Palladium-catalyzed reaction of a sterically constrained trialkyne: A dimerization-type reaction with a surprising finale

Article abstract of DOI:10.1016/S0040-4039(00)01139-4

The intramolecular reaction of a triyne promoted by palladium results in the formation of an enyne and coupling of the third alkyne with the phosphine. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4039(00)01139-4

Tetrahedron Letters 41 (2000) 6775±6779
Palladium-catalyzed reaction of a sterically constrained
trialkyne: a dimerization-type reaction with a surprising ®nale
Thierry Granier, Diego J. Cardenas and Antonio M. Echavarren*
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Departamento de Quõmica Organica, Universidad Autonoma de Madrid, Cantoblanco, 28049 Madrid, Spain
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Received 9 May 2000; accepted 3 July 2000
Abstract
The intramolecular reaction of a triyne promoted by palladium results in the formation of an enyne and
coupling of the third alkyne with the phosphine. # 2000 Elsevier Science Ltd. All rights reserved.
Keywords: cyclophanes; cyclization; dimerization; palladium; cobalt.
Among the variety of transition metals that are able to catalyze the [2+2+2] trimerization of
alkynes,1 cobalt-catalyzed processes have been the most widely applied in organic synthesis for
the preparation of substituted benzenes.2 We have recently described the synthesis of syn-truxene
derivatives 1 by the Stille coupling reaction of 2 with trimethylsilylethynyltributylstannane,
followed by desilylation.3 Although cyclotrimerization of alkynes has been so far very rarely
applied for the preparation of cyclophanes,4 we decided to examine the prospect of using 1 as a
starting material for the synthesis of cyclophane 35 or related cyclophanes. Herein we report the
synthesis of 3 by using a cobalt-mediated reaction and the formation of a new cyclophane by a
reaction promoted by a palladium complex in which the phosphine ligand leads to an unexpected
transmetalation reaction.
* Corresponding author. Fax: +34-91-397-3966; e-mail: anton.echavarren@uam.es
0040-4039/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01139-4

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Recently, new pathways for the trimerization of alkynes have been uncovered by Yamamoto
by using palladium catalysts.6,7 However, simple terminal alkynes usually undergo dimerization
in the presence of palladium catalysts to give either head-to-tail or head-to-head butenynes.8 10
The mechanism suggested by Trost for the formation of heat-to-tail butenynes is summarized in
Scheme 1.9b In this new proposal, three alkyne molecules are involved in the catalytic cycle.
Importantly, the last alkyne was proposed to cleave the alkenylpalladium intermediate III by
oxidative addition to form a Pd(IV) complex IV,11 which evolves by reductive elimination to form
the enyne and the catalytically active alkynylpalladium(II) complex I (Scheme 1). An alternative
to this mechanism involved trans-dialkynyl palladium complexes as intermediates (s-alkynyl
instead of OAc for I±IV).
Scheme 1.
Truxene 1 appeared to be ideally suited to undergo the reactions outlined in Scheme 1 to give,
after one turn of the cycle, palladium complex 4. By using stoichiometric amounts of palladium,
complex 4 was expected to be isolable due to the steric constraints introduced by the butenyne
and truxene portions. On the other hand, formation of the butenyne was not expected if the
process involved highly strained trans-dialkynyl palladium complexes as intermediates.
We therefore examined the reaction of triyne 1 by using di€erent palladium complexes. The use
.
of Pd(PPh3)4 or Pd2(dba)3 dba resulted in the formation of complex reaction mixtures. Interestingly,
when trialkyne 1 was treated with stoichiometric Pd(p-Tol3P)2(OAc)2, the new cyclic compound 5
was isolated in 30% yield.12 The EI-MS of this new truxenephane revealed the presence of an
additional p-tolyl group. The structure of this compound was assigned on the basis of its NMR
spectra, including NOESY, HMBC and HMBQ experiments.13 Particularly diagnostic were the
NOEs observed between the methylene hydrogens of the enyne (broad singlet at 4.94 ppm) with
two hydrogens of di€erent benzyl groups (4.01 and 2.10 ppm).

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The enyne of cyclophane 5 results from a head-to-tail coupling promoted by palladium.8,9
Remarkably, a p-tolyl group from the triarylphosphine is attached to the third alkyne. Formation
of 5 can be rationalized as shown in Scheme 2. Thus, insertion of the second alkyne into the
alkynyl±palladium bond of 6 would give 7. Presumably, and in accordance with Scheme 1,
oxidative addition of the terminal C±H bond of the alkyne would give rise to complex 8,11 that
could give 4 by reductive elimination (L=phosphine and/or enyne). The palladium of intermediate
4 could be either coordinating the enyne or a molecule of p-Tol3P. Surprisingly, 4 undergoes a
transmetalation-type reaction with p-Tol3P to form 9, which would give rise to the ®nal organic
product 5.
Scheme 2.
Under forcing conditions, PPh3 is known to react with Pd(OAc)2 to form [PhPd(PPh3)(m-
OAc)]2.14 Thus, this palladium complex may initiate the series of reactions outlined in Scheme 2
(Ph instead of OAc). Alternatively, the penultimate step (4!9) could proceed by coupling of the
terminal arylacetylene with a phosphonium salt formed by the reductive elimination of an alkynyl
(i.e. 6 or 4) or alkenyl (i.e. 7) palladium intermediate.15,16 Indeed, this type of cross-coupling was
also observed in the reaction between phenylacetylene with p-Tol3P (2 mol equiv) in the presence
of Pd(OAc)2 (1 mol equiv.) (70ꢀC, 20 h), which a€ords p-tolylphenylacetylene, although in low
yield.17 Thus, the macrocycle prevents further coupling of alkynyl±Pd complex 4 and favors the
arylation reaction.
While benzannulation of the alkynes of 1 could not be achieved by using palladium catalysts,
heating 1 in xylene with a stoichiometric amount of CpCo(CO)2 lead to cyclophane 3 in 15%
yield.
In summary, while cobalt-mediated benzannulation of trialkyne 1 a€ords cyclophane 3, palladium-
promoted reaction of 1 leads to a head-to-tail enyne 5. Interestingly, an aryl group from the
triarylphosphine ligand is incorporated into the third alkyne. Formation of the new cyclophane 5
in the presence of palladium is in accordance with the catalytic cycle shown in Scheme 1 for the
synthesis of butenynes in the palladium-catalyzed dimerization of terminal alkynes.

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Acknowledgements
We are grateful to the DGES (Project PB97-0002-C2-02) for support of this research. T.G.
acknowledges the receipt of postdoctoral fellowships by the Swiss National Science Foundation.
We thank the referee for suggesting Ref. 14. We also acknowledge Johnson Matthey PLC for a
generous loan of palladium salts.
References
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12. A similar compound was obtained with Pd(PPh3)2(OAc)2. However, assignment of the 1H NMR of this
truxenephane was complicated due to superposition of several of the Ar±H resonances.
13. Experimental. A solution of palladium acetate (28 mg, 0.12 mmol) and tri(p-tolyl)phosphine (75 mg, 0.25 mmol) in
toluene (50 ml) was warmed to 60ꢀC and treated dropwise with a solution of 1 (50 mg, 0.073 mmol) in toluene (8
ml). The resulting black mixture was heated at 70ꢀC for 4.5 h. After being cooled to room temperature, the
mixture was evaporated and the residue was chromatographed (100:1:1 to 100:2:1 hexane:EtOAc:CH2Cl2) to give
5 (17 mg, 23%): 1H NMR (CDCl3, 300 MHz, 15 mM) ꢀ 7.99 (d, J=7.7 Hz, 1H), 7.98 (d, J=7.7 Hz, 1H), 7.96 (d,
J=7.7 Hz, 1H), 7.75 (d, J=7.7 Hz, 1H), 7.51 (dd, J=2.0, 6.9 Hz, 1H), 7.43 (d, J=7.3 Hz, 1H), 7.12±7.41 (m,
10H), 7.08 (br d, J=7.7 Hz, 1H), 7.01 (t, J=7.7 Hz, 1H), 6.97 (t, J=7.7 Hz, 1H), 6.88 (d, J=8.1 Hz, 2H), 6.50±
6.61 (m, 3H), 6.48 (d, J=7.3 Hz, 1H), 6.18 (d, J=6.9 Hz, 1H), 4.97 (t, J=3.6 Hz, 1H), 4.94 (s, 2H), 4.64±4.75 (m,
2H), 4.12 (dd, J=3.6, 12.5 Hz, 1H), 4.01 (dd, J=9.6, 14.1 Hz, 1H), 3.64 (dd, J=8.1, 13.7 Hz, 1H), 3.52 (dd,
J=4.8, 13.7 Hz, 1H), 3.41 (dd, J=4.0, 12.5 Hz, 1H), 2.10 (dd, J=10.9, 14.1 Hz, 1H), 2.07 (s, 3H); 13C NMR
(CDCl3, 75 MHz) ꢀ 147.21, 147.17, 143.28, 142.44, 141.60, 141.18, 140.84, 139.49, 138.62, 138.24, 137.96, 136.07,
135.73, 132.54, 132.23, 131.71, 130.69, 130.21, 129.37, 129.12, 128.68, 128.50, 128.03, 127.69, 127.46, 127.39,
127.00, 126.75, 126.62, 126.34, 126.24, 126.09, 125.97, 125.47, 123.61, 122.83, 122.18, 121.88, 120.40, 91.61, 91.37,
91.20, 88.26, 48.65, 47.82, 47.68, 37.42, 36.83, 35.52, 21.63; FAB-MS m/z 775 (71, M++1), 774 (M+, 72), 569 (61),
339 (100); FAB-HRMS calcd for C61H42 774.3286; found 774.3249.
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Yamamoto, A. Chem. Lett. 1995, 1101±1102. (c) Goodson, F. E.; Wallow, T. I.; Novak, B. M. J. Am. Chem. Soc.
1997, 119, 12441±12453.

6779
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17. It is interesting to note that the major new product was p,p0-dimethylbiphenyl. Heating p-Tol3P with Pd(OAc)2 in
toluene (70ꢀC, 20 h) in the absence of phenylacetylene leads also to the formation of this biphenyl as the major
new product (isolated in 3% yield).