Vol.:(0123456789) 1 3 Theoretical Chemistry Accounts (2018) 137:94 https://doi.org/10.1007/s00214-018-2256-6 REGULAR ARTICLE Ab initio static and metadynamics investigations of the Wittig reaction Abdelghani Adda 1,2  · Ratiba Hadjadj‑Aoul 1  · Fouad Lebsir 1  · Abdelghani Mohamed Krallafa 1 Received: 24 February 2018 / Accepted: 26 April 2018 © Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract To date, the Wittig reaction remains the most commonly used method in organic chemistry. The synthesis approach yields to a possible functionalization of the olefn product through the transformation of the carbonyl function (ketones or aldehydes) with a phosphoniumylide. In the present work, the two approaches are used to describe the mechanism of the Wittig reac- tion. Static quantum calculations at the DFT level of theory with a B3LYP functional and 6–31 g(d, p) basis set are carried out and correlated to metadynamics calculations, exploring the free energy landscape of the reaction. The free energy bar- riers are calculated along the trajectory path, and the mechanism is discussed with the main features observed in the MTD calculations when compared to static quantum investigations. The latter do not allow for the identifcation of all points that may occur along the reaction path. Static quantum calculation converges to limited geometry states, while the metadynamics converges to several metastable and stable geometries and confgurations. Moreover, the strong dependence of the reaction dynamics upon the functional and pseudopotential used highlights the importance of the dispersion forces along the reaction path. A complete description of the reaction mechanism from both the free energy standpoint and the structural confgura- tions of the molecular species is discussed in detail. The diferences in the free energy profle are discussed in terms of the limited account of the dispersion interactions within the DFT approach and the standard local XC functionals, confrming the strong non-covalent interactions and molecular rearrangement of charged species that take place all along the reaction path. Keywords Wittig reaction · Ab initio static · Metadynamics 1 Introduction Discovered in the early 50 s, the Wittig’s reaction [1, 2] is widely used in organic chemistry [3–6]. Recent reviews and articles have focused on the details of the mechanism [7–16]. In this synthesis approach, the reaction occurs between a carbonyl function (aldehydes or ketones) and a phosphorus ylide, producing an alkene with a phosphine oxide as fnal products. The Wittig reaction presents a huge interest in several areas of organic synthesis [17–19]; its power is obvious and justifes the considerable number of studies undertaken on this subject, with a large number of reviews focusing particularly on the mechanism [3, 11]. Although the mecha- nism of the reaction has long been subject to intensive inves- tigations, still, it remains probably the most debated subject over the last 50 years. Most theoretical investigations are performed within the static quantum calculation approach for the description of the mechanism of the Wittig chemical transformation. Metadynamics simulation is another pos- sible route available that may be used to investigate with more details the reaction path and to bring into evidence the mechanism and the stereochemistry involved in such chemi- cal reactions. The Wittig reaction is known to be a one pot reaction that depends upon the substituents of the reactants (ylide and the ketone or aldehyde), the solvent, the temperature and Li salts. The salt-free mechanism of the Wittig reac- tion is considered [3, 11] to be defnitely known. The frst step is an irreversible process resulting in the formation of the oxaphosphetane intermediate (obtained into two forms), and a second step, giving the products from form 2 of the oxaphosphetane. Most importantly, there is a general agree- ment about the stereochemistry of the reaction of the product * Abdelghani Mohamed Krallafa krallafa.abdelghani@univ-oran.dz; a.krallafa@yahoo.fr 1 LCPM, Chemistry Department, Faculty of Sciences, University of Oran 1, Ahmed Benbella, 31000 Es-Senia, Oran, Algeria 2 Research Centre in Analytical Chemistry and Physics (CRAPC), Algiers RP, BP 248, 16004 Algiers, Algeria