Oxidative cycloaddition of a 2-cyclohexenone or R-tetralone and an alkene with dried Mn(OAc) 3 in benzene at 80-140 °C provides a general route to dihydrobenzofurans 15 and dihydronaphthofurans 17. Although the yields are modest, this one-pot reaction provides simple access to these compounds, which have previously been prepared by multistep routes. Oxidative cycloaddition of 2-cyclohexenones with β-methylstyrenes provides a new route to benzofuranoid neolignans, which was applied to the synthesis of conocarpan ( 22). The formation of 2-acetoxyhexanedioic acids 27 and 47 from acetoxylation of 2-cyclohexenones in HOAc, but not in benzene, opens up a new class of Mn(OAc) 3 reactions and explains Watt and Demir's discovery that much higher yields of R′-acetoxy enones are obtained in benzene than in HOAc.In 1976, Williams and Hunter reported that Mn-(OAc) 3 ‚2H 2 O oxidation of enones in HOAc at reflux affords 6-35% of R′-acetoxy enones. 1,2 In a series of papers initiated in 1984, Watt, Demir, and co-workers reported that using Mn(OAc) 3 dried over P 2 O 5 in benzene at reflux for 1 h to 2 d improves the yields of R′acetoxylation to 50-90%. 3 These reactions proceed by kinetic enolization of 2-cyclohexenone (1a) to give Mn(III) enolate 2a, which loses Mn(II) to give R′-keto radical 3a, which is oxidized by a second equivalent of Mn(OAc) 3 to give R′-acetoxy enone 4a. No explanation was provided for the vastly improved yields obtained in benzene.We found that intramolecular trapping of the R′-keto radicals obtained from cyclohexenones by suitably situated double bonds is much faster than acetoxylation, affording good yields of bicyclic dienones in favorable cases. 4 For instance, oxidative cyclization of 5 with 5 equiv of Mn(OAc) 3 and 1 equiv of Cu(OAc) 2 in benzene at reflux for 40 h affords 61% of 6 as a 3.4:1 E/Z mixture. We therefore decided to examine the intermolecular reactions of cyclohexenones and alkenes. Results and DiscussionOxidative Cycloadditions in Benzene. To our surprise, we found that oxidative addition of 2-cyclohexenones 1a-e with methylenecyclohexane (7a) in benzene at 80 °C for 3 d using Mn(OAc) 3 dried over P 2 O 5 in vacuum as described by Watt affords 25-42% of dihydrobenzofurans 15aa-ea and 0-18% of 6-(1-cyclohexenylmethyl)-2-cyclohexenones 12aa-ea (the first letter corresponds to the 2-cyclohexenone (1a-g) and the second to the alkene 7a-c or 19ab). Grisan (15aa), so named because it contains the griseofulvin skeleton, has been prepared twice by multistep routes 5 and is now available in a single step. No monomeric products are formed from 1a and 1-octene under these reaction conditions.The following mechanistic scheme is consistent with these results. Oxidation of cyclohexenone 1 will form R′keto radical 3. Addition of radical 3 to methylenecyclohexane (7a) will give radical 8, which is tertiary and is therefore readily oxidized by Mn(OAc) 3 to cation 11. 2 Loss of a proton from cation 11 will give 2-alkenyl-2-cyclohexenone 12. Cyclization of 11 will give bicyclic cation 10. Loss of ...

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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).2H(2)O and 1 equiv of Cu(OAc)(2).H(2)O in AcOH at 80 degrees 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 beta,gamma-unsaturated ketones that can enolize are oxidized further to give gamma-acetoxy enones. The formation of bicyclo[3.3.1]non-2-en-9-one (57a) in 52% yield from 2-allylcyclohexanone (56a) suggests that kinetically controlled enolization is the rate-determining step in alpha-keto radical formation. A wide variety of examples delineating the scope, limitations, and stereoselectivity of this reaction are presented.

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