One-step synthesis and exploratory chemistry of [5]dendralene

Article abstract of DOI:10.1002/anie.200704470

(Chemical Equation Presented) Complex polycycles made simple: A practical synthesis of the simplest cross-conjugated pentaene, [5]dendralene, is reported. The hydrocarbon undergoes controllable and atom-efficient domino sequences (see scheme) to generate complex polycyclic frameworks in an operationally simple manner.

Full text of DOI:10.1002/anie.200704470

Communications
DOI: 10.1002/anie.200704470
Domino Reactions
One-Step Synthesis and Exploratory Chemistry of [5]Dendralene**
Gomotsang Bojase, Alan D. Payne, Anthony C. Willis, and Michael S. Sherburn*
The fundamental hydrocarbons known as dendralenes are the
neglected members of the family of conjugated oligoalkenes
(Scheme 1).[1–5] Whereas the synthesis and physical and
materials. Thus, the chloroprene Grignard reagent[8] under-
goes twofold Tamao–Kumada–Corriu coupling[9] with vinyl-
idene chloride at room temperature.[10] An aqueous workup
and vacuum distillation[11] affords [5]dendralene in 65% yield.
We routinely prepare five-gram batches of 1 using this
procedure. [5]Dendralene is a little more prone to decom-
position than the lower homologue [4]dendralene. Never-
theless, the hydrocarbon can be stored as an approximately
0.75m solution in light petrol, methylene chloride, or THF at
ꢀ158C with minimal decomposition over several months.
In principle, [5]dendralene could undergo a domino
sequence of diene-transmissive Diels–Alder reactions[12]
with four dienophile molecules. In practice, the hydrocarbon
reacts with an excess of N-methylmaleimide (NMM) at room
temperature in methylene chloride to furnish a mixture of six
products: two diastereomeric bis adducts 4 and 5 and four
Scheme 1. Four fundamental classes of conjugated oligoalkene
structures.
chemical properties of the linear polyenes, the annulenes,
and the radialenes have been examined in detail, little is
known about the dendralenes.[2,6] We recently reported a diastereomeric tris adducts 10, 11, 12, and 13 (Scheme 3).[13]
practical synthetic approach to [4]dendralene and some of its
cycloaddition reactions.[7] Herein we present the first practical
synthesis of the higher “ethenologue”, [5]dendralene (3,4,5-
trimethylenehepta-1,6-diene), and for the first time we
demonstrate its fascinating reactivity through domino
sequences of pericyclic reactions.
To date, the chemistry of [5]dendralene has remained
completely unexplored,[1–6] since the hydrocarbon has not
been available in synthetically useful amounts. Indeed, the
only published synthesis of the hydrocarbon from 3-sulfolene
takes five steps and proceeds with an overall yield of less than
2%.[6] In contrast, the practical synthesis of [5]dendralene (1),
which we now report (Scheme 2), avoids protection, proceeds
in one step, and uses cheap and widely available starting
The pathway from 1 to the six multiple adducts was elucidated
by a series of reactions involving the addition of one
equivalent of dienophile to 1, the mono adducts 2 and 3 and
the bis adducts 4–9.
The first dienophile addition to [5]dendralene occurs with
a preference for the terminal mono adduct 2 over its internal
congener 3. The latter gives rise to two diastereomeric bis
adducts 4 and 5 in roughly equal amounts at ambient
temperature and pressure. In contrast, terminal mono
adduct 2 furnishes a mixture of all six possible bis adducts
4–9 along with tris adducts 11 and 12. Linear conjugated
trienes 4 and 5 do not undergo further reaction with NMM
under these conditions. In contrast, the other four bis adducts
6–9, which contain cross-conjugated trienes, undergo cyclo-
additions to form the triple cycloadducts 10–13. Complete site
selectivity for the acyclic diene but very low p-diastereofacial
selectivity is witnessed during NMM cycloadditions to 7 and 9,
whereas the more symmetrical structures 6 and 8 exhibit
marked p-diastereofacial selectivities in reactions with NMM.
Thus, each of the six isolated products from the exhaustive
reaction depicted in Scheme 3 is formed from two different
precursors. The two major products from the reaction, tris
adducts 11 and 12, are the result of high levels of p-
diastereofacial selectivity in reactions of the meso and C2-
symmetric intermediates 6 and 8, respectively. It seems safe to
assume that the major pathway for the reaction is 1!2!6!
11, which represents a diene-transmissive terminal-terminal-
internal triple cycloaddition to [5]dendralene. Inspection of
the X-ray crystal structures of the four tris adducts 10–13
reveals a preference for a skewed s-cis-1,3-butadiene con-
formation, albeit one in which the diene is very sterically
hindered. None of the tris adducts underwent a fourth
cycloaddition with either NMM, diethyl acetylene dicarbox-
ylate, or N-phenyl triazolinedione under thermal, Lewis acid
promoted, or ultra-high-pressure conditions.
Scheme 2. Practical synthesis of [5]dendralene (1); dppp=1,3-bis(di-
phenylphosphanyl)propane.
[*] G. Bojase, Dr. A. D. Payne, Dr. A. C. Willis,[+] Prof. M. S. Sherburn[#]
Research School of Chemistry
Australian National University
Canberra, ACT 0200 (Australia)
Fax: (+61)2-6125-8114
E-mail: sherburn@rsc.anu.edu.au
Homepage: http://rsc.anu.edu.au/research/sherburn.php
[#] ARC Centre of Excellence for Free Radical Chemistry and
Biotechnology (Australia)
[+] Correspondence author for crystallographic data (willis@rsc.anu.
edu.au)
[**] We thank the Australian Research Council for funding.
Supporting information for this article is available on the WWW
under http://www.angewandte.org or from the author.
910
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Angewandte
Chemie
Scheme 3. Reaction of [5]dendralene withNMM. (Red =product breakdown (%) for reaction of 1 withexcess NMM. Green =product breakdown
(%) for reactions with1:1 precursor/NMM stoichiometry.) X-ray structure of 2: red O, blue N, yellow C, white H. X-ray crystal structures of 4, 7,
and 10–13 can be found in the Supporting Information.
If the Diels–Alder sequences between [5]dendralene and
dienophiles are to be useful in chemical synthesis, these
processes must be rendered more selective. Towards this end,
preliminary investigations show that the Diels–Alder reaction
site selectivities of [5]dendralene are dramatically improved
under Lewis acid promoted conditions (Scheme 4). Thus,
whereas an uncatalyzed single addition reaction with NMM
gives the products of terminal and internal addition in a 72:28
ratio (2/3; Scheme 2), promotion with methylaluminium
dichloride leads to significantly enhanced selectivity for 2
(terminal/internal = 96:4). Furthermore, whereas mono
adduct 2 undergoes a very unselective uncatalyzed reaction
with NMM to give no less than eight products (Scheme 2),
under Lewis acid promotion, a smooth conversion into the
terminal-terminal double addition products 6 and 8 is
witnessed.
The X-ray crystal structure of terminal mono adduct 2
(Scheme 3) is, to our knowledge, the first reported crystal
structure of a [4]dendralene. The tetraene system comprises
two s-trans-1,3-butadiene residues in an orthogonal relation-
ship. The solution UV spectrum of 2 is consistent with this
conformation, with a single absorption maximum at 225 nm
(CH2Cl2)—the same wavelength observed for the parent
[4]dendralene, [5]dendralene, and isoprene.[14] Electron dif-
fraction studies and calculations on the parent [4]dendralene
point to a 728 angle between the two p systems.[15] Perhaps
crystal packing forces are the origin of the conformational
difference between the parent hydrocarbon and mono adduct
2.[16] We are unable to identify any steric or electronic effects
within the structure which might explain this difference in
conformation.
Bis adducts 4 and 5 carry Z-triene moieties, which
undergo
a 6p electrocyclization/[4+2] cycloaddition cas-
cade[7,17] with dienophiles in toluene heated at reflux. In the
case of 5, reaction with N-phenylmaleimide gives a single
diastereomeric heptacycle 15 in 65% yield (Scheme 5). It is
noteworthy that 15 is produced in only two synthetic steps
from [5]dendralene (1), through a sequence involving the
ꢀ
generation of seven new C C bonds and nine stereocenters.
As mentioned above, [5]dendralene undergoes decom-
position: upon storage in neat form at ambient temperature, a
colorless solid is formed. Nevertheless, under controlled
conditions, Diels–Alder dimerization to 16 and 17 (Scheme 6)
Scheme 4. Enhanced Diels–Alder site selectivities with Lewis acid
promoters.
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Communications
bulb-to-bulb vacuum distillation to give [5]dendralene 1 (b.p. 258C,
0.4 Torr) as a colorless oil (5.37 g, 4.07 mmol, 65%). 1H NMR
(300 MHz, CDCl3): d = 6.44 (2H, dd, J = 17.4, 10.6 Hz), 5.34 (2H,
dd, J = 17.4, 1.5 Hz), 5.26 (2H, s), 5.23 (2H, d, J = 1.5 Hz), 5.14 (2H,
d, J = 10.6, 0.9 Hz), 5.12 ppm (2H, m); 13C NMR (75 MHz, CDCl3):
d = 146.9 (C), 146.5 (C), 136.9 (CH), 116.8 (CH2), 116.4 (CH2),
116.2 ppm (CH2); IR (thin film): n˜ = 3154, 3091, 1579 cmꢀ1; UV/Vis
(CH2Cl2): lmax = 224 nm (e = 44000 Lmꢀ1 cmꢀ1); MS (EI, 70 eV): m/z
(%): 132 ([M]+, 14), 131 (48), 117 (100); HRMS: calcd for C10H12
[M]+: 132.0939; found: 132.0914.
Scheme 5. A highly stereoselective domino pericyclic reaction of 5. Th e
X-ray crystal structure of 15 is shown in the Supporting Information.
Received: September 28, 2007
Published online: December 18, 2007
Keywords: dendralene · Diels–Alder reactions ·
.
domino reactions · electrocyclic reactions · hydrocarbons
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[10] Similar results were obtained when [Ni(dppe)Cl2] (dppe = 1,2-
bis(diphenylphosphanyl)ethane) was used in place of [Ni-
(dppp)Cl2].
[11] The crude product is contaminated with up to 10% [4]dendra-
lene, which is the result of an oxidative dimerization process.
This more volatile contaminant is easily removed by vacuum
distillation.
[12] For a review of diene-transmissive Diels–Alder reactions, see:
J. D. Winkler, Chem. Rev. 1996, 96, 167 – 176.
Scheme 6. Two-step synthesis of a fenestrane from [5]dendralene. The
X-ray crystal structure of 19 is shown in the Supporting Information.
occurs in high yield. Intriguingly, both products result from
the same olefinic residue reacting as the dienophile, with the
major product 17 ensuing from union with a terminal 4p
component.[18] Upon heating, the minor dimer 16 undergoes a
remarkable domino electrocyclization/intramolecular cyclo-
addition sequence to form tetracyclic [5.6.6.6]fenestrane[19]
hydrocarbon 19.
In summary, an undemanding preparation of [5]dendra-
lene employing standard laboratory equipment and methods
has been developed. The hydrocarbon undergoes a rich
variety of atom-efficient domino cycloaddition and electro-
cyclization reactions to furnish a diverse range of complex
fused and bridged polycyclic structures.
[13] All cycloadditions involving maleimide dienophiles were found
to proceed exclusively through the endo mode.
[14] The molar extinction coefficient measured for isoprene e
ꢁ 20000 Lmꢀ1 cmꢀ1 is one-half that measured for the other
three compounds.
[15] a) P. T. Brain, B. A. Smart, H. E. Robertson, M. J. Davis,
D. W. H. Rankin, W. J. Henry, I. Gosney, J. Org. Chem. 1997,
62, 2767 – 2773; b) M. H. Palmer, J. A. Blair-Fish, P. Sherwood, J.
Mol. Struct. 1997, 412, 1 – 18.
Experimental Section
1: Vinylidene chloride (5.00 mL, 6.07 g, 62.6 mmol), triphenylphos-
phine (801 mg, 3.05 mmol), and [Ni(dppp)Cl2] (789 mg, 1.46 mmol)
were added successively to a cooled (08C) solution of the chloroprene
Grignard reagent[20] (made from chloroprene (17.3 g, 195 mmol) and
magnesium (8.00 g, 329 mmol) in THF (200 mL)). The reaction was
then allowed to warm to room temperature, and stirring was
continued for 20 h. The reaction mixture was poured into a stirred
mixture of petroleum spirits (30–408C, 500 mL) and ice-cold water
(1 L), then 1m aqueous HCl (250 mL) was added to disperse the
resulting suspension. The organic layer was collected and washed with
saturated sodium carbonate solution (200 mL) and brine (200 mL),
dried over anhydrous magnesium sulfate, and concentrated under
reduced pressure (08C, 30 mbar). The resulting oil was subjected to
[16] See the Supporting Information for crystallographic details.
´
[17] R. von Essen, D. Frank, H. W. Sünnemann, D. Vidovic, J.
Magull, A. de Meijere, Chem. Eur. J. 2005, 11, 6583 – 6592.
[18] The diene site selectivity witnessed during this cycloaddition is
identical to that seen in the reaction of 1 with NMM (Scheme 3).
[19] a) R. Keese, Chem. Rev. 2006, 106, 4787 – 4808; b) M. Thommen,
R. Keese, Synlett 1997, 231 – 240.
[20] S. Nunomoto, Y. Yamashita, J. Org. Chem. 1979, 44, 4788 – 4791.
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