Synthesis and Properties of 2,3-Diethynyl-1,3-Butadienes

Article abstract of DOI:10.1002/anie.201914807

The first general preparative access to compounds of the 2,3-diethynyl-1,3-butadiene (DEBD) class is reported. The synthesis involves a one-pot, twofold Sonogashira-type, Pd⁰-catalyzed coupling of two terminal alkynes and a carbonate derivative

Full text of DOI:10.1002/anie.201914807

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Accepted Article
Title: Synthesis and Properties of 2,3-Diethynyl-1,3-Butadienes
Authors: Michael Sherburn, Madison Sowden, and Jas Ward
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201914807
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10.1002/anie.201914807
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RESEARCH ARTICLE
Synthesis and Properties of 2,3-Diethynyl-1,3-Butadienes
Madison J. Sowden, Jas S. Ward and Michael S. Sherburn*
Dedicated to Professor Henning Hopf
Abstract: The first general preparative access to compounds of the
2,3-diethynyl-1,3-butadiene (DEBD) class is reported. The
successful synthesis involves a one pot, twofold Sonogashira-type,
Pd(0)-catalyzed union of two terminal alkynes and a carbonate
derivative of a 2-butyne-1,4-diol. The synthesis is broad in scope, as
evidenced by the preparation of 30 diversely-substituted DEBDs.
Members of this structural family are sufficiently kinetically stable to
be handled using standard laboratory techniques at ambient
temperature. They decompose primarily through heat-promoted
cyclodimerizations. Alkyl substitution is shown to slow the rate of
decomposition whereas extended conjugation through aryl or alkenyl
substitution accelerates it. An iterative sequence of these
unprecedented Sonogashira-type couplings generates a new type of
expanded dendralene. A suitably-substituted DEBD carrying two
terminal alkyne groups undergoes Glaser-Eglinton cyclo-
oligomerization to produce a new class of expanded radialenes.
These unprecedented cyclic hydrocarbons are chiral, by virtue of
restricted rotation about the C2–C3 bond of their constituent 1,3-
butadiene residues. The structural features giving rise to
atropisomerism in these expanded radialenes are distinct from those
reported previously.
analogues since no general method for the synthesis of 2,3-
diethynyl-1,3-butadienes has been reported and no structure-
reactivity/stability reports have appeared.
DEBDs are by no means unprecedented. Substituted
DEBDs are scattered through the literature, with single
examples from the groups of Larock,[5] Gleiter,[6] Grigg,[7] and
Suzuki,[8] three compounds from Faust[9] and three from Hopf,[10]
including the parent hydrocarbon 1. Ru, Fe, and W complexes
containing DEBDs, which display interesting electronic
properties, have been studied by Bruce[11] and others.[12]
Introduction
In recent times, preparative syntheses of sp2- and sp-C
based acyclic architectures have challenged the widely-held, yet
false perception that such compounds are unmanageable.[1,2],
These studies are opening up regions of poorly chartered
structural space, which is revitalizing the field. Applications of
acyclic sp2- and sp-C rich molecules include their use as building
blocks in carbon-rich materials[3] and transform-driven step
economic total synthesis of natural products.[4] In order to
underpin these downstream developments, broad-spectrum and
operationally simple synthetic methods for acyclic sp2- and sp-C
rich molecule synthesis are needed, in addition to a good
working knowledge of the influence of substitution upon their
reactivity/stability.
Scheme 1. 2,3-Diethynyl-1,3-butadiene, DEBD, 1, reported substituted
analogues, and a summary of the approach reported herein.
This work focusses on the π-bond rich acyclic branched
hydrocarbon 2,3-diethynyl-1,3-butadiene (DEBD) 1 (Scheme 1),
a structure comprising only four sp2-carbons and four sp-
carbons. It contains two terminal 1,3-enyne units and a central
1,3-butadiene, hence two branch points of cross-conjugation.
Relatively little is known about this compound or its substituted
The contribution from the Hopf group uncovered almost
everything that is known about the reactivity of DEBDs, and
identified interesting applications. Thus, Hopf and co-workers
reported the Diels-Alder reaction of their compounds with
dienophiles to prepare cyclic Z-endiynes,[10] which found
application in both Bergman cycloaromatizations[13] and in the
synthesis of substituted phthalocyanines with potential in
photodynamic therapy.[9] Hopf also reported the formation of 1,4-
cyclooctadienes through the thermal [4+4]cycloaddition-
dimerization of DEBDs. This remarkable transformation
[*]
Madison J. Sowden, Dr Jas S. Ward
and Prof Michael S. Sherburn*
Research School of Chemistry
Australian National University
Canberra, ACT 2601 (Australia)
E-mail: michael.sherburn@anu.edu.au
represents
a
formally disallowed process according to
Woodward-Hoffman rules.[14] Finally, the Hopf group proposed,
but did not investigate, the use of DEBDs as precursors to
expanded radialenes.[10]
Supporting information and the ORCID identification numbers
for the authors of this article can be found under:
https://doi.org/10.1002/anie.xxxxxxx.
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RESEARCH ARTICLE
We supplement this already sizeable list of both proven and
predicted uses of DEBDs by noting their untapped potential as
building blocks for polymers, and as ligands for organometallic
π-complexes (those mentioned above are exclusively σ-
complexes). We suspect that a contributing factor to the lack of
use of DEBDs relates to the aforementioned poor reputation of
highly unsaturated acyclic hydrocarbons for instability.[15] We
unequivocally establish here that such concerns about DEBDs
are undeserved. By accessing 30 different categories of
substituents and patterns of substitution, we show that the
majority of these compounds can be handled neat for short
periods at ambient temperature without decomposition. In
addition to reporting the first general synthesis of DEBDs
(Scheme 1), we elucidate the influence of substitution upon
reactivity, we show that Hopf’s prediction regarding the potential
of DEBDs in the synthesis of expanded radialenes is correct,
and we identify the specific DEBD substitution pattern required
in order to achieve it.
We recently reported[19] that tetrasubstituted 2-butyn-1,4-
diols (5, R1-R4 ≠ H) undergo twofold Pd(0)-catalyzed couplings
with aryl (and some alkenyl) boronic acids, without the need to
pre-activate the hydroxyl functionality[20] through covalent
derivatization, to form densely-substituted 1,3-butadienes. The
twofold cross-coupling proceeds with 1,3-transposition at each
(C–O to C–C) bond change (cf. 2→[8]→4, Scheme 2). We
wanted to devise a synthesis of DEBDs 4 that would permit any
substitution pattern, hence the restriction of this earlier method
to highly substituted products precluded its application in this
case.
Table 1. Twofold Sonogashira-type cross-coupling of 2-butyn-1,4-diol
dicarbonate 10 with terminal alkynes furnishes 2,3-ethynyl-1,3-butadienes that
are symmetrically substituted at the alkyne termini 11a-m.
Results and Discussion
In terms of atom connectivity, the simplest way to visualize
the synthesis of a DEBD 4 (or any other 2,3-disubstituted-1,3-
butadiene) is by twofold cross-couplings of a 2,3-dihalo-1,3-
butadiene 6, which can be accessed from a propargylic diol 5 by
twofold substitution with 1,3-transposition (Scheme 2). The
reaction proceeds by way of mono-coupled intermediate 7. This
is the approach taken by Hopf for the preparation of DEBDs, and
one that we have used for dendralene[16] and radialene[17]
synthesis, and others have used for substituted 1,3-butadiene
synthesis.[18] Two challenges with this approach are: (a) 2,3-
dihalo-1,3-butadienes 6 are prone to polymerization, and (b) if
mono-coupled intermediate 7 is less reactive towards cross-
coupling than its precursor, then non-productive pathways (i.e.
decomposition) might ensue.
Scheme 2. The unprecedented twofold Sonogashira coupling approach to
substituted DEBDs (2→[8]→4) and the known pathway involving
polymerization-prone dihalides (6→[7]→4).
a Isolated and characterized as its N-methylmaleimide Diels-Alder cycloadduct.
See the SI for details.
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RESEARCH ARTICLE
Table 2. Twofold Sonogashira-type cross-coupling of variously-substituted 2-
butyn-1,4-diol dicarbonates 2a-j with terminal acetylenes furnishes 2,3-
diethynyl-1,3-butadienes 12a-l carrying one, two, three or four substituents at
the 1,3-butadiene termini.
While there are several examples of twofold, 1,3-
transpositive couplings involving activated derivatives of 2-
butyn-1,4-diols
5
in the literature[7,21,22] none involve
Sonogashira-type couplings. We were attracted to this process
since, unlike dihalides 6, carbonate precursors 2 are not prone
to polymerization. Moreover, mono-coupled intermediates 8
were anticipated to be more prone to oxidative insertion of Pd(0)
than precursor 7, which would facilitate the desired twofold
coupling. Table 1 documents the successful synthesis of thirteen
substituted DEBDs using this method. The DEBDs in this Table
differ in their substitution at the alkyne termini.
Standard Sonogashira coupling conditions[23] were effective
for the reaction between known 2-butyn-1,4-diol dicarbonate
10[24] and terminal alkynes 9 throughout, with [Pd(PPh3)4] and
CuI as co-catalysts and diisopropylamine as base. Alkyne
substituents that are tolerated include alkyl, alkenyl, trialkylsilyl,
aryl, heteroaryl, and hydroxyalkyl groups. Isolated yields are
generally good, the exceptions stemming from difficulties faced
during separation of the DEBD product from the alkyne oxidative
homocoupling product. While there are several reported
methods to address this issue, none were completely effective in
our hands.[25] The anomalously low yield of bis-cyclohexyl DEBD
11d is due to its heightened sensitivity to autoxidation.
The twelve new DEBD structures listed in Table 2 show that
all conceivable substitution patterns (mono-, 2 × di-, tri-, and
tetra-) at the two alkene termini are accessible through the new
twofold Sonogashira method. The propargylic substituents of the
2-butyne-1,4-diol precursor
5
are parlayed into alkene
substituents in DEBD product 4. A number of propargyl-
substituted 2-butyn-1,4-diol precursors are commercially
available, but their preparation from acetylene and
ketones/aldehydes is trivial.[26,27] Interestingly, the twofold
Sonogashira coupling is poorly E/Z-stereoselective with methyl
substituents (12a, 12h and 12i) but gives exclusive E-
stereoselectivity with a phenyl group (12b, 12c, 12d and 12j).
So far, the method has been shown to grant access to
DEBDs with a wide variety of terminal alkyne substituents, and
variation in the number and type of alkene substituents. The
preparation of DEBDs with a different substituent on each alkyne
terminus would require a sequence of couplings between a 2-
butyn-1,4-diol dicarbonate and two different alkynes, which
would be challenging since the second cross-coupling (8→4,
Scheme 2) is invariably faster than the first (2→8, Scheme 2).
We considered a stepwise synthesis, in which the second cross-
coupling could not proceed, for example by using a mono-
carbonate derivative of the 2-butyne-1,4-diol, but we were
discouraged by the necessity of several additional steps to
perform this synthesis, and instead opted for a one flask method
in which two alkynes and the di-carbonate were simultaneously
present. Thus, slow addition of the faster reacting acetylene,
namely TMS-acetylene 13 to a mixture of the other reaction
components delivered the best outcome, with a product ratio
approximating to the best-case statistical ratio of the three
products (i.e. 50:25:25) being obtained (Scheme 3). While the
yields are modest, it is challenging to come up with a better
approach, due to the very short step count (only 2 steps from
inexpensive, commercial precursors) and operational simplicity.
a
In every case where mixtures of geometrical isomers were produced, these
isomers were easily separated by flash chromatography. See the SI for
details.
Scheme 3. One flask synthesis of DEBDs 14 and 15 carrying two different
alkyne substituents.
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extended conjugation decreases stability
alkyl, silyl substitution increases stability
Me
SiMe3
Me3Si
11j
11e
1
11d
11a
11h
Me
5 mins
5 mins
10 mins
15 mins
15 mins
45 mins
increasing thermal stability
most reactive
least reactive
Me
Me
Me
SiMe3
SiMe3
SiMe3
SiMe3
n-Bu
Ph
E
E
Me3Si
Me3Si
Me3Si
Me3Si
n-Bu
Ph
Ph
Me
Me
12k
Me
Ph
Ph
12c
< 5 mins
12b
11h
12h
12d
10 mins
15 mins
45 mins
60 mins
no observable
reaction
extended conjugation
decreases stability
substituent effects are additive
alkyl substitution increases stability
Figure 1. Approximate first half-lives of substituted DEBDs at 70 °C, from an initial 1M concentration benzene solution, and empirical substituent effects.
With many new DEBDs in hand, representing a very wide
diversity of structural possibilities, we were in a position to
examine the influence of substitution upon kinetic stability. In
general, substituted DEBDs are robust compounds. While we
advocate long term storage of pure materials under Ar in a –
80 °C freezer, representative neat samples exposed to typical
laboratory conditions (ambient fluorescent laboratory light,
ambient temperature, in air) for an hour showed no sign of
decomposition.
much rarer events,[29] and heat promoted, concerted pericyclic
[4+4] cycloadditions are disallowed by Woodward-Hoffman
rules.[14] We suspect that [4+4] cyclodimers of DEBDs are either
the products of a stepwise biradical mechanism,[10b,17] or the
result of [2+2] cyclodimerization/Cope rearrangement.[29b] Diels-
Alder dimers 18 and 19 were found to decompose on prolonged
heating, which explains the absence of the [4+2] cycloadduct
from the product mixtures analyzed by the Hopf group.
It is clear from the results summarized in Figure 1 that both
the location and nature of substituents decorating a DEBD core
have a pronounced influence upon its kinetic stability. The most
reactive DEBDs are those carrying a conjugating substituent on
either the alkyne or alkene termini. Thus, diphenyl-DEBD 11j
and di-cyclohexenyl-DEBD 11e are even more prone to react on
heating than the parent DEBD 1 (prepared by desilylation of
11h). Alkyl and trialkylsilyl substitution slows down thermal self-
reaction, such that hexa-substituted DEBD 12k, for example, is
inert at 70 °C as a 1M solution.
Figure
1
depicts the results of induced thermal
decompositions of variously-substituted DEBDs, performed at
the same temperature with the same starting concentration
solution. As mentioned in the introduction, the Hopf laboratory
reported the [4+4] cyclodimerization of DEBD 11h in 34% yield
from an initial 1.0 M concentration solution, with no sign of the
[4+2] cyclodimer.[10b] In our hands, heating concentrated
solutions of DEBDs 11j and 11h led to substantial
polymerization and low yields of dimers, both in the presence or
absence of acid scavengers and radical traps. Moreover, we
observe the formation of a ca. 2:3 mixture of the [4+2]
cyclodimer (18, 19) and the [4+4] cyclodimer (16, 17) in both
cases (Scheme 4).
Combinations of stabilizing and destabilizing substituents
appear to be additive, as can be seen from the group 11a, 11j,
12c and 12d. Further evidence for this comes in the form of the
most reactive compound prepared, namely di-(4-cyanophenyl)-
DEBD
20
(Figure
2).
This
compound
underwent
cyclodimerization at ambient temperature so rapidly that the
monomer could not be isolated. Nonetheless, inclusion of four
methyl groups at the 1,3-butadiene termini furnished
a
compound (21) that was readily isolable.
Scheme 4. [4+4] and [4+2] cyclodimerization of DEBDs 11j and 11h. Yields in
parentheses are NMR estimates based upon crude product mixtures.
Figure 2. DEBD 20 is extremely prone to cyclodimerization but its tetramethyl
congener 21 is kinetically stable.
Whereas catalyzed [4+4] cyclodimerizations of 1,3-
butadienes are well established,[28] heat-promoted processes are
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Expanded radialenes and expanded dendralenes are
designed molecules in which (oligo)alkyne “spacers” are
inserted between a pair of sp2-carbons.[30] Work on expanded
dendralenes has been headed by the Tykwinski laboratory, who
have reported elegant, systematic studies on iso-
polydiacetylenes (iso-PDAs), iso-polytriacetylenes (iso-PTAs)
and unsymmetrical analogues.[31] These expanded dendralenes
contain a repeating unit comprising a single 1,1-disubstituted
C=C bond, connected by either a –C≡C– or a –C≡C–C≡C–
spacer (Figure 3). Dendralenes have recently been shown to
exhibit UV-vis absorption maxima that are consistent with s-
trans-1,3-butadiene units, and have been shown to react as
multi-dienes in sequences of Diels-Alder cycloadditions.[2c] With
DEBDs in hand, we wondered if they could be elaborated into
expanded dendralenes that are structurally distinct to those
previously accessed, which comprise dendralene behavior-
defining 1,3-butadiene units, connected through acetylenic
spacers (Figure 3).
by desilylation of 12k[27]) and 10, are symmetric bifunctional
building blocks. That a polymer is not the product of this reaction
is the result of a substantially faster rate for the second C–C
cross-coupling (8→4, Scheme 2) relative to the first (2→8,
Scheme 2). Evidently, the 38% yield for this reaction is an
indication that some of the product 23 reacts with bis-
electrophile 10, leading to higher oligomers. Triple DEBD
product 23 lacks stabilizing alkyl substitution at the central 1,3-
butadiene and carries conjugating groups at its alkyne termini,
hence it is amongst the least kinetically stable of the isolable
compounds reported herein, and higher oligomers with the same
repeating unit are anticipated to be less kinetically stable still,
which explains why they are not isolated from this reaction.
Finally, we return to test Hopf’s proposal[10b] that the cyclo-
oligomerization of DEBDs could generate expanded radialenes
(see Introduction). When this proposal was published in
1996,[10b] the first examples of expanded radialenes had recently
been published by the Diederich laboratory.[32a] The field has
since experienced significant growth, with many expanded
radialenes now known, comprising, as a repeating unit, a single
1,1-disubstituted C=C bond, connected by one or more –C≡C–
spacers. Such structures are the cyclic analogues of iso-PDAs,
iso-PTAs and their unsymmetrical congeners (Figure 3).
Nonetheless, there are no DEBD-based cyclo-oligomers known:
in fact, until now there have been no expanded radialenes
comprising cross-conjugated 1,3-butadiene units.[33] The
synthesis and single crystal X-ray analyses of the first such
compounds are depicted in Scheme 6, which were prepared by
Glaser-Eglinton oxidative cyclo-oligomerization of tetramethyl-
DEDB monomer 22.
Me
Figure 3. The known iso-polydiacetylenes (iso-PDAs) and iso-
polytriacetylenes (iso-PTAs) “expand” a dendralene by separating individual
C=C units. Here, we report the first expanded dendralene comprising 1,3-
butadiene units. The repeating unit is shaded in each structure.
Me
Me
C3’
C3
Me
C2
Me
C2’
Me
22
(slow addition)
Me
22
X-ray
Me
ꢀ
(C2’–C2–C3–C3’) = 67°
The synthesis of the first such molecule, an expanded
[6]dendralene comprising three 1,3-butadienes spaced by
–C≡C– units, is depicted in Scheme 5, in a process that is an
iterative application of the methodology described earlier (Tables
1 and 2).
CuCl
Cu(OAc)2
pyridine
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
24, up to 18% yield
X-ray
+
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Scheme 5. Synthesis of the first expanded dendralene comprising 1,3-
butadiene units, 23.
Me
Me
Me
Me
Me
X-ray
Me
Me
25, up to 20% yield
On first inspection, the successful outcome of this reaction is
surprising, in light of the fact that both precursors, 22 (generated
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Scheme 6. Glaser-Eglinton cyclo-oligomerization of tetramethyl-DEBD 22
gives chiral, carbon-rich cyclodimer 24 and cyclotrimer 25. H atoms are
omitted from the X-ray crystal structures for clarity.
conformers, both of which lie around 21-24 kJ/mol above the
preferred s-trans conformation. For cyclo-oligomerization of 1 or
26 to occur, each individual DEBD unit within the acyclic
precursor to the cyclo-oligomer would need to simultaneously
adopt a conformation conducive to cyclization, which would
involve a substantial energetic penalty. Thus, vanishingly low
populations of cyclization-ready conformations are present in
solution, which results in a cyclization step that cannot compete
with intermolecular processes.
These compounds were prepared under high dilution
conditions. Specifically, slow addition of DEBD precursor 22 to
the reagent mixture gave cyclotrimer 25 (an expanded
[6]radialene) as major product, with even slower addition giving
rise to mixtures richer in the cyclodimer 24 (an expanded
[4]radialene).[27,34] The ideal shape[35] of molecules of cyclodimer
24 identified by crystallography have D2 symmetry, whereas
those of cyclotrimer 25 have C1 symmetry.[36] Perhaps the most
striking feature, on first inspection, is the significant distortion
from linearity that is visible around the 1,3-butadiyne portions of
cyclodimer 24. Related 12-membered carbocyclic structures
containing a pair of 1,3-butadiyne groups have been previously
reported,[37] and the bending around the 1,3-butadiynes in our
structure is similar to those published. 18-Membered
carbocycles related to cyclotrimer 25 have also been reported.[38]
Nonetheless, the new structures depicted in Scheme 6 have
unique structural and conformational features that warrant a
more detailed discussion.
Single crystal X-ray analyses of cyclodimer 24 and
cyclotrimer 25 were essential in order to identify the two
products. These analyses, along with associated VTNMR
studies and associated calculations, also reveal a fascinating
and, as far as we can ascertain, unprecedented form of
atropisomerism in 1,3-butadienes. Restricted rotation about the
C2–C3 bond in 1,3-butadienes carrying sterically demanding
substituents at C2 and C3 is well established, primarily due to
contributions from the Hopf group.[39] Cyclodimer 24 and
cyclotrimer 25 exhibit restricted rotation in their 1,3-butadiene
units owing to a combination of the inside (Z)-methyl groups at
C1 and C4 of each 1,3-butadiene, which disfavor in-plane
conformations, and the rather rigid nature of the tether
connection between the two ethynyl termini of each DEBD
residue, which precludes a through-the-ring rotation of one
exocyclic alkene to invert the configuration of a DEBD unit.
In stark contrast to the successful cyclo-oligomerization of
tetramethyl-DEBD 22, the parent DEBD 1, and its E,E-dimethyl
analogue 26 (generated by desilylation of 11h and 12h,
respectively[27]) did not furnish isolable monodisperse products.
We ascribe this lack of success to the lower kinetic stability of
DEBD precursors 1 and 26 and their cyclo-oligomeric products
relative to DEBD 22 and its products (cf. Figure 1). An additional
contributing factor is their preferred conformations. Molecular
structures from single crystal X-ray analyses and DFT studies[27]
(Figure 4) reveal that the parent DEBD 1 and its E,E-dimethyl
analogue 26 prefer the in-plane, s-trans 1,3-butadiene
conformation, in which the two ethynyl termini point in opposite
directions (Figure 4, (C≡)C2’–C2–C3–C3’(≡C) dihedral: X-ray,
calc: 훳=180°). In contrast, tetramethyl-DEBD 22 prefers a non-
planar conformation, with the two ethynyl groups in the same
hemisphere (Scheme 6, (C≡)C2’–C2–C3–C3’(≡C) dihedral: X-
ray: 훳=67°; calc: 훳=81°).
Both cyclodimer 24 and cyclotrimer 25 exhibit chiral
structures in the solid state, with both enantiomeric forms being
present in each crystal. These chiral structures stem from the
aforementioned twisted conformations of each 1,3-butadiene
unit.
1H and 13C NMR spectra of cyclodimer 24 at 25 °C reveal
two proton environments and six carbon environments. At –5 °C,
two sets of resonances are present in a ca. 70:30 ratio. Thus, 1H
and 13C NMR spectra reveal the presence of two diastereomeric
forms of 24 undergoing slow conformational interchange on the
NMR timescale at cooler temperatures. VTNMR studies with line
shape analysis estimate the barrier for interconversion between
these two forms at ca. 66 kJ/mol.
Scheme 7 depicts the three conformers of DEBD cyclodimer
24 and the mechanism of interconversion between them, which
explains these experimental observations. The two enantiomeric
forms, M,M-24 and P,P-24, differ in stereogenicity at both 1,3-
butadiene groups. Thus, stereochemical inversions at both 1,3-
butadiene groups must occur in order for a molecule to enantio-
isomerize. We propose that this process takes place in a
stepwise manner, by way of meso-diastereomer M,P-24, which
is the second diastereomeric form detected spectroscopically.
Me
C3’
C3
C3’
C3
Me
E
E
C2
C2’
C2
C2’
Me
Me
X-ray
DFT
26
(C2’–C2–C3–C3’) = 180°
1
ꢀ
Figure 4. The parent DEBD 1, and its E,E-dimethyl analogue 26 and their
molecular structures from calculations and single crystal X-ray analyses. H
atoms are omitted from the X-ray crystal structure and calculated structure for
clarity.
A DFT conformer search located only the chiral and meso
conformers, and predict a Boltzmann population (gas phase,
298.15K) of 79:21 for M,M-24/P,P-24 : M,P-24, which is in good
agreement with the experimentally-measured ratio of 70:30,
Calculations[27] on the parent DEBD 1 and its E,E-dimethyl
analogue 26 reveal a skew-conformation (similar to the preferred
conformation of tetramethyl-DEBD 22, Scheme 6) as a local
energy minimum, some 13-14 kJ/mol higher in energy than the
lowest energy s-trans conformation shown in Figure 4. The
rotational barriers about the central C(sp2)–C(sp2) single bond in
these molecules correspond to the s-cis and orthogonal
1
from integration of H NMR spectra (CDCl3) recorded at –5 °C.
The DFT calculated barrier for methyl/methyl crossing through
the s-cis conformation of tetramethyl-DEBD 22 is ca. 100 kJ/mol,
which is a little higher than the value of 66 kJ/mol from VTNMR
studies performed on cyclodimer 24. A lower barrier would be
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RESEARCH ARTICLE
expected for cyclodimer 24 due to ring strain, which has the
effect of splaying the 1,3-butadienes (C1=C2–C3 bond angles
from X-ray structures as follows: monomer 22, 훳=122.9°;
cyclodimer 24, 훳=125.3-125.5°), which would be expected to
increase the inside Me/Me distance at their crossing point.
Me
Me
Me
Me
M
Me
Me
Me
Me
flip
P
M
Me
flip
Me
Me
Me
Me
X-ray
Me
Me
Me
C1 point group, chiral
Me
Me
M
M
Me
inside
Me
Me/Me
crossing
X-ray
D2 point group; chiral
inside
Me/Me
crossing
Me
Me
Me
Me
flip
Me
Me
Me
Me
M
Me
Me
M
P
Me
Me
Me
Me
M
M
Me
Me
DFT
C2h point group; meso, achiral
inside
Me/Me
Me
Me
Me
Me
DFT
crossing
D3 point group, chiral
Me
Me
Me
Scheme 8. Interconversion between the two diastereomeric forms of DEBD
cyclotrimer 25. Only one enantiomer of each is depicted. H atoms are omitted
from the X-ray crystal structure and calculated structure for clarity.
Me
Me
P
P
Me
Me
D2 point group; chiral
Me
X-ray
Conclusion
Scheme 7. Conformational dynamics of DEBD cyclodimer 24. H atoms are
omitted from the X-ray crystal structures and calculated structure for clarity.
In summary, substituted 2,3-ethynyl-1,3-butadienes (DEBDs)
are now readily available, through a short and operationally
simple 2-4 step synthesis from commodity chemicals. All
possible arrangements of substituents and substitution patterns
are accessible from this broad-spectrum approach, which
deploys inexpensive and readily available building blocks that
are not prone to polymerization.
1H and 13C NMR spectra of cyclotrimer 25 show six proton
resonances and twenty-three 13C resonances. Interestingly, no
significant change was seen in NMR spectra within the
temperature range –60 °C → +70 °C. The C1 symmetry
conformation of cyclotrimer 25 should exhibit twelve 1H NMR
resonances and thirty-six 13C NMR resonances. A second
diastereomeric atropisomeric form with D3 symmetry is possible
for DEBD cyclotrimer 25, as shown in Scheme 8. This more
symmetric structure should give rise to 1H and 13C NMR spectra
with only two and six resonances, respectively. Evidently, either
the C1 form is populated exclusively, or a mixture of the C1 and
D3 forms are present throughout.
The vast majority of substituted DEBDs can be stored neat
for extended periods of time in a –80 °C freezer, or for short
periods at ambient temperature. Heat brings about
decomposition, with modest yields of mixtures of [4+2] and [4+4]
cyclodimers being isolable, and the majority of material
seemingly undergoing polymerization. Both the type and number
of substituents determine the rate of decomposition of DEBDs,
and systems have been designed to both accelerate and impede
this process. In general, conjugating substituents destabilise
DEBDs, whereas alkyl and silyl groups stabilize them.
The first steps towards incorporating DEBDs into novel
materials have been taken, with unprecedented expanded
dendralene and radialene systems being prepared. The novel
expanded radialenes 24 and 25 are 12- and 18-membered ring
systems comprising a 2:1 ratio of sp:sp2 carbons.[40] They exhibit
chiral conformations as a result of atropisomerism about the
constituent DEBD cores. While chiral 1,3-butadienes are known,
the structural features that give rise to atropisomerism in
expanded radialenes 24 and 25 (small C1 and C4 Z-substituents
on a 1,3-butadiene with a constrained cisoid conformation) are
distinct from those reported previously (sterically bulky C2 and
C3 substituents). There is significant scope for modification of
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10.1002/anie.201914807
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RESEARCH ARTICLE
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[7]
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[9]
The preparation of expanded dendralene 23 (Scheme 5) and
radialenes 24 and 25 (Scheme 6) represent a proof-of-principle.
Evidently, many variations on these themes can be envisaged,
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based spacers, with potential applications of these new cross-
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Experimental Section
Full experimental details are provided in the Supporting
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Acknowledgements
This work was supported by the Australian Research Council
(DP160104322). Some of this research was undertaken on the
MX1 beamline at the Australian Synchrotron, part of ANSTO.
We warmly thank Mitchell Blyth (ANU) for advice with
calculations, and Chris Blake (ANU) for assistance with VTNMR
experiments and line shape analysis.
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Keywords: hydrocarbons • 1,3-butadienes • cross-coupling •
conformation analysis • atropisomerism
[15] We support this statement with the following excerpt, taken from
reference 10(b): “Although structurally simple, these compounds
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connected with the very high propensity of the products – and often
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Entry for the Table of Contents
RESEARCH ARTICLE
Madison J. Sowden, Jas S. Ward and
Michael S. Sherburn*
Page No. – Page No.
Synthesis and Properties of
2,3-Diethynyl-1,3-Butadienes.
Just diene to be chiral. The first general synthesis of 2,3-diethynyl-1,3-butadienes
(DEBDs) uses commodity chemical precursors (acetylene, two terminal alkynes,
and two aldehydes/ketones) and involves, as a key step, an unprecedented twofold
Sonogashira-type cross-coupling of a 2-butyn-1,4-diol derivative. The process is of
extremely wide scope, with 30 structurally diverse examples reported. The value of
DEBDs as building blocks for novel expanded dendralenes and expanded
radialenes is demonstrated. The latter exhibit an unprecedented form of
atropisomerism.
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