Theoretical insight into the origins of chemo- and diastereo-selectivity in the palladium-catalysed (3 + 2) cyclisation of 5-alkenyl thiazolones

The palladium-catalysed diastereoselective (3 + 2) cyclisation of 5-alkenyl thiazolones with vinylethylene carbonates features unique chemoselectivity. Nevertheless, the detailed mechanisms of this cyclisation together with the origins of the unusual chemoselectivity and outstanding diastereoselectivity remain unknown. Herein, density functional theory calculations are performed to reveal a ligating-atom-dependent mechanistic pathway for this Pd-catalysed transformation. The reaction proceeds preferentially via C2′-selectivity through a unique Pd−N chelation-assisted inner-sphere pathway, producing the experimentally observed bicyclic product. Turnover frequency analysis shows that C–C bond formation for the intramolecular annulation is involved in the rate-determining step. The distortion/interaction model, non-covalent interaction and atom-in-molecule analyses reveal that the chelation effect and non-covalent interactions are key factors for the observed high selectivity. The strong chelation, favourable π-stacking and H-bonding interactions stabilise the selectivity-determining transition states for the C2′-selectivity and syn-selectivity pathways, facilitating the chemo- and diastereo-differentiation of several competing pathways for the experimentally observed selectivity.