10756
J. Am. Chem. Soc. 2001, 123, 10756-10757
Scheme 1. Rhenium-Promoted Diels-Alder Cycloaddition
Reaction with Benzene and a Maleimide
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 osmium5 and rhenium6,7 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.
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 1H 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
13C 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 E1/2 ) 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 CuBr2, AgOTf, [FeCp2]PF6, or O2/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
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 η2-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
(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.
10.1021/ja011689q CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/04/2001
Chordia
