Cope rearrangement versus a novel tandem retro-diels-alder-diels-alder reaction with role reversal

Article abstract of DOI:10.1021/ol0626793

A reinvestigation of the thermolysis of 4,4-dibromotetracyclo[6.2.1.0 ^2,7.0^3,5]undec-9-ene (2) affords diene 8 with a completely rearranged hydrocarbon skeleton via the isolable intermediate 4, along with cyclopentadiene and bromobenzene. DFT calculations show that the novel tandem retro-Diels-Alder-Diels-Alder reaction with role reversal is slightly less favored than the overall single-step Cope rearrangement. (Chemical Equation Presented)

Full text of DOI:10.1021/ol0626793

ORGANIC
LETTERS
2007
Vol. 9, No. 1
113-115
Cope Rearrangement versus a Novel
Tandem Retro-Diels Alder Diels Alder
Reaction with Role Reversal†
−
−
−
Kuan-Jen Su, Jean-Luc Mieusset, Vladimir B. Arion,‡ Lothar Brecker, and
Udo H. Brinker*
Institut fu¨r Organische Chemie, UniVersita¨t Wien, Wa¨hringer Strasse 38, A-1090 Wien,
Austria, and Institut fu¨r Anorganische Chemie, UniVersita¨t Wien,
Wa¨hringer Strasse 42, A-1090 Wien, Austria
udo.brinker@uniVie.ac.at
Received November 2, 2006
ABSTRACT
A reinvestigation of the thermolysis of 4,4-dibromotetracyclo[6.2.1.02,7.03,5]undec-9-ene (2) affords diene 8 with a completely rearranged
hydrocarbon skeleton via the isolable intermediate 4, along with cyclopentadiene and bromobenzene. DFT calculations show that the novel
tandem retro-Diels−Alder−Diels−Alder reaction with role reversal is slightly less favored than the overall single-step Cope rearrangement.
Organic chemists have always been fascinated by rearrange-
ments in which relatively simple compounds are being
transformed into more complex structures. The rigorous
clarification of the detailed reaction mechanism for such
conversions remains a challenging task.
According to an earlier report,1 heating of 4,4-dibromotetra-
cyclo[6.2.1.02,7.03,5]undec-9-ene (2), the product resulting
from a dibromocarbene addition to dicyclopentadiene (1), 2
at 130 °C for 1 h leads to the ring-opened3 compound 4
(Scheme 1). In addition, cyclopentadiene (5) and bromoben-
zene (7)4 are formed. A reinvestigation of the thermolysis
of 2, however, finds rac-(1R,2S,6R,7R,10R)-1,10-dibromotri-
cyclo[5.2.2.02,6]undeca-3,8-diene (8, 33% isolated yield), 5,
and 7 (42%, via GC calibration) as products. Moreover, 8
comprises 1H NMR and IR data identical with those reported
for 4.
A single-crystal X-ray analysis of 2 confirms the structure
of the starting material (Figure 2). Next, 2 was thermolized
in refluxing m-xylene (138 - 139 °C). In order to monitor
the thermolysis, every hour a sample for GC analysis was
taken. In Figure 1, peak areas of relevant signals are plotted
against reaction time.
* Corresponding author. Phone: +43-1-4277-52121. Fax: +43-1-4277-
52140.
† Carbene Rearrangements. 67. For part 66, see: Mieusset, J.-L.; Brinker,
U. H. J. Org. Chem., 2007, 72, 268.
‡ Institut fu¨r Anorganische Chemie.
The decrease of starting material 2 is unimolecular and
obeys first-order kinetics. The ring-opening product 4 is an
intermediate in the formation of final product 8. The
experiments were also performed at 111 °C with toluene as
(1) Molchanov, A. P.; Pecheritsyna, Ya. P.; Kostikov, R. R. J. Org. Chem.
USSR (Engl. Transl.) 1989, 25, 1076; Zh. Org. Khim. 1989, 25, 1195.
(2) (a) Ting, X.-T.; Liu, C.-P. Youji Huaxue 1988, 8, 511. (b) Huang,
N.-J.; Xu, L-H. Chin. Sci. Bull. 1991, 36, 831. (c) Zhao, Q.; Han, N.; Lin,
H; Yang, M. Huaxue Tongbao 2005, 68, w058/1.
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4537. (b) Weber, J.; Brinker, U. H. Angew. Chem., Int. Ed. Engl. 1997, 36,
1623. (c) Wagner, R. A.; Weber, J.; Brinker, U. H. Chem. Lett. 2000, 246.
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USSR (Engl. Transl.), 1984, 19, 1787; Zh. Org. Khim. 1983, 19, 2062.
10.1021/ol0626793 CCC: $37.00
© 2007 American Chemical Society
Published on Web 12/13/2006

Scheme 1
Figure 2. ORTEP representations of the single-crystal X-ray
diffraction structures of 2, 4 (crystallized in a 1:1 ratio of
enantiomers), and 8.
A plausible mechanism for the formation of bromobenzene
(7) encompasses a retro-Diels-Alder (rDA) reaction of 4 to
give 6 and a subsequent elimination of HBr (Scheme 1). A
mere Diels-Alder (DA) reaction6 of 6 and cyclopentadiene
(5) leads to 8. To our knowledge, the consecutive sequence
4 f 5 + 6 f 8 represents a novel tandem rDA-DA
reaction7 with role reVersal. An alternative possible pathway
to 8 consists of a stereoselective Cope rearrangement8 in 4.
Computations of the transition states for both pathways
using density functional theory (B3LYP/6-31G(d))9 suggest
that the Cope rearrangement 4 f 8 (∆G412 ) 30.6 kcal/
mol) is energetically preferred over the rDA reaction 4 f 5
+ 6 (∆G412 ) 34.2 kcal/mol) by 3.6 kcal/mol (Table 1).
Moreover, when compared with the Cope rearrangement, the
DA reaction 5 + 6 f 8 has a significant unfavorable entropic
contribution and should not occur at such high temperatures
(∆G412 ) 40.4 kcal/mol; ∆E0 ) 22.8 kcal/mol). Therefore,
if at all, the tandem rDA-DA reaction should be responsible
for the formation of only a very small fraction of 8. The
calculations also confirm that 8 is the kinetically favored
product of the DA reaction of cyclopentadiene with 6.10 In
the tandem pathway (e, h), a rDA reaction is followed by a
DA reaction in a new recombination of cyclopentadiene (5)
and 6.
solvent and afforded the same product distribution. Because
of toluene’s lower boiling point, the reaction rate is lower.
While the half-life of 2 in refluxing m-xylene is 1.5 h, it is
14.4 h in toluene. Both structures 4 and 8 were established
unequivocally by single-crystal X-ray analysis (Figure 2).
As expected, the ring opening of 2 to 4 proceeds according
to the Woodward-Hoffmann-DePuy rule5 in a stereose-
lective manner. The spectroscopic data obtained for 4 proved
to be totally different from NMR and IR data published
earlier.1 To corroborate the fact that 4 is an intermediate, it
was refluxed under the conditions applied for 2. The
conversion 4 f 8 also follows first-order kinetics. Further-
more, under the reaction conditions, isolated product 8 was
found to be almost completely stable (94%).
In an attempt to corroborate this tandem pathway, 6,6-
dibromobicyclo[3.1.0]hex-2-ene (9) was synthesized at -60
(5) (a) DePuy, C. H. Acc. Chem. Res. 1968, 1, 33. (b) Woodward, R.
B.; Hoffmann, R. Angew. Chem., Int. Ed. Engl. 1969, 8, 781. (c) Faza, O.
N.; Lo´pez, C. S.; AÄ lvarez, R.; de Lera, AÄ . R. J. Org. Chem. 2004, 69, 9002.
(6) Davies, H. M. L.; Dai, X. J. Am. Chem. Soc. 2004, 126, 2692.
(7) Goldschmidt, Z.; Levinger, S.; Gottlieb, H. E. Tetrahedron Lett. 1994,
35, 7273.
(8) (a) Chou, T.-C.; Chen, L.-L.; Lin, C.-T. Synth. Commun. 1991, 21,
1301. (b) Roma´n, E.; Ban˜os, M.; Higes, F. J.; Serrano, J. A. Tetrahedron:
Asymmetry 1998, 9, 449. (c) Hrovat, D. A.; Beno, B. R.; Lange, H.; Yoo,
H.-Y.; Houk, K. N.; Borden, W. T. J. Am. Chem. Soc. 1999, 121, 10529.
(9) (a) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785. (b)
Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(10) For example, for the formation of the isomeric compound 10 a
barrier needs to be overcome that is 3.2 kcal/mol higher in energy than the
one leading to 8.
Figure 1. Time-dependent decomposition of 2 in refluxing
m-xylene.
114
Org. Lett., Vol. 9, No. 1, 2007

According to B3LYP/6-31G(d) calculations, HBr catalyzes
the shift of the double bond by a concerted proton exchange.
Since this reaction is reversible and 10 (∆E0 ) -7.8 kcal/
mol in comparison to 4) possesses nearly the same relative
energy as 8 (∆E0 ) -7.9 kcal/mol) (Table 1), a statistical
distribution is obtained. Compound 11 formally derives from
a protonation of the double bond at C3 of the five-membered
ring in 8 followed by capture of the resulting cation by the
bromide ion from the exo-side (Scheme 3). However, 11 does
Table 1. Relative Energies of Compounds 2, 3 + HBr, 8, 10,
and Transition States for Conversions b-f, h (Scheme 1) in
Comparison to 4a
∆E0 (kcal/mol) ∆G412 (kcal/mol)
2
+16.3
+52.2
+15.3
0.0
+17.1
+51.1
+1.4
b: 2 f 4
3 + HBr
4
0.0
e: 4 f 5 + 6
c: 4 f 3 + HBr
f: 4 f 8
d: 3 + HBr f 5 + 7 + HBr
5 + 7 + HBr
5 + 6
h: 5 + 6 f 8
8
+36.0
+38.5
+30.4
+36.5
-5.7
+10.9
+33.7
-7.9
+34.2
+37.3
+30.6
+21.5
-37.8
-8.4
Scheme 3
32.0
-7.3
10
-7.8
-7.1
a Values in kcal/mol from B3LYP/6-31G(d) calculations.
not originate from the most stable carbenium ion that can
be generated from 8 by HBr attack at the double bond of
the cyclohexene moiety. Instead, the addition of HBr occurs
at the most electron-rich double bond (C3-C4) of 8 in a
concerted, strongly asymmetric fashion. Compound 11
proved to be stable under the reaction conditions (200 °C,
2 h, closed apparatus, without HBr), and both 8 and 10 were
not even formed in traces.
In conclusion, the thermal treatment of 2 leads to the
rearranged product 8 through isolable intermediate 4 along
with cyclopentadiene (5), and bromobenzene (7), by a deep-
seated rearrangement13 of the initial hydrocarbon skeleton.
In an earlier publication,1 structure 4 was mistaken for final
product 8. One mechanistic alternative, a novel tandem
rDA-DA reaction7 with role reVersal, is slightly less favored
than the one-step Cope rearrangement 4 f 8. Furthermore,
while the thermal reaction in an open vessel exclusively
provides 8, in a closed apparatus in addition its double bond
isomer 10 is formed from 8 by HBr catalysis.
to 0 °C11 and treated with cyclopentadiene (5) in order to
obtain 8. This experiment failed; instead, decomposition and
cleavage of HBr is favored and intermediate 6, which would
result from 9, could not be detected. Moreover, attempts to
trap 6 with 1,3-diphenylisobenzofuran did not succeed.
The thermal treatment of 2 in a closed apparatus (pressure
tube) at about 200 °C for 2 h afforded two isomeric products
8 (22%) and 1012 (5%). Isomer 10 could be the DA adduct
of 5 and 6, with a different orientation of diene and
dienophile. The fact that neither 10 nor any of the other
possible DA adducts were found under the standard condi-
tions (m-xylene reflux, open apparatus) is a further indication
for a Cope rearrangement in 4.
Thermolysis of 8 in m-xylene with added HBr gas at
∼200 °C in the closed apparatus (Scheme 2) yielded almost
Acknowledgment. We thank Prof. O. Hofer, Institut fu¨r
Organische Chemie, Universita¨t Wien, for his help with the
IUPAC nomenclature and Mr. A. Roller, Institut fu¨r Anor-
ganische Chemie, Universita¨t Wien, for performing X-ray
measurements.
Scheme 2
Supporting Information Available: Materials and meth-
ods, experimental procedures, spectral data, NMR spectra,
crystallographic data of 2, 4, 8, and 10, and computational
data. This material is available free of charge via the Internet
at http://pubs.acs.org.
a 1:1 ratio of isomers 8 (25%) and 10 (24%) along with
HBr addition product 11 (16%) and bromobenzene (7, 14%).
(11) Christl, M.; Braun, M.; Mu¨ller, G. Angew. Chem., Int. Ed. Engl.
1992, 31, 473.
(12) Structural verification by X-ray analysis.
OL0626793
(13) Padwa, A.; Ginn, J. D. J. Org. Chem. 2005, 70, 5197.
Org. Lett., Vol. 9, No. 1, 2007
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