On the Diels-Alder dimerisation of cross-conjugated trienes

Article abstract of DOI:10.1039/c2cc32520a

The first general synthesis of 1-substituted [3]dendralenes has led to the discovery that conjugating groups significantly enhance the rate of Diels-Alder dimerisation relative to both the parent [3]dendralene and to other substituted systems.

Full text of DOI:10.1039/c2cc32520a

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COMMUNICATION
On the Diels–Alder dimerisation of cross-conjugated trienesw
Henry Toombs-Ruane,a Emma L. Pearson,a Michael N. Paddon-Row*b and
Michael S. Sherburn*a
Received 8th April 2012, Accepted 8th May 2012
DOI: 10.1039/c2cc32520a
The first general synthesis of 1-substituted [3]dendralenes has led
to the discovery that conjugating groups significantly enhance
the rate of Diels–Alder dimerisation relative to both the parent
[3]dendralene and to other substituted systems.
sub-class 5 are prone to rapid DA dimerisation up to 200 times
faster than parent triene 1. We define the structural require-
ments for this reactivity and we explain it, with the assistance
of DFT calculations.
All published syntheses of 1-substituted [3]dendralenes
involve reports of isolated examples.9 Our plan for a more
general 1-substituted [3]dendralene synthesis initially focussed
on the direct formation of the 1,2-disubstituted CQC bond
using Wittig reactions of the previously unreported phosphonium
salt 610 (Scheme 1). Surprisingly, reaction of the semi-stabilised
ylide derived from 6 with benzaldehyde led to the generation
of mixtures of four products: a ca. 1 : 2 ratio of 1Z-phenyl-
[3]dendralene 7a and cyclohexenes 9a, 10a and 11a. Compounds
9a–11a appear to be the DA dimers of the 1E-phenyl-
[3]dendralene isomer 8a, which would be an anticipated
product since the Wittig reaction of semi-stabilised ylides is
often poorly stereoselective.11 Similar results to those depicted
in Scheme 1 were obtained in Wittig reactions of phosphonium
salt 6 with substituted benzaldehydes.
Interest in the dendralene family of fundamental hydro-
carbons (Fig. 1) is increasing,1 a fact that is ascribable to the
ease by which they can be elaborated into polycyclic systems
through diene-transmissive Diels–Alder (DA) sequences.2,3
Members of the [n]dendralene family higher than the triene 1
(n = 3) and tetra-ene 2 (n = 4) were reported for the first time
only twelve years ago4 and higher members of the series
(n = 5–8) were made available in useful amounts only in
2009.5 [3]Dendralene 1 is the most reactive of the parent
hydrocarbons in Diels–Alder (DA) cycloadditions, both in
reactions with the dienophile N-methylmaleimide and in DA
dimerisations. In contrast, [4]dendralene 2 is the least reactive
of the series of [n]dendralenes (n = 3–8).5 The difference in
stability between 1 and 2 is dramatic: whereas 2 can be stored
neat at ambient temparature over extended periods without
noticeable change, 1 has a half life of around 10 h under these
conditions. This behaviour was explained through computa-
tional studies, which attributed the greater reactivity of 1
versus 2 to higher populations of reactive conformers and a
more stable closed-shell singlet bis-pericyclic transition state
for the DA dimerisation.6
The isolation of DA dimers 9a–11a was surprising in light of
the mild temperature (i.e. room temperature) and relatively
low concentrations (0.1 M) employed in these reactions.10
Nevertheless, Mulzer and coworkers reported some time
ago12 that attempts to form 1E,5E-diphenyl-[3]dendralene
(i.e. the 5E-phenyl analogue of 8a) led to the isolation of the
DA dimer13 and, very recently, Singh and Ghosh14 showed
that attempts to form 2-carboethoxy-1,5-diaryl-[3]dendralenes
also resulted in the isolation of DA dimers. Based on the result
depicted in Scheme 1, it would appear that not two but
Three sites for substitution are available about a [3]dendra-
lene framework and previous reports have detailed the synth-
esis and properties of the 30- and 2-substituted derivatives, 3
and 4 respectively (Fig. 1).1,7,8 In both cases, substituted
derivatives 3 and 4 were found to be considerably more stable
than the parent hydrocarbon 1. Herein we report a general
synthetic approach to the remaining series, namely 1-substituted
[3]dendralenes 5. We report the unexpected observation that,
in stark contrast to the behaviour of 3 and 4, members of
a Australian Research Council Centre of Excellence for Free Radical
Chemistry and Biotechnology, Research School of Chemistry,
Australian National University, Canberra, ACT 0200, Australia.
E-mail: sherburn@rsc.anu.edu.au (synthetic)
b School of Chemistry, The University of New South Wales, Sydney,
NSW 2052, Australia. E-mail: m.paddonrow@unsw.edu.au
(computational)
w Electronic supplementary information (ESI) available: experimental
procedures and characterisation data, 1H and 13C NMR spectra of all
new compounds and computational details. See DOI: 10.1039/
c2cc32520a
Fig. 1 The parent [3]- and [4]dendralenes and the possible mono-
substituted trienes.
c
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Chem. Commun., 2012, 48, 6639–6641 6639

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Table 1 Experimental half life measurements for DA dimerisation of
1E-substituted [3]dendralenesa
Half life Starting triene Cycloadduct
conc. (M)
Starting triene 8 (R=) (t1/2/h)
ratio 9 : 10 : 11
c (4-nitrophenyl)
d (–CO2Me)
a (Ph)
b (4-methoxyphenyl)
e (–CH2OAc)
1 (–H)
1.7
8.6
13
15
92
0.030
0.030
0.030
0.028
0.091
0.087
56 : 44 : 0
39 : 32 : 29
61 : 37 : 2
59 : 33 : 8
36 : 25 : 39
—
150
Scheme 1 Wittig approach to 1-substituted [3]dendralenes.
a
Overall yields for the dimerisation are in the range 89–99%, as
1
measured by H NMR spectroscopy.
only one aromatic group is required to promote facile DA
dimerisation of a [3]dendralene, so long as the group is located
at the 1-position. Furthermore, within the mono-substituted
dendralene series, we note that the facile DA dimerisation
behaviour is specific to the 1E-aryl-[3]dendralene isomer: the
30-phenyl-,15 2-phenyl-8 and 1Z-phenyl-[3]dendralene conge-
ners are stable towards dimerisation and can be stored neat at
ambient temperature.
data provided in Table 1, the majority of 1E-substituted
[3]dendralenes undergo DA dimerisation significantly faster
than the parent unsubstituted triene 1.18 The acetoxymethyl-
substituted system 8e is the odd one out, with a propensity
to dimerise that is only slightly higher than the parent
[3]dendralene. Aryl or carbomethoxy-substituted systems 8a–d
exhibit much faster dimerisations than 1.
Both the intermediacy of 1E-phenyl-[3]dendralene 8a and its
rapid DA dimerisation are implied from the result depicted in
Scheme 1. A synthetic approach that could provide an authentic
sample of the triene would provide stronger evidence by
allowing the direct observation of the dimerisation event.
We recently demonstrated that 12, the iron tricarbonyl
complex of the parent [3]dendralene, undergoes cross metathesis
with various olefins to gave stable, isolable complexes of
1E-substituted [3]dendralenes 13 (Scheme 2).16 This work
was extended to complexes 13a–e, carrying aryl, alkyl and
ester substituents. Gratifyingly, oxidative decomplexation17
was sufficiently rapid at 0 1C to generate, after workup, CDCl3
solutions of 1E-aryl, alkyl and carboethoxy-substituted [3]den-
dralenes 8a–e that were free of DA dimerisation products and
other contaminants, as shown by NMR spectroscopic analysis.10
As expected, trienes 8a–e underwent DA dimerisation at
ambient temperature to form three isomeric cycloadducts,
namely 9–11. As can be seen from the experimental half-life
These findings may be explained in terms of the recently
proposed biradicaloid transition structure (TS) for the dimeri-
sations of dendralenes.6 DFT calculations revealed that
[3]dendralene dimerised via a bispericyclic TS, whose geometry
and electronic structure is best described by two pentadienyl
radicals which are sufficiently strongly coupled through the
developing C30ꢀ ꢀ ꢀC30 bond to produce a closed-shell singlet
state 14 (Scheme 3).6 Closure to the [3]dendralene dimer occurs
through two degenerate pathways involving C1–C3 bond
formation.
Scheme 3 Biradicaloid TS leading to [3]dendralene dimer.
This biradicaloid model predicts that the introduction of a
radical stabilising substituent at C1 of [3]dendralene should
accelerate the dimerisation reaction, relative to the parent
cognate system. This prediction was verified by calculating
the stabilisation enthalpies at 0 K (DH0 K) of 1-substituted penta-
dienyl radicals, defined by the reaction 8Hꢁ + 1 - 8 + 1Hꢁ.
This equation and the B3LYP/6-31G(d) DH0 K values are given
in Table 2.
Comparing these radical stabilising energies with the experi-
mental data, the relative reactivities of the three aryl substituted
dendralenes are correctly reflected in the relative radical stabi-
lisation energies for these substituents. The methoxycarbonyl
Scheme 2 Optimised synthesis of 1E-substituted [3]dendralenes.
6640 Chem. Commun., 2012, 48, 6639–6641
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Table 2 Calculated B3LYP/6-31G(d) radical stabilisation enthalpies
in kJ molꢂ1 at 0 K
positioning of a conjugating group at the 1E-site of [3]dendralene
leads to a very reactive compound indeed.
This work was supported by the Australian Research
Council. MNP-R acknowledges that the computational
component of this research was undertaken with the assistance
of resources provided at the NCI National Facility through
the National Computational Merit Allocation Scheme sup-
ported by the Australian Government.
Notes and references
R
B3LYP
1 Reviews: (a) H. Hopf and M. S. Sherburn, Angew. Chem., Int. Ed.,
2012, 51, 2298–2338; (b) H. Hopf, in Classics in Hydrocarbon
Chemistry, Wiley-VCH, Weinheim, 2000, pp. 218–227;
(c) H. Hopf, Angew. Chem., Int. Ed. Engl., 1984, 23, 948–960.
2 A. D. Payne, A. C. Willis and M. S. Sherburn, J. Am. Chem. Soc.,
2005, 127, 12188–12189.
–CH3
–CH2OAc
–CO2Me
4-Methoxyphenyl
Phenyl
4-Nitrophenyl
ꢂ0.9
ꢂ0.3
7.0
8.7
8.9
3 G. Bojase, A. D. Payne, A. C. Willis and M. S. Sherburn, Angew.
Chem., Int. Ed., 2008, 47, 910–912.
11.8
4 S. Fielder, D. D. Rowan and M. S. Sherburn, Angew. Chem., Int.
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5 A. D. Payne, G. Bojase, M. N. Paddon-Row and M. S. Sherburn,
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6 M. N. Paddon-Row and M. S. Sherburn, Chem. Commun., 2012,
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7 N. A. Miller, A. C. Willis, M. N. Paddon-Row and M. S. Sherburn,
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substituent is predicted to be slightly less effective than aryl
groups at stabilising a pentadienyl radical but experimentally,
it lies between that of the 4-nitrophenyl and the phenyl
systems. Nevertheless, theory correctly predicts that all four
conjugating substituents will lead to faster DA dimerisations
than alkyl substituents, which are predicted to have no stabi-
lising influence on the pentadienyl radical.
8 T. A. Bradford, A. D. Payne, A. C. Willis, M. N. Paddon-Row and
M. S. Sherburn, Org. Lett., 2007, 9, 4861–4864.
The biradicaloid TS model also explains the dienophile site
selectivity of the DA dimerisation. All three DA dimers 9, 10
and 11 (Table 1) result from the internal 1,1-disubstituted
alkene functioning as dienophile, which can be formed from
TS 15 (Scheme 4). If one of the two terminal alkenes were to
react as dienophile then the TS would bear a much less stable
allyl radical component, as shown in TS 16.
9 (a) U. H. Brinker and L. Konig, J. Am. Chem. Soc., 1981, 103,
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10 See the Electronic Supplementary Information for detailsw.
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12 J. Mulzer, U. Kuhl, G. Huttner and K. Evertz, Chem. Ber., 1988,
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13 This property is by no means limited to cross-conjugated trienes.
Mulzer showed that 1E,3-diphenyl-1,3-butadiene and related
compounds exhibit the same behaviour: (a) J. Mulzer,
G. Bruntrup, U. Kuhl and G. Hartz, Chem. Ber., 1982, 115,
¨
¨
Scheme 4 Possible biradicaloid TSs leading to 1-substituted
3453–3469; (b) J. Mulzer and K. Melzer, Angew. Chem., Int. Ed.
Engl., 1995, 34, 895–898.
[3]dendralene dimers.
14 R. Singh and S. K. Ghosh, Chem. Commun., 2011, 47, 10809–10811.
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Interesting trends can be found on inspection of the ratios of
the three DA dimers (Table 1). Perhaps pꢀ ꢀ ꢀp stacking between
the two aryl groups stabilises a TS leading to 9, the dominant
isomer formed during DA dimerisation of the 1E-aryl-
[3]dendralenes, whereas the TS en route to this isomer could
be destabilised by steric strain when R = alkyl. While a better
understanding of some aspects of this DA dimerisation
must await further studies, it is abundantly clear that the
17 (a) M. Franck-Neumann, M. P. Heitz and D. Martina, Tetra-
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c
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Chem. Commun., 2012, 48, 6639–6641 6641