Radical Cyclisation of α-Halo Aluminium Acetals: A Mechanistic Study.

Abstract

α-Bromo aluminium acetals are suitable substrates for Ueno-Stork-like radical cyclisations affording γ-lactols and acid-sensitive methylene-γ-lactols in high yields. The mechanistic study herein sets the scope and limitation of this reaction. The influence of the halide (or chalcogenide) atom X (X=Cl, Br, I, SPh, SePh) in the precursors α-haloesters, as well as influence of the solvent and temperature was studied. The structure of the aluminium acetal intermediates resulting from the reduction of the corresponding α-haloesters has been investigated by low-temperature (13) C-INEPT diffusion-ordered NMR spectroscopy (DOSY) experiments and quantum calculations, providing new insights into the structures of these thermally labile intermediates. Oxygen-bridged dimeric structures with a planar Al2 O2 ring are proposed for the least hindered aluminium acetals, while monomeric structures seem to prevail for the most hindered species. A comparison against the radical cyclisation of aluminium acetals derived from allyl and propargyl alcohols with the parent Ueno-Stork has been made at the BHandHLYP/6-311++G(d,p) level of theory, highlighting mechanistic similarities and differences.