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J. Org. Chem. 1996, 61, 7832-7847
Mn(III)-Based Oxidative Free-Radical Cyclizations of Unsaturated Ketones Bridget McCarthy Cole, Luning Han, and Barry B. Snider* Department of Chemistry, Brandeis University, Waltham, Massachusetts 02254-9110 Received June 24, 1996X
Mn(III)-based oxidative free-radical cyclization of unsaturated ketones is a versatile synthetic procedure with broad applicability. For example, oxidation of cyclopentanone 1a with 2 equiv of Mn(OAc)3‚2H2O and 1 equiv of Cu(OAc)2‚H2O in AcOH at 80 °C for 1.5 h affords 75% of bicyclo[3.2.1]oct-3-en-8-one 8a and 15% of bicyclo[3.2.1]oct-2-en-8-one 9a. Bridged bicyclic ketones that cannot enolize further are isolated in good yield. Monocyclic β,γ-unsaturated ketones that can enolize are oxidized further to give γ-acetoxy enones. The formation of bicyclo[3.3.1]non-2-en-9one (57a) in 52% yield from 2-allylcyclohexanone (56a) suggests that kinetically controlled enolization is the rate-determining step in R-keto radical formation. A wide variety of examples delineating the scope, limitations, and stereoselectivity of this reaction are presented. During the past decade, Mn(III)-based oxidative freeradical cyclizations have been developed into a versatile protocol for the formation of highly functionalized products from simple precursors.1 These cyclizations have been initiated by reaction of relatively acidic compounds, such as 1,3-diketones, acetoacetates, malonates, and R-sulfinyl or R-nitro ketones, with Mn(OAc)3 to form Mn(III) enolates, which undergo electron transfer to give Mn(II) and radicals. The Mn(III)-based oxidative freeradical addition of simple symmetrical ketones to simple alkenes is well known.1c-e In these reactions, the ketone must be used in large excess to prevent further oxidation of the product. Accordingly, the reported yields are based on oxidant consumed, and these reactions are of limited preparative value. Oxidative free-radical cyclizations of unsaturated ketones have not been examined, presumably because of anticipated problems with both the regioselectivity of radical formation and further oxidation of the cyclic ketone products when the starting ketone is too valuable to use in large excess. Cyclization of 5-Hexenyl Radicals. Oxidative Cyclization of 1-Allyl-2-oxocycloalkanecarboxylates 1a-d. We have found that Mn(III)-based oxidative free-radical cyclization of unsaturated ketones is in fact a versatile synthetic procedure with broad applicability.2 For instance, reaction of cyclopentanone 1a as a 0.1 M solution in AcOH with 2.25 equiv of Mn(OAc)3‚2H2O and 1 equiv of Cu(OAc)2‚H2O for 1.5 h at 80 °C affords 75% of bicyclo[3.2.1]oct-3-en-8-one 8a,3 15% of bicyclo[3.2.1]oct-2-en-8-one 9a, and
