Manganese(III)-Based Oxidative Free-Radical Cyclization of Unsaturated β-Keto Esters, 1,3-Diketones, and Malonate Diesters

Abstract

Oxidative free-radical cyclizations of unsaturated 3-keto esters, 1,3-diketones, and malonate diesters with 2 equiv of Mn(0Ac)3'2H20 and 1 equiv of Cu(0Ac)2-H20 are described. Oxidation of β-keto ester 1 with Mn(III) to enol radical 2 followed by 6-exo cyclization gives radical 4, which is oxidized by Cu(II) to give alkene 7 in 64-71% yield. Oxidation of 9 gives a lower yield of 5-exo cyclization product 11 due to competing overoxidation to give 13. Oxidative cyclization of 18 gives the tertiary radical 19, which is further oxidized to cation 20. Oxidation of α-substituted β-keto esters 23, 33, and 37 proceeds in high yield since the product cannot be oxidized further. Oxidative cyclization of unsaturated cyclic β-keto esters 40a and 45 proceeds efficiently to give bicyclic adducts 42, 44, and 47. Oxidative cyclizations of 4-alkenyl-2-methylcyclopentane-l,3-diones 54, 61, and 64 provide bicyclo[3.2.1]octanediones 57, 63, and bicyclo[3.3.1]nonanediones 66 and 67 in moderate yields. These studies indicate that Mn(III)-based oxidative free-radical cyclization is a powerful synthetic method, delineate the scope and limitations of this reaction, and suggest further avenues for exploration. © 1990, American Chemical Society. All rights reserved.