A Facile Diels-Alder Reaction with Benzene: Synthesis of the Bicyclo[2.2.2]octene Skeleton Promoted by Rhenium Mahendra D. Chordia, Philip L. Smith, Scott H. Meiere, Michal Sabat, and W. Dean Harman* Department of Chemistry, UniVersity of Virginia CharlottesVille, Virginia 22901 ReceiVed July 11, 2001 The Diels-Alder reaction, in which a diene is combined with an alkene to form a cyclohexene, is one of the most synthetically useful of all cyclization reactions. 1,2 Since the reaction is both concerted and stereoselective, two new C-C bonds and up to four new stereocenters may be generated in a single step with a high degree of stereocontrol. Although ubiquitous in nature, simple aromatic molecules are rarely employed as dienes in Diels-Alder reactions due to their inherent aromatic stability. A thermodynamic barrier of 20-40 kcal/mol must be overcome in order to induce such reactivity from benzene, the benchmark of aromatic systems. 3,4 In the proper coordination environment, both osmium 5 and rhenium 6,7 can form stable complexes with arenes in which only two of the six carbons are coordinated. Once complexed in a dihapto fashion, the uncoordinated portion of the arene more closely resembles a conjugated diene. We therefore hypothesized that the complex- ation should increase the propensity of arenes to undergo cycloaddition reactions. Only a small number of Diels-Alder reactions with aromatic compounds have been reported. 8,9 These examples fall roughly into two categories based on the approach employed in overcom- ing the resonance energy of the starting materials. One technique exploits the reactivity of highly strained aromatic compounds so that the relief of this strain compensates for the loss in aromaticity. Alternatively, employing harsh conditions such as high temper- atures and pressures or the use of strong Lewis acids has been moderately successful. Usually, however, side reactions domi- nate: the adducts are isolated in low yields (typically less than 10%) and are prone to retrocycloaddition. Over the past decade, one of the primary goals of our research has been to develop metal fragments that bind aromatic com- pounds in an η 2 -fashion in order to activate them toward reactions with electrophiles. Recently, we have developed an electron-rich metal fragment, {TpRe(CO)(MeIm)}, 10 that binds benzene to form complex 1. The crystal structure of this complex shows dearo- matization of the π-system to such an extent that the uncoordi- nated portion of the ring closely resembles cyclohexadiene. 7 When 1 is combined with NMM in a cosolvent mixture of benzene/THF and allowed to stir at 20 °C for 2 days, a Diels- Alder cycloaddition occurs to form product 2, recovered as a single diastereomer in 65% yield (Scheme 1). This complex is stable in air and water and may be purified by column chroma- tography on silica gel. The 1 H NMR spectrum of 2 features a set of doublet-of-doublets assigned to the bound olefin protons at 2.84 ppm for H(6) and 2.25 ppm for H(5), a sharp singlet assigned to the imidazole methyl at 3.81 ppm, and a second sharp singlet assigned to the succinamide N-methyl group at 2.74 ppm. The 13 C NMR spectrum shows the metal-bound carbons at 69.1 and 61.2 ppm, assigned to C(6) and C(5), respectively. Additionally, the infrared spectrum displays prominent carbonyl absorptions at 1785 (CO) and 1688 cm -1 (amide). The cyclic voltammagram of 2 features a reversible oxidation wave with E 1/2 ) 160 mV, indicative of a Re(I)-olefin complex. 7 The stereochemistry of the cycloaddition was first elucidated through NOESY spectral data that suggested that the reaction occurred to the arene face opposite metal coordination with exclusively endo selectivity. This assignment was later confirmed by an X-ray crystal structure analysis (Figure 1). Liberation of the organic cycloadduct 3 from the metal complex was achieved through oxidation of the rhenium center under a variety of conditions in up to 90% yield (Supporting Information). Convenient oxidants were CuBr 2 , AgOTf, [FeCp 2 ]PF 6 , or O 2 /TFA. No attempt was made to recover the metal from these reactions. We were surprised to discover that under certain conditions, the bound olefin underwent further oxidation, yielding the enone cycloadduct 4 (55% isolated yield). Although the exact mechanism of this oxidation is yet to be fully understood, it is apparent that the rhenium in a higher oxidation state inserts an oxygen atom, presumably originating from adventitious water, into the C-H bond of the bound olefin. The putative enol resulting would tautomerize to the enone after decomplexation. The spectroscopic (1) Hamer, J. Ed. 1,4-Cycloaddition Reactions. The Diels-Alder Reactions in Heterocyclic Syntheses; Academic Press: New York, 1967. (2) Fringuelli, F.; Taticchi, A. Dienes in the Diels-Alder reaction; Wiley & Sons: New York, 1990. (3) Rogers, D. W.; McClafferty, F. J. J. Org. Chem. 2001, 66, 1157. (4) Carey, F. A.; Sundberg, R. A. AdVanced Organic Chemistry, 3rd ed.; Part A: Structure and Mechanism; Plenum Press: New York, 1990; pp 499- 503. (5) Harman, W. D. Chem. ReV. 1997, 97, 1953. (6) Brooks, B. C.; Gunnoe, T. B.; Harman, W. D. Coord. Chem. ReV. 2000, 206, 3. (7) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. Organometalics 2001, 20, 1038. (8) Cossu, S.; Garris, F.; DeLucchi, O. Synlett 1997, 12, 1327. (9) Cossu, S.; Battaggia, S.; DeLucchi, O. J. Org. Chem. 1997, 62, 4162. (10) Abbreviations used throughout the text: MeIm, 1-methylimidazole; Tp, hydrido(tris)pyrazolyl borate; NMM, N-methylmaleimide; DMAD, di- methylacetylene dicarboxylate; pz, pyrazole. Scheme 1. Rhenium-Promoted Diels-Alder Cycloaddition Reaction with Benzene and a Maleimide 10756 J. Am. Chem. Soc. 2001, 123, 10756-10757 10.1021/ja011689q CCC: $20.00 © 2001 American Chemical Society Published on Web 10/04/2001