J. Am. Chem. Soc. 1999, 121, 5827-5828
5827
Scheme 1
Palladium-Catalyzed Cocyclization of Arynes with
Alkynes: Selective Synthesis of Phenanthrenes and
Naphthalenes
Diego Pen˜a, Dolores Pe´rez,* Enrique Guitia´n,* and
Luis Castedo
Departamento de Qu´ımica Orga´nica
UniVersidad de Santiago de Compostela y
Unidad Asociada al CSIC
15706 Santiago de Compostela, Spain
Scheme 2
ReceiVed March 5, 1999
Reactions mediated by transition metals have played a crucial
role in the development of synthetic methodology during the last
quarter of this century. A paradigm of the synthetic potential of
these transformations is the metal-catalyzed cyclotrimerization
of alkynes to afford aromatic compounds.1 This extensively
exploited reaction has been studied from the mechanistic point
of view and has been expanded in scope to embrace cocyclizations
of alkynes, alkenes, nitriles, and other species. Our experience
in aryne chemistry led us to consider the possibility of using
transition metals to catalyze cycloaddition reactions of arynes,2,3
a possibility recently confirmed by the finding that arynes can
be transformed into triphenylenes by efficient palladium(0)-
catalyzed cyclotrimerization.4 To explore further the scope of this
novel palladium-mediated aryne chemistry, we have investigated
the cocyclization of arynes with other species. Here we report
preliminary results on the cocyclization of arynes and alkynes to
afford phenanthrenes and naphthalenes.
In our earlier work4 we found that Pd(0) complexes are the
catalysts of choice for trimerization of benzyne, which is strongly
electrophilic. By contrast, there are few published examples of
the cyclotrimerization of alkynes using Pd(0) complexes, and those
that have been reported are mostly limited to electron-poor
alkynes.5-7 We envisaged that the difference between arynes and
alkynes as regards reactivity with Pd(0) complexes, rather than
being a disadvantage, might provide the chemoselectivity required
for a synthetically useful cocyclization reaction. With this in mind
we started our study with the reactions of arynes with an electron-
deficient alkyne, dimethyl acetylenedicarboxylate (DMAD, 3),
catalyzed by Pd(0) complexes (Schemes 1 and 2).
We found that slow generation of benzyne, by treatment of 1a
with CsF in acetonitrile at room temperature, in the presence of
3 and catalytic amounts of Pd(0), afforded mixtures of phenan-
threne 4a, naphthalene 5a, and minor amounts of triphenylene.
Various reaction conditions were tried in order to direct the
reaction toward the formation of either the phenanthrene or the
naphthalene. The best yield of 4a was obtained using 1.4 equiv
of the alkyne and Pd(PPh3)4 as catalyst (Table 1, entry 1). Larger
excesses of the alkyne produced less phenanthrene and more
naphthalene, but selective formation of 5a was not achieved even
with 10 equiv of alkyne. TLC monitoring of these experiments
showed the initial formation and eventual disappearance of a
compound that upon isolation was characterized as complex 68
and is assumed to be one of the intermediates in the formation of
4a and 5a. Naphthalene 5a was obtained in good yield and with
very good selectivity when Pd2(dba)3 was used as the catalyst
(entry 2). It is possible that reaction of DMAD with Pd2(dba)3
gave complex 7, as previously reported,6,9 and that 5a resulted
from reaction of 7 with a molecule of benzyne.
(1) (a) Vollhardt, K. P. C. Angew. Chem., Int. Ed. Engl. 1984, 23, 539-
556. (b) Schore, N. E. Chem. ReV. 1988, 88, 1081-1119. (c) Grotjahn, D. B
In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone, F. G.
A., Wilkinson, G. Eds.; Hegedus, L. H., volume Ed.; Pergamon: Oxford,
1995; Vol. 12, pp 741-770.
(2) For general reviews on aryne chemistry, see: (a) Hoffmann, R. W.
Dehydrobenzene and Cycloalkynes; Academic Press: New York, 1967. (b)
Hart, H. In The Chemistry of Functional Groups, Suppl. C2: The Chemistry
of Triple-Bonded Functional Groups; Patai, S., Ed.; Wiley: Chichester, 1994;
pp 1017-1134.
(3) For recent reviews on transition metal complexes of arynes, see: (a)
Buchwald, S. L.; Broene, R. D. In ComprehensiVe Organometallic Chemistry
II; Abel, E. W., Stone, F. G. A., Wilkinson, G., Eds.; Hegedus, L. H., volume
Ed.; Pergamon: Oxford, 1995; Vol. 12, pp 771-784. (b) Bennett, M. A.;
Wenger, E. Chem. Ber./Recueil 1997, 130, 1029-1042.
The same chemoselectivity was observed when DMAD was
reacted with the substituted arynes 2b and 9 under similar reaction
conditions. Thus, generation of 4,5-difluorobenzyne (2b) by
treatment of triflate 1b with CsF, in the presence of excess DMAD
and 0.1 equiv of Pd(PPh3)4, afforded a mixture of phenanthrene
4b (64%), naphthalene 5b (9%), and 2,3,6,7,10,11-hexafluoro-
triphenylene (8%) (Table 1, entry 3). The use of Pd2(dba)3 as
(4) Pen˜a, D.; Escudero, S.; Pe´rez, D.; Guitia´n, E.; Castedo, L. Angew.
Chem., Int. Ed. 1998, 37, 2659-2661.
(5) Maitlis, P. M. Pure Appl. Chem. 1973, 33, 489-512.
(6) Very electron-deficient alkynes (e.g., DMAD) undergo cycloaddition
reactions when palladacyclopentadiene complexes are used as precursors of
Pd(0) catalysts: (a) Brown, L. D.; Itoh, K.; Suzuki, H.; Hirai, K.; Ibers, J. A.
J. Am. Chem. Soc. 1978, 100, 8232-8238. (b) Stephan, C.; Munz, C.; Dieck,
H. J. Organomet. Chem. 1993, 452, 223-227.
(8) The formation of complexes of this kind by reaction of Pd(PPh3)4 and
electron-deficient alkynes has been described previously: Greaves, E. O.; Lock,
C. J. L.; Maitlis, P. M. Can. J. Chem. 1968, 46, 3879-3891.
(9) (a) Moseley, K.; Maitlis, P. M. J. Chem. Soc., Chem. Commun. 1971,
1604-1606. (b) Moseley, K.; Maitlis, P. M. J. Chem. Soc., Dalton Trans.
1974, 169-175.
(7) Cyclization of alkynes by Pd(0) complexes and AcOH occurs via a
different mechanism, involving Pd(II)-H complexes as active catalysts: (a)
Negishi, E.; Harring, S. L.; Owczarczyk, Z.; Mohamud, M. M.; Ay, A.
Tetrahedron Lett. 1992, 33, 3253-3256. (b) Brown, S.; Clarkson, S.; Grigg,
R.; Sridharan, V. Tetrahedron Lett. 1993, 34, 157-160.
10.1021/ja9907111 CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/03/1999