Domino pericyclic reactions of acyclic conjugated (E,Z,E,E)-tetraenes

Article abstract of DOI:10.1016/j.tetlet.2007.03.011

Acyclic conjugated (E,Z,E,E)-tetraenes, upon thermolysis, undergo a domino pericyclic process involving 6π electrocyclisation of the (E,Z,E)-triene moiety to give the corresponding cis-disubstituted 5-vinyl-1,3-cyclohexadienes, followed by an intramolecul

Full text of DOI:10.1016/j.tetlet.2007.03.011

Tetrahedron Letters 48 (2007) 3281–3284
Domino pericyclic reactions of acyclic conjugated
(E,Z,E,E)-tetraenes
a
Danielle Skropetaa,b, and Rodney W. Rickards
*
aResearch School of Chemistry, Australian National University, Canberra, ACT 0200, Australia
bDepartment of Chemistry, University of Wollongong, Wollongong, NSW 2522, Australia
Received 29 January 2007; revised 17 February 2007; accepted 1 March 2007
Available online 4 March 2007
Abstract—Acyclic conjugated (E,Z,E,E)-tetraenes, upon thermolysis, undergo a domino pericyclic process involving 6p electro-
cyclisation of the (E,Z,E)-triene moiety to give the corresponding cis-disubstituted 5-vinyl-1,3-cyclohexadienes, followed by an intra-
molecular Diels–Alder reaction with the vinyl side chain to give tricyclo[3.2.1.02,7]oct-3-enes.
Ó 2007 Elsevier Ltd. All rights reserved.
Upon thermolysis, acyclic conjugated (E,Z,Z,E)-tetra-
enes typically undergo a conrotatory 8p electro-
cyclisation to a cyclooctatriene, often followed by a
disrotatory 6p electrocyclisation to a bicyclo[4.2.0]oct-
adiene (Path A, Fig. 1).1 Such periselectivity for Wood-
ward–Hoffmann processes which involve the longest
part of the conjugated system is not absolute, but is
dependent upon the reaction conditions and the polyene
substitution. Thus, the same (E,Z,Z,E)-tetraene can also
be viewed as an (E,Z,Z)-triene conjugated to an (E)-
alkene, and as such is capable of undergoing a disrotatory
6p electrocyclisation to a 5-vinyl-1,3-cyclohexadiene,2,3
followed by an intramolecular Diels–Alder (IMDA)
reaction to give a tricyclo[3.2.1.02,7]oct-3-ene,4 as has
been reported3a (Path B, Fig. 1). Isomerisation of one
of the inner Z olefinic bonds of the (E,Z,Z,E)-tetraene
to the E configuration should preclude adoption of a
conformation suitable for 8p electrocyclisation, forcing
the alternative 6p process to prevail (Fig. 1). We exam-
ine here the occurrence of pericyclic reactions in such
acyclic conjugated (E,Z,E,E)-tetraenes (cf. Figs. 1 and
3).
We have previously shown that a stereochemically
related (E,Z,E,Z)-tetraene, that is, the 7E,9Z,11E,13Z-
hexadeca-7,9,11,13-tetraene shown in Figure 2,
Path A
Path B
6π electrocyclic
8π electrocyclic
R
6π electrocyclic
Diels-Alder
reaction
reaction
reaction
reaction
R
R
R
R
R'
R'
R'
R'
R'
R
R'
(E,Z,Z,E)-tetraene
R
8π electrocyclic
6π electrocyclic
R
Diels-Alder
reaction
reaction
reacXtion
R
R'
R'
R'
R'
R
(E,Z,E,E)-tetraene
Figure 1. Pericyclic reaction pathways of (E,Z,Z,E)- and (E,Z,E,E)-tetraenes (solid arrows show established pathways, dashed arrows show potential
pathways).
Keywords: Electrocyclic reaction; Intramolecular Diels–Alder reaction; Tetraenes; Polyenes.
*
Corresponding author. Tel.: +61 2 42214360; fax: +61 2 42214287; e-mail: skropeta@uow.edu.au
0040-4039/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2007.03.011

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D. Skropeta, R. W. Rickards / Tetrahedron Letters 48 (2007) 3281–3284
Table 2. Thermolysis of polyenes 1a–c to tricyclo[3.2.1.02,7]oct-3-enes
3a–c
6π electrocyclic
Diels-Alder
reaction
13
reaction
X
R
R
9
CH3
toluene, 170 ºC
R = CH2OTBDMS
sealed tube, 34 h
R
R
1a-c
H3C
3a-c
Figure 2. 6p Electrocyclisation of an (E,Z,E,Z)-tetraene.
Entry
R
Z/E Ratioa
Product
Yieldb (%)
1
2
3
(E)-CH@CHMe
Me
Ph
70:30
67:33
>98:2
3a
3b
3c
60c (51)d
87c (15)d
17c (16)d
undergoes thermal electrocyclisation to a 5,6-cis-disub-
stituted cyclohexadiene.5 This process provides a biomi-
metic precedent for the possible involvement of
‘electrocyclase’ enzymes in the biosynthesis of certain
o-dialkyl-substituted benzenoid microbial products
which lack oxygen functionality on or adjacent to the
aromatic ring. In this case the electrocyclisation is cen-
tred about the 9Z-olefinic bond, the flanking 7E and
11E bonds undergoing disrotatory thermal motion as
predicted by Woodward and Hoffmann.1 The conju-
gated 13Z-bond here plays only a spectator role, with
steric hindrance by its Z-substituents preventing its
IMDA reaction with the cyclohexadiene moiety to form
a tricyclo[3.2.1.02,7]oct-3-ene.
a Refers to the (Z/E)-ratio of the newly formed double bond.
b Yields are corrected for the amount of (all-E)-isomer present in the
starting material.
c Yields based on analytical GC.
d Isolated yields, which are low due to the high volatility of the
compounds.
ratios compared to freshly prepared material (cf. Tables
1 and 2).
(E,E,Z,E,E)-Pentaene 1a was the first polyene to be
thermolysed, since symmetry properties should distin-
guish the expected product, the cis-disubstituted cyclo-
hexadiene 2a, from the alternative trans-disubstituted
isomer. Thus, a dilute solution of pentaene 1a {contain-
ing 30% of the (all-E)-stereoisomer9} was heated in a
sealed tube at 170 °C for 34 h.7 Analysis by GC revealed
that essentially all the starting material had reacted to
form one major compound,10 in 60% yield when cor-
rected for the initial presence of the (all-E)-stereoisomer,
the remainder of the starting material presumably
polymerising into non-volatile material not observable
by GC (Table 2).
The present (E,Z,E,E)-systems 1a–c (Fig. 3) would be
expected to yield the 5,6-cis-disubstituted cyclohexadi-
enes 2a–c. These cyclohexadienes, however, carry at last
one vinyl substituent with an E-, not Z, configuration,
and it was unclear whether this E-olefin would undergo
an IMDA reaction. While precedents for such an intra-
molecular cycloaddition of a pendant 5E-olefin in 5,6-
cis-disubstituted cyclohexadienes exist,3c,d the examples
are unrelated to the present systems 2a–c. Molecular
modelling studies indicate that the enthalpy of activa-
tion for the IMDA reaction of cyclohexadiene 2b,
depicted in Figure 3, is almost twice that for the 6p
electrocyclisation by which it is formed.6
EI-MS confirmed, as expected, that the major product
was isomeric with the starting material (1a). NMR spec-
troscopy, however, revealed the presence of only two
double bonds and therefore the product was tricyclic.
Thus, the most likely explanation is that the acyclic
(E,E,Z,E,E)-pentaene 1a upon heating does indeed
undergo disrotatory 6p electrocyclisation of its central
(E,Z,E)-triene moiety to give the corresponding cis-
5,6-disubstituted 1,3-cyclohexadiene 2a,1a followed by
an IMDA reaction3,4 involving one of its (E)-prop-1-
enyl side chains to give the endo,exo-6,8-disubstituted
tricyclo[3.2.1.02,7]oct-3-ene 3a (cf. Figs. 3 and 4). The
alternative conrotatory 6p electrocyclisation of pentaene
1a would produce the corresponding trans-5,6-disubsti-
tuted cyclohexadiene, whereupon an IMDA reaction
would then form the analogous exo,exo-isomer (not
shown). The Woodward–Hoffmann rules predict the
former reaction sequence.1a
Polyenes 1a–c were prepared by Wittig reactions
between (2E,4E)-hexa-2,4-dienyltriphenylphosphonium
bromide and sorbic aldehyde, crotonaldehyde and
cinnamaldehyde and obtained as 1:1 mixtures of
(Z/E)-stereoisomers about the new double bond (Table
1).7,8 Immediately prior to thermolysis, the polyenes
were chromatographed to remove any polymer formed
during storage. This gave rise to altered (Z/E)-isomer
Table 1. Preparation of polyenes 1a–c by Wittig reactions
CH2PPh3Br
CHO
H3C
R
LiOEt, EtOH
rt, 17 h
CH3
R
CH3
R
The proposed endo,exo-6,8-disubstituted tricyclo-
[3.2.1.02,7]oct-3-ene structure of the tricyclic diene 3a
was supported by 1H NMR spectroscopy, including
selective homonuclear decoupling and 1H,1H-correla-
tion spectroscopy (COSY). In particular, designation
of the propenyl substituent as endo is based on the
COSY contour map where the signal belonging to the
bridgehead proton 5-H shows no correlation whatsoever
to the signal for the allylic proton 8-H (cf. Fig. 4). This
1a-c
Entry
R
Producta
Yieldb (%)
1
2
3
(E)-CH@CHMe
Me
Ph
1a
1b
1c
79
49
80
a Polyenes 1a–c were obtained as 1:1 mixtures of (Z/E)-isomers about
the new double bond.
b Isolated yields.

D. Skropeta, R. W. Rickards / Tetrahedron Letters 48 (2007) 3281–3284
3283
edge of the occurrence of pericyclic processes in acyclic
conjugated polyenes, and may provide an expedient
entry into the tricyclic skeleton present in some complex
natural products.15
Δ
CH3
CH3
R
R
H3C
3a-c
R
1a-c
2a-c
a: R = (E)-CH=CHMe; b: R = Me; c: R = Ph
Figure 3. Pericyclic reactions of (E,Z,E,E)-tetraenes.
Acknowledgements
The authors thank Tony Herlt for his invaluable techni-
cal support, and D.S. thanks the Australian National
University for the award of a Ph.D. Scholarship.
H
H
H
6
H
8
H
8
CH3
H
5
H3C
(exo)
6 CH3
H5
H
3a
(endo)
CH3
Supplementary data
Figure 4. Structure of the endo,exo-6,8-disubstituted tricyclo[3.2.1.02,7]-
oct-3-ene (3a).
Supplementary data (experimental procedures and
selected data for compounds 1a, 3a, 3b and 3c)
associated with this article can be found, in the online
version, at doi:10.1016/j.tetlet.2007.03.011.
lack of vicinal coupling between 5-H and 8-H is charac-
teristic for these compounds when 8-H is oriented
exo,3a,11 and is consistent with a measured dihedral
angle between these protons of 81°, obtained from
the minimised structure computed using molecular
mechanics.12
References and notes
1. (a) Woodward, R. B.; Hoffmann, R. J. Am. Chem. Soc.
1965, 87, 395; (b) Huisgen, R.; Dahmen, A.; Huber, H. J.
Am. Chem. Soc. 1967, 89, 7130; (c) Marvell, E. N. Thermal
Electrocyclic Reactions; Academic Press: New York, 1980;
pp 376–401; (d) Okamura, W. H.; de Lera, A. R. 1,3-
Cyclohexadiene Formation Reactions. In Comprehensive
Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 5, pp 743–745.
As it was now apparent that an IMDA could occur in
these cis-disubstituted cyclohexadienes carrying an E-
olefin substituent, (E,Z,E,E)-decatetraene 1b was exam-
ined next, on the premise that the endo,exo-isomer of the
expected thermal product, tricyclooctene 3b, could be
easily distinguished from the symmetrical exo,exo-iso-
mer, lending further support to the proposed pericyclic
cascade. Thus, a dilute solution of tetraene 1b {contain-
ing 33% of the (all-E)-isomer13} was heated at 170 °C
for 34 h7 and analysed by GC, which revealed that most
of the starting material had reacted to form one major
compound14 in 87% yield when corrected for the initial
presence of the (all-E)-isomer in the starting material
(Table 2). The product of the reaction was confirmed
by a combination of MS and NMR spectroscopy as
endo,exo-6,8-dimethyltricyclo[3.2.1.02,7]oct-3-ene 3b.8
2. Morwick, T. M.; Paquette, L. A. J. Org. Chem. 1997, 62,
627.
3. (a) Marvel, E. N.; Seubert, J.; Vogt, G.; Zimmer, G.; Moy,
G.; Siegmann, J. R. Tetrahedron 1978, 34, 1323; (b) Roth,
W. R.; Peltzer, B. Liebigs Ann. 1965, 685, 56; (c) ten Have,
R.; van Leusen, A. M. Tetrahedron 1998, 54, 1913; (d)
Loeliger, P.; Mayer, H. Helv. Chim. Acta 1980, 63, 1604.
4. For examples of intramolecular Diels–Alder reactions of
5-vinyl-1,3-cyclohexadienes see: (a) Giomi, D.; Nesi, R.;
Turchi, S.; Mura, E. J. Org. Chem. 2000, 65, 360; (b) Ng,
S. M.; Beaudry, C. M.; Trauner, D. Org. Lett. 2003, 5,
´
1701; (c) Abad, A.; Agullo, C.; Cunat, A. C.; de Alfonso,
˜
I.; Navarro, I.; Vera, N. Molecules 2004, 9, 287; (d)
D’Souza, D. M.; Rominger, F.; Muller, T. J. J. Chem.
Commun. 2006, 4096.
¨
Finally, similar thermolysis (170 °C for 34 h) of
(E,Z,E,E)-phenylnonatetraene 1c gave somewhat differ-
ent results (Table 2). In this case, GC analysis of the
crude reaction products showed that all the starting
material had reacted to form the now expected exo,
endo-6-methyl-8-phenyltricyclo[3.2.1.02,7]oct-3-ene 3c in
17% yield. Also obtained was a complex mixture of sev-
eral as yet unidentified compounds, which by GC reten-
tion times appeared to be isomeric with product 3c,
together with polymerised material.
5. Rickards, R. W.; Skropeta, D. Tetrahedron 2002, 58, 3793.
6. SPARTAN SG1, version 5.0.1, Open GL; Wavefunction Inc:
California, 1991–1997.
7. Typical procedures for the synthesis of polyenes 1a–c
and their thermolysis to the corresponding tricyclo-
[3.2.1.02,7]oct-3-enes 3a–c are available as Supplementary
data.
8. All new compounds gave satisfactory spectral and ana-
lytical data. Selected spectral data for compounds 1a, 3a,
3b and 3c are available as Supplementary data.
9. Ratio determined by analytical GC (BP1 column:
In conclusion, acyclic conjugated polyenes containing
an (E,Z,E,E)-tetraene moiety predominantly undergo
smooth thermal transformation to endo,exo-6,8-disub-
stituted tricyclo[3.2.1.02,7]oct-3-enes, via a domino pro-
cess involving a disrotatory 6p electrocyclisation of the
(E,Z,E)-triene moiety of the polyene to give cis-5,6-
disubstituted 1,3-cyclohexadienes, followed by an
IMDA reaction in which the (E)-prop-1-enyl substituent
behaves as a dienophile. This work extends our knowl-
T0 = 50 °C, grad. = 10 °C/min, inj. temp. = 125 °C, tR
11.89, 11.98 min).
=
10. One other product was detected by GC in ꢀ5% yield,
however, its retention time differed to that of the tricylic
product by only 0.1 min and the two products were
inseparable; their close retention times suggest they are
isomeric.
11. Zimmerman, H. E.; Grunewald, G. L.; Paufler, R. M.;
Sherwin, M. A. J. Am. Chem. Soc. 1969, 91, 2330.

3284
D. Skropeta, R. W. Rickards / Tetrahedron Letters 48 (2007) 3281–3284
12. CS Chem-3D Pro., Version 3.1 for Apple Macintosh;
CambridgeSoft Corporation: Cambridge, 1995.
13. Ratio determined by analytical GC (BP1 column:
14. Two minor products (<5% yield) were also detected by GC.
15. (a) Bohlmann, F.; Jakupovic, J.; Ahmed, M.; Grenz, M.;
Suding, H.; Robinson, H.; King, R. M. Phytochemistry
1981, 20, 113; (b) Pelletier, S. W.; Djarmati, Z.; Mody, N.
V. Tetrahedron Lett. 1976, 21, 1749.
T0 = 50 °C, grad. = 5 °C/min, inj. temp. = 150 °C, tR
11.69, 11.89 min).
=