The use of Lewis acids in radical chemistry.: Chelation-controlled radical reductions of substituted α-bromo-β-alkoxy esters and chelation-controlled radical addition reactions

The radical reduction of a series of alpha-bromo-beta-alkoxy esters under chelation-controlled conditions is reported. Proceeding with high stereoselectivity in the presence of MgBr2. OEt2, reductions give access to syn, products. Systematic variations in substrate substituents show that these reactions tolerate a wide variety of alkyl functionalities at positions 2 and 3 and are relatively unaffected by the nature of the ester group. Changes to the alkoxy function indicate that a bidentate chelate is involved in the reaction and that an excess of MgBr2. OEt2 is required for optimum selectivity by favoring this species in preference to the anti-selective monodentate or nonchelated pathways. Competition experiments suggest that the monodentate pathway is kinetically favored over the bidentate one. The suppressibility of the reaction by radical chain inhibitors and the need for initiation indicate the intermediacy of radicals. Further support for this mechanism includes both radical addition to alpha,beta-unsaturated esters and reduction of bromides conducted in the presence of a Lewis acid.