Synthesis of unsymmetrical 1,3-diynes via alkyne cross-metathesis

Article abstract of DOI:10.1039/c3cc43108h

The tungsten benzylidyne complex [PhC≡W{OSi(OtBu)₃} ₃] (1) efficiently catalyses the metathetic conversion between symmetrical and unsymmetrical 1,3-diynes, which provides the opportunity to prepare the latter species directly from terminal alkynes by a combination of copper-catalysed homocoupling and catalytic alkyne cross-metathesis (ACM).

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Synthesis of unsymmetrical 1,3-diynes via alkyne
cross-metathesis†
Cite this: DOI: 10.1039/c3cc43108h
Sin Ting Li, Tobias Schnabel, Sergej Lysenko, Kai Brandhorst and Matthias Tamm*
Received 26th April 2013,
Accepted 12th May 2013
DOI: 10.1039/c3cc43108h
www.rsc.org/chemcomm
R
The tungsten benzylidyne complex [PhC W{OSi(OtBu)3}3] (1) efficiently
catalyses the metathetic conversion between symmetrical and unsym-
metrical 1,3-diynes, which provides the opportunity to prepare the latter
species directly from terminal alkynes by a combination of copper-
catalysed homocoupling and catalytic alkyne cross-metathesis (ACM).
Recent years have clearly seen ‘‘alkyne metathesis on the rise’’1 with
the development of a substantial number of novel well-defined
molybdenum and tungsten alkylidyne complexes,2,3 which are able
to efficiently promote the catalytic metathesis of internal and recently
even terminal alkynes.4 One of these (pre-)catalysts, the siloxy-
supported tungsten benzylidyne complex 1 (Scheme 1), did not only
metathesize methyl-capped alkynes (RCRCMe),5 but also proved to
be active in the catalytic metathesis of conjugated diynes of type
RCRC–CRCMe (R = aryl, alkyl).6 Surprisingly, this method did
not yield the anticipated triynes RCRC–CRC–CRCR together
with 2-butyne (MeCRCMe), but selectively produced stoichiometric
amounts of the symmetrical diynes RCRC–CRCR and MeCRC–
CRCMe (dimethyldiacetylene, DMDA). These equilibrium reac-
Scheme 1 Synthesis of unsymmetrical 1,3-diynes by a combination of copper-
catalysed homocoupling of terminal alkynes and diyne cross-metathesis (DYCM).
tions are driven to completion in the presence of powdered mole- however, that C–C bond formation in the copper-mediated trans-
cular sieves (5 Å), which adsorb DMDA in a similar fashion as it acts formations proceeds irreversibly, whereas the fully reversible
as a 2-butyne scavenger in the molecular-sieve-promoted alkyne making and breaking of carbon–carbon triple-bonds during the
metathesis protocol developed by Fu¨rstner et al.7
alkyne metathesis steps offers full thermodynamic control, which
In view of the established methods for the synthesis of was successfully exploited for the synthesis of macrocyclic diynes
symmetrical 1,3-diynes such as copper(I)- or copper(II)-catalysed by ring-closing diyne metathesis (RCDM).6
Glaser, Eglington, and Hay homocoupling of terminal alkynes,8
Furthermore, the reversibility of this transformation should also
the usefulness and applicability of this diyne metathesis reaction allow establishment of an equilibrium between two symmetrical
might be questioned with good reason, in particular, since the 1,3-diynes 2 and 20 and their unsymmetrical counterpart 3, allowing
stoichiometric loss of the C6-building block DMDA results in us in principle to combine copper-catalysed homocoupling of
a poor, if not dreadful, atom economy.9 It should be noted, terminal alkynes with subsequent diyne cross-metathesis (DYCM)10
of the resulting symmetrical 1,3-diynes (Scheme 1). A somewhat
related approach had already been pursued by Gross and Moore,
¨
¨
Institut fur Anorganische und Analytische Chemie, Technische Universitat
who polymerised a diethynylcarbazole under Hay conditions and
subjected the resulting diyne polymer to standard alkyne metathesis
conditions by use of the catalyst system [EtCRW{N(Ar)(tBu)}3]–
Ph3SiOH (11/18 wt%). In contrast to 1, however, the generated
catalyst did not exhibit selectivity towards diyne formation, and
the resulting tetrameric macrocycles showed a statistical distribution
of yne (C2) and diyne (C4) bridges.11
Braunschweig, Hagenring 30, 38106 Braunschweig, Germany.
E-mail: m.tamm@tu-bs.de; Fax: +49 531 391 5387; Tel: +49 531 391 5309
† Electronic supplementary information (ESI) available: Full details of all experi-
mental procedures involving copper-catalysed homocoupling of terminal alkynes
and diyne cross-metathesis (DYCM); selected 1H and 13C NMR spectra; details of
the electronic structure calculations and X-ray crystal structure determination.
CCDC 935939. For ESI and crystallographic data in CIF or other electronic format
see DOI: 10.1039/c3cc43108h
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Considering the importance of conjugated diynes as building
Preparative DYCM was then carried out at room temperature for
blocks in natural products and materials science,12–14 the route out- all diyne combinations listed in Table 2 (entries 1–11). The conver-
lined in Scheme 1 offers an alternative to classical methods for con- sion was followed by gas chromatography and, after equilibration,
structing unsymmetrical diynes such as the Cadiot–Chodkiewicz the reaction mixtures were filtered through alumina, followed by
coupling and its variants.8 However, the preparation of alkynyl separation of the diynes by column chromatography. The isolated
halides by halogenation of terminal alkynes is required, which is yields of 3 are based on the conversion of the minor diyne
clearly less economical and environmentally benign than a method component 2 and range from 62% (entry 5) to 87% (entry 9). In
directly coupling two different terminal alkynes. Accordingly, direct most cases, the starting materials can be recovered in excellent to
cross-coupling of two different terminal alkynes has been reported quantitative yield, depending on the separability of the 1,3-diyne
several times,15,16 and, for instance, unsymmetrical 1,3-diynes were substrates (see ESI† for full details).
obtained in modest to good yields by Ni/Cu- or Fe/Cu-catalysed
aerobic oxidative coupling reactions in the presence of a 5- or 6-fold at this stage whether the range of yields could be ascribed to
excess of one of the alkynes, respectively.16a–c
differences in DG298K for the various DYCM systems or is merely a
It should also be noted that it cannot be unequivocally deduced
In contrast to these examples, where the irreversibility of the C–C result of the specific work-up and separation process during each
bond forming steps affords statistical diyne mixtures, it is safe to
assume that alkyne metathesis catalysed by 1 is under thermo-
Table 2 Diyne cross-metathesis of symmetrical to unsymmetrical 1,3-diynes
dynamic control with an equilibrium constant K = [3]2/([2][20]). To
a
catalysed by 1 using a 1 : 4 ratio of 2 and 20
test the feasibility of the proposed DYCM protocol, several symme-
trical 1,4-diaryl- and 1,4-dialkyl-1,3-butadiynes 2 and 20 were synthe-
sised by CuCl-catalysed alkyne homocoupling in dimethylsulfoxide at
90 1C (Scheme 1, see also Table 2).17 Preliminary NMR experiments
were carried out in CD2Cl2 for the equilibrium reaction between
1,4-bis(p-anisyl)-1,3-butadiyne (R = p-MeOC6H4) and 5,7-dodecadiyne
(R0 = n-Bu), revealing that an equilibrium is established within
four hours at room temperature in the presence of 1.7 mol% of
catalyst 1. Integration of the sufficiently well separated 1H NMR
signals for the OCH3 groups in 2 (6H, d E 3.75 ppm) and 3 (3H,
d E 3.73 ppm) allows us to determine their relative equilibrium
concentrations and the resulting equilibrium constant K. These
measurements were performed for various ratios of the starting
concentrations [20]0 :[2]0, and the results are summarised in Table 1.
In agreement with Le Chatelier’s principle, increasing the excess of
20 over 2 from 1 : 1 to 4 : 1 shifts the equilibrium towards 3 with an
increasing [3]:[2] ratio. For all four experiments, K is satisfactorily
Entry
1
R
R0
Yieldb [%] Time
76
83
4 h
5 h
2
3
65
11 h
4
5
6
75
62
76
4 h
%
well reproduced with an average K = 5.83. The resulting Gibbs free
energy (DG298K ¼ ꢀ4:4 kJ molꢀ1) indicates that the formation of the
unsymmetrical 1,3-diyne is slightly exergonic, and theoretical values
of DG298K derived by DFT calculations for this and other diyne
combinations are of the same order of magnitude (see ESI†).
6 h
8 min
7
81
5 h
Table 1 NMR study of the equilibrium reaction between 1,4-bis(p-anisyl)-1,3-
butadiyne (2, R = p-MeOC6H4) and 5,7-dodecadiyne (20, R0 = nBu) affording
1-p-anisyl-1,3-octadiyne (see also Table 2, entry 1)a
8
9
79
87
5 h
b
e
[20]0 : [2]0
[3] : [2]c
Kd
DG298K [kJ molꢀ1
]
Yieldf [%]
1 : 1
2 : 1
3 : 1
4 : 1
2.36
5.31
7.98
5.57
6.06
5.80
5.88
ꢀ4.3
ꢀ4.5
ꢀ4.4
ꢀ4.4
54
73
80
85
13 min
10.97
a
NMR samples were prepared by mixing the appropriate aliquots from
0.1 M standard solutions of 2 and 20 in CD2Cl2 (total volume = 0.6 mL),
followed by addition of 0.1 mL of a 0.01 M solution of 1 in CD2Cl2 (total
sample volume = 0.7 mL, total alkyne concentration = 0.086 M, catalyst
10
11
a
85
84
8 min
8 h
b
loading = 1.7 mol%); see ESI for full details. Ratio of the starting
c
concentrations. Ratio of equilibrium concentrations determined
by integration of the OCH3 1H NMR signals in 3 (3H) and 2 (6H).
Conditions: substrate 2 (0.025 M), substrate 20 (0.1 M), catalyst 1 (2 mol%),
CH2Cl2, room temperature; see ESI for full details. b Yield of product 3
isolated after filtration through alumina and purification by column chro-
matography; the yields are based on the conversion of the minor diyne 2.
K = [3]2/([2][20]) = [3]2/[([2]0 ꢀ [3]/2)(X[2]0 ꢀ [3]/2)] = 2Y2/(X(2 + Y) ꢀ Y)
d
e
with X = [20]0/[2]0 and Y = [3]/[2]. DG298K = ꢀRT ln K with R =
8.314 J Kꢀ1 molꢀ1 and T = 298 K. Yield based on the conversion of
f
2; yield = Y/(Y + 2) with Y = [3]/[2].
c
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was exploited for the preparation of unsymmetrical 1,3-diynes
by cross-metathesis of their symmetrical counterparts, which
are conveniently accessible by copper-catalysed homocoupling
of terminal alkynes. It should be emphasized again that copper-
catalysed routes alone are not competitive with the DYCM
reaction, since the irreversibility of the C–C bond forming step
affords the symmetrical diynes 2 and 20 as side products, which
have to be discarded, if only the unsymmetrical diyne 3 was of
further use. In contrast, the combination of copper catalysis
and alkyne metathesis allows recycling of the symmetrical
diynes and feeding them back into a (potentially continuous)
DYCM process. Ideally, full exploitation and optimisation of
this new method would be achieved by constantly removing the
product 3 from the reaction mixture, e.g. by precipitation or
evaporation, in order to drive the equilibrium reaction to
completion with regard to full conversion of 2 and 20 into 3.
Further work in this direction is currently in progress in
our group.
Fig. 1 Conversion–time diagram for the diyne cross-metathesis (DYCM)
between 2 (R = p-C6H4COOMe) and 20 (R0 = nBu), see Table 2, entry 6.
experiment. Clearly, steric and electronic properties have a marked
impact on the metathesis rate, as shown for instance by the
significantly longer equilibration time found for the reaction of
5,7-dodecadiyne with 1,4-bis(o-anisyl)-1,3-butadiyne (11 h, entry 3) in
comparison to those observed for its para- and meta-substituted
isomers (4 and 5 h, entries 1 and 2). Whereas several other diyne
combinations require similar reaction times (entries 4,‡ 5, 7 and 8),
the use of the symmetrical butadiyne with methyl benzoate
1,4-substituents leads to rapid equilibration and very short
reaction times, irrespective of whether the other diyne is aliphatic
(8 min, entry 6) or aromatic (8 and 10 min, entries 9 and 10).
Finally, aliphatic 1,3-diynes can also be cross-metathesized,
albeit at a rather slow rate (8 h, entry 11).
Notes and references
‡ The molecular structure of the product 1-(p-methylphenyl)-1,3-octa-
diyne (Table 2, entry 4) was determined by X-ray diffraction analysis; see
ESI† for the representation.
1 A. Fu¨rstner, Angew. Chem., Int. Ed., 2013, 52, 2794.
2 (a) K. Jyothish and W. Zhang, Angew. Chem., Int. Ed., 2011, 50, 8478;
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J. S. Moore, Adv. Synth. Catal., 2007, 349, 93.
3 R. Schrock, Chem. Rev., 2002, 102, 145.
4 B. Haberlag, M. Freytag, C. G. Daniliuc, P. G. Jones and M. Tamm,
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Ed., 2012, 51, 6757.
7 (a) J. Heppekausen, R. Stade, A. Kondoh, G. Seidel, R. Goddard and
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2000, 39, 2632 and references cited therein.
9 B. M. Trost, Angew. Chem., Int. Ed. Engl., 1995, 34, 259.
10 We wish to introduce the acronym DYCM for diyne cross-metathesis,
although this term then might also be used for the titanocene-
mediated and photocatalysed metathesis of 1,3-diynes via C–C single
bond cleavage, see: S. Pulst, F. G. Kirchbauer, B. Heller, W. Baumann
and U. Rosenthal, Angew. Chem., Int. Ed., 1998, 37, 1925.
11 D. E. Gross and J. S. Moore, Macromolecules, 2011, 44, 3685.
12 Acetylene Chemistry: Chemistry, Biology and Material Science,
ed. F. Diederich, P. J. Stang and R. R. Tykwinski, Wiley-VCH,
Weinheim, 2005.
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It should be emphasized that it is crucial to establish the
appropriate reaction time for each diyne combination, since
degradation of the products is observed upon stirring the
equilibrated reaction mixtures for prolonged periods. This is
exemplified by the conversion–time diagram shown in Fig. 1 for
one of the fastest DYCM reactions (Table 2, entry 6), indicating
slow and continuous consumption of the unsymmetrical diyne
3. In other cases, where longer reaction times are required, the
degradation is also significantly slower, and consequently, the
yields are hardly affected by this secondary process (see ESI† for
other conversion–time diagrams). For all RCRC–CRCR0 systems
studied so far, the corresponding alkynes RCRCR0 and triynes
RCRC–CRC–CRCR0 (and over time also tetraynes) are identified
as secondary reaction products by GC/MS analysis (Fig. 1),
suggesting that disproportionation of diynes into monoynes
and triynes (and subsequently into polyynes)14c takes place, but
favourably at a significantly slower rate than the desired DYCM
reaction. Apparently, this disproportionation can be faster with
other alkylidyne catalyst systems, which might explain the
observation made by Gross and Moore upon isolation of tetra-
meric macrocycles with yne (C2) and diyne (C4) moieties from a
diyne polymer under alkyne metathesis conditions (vide supra).11
The reasons as to why disproportionation with catalyst 1 is
relatively slow remain unclear at the moment, and this needs
to be further addressed by means of theoretical calculations
concerning possible competing reaction mechanisms.6
16 (a) W. Yin, C. He, M. Chen, H. Zhang and A. Lei, Org. Lett., 2009,
11, 709; (b) X. Meng, C. Li, B. Han, T. Wang and B. Chen, Tetra-
hedron, 2010, 66, 4029; (c) D. Wang, J. Li, N. Li, T. Gao, S. Hou and
B. Chen, Green Chem., 2010, 12, 45; (d) S. Zhang, X. Liu and T. Wang,
Adv. Synth. Catal., 2011, 353, 1463.
In conclusion, the recent observation that the tungsten
alkylidyne complex 1 is able to promote the metathesis of
1,3-diynes in a surprisingly selective and efficient manner5 17 K. Yin, C. Li, J. Li and X. Jia, Green Chem., 2011, 13, 591.
c
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Chem. Commun.