Stepwise vs concerted mechanisms in the Wittig reaction in vacuo and in THF: the case of 2,4-dimethyl-3-pyrrol-1-yl-pentanal and triphenylphosphonium ylide

The Wittig reaction of the unsubstituted triphenylphosphonium ylide (Ph3PCH2) on an aldehyde with two stereogenic centres (2S,3R)-2,4-dimethyl-3-pyrrol-1-yl-pentanal) has been investigated with a density functional (DF) approach at the B3P86/6-31G* level in vacuo and in tetrahydrofuran (THF) to shed some light on the mechanistic details when bulky chiral substrates are employed in the absence of E/Z selectivity issues. The interest is focused on the reaction intermediates, primarily on those that cannot be observed spectroscopically. Both the concerted mechanism (with a four-centre transition state (TS)) and the stepwise one (occurring via a betaine-type zwitterionic intermediate) have been explored, examining the potential energy profiles as well as the free energy ones. The solvent effect in the integral equation formalism-polarizable continuum model (IEF-PCM) framework has been also considered for THF. Interestingly, the early TS found in vacuo for both mechanisms becomes vanishingly small in THF, while the reactant adducts turn out to be somewhat destabilized, with an overall similarity in the relevant profiles.