. Recently, we reported a new precatalyst scaffold based on an η3-indenyl ligand, (η3-indenyl)Pd(L)(Cl), which typically provides higher activity than even η3-cinnamyl supported systems. In particular, precatalysts of the type (η3-1-tBu-indenyl)Pd(L)(Cl) give the highest activity. In cross-coupling reactions using this type of Pd(II) precatalyst, it is proposed that the active species is monoligated Pd(0), and the rate of reduction to Pd(0) is crucial. Here, we describe detailed experimental and computational studies which explore the pathway by which the Pd(II) complexes (η3-allyl)Pd(IPr)(Cl) (IPr = 1,3-bis(2,6-diisopropylphenyl)-1,3-dihydro-2H-imidazol-2-ylidene), (η3-cinnamyl)Pd(IPr)(Cl), (η3-indenyl)Pd(IPr)(Cl) and (η3-1-tBu-indenyl)Pd(IPr)(Cl) are reduced to Pd(0) in alcoholic solvents, which are commonly used in Suzuki–Miyaura and α-arylation reactions. The rates of reduction for the different precatalysts are compared and we observe significant variability based on the exact reaction conditions. However, in general, η3-indenyl systems are reduced faster than η3-allyl systems, and DFT calculations show that this is in part due to the ability of the indenyl ligand to undergo facile ring slippage. Our results are consistent with the η3-indenyl systems giving increased catalytic activity and provide fundamental information about how to design systems that will rapidly generate monoligated Pd(0) in the presence of alcohols.