Dyotropic rearrangement of α-lactone to β-lactone: a computational study of small-ring halolactonisation

Abstract

Transition structures have been optimised using the B3LYP/6-31+G* density functional level method, in vacuum and in implicit (PCM) and explicit (DFT/MM) aqueous solvation, for the degenerate rearrangement of the α-lactone derived by the formal addition of Cl⁺ to acrylate anion and for the dyotropic rearrangement of this to the β-lactone. Despite being lower in energy than the α-lactone, there is no direct pathway to the β-lactone from the acrylate chloronium zwitterion, which is the transition structure for the degenerate rearrangement. This may be rationalised by consideration of the unfavorable angle of attack by the carboxylate nucleophile on the β-position; attack on the α-position involves a less unfavorable angle. Formation of the β-lactone may occur by means of a dyotropic rearrangement of the α-lactone. This involves a high energy barrier for the acrylate derived α-lactone, but dyotropic rearrangement of the β,β-dimethyl substituted α-lactone to the corresponding β-lactone involves a much lower barrier, estimated at about 46 kJ mol⁻¹ in water, and is predicted to be a facile process.