909 Special Issue on "Theoretical and Computational Chemistry" J. Indian Chem. Soc., Vol. 96, July 2019, pp. 909-919 Density Functional Theory study on the formation of the active catalysts in palladium catalysed reaction Davuluri Yogeswara Rao and Anakuthil Anoop* Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur-721 302, West Bengal, India E- mail: anoop@chem.iitkgp.ac.in Manuscript received online 03 May 2019, revised and accepted 22 May 2019 The formation of active catalyst species in the Pd-catalyzed reactions is studied using Density Functional Theory calculations. Taking palladium acetate and simple phosphine as the models, we estimated the energetics for the addition of phosphines, release of acetates, and associative exchange or ligands which convert the unreactive PdOAc 2 to reactive species that takes part in the catalysis. Two consecutive addition of two phosphines, PdOAc 2 + 2PH 3  Pd(OAc) 2 (PH 3 ) 2 ) are exergonic steps with the free energies of activation 8.16 kcal mol –1 and 5.33 kcal mol –1 . The associative exchange of acetate by PH 3 in Pd(OAc) 2 (PH 3 ) 2 has 14.56 kcal mol –1 of activation barrier, while the exchange in [Pd(OAc)(PH 3 ) 3 ] – has the barrier of 5.22 kcal mol –1 . Exchange reactions on neutral species that yields ionic species are endothermic in gas phase which is drastically reduced by solvation model. The addition of phosphines are exothermic. The dissociative steps are the removal of acetate anion, AcO – , or intramolecular dissociation of [AcO-PH 3 ] + . This study is a basis for future studies of the active catalyst formation of various such catalysts involving different ligands. Keywords: DFT, active catalyst formation, Pd-catalysed reaction, ligand exchange reactions, computational study. Introduction Palladium catalyzed coupling reactions – Heck 1,2 , Negshi 3,4 , Suzuki 5–7 , Stille 8 , and so on – are widely used for making carbon-carbon and carbon-heteroatom bonds. The common catalysts used in these coupling reactions are, Pd(OAc) 2 , Pd(PR 3 ) 4 , PdCl 2 (PR 3 ) 2 , etc. These materials act as pro-catalysts or pre-catalysts, which in situ gets converted to the active catalyst species in the catalytic cycle. The ac- tive-catalysts are coordinatively unsaturated Pd complexes with one, two, or three ligands. The activity of each of these species may be different, and can have significant impact on the overall catalytic efficiency. In some cases, as shown by computational studies, each species may follow separate pathways in the catalytic cycle 9 . The steps involved in the formation of active catalyst is much less explored compared to the studies on the catalytic cycle, although the identity of active catalyst is crucial in understanding the mechanism. The attempts to experimentally detect the species in the Pd catalysis were pioneered by the seminal works by Chris- tian Amatore et al. 10–14 on neutral catalysts and by John D. Protasiewicz and co-workers on ionic catalysts 15,16 . Amatore et al. have explained how zero-valent palladium is formed from divalent palladium triphenylphosphine complexes with the help of {31} P NMR and cyclic voltammetry to detect and characterize. Later, they traced the reactive mono-phosphine- ligated palladium intermediates by mass spectrometry in the Pd-catalyzed coupling reaction 17 . These works provide some valuable insight for the proposed steps towards the catalyst formation which is shown in Fig. 1. Amatore and Jutand re- ported the finding of the intermediate species by electrochemi- cal techniques where reduction and oxidation process oc- cur. The importance of ligation states are established by nu- merous computational studies on Pd-catalyzed reactions. The steric and electronic properties of the ligands decide which ligation states are favourable for each reaction. The com- monly studied Pd-catalyst is PdL 18–26 , or Pd-L 2 27,28 . In some studies, the mechanism starts with PdL 2 and becomes PdL along the pathway 29–33 . A tetrahedral Pd(0)-catalyst is formed before the formation of activated Pd(0) pre-catalysts. Tamas Kegl et al. studied the formation of PdL by step-by-step dis- sociation of L 4 Pd 28 using Density Functional Theory (DFT) JICS-24